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1.
Mucosal Immunol ; 12(3): 784-794, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30846831

RESUMO

Helicobacter suis is the most prevalent non-Helicobacter pylori Helicobacter species in the human stomach and is associated with chronic gastritis, peptic ulcer disease, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. H. suis colonizes the gastric mucosa of 60-95% of pigs at slaughter age, and is associated with chronic gastritis, decreased weight gain, and ulcers. Here, we show that experimental H. suis infection changes the mucin composition and glycosylation, decreasing the amount of H. suis-binding glycan structures in the pig gastric mucus niche. Similarly, the H. suis-binding ability of mucins from H. pylori-infected humans is lower than that of noninfected individuals. Furthermore, the H. suis growth-inhibiting effect of mucins from both noninfected humans and pigs is replaced by a growth-enhancing effect by mucins from infected individuals/pigs. Thus, Helicobacter spp. infections impair the mucus barrier by decreasing the H. suis-binding ability of the mucins and by decreasing the antiprolific activity that mucins can have on H. suis. Inhibition of these mucus-based defenses creates a more stable and inhabitable niche for H. suis. This is likely of importance for long-term colonization and outcome of infection, and reversing these impairments may have therapeutic benefits.


Assuntos
Mucinas Gástricas/metabolismo , Mucosa Gástrica/fisiologia , Gastrite/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter heilmannii/fisiologia , Muco/fisiologia , Úlcera/metabolismo , Adulto , Animais , Proliferação de Células , Doença Crônica , Feminino , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Glicosilação , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Suínos , Úlcera/microbiologia
2.
Diabetes Metab Syndr ; 13(1): 30-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641715

RESUMO

STATEMENT OF THE PROBLEM: The rate of diabetes mellitus is increasing globally as a result of increased levels of blood glucose. The elevated blood glucose level results due to impairment in the production and action of insulin. An increase in glycated hemoglobin is associated with higher blood glucose levels that further results in nephropathy, neuropathy, retinopathy, and cardiovascular disease. Therefore, the study has investigated the correlation between HbA1c and creatinine levels among diabetic patients, suffering from foot ulcerations. METHODS: A prospective cohort hospital based-study has retrieved hospital records of patients during January 2009 and February 2015. A total of 192 patients, admitted in the Rajiv Gandhi Centre for Diabetes and Endocrinology, of Jawaharlal Nehru Medical College Hospital, Aligarh Muslim University, Aligarh, India were recruited. RESULTS: It has been examined that there is a positive correlation between ulcer duration and BMI, amputation rate and BMI, gender and BMI, hospital stay and BMI, HbA1c and BMI, Hb and BMI and triglyceride and BMI at 5% level of significance. CONCLUSION: Findings have shown positive association with gender, diabetes duration, ulcer size, grade of ulcer, amputation rate, hospital stay, Hb, SGOT/AST and triglyceride.


Assuntos
Infecções Bacterianas/epidemiologia , Biomarcadores/metabolismo , Creatinina/metabolismo , Diabetes Mellitus/fisiopatologia , Pé Diabético/complicações , Hemoglobina A Glicada/metabolismo , Úlcera/complicações , Adulto , Amputação/estatística & dados numéricos , Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Glicemia/análise , Pé Diabético/metabolismo , Pé Diabético/patologia , Feminino , Seguimentos , Humanos , Incidência , Índia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Úlcera/metabolismo , Úlcera/patologia , Adulto Jovem
3.
Clin Exp Rheumatol ; 36(6 Suppl 115): 90-96, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30582504

RESUMO

OBJECTIVES: The faecal calprotectin (FC) test is widely used as a non-invasive method for identifying intestinal inflammation. A recent study suggested FC may help to diagnose gastrointestinal involvement of Behçet's syndrome (GIBS). We aimed to determine whether FC helps to distinguish active from inactive intestinal involvement in GIBS. METHODS: We tried to contact 70 GIBS patients registered in our tertiary multidisciplinary clinic. We prospectively collected faecal specimens and serum from 39 GIBS patients who gave informed consent assessing calprotectin and CRP levels followed by a colonoscopy. We included 47 Crohn's disease (CD) patients as controls. Active disease was defined as having ulcer/s on colonoscopy. We filled the Disease Activity Index for Intestinal Behçet's Disease (DAIBD) and Crohn's Disease Activity Index (CDAI). The cut-off for positive FC was defined as ≥150 µg/g. RESULTS: Ulcers were detected in 12/39 GIBS patients. Sensitivity and specificity of the FC test for active disease was 91.7 (95%CI:61.5-99.8) and 74.1% (95%CI:53.7-88.9). Median FC and CRP levels and DAIBD scores were higher among patients with ulcers, whereas serum calprotectin and CDAI scores were not. A negative FC test was the only significant predictor of remission (OR:37.04, 95%CI:2.4-561.6; p=0.009) on multivariate analysis. Among CD patients, 16/25 active patients and 3/22 patients in endoscopic remission had a positive FC test (OR:11, 95%CI:11-49). CONCLUSIONS: FC, but not serum calprotectin seems to be a useful non-invasive tool for assessing disease activity in GIBS. Whether the presence of oral ulcers can cause false positive results remains to be studied.


