RESUMO
BACKGROUND: Superior mesenteric artery (SMA) syndrome is a rare cause of duodenal obstruction by extrinsic compression between the SMA and the aorta (SMA-Ao). Although the left lateral recumbent position is considered effective in the treatment of SMA syndrome, individual variations in the optimal patient position have been noted. In this report, we present two elderly cases of SMA syndrome that exhibited rapid recovery due to ultrasonographic dynamic evaluation of the optimal position for each patient. CASE SUMMARY: Case 1: A 90-year-old man with nausea and vomiting. Following diagnosis of SMA syndrome by computed tomography (CT), ultrasonography (US) revealed the SMA-Ao distance in the supine position (4 mm), which slightly improved in the lateral position (5.7-7.0 mm) without the passage of duodenal contents. However, in the sitting position, the SMA-Ao distance was increased to 15 mm accompanied by improved content passage. Additionally, US indicated enhanced passage upon abdominal massage on the right side. By day 2, the patient could eat comfortably with the optimal position and massage. Case 2: An 87-year-old woman with vomiting. After the diagnosis of SMA syndrome and aspiration pneumonia by CT, dynamic US confirmed the optimal position (SMA-Ao distance was improved to 7 mm in forward-bent position, whereas it remained at 5 mm in the supine position). By day 7 when her pneumonia recovered, she could eat with the optimal position. CONCLUSION: The optimal position for SMA syndrome varies among individuals. Dynamic US appears to be a valuable tool in improving patient outcomes.
Assuntos
Obstrução Duodenal , Síndrome da Artéria Mesentérica Superior , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Síndrome da Artéria Mesentérica Superior/diagnóstico por imagem , Síndrome da Artéria Mesentérica Superior/terapia , Síndrome da Artéria Mesentérica Superior/complicações , Obstrução Duodenal/diagnóstico , Ultrassonografia/efeitos adversos , Vômito/diagnóstico por imagem , Vômito/etiologia , Tomografia Computadorizada por Raios X/efeitos adversos , Artéria Mesentérica Superior/diagnóstico por imagemRESUMO
OBJECTIVES: Medieval yoga texts claim that a special exercise of the muscles of the anterior abdominal wall, called agnisara, improves digestive function. Main objective of the study was to demonstrate change in the blood flow through superior mesenteric artery (if any) after performance of agnisara. METHODS: Ultrasound examination of the linear and volumetric indicators of blood flow in the superior mesenteric artery (SMA) before and after performing the agnisara yoga exercise 100 times was carried out in 12 healthy volunteers of both sexes (8 of them women). RESULTS: A significant increase in the diameter of the SMA, peak systolic and diastolic velocities, and blood flow in the superior mesenteric artery after performing the agnisara exercise 100 times was found, which contrasts with the established data on a decrease in splanchnic blood flow in humans in response to normal physical activity. CONCLUSION: Properly performed agnisara increases blood flow to the splanchnic region, registered by the SMA, which should contribute to adequate blood supply to the gastrointestinal tract for successful performance of digestive function.
Assuntos
Artéria Mesentérica Superior , Circulação Esplâncnica , Abdome , Velocidade do Fluxo Sanguíneo , Feminino , Hemodinâmica , Humanos , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/fisiologia , Circulação Esplâncnica/fisiologiaRESUMO
Background The vascular pharmacodynamics of anthocyanins is only partially understood. To examine whether the anthocyanin-induced vasorelaxation is related to membrane estrogen receptor activity, the role of ERα or GPER antagonism was ascertained on anthocyanins or 17-ß estradiol-(E2) induced vasodilatations and NO production. Methods and Results The rat arterial mesenteric bed was perfused with either anthocyanins or corresponding 3-O-glycosides, or E2, to examine rapid concentration-dependent vasorelaxations. The luminally accessible fraction of NO in mesenteric perfusates before and after anthocyanins or E2 administration was quantified. Likewise, NO-DAF signal detected NO production in primary endothelial cells cultures incubated with anthocyanins or E2 in the absence and presence of ERα (ICI 182,780) or GPER (G-36) selective antagonists. Anthocyanins or corresponding glycosides elicited, within minutes, vasodilation with nanomolar potencies; half maximal anthocyanin response reached 50% to 60% efficacy, in contrast to acetylcholine. The vasorelaxation is of rapid onset and exclusively endothelium-dependent; NOS inhibition annulled the vasorelaxation. The delphinidin vascular response was not modified by 100 nmol/L atropine but significantly attenuated by joint application of ICI plus G-36 (52±4.6 versus 8.5±1.5%), revealing the role of membrane estrogen receptors. Moreover, the anthocyanin or E2-induced NO production was antagonized up to 70% by these antagonists. NO-DAF signal elicited by anthocyanins was annulled by NOS inhibition or by ICI plus G-36 addition. Conclusions The biomedical effect of anthocyanins or 3-O-glycosylates derivatives contained in naturally purple-colored foods or berries is due to increased NO production, and not to the phytochemical's antioxidant potential, highlighting the nutraceutical role of natural products in cardiovascular diseases.
