Synthesis of cannabidiol-based compounds as ACE2 inhibitors with potential application in the treatment of COVID-19.

Cannabis is a general name for plants of the genus Cannabis. Used as fiber, medicine, drug, for religious, therapeutic, and hedonistic purposes along the millenia, it is mostly known for its psychoactive properties. One of its major constituents, cannabidiol (CBD), a non-psychoactive substance, among many other biological activities, has shown potential as an anti-SARS-CoV-2 drug. In this work, three derivatives and an analogue of CBD were synthesized, and cell viability and antiviral activities were evaluated. None of the compounds showed cytotoxicity up to a maximum concentration of 100 µM and, in contrast, displayed a significant antiviral activity, superior to remdesivir and nafamostat mesylate, with IC50 values ranging from 9.4 to 1.9 µM. In order to search for a possible molecular target, the inhibitory activity of the compounds against ACE2 was investigated, with expressive results (IC50 ranging from 3.96 µM to 0.01 µM).

Foliar Calcium Absorption by Tomato Plants: Comparing the Effects of Calcium Sources and Adjuvant Usage.

The deficiency of calcium (Ca) reduces the quality and shelf life of fruits. In this scenario, although foliar spraying of Ca2+ has been used, altogether with soil fertilization, as an alternative to prevent deficiencies, little is known regarding its absorption dynamics by plant leaves. Herein, in vivo microprobe X-ray fluorescence was employed aiming to monitor the foliar absorption of CaCl2, Ca-citrate complex, and Ca3(PO4)2 nanoparticles with and without using adjuvant. We also investigated whether Sr2+ can be employed as Ca2+ proxy in foliar absorption studies. Moreover, the impact of treatments on the cuticle structure was evaluated by scanning electron microscopy. For this study, 45-day-old tomato (Solanum lycopersicum L., cv. Micro-Tom) plants were used as a model species. After 100 h, the leaves absorbed 90, 18, and 4% of aqueous CaCl2, Ca-citrate, and Ca3(PO4)2 nanoparticles, respectively. The addition of adjuvant increased the absorption of Ca-citrate to 28%, decreased that of CaCl2 to 77%, and did not affect Ca3(PO4)2. CaCl2 displayed an exponential decay absorption profile with half-lives of 15 h and 5 h without and with adjuvant, respectively. Ca-citrate and Ca3(PO4)2 exhibited absorption profiles that were closer to a linear behavior. Sr2+ was a suitable Ca2+ tracer because of its similar absorption profiles. Furthermore, the use of adjuvant affected the epicuticular crystal structure. Our findings reveal that CaCl2 was the most efficient Ca2+ source. The effects caused by adjuvant suggest that CaCl2 and Ca-citrate were absorbed mostly through hydrophilic and lipophilic pathways.

Total nitrogen and pH are key variables for functional structure of zooplanktonic communities in an agropastoral landscape.

Changes in land use are one of the main impacts on aquatic ecosystems. The conversion of natural areas into agropastoral, such as pasture or monocultures, can affect the limnological characteristics of the water that in turn influence the structure of aquatic communities. But the impact is still unclear, particularly on zooplankton communities. The objective of this study was to evaluate the effect of water parameters from eight reservoirs inserted in an agropastoral landscape on the functional structure of zooplankton. The functional characterization of the zooplankton community was based on four traits: body size, feeding type, habitat type, and trophic group. Functional diversity indices (FRic FEve and FDiv) were estimated and modeled water parameters, using generalized additive mixed models (GAAM). The water parameters investigated were total nitrogen (TN) and total phosphorus (TP), dissolved oxygen (OD), temperature and pH. Moreover, we used RDA to analyze the influence of these environmental variables on the sharing of traits among the sample sites. FRic was high in the reservoirs with low TN concentration and low pH values. FEve was also high in low pH and high TP concentration. FDiv was high with unsharp increases of pH and high concentrations of TN and DO. Our analyses showed pH as a key variable for functional diversity, since it was related to the variation in all indices. Data also pointed out changes in diversity functional with small pH changes. The big and medium size, raptorial-cop and filtration-clad functional traits were positively associated with high concentrations of TN and alkaline pH. The small size and filtration-rot were negatively associated with high concentrations of TN and alkaline pH. Density of filtration-rot was lower in pasture landscapes. In conclusion, our study indicated that pH and TN are key variables for the functional structure of zooplanktonic communities in an agropastoral landscape.

