Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3.

Hyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologically hypoxic, remains unclear. Here, we demonstrated that daily treatment with hyperbaric oxygen affects gut microbiome composition, worsening antibiotic-induced dysbiosis. Accordingly, HBO-treated mice were more susceptible to Clostridioides difficile infection (CDI), an enteric pathogen highly associated with antibiotic-induced colitis. These observations were closely linked with a decline in the level of microbiota-derived short-chain fatty acids (SCFAs). Butyrate, a SCFA produced primarily by anaerobic microbial species, mitigated HBO-induced susceptibility to CDI and increased epithelial barrier integrity by improving group 3 innate lymphoid cell (ILC3) responses. Mice displaying tissue-specific deletion of HIF-1 in RORγt-positive cells exhibited no protective effect of butyrate during CDI. In contrast, the reinforcement of HIF-1 signaling in RORγt-positive cells through the conditional deletion of VHL mitigated disease outcome, even after HBO therapy. Taken together, we conclude that HBO induces intestinal dysbiosis and impairs the production of SCFAs affecting the HIF-1α-IL-22 axis in ILC3 and worsening the response of mice to subsequent C. difficile infection.

Implications of the endocannabinoid system and the therapeutic action of cannabinoids in autism spectrum disorder: A literature review.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, onset in early childhood and associated with cognitive, social, behavioral, and sensory impairments. The pathophysiology is still unclear, and it is believed that genetic and environmental factors are fully capable of influencing ASD, especially cell signaling and microglial functions. Furthermore, the endocannabinoid system (ECS) participates in the modulation of various brain processes and is also involved in the pathophysiological mechanisms of this condition. Due to the health and quality of life impacts of autism for the patient and his/her family and the lack of effective medications, the literature has elucidated the possibility that Cannabis phytocannabinoids act favorably on ASD symptoms, probably through the modulation of neurotransmitters, in addition to endogenous ligands derived from arachidonic acid, metabolizing enzymes and even transporters of the membrane. These findings support the notion that there are links between key features of ASD and ECS due to the favorable actions of cannabidiol (CBD) and other cannabinoids on symptoms related to behavioral and cognitive disorders, as well as deficits in communication and social interaction, hyperactivity, anxiety and sleep disorders. Thus, phytocannabinoids emerge as therapeutic alternatives for ASD.

Turmeric supplementation with piperine is more effective than turmeric alone in attenuating oxidative stress and inflammation in hemodialysis patients: A randomized, double-blind clinical trial.

PURPOSE: Turmeric has renop rotective effects that can act to reduce oxidative stress and inflammation in hemodialysis (HD) patients. Piperine has been indicated as a bioavailability enhancer of turmeric and consequently of its biological effects. However, data on the efficacy of the turmeric/piperine combination in HD patients are limited. We aimed to verify whether turmeric supplementation in combination with piperine has a superior effect to turmeric alone in increasing antioxidant capacity and reducing oxidative stress and inflammation in HD patients. METHODS: This randomized, double-blind clinical trial was conducted in HD patients (age 20-75 years). Patients were supplemented with turmeric (3 g/day) or turmeric/piperine (3 g turmeric + 2 mg piperine/day) for 12 weeks. Malondialdehyde (MDA), antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), high-sensitivity C-reactive protein (hs-CRP), and ferritin were evaluated at baseline and the end of the study. RESULTS: There was a reduction in the MDA and ferritin levels in the turmeric/piperine group and in the comparison between groups at the end of the study [MDA: -0.08(-0.14/0.01) nmol/mL versus -0.003(-0.10/0.26) nmol/mL, p = 0.003; ferritin: -193.80 ±â€¯157.29 mg/mL versus 51.99 ±â€¯293.25 mg/mL, p = 0.018]. In addition, GPx activity reduced in the turmeric group (p = 0.029). No changes were observed for CAT, GR, and hs-CRP. CONCLUSION: Turmeric plus piperine was superior to turmeric alone in decreasing MDA and ferritin levels. The use of a combination of turmeric and piperine as a dietary intervention may be beneficial for modulating the status oxidative and inflammation in HD patients. BRAZILIAN REGISTRY OF CLINICAL TRIALS NUMBER: RBR-2t5zpd; Registration Date: May 2, 2018.