Assuntos
Antocianinas/farmacologia , Receptor alfa de Estrogênio/agonistas , Artéria Mesentérica Superior/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fitoestrógenos/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Masculino , Artéria Mesentérica Superior/metabolismo , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Transdução de SinaisRESUMO
Magnesium lithospermate B (MLB) is an active component of Salvia miltiorrhiza Radix, a traditional Chinese herb used in treating cardiovascular diseases. In this study, we investigated the protective effects of MLB against inflammation-induced endothelial dysfunction in vitro and in vivo, and the underlying mechanisms. Endothelial dysfunction was induced in human dermal microvascular endothelial cells (HMEC-1) in vitro by lipopolysaccharide (LPS, 1 µg/mL). We showed that pretreatment with MLB (10-100 µM) dose-dependently inhibited LPS-induced upregulation of inflammatory cytokines ICAM1, VCAM1, and TNFα, which contributed to reduced leukocytes adhesion and attenuation of endothelial hyperpermeability in HMEC-1 cells. SD rats were injected with LPS (10 mg/kg, ip) to induce endothelial dysfunction in vivo. We showed that pretreatment with MLB (25-100 mg/kg, ip) dose-dependently restored LPS-impaired endothelial-dependent vasodilation in superior mesenteric artery (SMA), attenuated leukocyte adhesion in mesenteric venules and decreased vascular leakage in the lungs. We further elucidated the mechanisms underlying the protective effects of MLB, and revealed that MLB pretreatment inhibited NF-κB activation through inhibition of IκBα degradation and subsequent phosphorylation of NF-κB p65 in vitro and in vivo. In HMEC-1 cells, MLB pretreatment activated the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. Knockdown of Nrf2 with siRNA abolished the inhibitory effects of MLB on IκBα degradation and ICAM1 up-regulation, which were mimicked by PKC inhibition (Gö6983) or PI3K/Akt inhibition (LY294002). In summary, our results demonstrate that MLB inhibits NF-κB activation through PKC- and PI3K/Akt-mediated Nrf2 activation in HMEC-1 cells and protects against LPS-induced endothelial dysfunction in murine model of acute inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/farmacologia , Animais , Linhagem Celular , Citocinas/metabolismo , Células Endoteliais/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Lipopolissacarídeos , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacosAssuntos
Adenocarcinoma/terapia , Angioplastia/métodos , Neoplasias Duodenais/terapia , Artéria Hepática/anormalidades , Pancreaticoduodenectomia/métodos , Veia Porta/cirurgia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/patologia , Duodeno/irrigação sanguínea , Duodeno/patologia , Duodeno/cirurgia , Endoscopia do Sistema Digestório , Feminino , Fluoruracila/uso terapêutico , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/cirurgia , Humanos , Leucovorina/uso terapêutico , Artéria Mesentérica Superior/transplante , Microcirurgia/métodos , Invasividade Neoplásica , Compostos Organoplatínicos/uso terapêutico , Veia Porta/diagnóstico por imagem , Veia Porta/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resultado do Tratamento , Ultrassonografia DopplerAssuntos
Complicações na Gravidez , Gravidez , Síndrome da Artéria Mesentérica Superior , Adulto , Aorta/diagnóstico por imagem , Duodeno/diagnóstico por imagem , Feminino , Humanos , Intestino Delgado/diagnóstico por imagem , Desnutrição/etiologia , Desnutrição/terapia , Artéria Mesentérica Superior/diagnóstico por imagem , Terapia Nutricional/métodos , Remissão Espontânea , Síndrome da Artéria Mesentérica Superior/diagnóstico por imagem , Síndrome da Artéria Mesentérica Superior/terapia , Tomografia Computadorizada por Raios XRESUMO
Critical illness is accompanied by hypothalamic-pituitary-adrenal axis activation, but adrenal insufficiency characterized by inadequate glucocorticoid synthesis is common in critically ill cirrhotic patients, the "hepato-adrenal syndrome." Adrenal cortex also synthesizes androgen (dehydroepiandrosterone, DHEA). DHEA maintains microcirculation by enhancing vascular endothelial nitric oxide synthase (eNOS) activity. In critical patients of other disease entities, a shift of adrenal steroidogenesis away from androgens toward glucocorticoid has been noted, arousing interests in androgen replacement in critical settings. Nevertheless, this has not been surveyed in cirrhosis with hemorrhage. In this study, liver cirrhosis was induced with common bile duct ligation (BDL) in Spraque-Dawley rats. Sham rats were controls. DHEA or vehicle was injected at the beginning of hemorrhage-transfused procedure, followed by terlipressin injection. Hemodynamic parameters were measured. Then abdominal aorta, superior mesenteric arteries (SMA) and splenorenal shunt (prominent portosystemic collateral vessel in rodents) eNOS and inducible NOS protein expressions were evaluated. In bleeding BDL groups without terlipressin injection, adrenocorticotropic hormone (ACTH) stimulation test was performed to evaluate the DHEA response. The results showed that DHEA significantly elevated mean arterial pressure, cardiac output, and stroke volume of bleeding cirrhotic rats treated with terlipressin and reduced systemic vascular resistance without affecting SMA flow, resistance, and portal pressure. DHEA upregulated abdominal aorta and SMA eNOS expressions. ACTH did not stimulate DHEA synthesis in bleeding BDL rats. In conclusion, androgen deficiency exists in bleeding cirrhotic rats. DHEA augments terlipressin-induced amelioration of shock without influencing splanchnic hemodynamics, possibly rendering it a feasible adjunct to vasoconstrictors in variceal hemorrhage.
