Antitussive, Expectorant and Antipyretic Effect of the Ethanolic Extract of the Leaves of Momordica charantia L.

The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.

Single-operator cholangioscopy unveiling a pinehole post-cholecystectomy biliary strictures.

77-year-old female with history of cholecystectomy was admitted at emergency department with fever and myalgia, without other complaints. Physical examination revealed fever, and laboratory tests indicated cholestasis (total bilirubin: 1.5xULN, glutamyltransferase: 20xULN, alkaline phosphatase: 5xULN). Computed Tomography revealed common bile duct (CBD) dilation (9mm), with suspected choledocholithiasis. Given the diagnosis of acute cholangitis, antibiotics were started and ERCP was performed. ERCP revealed a short CBD stenosis (< 2mm length), close to surgical clip, with upstream dilation of the CBD; an 8mm stone in the distal CBD was observed and successfully removed. As guidewire advancement failed after multiple attempts, a SpyGlass DS cholangioscopy was performed showing a fibrotic pinehole stenosis. Guidewire was passed through the stenosis under direct visualization, and an 80-mmx10mm fully covered metal stent deployed.

Phytochemical Characterization of Cannabis sativa L. Roots from Northeastern Brazil.

This article describes the phytochemical study of Cannabis sativa roots from northeastern Brazil. The dried plant material was pulverized and subjected to exhaustive maceration with ethanol at room temperature, obtaining the crude ethanolic extract (Cs-EEBR). The volatile compounds were analyzed by gas chromatography coupled with mass spectrometry (GC/MS), which allowed to identify 22 compounds by comparing the linear retention index (LRI), the similarity index (SI) and the fragmentation pattern of the constituents with the literature. By this technique the major compounds identified were: friedelan-3-one and ß-sitosterol. In addition, two fractions were obtained from Cs-EEBR by classical column chromatography and preparative thin layer chromatography. These fractions were analyzed by NMR and IR and together with the mass spectrometry data allowed to identify the compounds: epifriedelanol, friedelan-3-one, ß-sitosterol and stigmasterol. The study contributed to the phytochemical knowledge of Cannabis sativa, specifically the roots, as there are few reports on the chemical constituents of this part of the plant.

Giant thoracic aorta aneurysm below an endovascular stent - An unexpected finding during linear endoscopic ultrasound.

A 50-year-old woman with a history of bicuspid aortic valve (BAV) and ascending aorta dissection was referred for endoscopic ultrasound (EUS) for suspected choledocholithiasis. Twelve years earlier she had undergone a Bentall-de Bone procedure and 7 years earlier a thoracic aorta aneurysm (TAA) was repaired with an endovascular prosthesis. EUS confirmed choledocholithiasis, however a large aneurysm (60 mm of diameter), was incidentally detected at the distal end of the aortic endoprosthesis. Computed tomography (CT) later confirmed the aneurysm, extending 4.5 cm above the renal arteries. The patient underwent a successful new endovascular repair. This rare incidental finding underscores the usefulness of a systematic approach when performing EUS, enabling the detection of significant abnormalities beyond the initial indication and allowing for early intervention in TTA patients.

Factors Influencing Performance of Cholangioscopy-Guided Lithotripsy Including Available Different Technologies: A Prospective Multicenter Study with 94 Patients.

BACKGROUND: Peroral cholangioscopy (POC)-guided lithotripsy is an effective treatment for difficult biliary stones. A clear definition of factors associated with the efficacy of POC-guided lithotripsy in one session and the performance of electrohydraulic lithotripsy (EHL) and laser lithotripsy (LL) have not clearly emerged. METHODS: This was a non-randomized prospective multicenter study of all consecutive patients who underwent POC lithotripsy (using EHL and/or LL) for difficult biliary stones. The primary endpoint of the study was the number of sessions needed to achieve complete ductal clearance and the factors associated with this outcome. Secondary endpoints included the evaluated efficacies of LL and EHL. RESULTS: Ninety-four patients underwent 113 procedures of EHL or LL. Complete ductal clearance was obtained in 93/94 patients (98.94%). In total, 80/94 patients (85.11%) achieved stone clearance in a single session. In the multivariate analysis, stone size was independently associated with the need for multiple sessions to achieve complete ductal clearance (odds ratio = 1.146, 95% confidence interval: 1.055-1.244; p = 0.001). Using ROC curves and the Youden index, 22 mm was found to be the optimal cutoff for stone size (95% confidence interval: 15.71-28.28; p < 0.001). The majority of the patients (62.8%) underwent LL in the first session. Six patients failed the first session with EHL after using two probes and therefore were crossed over to LL, obtaining ductal clearance in a single additional session with a single LL fiber. EHL was significantly associated with a larger number of probes (2.0 vs. 1.02) to achieve ductal clearance (p < 0.01). The mean procedural time was significantly longer for EHL than for LL [72.1 (SD 16.3 min) versus 51.1 (SD 10.5 min)] (p < 0.01). CONCLUSIONS: POC is highly effective for difficult biliary stones. Most patients achieved complete ductal clearance in one session, which was significantly more likely for stones < 22 mm. EHL was significantly associated with the need for more probes and a longer procedural time to achieve ductal clearance.