Ancient DNA at the edge of the world: Continental immigration and the persistence of Neolithic male lineages in Bronze Age Orkney.

Orkney was a major cultural center during the Neolithic, 3800 to 2500 BC. Farming flourished, permanent stone settlements and chambered tombs were constructed, and long-range contacts were sustained. From ∼3200 BC, the number, density, and extravagance of settlements increased, and new ceremonial monuments and ceramic styles, possibly originating in Orkney, spread across Britain and Ireland. By ∼2800 BC, this phenomenon was waning, although Neolithic traditions persisted to at least 2500 BC. Unlike elsewhere in Britain, there is little material evidence to suggest a Beaker presence, suggesting that Orkney may have developed along an insular trajectory during the second millennium BC. We tested this by comparing new genomic evidence from 22 Bronze Age and 3 Iron Age burials in northwest Orkney with Neolithic burials from across the archipelago. We identified signals of inward migration on a scale unsuspected from the archaeological record: As elsewhere in Bronze Age Britain, much of the population displayed significant genome-wide ancestry deriving ultimately from the Pontic-Caspian Steppe. However, uniquely in northern and central Europe, most of the male lineages were inherited from the local Neolithic. This suggests that some male descendants of Neolithic Orkney may have remained distinct well into the Bronze Age, although there are signs that this had dwindled by the Iron Age. Furthermore, although the majority of mitochondrial DNA lineages evidently arrived afresh with the Bronze Age, we also find evidence for continuity in the female line of descent from Mesolithic Britain into the Bronze Age and even to the present day.

Antioxidant and anti-inflammatory response to curcumin supplementation in hemodialysis patients: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND AND OBJECTIVES: Hemodialysis (HD) patients are vulnerable to malnutrition and cardiovascular complications due to many factors, including oxidative stress and inflammation. Curcumin supplementation is associated with attenuation of proinflammatory cytokines and increased activity of antioxidant enzymes, but its effects in HD patients are unknown. This study aimed to evaluate the effect of curcumin supplementation on oxidative stress and inflammation in HD patients. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 43 HD patients and divided them into two groups: supplemented with curcumin (1 g/day) or placebo (corn starch) for 12 weeks. Demographic information and blood samples were taken at the start and the end of the study to determine serum malondialdehyde (MDA) concentrations, antioxidant enzyme activity, and high-sensitivity C-reactive protein (hs-CRP). RESULTS: The curcumin group showed a significant increase in catalase activity [Δ = 1.13 ± 2.87 versus Δ = -1.08 ± 2.68; p = 0.048] and preserved glutathione peroxidase activity [Δ = -4.23 ± 11.50 versus Δ = -14.44 ± 13.96; p < 0.01] compared with the placebo group. However, no significant changes were found in MDA concentrations, glutathione reductase activity, and hs-CRP concentrations after the intervention. CONCLUSION: Curcumin supplementation for 12 weeks had potential effects on antioxidant response, but it was not enough to reduce oxidative stress markers and inflammation in HD patients. This trial was registered at EnsaiosClínicos.gov.br under registration number RBR-2t5zpd.

Anti-inflammatory activity of ayahuasca: therapeutical implications in neurological and psychiatric diseases.

Ayahuasca is a decoction with psychoactive properties, used for millennia for therapeutic and religious purposes by indigenous groups and the population of amazonian countries. As described in this narrative review, it is essentially constituted by ß-carbolines and tryptamines, and it has therapeutic effects on behavioral disorders due to the inhibition of the monoamine oxidase enzyme and the activation of 5-hydroxytryptamine receptors, demonstrated through preclinical and clinical studies. It was recently observed that the pharmacological response presented by ayahuasca is linked to its anti-inflammatory action, attributed mainly to dimethyltryptamines (N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine), which act as endogenous systemic regulators of inflammation and immune homeostasis, also through sigma-1 receptors. Therefore, since neuroinflammation is among the main pathophysiological mechanisms related to the development of neurological and psychiatric diseases, we suggest, based on the available evidence, that ayahuasca is a promising and very safe therapeutic strategy since extremely high doses are required to reach toxicity. However, even so, additional studies are needed to confirm such evidence, as well as the complete elucidation of the mechanisms involved.