Assuntos
Androgênios/farmacologia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Western Blotting , Desidroepiandrosterona/farmacologia , Hemodinâmica/efeitos dos fármacos , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Terlipressina/farmacologiaRESUMO
AIMS AND OBJECTIVES: To prove the effects of an enteral feeding improvement massage for premature infants with regard to their feeding, growing and superior mesentery artery blood flow aspect by a randomised controlled trial. BACKGROUND: Premature infants have feeding-related problems related to eating and absorbing nutrition due to their immature gastrointestinal function. Studies regarding the effectiveness of premature infants' enteral feeding improvement by tactile stimulation massage are rare. DESIGN: The study group was composed of 55 patients. Of the 55 patients, 26 were randomised into an experimental group and 29 were randomised into a control group. METHODS: They were all born <34 weeks of gestational age between 1 July 2011 and 30 March 2012. Premature infants in the experimental group received enteral feeding improvement massage twice a day for 14 days, and infants in the control group received a sham exercise. The collected data were analysed by spss 19.0, through t test, chi-square test (Fisher's exact) and ANCOVA. RESULTS: (i) The experimental group had reached the day of full enteral feeding significantly faster. (ii) The experimental group had a higher superior mesentery artery peak velocity (Vmax ) and lower RI (resistant index). (iii) The experimental group of the feeding-intolerant subgroup had a higher superior mesentery artery Vmax and Vmin . (iv) The experimental group had a heavier weight and larger head circumference after 14 days. CONCLUSIONS: This study demonstrates that enteral feeding improvement massage can be helpful for achieving earlier full enteral feeding, more increased superior mesentery artery, and faster growing. In particular, it can be a therapeutic, independent and evidence-based nursing intervention for feeding-intolerant premature infants. RELEVANCE TO CLINICAL PRACTICE: Neonatal nurses in neonatal intensive care unit can apply enteral feeding improvement massage massage for feeding-intolerant infants.
Assuntos
Nutrição Enteral/métodos , Recém-Nascido Prematuro/crescimento & desenvolvimento , Massagem/métodos , Nutrição Enteral/enfermagem , Transtornos da Alimentação e da Ingestão de Alimentos/enfermagem , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Recém-Nascido/enfermagem , Doenças do Recém-Nascido/prevenção & controle , Doenças do Recém-Nascido/terapia , Unidades de Terapia Intensiva Neonatal , Masculino , Massagem/enfermagem , Artéria Mesentérica Superior/fisiologiaRESUMO
INTRODUCTION: Modern-era systemic therapy for locally advanced pancreatic adenocarcinoma (LAPC) offers improved survival relative to historical regimens but not necessarily improved radiographic downstaging to allow more patients to undergo resection. The aim of this study was to evaluate the survival, progression, and pathologic outcomes after resection of LAPC that did not regress from > 180 degrees arterial encasement after neoadjuvant therapy. METHODS: Sixty-one LAPC patients were brought to the operating room after neoadjuvant therapy for NCCN-defined unresectable pancreatic cancer between 2012 and 2017. Pts were explored with intent of pancreatectomy and irreversible electroporation for margin extension; 5 (8%) had metastatic lesions on exploratory laparoscopy and were excluded from analyses. Imaging was re-examined to confirm LAPC prior to surgery. Data were analyzed from a prospective pancreatic cancer database. RESULTS: Patients had arterial involvement of the celiac axis (37.5%) and/or superior mesenteric artery (42.9%) and/or an extended length of the common hepatic (n = 44.6%) artery. Twenty-nine males and 27 females, median 65 years of age, received neoadjuvant gemcitabine-based (58.9%) or FOLFIRINOX (35.7%) chemotherapy and stereotactic body (42.9%) or intensity-modulated (51.8%) radiation therapy. Median months from initiation of neoadjuvant therapy to surgery was 7.5. Sixty-one percent underwent Whipple, 21% distal, and 18% modified Appleby procedures; 57% patients underwent venous reconstruction. Ninety-day mortality was 2%. An R0 margin was achieved in 80%, and 53% were N0. Median overall and progression-free survival was 18.5 (95%CI 12.27-32.33) and 8.5 months (95%CI 6.0-15.0), respectively. One- and 3-year survival from surgery was 68.5% (95%CI 53.0-79.7) and 39.0% (95%CI 23.7-53.8), respectively. CONCLUSION: With modern-era neoadjuvant therapy, R0 resections can be achieved in a majority of non-metastatic patients with locally advanced, unresectable disease based on cross-sectional imaging.