Accuracy of Palpation Procedures for Locating the C1 Transverse Process and Masseter Muscle as Confirmed by Computed Tomography Images.

OBJECTIVE: The purpose of this study was to examine the accuracy of palpation methods for locating the transverse processes of the first cervical vertebra and masseter muscle using radiographic images as the gold-standard method and the association between personal characteristics with the observed accuracy. METHODS: This was a single-blinded, diagnostic accuracy study. Ninety-five participants (49 women, 58 ± 16 years of age) were enrolled in this study. A single examiner palpated the neck and face region of all participants to identify the transverse processes of the first cervical vertebra and masseter muscles bilaterally. In sequence, participants underwent a multislice computed tomography scan for assessment of the superimposed inner body structure. Two radiologists assessed the computed tomography images using the same criteria and were blinded regarding each other's assessment and the anatomic landmarks under investigation. The palpation accuracy was calculated as the proportion of the correctly identified landmarks in the studied sample. The correlation of the palpation outcome (correct = 1; incorrect = 0) with age, sex (male = 1; female = 0), and body mass index was investigated using the point-biserial correlation coefficient. RESULTS: The right and left transverse processes were correctly located in 76 (80%) and 81 (85%) participants, respectively, and bilaterally in 157 events (83%), as evaluated by the consensus of the 2 radiologists. The masseter muscles were correctly localized bilaterally in 95 of 95 (100%) participants. Body mass showed statistical evidence of a weak, positive correlation with the correct location of the transverse processes of the first cervical vertebra at the right body side (r = .219; 95% confidence interval, 0.018-0.403; P = .033). CONCLUSION: Palpation methods used in this study accurately identified the location of the first cervical vertebra spinous processes and the masseter muscles.

2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis.

BACKGROUND: An important but often insufficient aspect of care in people with inflammatory arthritis (IA) is empowering patients to acquire a good understanding of their disease and building their ability to deal effectively with the practical, physical and psychological impacts of it. Self-management skills can be helpful in this regard. OBJECTIVES: To develop recommendations for the implementation of self-management strategies in IA. METHODS: A multidisciplinary taskforce of 18 members from 11 European countries was convened. A systematic review and other supportive information (survey of healthcare professionals (HCPs) and patient organisations) were used to formulate the recommendations. RESULTS: Three overarching principles and nine recommendations were formulated. These focused on empowering patients to become active partners of the team and to take a more proactive role. The importance of patient education and key self-management interventions such as problem solving, goal setting and cognitive behavioural therapy were highlighted. Role of patient organisations and HCPs in promoting and signposting patients to available resources has been highlighted through the promotion of physical activity, lifestyle advice, support with mental health aspects and ability to remain at work. Digital healthcare is essential in supporting and optimising self-management and the HCPs need to be aware of available resources to signpost patients. CONCLUSION: These recommendations support the inclusion of self-management advice and resources in the routine management of people with IA and aim to empower and support patients and encourage a more holistic, patient-centred approach to care which could result in improved patient experience of care and outcomes.

Non-pharmacological interventions for acute pain management in adult trauma victims: a scoping review.

