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4.
Clin J Gastroenterol ; 12(6): 552-555, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30955165

RESUMO

Everolimus is an mTOR (the mammalian target of rapamycin) inhibitor, which is used for the treatment of advanced renal cell carcinoma. Life-threatening hemorrhages are extremely rare adverse effect of everolimus. We herein report a successfully treated case of severe everolimus-related gastrointestinal hemorrhage by emergency surgical resection for patient with advanced renal cell carcinoma. A 72-year-old male was diagnosed with renal cell carcinoma, for which everolimus was administered after unsuccessful treatment with sunitinib and sorafenib. The patient suddenly developed hematemesis 4 weeks after administration. Upper gastrointestinal endoscopy showed gastric antral vascular ectasia. Once the hemorrhage was successfully cauterized by argon plasma coagulation, everolimus was discontinued. However, the patient after re-administration of everolimus developed hematemesis again and exhibited hemorrhage shock. Since therapeutic endoscopy could not achieve hemostasis, the patient underwent emergency distal gastrectomy with Billroth I reconstruction. The patient's vital signs and hemoglobin level stabilized after the surgery. Thereafter, the patient made a satisfactory recovery, and was discharged on postoperative day 10.


Assuntos
Antineoplásicos/efeitos adversos , Everolimo/efeitos adversos , Hematemese/induzido quimicamente , Gastropatias/induzido quimicamente , Idoso , Coagulação com Plasma de Argônio , Carcinoma de Células Renais/tratamento farmacológico , Cauterização/métodos , Substituição de Medicamentos , Hematemese/prevenção & controle , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Gastropatias/prevenção & controle
5.
BMC Gastroenterol ; 19(1): 62, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023238

RESUMO

BACKGROUND: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) can present as a benign lymphoid proliferation or a malignant lymphoma in patients taking MTX. Almost 50% of MTX-LPD cases show spontaneous remission after withdrawal of MTX treatment. Studies have suggested that the hyper-immune state of rheumatoid arthritis, the immunosuppressive state associated with MTX, and the carcinogenicity of the Epstein-Barr virus might contribute to MTX-LPD development. Although most cases of MTX-LPD occur at extranodal sites, few cases of MTX-LPD affecting the stomach and duodenum have been reported. To our knowledge, no other study has reported on the endoscopic observations of dramatic withdrawal and appearance of multiple digestive tract lesions in a short period of time. Herein, we report the clinical course and imaging findings of our case, which may be useful for understanding the pathological condition of MTX-LPD. CASE PRESENTATION: We describe the case of a 70-year-old woman with MTX-LPD of the stomach and duodenum. Disease regression was temporarily achieved after cessation of MTX treatment; however, it subsequently recurred, and complete response was only achieved after six cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (R-CHOP) chemotherapy. CONCLUSIONS: The first-choice therapy for patients taking MTX who develop suspected MTX-LPD should be the withdrawal of MTX treatment. Even after remission is achieved, patients should be kept under careful observation, and if the disease recurs, chemotherapy should be commenced promptly.


Assuntos
Antirreumáticos/efeitos adversos , Duodenopatias/induzido quimicamente , Transtornos Linfoproliferativos/induzido quimicamente , Metotrexato/efeitos adversos , Gastropatias/induzido quimicamente , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Duodenopatias/diagnóstico por imagem , Duodenopatias/tratamento farmacológico , Duodenopatias/patologia , Endoscopia do Sistema Digestório , Feminino , Humanos , Transtornos Linfoproliferativos/diagnóstico por imagem , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/patologia , Prednisona/uso terapêutico , Recidiva , Rituximab , Gastropatias/diagnóstico por imagem , Gastropatias/tratamento farmacológico , Gastropatias/patologia , Vincristina/uso terapêutico , Suspensão de Tratamento
6.
J Vet Med Sci ; 81(3): 418-424, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30674748