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artérias/patologia , Neoplasias Pancreáticas/terapia , Idoso , Artéria Celíaca/patologia , Quimiorradioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática/patologia , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Artéria Mesentérica Superior/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasia Residual , Segunda Neoplasia Primária/etiologia , Compostos Organometálicos/administração & dosagem , Oxaliplatina , Pancreatectomia/métodos , Intervalo Livre de Progressão , Radiocirurgia , Radioterapia de Intensidade Modulada , Taxa de Sobrevida , GencitabinaRESUMO
Objective To investigate the vasodilative and endothelial-protective effects and the underlying mechanisms of total flavonoids from Astragalus (TFA). Methods The vasodilative activities of TFA were measured with a myograph ex vivo using rat superior mesenteric arterial rings. The primary human umbilical vein endothelial cell (HUVEC) viabilities were assayed using the cell counting kit-8 after hypoxia or normoxia treatment with or without TFA. Akt, P-Akt, eNOS, P-eNOS, Erk, P-Erk, Bcl-2 and Bax expression were analyzed using western blotting. Results TFA showed concentration-dependent vasodilative effects on rat superior mesenteric arterial rings, but had no effects on normal or potassium chloride precontracted arterial rings. TFA did not affect HUVEC viabilities in normoxia, but dramatically promoted cell proliferation in the concentration range of 1 to 30 µg/mL under hypoxia. Moreover, TFA significantly increased the ratios of P-Akt/Akt and P-eNOS/eNOS in vascular endothelial cells under hypoxic conditions, but did not change the P-Erk/Erk or Bcl-2/Bax ratios. Conclusions TFA might exhibit vasorelaxant and endothelial-protective effects via the Akt/eNOS signaling pathway.
Assuntos
Astrágalo , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Flavonoides/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hipóxia/fisiopatologia , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , Modelos Animais , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Percutaneous endoscopic gastrostomy (PEG) is widely used to provide nutritional support for patients with dysphagia and/or disturbed consciousness preventing oral ingestion, and PEG tube placement is a relatively safe and convenient non-surgical procedure performed under local anesthesia. However, the prevention of PEG-insertion-related complications is important. A 64-year-old man with recurrent pneumonia underwent tracheostomy and nasogastric tube placement for nutritional support and opted for PEG tube insertion for long-term nutrition. However, during the insertion procedure, needle puncture had to be attempted twice before successful PEG tube placement was achieved, and a day after the procedure his hemoglobin had fallen and he developed hypotension. Abdominal computed tomography revealed injury to a pancreatic branch of the superior mesenteric artery (SMA) associated with bleeding, hemoperitoneum, and pancreatitis. Transarterial embolization was performed using a microcatheter to treat hemorrhage from the injured branch of the SMA, and the acute pancreatitis was treated using antibiotics and supportive care. The patient was discharged after an uneventful recovery. Clinicians should be mindful of possible pancreatic injury and bleeding after PEG tube insertion. Possible complications, such as visceral injuries or bleeding, should be considered in patients requiring multiple puncture attempts during a PEG procedure.