Uso de la terapia floral y de la homeopatía / Use of flower therapy and homeopathy

Introducción: Los procedimientos de la Medicina Natural Tradicional tienen en común el objetivo de prevenir y tratar las enfermedades. Este tipo de medicina es una mezcla de todas aquellas artes curativas que han formado parte del patrimonio cultural de cada nación. Su empleo data desde los tiempos más remotos en los que el hombre buscaba remedio para sus males en la flora de su hábitat. Objetivo: Describir el uso de la terapia floral así como de los medicamentos homeopáticos. Método: Se realizó una revisión de la literatura disponible en formato digital. Para su elaboración se utilizaron los diferentes métodos teóricos como el análisis, la síntesis, la inducción y la deducción, y fueron consultadas las bases de datos nacionales como Scielo; así como los principales sistemas de indización, se revisó un total de 26 referencias, todas fueron incluidas. Los descriptores más empleados en la búsqueda fueron: flores; homeopatía; plantas medicinales; terapia. Resultados: La terapia floral se trata de una terapia medicamentosa pero no farmacológica y que brinda un conjunto de remedios vibracionales que no poseen principios activos ni químicos ni biológicos. Se la ha caracterizado como "holística", porque los remedios actúan sobre la totalidad del organismo. En cierto sentido toda intervención bioquímica es holística, pues el organismo es un sistema y, como ocurre con todo sistema, la modificación de una de sus partes constituyentes gravita sobre las restantes. La confección de un medicamento homeopático se realiza a través de sustancias que en una persona sana producen síntomas de las enfermedades a tratar. De manera inicial se toma una parte de la sustancia en su estado puro y se mezcla con 99 partes de disolvente (por lo general agua). Cnclusiones: Entre los elementos fundamentales de la Medicina Natural y Tradicional juega un papel importante la terapia floral y la homeopatía; puesto que estas son eficaces, económicas e inocuas que generalmente puede producir analgesia, mejoría o curación de diversas enfermedades. Se debe fomentar el uso de estas alternativas ya que son una forma de prevenir y mejorar a muchos pacientes.

Aplicación de la Medicina Natural y Tradicional en Odontología / Application of Natural and Traditional Medicine in Dentistry

Los procedimientos de la Medicina Natural Tradicional tienen en común el objetivo de prevenir y tratar las enfermedades. Este tipo de medicina es una mezcla de todas aquellas artes curativas que han formado parte del patrimonio cultural de cada nación. Su empleo data desde los tiempos más remotos en los que el hombre buscaba remedio para sus males en la flora de su hábitat. Con el objetivo de analizar las plantas medicinales de interés estomatológico, se realizó una consulta bibliográfica de 26 documentos en bibliotecas y portales digitales como Infomed, Pubmed y Scielo, haciéndose uso de la información más actualizada y relacionada con el tema. Se llegó a la conclusión de que las plantas medicinales tienen una aplicación terapéutica importante en la estomatología, lo que indica que se debe continuar perfeccionando la cultura sobre su empleo en esta ciencia.

[Professional practices in situations of violence in home care: an integrative review]. / Práticas profissionais em situações de violência na atenção domiciliar: revisão integrativa.

This article aims to describe the practices of health professionals in situations of violence in the provision of home care. It involved an integrative review of the literature conducted between December 2016 and December 2017 in the LILACS, BDENF and MEDLINE databases. The sample was composed of 15 articles, organized and characterized by author, publication journal, country, year, title, method, main idea, category and level of evidence. The violent situations found most often were abuse of elderly and children and domestic violence towards women and children. Different practices were adopted during violent situations against patients, like interventions, notifications, orientation, and professional qualification. Practices of health professionals in home care focuses on actions of patient care,seek to minimize the effects of violence.