Chemical Analysis by LC-MS of Cannabis sativa Root Samples from Northeast Brazil and Evaluation of Antitussive and Expectorant Activities.

Cannabis sativa is a millenary medicinal plant. However, contrary to worldwide paradigm-shifting, countries like Brazil still prohibit C. sativa cultivation and its medicinal use, even though many populations use aerial parts and roots of this plant for healthcare. As such, the objective of this work was to identify substances in the samples of the C. sativa roots, tracing a correlation with antitussive and expectorant effects. Therefore, samples of C. sativa roots were donated by the Polícia Federal Brasileira, and its aqueous extract (AECsR) was prepared with subsequent lyophilization, to maintain the material stability. After that, the material was analyzed by LC-MS to observe its chemical profile. Four samples (AECsR-A, B, C, and D) were tested in animal models of citric acid-induced cough (0.4 M) and phenol red expectoration (500 mg/kg). Using LC-MS it was possible to identify 5 molecules in C. sativa roots: p-coumaroyltyramine, tetrahydrocannabinol-C4, feruoiltyramine, anhydrocanabisativine, and cannabisativine. In experimental protocols, male mice (Mus musculus) were treated with samples of AECsR at doses of 12.5, 25, or 50 mg/kg regardless of the pharmacological test. In these tests, all samples showed the potential to treat cough and promote fluid expectoration, differing only in the dose at which these effects were observed. Therefore, the data showed that the C. sativa roots of the Brazilian Northeast showed antitussive and expectorant effects, even with intense secondary metabolites' variation, which alters its potency, but not its effect. This highlights the importance of this medicinal plant for future therapy and corroborates to traditional use.

Needle knife fistulotomy in flat and diverticular papillae: Is it time for redemption?

BACKGROUND: European Society of Gastrointestinal Endoscopy (ESGE) recommends needle-knife fistulotomy (NKF) as the preferred precut technique in cases when standard cannulation techniques fail. Despite scarce scientific evidence, flat and diverticular papillae are thought not to be ideal for NKF, as they are associated with poor outcomes. The present study aimed to determine the outcomes of the use of NKF in relation to flat and intradiverticular papillae. METHODS: This prospective multicenter study enrolled consecutive patients, evidencing naïve flat (group A, n = 49) or diverticular papilla (group B, n = 28), who underwent NKF after failure of standard cannulation techniques. Diverticular morphology was subdivided into intradiverticular (group B1, n = 14) and diverticular border papillae (group B2, n = 14), using a previously validated endoscopic classification of the major papilla. The success of biliary cannulation at initial endoscopic retrograde cholangiopancreatography (ERCP), overall biliary cannulation, overall cannulation time, and the rate of adverse events were assessed in the study. RESULTS: The initial cannulation rates were 93.9%, 64.3% and 71.4% for group A, B1, and B2, respectively (P = 0.005); overall cannulation rates after a second ERCP were 98.0%, 92.9% and 85.7%, respectively (P = 0.134). Adverse events occurred in 11.7% of patients, with post-ERCP pancreatitis (PEP) being the most common adverse event (10.4%). Although there was a trend towards a higher incidence of PEP in flat papillae, univariate and multivariate analyses did not show any significant relationship between pancreatitis and trainee involvement, papillary morphology, nor overall cannulation time. CONCLUSIONS: Although flat papillae are associated with high success rates of biliary cannulation using NKF, the rate of PEP is not negligible. NKF is feasible in diverticular papillae, but it is associated with a modest success rate in the initial ERCP.