Assuntos
Síndrome de Behçet/diagnóstico , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Doenças do Colo/metabolismo , Fezes/química , Mediadores da Inflamação/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Úlcera/diagnóstico , Adulto , Síndrome de Behçet/sangue , Síndrome de Behçet/metabolismo , Biomarcadores/metabolismo , Calgranulina A/sangue , Calgranulina B/sangue , Doenças do Colo/sangue , Doenças do Colo/diagnóstico , Colonoscopia , Feminino , Humanos , Mediadores da Inflamação/sangue , Complexo Antígeno L1 Leucocitário/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Úlcera/sangue , Úlcera/metabolismo
4.
Future Med Chem ; 10(1): 53-70, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29235887

RESUMO

AIM: There has been an enormous commercial development following the introduction of selective COX-2 inhibitors. Efforts are continuously done to discover efficient and safe COX-2 inhibitors. RESULTS: A series of 4-methylsulfonylphenyl derivatives was designed, synthesized and screened for preferential inhibition of COX-2 over COX-1 isoforms and in vivo anti-inflammatory activity using the rat paw edema method. The most active ones were investigated via ulcerogenic liability and molecular docking. Physicochemical parameters were calculated for all the newly synthesized compounds. CONCLUSION: The new compounds showed clear preferential COX-2 over COX-1 inhibition. Selective indices for compounds 4, 6b and 6e were 124, 131 and 119, respectively. Compound 4 reached 71% in vivo anti-inflammatory inhibition. The compounds obeyed 'Lipinski's rule of five'.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Edema/tratamento farmacológico , Úlcera/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Carragenina/administração & dosagem , Ciclo-Oxigenase 1/metabolismo , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/metabolismo , Masculino , Estrutura Molecular , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Úlcera/metabolismo
5.
J Med Food ; 21(4): 408-415, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29216438

RESUMO

Several studies have shown the protective effect of dairy products, especially α-lactalbumin and derived hydrolysates, against induced gastric ulcerative lesions. The mucus strengthening represents an important mechanism in the defense of gastrointestinal mucosa. Previously, a hydrolysate from casein (CNH) and a hydrolysate from whey protein concentrate rich in ß-lactoglobulin (WPH) demonstrated a stimulatory activity on mucus production in intestinal goblet cells. The aim of this work was to evaluate the possible antiulcerative activity of these two hydrolysates in an ethanol-induced ulcer model in rats. All tested samples significantly reduced the ulcerative lesions index (ULI), compared with the saline solution, using doses of 300 and 1000 mg kg-1 body weight with decreases up to 66.3% ULI. A dose-response relationship was found for both hydrolysates. The involvement of endogenous sulfhydryl (SH) groups and prostaglandins (PGs) in the antiulcerative activity was evaluated using their blockage. The antiulcerative activity of WPH showed a drastic decrease in presence of N-ethylmaleimide (from 41.4% to 9.2% ULI). However, the CNH antiulcerative properties were not significantly affected. The cytoprotective effect of WPH appears to depend on a PG-mediated mechanism. In conclusion, CNH and WPH demonstrated in vivo antiulcerative properties and represent a promising alternative as protectors of the gastric mucosa.


Assuntos
Antiulcerosos/uso terapêutico , Caseínas/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Leite/química , Hidrolisados de Proteína/uso terapêutico , Úlcera/prevenção & controle , Proteínas do Soro do Leite/uso terapêutico , Animais , Antiulcerosos/farmacologia , Caseínas/farmacologia , Etanol/efeitos adversos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Muco/metabolismo , Hidrolisados de Proteína/farmacologia , Ratos Wistar , Úlcera/induzido quimicamente , Úlcera/metabolismo , Proteínas do Soro do Leite/farmacologia
6.
J Complement Integr Med ; 14(4)2017 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-28665790

RESUMO

Background Quinine (QT) is an important anti-malarial drug; however, there is little information about its effects on the gut. Therefore, this study aimed to investigate the effects of a therapeutic dose of QT on the healing of gastric ulcer in rats. Methods Male Wistar rats weighing 150-200 g were divided into three groups: control rats without ulcer (group 1), ulcerated rats treated with 1 mL/kg (p.o.) normal saline (NS) (group 2), and ulcerated rats treated with 10 mg/kg (p.o.) QT (group 3). Ulcers were induced by serosal application of 80 % acetic acid to the stomach of rats anaesthetized with 50 mg/kg thiopentone sodium and treatment was given three times daily. Healing was assessed on days 3, 7 and 10 after ulcer induction by macroscopic measurement of: ulcer area, histology, lipid peroxidation, superoxide dismutase activity and gastric mucus secretion. Results At day 3, there was no significant difference (p>0.05) in ulcer areas between NS- and QT-treated rats. By day 10, however, the percentage area healed in NS treated (59.6±2.35 %) was significantly higher (p<0.05) than in QT rats (49.0±2.20 %) and clearing of inflammatory cells and re-epithelization was greater in NS-treated group. By days 7 and 10, lipid peroxidation was significantly higher in QT animals, when compared with NS-treated rats and controls (p<0.05). Superoxide dismutase activity and mucus secretion were significantly (p<0.05) higher in NS-treated than QT-treated rats. Conclusions QT delayed ulcer healing by prolonging the inflammatory phase of healing, increasing oxidative stress, reducing antioxidant activity and gastric mucus secretion.


