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BACKGROUND: Collaterals are a strong determinant of clinical outcome in acute ischemic stroke (AIS) patients undergoing Endovascular Treatment (EVT). Careggi Collateral Score (CCS) is an angiographic score that demonstrated to be superior to the widely suggested ASITN/SIR score. Multi-phase CT-Angiography (mCTA) could be alternatively adopted for collateral assessment. We investigated whether mCTA had an equivalent predictive performance for functional outcome compared to CCS. METHODS: Consecutive AIS patients undergoing EVT for large vessel occlusion within 24 h from onset were analyzed. Receiver operating characteristic curves and multivariable logistic regression were investigated to evaluate the predictive performance of mCTA collateral score (range 0-5) and CCS (range 0-4) for good functional outcome (three-months modified Rankin Scale 0-2). RESULTS: We included 201 subjects (59.7% females, mean age 75), of whom 96 (47.7%) had good outcome at three-months. Both CCS (OR = 14.4, 95% CI = 6.3-33.8) and mCTA (OR = 23.8, 95% CI = 10.1-56.4) collateral scores were independent predictors of outcome. The AUC of CCS was 0.80 (95% CI 0.73-0.86) and the best cut-off was ≥ 3 (87% sensitivity, 71% specificity), while the AUC of mCTA collateral score was 0.84 (95% CI 0.78-0.90) with an optimal cut-off of ≥ 4 (85% sensitivity, 87% specificity). Patients with good mCTA collaterals experienced smaller (16.6 vs. 63.7 mL, p < 0.001) infarct lesion as compared to those with mCTA poor collaterals. CONCLUSION: mCTA discriminative ability for three-months 0-2 mRS was found to be comparable to CCS. mCTA appears a valid, non-invasive imaging modality for evaluating collaterals of AIS patients potentially eligible for EVT.
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BACKGROUND: Mechanical thrombectomy (MT) was found to be beneficial in acute ischemic stroke patients with anterior tandem occlusion (a-TO). Instead, little is known about the effectiveness of MT in stroke patients with posterior tandem occlusion (p-TO). We aimed to compare MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO. METHODS: We conducted a cohort study on prospectively collected data of patients registered in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) who were treated with MT within 24 h from last known well time for acute ischemic stroke with p-TO (n = 275) or a-TO (n = 1853). RESULTS: After adjustment for unbalanced pre-procedure variables (year 2015-2021, age, sex, NIHSS score, ASPECTS, and time strata for puncture groin) and pre-stroke mRS score as pre-defined predictor, p-TO was significantly associated with lower probability of mRS score 0-2 (OR 0.415, 95% CI 0.268-0.644) and with higher risk of death (OR 2.813, 95% CI 2.080-3.805) at 3 months. After adjustment for unbalanced procedural and post-procedure variables (IVT, general anesthesia, TICI 3, and 24-h HT) and pre-stroke mRS score as pre-defined predictor, association between p-TO and lower probability of mRS score 0-2 (OR 0.444, 95% CI 0.304-0.649) and association between p-TO and with higher risk of death (OR 2.971, 95% CI 1.993-4.429) remained significant. CONCLUSIONS: MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO was associated with worse outcomes at 3 months.
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The management of acute ischemic stroke is changing. Over the period of 2010-2050, the number of incident strokes is expected to be more than double. Rapid access to mechanical thrombectomy for patients with large vessel occlusion is critically associated with their functional outcome. Moreover, patients with first pass effect had a better clinical outcome, lower mortality, and fewer procedural adverse events. We discuss some advances in acute ischemic stroke regarding the organization, the diagnosis and the treatment.