Outcomes of single-endoscopist-performed needle-knife fistulotomy for selective biliary access in 842 consecutive patients: learning curve and changes over a 14-year period in a retrospective study.

BACKGROUND AND AIMS: Needle-knife fistulotomy (NKF) has emerged as the preferred precut technique. From a late strategy, NKF has shifted to an early rescue technique and has been used recently as a primary method for biliary access. It is unknown how these changes have affected NKF outcomes. We analyzed the outcomes of NKF over time in a large cohort of patients. METHODS: Multicenter retrospective cohort study of 842 patients who underwent NKF for biliary access between 2006 and 2019. Patients were divided into four study periods according to a late or early cannulation strategy and to the use of post-ERCP pancreatitis prophylaxis (Period 1-Period 4). We assessed outcomes of NKF, learning curves and shifts over time. RESULTS: Bile duct access was obtained in 88.0% of the patients. The initial cannulation rate increased significantly from 77.5% in P1 to 92.0% in P4 (p < .001). An endoscopist can obtain 80% success rate after performing 100 NKF procedures (95% CI: 0.79-0.86) and a 95% success rate after 830 procedures (95% CI: 0.92-0.98). Adverse events and pancreatitis were observed in 6.5% and 4.9% of patients respectively. The rate of pancreatitis was not significantly different during the 4 periods (p = .190). A decline in the pancreatitis rate was observed from 2006 until 2016 (no trainees) and then an increase until 2019 (trainees involved). The presence of trainees increased the rate of pancreatitis in the last period by 9.9%. CONCLUSIONS: The success of NKF has increased significantly over the years, initially in a rapid manner and then more slowly. It is associated with a low rate of complications, which tend to decrease with experience. The involvement of trainees is associated with an increased rate of pancreatitis.

3D echoendoscopy and miniprobes for rectal cancer staging.

BACKGROUND: rectal cancer staging using rigid probes or echoendoscopes has some limitations. The aim of the study was to compare rectal cancer preoperative staging using conventional endoluminal ultrasonography with three-dimensional endoscopic ultrasonography and miniprobes. MATERIALS AND METHODS: sixty patients were included and evaluated with: a) a conventional echoendoscope (7.5 and 12 MHz); b) miniprobes (12 MHz); and c) the Easy 3D Freescan software for three-dimensional endoscopic ultrasonography. The reference or gold standard was conventional endoluminal ultrasonography in all cases and pathological assessment for those without preoperative therapy. The differences in T and N staging accuracy in both longitudinal and circumferential extension were evaluated. RESULTS: with regard to T staging, conventional endoluminal ultrasonography had an accuracy of 85% (compared to pathological analysis), and the agreement between miniprobes vs conventional endoluminal ultrasonography (kappa = 0.81) and three-dimensional endoscopic ultrasonography vs conventional endoluminal ultrasonography (k = 0.87) was significant. In addition, miniprobes had an accuracy of 82% and three-dimensional endoscopic ultrasonography had a higher accuracy (96%). With regard to N staging, conventional endoluminal ultrasonography had an accuracy of 91% with a sensitivity of 78%. However, the agreement between miniprobes and conventional endoluminal ultrasonography and three-dimensional endoscopic ultrasonography and conventional endoluminal ultrasonography (k = 0.70) was lower. Interestingly, miniprobes had a lower accuracy of 81% whereas three-dimensional endoscopic ultrasonography had an accuracy of 100% without any false negative. No false positives were observed in any of the techniques. Accuracy for T and N staging was not influenced by longitudinal or circumferential extensions of the tumor in all types of endoscopic ultrasonography analyzed. CONCLUSIONS: miniprobes and especially three-dimensional endoscopic ultrasonography may be relevant during rectal cancer staging.

Echoendoscopic characterization of the human colon.