OBJECTIVE: This scoping review aimed to map non-pharmacological interventions to reduce acute pain in adult trauma victims. INTRODUCTION: Acute pain is a consequence of a pathological or traumatic event, and a result of invasive or non-invasive health care procedures. Acute trauma pain, as well as its treatment, is one of the least-studied areas of acute pain. Although non-pharmacological interventions are responsible for pain relief among a significant number of patients, only a small percentage of patients receive non-pharmacological interventions. INCLUSION CRITERIA: This scoping review considered all studies conducted on adult victims of trauma, aged 18 years or over, in pre-hospital emergency care, emergency rooms, and trauma-center settings. Studies were considered if they focused on non-pharmacological interventions designed to reduce acute pain, and were implemented and evaluated by health professionals. Non-pharmacological interventions of any type, duration, frequency, and intensity were considered. METHODS: A comprehensive search strategy across 11 bibliometric databases and gray literature sources was developed. Full texts of selected citations were assessed in detail for eligibility by two independent reviewers. No other relevant studies were identified by searching the references of the included articles. Data extraction was performed independently by two reviewers using an instrument previously developed, and those reviewers were later responsible for its validation. Findings were then extracted directly into tables that are accompanied by a narrative summary to show how they relate to the objectives of the review conducted. RESULTS: This scoping review included nine studies: two retrospective cohort studies, five randomized controlled trials, one case report, and one literature review for five different countries. Non-pharmacological interventions identified and administered to trauma victims in pre-hospital settings, emergency services, and trauma centers were as follows: acupressure, auricular acupressure, auricular acupuncture, transcutaneous electrical nerve stimulation, repositioning, use of pressure relief devices, massage, heat therapy, music therapy, relaxation therapy, immobilization, ice therapy, compression, elevation, and bandage. Non-pharmacological interventions were mainly developed by nurses, physicians, and paramedics. They were, in most studies, poorly described in terms of their efficacy and were mostly reported in minor traumas, such as simple fractures or small wounds. CONCLUSIONS: Currently, there is no consensus for the implementation of non-pharmacological interventions in the treatment of acute trauma pain. Their application is primarily used for minor traumas, and their potential for the treatment of major traumas is yet unknown. No studies on the use of non-pharmacological interventions aimed at reducing the impact of traumatic adverse environments were identified. Further investigation on the effects of these interventions should be encouraged so that robust decisions and recommendations can be made.

Naphthoquinones and Derivatives for Chemotherapy: Perspectives and Limitations of their Anti-trypanosomatids Activities.

Chagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited, and a search for alternatives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among all the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF3 on a phenyl amine ring inhibited T. brucei proliferation in the nanomolar range, and naphthopterocarpanquinones stood out for their activity on a range of Leishmania species. Some of these compounds showed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. Indeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo is essential for the development of a novel, specific and safe derivative, minimizing adverse effects.

Challenges and Opportunities for Clinical Pharmacogenetic Research Studies in Resource-limited Settings: Conclusions From the Council for International Organizations of Medical Sciences-Ibero-American Network of Pharmacogenetics and Pharmacogenomics Meeting.

PURPOSE: The symposium Health and Medicines in Indigenous Populations of America was organized by the Council for International Organizations of Medical Sciences (CIOMS) Working Group on Clinical Research in Resource-Limited Settings (RLSs) and the Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF). It was aimed to share and evaluate investigators' experiences on challenges and opportunities on clinical research and pharmacogenetics. METHODS: A total of 33 members from 22 countries participated in 2 sessions: RIBEF studies on population pharmacogenetics about the relationship between ancestry with relevant drug-related genetic polymorphisms and the relationship between genotype and phenotype in Native Americans (session 1) and case examples of clinical studies in RLSs from Asia (cancer), America (diabetes and women health), and Africa (malaria) in which the participants were asked to answer in free text their experiences on challenges and opportunities to solve the problems (session 2). Later, a discourse analysis grouping common themes by affinity was conducted. FINDINGS: The main result of session 1 was that the pharmacogenetics-related ancestry of the population should be considered when designing clinical studies in RLSs. In session 2, 21 challenges and 20 opportunities were identified. The social aspects represent the largest proportion of the challenges (43%) and opportunities (55%), and some of them seem to be common. IMPLICATIONS: The main discussion points were gathered in the Declaration of Mérida/T'Hó and announced on the Parliament of Extremadura during the CIOMS-RIBEF meeting in 4 of the major Latin American autochthonous languages (Náhualth, Mayan, Miskito, and Kichwa). The declaration highlighted the following: (1) the relevance of population pharmacogenetics, (2) the sociocultural contexts (interaction with traditional medicine), and (3) the education needs of research teams for clinical research in vulnerable and autochthonous populations.

Depression, disability and sleep disturbance are the main explanatory factors of fatigue in rheumatoid arthritis: a path analysis model.

