Factors to consider for fascial plane blocks' success in acute and chronic pain management.

The outcome of fascial plane blocks (FPBs) has a certain variability that may depend on many factors, which can be divided into three main categories: operator-related, patient-related and drug-related. Operator-related factors include personal skills, choice of needle and injection modalities. Patient variables include anthropometric features, the type of targeted fascia, anatomical variants, patient positioning, muscle tone and breathing. Ultimately, efficacy, onset, and duration of fascial blocks may be affected by characteristics of the injected solution, including the type of local anesthetic, volume, concentration, pH, temperature and the use of adjuvants. In this article, we investigated all the factors that may influence the outcome of FPBs from a generic perspective, without focusing on any specific technique. Also, we provided suggestions to optimize techniques for everyday practitioners and insights to researchers for future studies.

Management of Cancer Therapy-Induced Oral Mucositis Using Photobiomodulation Therapy: An Overview of Systematic Reviews.

Objective: To systematically summarize the evidence for photobiomodulation therapy (PBMT) in the prevention and treatment of oral mucositis (OM) in patients undergoing cancer treatment. An electronic search was conducted in 8 databases and grey literature. Background: PBMT is recommended for the management of OM resulting from cancer treatment, with several systematic reviews (SRs) being published in recent years on this topic. Methods: Only SRs with outcomes from clinical trials were included, with no language or year restriction. The AMSTAR 2 tool was used to assess the methodological quality of the SRs. Results: Five thousand eight hundred fifty-six references were found, and 16 were selected for this review. OM prevention and treatment were favorable for PBMT in most studies, with a significant reduction in OM severity. Most studies obtained moderate confidence. Conclusions: PBMT represents an effective strategy in the management of OM, and this evidence is supported by studies with acceptable methodological quality.

Impacts of dielectric screening on the luminescence of monolayer WSe2.

Single layers of transition metal dichalcogenides (TMDCs), such as WSe2have gathered increasing attention due to their intense electron-hole interactions, being considered promising candidates for developing novel optical applications. Within the few-layer regime, these systems become highly sensitive to the surrounding environment, enabling the possibility of using a proper substrate to tune desired aspects of these atomically-thin semiconductors. In this scenario, the dielectric environment provided by the substrates exerts significant influence on electronic and optical properties of these layered materials, affecting the electronic band-gap and the exciton binding energy. However, the corresponding effect on the luminescence of TMDCs is still under discussion. To elucidate these impacts, we used a broad set of materials as substrates for single-layers of WSe2, enabling the observation of these effects over a wide range of electrical permittivities. Our results demonstrate that an increasing permittivity induces a systematic red-shift of the optical band-gap of WSe2, intrinsically related to a considerable reduction of the luminescence intensity. Moreover, we annealed the samples to ensure a tight coupling between WSe2and its substrates, reducing the effect of undesired adsorbates trapped in the interface. Ultimately, our findings reveal how critical the annealing temperature can be, indicating that above a certain threshold, the heating treatment can induce adverse impacts on the luminescence. Furthermore, our conclusions highlight the influence the dielectric properties of the substrate have on the luminescence of WSe2, showing that a low electrical permittivity favours preserving the native properties of the adjacent monolayer.

Polyphenols for Preventing Dental Erosion in Pre-clinical Studies with in situ Designs and Simulated Acid Attack.

Dental erosion is a chemical process characterized by acid dissolution of dental hard tissue, and its etiology is multifactorial. Dietary polyphenols can be a strategy for dental erosion management, collaborating to preserve dental tissues through resistance to biodegradation. This study describes a comprehensive review to interpret the effects of polyphenols on dental erosion of pre-clinical models with in situ designs and simulated acid attacks on enamel and dentin samples. We aim to evaluate evidence about Polyphenols' effects in the type of dental substrate, parameters of erosive cycling chosen in the in situ models, and the possible mechanisms involved. An evidence-based literature review was conducted using appropriate search strategies developed for main electronic databases (PubMed, Scopus, Web of Science, LILACS, EMBASE, LIVIVO, CINAHL, and DOSS) and gray literature (Google Scholar). The Joanna Briggs Institute checklist was used to evaluate the quality of the evidence. From a total of 1900 articles, 8 were selected for evidence synthesis, including 224 specimens treated with polyphenols and 224 control samples. Considering the studies included in this review, we could observe that polyphenols tend to promote a reduction in erosive and abrasive wear compared to control groups. However, as the few studies included have a high risk of bias with different methodologies and the estimated effect size is low, this conclusion should not be extrapolated to clinical reality.