Assuntos
Cinchona/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Extratos Vegetais/efeitos adversos , Quinina/efeitos adversos , Úlcera Gástrica , Cicatrização/efeitos dos fármacos , Ácido Acético , Animais , Cinchona/química , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Inflamação/etiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Muco/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Quinina/uso terapêutico , Ratos Wistar , Reepitelização/efeitos dos fármacos , Estômago , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Úlcera/induzido quimicamente , Úlcera/metabolismo , Úlcera/patologia
7.
Rheumatology (Oxford) ; 56(1): 134-144, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27744360

RESUMO

OBJECTIVES: Behçet's disease (BD), an auto-inflammatory vasculitis with oro-genital ulcerations, skin lesions and uveitis, is regarded as T cell mediated. A successful trial with rituximab suggests an additive role for B cells in the pathogenesis. Therefore, we studied B cell abnormalities in BD patients and the effect of TNF-blocking therapy. METHODS: B cells in blood (n = 36) and tissue (n = 6) of BD patients were analysed with flow cytometry and/or immunohistochemistry and compared with healthy controls (n = 22). BD current activity form (BDCAF) in relation to B cell somatic hypermutations (SHMs) and immunoglobulin class-switching were studied. RESULTS: Thirty-six patients (17 males) were included, mean age 44 years, average disease duration 10 years and mean BDCAF 2.7. Blood B cell numbers were significantly lower in patients than in controls (P = 0.0061), mostly due to decreased CD27+ memory B cells expressing IgM (P = 0.0001), IgG (P = 0.0002) and IgA (P = 0.0038) B cell subsets. CD27+ IgA+ B cells showed the highest magnitude of decrease in active disease, measured with BDCAF (P = 0.02). CD27+ IgM+ IgD+ B cells were impaired in replication history (P = 0.0133) and selection of SHM, whereas IgA+ B cells carried elevated SHM levels (P = 0.04) and lower IgA2 subclass usage (P = 0.0004) than controls. Immunohistochemistry revealed B cells in tissue of active mucosal ulcers. In adalimumab-treated patients, blood B cells were similar to controls. CONCLUSION: We show significant deviations in the memory B cell compartment, related to disease activity and therapeutic efficacy. Pronounced molecular impairments were seen in the fast-responding IgM+-memory and the mucosal IgA+-memory B cells. Because of the demonstrated abundance of B cells in affected tissue, we hypothesize relocation of memory B cells to the site of inflammation could account for the deviations found in blood of BD patients. These peripheral B cells are easily accessible as a marker to monitor therapeutic efficacy.


Assuntos
Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Síndrome de Behçet/imunologia , Memória Imunológica/imunologia , Úlcera/imunologia , Adalimumab/uso terapêutico , Adulto , Idoso , Antirreumáticos/uso terapêutico , Subpopulações de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/metabolismo , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina A/imunologia , Switching de Imunoglobulina , Imunoglobulina D/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Hipermutação Somática de Imunoglobulina , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Úlcera/etiologia , Úlcera/metabolismo , Adulto Jovem
8.
Dermatol Ther ; 30(1)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27723197

RESUMO

Behçet's disease (BD) involves oxidative stress (OS) aggression and imbalanced oxidant/antioxidant status. Owing to its antioxidant property, allicin is proposed for treating BD. In this study, we aimed to investigate the efficacy and safety of allicin on patients with BD with mucocutaneous involvement. Twenty patients with active BD were treated with allicin for 12 weeks and followed up to 16 weeks. A clinical manifestations index and scoring system was the primary technique for efficacy evaluation at baseline and Week 4, 12, 16. The secondary efficacy variables were OS-related biomarkers determined at first and final visit. Side effects were assessed at each visit. By the end of study, 18 patients completed the trail. Allicin was effective in decreasing ulcer and cutaneous parameters (p < .05). Especially, the greatest reduction of mucocutaneous scores emerged from baseline after the first four-week treatment (p < .05). Meanwhile, allicin remarkably ameliorated OS-related parameters. Besides, some side effects were observed on allicin, these adverse reactions, however, disappeared upon cessation of drugs. In conclusion, allicin is a safe and effective treatment for BD, which may be associated with its inhibiting OS and regulating oxidant/antioxidant status balance.