PURPOSE: To characterize colon and rectum walls, pericolic and perirectal spaces, using endoscopic ultrasonography miniprobes. METHODS: Sixty individuals (50% males), aged 18-80, were included. Using 12 and 20 MHz endoscopic ultrasonography miniprobes, all different colon segments (ascending, transverse, descending, sigmoid) and rectum were evaluated according to the number and thickness of the different layers in intestinal wall, to the presence and (largest) diameter of vessels in the submucosa and of peri-intestinal nodes. RESULTS: The 20 MHz miniprobe identified a higher number of layers than the 12 MHz miniprobe, with medians of 7 and 5 respectively (p < 0.001). The rectal wall (p = 0.001), its muscularis propria (p < 0.001) and mucosa (p = 0.01) were significantly thicker than the different segments of the colon, which had no significant differences between them. Patients aged 41-60 presented thicker colonic wall and muscularis propria in descending (p = 0.001 and p = 0.004) and rectum (p = 0.01 and p = 0.01). Submucosal vessels were identified in 30% of individuals in descending and rectum, and in 12% in ascending. Adenopathies were observed in 9% of the colon segments and 5% in rectum. CONCLUSIONS: A higher frequency enabled the identification of a higher number of layers. Rectal wall is thicker than the one from all the segments of the colon and there are no differences between these, namely in the ascending colon. Moreover, periintestinal adenopathies were rarely identified but present in asymptomatic individuals. All together, these results describe for the first time features which are relevant during staging and therapeutic management of colonic lesions.

Duodenal gastrointestinal stromal tumor and endoscopic ultrasound.

Duodenal gastrointestinal stromal tumors (GISTs) are a very rare condition. The pre-operative diagnosis can be a challenge but it is very important because GISTs have singularities that differ from other tumors and their location in the duodenum itself can have a major role in the choice of the surgical approach. We present two cases of duodenal GISTs where endoscopic ultrasound had a single role in their management, namely allowing the possibility to obtain material for immunocytochemical pre-operative diagnosis and regarding the precise relation to the papilla of Vater. The patients were operated and histological examination confirmed the diagnosis in both cases.

EUS-Guided Choledochoduodenostomy after Failed Endoscopic Retrograde Cholangiopancreatography in Distal Malignant Biliary Obstruction.

Introduction: Malignant biliary obstruction drainage is essential, since jaundice is associated with morbidity and mortality. Endoscopic retrograde cholangiopancreatography (ERCP) is the recommended procedure for biliary drainage, with percutaneous biliary drainage being the classic alternative in cases of unsuccessful ERCP. Recently, endoscopic ultrasound-guided biliary drainage has been emerged as a new option, with EUS-guided choledochoduodenostomy (EUS-CDS) being considered an effective and safe method in the drainage of distal obstructions of the common bile duct. Aim: The aim of the study was to evaluate the efficacy and safety of EUS-CDS performed in patients with distal malignant biliary obstructions, after failed ERCP. Methods: Single-center retrospective cohort study between July 2017 and June 2022 including all consecutive patients submitted to EUS-CDS in our center. The primary outcomes were "technical success" and "clinical success," defined as "resolution of jaundice or improvement in total serum bilirubin level above 50% at 7th day and above 75% at 30th day after the procedure." Secondary outcomes were procedure-related adverse events, endoscopic reintervention, and survival time. Results: EUS-CDS was performed in 20 patients (65.0% male; median age 76 years). The most frequent etiology for the biliary obstruction was pancreatic adenocarcinoma (n = 17; 85.0%), and most patients presented at advanced stages of cancer (12/60% in stages III or IV). ERCP failure was mainly due to the presence of obstruction in the duodenal lumen (n = 11; 55.0%). Fully covered metallic stents were used in all patients, mostly HotAxiosTM (n = 15; 75.0%). The technical success rate was 100%, and the clinical success rate was 89.5% (n = 17/19) at 7th day and 93.3% (n = 14/15) at 30th day. Four patients (20.0%) developed cholangitis within the first 30 days after the procedure; there were no late complications, and no patient died as a complication of the procedure. In 2 patients (10.0%), endoscopic reintervention was necessary due to stent migration, incidentally detected. Median survival was 93 days (minimum 5-maximum 751). Conclusion: EUS-CDS was effective in biliary decompression of malignant obstructions of the common bile duct, with high clinical success and a favorable safety profile.