Assuntos
Humanos , Pessoa de Meia-Idade , Anestesia Local , Angiografia , Antibacterianos , Estado de Consciência , Transtornos de Deglutição , Ingestão de Alimentos , Endoscopia , Gastrostomia , Hemoperitônio , Hemorragia , Hipotensão , Artéria Mesentérica Superior , Agulhas , Apoio Nutricional , Pancreatite , Pneumonia , Punções , TraqueostomiaRESUMO
BACKGROUND: The goal of this study was to investigate whether exogenous offer of L-arginine (LARG) modulates the gene expression of intestinal dysfunction caused by ischemia and reperfusion. METHODS: Eighteen Wistar-EPM1 male rats (250-300 g) were anesthetized and subjected to laparotomy. The superior mesenteric vessels were exposed, and the rats were randomized into 3 groups (n = 6): the control group (CG), with no superior mesenteric artery interruption; the ischemia/reperfusion group (IRG), with 60 minutes of ischemia and 120 minutes of reperfusion and saline injections; and the L-arginine group (IRG + LARG), with L-arginine injected in the femoral vein 5 minutes before ischemia, 5 minutes after reperfusion, and after 55 minutes of reperfusion. The total RNA was extracted and purified from samples of the small intestine. The concentration of each total RNA sample was determined by using spectrophotometry. The first-strand complementary DNA (cDNA) was synthesized in equal amounts of cDNA and the Master Mix SYBR Green qPCR Mastermix (SABiosciences, a Qiagen Company, Frederick, Md). Amounts of cDNA and Master Mix SYBR Green qPCR Mastermix were distributed to each well of the polymerase chain reaction microarray plate containing the predispensed gene-specific primer sets for Bax and Bcl2. Each sample was evaluated in triplicate, and the Student t test was applied to validate the homogeneity of each gene expression reaction (P < .05). RESULTS: The gene expression of Bax in IRG (+1.48) was significantly higher than in IRG-LARG (+9.69); the expression of Bcl2L1 in IRG (+1.01) was significantly higher than IRG-LARG (+22.89). CONCLUSIONS: The apoptotic cell pathway of 2 protagonists showed that LARG improves the gene expression of anti-apoptotic Bcl2l1 (Bcl2-like 1) more than the pro-apoptotic Bax (Bcl2-associated X protein).
Assuntos
Arginina/farmacologia , Intestino Delgado/irrigação sanguínea , Intestino Delgado/metabolismo , Isquemia/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Apoptose , Intestino Delgado/patologia , Isquemia/complicações , Isquemia/patologia , Masculino , Artéria Mesentérica Superior , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Proteína X Associada a bcl-2/genéticaRESUMO
BACKGROUND: Previous studies have shown that aqueous extract of the leaf of Tridax procuinbens is capable of lowering blood pressure through its vasodilatory effects. In the present study attempt was made to examine the biological active components of T procuinbens leaf using GC-MS methods. We further investigated the role of K+ channels in the vasorelaxation effects of Tridax procumbens using rat isolated mesenteric artery. METHODS: The superior mesenteric artery isolated from healthy, young adult Wistar rats (250-300 g) were precontracted with phenylephrine (PE) (10(-7) M) and potassium chloride (KCl) (60 mM) and were treated with Various concentrations of aqueous extract ofT procumbens (0.9.0 mg/ml). The changes in arterial tension were recorded using a force-displacement transducer (Model 7004; Ugo Basil Varese, Italy) coupled to data capsule acquisition system. RESULTS: The results of GG-MS revealed the presence of linoleic acid. The T. procumbens extract (TPE) ranging from 0.5-9.0 mg/mI significantly (p<0.05) reduced the, contraction induced by (PE) and (KCl) in a concentration-dependent manner. The extract also antagonised the calcium-induced vasoconstriction (1(-9) - 10(-5)) in calcium-free with high concentration of potassium as well as. in calcium- and potassium free physiological solutions. The vasorelaxing effect caused by TPE was significantly (p<0.05) attenuated with preincubation of potassium channels blockers (Barium chloride and apamin), NO synthaseinhibitor (L-NAME), prostacyclin inhibitor (indomethacin), atropine; propranolol, and methylene blue while it was not affected by preincubation with glibenclamide and tetra ethyl ammonium, 4-aminopyridine (4-AP) and oxadiazolo quinoxalin (ODQ). CONCLUSION: The results of this study demonstrate that T procumbens extract causes vasodilatory effects by blocking calcium channels and the vasodilatory effect of the extract may also be due to stimulation of prostacyclin production and opening of small-conductance Ga2+ activated potassium channels. The observed effect of this extract may be probably due to the presence of linoleic acid in this extract.