Assuntos
Antioxidantes/administração & dosagem , Síndrome de Behçet/tratamento farmacológico , Doenças dos Genitais Femininos/tratamento farmacológico , Doenças dos Genitais Masculinos/tratamento farmacológico , Úlceras Orais/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Ácidos Sulfínicos/administração & dosagem , Úlcera/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antioxidantes/efeitos adversos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/metabolismo , Biomarcadores/metabolismo , Feminino , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Femininos/metabolismo , Doenças dos Genitais Masculinos/diagnóstico , Doenças dos Genitais Masculinos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Úlceras Orais/diagnóstico , Úlceras Orais/metabolismo , Projetos Piloto , Indução de Remissão , Índice de Gravidade de Doença , Ácidos Sulfínicos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Úlcera/diagnóstico , Úlcera/metabolismo , Adulto Jovem
9.
Angiología ; 68(6): 471-477, nov.-dic. 2016. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-157710

RESUMO

Introducción: La isquemia crítica se define como dolor de reposo, úlcera o gangrena de la extremidad (estadios IV-VI de Rutherford) en pacientes con enfermedad arterial periférica. El tratamiento endovascular ha demostrado ser una opción válida en el sector infrapoplíteo. Material y métodos: Estudio retrospectivo, descriptivo, registrado en nuestro centro desde 2005 hasta 2015. El diagnóstico se hizo mediante cartografía doppler prequirúrgica y arteriografía intraoperatoria. Describimos como resultado primario el porcentaje de amputación. Como resultados secundarios describimos el éxito clínico a los 6, 12 y 24 meses, el tiempo de hospitalización y la necesidad de amputación menor. El éxito técnico se define como la posibilidad de realizar angioplastia de al menos un vaso y lograr permeabilidad hasta algún arco. Se describe también la mortalidad. Resultados: Incluye 72 extremidades y a 68 pacientes (53 hombres y 15 mujeres) con edad media de 73,4±11,4 años, 75% hipertensos, 80,5% diabéticos, 54% dislipidémicos, 13,8% fumadores activos, 33% con cardiopatía isquémica, 22% con insuficiencia renal, que presentaban isquemia crítica (87,5% en estadio V-VI de Rutherford) debida exclusivamente a enfermedad del sector infrapoplíteo. Realizamos angioplastias simples de un vaso distal (59,8%) o más (40,2%), con éxito técnico del 97%. Las lesiones se definieron como 48,6% de miembros con estenosis y 51,4% miembros con oclusión. El porcentaje de amputación mayor fue del 25%. En el análisis univariante con las variables estudiadas, la amputación mayor tuvo relación estadísticamente significativa (p = 0,014) con el intento fallido de recanalización de alguno de los vasos enfermos. El éxito clínico fue del 72, 47,2 y del 26,4% a los 6, 12 y 24 meses, respectivamente. La mediana de hospitalización fue de 18 días (rango 3-45). La mediana de seguimiento fue de 365 días (rango 6-2.555) y la mortalidad del 25%. Conclusión: Nuestros resultados demuestran que la angioplastia simple en el tratamiento de la isquemia crítica debida a enfermedad del sector infrapoplíteo es una técnica válida, ya que permite tratar pacientes con elevada morbilidad con una aceptable tasa de salvamento del miembro (AU)


Introduction: Critical limb ischaemia is defined as rest pain, limb ulcers, or gangrene (IV- VI Rutherford Classification) in patients with peripheral arterial disease. Endovascular treatment has been shown to be a suitable option in below-the-knee lesions. Materials and methods: A retrospective, descriptive study was conducted on patients diagnosed with critical limb ischaemia secondary to isolated infrapopliteal lesions, registered in our centre from 2005 to 2015. Diagnosis was made with Doppler ultrasonound mapping and intraoperative angiography. Technical success was defined as performing one vessel angioplasty. Primary end-point was overall limb salvage. Secondary end-points were described as clinical success, and overall mortality. Results: The study included a total 72 limbs of 68 patients (53 men and 15 women) with a mean age of 73.4±11.4 years. Of these, 75% were hypertensive, 80.5% were diabetics, 22% had renal failure. A Rutherford classification of V-VI was observed in 86% of patients. One-vessel angioplasty was the most frequent treatment in 59.8%, and 2 or more vessels in 40.2%. There was 97% technical success. Overall limb salvage was 75%. Clinical success rates at 6, 12 and 24 months were 72, 47.2, and 26.4%, respectively. The median hospital stay was 18 days (range 12-35), with a median follow-up of 365 days (range 180-730). Overall mortality during follow up was 25%. Conclusion: Our results are similar as those described in the literature, and demonstrate that balloon angioplasty is a useful technique in critical limb ischaemia patients with infrapopliteal lesions, and has an adequate limb rate salvage (AU)


Assuntos
Humanos , Masculino , Feminino , Angioplastia/métodos , Isquemia/metabolismo , Isquemia/patologia , Úlcera/diagnóstico , Doença Arterial Periférica/patologia , Estudos Retrospectivos , Procedimentos Endovasculares/métodos , Efeito Doppler , Angioplastia , Isquemia/sangue , Isquemia/complicações , Úlcera/metabolismo , Doença Arterial Periférica/metabolismo , Epidemiologia Descritiva , Procedimentos Endovasculares/normas
10.
Angiología ; 68(6): 484-490, nov.-dic. 2016. tab, graf, ilus
Artigo em Espanhol | IBECS | ID: ibc-157712