Introdução: A drenagem das obstruções biliares malignas é essencial, uma vez que a icterícia está associada a morbimortalidade. A colangiopancreatografia retrógrada endoscópica (CPRE) é o procedimento recomendado para a drenagem biliar, sendo a drenagem biliar percutânea (DBP) a alternativa clássica, se verificado insucesso. Recentemente, a drenagem da via biliar guiada por ecoendoscopia tem-se apresentado como uma nova opção, sendo a coledocoduodenostomia guiada por ecoendoscopia (CGE) considerado um método eficaz e seguro na drenagem de obstruções da via biliar distal. Objetivo: Avaliar o sucesso técnico e clínico e a segurança da CGE em doentes com obstrução da via biliar distal, após falência da CPRE. Métodos: Estudo de coorte retrospetivo, entre Julho/2017 e Junho/2022, de todos os doentes submetidos a CGE no nosso centro. Determinaram-se como outcomes primários o "sucesso técnico" e o "sucesso clínico" ("melhoria ≥50% na bilirrubinemia ao 7.º e ≥ 75% ao 30.º dias após o procedimento"). Os outcomes secundários incluíram a frequência de eventos adversos, necessidade de reintervenção e taxa de sobrevida. Foram utilizadas curvas de Kaplan-Meier para descrever a sobrevida. Resultados: A CGE foi realizada em 20 doentes (65.0% do sexo masculino; idade mediana 76 anos). A etiologia mais frequente para a obstrução foi o adenocarcinoma pancreático (n = 17; 85.0%) e a maioria dos doentes apresentava- se em estadios avançados da neoplasia (12/60% em estadios III ou IV). A falência da CPRE deveu-se à presença de obstrução no lúmen duodenal em 55.0% dos doentes (n = 11). Em todos os doentes foram utilizadas próteses metálicas totalmente cobertas, maioritariamente HotAxiosTM (n = 15; 75.0%). A taxa de sucesso técnico foi de 100% e de sucesso clínico foi de 89.5% ao 7.º dia (n = 17/19) e 93.3% ao 30.º dia (n = 14/15). Quatro doentes (20.0%) desenvolveram colangite nos primeiros 30 dias após o procedimento; não se verificaram complicações tardias e nenhum doente faleceu como complicação do procedimento. Em 2 doentes (10.0%) foi necessária reintervenção por migração da prótese, detetada incidentalmente. A sobrevida mediana foi de 93 dias (mínimo 5 - máximo 751). Conclusões: A CGE foi efetiva na descompressão biliar de obstruções malignas da via biliar distal, com elevado sucesso clínico e um perfil de segurança favorável.

Side-Viewing Duodenoscope versus Forward-Viewing Gastroscope for Endoscopic Retrograde Cholangiopancreatography in Billroth II Gastrectomy Patients.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Billroth II gastrectomy is still a challenging procedure. The optimal approach, namely the type of endoscope and sphincter management, has yet to be defined. Aim: To compare the efficacy and safety of forward-viewing gastroscope and the side-viewing duodenoscope in ERCP of patients with Billroth II gastrectomy. Methods: We conducted a retrospective, single-center cohort study of consecutive patients with Billroth II gastrectomy submitted to ERCP in an expert center for ERCP between 2005 and 2021. The outcomes assessed were: papilla identification, deep biliary cannulation, and adverse events (AEs). Multivariate analysis was performed to evaluate potential associations and predictors of the main outcomes. Results: We included 83 patients with a median age of 73 (IQR 65-81) years. ERCP was performed using side-viewing duodenoscope in 52 and forward-viewing gastroscope in 31 patients. Patients' characteristics were similar in the two groups. The global rate of papilla identification was 66% (n = 55). The rate of deep cannulation was 58% considering all patients and 87% in the subgroup of patients in which the papilla major was identified. Cannulation was performed with standard methods in 65% of cases and with needle-knife fistulotomy in 35%. AEs occurred in 4 patients. There was no difference between duodenoscope and gastroscope in papilla identification (64% [95% CI: 51-77] vs. 71% [55-87]). Although not statistically significant, duodenoscope had a lower deep cannulation rate when considering all patients (52% [15-39] vs. 68% [7-35]) and a higher AEs rate (8% [1-15] vs. 0% [0-1]). In a multivariate analysis, the use of gastroscope significantly increased the deep cannulation rate (OR = 152.62 [2.5-9,283.6]). Conclusion: This study demonstrates that forward-viewing gastroscope is at least as effective and safe as side-viewing duodenoscope for ERCP in patients with Billroth II gastrectomy. Moreover, our study showed that gastroscope is an independent predictor of successful cannulation.