Red light-emitting diode treatment improves tissue recovery in DSS-induced colitis in mice.

Inflammatory bowel diseases are debilitating illnesses characterized by severe inflammation of the gastrointestinal tract. Treatments currently available are expensive and ineffective. We here investigated the role of red-light emitting diode (LED) on dextran sodium sulfate (DSS)-induced colitis. DSS was added to the drinking water of male mice at days 0, 2, 4 and withdrawn at day 6. LED irradiation was performed daily for 90s from day 6 to 9 on the right and left sides of the ventral surface and beside the external anal region. LED treatment decreased the amount of crypt dysplasia/edema, inflammatory infiltrates and ulcers, attenuated apoptosis and increased proliferation of crypt cells. Also, LED treatment induced expression of annexin A1 in the damaged epithelium, preserved the organization of claudin-1 and skewed cytokine profiling towards a more anti-inflammatory status. Thus, LED treatment promotes structural protection and modulates the inflammatory response, constituting a potential non-invasive and low-cost combined therapy to help patients achieve disease remission.

Práticas profissionais em situações de violência na atenção domiciliar: revisão integrativa / Professional practices in situations of violence in home care: an integrative review

Resumo O objetivo deste artigo é descrever as práticas de profissionais de saúde em situações de violência nos cuidados da Atenção domiciliar. Trata-se de uma revisão integrativa da literatura realizada entre dezembro de 2016 e dezembro de 2017 nas bases de dados LILACS, BDENF e MEDLINE. A amostra foi composta por 15 artigos, organizados e caracterizados de acordo com autor, periódico de publicação, país, ano, título, método, ideia central, categoria e nível de evidência. As situações de violência mais encontradas foram abuso em idosos e crianças e violência doméstica em mulheres e crianças. Práticas distintas foram adotadas nas situações de violência contra os pacientes, como intervenções, notificações, orientação, e capacitação profissional. As práticas dos profissionais na atenção domiciliar focalizam ações de cuidado dos pacientes, buscando minimizar os efeitos da violência.

Abstract This article aims to describe the practices of health professionals in situations of violence in the provision of home care. It involved an integrative review of the literature conducted between December 2016 and December 2017 in the LILACS, BDENF and MEDLINE databases. The sample was composed of 15 articles, organized and characterized by author, publication journal, country, year, title, method, main idea, category and level of evidence. The violent situations found most often were abuse of elderly and children and domestic violence towards women and children. Different practices were adopted during violent situations against patients, like interventions, notifications, orientation, and professional qualification. Practices of health professionals in home care focuses on actions of patient care,seek to minimize the effects of violence.

Baru Almonds Increase the Activity of Glutathione Peroxidase in Overweight and Obese Women: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Obesity-induced inflammation is frequently associated with higher oxidative stress. In vitro and experimental studies have considered baru almonds (Dipteryx alata Vog) as a legume seed with high antioxidant capacity. The aim of this study was to evaluate whether baru almonds are capable of improving the inflammatory and antioxidant status in overweight and obese women. METHODS: In a parallel-arm, randomized placebo-controlled trial, 46 overweight and obese women (age: 40 ± 11 years; body mass index: 33.3 ± 4.3) were randomly assigned to receive advice to follow a normocaloric and isoenergetic diet with placebo (PLA, n = 22) or similar advice plus 20 g baru almonds (BARU, n = 24) for 8 wk. Malondialdehyde (MDA), adiponectin, tumor necrosis factor-α, interleukin-6, interleukin-10, antioxidant enzymes activities (catalase-CAT; glutathione peroxidase-GPx; superoxide dismutase-SOD), and minerals were analyzed in plasma samples. RESULTS: At baseline, groups were similar regarding the body composition, oxidative, and inflammatory parameters. The BARU group increased the activity of GPx (+0.08 U/mg, 95%CI + 0.05 to +0.12 vs. -0.07, 95%CI -0.12 to -0.03, p < 0.01) and plasma copper concentration (p = 0.037) when compared to the PLA group. No differences were observed between groups in CAT and SOD activity or MDA and cytokines concentrations. CONCLUSIONS: Baru almond supplementation increased the GPx activity in overweight and obese women.