RESUMO

Introducción: Las úlceras venosas (UV) son las úlceras más frecuentes de las extremidades, y generan morbilidad importante y altos costos para los sistemas de salud. Las técnicas quirúrgicas usadas para el control de la hipertensión venosa han venido siendo remplazadas con mayor frecuencia por procedimientos mínimamente invasivos como la escleroespuma. Objetivo: Determinar el tiempo de cicatrización de la UV con un protocolo de manejo que incluyó la oclusión venosa endoluminal con escleroespuma ecoguiada del eje axial, perforantes y terminal insuficientes (técnica TAPIRS) más curaciones con vendaje multicapas (VM) hasta la cicatrización de la herida. Material y métodos: Ensayo clínico prospectivo no controlado (cuasiexperimental) en pacientes con UV (CEAP C6) realizado en la consulta externa de cirugía vascular, durante 2013-2014. Se incluye a 17 pacientes mayores de 18 años, portadores de una UV con eje axial insuficiente, e índice tobillo-brazo mayor a 0,8. Se analizaron en total 17 extremidades. Se realizó inyección de escleroespuma (técnica de Tessari) usando polidocanol al 3% en el sistema venoso superficial con oclusión del eje venoso axial, perforantes y terminal asociados al lecho de la úlcera, guiada por ecodoppler junto con aplicación de VM y curación según las condiciones de la herida. Se realizaron controles clínicos y fotográficos en cada curación, aplicación de VM hasta el cierre de la UV y controles ecográficos a la 4 y 12 semanas. Resultados: El promedio de edad fue de 56,4 años, la duración de la úlcera activa previamente al tratamiento fue de 2,96 años, todas las UV cicatrizaron antes de las 7 semanas, con una tasa de cierre de 3,92 cm2/semana y el tiempo de cierre de la úlcera fue de 3,92 semanas (24 días). Conclusión: La oclusión endoluminal venosa usando la técnica TAPIRS (cierre de los ejes axiales, perforantes y terminales insuficientes con escleroespuma ecoguiada) junto a la aplicación de VM es una técnica que favorece la rápida cicatrización de las UV (AU)


Introduction: Chronic venous ulcers (CVU) are the most common ulcers occurring in the lower limbs, having a high morbidity and place a high financial strain on the health system. The traditional surgical techniques are being replaced by minimally invasive procedures, such as foam sclerotherapy. Objective: The aim of this study was to determine CVU healing times and rates using the terminal, axial and perforator interruption of the reflux source (TAPIRS) protocol, which included an endoluminal venous occlusion with ultrasound-guided foam and a multilayer bandage system until achieving ulcer healing. Material and methods: A prospective uncontrolled trial was conducted on patients with chronic venous leg ulcers (CEAP [clinical, etiological, anatomical and pathological elements] C6) during 2013 and 2014. A total of 17 patients aged 18 years and over, presenting with venous insufficiency, CVU, and an ankle-brachial index greater than 0.8, were included, and total of 17 limbs were analysed. All of the patients were subjected to endoluminal occlusion with ultrasoundguided foam in the axial superficial venous system and perforator and terminal veins near to the ulcer, using Tessari method with 3% polidocanol. Follow-up was carried out at every week and a doppler test was conducted after 4 and 12 weeks. Results: The mean age of the patients was 56.4 years. The active ulcer duration prior to treatment was 2.96 years. The study showed that all CVU were healing before 7 weeks, the healing rate was 3.92 cm2/week, and the time until the ulcer was healed was 3.53 weeks (24 days). Conclusions: The minimally invasive ablation of terminal, axial and perforator reflux with compression in patients is a technique that leads to faster healing times of CVU (AU)


Assuntos
Humanos , Masculino , Feminino , Cicatrização/genética , Úlcera/patologia , Esclerose/complicações , Esclerose/metabolismo , Bandagens/classificação , Bandagens/normas , Pressão Venosa/fisiologia , Cicatrização/fisiologia , Úlcera/metabolismo , Esclerose/diagnóstico , Esclerose/patologia , Bandagens/provisão & distribução , Bandagens , Pressão Venosa/genética
11.
Gut Liver ; 10(6): 881-889, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27784845

RESUMO

Potassium channels and transporters maintain potassium homeostasis and play significant roles in several different biological actions via potassium ion regulation. In previous decades, the key revelations that potassium channels and transporters are involved in the production of gastric acid and the regulation of secretion in the stomach have been recognized. Drugs used to treat peptic ulceration are often potassium transporter inhibitors. It has also been reported that potassium channels are involved in ulcerative colitis. Direct toxicity to the intestines from nonsteroidal anti-inflammatory drugs has been associated with altered potassium channel activities. Several reports have indicated that the long-term use of the antianginal drug Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, increases the chances of ulceration and perforation from the oral to anal regions throughout the gastrointestinal (GI) tract. Several of these drug features provide further insights into the role of potassium channels in the occurrence of ulceration in the GI tract. The purpose of this review is to investigate whether potassium channelopathies are involved in the mechanisms responsible for ulceration that occurs throughout the GI tract.