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BACKGROUND AND OBJECTIVES: This multicenter study aimed to assess the safety and efficacy of the Woven EndoBridge (WEB) device for treating unruptured wide-neck intracranial bifurcation aneurysms (WIBAs) with short-, mid-, and long-term follow-ups (FUPs). METHODS: Consecutive patients with unruptured WIBAs treated with WEB between December 2014 and January 2018 were included. Patient, aneurysm, and device characteristics were collected and analyzed retrospectively. Morbidity and mortality rates were determined by collecting intraprocedural, periprocedural, and delayed complications. Aneurysm occlusion was assessed at 1, 3, and 5 years using a 3-grade scale: complete occlusion, neck remnant, and residual aneurysm. Complete occlusion and neck remnant were considered as adequate occlusion. Patients who received re-treatment were also evaluated. RESULTS: The study included 104 consecutive patients (55.8% female, mean age 58.6 ± 11.8 years). Aneurysm maximum size, neck, and dome-to-neck mean were, respectively, 6.9 ± 2.1 mm, 4.5 ± 1.2 mm, and 1.4 ± 0.3 mm. One-year FUP was collected for 95 patients, and 3- and 5-year FUPs were collected for 83 patients. Adequate occlusion was observed at 1-year FUP in 90.5% (86/95), 91.6% (76/83) was observed at 3-year FUP, and 92.8% (77/83) at 5-year FUP. None of the aneurysms bled after treatment. During FUP, 6/83 patients (7.2%) were re-treated for residual aneurysm. Morbidity and mortality rates closely related to aneurysm occlusion were 0% (0/104). CONCLUSION: The WEB device was safe and effective for treating unruptured WIBAs, both in short-term and long-term FUPs.
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BACKGROUND: Predictors of radiological complications attributable to reperfusion injury remain unknown when baseline setting is optimal for endovascular treatment and procedural setting is the best in stroke patients with large vessel occlusion (LVO). AIMS: To identify clinical and radiological/procedural predictors for hemorrhagic transformation (HT) and cerebral edema (CED) at 24 hr in patients obtaining complete recanalization in one pass of thrombectomy for ischemic stroke ⩽ 6 h from symptom onset with intra-cranial anterior circulation LVO and ASPECTS ⩾ 6. METHODS: We conducted a cohort study on prospectively collected data from 1400 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. RESULTS: HT was reported in 248 (18%) patients and early CED was reported in 260 (19.2%) patients. In the logistic regression model including predictors from a first model with clinical variables and from a second model with radiological/procedural variables, diabetes mellitus (odds ratio (OR) = 1.832, 95% confidence interval (CI) = 1.201-2.795), higher National Institutes of Health Stroke Scale (NIHSS) (OR = 1.076, 95% CI = 1.044-1.110), lower Alberta Stroke Program Early CT (ASPECTS) (OR = 0.815, 95% CI = 0.694-0.957), and longer onset-to-groin time (OR = 1.005, 95% CI = 1.002-1.007) were predictors of HT, whereas general anesthesia was inversely associated with HT (OR = 0.540, 95% CI = 0.355-0.820). Higher NIHSS (OR = 1.049, 95% CI = 1.021-1.077), lower ASPECTS (OR = 0.700, 95% CI = 0.613-0.801), intravenous thrombolysis (OR = 1.464, 95% CI = 1.061-2.020), longer onset-to-groin time (OR = 1.002, 95% CI = 1.001-1.005), and longer procedure time (OR = 1.009, 95% CI = 1.004-1.015) were predictors of early CED. After repeating a fourth logistic regression model including also good collaterals, the same variables remained predictors for HT and/or early CED, except diabetes mellitus and thrombolysis, while good collaterals were inversely associated with early CED (OR = 0.385, 95% CI = 0.248-0.599). CONCLUSIONS: Higher NIHSS, lower ASPECTS, and longer onset-to-groin time were predictors for both HT and early CED. General anesthesia and good collaterals were inversely associated with HT and early CED, respectively. Longer procedure time was predictor of early CED.
