Development and validation of a multi-substance method for routine analysis of pesticides in post-mortem samples by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry.

Pesticides play an important role in forensic toxicology and are usually classified as a single class of chemicals. Despite their commonly perceived unity, pesticides encompass a spectrum of compounds, including organophosphates, carbamates, pyrethroids or organochlorines, among others, each with varying degrees of toxicity. Pesticide analysis in post-mortem samples can be difficult due to the complexity of the samples and to the high toxicity of these compounds. The aim of this study was to develop and validate an easy to use, sensitive, and robust method, using ultra-performance liquid chromatography-tandem mass spectrometry to be incorporated in the routine flow for pesticide analysis in post-mortem blood samples. Described herein is a streamlined, expeditious, yet highly efficient method facilitating the screening, qualitative assessment, and quantitative confirmation of 15 pesticides, including acetamiprid, azinphos-ethyl, bendiocarb, carbofuran, chlorfenvinphos, dimethoate, imidaclopride, malathion, methiocarb, methomyl, parathion, pirimicarb, strychnine, tetrachlorvinphos, and thiacloprid in post-mortem blood, recognizing the pivotal role blood plays in forensic investigations. The developed method was linear from 10 to 200 ng/mL; limits of detection were between 1 and 10 ng/mL, depending on the compound; it was successfully evaluated a dilution ratio of 1-2, 5 and 10; and 8 substances showed maximum stability for the time interval studied. This UHPLC-MS/MS method is useful and a powerful tool in a toxicology lab because it is fast, simple, effective, and trustworthy. The results of this validation highlight the robustness of the analytical method, providing a valuable tool for the accurate and sensitive detection of pesticides in post-mortem blood. Poised for routine implementation, this method has already found success in suspected intoxication cases, promising to elevate the standards of forensic pesticide analysis.

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve.

Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8 + T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

Addressing the Relationship Between Testosterone Levels and Urethral Stricture: A Case-Control Study.

PURPOSE: Hypoandrogenism may have an association with urethral stricture. This study aimed to identify and quantify the association between testosterone levels and urethral stricture. MATERIALS AND METHODS: A case-control study was conducted from January 2019 to January 2021. The case group included patients diagnosed with anterior urethral stricture who visited our urethral office of the urology department, while the control group included patients who visited our practice due to clinical conditions unrelated to voiding. In both groups, a 10 cc blood sample collection was scheduled between 7:30 and 9:30 a.m. The outcome was case/control status. The exposure variables were total testosterone, free testosterone, bioavailable testosterone, and hypoandrogenism (total testosterone < 300 ng/dL). The adjusted ORs were calculated for each exposure. Age, body mass index, hypertension, diabetes, smoking, and thyroxine levels were considered possible confounding factors. RESULTS: A total of 149 cases (mean age 59.5) were compared to 67 controls (64.3). Urethral stricture cases showed significantly lower mean total testosterone than controls (394 ng/dL vs 488 ng/dL). Similarly, the hypoandrogenism rate was significantly higher in the urethral stricture group (26% vs 7.5%). Each 100 unit increase in total testosterone was related to a 34% decrease in the odds of urethral stricture (adjusted OR 0.66, 95% CI: 0.51-0.86). Similarly, each increase of 1 unit of free testosterone and 10 units of bioavailable testosterone was associated with a decrease of 18% and 10%, respectively. A strong direct relationship was observed between hypoandrogenism and urethral stricture (adjusted OR 4.01, 95% CI: 1.37-11.7). CONCLUSIONS: Our study demonstrates an independent association between hypoandrogenism and anterior urethral stricture.

Meningitis due to Streptococcus suis in Two Patients with Occupational Exposure from Northeastern Brazil.