Assuntos
Canalopatias , Gastroenteropatias/patologia , Úlcera Péptica/patologia , Canais de Potássio/fisiologia , Úlcera/patologia , Animais , Antiarrítmicos/efeitos adversos , Colo/metabolismo , Gastroenteropatias/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Humanos , Camundongos , Nicorandil/efeitos adversos , Úlcera Péptica/metabolismo , Úlcera/metabolismo
12.
Biopharm Drug Dispos ; 37(9): 522-532, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27666336

RESUMO

The liver and the small intestine are closely related in the processes of drug absorption, metabolism and excretion via the enterohepatic circulation. Small intestinal ulcers are a serious adverse effect commonly occurring in patients taking nonsteroidal anti-inflammatory drugs. However, the influence of small intestinal ulcers on drug metabolism has not been established. This study examined the expressional changes of cytochrome P450 (CYP) in the liver using an indomethacin-induced small intestinal ulcer rat model and in cultured cells. After the administration of indomethacin to rats, ulcers were observed in the small intestine and expression of CYP3A1, the major isoform of hepatic CYP, was significantly down-regulated in the liver, accompanied by increased expression of inducible nitric oxide synthase, tumor necrosis factor α, interleukin (IL)-1ß and IL-6, in the small intestine and the liver. The indomethacin-induced small intestinal ulceration, the increase in inflammatory mediators in the small intestine and the liver, and the down-regulation of CYP3A1 expression in the liver were inhibited by co-administration of ampicillin, an antibacterial agent. In the human hepatic HepG2 cell line, IL-1ß, IL-6 and NOC-18, an NO donor, caused down-regulation of CYP3A4, the major isoform of human CYP3A. Thus, this study suggests that after indomethacin treatment small intestinal ulcers cause the down-regulation of CYP3A1 in the rat liver through an increase in ulcer-derived inflammatory mediators. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Citocromo P-450 CYP3A/biossíntese , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica , Indometacina/toxicidade , Intestino Delgado/metabolismo , Úlcera/metabolismo , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Citocromo P-450 CYP3A/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Células Hep G2 , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Úlcera/induzido quimicamente , Úlcera/patologia
14.
J Ethnopharmacol ; 189: 277-89, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27208868

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Blechnum orientale Linn. (B. orientale) is a fern traditionally used by the natives as a poultice to treat wounds, boils, ulcers, blisters, abscesses, and sores on the skin. AIM OF THE STUDY: To investigate the wound healing ability of a concentrated extract of B. orientale in a hydrogel formulation in healing diabetic ulcer wounds. MATERIALS AND METHODS: The water extract from the leaves of B. orientale was separated from the crude methanolic extract and subjected to flash column chromatography techniques to produce concentrated fractions. These fractions were tested for phytochemical composition, tannin content, antioxidative and antibacterial activity. The bioactive fraction was formulated into a sodium carboxymethylcellulose hydrogel. The extract-loaded hydrogels were then characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. Wound size was measured for 14 days. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. All possible mean values were subjected to statistical analysis using One-way ANOVA and post-hoc with Tukey's T-test (P<0.05). RESULTS: One fraction exhibited strong antioxidative and antibacterial activity. The fraction was also highly saturated with tannins, particularly condensed tannins. Fraction W5-1 exhibited stronger antioxidant activity compared to three standards (α-Tocopherol, BHT and Trolox-C). Antibacterial activity was also present, and notably bactericidal towards Methicillin-resistant Staphylococcus aureus (MRSA) at 0.25mg/ml. The extract-loaded hydrogels exhibited shear-thinning properties, with high moisture retention ability. The bioactive fraction at 4% w/w was shown to be able to close diabetic wounds by Day 12 on average. Other groups, including controls, only exhibited wound closure by Day 14 (or not at all). Histopathological studies had also shown that extract-treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis. CONCLUSION: The ethnopharmacological effects of using B. orientale as a topical treatment for external wounds was validated and was also significantly effective in treating diabetic ulcer wounds. Thus, B. orientale extract hydrogel may be presented as a potential treatment for diabetic ulcer wounds.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Angiopatias Diabéticas/tratamento farmacológico , Gleiquênias/química , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Taninos/farmacologia , Úlcera/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/isolamento & purificação , Antioxidantes/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Compostos de Bifenilo/química , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Hidrogéis , Hidroxiprolina/metabolismo , Masculino , Testes de Sensibilidade Microbiana , Neovascularização Fisiológica/efeitos dos fármacos , Fitoterapia , Picratos/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Plantas Medicinais , Ratos Sprague-Dawley , Reepitelização/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Estreptozocina , Taninos/isolamento & purificação , Fatores de Tempo , Úlcera/etiologia , Úlcera/metabolismo , Úlcera/patologia
15.
Pain Physician ; 19(4): E581-7, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27228524