Peri-personal space encoding in patients with disorders of consciousness and cognitive-motor dissociation.

Behavioral assessments of consciousness based on overt command following cannot differentiate patients with disorders of consciousness (DOC) from those who demonstrate a dissociation between intent/awareness and motor capacity: cognitive motor dissociation (CMD). We argue that delineation of peri-personal space (PPS) - the multisensory-motor space immediately surrounding the body - may differentiate these patients due to its central role in mediating human-environment interactions, and putatively in scaffolding a minimal form of selfhood. In Experiment 1, we determined a normative physiological index of PPS by recording electrophysiological (EEG) responses to tactile, auditory, or audio-tactile stimulation at different distances (5 vs. 75 cm) in healthy volunteers (N = 19). Contrasts between paired (AT) and summed (A + T) responses demonstrated multisensory supra-additivity when AT stimuli were presented near, i.e., within the PPS, and highlighted somatosensory-motor sensors as electrodes of interest. In Experiment 2, we recorded EEG in patients behaviorally diagnosed as DOC or putative CMD (N = 17, 30 sessions). The PPS-measure developed in Experiment 1 was analyzed in relation with both standard clinical diagnosis (i.e., Coma Recovery Scale; CRS-R) and a measure of neural complexity associated with consciousness. Results demonstrated a significant correlation between the PPS measure and neural complexity, but not with the CRS-R, highlighting the added value of the physiological recordings. Further, multisensory processing in PPS was preserved in putative CMD but not in DOC patients. Together, the findings suggest that indexing PPS allows differentiating between groups of patients whom both show overt motor impairments (DOC and CMD) but putatively distinct levels of awareness or motor intent.

The genomic history of the Iberian Peninsula over the past 8000 years.

We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula. We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming. We reveal sporadic contacts between Iberia and North Africa by ~2500 BCE and, by ~2000 BCE, the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with Steppe ancestry. We show that, in the Iron Age, Steppe ancestry had spread not only into Indo-European-speaking regions but also into non-Indo-European-speaking ones, and we reveal that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia. Additionally, we document how, beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean.

Terapias alternativas para o tratamento da estomatite por prótese total: modelo experimental in vivo em ratos / Alternative therapies for denture stomatitis treatment: in vivo experimental model in rats

A estomatite por prótese (EP) é uma condição multifatorial que acomete frequentemente usuários de prótese total e geralmente é relacionada com Candida albicans. Devido aos efeitos tóxicos da terapia antifúngica, novas terapias para EP são necessárias. Objetivos: O objetivo deste estudo foi avaliar a eficácia do extrato aquoso de Buchenavia tomentosa e bicarbonato de sódio frente a C. albicans em um modelo de EP em ratos. Material e Métodos: Um aparelho de resina acrílica simulando a base da prótese total foi fixado cobrindo o palato de 48 ratos machos seguido por indução da candidose. Os ratos foram divididos em 4 grupos (n=12): controle, bicarbonato de sódio, B. tomentosa e nistatina (controle positivo). Cada grupo foi subdividido de acordo com o período de tratamento; 24 horas (n=6) e 48 horas (n=6). Os animais foram sacrificados e os aparelhos foram removidos para contagem de C. albicans e análise por microscopia eletrônica de varredura. Resultados: Após 24 horas de tratamento, observou-se redução significativa da contagem de C. albicans tanto B. tomentosa quanto nistatina (nistatina x controle, p<0,01; B. tomentosa x controle, p=0,03). Os resultados foram confirmados pela análise histológica. Conclusão: Tanto o extrato aquoso de B. tomentosa e o bicarbonato de sódio foram capazes de reduzir significativamente as contagens de C. albicans em modelo experimental de EP (AU)