Streptococcus suis is an emerging zoonotic agent that causes bacterial meningitis. S. suis is an encapsulated Gram-positive, facultative anaerobic bacterium. This infection usually manifests in humans as meningitis, endocarditis, septicemia, and/or arthritis. The primary groups at risk for S. suis infection are individuals occupationally exposed to pigs and/or pork, for example, farmers, butchers, and hunters. Herein, we report two cases of meningitis related to S. suis with occupational exposure from the Ceará state, northeastern Brazil.

Mixed-realism simulation of adverse event disclosure: an educational methodology and assessment instrument.

INTRODUCTION: Physicians have an ethical duty to disclose adverse events to patients or families. Various strategies have been reported for teaching disclosure, but no instruments have been shown to be reliable for assessing them.The aims of this study were to report a structured method for teaching adverse event disclosure using mixed-realism simulation, develop and begin to validate an instrument for assessing performance, and describe the disclosure practice of anesthesiology trainees. METHODS: Forty-two anesthesiology trainees participated in a 2-part exercise with mixed-realism simulation. The first part took place using a mannequin patient in a simulated operating room where trainees became enmeshed in a clinical episode that led to an adverse event and the second part in a simulated postoperative care unit where the learner is asked to disclose to a standardized patient who systematically moves through epochs of grief response. Two raters scored subjects using an assessment instrument we developed that combines a 4-element behaviorally anchored rating scale (BARS) and a 5-stage objective rating scale. RESULTS: The performance scores for elements within the BARS and the 5-stage instrument showed excellent interrater reliability (Cohen's κ = 0.7), appropriate range (mean range for BARS, 4.20-4.47; mean range for 5-stage instrument, 3.73-4.46), and high internal consistency (P < 0.05). CONCLUSIONS: We have demonstrated a comprehensive methodology using a mixed-realism simulation that engages learners in an adverse event and allows them to practice disclosure to a structured range of patient responses. We have developed a reliable 2-part instrument with strong psychometric properties for assessing disclosure performance.

O oleo essencial de Lippia gracilis Schauer, Verbenaceae, em ratos diabeticos / The essential oil from Lippia gracilis Schauer, Verbenaceae, in diabetic rats

O óleo essencial das folhas de Lippia gracilis Schauer, Verbenaceae, foi examinado por CG e CG-MS. Quinze constituintes foram identificados, onde o carvacrol, p-cimeno e o γ-terpineno foram as substâncias majoritárias. No estudo in vitro, a solução a 5 por cento do óleo de L. gracilis Schauer apresentou atividade antibacteriana para Staphylococcus aureus isolado de úlcera infectada de paciente diabético. O estudo avaliou a atividade antibacteriana da solução a 5 por cento do óleo de L. gracilis Schauer em modelo experimental em diabetes utilizando ratos albinos Wistar machos com membro pélvico infectado com cepa de Staphylococcus aureus. No experimento foram utilizados 28 ratos Wistar distribuídos em quatro grupos (G1-branco, G2-controle negativo, G3-controle positivo, G4-teste) de sete ratos. Quando comparado o grupo G4 com G3, observou-se que a solução a 5 por cento promoveu uma redução nas CFU/mL após 24h da administração do inóculo (S.aureus sem L. gracilis Schauer 10(8) ± 313 versus S.aureus com L. gracilis Schauer 13,28 ± 4,03). Os resultados foram expressos através do cálculo da média±EPM) e análise de variança (ANOVA). A diferença entre a concentração inibitória mínima no estudo in vitro foi determinada pelo teste Turkey (p<0.05). O teste Newman-Keuls com nível de significância (p<0.05) foi utilizado para o cálculo dos resultados obtidos no experimento in vivo. A solução a 5 por cento do óleo essencial de Lippia gracilis Schauer apresentou boa atividade antibacteriana tanto no estudo in vivo como no in vitro.