OBJECTIVES: Fatigue is one of the most prevalent and disabling symptoms among patients with rheumatoid arthritis (RA), however, it is frequently neglected by health professionals. This study aimed to develop a multidimensional explanatory model of fatigue in patients with RA as a basis for better understanding and intervention. METHODS: This was an ancillary analysis of an observational, cross-sectional, single centre study. Patients completed a questionnaire including demographic data and measures of pain, sleep, disability, anxiety, depression, and personality. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). Disease activity and haemoglobin levels were assessed. Path analysis was performed to test and improve a hypothesised model for fatigue. RESULTS: This analysis included 142 patients, with a mean (SD) age of 61.1 (11.7) years. The final path analysis model presented acceptable fit and explained 60.0% of the variance of fatigue. The predominant direct explanatory factors identified were disability (46.5%) and depression (41.2%), the latter having an additional indirect influence of 19% through disability. Age (-16.2%) and sleep disturbance (15.7%) were also directly linked to fatigue. Personality trait extroversion (-22.4%), pain (20.0%), and disease activity (14.9%) are only indirectly related to fatigue. CONCLUSIONS: Depression, disability and sleep disturbance appear to be the main factors explaining fatigue in patients with RA. Disease activity, pain, and personality seem to play only a secondary role, extroversion being the only personality trait associated with fatigue. These findings foster a shift in the paradigm of care towards a more holistic management of fatigue, integrating adjunctive therapies beyond measures targeted solely at disease remission.

Anti-Mycobacterium tuberculosis activity of essential oil and 6,7-dehydroroyleanone isolated from leaves of Tetradenia riparia (Hochst.) Codd (Lamiaceae).

BACKGROUND: The global resurgence of tuberculosis (TB) and the development of drug resistance, as multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis isolates, are a threat to TB control and have created a need for new and more effective anti-TB drugs. AIM: The current study evaluated the in vitro cytotoxicity and activity of Tetradenia riparia essential oil (TrEO) and 6,7-dehydroroyleanone pure compound against M. tuberculosis H37Rv and susceptible and resistant clinical isolates. METHODS: The in vitro activities of TrEO and 6,7-dehydroroyleanone were determined by Resazurin Microtiter Assay Plate (REMA). The cytotoxicity was evaluated in murine peritoneal macrophages by Alamar Blue assay. The cytotoxic effects were expressed as median concentration cytotoxicity (CC50) and the selectivity index (SI) was calculated. RESULTS: TrEO and 6,7-dehydroroyleanone showed activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) 62.5 µg/ml and 31.2 µg/ml, respectively. Both of them exhibited activities against resistant and susceptible M. tuberculosis clinical isolates with MIC values between 31.2 and 62.5 µg/ml. Cytotoxicity assays showed SI 1.9 and 7.9 for TrEO and 6,7-dehydroroyleanone, respectively. CONCLUSION: These results revealed that TrEO isolated from leaves of T. riparia and the pure compound 6,7-dehydroroyleanone display good activity against M. tuberculosis clinical isolates, including MDR isolates, with low cytotoxicity to murine macrophages. The 6,7-dehydroroyleanone compound is a potential candidate for anti-TB drug.

Evolutionary genomic dynamics of Peruvians before, during, and after the Inca Empire.

Native Americans from the Amazon, Andes, and coastal geographic regions of South America have a rich cultural heritage but are genetically understudied, therefore leading to gaps in our knowledge of their genomic architecture and demographic history. In this study, we sequence 150 genomes to high coverage combined with an additional 130 genotype array samples from Native American and mestizo populations in Peru. The majority of our samples possess greater than 90% Native American ancestry, which makes this the most extensive Native American sequencing project to date. Demographic modeling reveals that the peopling of Peru began ∼12,000 y ago, consistent with the hypothesis of the rapid peopling of the Americas and Peruvian archeological data. We find that the Native American populations possess distinct ancestral divisions, whereas the mestizo groups were admixtures of multiple Native American communities that occurred before and during the Inca Empire and Spanish rule. In addition, the mestizo communities also show Spanish introgression largely following Peruvian Independence, nearly 300 y after Spain conquered Peru. Further, we estimate migration events between Peruvian populations from all three geographic regions with the majority of between-region migration moving from the high Andes to the low-altitude Amazon and coast. As such, we present a detailed model of the evolutionary dynamics which impacted the genomes of modern-day Peruvians and a Native American ancestry dataset that will serve as a beneficial resource to addressing the underrepresentation of Native American ancestry in sequencing studies.