Crotofolane Diterpenoids and Other Constituents Isolated from Croton kilwae.

Six new crotofolane diterpenoids (1-6) and 13 known compounds (7-19) were isolated from the MeOH-CH2Cl2 (1:1, v/v) extracts of the leaves and stem bark of Croton kilwae. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and mass spectrometric data. The structure of crotokilwaepoxide A (1) was confirmed by single-crystal X-ray diffraction, allowing for the determination of its absolute configuration. The crude extracts and the isolated compounds were investigated for antiviral activity against respiratory syncytial virus (RSV) and human rhinovirus type-2 (HRV-2) in HEp-2 and HeLa cells, respectively, for antibacterial activity against the Gram-positive Bacillus subtilis and the Gram-negative Escherichia coli, and for antimalarial activity against the Plasmodium falciparum Dd2 strain. ent-3ß,19-Dihydroxykaur-16-ene (7) and ayanin (16) displayed anti-RSV activities with IC50 values of 10.2 and 6.1 µM, respectively, while exhibiting only modest cytotoxic effects on HEp-2 cells that resulted in selectivity indices of 4.9 and 16.4. Compounds 2 and 5 exhibited modest anti-HRV-2 activity (IC50 of 44.6 µM for both compounds), while compound 16 inhibited HRV-2 with an IC50 value of 1.8 µM. Compounds 1-3 showed promising antiplasmodial activities (80-100% inhibition) at a 50 µM concentration.

Effect of preemptive photobiomodulation associated with nimesulide on the postsurgical outcomes, oxidative stress, and quality of life after third molar surgery: a randomized, split-mouth, controlled clinical trial.

OBJECTIVE: The aim of this study is to compare the effect of photobiomodulation with low-level laser therapy (LLLT) and nimesulide on inflammatory parameters, biomarkers of oxidative stress and inflammation, and quality of life after lower third molar (L3M) surgery. MATERIAL AND METHODS: A randomized, two-factor, triple-blind, controlled, split-mouth clinical trial was performed with 40 volunteers who required bilateral L3M removal. Patients were allocated depending on the use or not of 100 mg nimesulide 1 hbefore surgery, as well as the use or not of LLLT in the preoperative period. RESULTS: Pain peaks occurred after 6 h (nimesulide-placebo [N-P] group) and 8 h (nimesulide group). In the N-P group, LLLT resulted in significantly lower mean pain scores than the subgroup without LLLT after 4 h (p = 0.009) and 6 h (p = 0.048). As for edema, a shorter distance between the mandibular angle and the outer canthus of the eyes after 7 days (p = 0.037) and a smaller cumulative effect (p = 0.036) were observed in the N-P group associated with LLLT. A direct effect between LLLT (p = 0.047) and a reduction in the mean scores of overall dissatisfaction with quality of life was detected. CONCLUSIONS: Preemptive use of nimesulide only delayed peak pain. LLLT reduced edema, trismus, and contributed to a better perception of quality of life. Nimesulide inhibits peroxidation by increasing GSH and stopping neutrophil migration. The benefit of the association of both strategies was not superior to the use of LLLT alone. CLINICAL RELEVANCE: Translational study with impact on clinical-surgical protocols involving L3M surgery related to pharmacological and non-pharmacological methods.