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Edema Encefálico , Isquemia Encefálica , Diabetes Mellitus , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Estudos de Coortes , Edema Encefálico/etiologia , Trombectomia/métodos , Resultado do Tratamento , Estudos Retrospectivos , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Procedimentos Endovasculares/métodosRESUMO
We present the technical aspects of embolization for two unruptured medium-sized aneurysms of the anterior cerebral artery treated with balloon-remodeling technique and loose coiling of the sac with the final deployment of a 0. 017-compatible flow diverter. Both procedures were performed with dual antiplatelet therapy premedication and under general anesthesia. The anatomy of the two aneurysms was similar with a wide neck and the presence of a collateral artery branching off it, which required the additional use of a compliant balloon in order to retain patency and avoid coil protrusion. After initial coiling, a nitinol flow-diverter was deployed through a coaxial dual lumen balloon microcatheter. Both these interventions encountered no complications, and the patient was discharged on day 2. At 6-month clinical and radiological follow-up, neither patient had neurological deficits, the aneurysms were both completely occluded, nor the stented arteries were patent along with their collateral branches.
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Atherosclerotic stenosis of the internal carotid artery is a rare cause of pulsatile tinnitus. Stenosis responsible for tinnitus is usually located in the petrous segment of the vessel or, even more uncommonly, in the extracranial segment. However, to the best of our knowledge, a stenosis of the intradural supraclinoid segment of the internal carotid had never been reported as a source of pulsatile tinnitus. We describe the case of a man with a history of previous ischaemic stroke and invalidating pulsatile tinnitus, caused by a high grade, diaphragm-like shaped, stenosis of the supraclinoid internal carotid artery. The stenosis was treated with angioplasty and stenting with a low-profile self-expanding high radial force stent (Acclino flex HRF, Acandis). Tinnitus disappeared immediately after the procedure. At the two-year follow-up no recurrence of the tinnitus and the stenosis occurred. Intradural internal carotid artery stenosis should be considered as a very rare cause of pulsatile tinnitus.
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Introduction: Although stroke occurs frequently in patients with cancer, there is scarce evidence regarding the safety and efficacy of endovascular treatment (EVT) in patients with acute ischemic stroke and concurrent cancer. We performed a systematic review and meta-analysis to summarize the existing literature. Methods: We searched for English written observational studies reporting data on safety and efficacy of EVT in patients with acute ischemic stroke and concurrent cancer. Outcomes of interest were: functional independence (modified Rankin Scale (mRS) ⩽ 2); mortality at 3 months; rate of successful recanalization (modified Treatment In Cerebral Ischemia (mTICI) 2b or 3); occurrence of any hemorrhagic transformation (both symptomatic and asymptomatic). We pooled data with Maentel-Haenszel model to calculate cumulative odds ratios (ORs). Results: We included seven studies with a total of 4465 patients, of whom 262 (6%) with cancer. We observed various definitions of cancer across included studies. Patients with cancer had less likely mRS⩽2 at 3 months (24% vs 42%, OR = 0.44; 95% CI = 0.32-0.60) and increased probability of death (43% vs 19%, OR = 5.02; 95% CI = 2.90-8.69). There was no difference in successful recanalization (70% vs 75%, OR = 0.84; 95% CI = 0.49-1.44); patients with cancer had increased risk of any intracerebral hemorrhage after treatment (49% vs 34%, OR = 1.95; 95% CI = 1.28-2.96), though not for symptomatic ICH (OR 1.04; 95% CI = 0.59-1.85). Conclusion: Patients with acute ischemic stroke and cancer have similar EVT recanalization but higher probability of functional dependence, death, and any hemorrhagic transformation, though not necessarily symptomatic, compared with patients without cancer. Our results may help communication with patients and carers.
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Background: The application of a new coating to the delivery wire of the Trevo retriever has the potential to improve its handling. We therefore report our initial experience with this new stent retriever for mechanical thrombectomy of large and medium vessel occlusions. Methods: We pooled data of four high-volume European stroke centers over the time period from October 2020 to February 2021. Patients were included in our study if the Trevo NXT stent retriever was used as a first-line device. Primary endpoints were first-pass near-complete or complete reperfusion, defined as mTICI score of ≥2c. Secondary endpoints were final reperfusion, National Institutes of Health Stroke Scale (NIHSS) at 24 h and discharge, device malfunctions, complications during the procedure, and subjective ratings of the interventionalists regarding device functionality. Results: Eighty patients (39 women, mean age 74 ± 14 years) were eligible for our study. Median NIHSS at admission was 15 (IQR, 8-19), and median Alberta Stroke Program Early CT Score at baseline was 9 (IQR, 8-10). In 74 (93%) patients a primary combined approach was used as first-line technique. First-pass near-complete reperfusion was achieved in 43 (54%) and first-pass complete reperfusion in 34 (43%) patients. Final near-complete reperfusion was achieved in 66 (83%) patients after a median of 1.5 (1-3) passes, while final successful reperfusion was observed in 96% of our cases. We observed no device malfunctions. Median NIHSS at discharge was 2 (IQR, 0-5), and 3 patients (4%) suffered a symptomatic intracranial hemorrhage. Conclusions: Based on our initial data, we conclude that the Trevo NXT is an effective and safe tool for mechanical thrombectomy especially when used for combined approaches.