Background: Denture stomatitis (DS) is a multifactorial condition that commonly affects denture users and is mainly caused by Candida albicans. Due to the toxic effects of antifungal therapy, new therapies for DS are claimed. Objective: The aim of the study was to evaluate the efficacy of aqueous extract of Buchenavia tomentosa and sodium bicarbonate against C. albicans in a model of DS in rats. Material and Methods: An acrylic resin device simulating a denture base was fixed covering the palate of forty-eight male rats followed by candidiasis induction. Rats were divided into 4 groups (n = 12): Control, sodium bicarbonate, B. tomentosa and nystatin (positive control). Each group was subdivided according to the period of treatment; 24 h (n = 6) and 48 h (n = 6). Animals were sacrificed and had their devices removed for C. albicans counts and SEM analysis. The palate mucosa was removed and processed for histopathologic analysis. Results: After 24 h of treatment, both B. tomentosa and nystatin groups reduced significantly C. albicans counts when compared to control (nystatin x control, p < 0.01; B. tomentosa x control, p = 0.03). The results were confirmed by the histologic analysis. Conclusion: Both the aqueous extract of B. tomentosa and sodium bicarbonate was able to significantly decrease C. albicans counts in an experimental model of DS (AU)

A terapia fotodinâmica como benefício complementar na clínica odontológica / Photodynamic therapy as a complementary benefit in the dental clinic

Um dos grandes desafios do Cirurgião-Dentista é o controle microbiológico nas patologias dentárias. Independentemente da especialidade, a redução microbiana para o sucesso do tratamento é necessária. A terapia fotodinâmica vem sendo utilizada como coadjuvante ao tratamento tradicional, reduzindo significativamente a quantidade de microrganismos nos sítios-alvo e contribuindo para a solução de casos, principalmente na presença de infecções resistentes. Esta revisão de literatura tem como objetivo apresentar estudos laboratoriais e clínicos relacionados à terapia fotodinâmica em Periodontia, Endodontia e Estomatologia. Apesar da variedade de protocolos utilizados nas recentes pesquisas, a terapia fotodinâmica mostra-se promissora como coadjuvante ao tratamento convencional. Além disso, apresenta grande utilidade, fácil acessibilidade e baixo custo para o Cirurgião-Dentista frente a processos infecciosos em Odontologia.

One of the great challenges of the dentist is the microbiological control in dental pathologies. Regardless of specialty, microbial reduction for successful treatment is necessary. Photodynamic therapy has been used as an adjunct to traditional treatment, significantly reducing the amount of microorganisms in the target sites and contributing to the solution of cases, especially in the presence of resistant infections. This literature review aims to present laboratory and clinical studies related to photodynamic therapy in Periodontics, endodontics and Stomatology. Despite the variety of protocols used in recent research, photodynamic therapy is potentially used as an adjunct to conventional treatment. In addition, it is useful, easy to apply and with low cost to the dentist.

Laser treatment of recurrent herpes labialis: a literature review.

Recurrent herpes labialis is a worldwide life-long oral health problem that remains unsolved. It affects approximately one third of the world population and causes frequent pain and discomfort episodes, as well as social restriction due to its compromise of esthetic features. In addition, the available antiviral drugs have not been successful in completely eliminating the virus and its recurrence. Currently, different kinds of laser treatment and different protocols have been proposed for the management of recurrent herpes labialis. Therefore, the aim of the present article was to review the literature regarding the effects of laser irradiation on recurrent herpes labialis and to identify the indications and most successful clinical protocols. The literature was searched with the aim of identifying the effects on healing time, pain relief, duration of viral shedding, viral inactivation, and interval of recurrence. According to the literature, none of the laser treatment modalities is able to completely eliminate the virus and its recurrence. However, laser phototherapy appears to strongly decrease pain and the interval of recurrences without causing any side effects. Photodynamic therapy can be helpful in reducing viral titer in the vesicle phase, and high-power lasers may be useful to drain vesicles. The main advantages of the laser treatment appear to be the absence of side effects and drug interactions, which are especially helpful for older and immunocompromised patients. Although these results indicate a potential beneficial use for lasers in the management of recurrent herpes labialis, they are based on limited published clinical trials and case reports. The literature still lacks double-blind controlled clinical trials verifying these effects and such trials should be the focus of future research.