The essential oil from Lippia gracilis Schauer (Verbenaceae) leaves was examined by GC and GC-MS. Fifteen constituents were identified. Carvacrol, p-cymene and γ-terpinene were found to be the major components. In the in vitro study, 5 percent solution of the Lippia gracilis Schauer oil presented antibacterial activity against Staphylococcus aureus isolated from diabetic patients with infected ulcers. The study evaluated the antibacterial activity of the 5 percent solution of the Lippia gracilis Schauer oil on the experimental model of diabetic adult male albino Wistar rats with leaft pelvic limb infected by Staphylococcus aureus strain. In this experiment, 28 diabetic Wistar rats were used, randomly distributed in four different groups of seven rats, (G1-white; G2-negative control; G3-positive control and G4-test). When comparing group G4 with G3, it was observed that the 5 percent solution presented a reduced CFU/mL level showing the antibacterial effect of the oil 24 hours after the administration of the inoculum (S .aureus without Lippia gracilis Schauer 108 ±313 versus S.aureus with Lippia gracilis Schauer 13.28±4.03). The results were expressed as mean±S.E.M. One-way analysis of the variance (ANOVA) was used. The differences between the minimum inhibitory concentration in vitro test were determined by the Tukey test (p<0.05). The Newman-Keuls test with level of significance (p<0.05) was used to measure the results in vivo. The findings have shown that 5 percent solution of the Lippia gracilis Schauer oil presented antibacterial activity in vitro and in vivo.

Relaxant effects of the essential oil of Eucalyptus tereticornis and its main constituent 1,8-cineole on guinea-pig tracheal smooth muscle.

The effects of the essential oil of Eucalyptus tereticornis Sm. (EOET) on guinea-pig tracheal smooth muscle were investigated. EOET (10 - 1000 microg/mL) relaxed the tracheal basal tonus with an EC (50) value of 125.3 [52.2 - 300.9] microg/mL. Its maximal relaxation (40 +/- 6 %) was significantly lower than that evoked by aminophylline (209 +/- 34 %). The K (+)-(60 mM)-induced contractions were significantly reduced by both EOET (200 - 1000 microg/mL) and its main constituent 1,8-cineole (600 - 1000 microg/mL). Acetylcholine (1 microgM)-induced contractions were significantly enhanced by 1,8-cineole (10 - 1000 microg/mL). However, they were significantly enhanced and reduced by lower (200 - 400 microg/mL) and higher (800 - 1000 microg/mL) concentrations of EOET, respectively. Electrical field stimulation-induced contractions were significantly increased by EOET (100 - 600 microg/mL). In conclusion, EOET produces myorelaxant effects on guinea-pig isolated trachea, an effect that seems to result from a complex interaction between its monoterpenoid constituents.

Relaxant effects of the essential oil of Ocimum gratissimum on isolated ileum of the guinea pig.

The effects of the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) on guinea pig ileum were studied. EOOG (0.1-1000 microg/ml) reversibly and concentration-dependently relaxed the basal tone of the ileum and reversed the tonic contractions induced by 60 mM KCl and 10 microM acetylcholine, with IC(50) values of 23.8+/-5.2, 18.6+/-4.0 and 70.0+/-4.6 microg/ml, respectively. Our results show that EOOG exerts relaxant effects on intestinal smooth muscle, consistent with the popular use of the plant to treat gastrointestinal disorders.

Dermatite de contato por plantas (DCP) / Plant contact dermatitis (PCD)

Os autores fazem s1ntese sobre o tema dermatite de contato por plantas, mostrando a importância desse assunto para os dermatologistas, relatando conhecimentos existentes na literatura médica, ao mesmo tempo em que correlacionam esses estudos com os conhecimentos botânicos e químicos de muitas das plantas brasileiras,especialmente nordestinas, que possuem composiçäo química e similar àquelas bem estudadas ou conhecidas como causadoras de dermatites alérgicas, irritativas, fototóxicas, fotoalérgiccas ou de outras reaçöes na pele. Discutem diagnóstico, sugerindo nomes de substâncias que podem ser empregadas em bateria para teste decontato, bem como o valor de possíveis testes positivos, de acordo com o quadro clínico. Também säo sugeridas medidas terapêuticas e preventivas

Living pharmacies

After a short explanation of WHO recommendations and public health level in the Northeast of Brazil, a description of a social pharmaceutical assistance project named "Living pharmacies" is presented. The project covers the use of medicinal plants selected by their efficacy and low toxicity, whose information and seedlings are transferred to the communities. Comments on the literature of local medicinal plants and a list of the main practically validated local plants are included.