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In recent years, the use of anthraquinone laxatives, in particular senna, has been associated with damage to the intestinal epithelial layer and an increased risk of developing colorectal cancer. In this study, we evaluated the cytotoxicity of rhein, the active metabolite of senna, on human colon adenocarcinoma cells (Caco-2) and its effect on cell proliferation. Cytotoxicity studies were performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and trans-epithelial electrical resistance (TEER) assays whereas (3)H-thymidine incorporation and Western blot analysis were used to evaluate the effect of rhein on cell proliferation. Moreover, for genoprotection studies Comet assay and oxidative biomarkers measurement (malondialdehyde and reactive oxygen species) were used. Rhein (0.1-10 microg/ml) had no significant cytotoxic effect on proliferating and differentiated Caco-2 cells. Rhein (0.1 and 1 microg/ml) significantly reduced cell proliferation as well as mitogen-activated protein (MAP) kinase activation; by contrast, at high concentration (10 microg/ml) rhein significantly increased cell proliferation and extracellular-signal-related kinase (ERK) phosphorylation. Moreover, rhein (0.1-10 microg/ml): (i) did not adversely affect the integrity of tight junctions and hence epithelial barrier function; (ii) did not induce DNA damage, rather it was able to reduce H(2)O(2)-induced DNA damage and (iii) significantly inhibited the increase in malondialdehyde and reactive oxygen species (ROS) levels induced by H(2)O(2)/Fe(2+). Rhein was devoid of cytotoxic and genotoxic effects in colon adenocarcinoma cells. Moreover, at concentrations present in the colon after a human therapeutic dosage of senna, rhein inhibited cell proliferation via a mechanism that seems to involve directly the MAP kinase pathway. Finally, rhein prevents the DNA damage probably via an anti-oxidant mechanism.
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Antraquinonas/farmacologia , Cassia/química , Células CACO-2 , Linhagem Celular Tumoral , HumanosRESUMO
Silybum marianum or milk thistle (MT) is the most well-researched plant in the treatment of liver disease. The active complex of MT is a lipophilic extract from the seeds of the plant and is composed of three isomer flavonolignans (silybin, silydianin, and silychristin) collectively known as silymarin. Silybin is a component with the greatest degree of biological activity and makes up 50% to 70% of silymarin. Silymarin is found in the entire plant but it is concentrated in the fruit and seeds. Silymarin acts as an antioxidant by reducing free radical production and lipid peroxidation, has antifibrotic activity and may act as a toxin blockade agent by inhibiting binding of toxins to the hepatocyte cell membrane receptors. In animals, silymarin reduces liver injury caused by acetaminophen, carbon tetrachloride, radiation, iron overload, phenylhydrazine, alcohol, cold ischaemia and Amanita phalloides. Silymarin has been used to treat alcoholic liver disease, acute and chronic viral hepatitis and toxin-induced liver diseases.