Introdução: Colangiopancreatografia retrógrada endoscópica (CPRE) em doentes submetidos previamente a gastrectomia com reconstrução Billroth II é ainda um exame desafiante. A melhor abordagem, nomeadamente o tipo de endoscópio e a técnica de canulação biliar, ainda não está definida. Objectivo: Comparar a eficácia e segurança do gastroscópio de visão frontal e do duodenoscópio de visão lateral na CPRE de doentes com gastrectomia com reconstrução Billroth II. Métodos: Conduzimos um estudo de coorte retrospectivo e unicêntrico que incluiu consecutivamente doentes com gastrectomia com reconstrução Billroth II submetidos a CPRE num centro de referência para CPRE entre 2005 e 2021. Os outcomes avaliados foram: identificação da papila, canulação biliar profunda e efeitos adversos (EAs). Regressão logística foi realizada para avaliar possíveis associações e preditores dos outcomes. Resultados: Incluímos 83 doentes com uma idade mediana de 73 (IIQ 65­81) anos. A CPRE foi realizada usando duodenoscópio em 52 doentes e usando o gastroscópio de visão frontal em 31 doentes. As características dos doentes foram semelhantes entre os dois grupos. A taxa global de identificação da papila foi de 66% (n = 55). A taxa de canulação profunda foi de 58% considerando todos os doentes e de 87% considerando apenas o subgrupo de doentes nos quais a papila major foi identificada. A canulação foi realizada usando métodos convencionais em 65% e usando fistulotomia com faca em 35% dos doentes. EAs ocorreram em 4 doentes. Não houve diferenças entre duodenoscópio e gastroscópio relativamente à identificação da papila [64% (95% CI: 51­77) vs 71% (55­87)]. Apesar de estatisticamente não significativo, o uso de duodenoscópio teve uma menor taxa de canulação profunda quando considerados todos os doentes [52% (15­39) vs 68% (7­35)] e uma maior taxa de EAs [8% (1­15) vs 0% (0­1)]. Na regressão logística, o uso de gastroscópio significativamente aumentou a taxa de canulação profunda [OR = 152.62 (2.5­9,283.6)]. Conclusão: Este estudo demonstra que o uso de gastroscópio de visão frontal é pelo menos igualmente eficaz e seguro ao duodenoscópio na CPRE de doentes com gastrectomia com reconstrução Billroth II. Para além disso, o nosso estudo demonstrou que o uso de gastroscópio é um predictor independente para canulação.

Efficacy and safety of primary, early and late needle-knife fistulotomy for biliary access.

European Society of Gastrointestinal Endoscopy recommends needle-knife fistulotomy (NKF) as the preferred precut technique. However, there is little information on whether NKF performed at different times is associated with different success and adverse event rates. We compared the outcomes of 3 different timings of NKF. This was an observational study conducted at 4 institutions and this was a retrospective analysis of prospectively collected data. We included 330 consecutive patients submitted to NKF attempt for biliary access. Patients were divided into three groups: NKF as an initial procedure for biliary access (group A, n = 121); early NKF defined as after 5 min, 5 attempts, or 2 pancreatic passages (group B, n = 99); and late NKF: after at least 10 min of unsuccessful standard biliary cannulation (group C, n = 110). We assessed the success rate of biliary cannulation at initial ERCP, time to perform NKF until biliary cannulation, overall biliary cannulation rate (second ERCP when initial failure), adverse event rate, and predictors of post-ERCP pancreatitis (PEP). The initial cannulation rate was 98%, 91% and 94% for groups A, B and C respectively, p = 0.08, whereas overall biliary cannulation rate was 100%, 95% and 98%, p = 0.115. The adverse event rate/PEP was 4.1%/2.5%, 7.1%/4% and 10.9%/8.2%, for groups A, B and C respectively, (p = 0.197 and p = 0.190). Median time for creating the fistula was A = 4.0 min, B = 3.2 min, and C = 5.6 min, p < 000.1. Each additional minute spent attempting cannulation increased the odds ratio (OR) for PEP by 1.072, and patients with 3 or more risk factors for pancreatitis had a higher chance of PEP. In conclusion, the timing of NFK does not appear to influence success rates but late NFK is associated with a higher time to create a fistula and an increased risk of pancreatitis. Primary NFK is associated with a high rate of success and a low rate of PEP and deserves additional investigation.