Plantas medicinais: guia de seleçäo e emprego de plantas medicinais de açäo cocmprovada usadas no nordeste do Brasil: volume 1; parte geral / Medical plants: guide of selection and use of medical plants from northeast of the Brazil

Apresenta cinco conjuntos de informaçöes que abrangem a seleçäo de plantas a partir da informaçäo popular regional, a preparaçäo de plantas secas ou drogas vegetais e suas formas de utilizaçäo, os riscos do uso indiscriminado de plantas medicinais, as plantas medicinais perigosas e tabelas referentes as principais plantas usadas como medicinais no Nordeste

Avaliaçäo da toxicidade de extratos de plantas medicinais através de bioensaio com Artemia salina Leach / Toxicity evaluation of medicinal plant extracts by brine shrimp bioassay

Este trabalho visa avaliar a toxicidade dos extratos de nove plantas medicinais que apresentam atividade antibiótica e que säo consumidas ampla e indiscriminadamente pela populaçäo (Lippia didoides, Lippia gracillis, Stenocalyx michelli, Punica granatum, Mimosa hostilis, Psidium guajava, Ccombretum leprosum, Mentha cf. rotundifolia e Coleus amboinicus). Para tanto, optou-se pelo uso de um bioensaio que utiliza um microcrustáceo (Artemia salina Leach) como organismo-teste. Cada extrato de planta (aquoso, acetônico e hidroalcoólico) foi testado na concentraçäo inibitória mínima. Os resultados mostraram que o extrato aquoso de Punica granatum, Stenocalyx michelli e Psidium guajava apresentaram uma taxa de sobrevivência de 92, 79 e 91%, respectivamente; o extrato acetônico de Stenocalyx michelli e Combretum leprosum, uma taxa de sobrevivência de 81 e 96%, respectivamente, e o extrato hidroalcoólico de Combretum leprosum uma taxa de sobrevivyencia de 73%. Os outros extratos testado näo apresentaram sobreviventes. Com esses resultados chegou-se a conclusäo de que, entre dezoito extratos diferentes de plantas, somente seis extratos näo apresentaram toxicidade chegou-se a conclusäo de que, entre dezoito extratos diferentes de plantas, somente seis extratos näo apresentaram toxicidade a Artemia salina, o que sugere que as concentraçöes testadas (CIMs) estavam abaixo da LC50 de cada extrato

Contribuição ao conhecimento químico de plantas do nordeste - Lippia sidoides Cham

A new naphthoquinoid identified as 6-oxo-3, 4, 4a, 5-tetrahydroxy-2, 2-dimethylnaphtho-1, 2-pirane (6) has been isolated from an antibacterial, methanolic extract of leaves and branches of Lippia sidoides cham. Beside to the new quinone, five other know substances were isolated, and isocatalponol. The following fatty acids were also identified: palmitic, stearic, behenic, arachidic and lignoceric.

Um novo na ftoquinoide identificado como 6-oxo-3, 4, 4a, 5 -tetrahidro-3-hiroxi-2, 2-dimetilnafto-1, 2-pirano (6) foi isolado dos extratos metanólicos do caule e das folhas de Lippia sidoides Cham.. Ao lado da nova quinona (6) foram isoladas e identificadas outras substâncias conhecidas, tais como: ácido vanílico, carvacrol, 6, 7-dimetoxi-4', 5-dihidroxiflavona, lapachenol e isocatalponol. Foram ainda identificados os seguintes ácidos graxos: palmitico estéarico, araquidico, behênico e lignocérico.