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Hepatopatias/tratamento farmacológico , Fitoterapia , Silybum marianum/química , Animais , Antioxidantes/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Peroxidação de Lipídeos , Estrutura Molecular , Silibina , Silimarina/uso terapêuticoRESUMO
Gastric emptying regulates food intake. Oleoylethanolamide (OEA), an endogenous acylethanolamide chemically related to the endocannabinoid anandamide, inhibits food intake, but its effect on gastric emptying is unknown. Here, we investigated the effect and the role of OEA on gastric emptying in mice fed either a standard (STD) or a high-fat diet (HFD) for 14 weeks. Gastric emptying was reduced by OEA, but not by its saturated analog, palmitoylethanolamide. The effect of OEA was unaffected by rimonabant (cannabinoid CB1 receptor antagonist), SR144528 (cannabinoid CB2 receptor antagonist), 5'-iodoresiniferatoxin (transient receptor potential vanilloid type 1 antagonist), or MK886 (peroxisome proliferator-activated receptor-alpha) antagonist. Compared to STD mice, HFD mice showed delayed gastric emptying and higher levels of gastric OEA. HFD-induced increase in OEA levels was accompanied by increased expression of the OEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-selective phospholipase D and decreased expression of the OEA-degrading enzyme fatty acid amide hydrolase. These results might suggest that elevation of gastric OEA could possibly contribute to the delayed gastric emptying observed in HFD-fed animals. HFD regulates OEA levels in the stomach through an increase of its biosynthesis and a decrease of its enzymatic degradation. The inhibitory effect of OEA on gastric emptying here observed might underlie part of the anorexic effects of this compound previously reported.
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Depressores do Apetite/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Amidas , Animais , Canabinoides/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Endocanabinoides , Etanolaminas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Ácidos Palmíticos/farmacologiaRESUMO
Accessory spleens are often encountered in radiologic studies and they are not usually associated with symptoms. They could arise from autotransplantation of splenic tissue after splenic trauma or splenectomy (splenosis) [1]. In this case we describe a woman treated for splenectomy 20 years before and subsequently for adhesions, that suffered sudden left upper abdominal quadrant pain, weakness, and pale color. Contrast-enhanced computed tomography revealed free spilling in the abdomen and venous bleeding of a big accessory spleen; thus the patient underwent transcatheter arterial embolization with coils. Due to the 2 previous surgical operations in the splenic loggia, endovascular treatment compared to "open surgery" was the best choice in this case because of determined less complications, a shorter period of hospitalization, and a reduction of health cost.
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St. John's wort (Hypericum perforatum) is a highly popular and effective herbal antidepressant that clinically interacts with a number of conventional drugs. Because alterations in gastric emptying can cause pharmacokinetic interactions, in the present study we evaluated the effect of a standardized extract prepared from the flowering tops of Hypericum perforatum (SJW extract) on rat gastric motility. Orally administered SJW extract delayed gastric emptying in vivo. In vitro studies showed that SJW extract was significantly more active in inhibiting acetylcholine (or prostaglandin E2)-induced contractions than electrical field stimulation (EFS)-induced contractions. The effect of SJW extract on EFS-induced contractions was unaffected by drugs that inhibit intrinsic inhibitory nerves or by tachykinin antagonists, but it was reduced by the 5-hydroxytryptamine antagonist methysergide. The inhibitory effect of SJW extract on acetylcholine-induced contractions was reduced by the sarcoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid, but not by the L-type Ca2+ channel blocker nifedipine or by methysergide. Among the chemical constituents of SJW extract tested, hyperforin and, to a lesser extent, the flavonoids kaempferol and quercitrin, inhibited acetylcholine-induced contractions. It is concluded that SJW has a direct inhibitory effect on smooth muscle and could also possibly modulate gastric neurotransmission. If extended to humans, the inhibitory effect of SJW extract on gastric emptying in vivo could contribute, at least in part, to the clinical pharmacokinetic interactions between conventional medicines and this herbal antidepressant.