Cannabis roots: Pharmacological and toxicological studies in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: There are many studies and therapeutic properties attributed to the flowers and leaves of the Cannabis species, but even with few pharmacological studies, Cannabis sativa L. (Cannabaceae) roots presents several therapeutic indications in folk medicine. AIM OF THE STUDY: This study aimed to evaluate the anti-inflammatory and spasmolytic effects as well as the toxicological profile of the aqueous extract of Cannabis sativa roots (CsAqEx) in mice. MATERIALS AND METHODS: We assessed the anti-inflammatory effect with carrageenan-induced leukocyte migration assay, and carrageenan and histamine-induced paw edema methods; The spasmolytic effect was assessed through in vitro assays with isolated mice trachea. To assess motor coordination and mobility, mice went through the rotarod and open field tests, respectively. For the single-dose toxicity study, we administered CsAqEx at the dose of 1000 mg/kg by gavage. In a repeated dose toxicity study, animals received CsAqEx at doses of 25 mg or 100 mg/kg for 28 days. RESULTS: The CsAqEx inhibited the migration of leukocytes at the doses of 25, 50, and 100 mg/kg. The CsAqEx showed anti-inflammatory activity after the intraplantar injection of carrageenan, presenting a reduction in edema formation at all tested doses (12.5, 25, 50 and 100 mg/kg). The dose of 12.5 mg/kg of CsAqEx prevented edema formation after intraplantar injection of histamine. In an organ bath, 729 µg/mL of CsAqEx did not promote spasmolytic effect on isolated mice tracheal rings contracted by carbachol (CCh) or potassium chloride (KCl). We did not observe clinical signs of toxicity in the animals after acute treatment with CsAqEx, which suggested that the median lethal dose (LD50) is greater than 1000 mg/kg. Repeated dose exposure to the CsAqEx did not produce significant changes in hematological, biochemical, or organ histology parameters. CONCLUSIONS: The results suggest that the anti-inflammatory effect of CsAqEx is related to the reduction of vascular extravasation and migration of inflammatory cells, without effects on the central nervous system. Moreover, there was no spasmolytic effect on airway smooth muscle and no toxicity was observed on mice.

Investigation of antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of Brazilian Cannabis sativa L. roots in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies are performed with the aerial parts of Cannabis sativa L. (Cannabaceae). However, roots remain poorly studied, despite citations in the scientific literature. The C. sativa roots are indicated for the treatment of pain, inflammation, fever, among other health problems. AIM OF THE STUDY: This study aimed to evaluate the antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of C. sativa roots in experimental models using mice and rats. MATERIAL AND METHODS: The chemical composition of the aqueous extract of C. sativa roots (AECsR) was evaluated by LC-MS. The antinociceptive activity was assessed in mice by the induction of writhing with acetic acid, paw licking with formalin, and reactivity in the hot plate test. Fever was induced by the administration of a suspension of Saccharomyces cerevisiae in young rats. The asthmatic activity was performed with ovalbumin (OVA)-immunized mice with cellular and histological analysis. Finally, the spasmolytic activity was performed using mice isolated trachea. For in vivo studies, the doses were 12.5, 25, or 50 mg/kg whereas for in vitro, the concentration of AECsR was 729 µg/mL. RESULTS: From the LC-MS data, we identified p-coumaroyltyramine, feruloyltyramine canabissativine in AECsR. The extract promoted a reduction of writhing in all tested doses (12.5, 25, or 50 mg/kg). Similarly, it reduced the pain in the formalin test at doses of 12.5 and 50 mg/kg (first phase) and 12.5 and 25 mg/kg (second phase). In the hot plate test, the doses of 12.5, 25, and 50 mg/kg promoted antinociceptive effect at different times, and the lowest dose maintained its action in the analyzes performed at 60, 90, and 120 min after administration. The anti-inflammatory activity of AECsR was observed in the mouse model of asthma, reducing the total leukocyte count in the bronchoalveolar fluid (BALF) at a dose of 25 mg/kg, as well as reducing eosinophilia in all tested doses (12.5, 25, and 50 mg/kg). Histological analysis of lungs stained with H&E and PAS showed a reduction in the number of inflammatory cells in the perivascular and peribronchial region, as well as reduced mucus production. CONCLUSION: The results suggest that AECsR promotes pain control, either by a central or inflammatory mechanism, and has antiasthmatic activity. However, there was no antipyretic or spasmolytic effect.