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1.
BMC Gastroenterol ; 21(1): 31, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478385

RESUMO

BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) can involve some complications, despite the good safety of its track record. The Buried Bumper Syndrome (BBS) is a rare, late and dangerous complication that consists in the erosion of the internal bumper through the gastric wall. Case presentation We report the development of BBS in a man with chronic obstructive pulmonary disease (COPD) who had a persistent chronic cough which was prevalently but not solely in the morning and required placement of a PEG tube for continuous infusion of Levodopa/carbidopa intestinal gel for advanced Parkinson's disease. CONCLUSION: We believe that COPD with chronic cough while not representing an absolute contraindication to PEG placement, may potentially cause BBS and therefore an appropriate regimen of tube care by expert personnel is mandatory in this setting.


Assuntos
Gastrostomia , Doença Pulmonar Obstrutiva Crônica , Contraindicações , Tosse/etiologia , Nutrição Enteral , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia
2.
Ann Oncol ; 26(4): 675-682, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25488686

RESUMO

BACKGROUND: Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. PATIENTS AND METHODS: We carried out a multicenter, randomized phase III study. Women aged 65-79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m(2) days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. RESULTS: From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83-1.76, P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80-2.22, P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. CONCLUSIONS: Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. CLINICALTRIALSGOV: NCT00331097.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Metotrexato/administração & dosagem , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Taxoides/administração & dosagem
3.
Biopolymers ; 103(7): 393-405, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25787348

RESUMO

The hydration of the polypeptide network is a determinant factor to be controlled on behalf of the design of precise functional tissue scaffolding. Here we present an exhaustive study of the hydrodynamic and crowding evolution of aqueous gelatin-hydroxyapatite systems with the aim of increasing the knowledge about the biomimesis of collagen mineralization; and how it can be manipulated for the preparation of collagenous derived frameworks with specific morphological characteristics. The solution's density and viscosity evaluation measurements in combination with spectroscopic techniques revealed that there is a progressive association of protein chain that can be influenced by the amount of hydroxyapatite nanorods. Gelatin and additives' concentration effect on the morphology of the gelatin scaffolds was investigated. Transverse and longitudinal sections of the obtained scaffolds were taken and analyzed using optical microscopy. It can be seen that the porous size and shape of gelatin assemblies can be easily adjusted by controlling the gelatin/HAp ratio in the solution used as template in agreement with our statement.


Assuntos
Durapatita/química , Gelatina/química , Alicerces Teciduais/química
4.
Biochim Biophys Acta ; 1830(11): 5014-26, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23891938

RESUMO

BACKGROUND: Nano-hydroxyapatite particles have better bioactivity than the coarse crystals. So, they can be utilized for engineered tissue implants with improved efficiency over other materials. The development of materials with specific bioactive characteristics is still under investigation. METHODS: The surface properties of four hydroxyapatite materials templated by different micelle-polymer structured network are studied. The synergistic interaction of each block copolymer in contact with CTAB rod-like micelles results in crystalline HAp nano-rods of 25-50nm length organized in hierarchical structures with different micro-rough characteristics. RESULTS: It was observed that the material in vitro bioactivity strongly depends on the surface structure while in a minor extent on their Ca/P ratio. So, MIII and MIV materials with Skewness parameter Rsk>2.62 favored the formation on their surfaces of net-like phase with a high growth kinetic constant; while MI and MII (Rsk≤2.62) induced the appearance of spherulitic-like structures and a growth rate 1.75 times inferior. Material biocompatibility was confirmed by interaction with rat calvarial osteoblasts. CONCLUSIONS: The different structures growth is attributed to a dissimilar matching of crystal planes in the material and the apatite layer formed. In specific synthesis conditions, a biocompatible material with a Ca/P ratio close to that for the trabecular bone and a morphology that are considered essential for bone-bonding was obtained. GENERAL SIGNIFICANCE: The creation of implantable devices with a specific bioactive characteristic may be useful to manipulate the attachment of cells on mineral coating directly affecting the stability and life of the implant.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Durapatita/química , Durapatita/farmacologia , Nanotubos/química , Animais , Células Cultivadas , Cinética , Micelas , Osteoblastos/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Ratos , Relação Estrutura-Atividade , Propriedades de Superfície , Engenharia Tecidual/métodos
5.
J Physiol Pharmacol ; 75(1)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38583434