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Antidepressivos/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Hypericum , Músculo Liso/efeitos dos fármacos , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Topos Floridos , Esvaziamento Gástrico/fisiologia , Técnicas In Vitro , Masculino , Músculo Liso/fisiologia , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/fisiologiaRESUMO
PURPOSE: Chronic coccygodynia is a difficult problem diagnostically and therapeutically. Moreover, there is no deep knowledge especially in the field of imaging of chronic coccygodynia. In this study several possible measurements are proposed, which all are able to demonstrate coccygeal movement during defecation, in order to assess coccygeal mobility using dynamic MRI during maximum contraction and during straining-evacuation. MATERIALS AND METHODS: A dynamic MRI study of the pelvic floor was performed in 112 patients. Five methods of measurement were assessed. Coccygeal movements were determined through the evaluation of three angles pair and two different distances measured during the phase of maximum contraction and during the phase of straining-evacuation. Results were compared according to age, sex, parity and experience of minor trauma. No patient included in the study had coccygodynia. Measurements taken by two radiologist were compared to determine interobserver agreement. RESULTS: The maximum measurement values of the two distances are homogeneous, between 9 and 9.4mm. The maximum measurement values of the three angles showed a difference that is between 21 degrees and 38 degrees . Two of three angles showed a major measurement values in the funtional texts. In only one patient the coccyx was not mobile. CONCLUSION: Our dynamic MRI study indicates that the coccyx is mobile during defecation and that it is possible to demonstrate coccygeal excursions by assessing the difference between its positions at maximum contraction and during straining-evacuation. The measurement methods used in this study for evaluating coccygeal movements resulted in variably sized observed differences, but all yielded statistically significant results in demonstrating coccygeal excursion. Among the five measurement methods, two resulted in the largest differences. Our data indicate no correlation between coccygeal movements and age, sex, parity, minor trauma and coccygodynia.
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Cóccix/patologia , Defecografia , Imageamento por Ressonância Magnética , Movimento/fisiologia , Dor Pélvica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cóccix/lesões , Cóccix/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Paridade , Gravidez , Ferimentos não PenetrantesRESUMO
Clinical studies suggest that the Ayurvedic plant Boswellia serrata may be effective in reducing diarrhoea in patients with inflammatory bowel disease. In the present study, we evaluated the effect of a Boswellia serrata gum resin extract (BSE) on intestinal motility and diarrhoea in rodents. BSE depressed electrically-, acetylcholine-, and barium chloride-induced contractions in the isolated guinea-pig ileum, being more potent in inhibiting the contractions induced by acetylcholine and barium chloride. The inhibitory effect of BSE on acetylcholine-induced contractions was reduced by the L-type Ca(2+) channel blockers verapamil and nifedipine, but not by the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid, by the phosphodiesterase type IV inhibitor rolipram or by the lipoxygenase inhibitor zileuton. 3-acetyl-11-keto-beta-boswellic acid, one of the main active ingredients of B. serrata, inhibited acetylcholine-induced contractions. BSE inhibited upper gastrointestinal transit in croton oil-treated mice as well as castor oil-induced diarrhoea. However, BSE did not affect intestinal motility in control mice, both in the small and in the large intestine. It is concluded that BSE directly inhibits intestinal motility with a mechanism involving L-type Ca(2+) channels. BSE prevents diarrhoea and normalizes intestinal motility in pathophysiological states without slowing the rate of transit in control animals. These results could explain, at least in part, the clinical efficacy of this Ayurvedic remedy in reducing diarrhoea in patients with inflammatory bowel disease.
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Boswellia , Diarreia/prevenção & controle , Motilidade Gastrointestinal/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/fisiologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Relação Dose-Resposta a Droga , Estimulação Elétrica , Trânsito Gastrointestinal/efeitos dos fármacos , Cobaias , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
The endocannabinoid system (i.e., the cannabinoid receptors and their endogenous ligands) plays an important role in the physiological control of intestinal motility. However, its participation in intestinal pathological states is still poorly understood. In the present study, we investigated the possible role of the endocannabinoid system in the pathogenesis of paralytic ileus, a pathological state consisting of decreased intestinal motility following peritonitis, surgery, or other noxious situations. Ileus was induced by i.p. administration of acetic acid, and gastrointestinal propulsion was assessed by the charcoal method. Endocannabinoid levels were measured by isotope-dilution gas chromatography-mass spectrometry, whereas cannabinoid CB1 receptors were identified by immunohistochemistry. Acetic acid administration inhibited gastrointestinal transit (ileus), and this effect was accompanied by increased levels of the endocannabinoid anandamide compared with control mice and by overexpression of CB1 receptors in myenteric nerves. Furthermore, acetic acid-induced ileus was alleviated by the CB1 receptor antagonist SR141716A and worsened by VDM11, a selective inhibitor of anandamide cellular uptake (and hence inactivation). From these findings, it can be concluded that the intestinal hypomotility typical of paralytic ileus is due, at least in part, to the enhancement of anandamide levels and CB1 expression during this condition, and that selective, nonpsychotropic CB1 receptor antagonists could represent new drugs to treat this disorder.