RESUMO

BACKGROUND: A previous study revealed elevated serum Immunoglobulin E (IgE) in ketamine related cystitis (KC) patients. IgE might participate the pathogenesis of different types of bladder pain syndromes, including KC and interstitial cystitis (IC). OBJECTIVES: To investigate the IgE expression in KC and IC bladder tissue. STUDY DESIGN: Prospective evaluation. SETTING: The study was conducted in a tertiary teaching hospital, Hualien Tzu Chi Hospital. METHODS: We investigated the bladder IgE with immunofluorescence staining and quanti?cation. The active mast cells were measuring using tryptase. The symptoms and urodynamic study results were recorded. Double immunofluorescence staining of tryptase and IgE was also performed. Sixteen KC patients, 10 ulcerative IC patients, and 20 non-ulcerative IC patients participated. The history and urodynamic parameters were investigated in these patients. The bladder mucosa was biopsied during cystoscopic hydrodistention. Bladder biopsies were also taken from 22 patients with bacterial cystitis and 12 healthy controls. RESULTS: Bladder IgE was positive in 15 (93.8%) KC patients, 9 (90%) ulcerative IC patients, one (5%) non-ulcer IC patient, 8 (36.4%) bacterial cystitis patients, and 2 (16.7%) controls (P < .001). The bladder IgE was greater in the patients with KC than in the others (P < .001). After excluding KC patients, bladder IgE was significantly higher in the patients with ulcerative IC than the others (P < .001). The bladder IgE was significantly correlated with pain on a visual analogue scale (r2 = 0.156, P = .017) and maximum bladder capacity (r2 = 0.423, P < .001). Tryptase expression did not show a significant difference between KC, ulcer IC, and non-ulcer IC (P = 0.222). Double immunofluorescence staining showed co-expression of tryptase and IgE. CONCLUSIONS: IgE-mediated inflammation played a significant role in the pathogenesis of KC and ulcerative IC. KEY WORDS: Immunoglobulin E, ketamine cystitis, interstitial cystitis.


Assuntos
Cistite Intersticial/metabolismo , Imunoglobulina E/biossíntese , Ketamina/efeitos adversos , Úlcera/metabolismo , Bexiga Urinária/química , Bexiga Urinária/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Cistite Intersticial/induzido quimicamente , Cistite Intersticial/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/induzido quimicamente , Dor/diagnóstico , Dor/metabolismo , Medição da Dor/métodos , Estudos Prospectivos , Úlcera/induzido quimicamente , Úlcera/diagnóstico , Bexiga Urinária/patologia
16.
J Pharmacol Exp Ther ; 357(3): 529-36, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26989141

RESUMO

Proton pump inhibitors such as omeprazole (OME) reduce the severity of gastrointestinal (GI) ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs) but can also increase the chance of dysbiosis. The aim of this study was to test the hypothesis that preventive use of a soluble epoxide hydrolase inhibitor (sEHI) such as TPPU can decrease NSAID-induced ulcers by increasing anti-inflammatory epoxyeicosatrienoic acids (EETs). Dose- [10, 30, and 100 mg/kg, by mouth (PO)] and time-dependent (6 and 18 hours) ulcerative effects of diclofenac sodium (DCF, an NSAID) were studied in the small intestine of Swiss Webster mice. Dose-dependent effects of TPPU (0.001-0.1 mg/kg per day for 7 days, in drinking water) were evaluated in DCF-induced intestinal toxicity and compared with OME (20 mg/kg, PO). In addition, the effect of treatment was studied on levels of Hb in blood, EETs in plasma, inflammatory markers such as myeloperoxidase (MPO) in intestinal tissue homogenates, and tissue necrosis factor-α (TNF-α) in serum. DCF dose dependently induced ulcers that were associated with both a significant (P < 0.05) loss of Hb and an increase in the level of MPO and TNF-α, with severity of ulceration highest at 18 hours. Pretreatment with TPPU dose dependently prevented ulcer formation by DCF, increased the levels of epoxy fatty acids, including EETs, and TPPU's efficacy was comparable to OME. TPPU significantly (P < 0.05) reversed the effect of DCF on the level of Hb, MPO, and TNF-α Thus sEHI might be useful in the management of NSAID-induced ulcers.