Mindfulness-based treatment for smoking cessation: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of a mindfulness-based treatment (MBT) for smoking cessation or reduction and compare it with that of cognitive behavioral therapy (CBT). METHODS: This was a single-center randomized controlled clinical trial including 113 patients divided into two groups: MBT (n = 54) and CBT (n = 59). The interventions comprised eight 90-min sessions. The primary outcome was smoking cessation at 16 weeks after program initiation. Secondary outcomes included reduction in the mean number of cigarettes smoked/day at 16 weeks after treatment initiation, as well as smoking cessation and reduction in the number of cigarettes smoked/day at the last program session. Participants had to attend ≥ 50% of the sessions to be included in the primary outcome analysis. An intention-to-treat analysis was also performed. RESULTS: There was no difference between the groups regarding the primary outcome (30.4% in the MBT group vs. 31.6% in the CBT group, p = 0.68) or immediate abstinence rates (47.8% in the MBT group vs. 36.8% in the CBT group, p = 0.47). Both treatments were equally effective in reducing the number of cigarettes smoked/day at the last program session (a reduction of 93.33% [0-100%] in the MBT group and of 70% [33.3-100%] in the CBT group, p = 0.92) and at 16 weeks after program initiation (a reduction of 57.1% [0-100%] in the MBT group and of 70% [25-100%] in the CBT group, p = 0.49). CONCLUSIONS: MBT appears to be as effective as CBT for smoking cessation or reduction and can be an option for the treatment of tobacco use disorders in Brazil (Brazilian Registry of Clinical Trials identifier: RBR-3w2scz [http://www.ensaiosclinicos.gov.br]).

Yeast-based high-throughput screens for discovery of kinase inhibitors for neglected diseases.

The discovery and development of a new drug is a complex, time consuming and costly process that typically takes over 10 years and costs around 1 billion dollars from bench to market. This scenario makes the discovery of novel drugs targeting neglected tropical diseases (NTDs), which afflict in particular people in low-income countries, prohibitive. Despite the intensive use of High-Throughput Screening (HTS) in the past decades, the speed with which new drugs come to the market has remained constant, generating doubts about the efficacy of this approach. Here we review a few of the yeast-based high-throughput approaches that can work synergistically with parasite-based, in vitro, or in silico methods to identify and optimize novel antiparasitic compounds. These yeast-based methods range from HTP screens to identify novel hits against promising parasite kinase targets to the identification of potential antiparasitic kinase inhibitors extracted from databases of yeast chemical genetic screens.

Artificial Intelligence Applied to the Rapid Identification of New Antimalarial Candidates with Dual-Stage Activity.

Increasing reports of multidrug-resistant malaria parasites urge the discovery of new effective drugs with different chemical scaffolds. Protein kinases play a key role in many cellular processes such as signal transduction and cell division, making them interesting targets in many diseases. Protein kinase 7 (PK7) is an orphan kinase from the Plasmodium genus, essential for the sporogonic cycle of these parasites. Here, we applied a robust and integrative artificial intelligence-assisted virtual-screening (VS) approach using shape-based and machine learning models to identify new potential PK7 inhibitors with in vitro antiplasmodial activity. Eight virtual hits were experimentally evaluated, and compound LabMol-167 inhibited ookinete conversion of Plasmodium berghei and blood stages of Plasmodium falciparum at nanomolar concentrations with low cytotoxicity in mammalian cells. As PK7 does not have an essential role in the Plasmodium blood stage and our virtual screening strategy aimed for both PK7 and blood-stage inhibition, we conducted an in silico target fishing approach and propose that this compound might also inhibit P. falciparum PK5, acting as a possible dual-target inhibitor. Finally, docking studies of LabMol-167 with P. falciparum PK7 and PK5 proteins highlighted key interactions for further hit-to lead optimization.

Mindfulness-based treatment for smoking cessation: a randomized controlled trial / Tratamento baseado em atenção plena (mindfulness) para cessação do tabagismo: ensaio clínico controlado randomizado

ABSTRACT Objective: To evaluate the efficacy of a mindfulness-based treatment (MBT) for smoking cessation or reduction and compare it with that of cognitive behavioral therapy (CBT). Methods: This was a single-center randomized controlled clinical trial including 113 patients divided into two groups: MBT (n = 54) and CBT (n = 59). The interventions comprised eight 90-min sessions. The primary outcome was smoking cessation at 16 weeks after program initiation. Secondary outcomes included reduction in the mean number of cigarettes smoked/day at 16 weeks after treatment initiation, as well as smoking cessation and reduction in the number of cigarettes smoked/day at the last program session. Participants had to attend ≥ 50% of the sessions to be included in the primary outcome analysis. An intention-to-treat analysis was also performed. Results: There was no difference between the groups regarding the primary outcome (30.4% in the MBT group vs. 31.6% in the CBT group, p = 0.68) or immediate abstinence rates (47.8% in the MBT group vs. 36.8% in the CBT group, p = 0.47). Both treatments were equally effective in reducing the number of cigarettes smoked/day at the last program session (a reduction of 93.33% [0-100%] in the MBT group and of 70% [33.3-100%] in the CBT group, p = 0.92) and at 16 weeks after program initiation (a reduction of 57.1% [0-100%] in the MBT group and of 70% [25-100%] in the CBT group, p = 0.49). Conclusions: MBT appears to be as effective as CBT for smoking cessation or reduction and can be an option for the treatment of tobacco use disorders in Brazil (Brazilian Registry of Clinical Trials identifier: RBR-3w2scz [http://www.ensaiosclinicos.gov.br])

RESUMO Objetivo: Avaliar a eficácia de um mindfulness treatment (MT, tratamento baseado em atenção plena) para a cessação ou redução do tabagismo e compará-la à da terapia cognitivo-comportamental (TCC). Métodos: Ensaio clínico controlado randomizado realizado em um único centro, com 113 pacientes divididos em dois grupos: MT (n = 54) e TCC (n = 59). As intervenções consistiram em oito sessões de 90 min cada. O desfecho primário foi a cessação do tabagismo 16 semanas após o início do programa. Os desfechos secundários foram a redução da média de cigarros fumados/dia em 16 semanas após o início do programa, bem como a cessação do tabagismo e redução do número de cigarros fumados/dia na última sessão do programa. Os participantes deveriam comparecer a ≥ 50% das sessões para que fossem incluídos na análise do desfecho primário. Foi também realizada uma análise por intenção de tratamento. Resultados: Não houve diferença entre os grupos quanto ao desfecho primário (30,4% no grupo MT vs. 31,6% no grupo TCC, p = 0,68) ou às taxas de abstinência imediata (47,8% no grupo MT vs. 36,8% no grupo TCC, p = 0,47). Ambos os tratamentos foram igualmente eficazes na redução do número de cigarros fumados/dia na última sessão do programa [redução de 93,33% (0-100%) no grupo MT e de 70% (33,3-100%) no grupo TCC, p = 0,92] e em 16 semanas após o início do programa [redução de 57,1% (0-100%) no grupo MT e de 70% (25-100%) no grupo TCC, p = 0,49]. Conclusões: A MT parece ser tão eficaz quanto a TCC para a cessação ou redução do tabagismo e pode ser uma opção para o tratamento do tabagismo no Brasil. [Registro Brasileiro de Ensaios Clínicos - ReBEC; número de identificação: RBR-3w2scz (http://www.ensaiosclinicos.gov.br)]

Importância dos aspectos imaginológicos no plano de tratamento da displasia óssea florida: relato de caso / Importance of imaginological aspects in the florid osseous Dysplasia treatment plan: case report

A displasia óssea florida (DOFL) é uma lesão fibro-óssea relativamente incomum dos maxilares, que acomete, principalmente, mulheres melanodermas de meia idade e geralmente é diagnosticada em radiografias de rotina. O presente trabalho tem como objetivo relatar o caso de uma paciente de 50 anos de idade, melanoderma, encaminhada ao Curso de Odontologia da Universidade Federal do Ceará para avaliação imaginológica. Clinicamente, não foi observada nenhuma alteração de volume de estruturas faciais ou intraorais. A radiografia panorâmica evidenciou imagens radiopacas circunscritas por halos radiolúcidos, localizadas bilateralmente em região edêntula de corpo mandibular, sugestivas de DOFL. Na tomografia computadorizada de feixe cônico (TCFC), observaram se áreas hiperdensas em regiões mandibulares edêntulas, sem expansão de corticais ósseas vestibulares e linguais, e recobertas por fina espessura de tecido ósseo, típicos da displasia. Diante do diagnóstico clínico-imaginológico de DOFL, a paciente foi encaminhada para tratamento odontológico multidisciplinar. Por meio da TCFC, foi possível se estabelecer um plano de tratamento que consistiu em procedimentos minimamente intervencionistas, considerando os aspectos clínicos e imaginológicos das lesões observadas. Em sumário, o presente trabalho reforça a importância do exame clínico meticuloso aliado à avaliação por meio de TCFC, com fins de embasar um plano de tratamento adequado em casos de DOFL assintomáticos... (AU)