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Ácidos Araquidônicos/fisiologia , Pseudo-Obstrução Intestinal/etiologia , Receptores de Droga/metabolismo , Animais , Ácidos Araquidônicos/análise , Ácidos Araquidônicos/farmacologia , Moduladores de Receptores de Canabinoides , Endocanabinoides , Sistema Nervoso Entérico/química , Motilidade Gastrointestinal/efeitos dos fármacos , Pseudo-Obstrução Intestinal/metabolismo , Pseudo-Obstrução Intestinal/fisiopatologia , Intestino Delgado/química , Intestino Delgado/inervação , Camundongos , Modelos Biológicos , Neurônios/química , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas , Pirazóis/farmacologia , Receptores de Canabinoides , Receptores de Droga/análise , Receptores de Droga/antagonistas & inibidores , RimonabantoRESUMO
Caffeic acid phenethyl ester (CAPE), one of the major components of propolis (honeybee resin), has demonstrated a wide spectrum of activities including suppression of eicosanoids by inhibition of cyclooxygenase-1 and cyclooxygenase-2 enzyme activities. The aim of this study was to investigate the effect of CAPE on basal and secretagogues-stimulated gastric acid secretion in vitro. In the isolated, lumen-perfused, stomach preparation of mouse, CAPE (10-100 microM) did not affect the basal gastric acid secretion nor the secretion stimulated by histamine, pentagastrin, isobutyl methylxanthine and high levels of K+. By contrast, CAPE increased the gastric acid secretion induced by the muscarinic receptor agonist, 5-methylfurmethide (5-MEF). CAPE also inhibited the acetylcholinesterase activity in an in vitro colorimetric assay. Eserine (10 microM), a well known acetylcholinesterase inhibitor, also increased 5-MEF-stimulated acid secretion. Our results show that CAPE increases gastric acid secretion stimulated by an acetylcholine agonist receptor likely through inhibition of acetylcholinesterase activity.
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Ácidos Cafeicos/farmacologia , Ácido Gástrico/metabolismo , Álcool Feniletílico/análogos & derivados , Estômago/efeitos dos fármacos , 1-Metil-3-Isobutilxantina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Inibidores da Colinesterase/farmacologia , Relação Dose-Resposta a Droga , Mucosa Gástrica/metabolismo , Fármacos Gastrointestinais/farmacologia , Histamina/farmacologia , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos ICR , Muscarina/análogos & derivados , Muscarina/farmacologia , Nifedipino/farmacologia , Pentagastrina/farmacologia , Álcool Feniletílico/farmacologia , Fisostigmina/farmacologia , Potássio/farmacologiaRESUMO
Essential oils extracted by hydrodistillation from fruits of Cuminum cyminum L. and Carum carvi L. were analyzed by gas chromatography (GC) and GC-mass spectrometry (MS). The main components of C. cyminum oil were p-mentha-1,4-dien-7-al, cumin aldehyde, gamma-terpinene, and beta-pinene, while those of the C. carvi oil were carvone, limonene, germacrene D, and trans-dihydrocarvone. Antibacterial activity, determined with the agar diffusion method, was observed against Gram-positive and Gram-negative bacterial species in this study. The activity was particularly high against the genera Clavibacter, Curtobacterium, Rhodococcus, Erwinia, Xanthomonas, Ralstonia, and Agrobacterium, which are responsible for plant or cultivated mushroom diseases worldwide. In general, a lower activity was observed against bacteria belonging to the genus Pseudomonas. These results suggest the potential use of the above essential oils for the control of bacterial diseases.