A tale of agriculturalists and hunter-gatherers: Exploring the thrifty genotype hypothesis in native South Americans.

OBJECTIVES: To determine genetic differences between agriculturalist and hunter-gatherer southern Native American populations for selected metabolism-related markers and to test whether Neel's thrifty genotype hypothesis (TGH) could explain the genetic patterns observed in these populations. MATERIALS AND METHODS: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36 rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701). Additionally, APOE genotypes from 39 individuals were obtained from the literature. AMOVA, main effects, and gene-gene interaction tests were performed. RESULTS: We observed differences in allele distribution patterns between agriculturalists and hunter-gatherers for some markers. For instance, between-groups component of genetic variance (FCT ) for APOE rs429358 showed strong differences in allelic distributions between hunter-gatherers and agriculturalists (p = 0.00196). Gene-gene interaction analysis indicated that the APOE E4/CD36 TT and APOE E4/IGF2BP2 A carrier combinations occur at a higher frequency in hunter-gatherers, but this combination is not replicated in archaic (Neanderthal and Denisovan) and ancient (Anzick, Saqqaq, Ust-Ishim, Mal'ta) hunter-gatherer individuals. DISCUSSION: A complex scenario explains the observed frequencies of the tested markers in hunter-gatherers. Different factors, such as pleotropic alleles, rainforest selective pressures, and population dynamics, may be collectively shaping the observed genetic patterns. We conclude that although TGH seems a plausible hypothesis to explain part of the data, other factors may be important in our tested populations.

Evaluation of Chemical Composition and Antileishmanial and Antituberculosis Activities of Essential Oils of Piper Species.

Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC-MS), and a total of 68 components were identified. Principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority of species analyzed. The composition of the essential oil of Piper mosenii was described for the first time. The cytotoxicity of the essential oils was evaluated in peritoneal macrophages and the oils of P. rivinoides, P. arboretum, and P. aduncum exhibited the highest values, with cytotoxic concentration at 50% (CC50) > 200 µg/mL. Both P. diospyrifolium and P. aduncum displayed activity against Leishmania amazonensis, and were more selective for the parasite than for the macrophages, with a selectivity index (SI) of 2.35 and >5.52, respectively. These SI values were greater than the 1 for the standard drug pentamidine. The antileishmanial activity of the essential oils of P. diospyrifolium and P. aduncum was described for the first time. P. rivinoides, P. cernuum, and P. diospyrifolium displayed moderate activity against the Mycobacterium tuberculosis H37Rv bacillus, with a minimum inhibitory concentration (MIC) of 125 µg/mL. These results are relevant and suggests their potential for therapeutic purposes. Nevertheless, further studies are required to explain the exact mechanism of action of these essential oils.

Antileishmanial Activity of Ezetimibe: Inhibition of Sterol Biosynthesis, In Vitro Synergy with Azoles, and Efficacy in Experimental Cutaneous Leishmaniasis.

Leishmaniasis affects mainly low-income populations in tropical regions. Radical innovation in drug discovery is time-consuming and expensive, imposing severe restrictions on the ability to launch new chemical entities for the treatment of neglected diseases. Drug repositioning is an attractive strategy for addressing a specific demand more easily. In this project, we have evaluated the antileishmanial activities of 30 drugs currently in clinical use for various morbidities. Ezetimibe, clinically used to reduce intestinal cholesterol absorption in dyslipidemic patients, killed Leishmania amazonensis promastigotes with a 50% inhibitory concentration (IC50) of 30 µM. Morphological analysis revealed that ezetimibe caused the parasites to become rounded, with multiple nuclei and flagella. Analysis by gas chromatography (GC)-mass spectrometry (MS) showed that promastigotes treated with ezetimibe had smaller amounts of C-14-demethylated sterols, and accumulated more cholesterol and lanosterol, than untreated promastigotes. We then evaluated the combination of ezetimibe with well-known antileishmanial azoles. The fractional inhibitory concentration index (FICI) indicated synergy when ezetimibe was combined with ketoconazole or miconazole. The activity of ezetimibe against intracellular amastigotes was confirmed, with an IC50 of 20 µM, and ezetimibe reduced the IC90s of ketoconazole and miconazole from 11.3 and 11.5 µM to 4.14 and 8.25 µM, respectively. Subsequently, we confirmed the activity of ezetimibe in vivo, showing that it decreased lesion development and parasite loads in murine cutaneous leishmaniasis. We concluded that ezetimibe has promising antileishmanial activity and should be considered in combination with azoles in further preclinical and clinical studies.