Florid osseous dysplasia (FOD) is a fibrous lesion relatively uncommon of maxillary bones, mainly affects middle-age black women and generally is diagnosed on routine radiographs. This paper aims to report a case of black woman, aged 50 years, referred to Dentistry Faculty of Federal University of Ceará for imaging evaluation. Clinically, there were no facial or intraoral structures alterations. Panoramic radiography showed radiopaque images circumscribed by radiolucent halos, located bilaterally in the edentulous mandibular body region suggestive of FOD. Cone beam computed tomography (CBCT) showed hyperdense areas in edentulous mandibular regions, with no expansion of buccal and lingual cortical bone, and covered by fine thickness of bone tissue, characteristic of FOD. After the clinical-imaging diagnosis of FOD, the patient was referred for multidisciplinary dental treatment. Through the CBCT, it was possible to establish a treatment plan that consisted of minimally interventional procedures considering the clinical and imaging limits of the observed lesions. In summary, the present case emphasizes a meticulous clinical examination along with an evaluation by means of CBCT allowing an adequate treatment plan for asymptomatic FOD... (AU)

Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed. Previously, we showed a hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, we provide molecular evidence that HBO targets brain endothelial cells by decreasing their activation and inhibits parasite and leukocyte accumulation, thus improving cerebral microcirculatory blood flow. HBO treatment increased the expression of aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), an oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 expression and kynurenine levels. Moreover, ablation of HIF-1α expression in endothelial cells in mice conferred protection against CM and improved survival. We propose that HBO should be pursued as an adjunctive therapy in CM patients to prolong survival and diminish deleterious proinflammatory reaction. Furthermore, our data support the use of HBO in therapeutic strategies to improve outcomes of non-CM disorders affecting the brain.-Bastos, M. F., Kayano, A. C. A. V., Silva-Filho, J. L., Dos-Santos, J. C. K., Judice, C., Blanco, Y. C., Shryock, N., Sercundes, M. K., Ortolan, L. S., Francelin, C., Leite, J. A., Oliveira, R., Elias, R. M., Câmara, N. O. S., Lopes, S. C. P., Albrecht, L., Farias, A. S., Vicente, C. P., Werneck, C. C., Giorgio, S., Verinaud, L., Epiphanio, S., Marinho, C. R. F., Lalwani, P., Amino, R., Aliberti, J., Costa, F. T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

Pathophysiological Mechanisms in Gaseous Therapies for Severe Malaria.

Over 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high, at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patient clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO), and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate the host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies.

Expressed sequence tags in venomous tissue of Scorpaena plumieri (Scorpaeniformes: Scorpaenidae)

Species of the family Scorpaenidae are responsible for accidents and sporadic casualties by the shore they inhabit. The species Scorpaena plumieri from this family populate the Northeastern and Eastern coast of Brazil causing human envenomation characterized by local and systemic symptoms. In experimental animals the venom induces cardiotoxic, hypotensive, and airway respiratory effects. As first step to identify the venom components we isolated gland mRNA to produce a cDNA library from the fish gland. This report describes the partial sequencing of 356 gland transcripts from S. plumieri. BLAST analysis of transcripts showed that 30% were unknown sequences, 17% hypothetical proteins, 17% related to metabolic enzymes, 14% belonged to signal transducing functions and the remaining groups (7-8%) composed by gene related with expressing proteins, regulatory proteins and structural proteins. A considerable number of these EST were not found in available databases suggesting the existence of new proteins and/or functions yet to be discovered. By screening the library with antibodies against a lectin fraction from S. plumieri venom we identified several clones whose DNA sequence showed similarities with lectins found in fish. In silico analysis of these clones confirm the identity of these molecules in the venom gland of S. plumieri. .

Espécies da família Scorpaenidae são responsáveis por acidentes e mortes esporádicas ao longo da costa que habitam. A espécie Scorpaena plumieri desta família povoam a costa Leste e Nordeste do Brasil, causando envenenamento humano caracterizado por sintomas locais e sistêmicos. Em modelos experimentais animais a peçonha induz cardiotoxicidade, efeitos hipotensivos e alterações nas vias aéreas respiratórias. Como primeiro passo para identificar os componentes da peçonha foram isolados os mRNA das glândulas do peixe para produzir uma biblioteca de cDNAs. Esse artigo descreve o sequenciamento parcial de 356 transcritos das glândulas de S. plumieri. Análises em bancos de dados (BLAST) dos transcritos demonstraram que 30% eram sequências desconhecidas, 17% proteínas hipotéticas, 17% relacionadas às enzimas do metabolismo, 14% pertenciam a funções de transdução de sinais e os demais grupos (7-8%) formados por genes relacionados com a expressão de proteínas, proteínas regulatórias e estruturais. Um número considerável destes EST não foi encontrado em bases de dados disponíveis, sugerindo a existência de novas proteínas e/ou funções ainda a serem descobertas. Ao fazer um barrido da biblioteca com anticorpos produzidos contra uma fração das lectinas do veneno de S. plumieri, identificamos vários clones, cuja sequência de DNA mostram semelhanças com lectinas encontradas em peixes. A análise in silico destes clones confirmam a identidade destas moléculas na glândula de peçonha de S. plumieri.

Effects of mepivacaine 2% with epinephrine in the cardiovascular activity of patients undergoing third molar surgery: a prospective clinical study.

BACKGROUND: Cardiovascular effects of epinephrine, especially on blood pressure (BP) and heart rate (HR), have been well documented. When present in dental local anesthetic solutions, epinephrine concentration ranges from 5 to 20 µg/mL. Doses less than 200 µg are recommended to be clinically safe. OBJECTIVES: This study investigated the effects of the anesthetic solution of mepivacaine (2%) with epinephrine (10 µg/mL) in cardiovascular activity (HR and BP). METHODS: Twenty-six patients underwent outpatient surgery for the removal of 2 unilateral (group I, n = 15) or 4 (group II, n = 11) third molars in a single session, being injected 5.4 and 10.8 mL of anesthetic solution, equivalent to 54 and 108 µg of epinephrine, respectively. The cardiovascular activity was monitored by cardioscope during the experimental period of 2 hours. Heart rate and BP were measured at the intervals of 0, 5, 10, 15, 20, 30, 40, 60, 90, and 120 minutes after anesthetic injection. RESULTS: After application of 2-way analysis of variance test, comparison between groups was not statistically significant for HR (P = 0.1388), systolic BP (P = 0.0228), and diastolic BP (P = 0.9846). However, patients from group II presented significantly greater sway in HR (P < 0.0001), systolic BP (P = 0.0169), and diastolic BP (P < 0.0001) in the course of 2 hours. CONCLUSIONS: Blood pressure did not present significant alterations after a local injection of 54 or 108 µg of epinephrine during surgery to remove 2 or 4 third molars. Although without significance, HR was more elevated in the 108-µg dose of epinephrine during the removal of 4 third molars.

Amazonian plant natural products: perspectives for discovery of new antimalarial drug leads.

Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cause severe manifestations and death; hence there is a need for P. vivax-directed research. Plants used in traditional medicine, namely Artemisia annua and Cinchona spp. are the sources of the antimalarial natural products artemisinin and quinine, respectively. Based on these compounds, semi-synthetic artemisinin-derivatives and synthetic quinoline antimalarials have been developed and are the most important drugs in the current therapeutic arsenal for combating malaria. In the Amazon region, where P. vivax predominates, there is a local tradition of using plant-derived preparations to treat malaria. Here, we review the current P. falciparum and P. vivax drug-sensitivity assays, focusing on challenges and perspectives of drug discovery for P. vivax, including tests against hypnozoites. We also present the latest findings of our group and others on the antiplasmodial and antimalarial chemical components from Amazonian plants that may be potential drug leads against malaria.

In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa.

BACKGROUND: To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. METHODS: Crude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7) and -resistant (S20) strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. RESULTS: At non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. CONCLUSIONS: The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.