Assuntos
Asteraceae , Epoprostenol/fisiologia , Fitoterapia , Extratos Vegetais , Canais de Potássio/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Masculino , Artéria Mesentérica Superior/fisiologia , Folhas de Planta , Canais de Potássio/efeitos dos fármacos , Ratos Wistar , Vasodilatação/fisiologiaRESUMO
BACKGROUND & AIMS: Droxidopa improves hemodynamic and renal alterations of cirrhotic rats without changing portal pressure. We aimed to evaluate the effects of a combined treatment with droxidopa and non-selective beta-blockers or statins in order to decrease portal pressure, while maintaining droxidopa beneficial effects. METHODS: Acute studies combining droxidopa with carvedilol, propranolol or atorvastatin in four-week bile-duct ligated (BDL) rats and a chronic study combining propranolol and droxidopa for 5 days in CCl4 -cirrhotic rats were performed. Hemodynamic values were registered and biochemical parameters from blood and urine samples analyzed. RESULTS: Bile-duct ligated rats treated with carvedilol + droxidopa showed no changes in mean arterial pressure (MAP) and portal pressure (PP) compared to vehicles. Atorvastatin + droxidopa combination also failed to reduce PP, but maintained the beneficial increase in MAP and superior mesenteric artery resistance (SMAR) and decrease in blood flow (SMABF) caused by droxidopa. In contrast, the acute administration of propranolol + droxidopa significantly reduced PP maintaining a mild increase in MAP and improving, in an additive way, the decrease in SMABF and increase in SMAR caused by droxidopa. This combination also preserved droxidopa diuretic effect. When chronically administered to CCl4 -cirrhotic rats, propranolol + droxidopa caused a decrease in PP, a significant reduction in SMABF and an increase in SMAR. The combination did not alter liver function and droxidopa diuretic and natriuretic effect, and even improved free water clearance. CONCLUSION: Droxidopa could be effective for the renal alterations of cirrhotic patients on propranolol therapy and the combination of both drugs may balance the adverse effects of each treatment.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Droxidopa/farmacologia , Cirrose Hepática Experimental/tratamento farmacológico , Propranolol/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , Atorvastatina , Bilirrubina/sangue , Carbazóis/uso terapêutico , Carvedilol , Creatinina/sangue , Creatinina/urina , Droxidopa/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada/métodos , Hemodinâmica/efeitos dos fármacos , Ácidos Heptanoicos/uso terapêutico , Artéria Mesentérica Superior/efeitos dos fármacos , Concentração Osmolar , Pressão na Veia Porta/efeitos dos fármacos , Potássio/sangue , Potássio/urina , Propanolaminas/uso terapêutico , Propranolol/uso terapêutico , Pirróis/uso terapêutico , Ratos , Albumina Sérica , Sódio/sangue , Sódio/urina , Resistência Vascular/efeitos dos fármacosRESUMO
BACKGROUND: Recently, protection in shock (hemorrhagic or septic) by physostigmine has been demonstrated. Here, we studied the protective effect of intravenous infusion of physostigmine in a rat model of severe intestinal ischemia-reperfusion (I/R) injury and shock. MATERIALS AND METHODS: Mesenteric I/R was induced in male Wistar rats by occlusion of the superior mesenteric artery (90 min) and subsequent reperfusion (120 min). Physostigmine (30 or 70 µg/kg) was administered as bolus injection before induction of I/R. One additional group received, subsequent to the bolus of 30-µg/kg physostigmine, a continuous infusion of 60-µg/kg physostigmine till the end of the experiment. RESULTS: Physostigmine at a dose of 70 µg/kg administered before I/R significantly decreased the macroscopically and microscopically visible intestinal damage. In addition to and presumably as a result of this local protective effect, physostigmine prevented shock induced by reperfusion of the ischemically injured intestine. Lower doses (30 µg/kg) or continuous application of physostigmine were less advantageous. CONCLUSIONS: Physostigmine is clearly protective in intestinal I/R injury and shock. However, for this purpose, physostigmine has to be applied at a dose (70 µg/kg), that is, approximately double the amount of the presently used clinical dose.
Assuntos
Inibidores da Colinesterase/administração & dosagem , Intestino Delgado/irrigação sanguínea , Fisostigmina/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Choque/prevenção & controle , Administração Intravenosa , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Intestino Delgado/efeitos dos fármacos , Masculino , Artéria Mesentérica Superior , Ratos Wistar , Traumatismo por Reperfusão/complicações , Choque/etiologiaRESUMO
The phytoestrogen genistein (GST) and magnesium have been independently shown to regulate vascular tone; however, their individual vasodilatory effects are limited. The aim of this study was to examine the combined effects of GST plus magnesium on vascular tone in mesenteric arteries. The effects of pretreatment with GST (0-200 µmol/L), MgCl2 (0-4.8 mmol/L) and GST plus MgCl2 on 10 µmol/L phenylephrine (PE) precontracted mesenteric arteries in rats were assessed by measuring isometric force. BK(Ca) currents were detected by the patch clamp method. GST caused concentration- and partial endothelium-dependent relaxation. Magnesium resulted in dual adjustment of vascular tone. Magnesium-free solution eliminated the vasodilatation of GST in both endothelium-intact and denuded rings. GST (50 µmol/L) plus magnesium (4.8 mmol/L) caused stronger relaxation in both endothelium-intact and denuded rings. Pretreatment with the nitric oxide synthase (NOS) inhibitor L-N-nitroarginine methyl ester (L-NAME, 100 µmol/L) significantly inhibited the effects of GST, high magnesium, and the combination of GST and magnesium. BK(Ca) currents were amplified to a greater extent when GST (50 µmol/L) was combined with 4.8 versus 1.2 mmol/L Mg(2+). Our data suggest that GST plus magnesium provides enhanced vasodilatory effects in rat mesenteric arteries compared with that observed when either is used separately, which was related to an eNOS pathway and BK(Ca) current amplification.