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.

HPLC analysis of supercritical carbon dioxide and compressed propane extracts from Piper amalago L. with antileishmanial activity.

Piper amalago L. leaves were extracted with supercritical carbon dioxide and compressed propane under different conditions, and with chloroform by the conventional maceration method. These methods were compared for the pyrrolidine alkaloid content. Supercritical carbon dioxide (SFE-CO2) at 313 K and 12.55 MPa showed the highest selectivity for the main compound (600.53 mg/g of extract). A gradient high-performance liquid chromatography (HPLC) method was developed and validated to quantify the alkaloid N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl]pyrrolidine in the extracts. The HPLC method showed linearity, precision and accuracy, allowing the quantitative analysis of the alkaloid in all the samples. All the extracts were tested against the promastigote and intracellular amastigote forms of Leishmania amazonensis. The antileishmanial activity was evaluated in terms of inhibitory concentration for 50% of protozoa (IC50). The cytotoxicity was also evaluated against J774A1 macrophages, and the cytotoxic concentrations for 50% of macrophages were obtained (CC50). The SFE-CO2 (313 K; 12.55 MPa) extract showed the highest antileishmanial activity with the following IC50 values of 16 and 7 µg/mL against the promastigotes and intracellular amastigotes forms, respectively. The extract showed low cytotoxicity with a CC50 value of 93 µg/mL.

Comparison of the shear bond strengths of conventional mesh bases and sandblasted orthodontic bracket bases.

This study aimed to compare in vitro the shear bond strength between metallic brackets (Abzil) with conventional mesh bases and metallic brackets with bases industrially sandblasted with aluminum oxide using three adhesive systems, in order to assess the influence of sandblasting on adhesiveness and to compare 3 different bonding systems. Two hundred and forty bovine incisors were used and randomly divided into 6 groups (40 teeth in each group), according to the bracket base and to the bonding system. The brackets were direct-bonded in bovine teeth with 3 adhesive systems: System A - conventional Transbond XT (3M - Unitek); System B - Transbond Plus Self Etching Primer + Transbond XT (3M - Unitek) and System C - Fuji ORTHO LC resin-reinforced glass ionomer cement in capsules (GC Corp.). Shear bond strength tests were performed 24 hours after bonding, in a DL-3000 universal testing machine (EMIC), using a load cell of 200 kgf and a speed of 1 mm/min. The results were submitted to statistical analysis and showed no significant difference between conventional and sandblasted bracket bases. However, comparison between the bonding systems presented significantly different results. System A (14.92 MPa) and system C (13.24 MPa) presented statistically greater shear bond strength when compared to system B (10.66 MPa). There was no statistically significant difference between system A and system C.

Comparison of the shear bond strengths of conventional mesh bases and sandblasted orthodontic bracket bases

This study aimed to compare in vitro the shear bond strength between metallic brackets (Abzil) with conventional mesh bases and metallic brackets with bases industrially sandblasted with aluminum oxide using three adhesive systems, in order to assess the influence of sandblasting on adhesiveness and to compare 3 different bonding systems. Two hundred and forty bovine incisors were used and randomly divided into 6 groups (40 teeth in each group), according to the bracket base and to the bonding system. The brackets were direct-bonded in bovine teeth with 3 adhesive systems: System A - conventional TransbondTM XT (3M - Unitek); System B - TransbondTM Plus Self Etching Primer + TransbondTM XT (3M - Unitek) and System C - Fuji ORTHO LC resin-reinforced glass ionomer cement in capsules (GC Corp.). Shear bond strength tests were performed 24 hours after bonding, in a DL-3000 universal testing machine (EMIC), using a load cell of 200 kgf and a speed of 1 mm/min. The results were submitted to statistical analysis and showed no significant difference between conventional and sandblasted bracket bases. However, comparison between the bonding systems presented significantly different results. System A (14.92 MPa) and system C (13.24 MPa) presented statistically greater shear bond strength when compared to system B (10.66 MPa). There was no statistically significant difference between system A and system C.