RESUMO

Equine Glandular Gastric Disease (EGGD) is a common disease in sport horses. This disease might be associated with usage of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating inflammatory diseases. Although gastroscopy has been an effective method for diagnosis, but a less invasive, and inexpensive method is preferred. This study used proteomic technology to identify candidate serum proteins that might be used as markers of NSAIDs induced EGGD. Five Thoroughbred horses were given high doses of NSAID, phenylbutazone to treat lameness. The experiment was divided into three periods: (i) Pre-EGGD period, (ii) during EGGD period, and (iii) Post-EGGD period. Gastroscopy were used to diagnose EGGD, serum was collected to perform gel electrophoresis (1D SDS-PAGE) and mass spectrometry (LC-MS) in order to identify serum proteins in each group. The candidate serum proteins were computationally predicted for the interaction between phenylbutazone and proteins, tissue specific expression, and association to gastric ulceration. After EGGD induction, all horses showed clinical signs of colic with marked congestion and erosion appearing in the mucosa of the glandular stomach whereas no change was observed in the mucosa of non-glandular stomach. Our proteomic results identified 14 proteins that might be used as EGGD markers. These proteins were highly expressed in the glandular stomach and some proteins were associated with phenylbutazone or ulcer development. However, confirmation of these candidate marker proteins is required with specific antibodies in the larger horse population before they can be considered for application in the field.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Proteínas Sanguíneas/metabolismo , Doenças dos Cavalos/induzido quimicamente , Fenilbutazona/toxicidade , Gastropatias/induzido quimicamente , Animais , Proteínas Sanguíneas/genética , Cavalos , Masculino
7.
Cutis ; 102(3): 169;170;175;176, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30372707

RESUMO

Reports of levamisole-induced vasculopathy (LIV) secondary to use of levamisole-contaminated cocaine largely have been limited to the skin. We report the case of a 35-year-old woman with painful purpuric lesions affecting the cheeks, nose, ears, arms, and legs of several days' duration. She recently had used crack cocaine. A biopsy of a lesion on the right arm demonstrated leukocytoclastic vasculitis. She also reported abdominal pain and gastric reflux of recent onset but denied any history of gastrointestinal tract disease. An upper gastrointestinal endoscopy was performed and demonstrated hemorrhagic erosions of the esophagus and stomach similar in appearance to the cutaneous lesions. Because dermatologists often are the specialists making the diagnosis of LIV, it is important they inform other involved clinicians that the skin may not be the sole repository of vascular insult.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/patologia , Cocaína Crack/efeitos adversos , Levamisol/efeitos adversos , Gastropatias/patologia , Estômago/patologia , Vasculite/patologia , Adulto , Transtornos Relacionados ao Uso de Cocaína/etiologia , Contaminação de Medicamentos , Feminino , Humanos , Levamisol/uso terapêutico , Púrpura/induzido quimicamente , Púrpura/patologia , Estômago/irrigação sanguínea , Gastropatias/induzido quimicamente , Vasculite/induzido quimicamente
8.
Nitric Oxide ; 78: 60-71, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29857061

RESUMO

Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H2S), NO, and CO. Mice were pretreated with AICAR (20 mg/kg, an AMPK activator) alone or with 50% ethanol. Other groups were pretreated with respective gaseous mediator inhibitors PAG, l-NAME, or ZnPP IX 30 min prior to AICAR, or with gaseous mediator donors NaHS, Lawesson's reagent and l-cysteine (H2S), SNP, l-Arginine (NO), Hemin, or CORM-2 (CO) 30 min prior to ethanol with or without compound C (10 mg/kg, a non-selective AMPK inhibitor). H2S, nitrate/nitrite (NO3-/NO2-), bilirubin levels, GSH and MDA concentration were evaluated in the gastric mucosa. The gastric mucosa was also collected for histopathological analysis and AMPK expression assessment by immunohistochemistry. Pretreatment with AICAR attenuated the ethanol-induced injury and increased H2S and bilirubin levels but not NO3-/NO2- levels in the gastric mucosa. In addition, inhibition of H2S, NO, or CO synthesis exacerbated the ethanol-induced gastric damage and inhibited the gastroprotection by AICAR. Pretreatment with compound C reversed the gastroprotective effect of NaHS, Lawesson's reagent, l-cysteine, SNP, l-Arginine, CORM-2, or Hemin. Compound C also reversed the effect of NaHS on H2S production, SNP on NO3-/NO2- levels, and Hemin on bilirubin levels. Immunohistochemistry revealed that AMPK is present at basal levels mainly in the gastric mucosa cells, and was increased by pretreatment with NaHS, SNP, and CORM-2. In conclusion, our findings indicate that AMPK activation exerts gastroprotection against ethanol-induced gastric damage and mutually interacts with H2S, NO, or CO to facilitate this process.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Monóxido de Carbono/metabolismo , Gasotransmissores/metabolismo , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Gastropatias/prevenção & controle , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Bilirrubina/metabolismo , Ativação Enzimática , Ativadores de Enzimas/farmacologia , Etanol , Feminino , Mucosa Gástrica/patologia , Masculino , Camundongos , Ribonucleotídeos/farmacologia , Gastropatias/induzido quimicamente
9.
Food Funct ; 9(3): 1713-1725, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29485160