Assuntos
Diclofenaco/efeitos adversos , Epóxido Hidrolases/antagonistas & inibidores , Intestinos/efeitos dos fármacos , Compostos de Fenilureia/química , Compostos de Fenilureia/farmacologia , Piperidinas/química , Piperidinas/farmacologia , Úlcera/induzido quimicamente , Úlcera/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Citoproteção/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Técnicas de Inativação de Genes , Mucosa Intestinal/metabolismo , Intestinos/patologia , Masculino , Camundongos , Peroxidase/metabolismo , Compostos de Fenilureia/uso terapêutico , Piperidinas/uso terapêutico , Solubilidade , Fator de Necrose Tumoral alfa/sangue , Úlcera/metabolismo , Úlcera/patologia
17.
Int J Biol Macromol ; 86: 772-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26861826

RESUMO

In order to obtain polysaccharides from green and black teas (Camellia sinensis), commercial leaves were submitted to infusion and then to alkaline extraction. The extracts were fractionated by freeze-thawing process, giving insoluble and soluble fractions. Complex arabinogalactan protein from the soluble fractions of both teas (GTPS and BTPS) were determined by methylation analysis and (1)H/(13)C-HSQC spectroscopy, showing a main chain of (1→3)-ß-Galp, substituted at O-6 by (1→6)-linked ß-Galp with side chains of α-Araf and terminal units of α-Araf, α-Fucp and α-Rhap. A highly branched heteroxylan from the insoluble fractions (GTPI and BTPI) showed in methylation analysis and (1)H/(13)C-HSQC spectroscopy the main chain of (1→4)-ß-Xylp, substituted in O-3 by α-Araf, ß-Galp and α-Glcp units. Evaluating their gastroprotective activity, the fractions containing the soluble heteropolysaccharides from green (GTPS) and black teas (BTPS) reduced the gastric lesions induced by ethanol. Furthermore, the fraction of insoluble heteropolysaccharides of green (GTPI) and black (BTPI) teas also protected the gastric mucosa. In addition, the maintenance of gastric mucus and reduced glutathione (GSH) levels was involved in the polysaccharides gastroprotection.


Assuntos
Camellia sinensis/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Chá/química , Úlcera/tratamento farmacológico , Ácido Acético/efeitos adversos , Animais , Etanol/efeitos adversos , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Glutationa/metabolismo , Folhas de Planta/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Ratos , Ratos Wistar , Solubilidade , Úlcera/induzido quimicamente , Úlcera/metabolismo , Úlcera/patologia
18.
Clin. transl. oncol. (Print) ; 17(12): 1030-1035, dic. 2015. tab
Artigo em Inglês | IBECS | ID: ibc-147442

RESUMO

All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 therapy. Up to 10 years follow up is recommended for melanoma patients with dermatologic examinations and physical exams (AU)


No disponible(AU)


Assuntos
Humanos , Masculino , Feminino , /normas , Melanoma/metabolismo , Melanoma/patologia , Biópsia de Linfonodo Sentinela/métodos , Biópsia de Linfonodo Sentinela/enfermagem , Metástase Linfática/genética , Úlcera/metabolismo , Úlcera/patologia , Terapêutica/métodos , Melanoma/induzido quimicamente , Melanoma/complicações , Biópsia de Linfonodo Sentinela/normas , Biópsia de Linfonodo Sentinela , Metástase Linfática/diagnóstico , Úlcera/complicações , Úlcera/diagnóstico , Terapêutica/instrumentação
19.
Biochem Biophys Res Commun ; 467(2): 303-9, 2015 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-26454169

RESUMO

Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-ß1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Exossomos/metabolismo , Células-Tronco Mesenquimais/química , Úlcera/metabolismo , Animais , Becaplermina , Movimento Celular , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Exossomos/química , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Comunicação Parácrina , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-sis/farmacologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/farmacologia , Úlcera/etiologia , Úlcera/genética , Úlcera/patologia , Cicatrização/efeitos dos fármacos
20.
Biol Pharm Bull ; 38(10): 1580-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26424019

RESUMO

It is well known that rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are more susceptible to NSAIDs-induced gastroenteropathy in comparison with other patients. In this study we demonstrate that expression levels of interleukin (IL)-18 are related to aggravation of intestinal ulcerogenic lesions in adjuvant-induced arthritis (AA) rats following oral administration of indomethacin. AA rats were administered oral indomethacin (40 mg/kg) and killed under deep isoflurane anesthesia after 24 h. The small intestinal mucosa was then examined. Oral administration of indomethacin caused hemorrhagic lesions in the small intestinal mucosa of AA rats, and the lesion score of AA rats 24 h after indomethacin treatment was approximately 5.6-fold higher than for normal rats administered indomethacin. IL-18 expression in the small intestinal mucosa of AA rats administered indomethacin was also higher in comparison with normal rats receiving indomethacin. In addition, interferon-γ and nitric oxide levels in the small intestinal mucosa of AA rats were increased following oral administration of indomethacin. It is possible that IL-18 expression in AA rats renders the small intestinal mucosa more sensitive to indomethacin, and that IL-18 may play a role in aggravating intestinal ulcerogenic lesions in AA rats treated with this drug.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Indometacina/efeitos adversos , Interleucina-18/metabolismo , Úlcera/induzido quimicamente , Úlcera/metabolismo , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Células CACO-2 , Pé/patologia , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Íleo/patologia , Interferon gama/metabolismo , Interleucina-18/genética , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/patologia , Lipopolissacarídeos , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Ratos , Úlcera/patologia
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