Assuntos
Genisteína/metabolismo , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/agonistas , Magnésio/metabolismo , Músculo Liso Vascular/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fitoestrógenos/metabolismo , Vasodilatação , Animais , Suplementos Nutricionais , Endotélio Vascular/fisiologia , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Masculino , Artéria Mesentérica Superior , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/enzimologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Concentração Osmolar , Técnicas de Patch-Clamp , Ratos Sprague-Dawley , Resistência Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
The treatment of neuropathic pain is a medical challenge. The responsiveness to the different classes of drugs is often unsatisfactory and frequently associated to a wide range of side effects. International guidelines suggest for the "localized" neuropathic pain the topical treatment with 5% lidocaine medicated plaster, alone or associated to systemic drugs, as the first choice since its favorable efficacy and tolerability profile. Many clinical experiences support the rationale for using 5% lidocaine medicated plaster in different kinds of localized neuropathic pain, such as postherpetic and trigeminal neuralgia, compressive syndromes, painful diabetic polyneuropathy and pain secondary to trauma or surgical interventions. This paper reports a series of clinical cases whose heterogeneity suggests the wide burden of applicability of the topical 5% lidocaine, either alone and associated to systemic drugs. All the described conditions were characterized by a highly intense pain, not adequately controlled by actual medications, which improved after the use of topical lidocaine. The good response to lidocaine allowed the reduction, of even the withdrawal, of concurrent drugs and improved the patients' quality of life.
Assuntos
Anestésicos Locais/uso terapêutico , Lidocaína/uso terapêutico , Neuralgia/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Anestésicos Locais/administração & dosagem , Implante de Prótese Vascular , Neuropatias do Plexo Braquial/tratamento farmacológico , Neuropatias do Plexo Braquial/etiologia , Neoplasias da Mama/cirurgia , Carcinoma/radioterapia , Carcinoma/cirurgia , Artéria Celíaca/cirurgia , Clavícula/lesões , Clavícula/cirurgia , Terapia por Estimulação Elétrica , Feminino , Fixação Interna de Fraturas , Herniorrafia , Humanos , Traumatismos da Perna/cirurgia , Lidocaína/administração & dosagem , Masculino , Mamoplastia , Artéria Mesentérica Superior/cirurgia , Pessoa de Meia-Idade , Neuralgia/etiologia , Neuralgia Pós-Herpética/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/etiologia , Radioterapia Adjuvante/efeitos adversos , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/fisiopatologia , Neoplasias Tonsilares/radioterapia , Neoplasias Tonsilares/cirurgia , Neuralgia do Trigêmeo/tratamento farmacológicoRESUMO
BACKGROUND: Patients with borderline resectable pancreatic head cancer (BRPHC) have been treated with neoadjuvant chemoradiation therapy (NACRT) using metallic stents. The aim of the present study was to evaluate the efficacy and complications of covered self-expanding metallic stents (CSEMS) during the NACRT and surgical period. PATIENTS AND METHODS: We reviewed the outcomes of patients with BRPHC, then divided them chronologically into three groups as follows. Group A: upfront surgery with plastic stent (PS) deployment; group B: PS deployment plus neoadjuvant chemotherapy (NAC) and/or NACRT; group C: CSEMS deployment plus NAC/NACRT. Patients were categorized as borderline resectable based on National Comprehensive Cancer Network Guidelines, 2010. Days to reintervention (DR), reintervention rate, and the rate of R0 and complications were studied. Safe margin-negative resection (R0) surgery was defined as R0 surgery without reintervention during the NACRT period and no postoperative complications. RESULTS: DR were as follows. Groups A, B and C were 32, 55 and 97 days, respectively (P < 0.05). R0 surgery obtained in groups A, B and C was 53% (9/17), 100% (17/17) and 93% (14/15), respectively. CSEMS did not interfere with surgery. Safe R0 surgery obtained in groups B and C was 11% (2/19) and 67% (10/15), respectively (P < 0.05). Multivariate analysis showed that the odds ratio for safe R0 surgery was 16.210 (95% CI 2.457-106.962, P = 0.003) for CSEMS placement. CONCLUSION: CSEMS should be considered to relieve symptomatic biliary obstruction in patients with BRPHC receiving NACRT in view of the high attainability rate of safe R0 surgery compared to that with PS deployment.
Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia , Neoplasias Pancreáticas/terapia , Stents , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos Clínicos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Masculino , Artéria Mesentérica Superior/patologia , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Neoplasias Pancreáticas/cirurgia , Cuidados Pré-Operatórios/instrumentação , Desenho de Prótese , Esfinterotomia Endoscópica , GencitabinaRESUMO
BACKGROUND: Activated macrophage infiltration into the lungs is paramount in the pathogenesis of acute lung injury (ALI) induced by intestinal ischemia-reperfusion (I/R). Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a potent activator of the Adenosine 5'-monophosphate-activated protein kinase-sirtuin1 (AMPK/SIRT1) pathway against macrophage inflammation. We aimed to evaluate whether ω-3 PUFAs may protect against ALI induced by intestinal I/R via the AMPK/SIRT1 pathway. METHODS: Ischemia in male Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of fish-oil emulsion (FO emulsion, containing major ingredients as ω-3 PUFAs) or normal saline (control) was administered by intraperitoneal injection for three consecutive days to each animal. All animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analysis. RESULTS: Intestinal I/R caused intestinal and lung injury, evidenced by severe lung tissue edema and macrophage infiltration. Pretreatment with FO emulsion improved the integrity of microscopic structures in the intestine and lungs. Intestinal I/R induced the expression of macrophage-derived mediators (macrophage migration inhibitory factor and macrophage chemoattractant protein-1), inflammatory factors (nuclear factor κB, tumor necrosis factor α, interleukin 6, and interleukin 1ß), and proapoptosis factor p66shc. There was a decrease in the expression of AMPK, SIRT1, and claudin 5. FO emulsion significantly inhibited macrophage infiltration into the lungs, inflammatory factor expression, and p66shc phosphorylation. Importantly, FO emulsion restored AMPK, SIRT1, and claudin 5 in the lungs. CONCLUSIONS: Pretreatment with ω-3 PUFAs effectively protects intestinal and lung injury induced by intestinal I/R, reduces macrophage infiltration, suppresses inflammation, inhibits lung apoptosis, and improves the lung endothelial barrier after intestinal I/R in a manner dependent on AMPK/SIRT1. Thus, there is a potential for developing AMPK/SIRT1 as a novel target for patients with intestinal I/R-induced ALI.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Traumatismo por Reperfusão/complicações , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Lesão Pulmonar Aguda/imunologia , Animais , Citocinas/metabolismo , Injeções Intraperitoneais , Intestinos/irrigação sanguínea , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Artéria Mesentérica Superior/fisiologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/imunologia , Sirtuína 1/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
AIM: To evaluate the effects of montelukast and Hypericum perforatum against ischemia/reperfusion (I/R)-induced intestinal damage. MATERIALS AND METHODS: Twenty-eight hamsters were divided into 4 groups following midline abdominal laparotomy: control group (n = 7), I/R group (n = 7), montelukast and I/R (MIR) group (n = 7), and Hypericum perforatum and I/R (HPIR) group (n = 7). After 60 min of ischemia through obstruction of the superior mesenteric artery, 24 h of reperfusion was maintained. Ten minutes prior to the reperfusion period, the MIR group received 7 mg/kg of intraperitoneal montelukast and the HPIR group received 7 mg/kg of intraperitoneal Hypericum perforatum. Malondialdehyde, glutathione, myeloperoxidase, and cardiotrophin-1 levels were measured from blood samples. A semiquantitative histological evaluation was performed. RESULTS: Montelukast and Hypericum perforatum significantly reduced malondialdehyde levels and increased glutathione levels compared to the I/R group (P < 0.008). A statistically significant difference was also found between the I/R group and MIR and HPIR groups in terms of myelqperoxidase levels (P < 0.008). The MIR and HPIR groups showed increased cardiotrophin- 1 levels compared to the control and I/R groups (P < 0.008 for all). The MIR and HPIR groups showed significantly lower histological scores compared to the I/R group (P = 0.03 and P = 0.007, respectively). CONCLUSION: This study demonstrated the preventive effects of montelukast and Hypericum perforatum on I/R-induced intestinal injury.