Avaliação da toxicidade aguda do extrato aquoso de Apeiba tibourbou Aubl (Tiliaceae), em camundongos e ratos / Assessment of acute toxicity of water extract from Apeiba tibourbou Aubl (Tiliaceae) in mice and rats

O teste de toxicidade aguda estima a dose letal mediana (DL50 ) e classifica os toxicantes quanto à periculosidade, inclusive para extratos de plantas. A espécie Apeiba tibourbou Aubl (Tiliaceae), conhecida como pau-de-jangada ou pente-de-macaco, é empregada popularmente como antirreumática, antiespasmódica e expectorante, embora seja desconhecida quanto aos seus efeitos tóxicos. Assim, o objetivo desta pesquisa foi investigar o potencial de toxicidade aguda do extrato aquoso de A. tibourbou (EAT), administrado por gavagem, em camundongos fêmeas e ratos fêmeas, seguindo as diretrizes OECD Guideline 423/2001 e o screening hipocrático. Os camundongos fêmeas foram divididos em três grupos de três animais cada (C1 – controle, água filtrada, 0,25 mL; C2 –300 mg/kg de EAT; e C3 – 2000 mg/kg de EAT). Os ratos fêmeas foram divididos em dois grupos de três animais cada (R1 – controle, água filtrada, 0,5 mL; e R2 – 2000 mg/kg de EAT). O grupo C2 consumiu 28% de água a mais que o grupo C1 (p < 0,05); o grupo C3 produziu 31% de excretas a mais que o grupo C1 (p < 0,0001); o grupo R2 reduziu o consumo de ração e a produção de excretas em 20% e 28% em relação ao grupo R1 (p < 0,05), respectivamente. No screening hipocrático, nenhuma alteração motora e/ou sensorial foi observada. Não houve morte nem estado moribundo de nenhum animal. Conclui-se que o EAT possui DL50 estimada maior que 2000 mg/kg (Classe 5 de toxicidade, segundo o Globally Harmonized System – GHS, ONU), demonstrando reduzido potencial de toxicidade aguda.

The acute toxicity test estimates the median lethal dose (LD50) against a given test organism and classifies toxic substances, including plant extracts, according to their intrinsic toxicity. Apeiba tibourbou Aubl (Tiliaceae), a tree known in Brazil as “raft-wood” or “monkey’s comb”, is popularly used as an antirheumatic, antispasmodic and expectorant agent, although its toxic effects are unknown. The objective of this research was therefore to investigate the potential acute toxicity to female mice and rats of a water extract of A. tibourbou leaves (WET), administered by gavage, following OECD Guideline 423/2001 and hippocratic screening. The female mice were divided into three groups of three animals each (C1 – control, given 0.25 mL filtered water; C2 – treated with 300 mg/kg WET; C3 – with 2000 mg/kg WET). The female rats were divided into two groups of three animals each (R1 – control, given 0.5 mL filtered water; R2 – 2000 mg/kg WET). Group C2 consumed 28% more water than group C1 (p < 0.05); group C3 produced 31% more excreta than group C1 (p < 0.0001); group R2 reduced food consumption and excretion by 20% and 28%, relative to group R1 (p < 0.05), respectively. During the Hippocratic screening, no motor and/or sensorial alterations were observed. Neither death nor symptoms of impending death were observed in any animals. It can be concluded that WET has an estimated LD50greater than 2000 mg/kg (Class 5 toxicity, according to the UN Globally Harmonized System – GHS), demonstrating low acute toxicity potential.

A new strategy based on SmRho protein loaded chitosan nanoparticles as a candidate oral vaccine against schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. METHODS AND FINDINGS: Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. CONCLUSIONS: Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis.