Реферат
Se presenta el caso clínico de persona viviendo con VIH, con mala adherencia a tratamiento, sin vacunación previa para mpox, que evolucionó con un cuadro clínico probable de síndrome de reconstitución inmune posterior a reinicio de TAR, debido a la progresión de las lesiones cutáneas. Recibió tratamiento con tecovirimat por siete días, con evolución clínica favorable. Corresponde al primer caso reportado que recibió terapia con tecovirimat en Chile.
We report a clinical case of a person living with HIV with poor adherence to treatment, no previous mpox vaccination, who had a probable mpox syndrome immune reconstitution after restarting ART, due to worsening of skin lesions. He received treatment with tecovirimat for 7 days, clinically improved and was discharged in good condition. We reported this first clinical case that received tecovirimat in Chile.
Тема - темы
Humans , Male , Adult , HIV Infections/complications , Mpox (monkeypox)/complications , Mpox (monkeypox)/drug therapy , Immune Reconstitution Inflammatory Syndrome/etiology , Antiviral Agents/therapeutic use , Phthalimides/therapeutic use , Benzamides/therapeutic useРеферат
OBJECTIVE@#To analyze the efficacy and safety of flumatinib in the treatment of patients with chronic myeloid leukemia (CML).@*METHODS@#The clinical data of 56 CML patients treated with flumatinib from January 2020 to December 2021 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. Patients were divided into three groups: 35 new diagnosed CML patients treated with flumatinib (group A), 10 patients with imatinib/dasatinib intolerance (group B) and 11 patients with imatinib/dasatinib resistance (group C) switched to flumatinib treatment, respectively. The molecular response and adverse effects of flumatinib treatment were evaluated.@*RESULTS@#In group A, the early molecular response (EMR) at 3 months was 40.0%, and the major molecular response (MMR) at 6 and 12 months was 43.7% and 46.2%, respectively. In group B, the EMR was 50.0% at 3 months, and the MMR was 70.0% and 66.2% at 6 and 12 months, respectively. Among evaluable patients, 6 cases in group B achieved molecular response of 4.5 (MR4.5) at 12 months after switching to flumatinib treatment. In group C, 3 cases who switched from imatinib resistance to flumatinib achieved MR4.5 at 12 months, but 2 cases who switched from dasatinib resistance to flumatinib failed. Subgroup analysis showed significant differences in EUTOS long-term survival (ELTS) scores for patients in the medium-risk/high-risk group compared with those in the low-risk group for 3-month EMR (18.8% vs 57.9%), 6-month MMR (15.4% vs 63.2%) and 12-month MR4.5 (15.4% vs 69.2%) (P =0.036, P =0.012,P =0.015). The most common adverse effect in group A was thrombocytopenia, accounting for 54.5%, and 22.8% (8/35) patients discontinued the drug due to haematological adverse effects. Compared with patients who did not discontinue the drug or whose recovery time from discontinuation due to haematological toxicity was <1 month, patients whose recovery time from discontinuation was ≥1 month had a significantly worse 3-month EMR, 6-month MMR and 12-month MR4.5 (P =0.028, P =0.021, P =0.002).@*CONCLUSIONS@#Flumatinib has better molecular response and tolerance in patients with primary, imatinib/dasatinib-intolerant or resistant CML. Medium-risk/high-risk in ELTS score and time to recovery from discontinuation due to haematological toxicity ≥1 month are important factors influencing achievement of better molecular response in flumatinib treatment.
Тема - темы
Humans , Imatinib Mesylate/therapeutic use , Dasatinib/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Benzamides/therapeutic use , Chronic Disease , Treatment Outcome , Antineoplastic Agents/therapeutic useРеферат
OBJECTIVE@#To evaluate the clinical efficacy and safety of domestic imatinib (made in China) in patients with newly diagnosed chronic myeloid leukemia chronic phase(CML-CP).@*METHODS@#Fifty-seven newly diagnosed CML-CP patients who did not receive any other anti-CML treatment were treated by domestic imatinib 400 mg once a day. The hematological, cytogenetic and molecular reactions and safety were observed and evaluated after 3, 6 and 12 months of treatment.@*RESULTS@#Fifty-six patients were treated for ≥3 and 6 months, among which 50 patients were treated for ≥12 months. After 3 months of treatment, 49 patients underwent hematological examination, 47 patients (95.9%) achieved complete hematological response (CHR), 49 patients underwent cytogenetic examination, 39 patients (79.6%) achieved major cytogenetic response (MCyR), and 12 patients (24.5%) achieved complete cytogenetic response (CCyR). 49 patients underwent the level of BCR-ABL test, including 41 patients (83.7%) with BCR-ABL@*CONCLUSION@#In the real world, Domestics imatinib mesylate is effective and safe in the treatment of newly diagnosed CML-CP patients, but long-term follow-up data are still necessary to verify its long-term efficacy.
Тема - темы
Humans , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , China , Fusion Proteins, bcr-abl/genetics , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines , Pyrimidines/therapeutic use , Treatment OutcomeРеферат
Abstract The universal definition of myocardial infarction (MI) provides five subtypes of acute myocardial infarction (AMI). We present an interesting case of a type 2 myocardial infarction caused by the dilation of the left thoracic stomach.
Тема - темы
Humans , Male , Aged , Stomach/surgery , Gastric Dilatation/etiology , Anastomosis, Surgical/adverse effects , Esophagus/surgery , Inferior Wall Myocardial Infarction/etiology , Gastric Dilatation/drug therapy , Gastric Dilatation/diagnostic imaging , Benzamides/therapeutic use , Gastrointestinal Agents/therapeutic use , Morpholines/therapeutic use , Acute Disease , Esophagectomy/methods , Gastroparesis/etiology , Gastroparesis/drug therapy , Gastroparesis/diagnostic imaging , Coronary Stenosis/etiology , Coronary Stenosis/drug therapy , Coronary Stenosis/diagnostic imaging , Electrocardiography , Esophagus/diagnostic imaging , Inferior Wall Myocardial Infarction/diagnosisРеферат
ABSTRACT Imatinib, which inhibits tyrosine kinase activity of Bcr-Abl protein, is a standard form of treatment for chronic myeloid leukemia (CML). Through its immunomodulatory effect it affects T cell function in a number of ways. It inhibits antigen-induced T cell activation and proliferation. Antigen-specific T-cells and macrophages are vital for protection against Mycobacterium tuberculosis. Here we present a case of renal tuberculosis associated with imatinib therapy in the maintenance phase of CML. With granulomatous interstitial nephritis and positive tubercular DNA on renal biopsy, the condition was successfully treated with anti-tubercular therapy. This case provides support to the hypothesis that imatinib therapy in CML increases the susceptibility to tuberculosis and strict vigilance is required to enable its early detection and treatment.
RESUMO O imatinibe, um inibidor da atividade da tirosina-quinase da proteína BCR-ABL, faz parte do padrão de tratamento para leucemia mieloide crônica (LMC). Por conta de seu efeito imunomodulador, o imatinibe afeta a função dos linfócitos T de várias maneiras ao inibir a sua ativação e proliferação induzidas por antígenos. Linfócitos T e macrófagos antígeno-específicos são vitais para a proteção contra o Mycobacterium tuberculosis. O presente artigo relata um caso de tuberculose renal associada a terapia com imatinibe na fase de manutenção da LMC. Com nefrite intersticial granulomatosa e positividade para DNA de M. tuberculosis na biópsia renal, o paciente foi tratado com sucesso com terapia antituberculínica. O presente caso corrobora a hipótese de que a terapia com imatinibe na LMC aumenta a suscetibilidade à tuberculose, exigindo vigilância rigorosa para permitir sua detecção e tratamento precoces.
Тема - темы
Humans , Male , Adult , Tuberculosis, Renal/chemically induced , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Imatinib Mesylate/administration & dosage , Imatinib Mesylate/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Benzamides/therapeutic use , Drug Resistance, Neoplasm/drug effectsРеферат
PURPOSE: Roflumilast is the only oral phosphodiesterase 4 inhibitor approved to treat chronic obstructive pulmonary disease (COPD) patients [post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted] with chronic bronchitis and a history of frequent exacerbations. This study evaluated the efficacy and safety of roflumilast in Korean patients with COPD and compared the efficacy based on the severity of airflow limitation. MATERIALS AND METHODS: A post-hoc subgroup analysis was performed in Korean COPD patients participating in JADE, a 12-week, double-blinded, placebo-controlled, parallel-group, phase III trial in Asia. The primary efficacy endpoint was the mean [least-squares mean adjusted for covariates (LSMean)] change in post-bronchodilator FEV1 from baseline to each post-randomization visit. Safety endpoints included adverse events (AEs) and changes in laboratory values, vital signs, and electrocardiograms. RESULTS: A total of 260 Korean COPD patients were recruited, of which 207 were randomized to roflumilast (n=102) or placebo (n=105) treatment. After 12 weeks, LSMean post-bronchodilator FEV1 increased by 43 mL for patients receiving roflumilast and decreased by 60 mL for those taking placebo. Adverse events were more common in the roflumilast group than in the placebo group; however, the types and frequency of AEs were comparable to those reported in previous studies. CONCLUSION: Roflumilast significantly improved lung function with a tolerable safety profile in Korean COPD patients irrespective of the severity of airflow limitation.
Тема - темы
Aged , Female , Humans , Male , Middle Aged , Aminopyridines/therapeutic use , Asian People , Benzamides/therapeutic use , Cyclopropanes/therapeutic use , Double-Blind Method , Phosphodiesterase 4 Inhibitors/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Republic of Korea , Respiratory Function Tests , Treatment OutcomeРеферат
Prokinetics are commonly used for Functional Dyspepsia (FD) and GastroEsophageal Reflux Disease (GERD). Aims and Objectives: To evaluate the safety and efficacy of cinitapride Extended-Release (ER) tablets versus conventional cinitapride Immediate-Release (IR) tablets for the treatment of FD and GERD. Materials and Methods: Patients with FD and GERD received either cinitapride ER 3 mg tablets OD or cinitapride IR 1 mg tablets TID for 4 weeks in this randomized, multicentre study. Change in the mean intensity score of gastrointestinal (GI) symptoms (overall and individual) at the end of the study and at each weekly follow up visit as compared to baseline, patients with complete resolution of GI symptoms, patients with > 50% reduction from baseline in overall intensity score, rescue medication use and overall efficacy were recorded. The safety variables were reported adverse events (AEs), laboratory parameters, electrocardiogram, and overall tolerability. Unpaired t test, chi square test or Fisher’s exact test were used for analysis. p < 0.05 was considered significant. Results: Total 218 patients were enrolled Cinitapride ER tablets were non-inferior (non-inferiority margin -2.5) to cinitapride IR tablets for the change in the mean overall GI symptom intensity score at the end of the study as compared to the baseline (treatment difference - 0.2 (95% CI: -2.2, 1.7)); also, no significant difference was found for other efficacy variables (p > 0.05). Eight AEs of mild-to-moderate intensity were reported. There was also no difference in the overall tolerability between the study groups (p = 0.875). Conclusions : Both the study treatments were comparable in terms of safety and efficacy for the treatment of FD and GERD.
Тема - темы
Adult , Benzamides/administration & dosage , Benzamides/analogs & derivatives , Benzamides/pharmacokinetics , Benzamides/therapeutic use , Delayed-Action Preparations , Dosage Forms , Dyspepsia/drug therapy , Female , Gastroesophageal Reflux/drug therapy , Humans , Male , Middle Aged , Randomized Controlled Trials as Topic , Solubility , TabletsРеферат
OBJECTIVES: Despite its rising popularity, reports on the use of preoperative imatinib mesylate (IM) in patients with advanced gastrointestinal stromal tumor (GIST) are limited. This study aims to explore the clinical efficacy of preoperative IM in patients with primarily unresectable or metastatic/recurrent GIST. METHODS: Between September 2009 and February 2014, patients with primarily unresectable or metastatic/recurrent GIST treated by a single medical team were recruited and considered for preoperative IM therapy. Re-examination was conducted regularly and abdominal enhanced CT data, blood biochemistry and responses to IM were recorded. RESULTS: A total of 18 patients were enrolled, including 13 with a primary tumor (7 stomach, 3 small bowel, 2 rectal and 1 pelvic tumor) and 5 with recurrent or metastatic GIST (2 with liver metastasis, 2 with anastomotic recurrence and 1 with pelvic GIST). The median follow-up time was 9.5 months (range of 3-63). The median tumor sizes before and after initiation of IM treatment were 9.1 cm and 6.0 cm (p = 0.003) based on the CT findings, respectively. All patients showed a decrease in tumor burden and the median tumor size reduction was 35%. Sixteen of the 18 patients showed a partial response to IM and two possessed stable disease. Nine of the 18 patients (50%) underwent surgical resection of primary or metastatic/recurrent tumors, with a median of 7 months of IM therapy. One case each of multivisceral resection and tumor recurrence were noted. CONCLUSIONS: IM as a preoperative therapy is feasible and safe for unresectable or metastatic/recurrent GIST that can effectively decrease tumor size, facilitating resection. .
Тема - темы
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Stromal Tumors/drug therapy , Neoplasm Recurrence, Local/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/surgery , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/secondary , Gastrointestinal Stromal Tumors/surgery , Liver Neoplasms/secondary , Neoadjuvant Therapy , Neoplasm Metastasis/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Preoperative Care , Preoperative Period , Reproducibility of Results , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Tumor BurdenРеферат
We report a 58 year-old-man without comorbid conditions, with a history of two months of weight loss, malaise and headache. His initial laboratory analysis showed leukocytosis of 16,100/mL with 65% eosinophils and an absolute eosinophil count of 10,465/mL. Both bone marrow biopsy and aspirate showed infiltration by mature appearing eosinophils. Treatment was started with hydroxyurea, associated with prednisone without satisfactory decrease in the eosinophil count. Polymerase chain reaction showed the presence of the gene fusion product FIP1L1/PDGFRA. Imatinib therapy was initiated, resulting in a rapid and progressive reduction in the absolute eosinophil count, with normalization at the second week of treatment. The incidence of the myeloproliferative variant causing hypereosinophilic syndrome is rare. However, the dramatic response to imatinib emphasizes the need to study the presence of the fusion product FIP1L1/PDGFRA in all patients with eosinophilia of unknown etiology.
Тема - темы
Humans , Male , Middle Aged , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Hypereosinophilic Syndrome/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Treatment OutcomeРеферат
INTRODUCTION: Imatinib is a bcr‑abl tyrosine kinase inhibitor which has revolutionized the treatment for chronic myeloid leukemia (CML). Even though there is much data on CML chronic phase, there is limited data on imatinib‑naïve advanced phase CML. MATERIALS AND METHODS: We retrospectively analysed 90 patients with advanced phase CML (accelerated phase [AP]: 51 and blast crisis [BC]: 39), patients who received imatinib as frontline therapy. RESULTS: The median age of presentation in CML‑AP and CML‑BC were 32 years (12‑61) and 39 years (8‑59), respectively. Imatinib at 600 mg/day was initiated within 2 weeks of diagnosis. Median time to complete hematological response in both CML‑AP and CML‑BC was 3 months (CML‑AP: 1‑9 months and CML‑BC: 1‑14 months). At 6 months 30 (59%) CML‑AP and 15 (38%) CML‑BC patients achieved major cytogenetic response (MCyR), of them 24 (47%) and 10 (25.6%) being the complete cytogenetic response, respectively. At a median follow‑up of 41 months, the median overall survival in CML‑AP was 61 months, but in CML‑BC it was 14 months. The median progression‑free survival and event‑free survival were 30 months and 23 months in CML‑AP and 14 and 12 months in CML‑BC, respectively. On univariate analysis, performance status (PS), spleen size, and MCyR predicted survival in AP, whereas in BC, platelet count, PS, and early MCyR were predictive. Non‑hematologic and hematologic adverse events were observed in 80% and 60% of patients, respectively. Dose was reduced in 10% of patients for grade IV toxicity and interrupted in 30% for grade III toxicity. CONCLUSION: Front‑line imatinib is an option in advanced phases of CML especially in CML‑AP in low‑resource countries, where stem cell transplantation and alternate TKIs are not available.
Тема - темы
Adolescent , Adult , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Blast Crisis/drug therapy , Blast Crisis/mortality , Blast Crisis/pathology , Child , Drug Resistance, Neoplasm/drug effects , Female , Follow-Up Studies , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Neoplasm Staging , Piperazines/therapeutic use , Prognosis , Pyrimidines/therapeutic use , Remission Induction , Retrospective Studies , Survival Rate , Young AdultРеферат
No abstract available.
Тема - темы
Adult , Humans , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzamides/therapeutic use , Bone Marrow Examination , Chemoradiotherapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Neoplasms, Second Primary , Piperazines/therapeutic use , Positron-Emission Tomography , Prednisolone/administration & dosage , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Vincristine/administration & dosage , Whole Body Imaging/methodsРеферат
No abstract available.
Тема - темы
Female , Humans , Middle Aged , Base Sequence , Benzamides/therapeutic use , Bone Marrow/pathology , Fusion Proteins, bcr-abl/genetics , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Philadelphia Chromosome , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Sequence Analysis, DNA , Thiazoles/therapeutic use , Translocation, GeneticРеферат
No abstract available.
Тема - темы
Humans , Male , Middle Aged , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Central Nervous System Neoplasms/diagnosis , Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukocytes/metabolism , Neoplasm Recurrence, Local , Piperazines/therapeutic use , Pyrimidines/therapeutic useРеферат
The availability of imatinib followed by other tyrosine kinase inhibitors (TKIs) has dramatically altered the outcome of gastrointestinal stromal tumor (GIST). Patients with advanced or poor risk disease can now expect survival measured in years instead of months. An experienced multi disciplinary team (MDT) will be able to personalize therapy to ensure maximum benefit. This review will provide the updated information and finer points regarding state of the art management of GIST with the use of imatinib and other TKIs.
Тема - темы
Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Female , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Stromal Tumors/drug therapy , Humans , Precision Medicine , Male , Molecular Targeted Therapy , Patient Care Team , Piperazines/therapeutic use , Practice Guidelines as Topic , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Treatment OutcomeРеферат
No abstract available.
Тема - темы
Adolescent , Humans , Male , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Chromosome Deletion , Chromosomes, Human, Pair 7 , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl/genetics , Immunophenotyping , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Real-Time Polymerase Chain ReactionРеферат
FUNDAMENTO: O Imatinib é um inibidor do receptor tirosina-quinase que foi confirmada como exercendo um efeito inibidor sobre a atividade do receptor do PDGF, fator de crescimento plaquetário (PDGFRα e PDGFRβ). OBJETIVO: Investigar o efeito protetor do Imatinib na fibrose miocárdica em acetato de deoxicorticosterona (DOCA)/ratos com hipertensão induzida por sal. MÉTODOS: Sessenta ratos Sprague-Dawley machos, uninefrectomizados foram distribuídos em três grupos: ratos controles (grupo CON): grupo deoxicorticosterona (grupo DOCA); grupo deoxicorticosterona e Imatinib (grupo DOCA IMA). A Pressão Arterial Sistólica (PAS) foi medida quinzenalmente. Foi estudada a porção apical do ventrículo esquerdo. Foram empregados: coloração vermelho sirius, coloração de hematoxilina-eosina, imuno-histoquímica e ensaio de western blot. RESULTADOS: A PAS nos grupos DOCA e IMA+DOCA foi maior que no grupo CON nos dias 14 e 28. Os animais do grupo DOCA apresentaram fibrose intersticial e perivascular grave no dia 28, e as expressões de PI, PIII, tenascina-C e fibronectina foram significativamente maiores que nos grupos DOCA+IMA e CON. Quando comparados com o grupo CON, os grupos DOCA e DOCA+IMA apresentaram resposta inflamatória de tecido miocárdico e infiltração de monócitos/macrófagos de diferentes graus. As expressões proteicas do PDGF-A, PDGF-C e PDGFRα foram significativamente maiores nos grupos DOCA e DOCA+IMA que no grupo CON, mas a expressão proteica do p-PDGFRα no grupo DOCA+IMA foi menor que no DOCA. CONCLUSÃO: O Imatinib pode exercer efeitos inibitórios sobre a fibrose miocárdica em ratos com hipertensão induzida por DOCA/sal, os quais podem ser atribuídos à inibição da atividade do PDGFR-α.
BACKGROUND: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRβ) activity. OBJECTIVE: To investigate the protective effect of imatinib on the myocardial fibrosis in deoxycorticosterone-acetate (DOCA)/salt induced hypertensive rats. METHODS: Sixty male uninephrectomized Sprague-Dawley rats were assigned to three groups: control rats (CON group); deoxycorticosterone group (DOCA group); deoxycorticosterone and imatinib group (DOCA+IMA group). Systolic blood pressure (SBP) was measured biweekly. The apical portion of the left ventricle was studied. Sirius-Red staining, Hematoxylin-Eosin staining, immunohistochemistry and Western blot assay were employed. RESULTS: SBP in the DOCA group and DOCA+IMA group was higher than that in the CON group on day 14 and 28. Animals in the DOCA group showed severe interstitial and perivascular fibrosis on day 28, and the expressions of PI, PIII, tenascin-C and fibronectin were significantly higher than those in the DOCA+IMA group and CON group. When compared with the CON group, myocardial tissue inflammatory response and monocyte/macrophage infiltration of different degrees were observed in the DOCA group and DOCA+IMA group. Protein expressions of PDGF-A, PDGF-C and PDGFRα were signiflcantly higher in the DOCA and DOCA+IMA groups than those in the CON group, but the p-PDGFRα protein expression in the DOCA+IMA group was lower than that in the DOCA group. CONCLUSION: Imatinib can exert inhibitory effects on myocardial fibrosis in DOCA/salt induced hypertensive rats, which may be attributed to the inhibition of PDGFR-α activity.
Тема - темы
Animals , Male , Rats , Benzamides/pharmacology , Endomyocardial Fibrosis/drug therapy , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Receptor, Platelet-Derived Growth Factor alpha/antagonists & inhibitors , Blotting, Western , Benzamides/therapeutic use , Blood Pressure/drug effects , Desoxycorticosterone , Disease Models, Animal , Endomyocardial Fibrosis/pathology , Fibronectins/analysis , Fibronectins/metabolism , Fibrosis/drug therapy , Fibrosis/pathology , Hypertension/chemically induced , Hypertension/physiopathology , Nephrectomy/methods , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Rats, Sprague-Dawley , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Receptor, Platelet-Derived Growth Factor beta/antagonists & inhibitors , Receptor, Platelet-Derived Growth Factor beta/metabolism , Treatment Outcome , Tenascin/analysis , Tenascin/metabolismРеферат
Los tumores estromales gastrointestinales (GIST) son neoplasias mesenquimales que típicamente surgen a nivel del estómago, intestino delgado, colon, y otros sitios en la cavidad abdominal y su identificación se ha incrementado por mejoras en los criterios de detección. La mayor parte de los tumores GIST son causados por mutaciones activadoras en los genes de receptores transmembranares tirosina quinasa c-KIT y receptor alpha del factor de crecimiento derivado de plaquetas (PDGFRA). Las mutaciones causales de GIST se restringen solo a ciertas regiones del gen que corresponden a importantes zonas funcionales de c-KIT o PDGFRA. Se reporta que hasta 70% de casos de GIST se debe a mutaciones en el exón 11 del gen c-Kit que corresponde a la región yuxtamembrana del receptor. La región y el tipo de mutación determinan diferencialmente cómo se desarrolla la neoplasia, el pronóstico y su respuesta a inhibidores de las tirosina quinasas como el Imanatib. Por tal motivo, el genotipado de KIT y PDGFRA es importante para el diagnóstico y establecimiento de la sensibilidad a los inhibidores tirosina quinasa.
Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms typically arising in the stomach, small intestine, colon, and other sites in the abdominal cavity and its identification has improved dramatically mainly due to better criteria in its detection. Most GISTs tumors harbor activating mutations in the tyrosine kinase receptor c-KIT or platelet derived growth factor receptor-alpha (PDGFRA). Those mutations are restricted to a few regions corresponding to important functional domains of c-KIT or PDGFRA. Upto 70% of cases are due to mutations in exon 11 of c-KIT corresponding to its juxtamembrane region of the receptor. The location and type of mutation will differentially determine the development of the disease, its prognosis and the response to inhibitors of tyrosine kinases as Imanatib. For this reason, genotyping c-KIT and PDGFRA is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors.
Тема - темы
Humans , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Stromal Tumors/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Biomarkers, Tumor/metabolism , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Drug Resistance, Neoplasm , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/genetics , Mutation , Piperazines/therapeutic use , Proto-Oncogene Proteins c-kit/genetics , Pyrimidines/therapeutic use , Receptor, Platelet-Derived Growth Factor alpha/genetics , Treatment Outcome , Biomarkers, Tumor/geneticsТема - темы
Adult , Alkalosis/etiology , Antiemetics/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzamides/therapeutic use , Carboplatin/administration & dosage , Carcinoma/therapy , Cisplatin/adverse effects , Combined Modality Therapy , Dehydration/etiology , Dexamethasone/therapeutic use , Female , Gastrointestinal Agents/therapeutic use , Humans , Hypocalcemia/etiology , Hypokalemia/etiology , Metoclopramide/therapeutic use , Morpholines/therapeutic use , Nasopharyngeal Neoplasms/therapy , Nausea/chemically induced , Nausea/drug therapy , Neoplasm Staging , Ondansetron/therapeutic use , Paclitaxel/administration & dosage , Peripheral Nervous System Diseases/chemically induced , Radiotherapy , Vomiting/chemically induced , Vomiting/complications , Vomiting/drug therapyРеферат
Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-â (TGF-â). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-â T. cruzi, or SB-431542, an inhibitor of TGF-â receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-â signalling had been shown previously to be highly activated. We demonstrated that TGF-â treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-â secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-â levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease.
Тема - темы
Adult , Animals , Female , Humans , Male , Mice , Middle Aged , Benzamides/therapeutic use , Chagas Disease/metabolism , /metabolism , Dioxoles/therapeutic use , Gap Junctions/metabolism , Myocytes, Cardiac/chemistry , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/therapeutic use , Chagas Disease/drug therapy , Fluorescent Antibody Technique , Gap Junctions/drug effects , Immunohistochemistry , Microscopy, Confocal , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolismРеферат
The most common cause of gastroparesis is diabetes mellitus. The present study was carried out to asses the combination of itopride and pantoprazole in the treatment of diabetic gastroparesis. The study was an open label, multicentre, conducted in 743 patients with diabetic gastroparesis for a period of 3 weeks. The efficacy parameters included nausea, vomiting, early satiety, bloating, postprandial fullness, epigastric pain and regurgitation. The patients were evaluated based on the frequency and severity of symptoms and compared with the baseline scores. There were significant improvement in severity as well as the frequency of all the symptom parameters of the disease (p<0.001). The physicians' evaluation to the therapy was rated either excellent or good.