RESUMO

We conducted the present study to determine the gastric injury preventive effects of polyphenols in Kuding tea (KTPs) in Kunming (KM) mice through the inhibition of gastric-acid secretion and the protection of the gastric mucosa. Mice treated with a high concentration of Kuding tea polyphenols (HKTP) had lower serum levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), motilin (MOT), substance P (SP), and endothelin-1 (ET-1), and higher serum levels of somatostatin (SS) and vasoactive intestinal peptide (VIP) than did the mice in the control group. Serum and gastric tissue levels of nitrous oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and GSH were higher in the HKTP-treated mice than in the control mice, but malondialdehyde (MDA) levels were lower in the HKTP-treated mice than in the control mice. The expression of occludin, epidermal growth factor (EGF), EGF receptor (EGFR), vascular endothelial growth factor (VEGF), nuclear factor of κ-light polypeptide gene enhancer in B-cells inhibitor-α (IκBα), Cu/Zn-SOD (cuprozinc-superoxide dismutase), Mn-SOD (manganese-superoxide dismutase), GSH-Px (glutathione peroxidase), neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), messenger RNA (mRNA) and protein in gastric tissue was stronger in the HKTP-treated mice than in the control mice, while the expression of p38 mitogen-activated protein kinase (P38MAPK, or p38), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), inducible NOS (iNOS), and cyclooxygenase-2 (COX-2) was weaker in the HKTP group than in the control group. And HKTP also could reduce the TNF-α, IL-1ß (interleukin-1 beta), and IL-6 mRNA expression in gastric injury mice. A high performance liquid chromatography (HPLC) assay showed that Kuding tea polyphenols (KTPs) contained chlorogenic acid, cryptochlorogenic acid, and isochlorogenic acids A, B, and C. These constituents contributed to the preventive effects of KTPs on gastric injury. According to these results, KTPs are a kind of active component that have a strong preventive effect on gastric injury.


Assuntos
Camellia sinensis/química , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Gastropatias/tratamento farmacológico , Estômago/lesões , Animais , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Ácido Clorídrico/efeitos adversos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Estômago/efeitos dos fármacos , Gastropatias/induzido quimicamente , Gastropatias/genética , Gastropatias/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Chá/química , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Brain Res Bull ; 139: 224-234, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29438780

RESUMO

Previous findings showed that inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), degrading enzymes of anandamide (2-AEA) and 2-arachidonoylglycerol (2-AG), reduced the nonsteroidal anti-inflammatory drug-induced gastric lesions. The present study aimed to investigate: i./whether central or peripheral mechanism play a major role in the gastroprotective effect of inhibitors of FAAH, MAGL and AEA uptake, ii./which peripheral mechanism(s) may play a role in mucosal protective effect of FAAH, MAGL and uptake inhibitors. METHODS: Gastric mucosal damage was induced by acidified ethanol. Gastric motility was measured in anesthetized rats. Catalepsy and the body temperature were also evaluated. Mucosal calcitonin gene-related peptide (CGRP), somatostatin concentrations and superoxide dismutase (SOD) activity were measured. The compounds were injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). RESULTS: 1. URB 597, JZL184 (inhibitors of FAAH and MAGL) and AM 404 (inhibitor of AEA uptake) decreased the mucosal lesions significantly given either i.c.v. or i.p. 2. URB 937, the peripherally restricted FAAH inhibitor failed to exert significant action injected i.p. 3. Ethanol-induced decreased levels of mucosal CGRP and somatostatin were reversed by URB 597, JZL 184 and AM 404, the decreased SOD activity was elevated significantly by URB 597 and JZL 184. 4. Neither compounds given i.c.v. influenced gastric motility, elicited catalepsy, or hypothermia. CONCLUSION: Elevation of central endocannabinoid levels by blocking their degradation or uptake via stimulation of mucosal defensive mechanisms resulted in gastroprotective action against ethanol-induced mucosal injury. These findings might suggest that central endocannabinoid system may play a role in gastric mucosal defense and maintenance of mucosal integrity.


Assuntos
Endocanabinoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Gastropatias/terapia , Análise de Variância , Animais , Ácidos Araquidônicos/farmacologia , Benzamidas/farmacologia , Benzodioxóis/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Carbamatos/farmacologia , Catalepsia/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Etanol/toxicidade , Mucosa Gástrica/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Hipotermia/induzido quimicamente , Masculino , Piperidinas/farmacologia , Ratos , Ratos Wistar , Somatostatina/metabolismo , Gastropatias/induzido quimicamente , Superóxido Dismutase/metabolismo
11.
Gan To Kagaku Ryoho ; 45(2): 377-379, 2018 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-29483453

RESUMO

A 70's man presenting with a chief complaint of stomachache was found to have advanced gastric cancer with a deep ulcer and some lymph-node metastases. We decided performing a curative operation after 2 courses of S-1 plus cisplatin. On the first course day 13 of chemotherapy, he complained of severe epigastralgia, and we diagnosed as generalized peritonitis due to perforation of gastric cancer. We performed an urgent laparoscopic operation, which made perforation simple closure and omentopexy. Curative distal gastrectomy with D2 lymph node dissection was successfully performed on postoperative day 16.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Ácido Oxônico/efeitos adversos , Gastropatias/induzido quimicamente , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Combinação de Medicamentos , Gastrectomia , Humanos , Masculino , Ácido Oxônico/administração & dosagem , Gastropatias/cirurgia , Tegafur/administração & dosagem
12.
Am J Emerg Med ; 36(1): 169.e5-169.e7, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29033342

RESUMO

Cyanoacrylate (LOCTITE® 401™) is a fast-acting adhesive available nationwide, with medical and household uses. Most cases of cyanoacrylate exposure are accidental and occur in children less than 5years old. Various routes of exposure have been reported including the dermal, oral, ocular, otic, nasal, and urethral routes; however, very few result in serious complication and mortality. Although a few cases of airway obstruction related to cyanoacrylate ingestion have been reported, intentional cyanoacrylate ingestion-induced gastrointestinal tract injury has scarcely been reported. In addition, there have been no reports of serious complications following intentional cyanoacrylate ingestion requiring surgical intervention. Herein, we report a case of intentional ingestion of cyanoacrylate in a 70-year-old man who required gastric wedge resection due to delayed gastric perforation.


Assuntos
Cianoacrilatos/envenenamento , Gastropatias/diagnóstico por imagem , Gastropatias/cirurgia , Estômago/cirurgia , Idoso , Endoscopia Gastrointestinal , Humanos , Masculino , Radiografia , Estômago/lesões , Gastropatias/induzido quimicamente , Tentativa de Suicídio
14.
J Vet Pharmacol Ther ; 41(2): 239-245, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29148168

RESUMO

In equids, phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups. Before treatment and 3 and 7 days after initiation of treatment, gastroscopy was performed and glandular gastric biopsies were collected and frozen at -80°C. Glandular disease was assessed on a scale of 0-4. Prostaglandin E2 concentrations in biopsies were measured using a commercially available enzyme-linked immunosorbent assay. All phenylbutazone-treated horses developed grade ≥2 glandular disease. Prostaglandin concentrations increased over time (p = .0017), but there was no effect of treatment (p = .49). These findings indicate that despite induction of glandular disease grade ≥2, phenylbutazone did not decrease basal glandular gastric prostaglandin E2 concentration.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Dinoprostona/análise , Mucosa Gástrica/química , Doenças dos Cavalos/induzido quimicamente , Fenilbutazona/efeitos adversos , Gastropatias/veterinária , Animais , Ensaio de Imunoadsorção Enzimática/veterinária , Mucosa Gástrica/patologia , Gastroscopia/veterinária , Doenças dos Cavalos/patologia , Cavalos , Gastropatias/induzido quimicamente , Gastropatias/metabolismo , Gastropatias/patologia
15.
J Gastroenterol ; 53(5): 618-630, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28856444

RESUMO

BACKGROUND: Curcumin, a pleiotropic substance used for centuries in traditional medicine, exhibits antioxidant, anti-inflammatory and antiproliferative efficacy against various tumours, but the role of curcumin in gastroprotection is little studied. We determined the effect of curcumin against gastric haemorrhagic lesions induced by 75% ethanol and alterations in gastric blood flow (GBF) in rats with cyclooxygenase-1 (COX-1) and COX-2 activity inhibited by indomethacin, SC-560 or rofecoxib, inhibited NO-synthase activity, capsaicin denervation and blockade of TRPV1 receptors by capsazepine. METHODS: One hour after ethanol administration, the gastric mucosal lesions were assessed by planimetry, the GBF was examined by H2 gas clearance, plasma gastrin was determined by radioimmunoassay, and the gastric mucosal mRNA expression of Cdx-2, HIF-1α, HO-1 and SOD 2 was analysed by RT-PCR. RESULTS: Curcumin, in a dose-dependent manner, reduced ethanol-induced gastric lesions and significantly increased GBF and plasma gastrin levels. Curcumin-induced protection was completely reversed by indomethacin and SC-560, and significantly attenuated by rofecoxib, L-NNA, capsaicin denervation and capsazepine. Curcumin downregulated Cdx-2 and Hif-1α mRNA expression and upregulated HO-1 and SOD 2, and these effects were reversed by L-NNA and further restored by co-treatment of L-NNA with L-arginine. CONCLUSIONS: Curcumin-induced protection against ethanol damage involves endogenous PG, NO, gastrin and CGRP released from sensory nerves due to activation of the vanilloid TRPV1 receptor. This protective effect can be attributed to the inhibition of HIF-1α and Cdx-2 expression and the activation of HO-1 and SOD 2 expression.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Mucosa Gástrica/patologia , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Gastropatias/prevenção & controle , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Fator de Transcrição CDX2/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Curcumina/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/farmacologia , Denervação , Regulação para Baixo/efeitos dos fármacos , Etanol , Feminino , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/metabolismo , Gastrinas/sangue , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Indometacina/farmacologia , Lactonas/farmacologia , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Pirazóis/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Gastropatias/induzido quimicamente , Sulfonas/farmacologia , Superóxido Dismutase/genética , Canais de Cátion TRPV/antagonistas & inibidores , Regulação para Cima/efeitos dos fármacos
16.
J Med Food ; 20(11): 1113-1120, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29120271

RESUMO

Indomethacin is a nonsteroid anti-inflammatory drug (NSAID) that is used to alleviate pain and inflammation in clinical medicine. Previous studies indicated that NSAIDs can cause gastrointestinal mucosal complications, and it is associated with mucosal lipid peroxidation and oxidative damage. Based on the evidences, decreasing oxidative stress may be an ideal therapeutic strategy for preventing gastrointestinal ulcer. Apple (Rosaceae Malus sp.) is one of the most commonly consumed fruits worldwide. The abundant polyphenolic constituents have received increasing attention for decades. In both in vivo and in vitro studies, the reports showed that apple polyphenol (AP) seems to provide an indirect antioxidant protection by activating cellular antioxidant enzymes to defend against oxidative stress. To address this issue and develop AP into a healthy improvement supplement, we studied the effect and potential mechanisms of AP in indomethacin-treated animal. The results showed AP can decelerate the gastric lesion, significantly suppress lipid peroxidation, increase the level of glutathione and the activity of catalase, and regulate the MAPK signaling proteins. These findings imply that AP protects the gastric mucosa from indomethacin-caused lesions and the protection is at least partially attributable to its antioxidative properties. This alternative medical function of AP may be a safe and effective intervention for preventing indomethacin-induced gastric complications.


Assuntos
Indometacina/efeitos adversos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Malus/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Gastropatias/tratamento farmacológico , Animais , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Ratos Sprague-Dawley , Gastropatias/induzido quimicamente , Gastropatias/metabolismo
17.
Nat Rev Gastroenterol Hepatol ; 14(12): 697-710, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28930292

RESUMO

Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.


Assuntos
Inibidores da Bomba de Prótons/efeitos adversos , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Medicina Baseada em Evidências/métodos , Gastrite/etiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Fatores de Risco , Gastropatias/induzido quimicamente
19.
Am J Case Rep ; 18: 794-798, 2017 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-28706179

RESUMO

BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.


Assuntos
Pólipos/induzido quimicamente , Proteínas Tirosina Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Gastropatias/induzido quimicamente , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva
20.
Cell Death Dis ; 8(7): e2939, 2017 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-28726772

RESUMO

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage.


Assuntos
Dano ao DNA , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Subunidade p50 de NF-kappa B/deficiência , Gastropatias/metabolismo , Tamoxifeno/efeitos adversos , Animais , Feminino , Mucosa Gástrica/patologia , Infecções por Helicobacter/induzido quimicamente , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Helicobacter felis/metabolismo , Camundongos , Camundongos Knockout , Subunidade p52 de NF-kappa B/genética , Subunidade p52 de NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-rel/genética , Proteínas Proto-Oncogênicas c-rel/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Gastropatias/induzido quimicamente , Gastropatias/genética , Gastropatias/patologia , Tamoxifeno/farmacologia
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