Avaliaçäo da atividade moluscicida de 32 plantas do Nordeste brasileiro / Avaliation of malluscocidal activity from 32 native plants of the Norhteast of Brazil

Com vista à descoberta de novos agentes moluscicidas naturais, 93 preparaçöes obtidas de 32 diferentes plantas da flora do nordeste do Brasil foram submetidas a teste frente a espécimes adultos de Biomphalaria glabrata. Os testes foram feitos com extratos-hidroalcóolicos (privados do ácool) e hidrolatos (água destilada na obtençäo de óleo essencial por arraste de vapor), em várias concentraçöes, observando-se os caramujos durante 24 horas. Os resultados säo apresentados em três tabelas. Mostraram-se ativas 45 preparaçöes, sendo 36% dos extratos e 25,7% dos hidrolatos. Entre as plantas ativas exibiram maior açäo moluscicida Astronium urundeuva Engl. (Anacardiaceae), Agonandra brasiliensis Miers. (opiliacea) e Croton mucrofolius Mull. Arg. Euphorbiaceae).

Alcalóides de Peschiera affinis (Muell. Arg) Miers (Apocynaceae)

The methanolic extracts of bark and woody roots from three especimens of Peschiera affinis (Apocynaceae) collected at different geographical sites (Fortaleza , Ubajara-CE e Cical-PI) afforded, after chromatographical separation, the following alkaloids: coronanidine, epiheyneanine, affinisine, vobasine, olivacine, voacangine, voacristine, iboxygaine and l9-hidroxi-ibogamine. The latter four substances were found previously in the genus Tabernanthe and Voacanga and are registered here for Peschiera affinis for the first time.

A vista da discordância dos dados registrados na literatura (Cava, 1964, 1968 ; Jerry, 1963 e Matos, 1976) quanto aos alcalóides de Peschierra affinis, retomou-se seu estudo com o objetivo desta espécie. Foram analisados amostras das cascas e do lenho das raízes de material coletado em locais diferentes em altitude, longitude e latitude. Foram identificados além de substâncias de natureza alifática (sitosterol,-amirina e lupenol). os seguintes alcalóides indólicos: coronaridina, voacangina, 20-epiheyneanina, voacristina, affinisina, vobasina, olivacina e uma mistura de 19-hidroxi-ibogamina e iboxigaína). Dentre estes, quatro são inéditos na espécie (voacangina, voacristina, 19-hidroxi-ibogaina e eboxigaína). Apenas pequenas diferenças foram observadas nos três materiais estudados, observando-se porém, acentuada diferença quando comparadas com os resultados obtidos no primeiro trabalho químico sobre os alcalóides desta espécie (Jerry, 1963).

Atividade moluscicida de óleos essenciais de plantas do nordeste brasileiro / Molluscacidal activity of essential oils from Brazilian Northeast plants

Os autores apresentam sua experiência sobre atividade moluscicida de hidrolatos de óleos essenciais de plantas do Nordeste Brasileiro e comentam os estudos pertinentes ao assunto sobre produtos naturais de vegetais superiores. Na 1ª abordagem foram testados 82 hidrolatos, sobressaindo-se doze plantas por sua considerável atividade moluscicida. Na 2ª e 3ª abordagens destacaram-se principalmente quatro espécies: Lippia aristata Schauer procedente de Ubajara-Ce. Lippia aff chamissonis D. Dietr. de Mossoró-RN, Piper sp (0292) de Grajaú-Ma. e Eucaliptus citriodora Hook coletada em Ubajara-Ce. Os hidrolatos das referidas plantas mostraram atividade moluscicida em baixas concentraçöes, contra Biomphalaria grabrata em vários estágios de desenvolvimento (desovas, recém-nascidos e adultos), conferindo-lhes potencialidade no combate à esquistossomose mansônica