Avaliação do Índice de Remanescente Adesivo utilizando braquetes com e sem tratamento na base e a interação com três sistemas de colagem / Evaluation of Adhesive Remnant Index using conventional mesh bases and sandblasted orthodontic bracket bases and three bonding systems

OBJETIVO: avaliar o Índice de Remanescente Adesivo (IRA) em dentes bovinos após a descolagem de braquetes com e sem tratamento na base. METODOLOGIA: foram utilizados três sistemas de colagem ortodôntica para os dois padrões de base. Os dentes bovinos foram divididos em seis grupos de 40, de acordo com a base do braquete e o sistema de colagem. Vinte e quatro horas após a colagem foram realizados os testes de compressão em uma máquina de ensaios. A avaliação do IRA foi realizada em um estereomicroscópio por três examinadores calibrados. Foi utilizado o teste não paramétrico de Kruskal-Wallis, seguido do método de Dunn, para fazer as comparações múltiplas entre todos os grupos. RESULTADOS E CONCLUSÕES: observou-se que o tratamento das bases dos braquetes com óxido de alumínio não foi determinante para o aumento da adesividade entre o braquete e o adesivo. O grupo em que se utilizou braquetes com tratamento na base e adesivo TXT (3M-Unitek) + Transbond Plus SEP (3M-Unitek) apresentou a maior parte das fraturas na interface dente-adesivo (escore 4).

AIM: To assess the Adhesive Remnant Index (ARI) in bovine teeth after debonding mesh bases and sandblasted orthodontic bracket bases. METHODS: Were used three bonding systems for the two standards of base. The bovine teeth were divided into 6 groups of 40, according to the bracket base and to the bonding system. Twenty four hours after bonding they had been carried through shear bond strength tests in a universal testing machine. The assessment of ARI was performed in a stereomicroscopy by three calibrated examiners. It was used the non-parametric Kruskall-Wallis test, followed by Dunn's method, to do the multiple comparisons among all groups. RESULTS AND CONCLUSIONS: It was observed that the aluminum oxide sandblasting bracket bases was not determinative to the increase of the adhesiveness between bracket and adhesive. The group where it was used sandblasted orthodontic bracket bases and bonding system TXT (3M-Unitek) + Transbond Plus SEP (3M-Unitek) presented the majority of the failures at the teeth-adhesive interface (score 4).

[Healing process in bladder suture of rats with and without the administration of intraperitoneal Jatropha gossypiifolia L. gross extract]. / Estudo da cicatrização de suturas na bexiga urinária de ratos com e sem a utilização de extrato bruto de Jatropha gossypiifolia L. intraperitoneal.

INTRODUCTION: The suture of tissues and their healing process is one of the basic fundamentals of surgery, and the research on substances which could improve the process is an ongoing challenge. The use of plants has been tested but till nowadays without scientific demonstration. PURPOSE: To compare the macroscopic and histological alterations done by the use of intraperitoneal Jatropha gossypiifolia L. gross extract, in the healing process of sutures performed on the bladder of rats. METHODS: Forty adult, male, Wistar rats were distributed into two animal groups. One centimeter longitudinal incision on the bladder ventral wall, and single plane synthesis with separated polyglactine 910 5-0 (Ethicon) stitches was done in all the animals. In the control group an intraperitoneal cavity instillation of distilled water at a ratio of 1 ml/kg/weight, and a 1 ml/kg/weight of Jatropha gossypiifolia L. extract for the Jatropha group was done representing 200 mg of the substance. Each group was subdivided into two with 10 animals in each, being submitted to euthanasia on 3rd and 7th post-operative days. Comparative histological, macroscopic and statistical analysis were undertaken between the subgroups. RESULTS: Statistical significant difference was observed in the acute inflammation changes, vascular neoformation and bonding on day 3; the first one was greater in the control group, and the latter two greater in the Jatropha group; acute inflammation variables and fibroblastic proliferation presented to be more intense on day 7, with statistical significance favoring the control group. CONCLUSION: No favorable healing effect was observed with the administration of single intraperitoneal dose of Jatropha gossypiifolia L. gross extract on the sutures of bladder in rats.