RESUMO

In this review we focused on the putative therapeutic effect of Hericium erinaceus extract in the treatment of pathologic conditions of the lower urinary tract in which intestinal inflammation may play a role. To this aim we reviewed the available evidence on pelvic cross-organ sensitization as a possible mechanism through which intestinal inflammation and dysbiosis may affect the lower urinary tract. Also, we reviewed the clinical and experimental evidence supporting the role of Hericium erinaceus extract as an anti-inflammatory agent highlighting the role of a number of putative mediators and mechanisms which might make this nutraceutical suitable for the management of 'difficult to treat' lower urinary tract disorders.


Assuntos
Basidiomycota , Hericium , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
6.
ESMO Open ; 9(3): 102941, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452437

RESUMO

BACKGROUND: Oncologists tend to under-report subjective symptoms during cancer treatment. This study describes the under-reporting rate of selected symptoms and explores its association with overall survival (OS). A secondary aim is to test the association of patient-reported symptoms with OS. PATIENTS AND METHODS: This is a post hoc analysis on data pooled from 12 randomized trials, promoted by the National Cancer Institute of Naples (Italy), enrolling patients between 2002 and 2019, with published primary analyses. Occurrence and grade of six side-effects (anorexia, nausea, vomiting, constipation, diarrhea and fatigue) reported by physicians were compared with corresponding symptoms reported by patients in quality-of-life (QoL) questionnaires. Under-reporting was defined as the rate of cases reported grade 0 by the physician while grade ≥1 by the patient. Prognostic value was tested in a multivariable model stratified by trial, including age, sex and performance status as confounders. A landmark threshold was defined for OS analyses. RESULTS: 3792 patients with advanced lung, ovarian, pancreatic, breast or colorectal cancer were pooled; 2603 (68.6%) were eligible having at least one toxicity assessment and one QoL questionnaire, before the first planned disease restaging. Concordance between physicians' and patients' reporting was low with Cohen's k coefficients ranging from 0.03 (fatigue) to 0.33 (vomiting). Under-reporting ranged from 52.7% (nausea) to 80.5% (anorexia), and was not associated with OS. Patient-reported anorexia, vomiting and fatigue ('a little' or more) were significantly associated with shorter OS. CONCLUSIONS: Under-reporting of treatment side-effects is frequent, but it does not affect OS. Patients' reported symptoms should be used for prognostic evaluation.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Anorexia/complicações , Fadiga/etiologia , Náusea/etiologia , Neoplasias/terapia , Neoplasias/complicações , Prognóstico , Vômito , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Ann Oncol ; 23(8): 2027-2033, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22412041

RESUMO

BACKGROUND: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. PATIENTS AND METHODS: A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. RESULTS: Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). CONCLUSIONS: In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Tamoxifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Estradiol/metabolismo , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Tamoxifeno/efeitos adversos , Triazóis/efeitos adversos , Triazóis/uso terapêutico , Ácido Zoledrônico
8.
ACS Appl Mater Interfaces ; 14(4): 5843-5855, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35048694

RESUMO

Near-infrared (NIR) radiation plays an important role in guided external stimulus therapies; its application in bone-related treatments is becoming more and more frequent. Therefore, metallic biomaterials that exhibit properties activated by NIR are promising for further orthopedic procedures. In this work, we present an adapted electroforming approach to attain a biomorphic nano-holed TiO2 coating on Ti6Al4V alloy. Through a precise control of the anodization conditions, structures revealed the formation of localized nano-pores arranged in a periodic assembly. This specific organization provoked higher stability against thermal oxidation and precise hydrophobic wettability behavior according to Cassie-Baxter's model; both characteristics are a prerequisite to ensure a favorable biological response in an implantable structure for guided bone regeneration. In addition, the periodically arranged sub-wavelength-sized unit cell on the metallic-dielectric structure exhibits a peculiar optical response, which results in higher NIR reflectivity. Accordingly, we have proved that this effect enhances the efficiency of the scattering processes and provokes a significant improvement of light confinement producing a spontaneous NIR fluorescence emission. The combination of the already favorable mechanical and biocompatibility properties of Ti6Al4V, along with suitable thermal stability, wetting, and electro-optical behavior, opens a promising path toward strategic bone therapeutic procedures.


Assuntos
Ligas/química , Materiais Biomiméticos/química , Materiais Revestidos Biocompatíveis/química , Ligas/efeitos da radiação , Materiais Biomiméticos/efeitos da radiação , Materiais Revestidos Biocompatíveis/efeitos da radiação , Interações Hidrofóbicas e Hidrofílicas , Raios Infravermelhos , Porosidade , Titânio/química , Titânio/efeitos da radiação , Molhabilidade
9.
J Physiol Pharmacol ; 72(4)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34987127

RESUMO

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).


Assuntos
Doença de Crohn , Ustekinumab , Terapia Biológica , Doença de Crohn/tratamento farmacológico , Humanos , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento , Ustekinumab/uso terapêutico
10.
Horm Metab Res ; 42(1): 8-13, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19735057

RESUMO

The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/imunologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Endotélio Vascular/imunologia , Endotélio/imunologia , Adulto , Glicemia , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/imunologia , Feminino , Teste de Tolerância a Glucose , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Molécula 1 de Adesão de Célula Vascular/sangue
11.
J Clin Pharm Ther ; 35(5): 565-79, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20831680

RESUMO

WHAT IS KNOWN: The increased risk of cardiovascular events in diabetic patients has been related to numerous metabolic and haemoreological factors. Some of these factors appear to be particularly evident during the post-prandial phases and to be related to peak plasma glucose level. AIM: To compare the effect of addition of pioglitazone and acarbose to sulphonylureas and metformin therapy on metabolic parameters and on markers of endothelial dysfunction and vascular inflammation in type 2 diabetic patients. MATERIALS AND METHODS: We enrolled 473 caucasian type 2 diabetic patients. All patients underwent measurements of height and body weight, body mass index (BMI), glycated haemoglobin (HbA1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), post-prandial plasma insulin (PPI), homeostasis model assessment (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), sICAM-1, IL-6, high-sensitivity C reactive protein (hsCRP), sVCAM-1, sE-selectin and tumour necrosis factor (TNF-α). Assessments were made at start of titration, after 3 months [before a first oral glucose tolerance test (OGTT)], after 6 months and at the study end (before a second OGTT). RESULTS: Two-hundred and seventy four patients completed the study: 138 were randomized to double-blind treatment with pioglitazone and 136 with acarbose. Significant BMI and weight increase were observed after full treatment in the pioglitazone group relative to the acarbose group. A decrease in glycated haemoglobin was observed after the titration period in the pioglitazone group compared to both baseline value and the acarbose group. A decrease in glycated haemoglobin was also obtained after full treatment in the pioglitazone group when compared to the end of titration period and to the acarbose group. Significant decrease in FPG was obtained in the pioglitazone group after full treatment compared to the end of titration period. Post-prandial plasma glucose decrease was observed in acarbose group compared to the baseline value and to the end of titration period. Fasting plasma insulin decreased in the pioglitazone group after both the titration period and the full treatment period compared to both the baseline value and the acarbose group. The HOMA index decreased significantly after the full treatment in pioglitazone group compared to the end of titration period and to the acarbose group. Interleukin-6 and tumour necrosis factor-α decreased after full treatment in the pioglitazone group relative to the end of titration period. Significant hsCRP decrease was obtained after the titration period when compared to the baseline value in the pioglitazone group. High-sensitivity C reactive protein decreased in the pioglitazone group after full treatment compared to the end of titration period and to the acarbose group. WHAT IS NEW AND CONCLUSION: Pioglitazone reduces the inflammatory response to a glucose challenge more than acarbose in type 2 diabetic patients, already treated with maximal doses of sulphonylureas and metformin.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêutico , Acarbose/administração & dosagem , Acarbose/uso terapêutico , Biomarcadores , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Inflamação/sangue , Interleucina-6/sangue , Lipídeos/sangue , Masculino , Metformina/administração & dosagem , Metformina/uso terapêutico , Pessoa de Meia-Idade , Pioglitazona , Compostos de Sulfonilureia/administração & dosagem , Tiazolidinedionas/administração & dosagem , Fator de Necrose Tumoral alfa/sangue
12.
J Eur Acad Dermatol Venereol ; 23(9): 1008-17, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19470075

RESUMO

Pyoderma gangrenosum is a rare, ulcerative, cutaneous condition. First described in 1930, the pathogenesis of pyoderma gangrenosum remains unknown, but it is probably related to a hyperergic reaction. There are various clinical and histological variants of this disorder. Pyoderma gangrenosum often occurs in association with a systemic disease such as inflammatory bowel disease, rheumatologic disease, paraproteinaemia, or haematological malignancy. The diagnosis, mainly based on the clinical presentation and course, is confirmed through a process of elimination of other causes of cutaneous ulcers. Local treatment may be sufficient for mild disease, while for severe cases, systemic immunosuppressants are the mainstay. Long-term treatment with these agents is often required, but this can expose patients to adverse side-effects.


Assuntos
Pioderma Gangrenoso , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Diagnóstico Diferencial , Humanos , Prognóstico , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/patologia
13.
J Clin Pharm Ther ; 34(1): 13-23, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19125899

RESUMO

BACKGROUND AND OBJECTIVE: Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus. METHODS: We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run-in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7.5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean +/- standard deviation), 300 +/- 60, 12.5 +/- 2.5, and 2500 +/- 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post-prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA(1c)), fasting (FPI) and post-prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run-in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups. RESULTS AND DISCUSSION: Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA(1c) (P < 0.01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0.01 vs. baseline), PPG (P < 0.01 vs. baseline), and on HOMA index (P < 0.05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA(1c) (P < 0.05 vs. baseline), FPG (P < 0.01 vs. baseline), PPG (P < 0.05 vs. baseline), and HOMA index (P < 0.05 vs. baseline). No significant change was observed in TC, LDL-C, HDL-C, Tg, Apo A-I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin-resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control. CONCLUSION: Nateglinide improved glycemic control better than glibenclamide in combination with metformin.


Assuntos
Cicloexanos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Metformina/uso terapêutico , Fenilalanina/análogos & derivados , Glicemia/análise , Índice de Massa Corporal , Cicloexanos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glibureto/uso terapêutico , Hemoglobinas Glicadas/análise , Hemodinâmica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Nateglinida , Fenilalanina/farmacologia , Fenilalanina/uso terapêutico
14.
United European Gastroenterol J ; 6(9): 1428-1436, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30386616

RESUMO

BACKGROUND AND AIMS: Hp(2-20), a Helicobacter pylori-derived peptide interacting with N-formyl peptide receptors (FPRs), accelerates the healing of gastric injury in rats. Whether Hp(2-20) affects the recovery of inflamed colonic mucosa is unknown. We evaluated whether Hp(2-20) accelerated the healing of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis and explored the mechanism(s) underlying any such effect. METHODS: Fifteen rats underwent rectal administration of Hp(2-20) 250-500 µg/kg/day, or of its control peptide Hp1 for 10 days, following induction of colitis with TNBS. Macroscopic and histological damage was quantified using predetermined injury scores. FPR1, COX-2, TNF-α, TGF-ß, HB-EGF and tissue transglutaminase (t-TG) messenger RNA (mRNA) expression in colonic tissue was determined by quantitative polymerase chain reaction; FPR1, TNF-α and COX-2 protein levels by Western blotting. RESULTS: (1) Hp(2-20) accelerated healing of TNBS-induced colitis compared to controls consistently with the expression of FPRs in colonic mucosa; (2) TNBS upregulated mRNA mucosal expression of COX-2, TNF-α, TGF-ß, HB-EGF and t-TG and (3) this, with the exception of HB-EGF, was significantly counteracted by Hp(2-20). CONCLUSIONS: Hp(2-20), an FPR agonist, accelerates the healing of TNBS-induced colitis in the rat. This effect is associated with a significant reduction in colonic tissue levels of COX-2, TGF-ß, TNF-α and t-TG. We postulate that FPR-dependent pathways may be involved in the repair of inflamed colonic mucosa.

15.
Aliment Pharmacol Ther ; 47(6): 826-837, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29322544

RESUMO

BACKGROUND: Bisphenol A is an endocrine disrupting chemical associated with type 2 diabetes mellitus (T2DM), cardiovascular disease and liver enzyme abnormalities. AIM: To evaluate bisphenol A plasma and urine levels in non-alcoholic fatty liver disease (NAFLD) patients compared to healthy subjects. Furthermore, we evaluated, in human HepG2 cells, the effects of exposure to different concentrations of bisphenol A on both oxidative stress induction and cell proliferation. METHODS: We enrolled 60 patients with histological diagnosis of NAFLD with or without T2DM and sixty healthy subjects. In vitro, the proliferation of bisphenol A-exposed HepG2 cells at two different concentrations (0.025 and 0.05 µM) was evaluated, both at high (H-HepG2) and at low (L-HepG2) glucose concentrations for 48 h. Lipoperoxidation was assessed by thiobarbituric acid reactive substances (TBARS) assay. RESULTS: Bisphenol A levels were significantly higher in 60 NAFLD subjects, both in urine and in plasma (P < 0.0001) when compared to controls and, in this group, it appeared to be higher in 30 non-alcoholic steatohepatitis patients compared to 30 simple steatosis subjects (P < 0.05), independently from the presence of T2DM. After a bisphenol A-free diet for 1 month, NAFLD patients showed a significant reduction in bisphenol A circulating levels (P < 0.05), without a significant reduction in urine levels. H-HepG2 cells treated with bisphenol A (0.05 µM) increased proliferation compared to controls at 48 h (P < 0.0001). Bisphenol A increased TBARS levels at 48 h versus controls. CONCLUSIONS: Our study reveals a possible role of bisphenol A as an environmental factor involved in the promotion of NAFLD, particularly in T2DM patients.


Assuntos
Compostos Benzidrílicos/toxicidade , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fenóis/toxicidade , Adulto , Idoso , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Poluentes Ambientais/toxicidade , Ácidos Graxos/farmacologia , Feminino , Células Hep G2 , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia
16.
Tree Physiol ; 27(4): 527-35, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17241995

RESUMO

Girdling effects on fruitlet abscission, leaf chlorophyll, chlorophyll a fluorescence and carbohydrate concentration in various flowering and vegetative shoots were studied during natural fruit drop in two Citrus cultivars. Irrespective of shoot type, girdling delayed fruitlet abscission, but only fruitlets borne on leafy shoots had increased final fruit set. Chlorophyll a fluorescence analysis revealed differences in quantum yield efficiency of photosystem II of light adapted leaves (Phi(PSII)) among shoot types and in response to girdling. In young leaves of vegetative shoots, girdling decreased Phi(PSII), whereas Phi(PSII) increased from Day 30 after girdling in young leaves of leafy flowering shoots; however, Phi(PSII) did not change in mature leaves during fruit set in either control or girdled trees. Girdling altered leaf carbohydrate concentrations and the photosynthetic performance of the various shoot types. Our results indicate that, in Citrus, several carbohydrate-based regulatory mechanisms of photosynthesis coexist during carbohydrate accumulation brought about by girdling. It is concluded that the delay in fruitlet abscission and the increase in Phi(PSII )observed in girdled leafy flowering shoots are the mechanisms underlying the enhancement of fruit set after girdling.


Assuntos
Citrus/crescimento & desenvolvimento , Citrus/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Proteínas de Plantas/metabolismo , Metabolismo dos Carboidratos , Clorofila/metabolismo , Clorofila A , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Folhas de Planta/metabolismo , Teoria Quântica
17.
Intern Med J ; 37(2): 79-86, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17229249

RESUMO

BACKGROUND: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin, whereas the combination of metformin with thiazolidinediones is relatively less studied. The aim of the present study was to assess the differential effect on glycaemic metabolism and lipid variables of the combination of metformin plus pioglitazone or metformin plus rosiglitazone in diabetic patients with metabolic syndrome. METHODS: All patients began metformin and were randomized to receive pioglitazone or rosiglitazone for 12 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, homeostasis model assessment index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B. RESULTS: Significant decreases in glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, and postprandial plasma insulin were seen after 9 and 12 months in both groups. Homeostasis model assessment index improved at 12 months in both groups. Significant total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B improvement was observed in pioglitazone group after 12 months, but not in the rosiglitazone group. These variations were significant between groups. CONCLUSION: The combination of metformin plus thiazolidinediones was able to improve glycaemic control compared with previous therapy. Pioglitazone was associated with a significant improvement in lipid and lipoprotein variables.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Síndrome Metabólica/metabolismo , Metformina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/tratamento farmacológico , Pessoa de Meia-Idade , Pioglitazona , Rosiglitazona
18.
J Int Med Res ; 34(5): 545-55, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17133785

RESUMO

In this multicentre, randomized, double-blind, controlled, parallel-group trial, 103 patients with type 2 diabetes mellitus and metabolic syndrome were randomized to receive one of two thiazolidinediones--pioglitazone or rosiglitazone--in combination with 1500 mg/day of metformin, increasing up to 3000 mg/day, for 12 months. Anthropometric, metabolic, coagulation and fibrinolysis parameters were assessed at baseline and after 3, 6, 9 and 12 months. Significant decreases in glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose levels were seen after 9 and 12 months in both groups, and significant decreases in fasting plasma insulin and post-prandial plasma insulin levels were seen after 12 months in both groups. In both groups, improvement in the homeostasis model assessment index compared with baseline was obtained only after 12 months. Plasminogen activator inhibitor-1 levels were significantly lower in both groups after 12 months compared with baseline values. In patients with type 2 diabetes mellitus and metabolic syndrome, the combination of metformin plus thiazolidinediones improved glycaemic control and produced a slight but significant reduction in plasminogen activator inhibitor-1 levels.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Síndrome Metabólica/tratamento farmacológico , Trombofilia/tratamento farmacológico , Glicemia/análise , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Metformina/administração & dosagem , Metformina/farmacologia , Pessoa de Meia-Idade , Pioglitazona , Inibidor 1 de Ativador de Plasminogênio/sangue , Rosiglitazona , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/farmacologia , Resultado do Tratamento
19.
United European Gastroenterol J ; 4(2): 165-71, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27087942

RESUMO

Crohn's disease is a chronic inflammatory bowel disease potentially involving any segment of the gastrointestinal tract. Extra-intestinal manifestations may occur in 6%-40% of patients, and disorders of the skin are among the most common. This manuscript will review skin manifestations associated to Crohn's disease, with a particular focus on lesions associated to anti-tumour necrosis factor therapy.

20.
Colloids Surf B Biointerfaces ; 145: 382-391, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27220014

RESUMO

Intrinsic material skills have a deep effect on the mechanical and biological performance of bone substitutes, as well as on its associated biodegradation properties. In this work we have manipulated the preparation of collagenous derived fiber mesh frameworks to display a specific composition, morphology, open macroporosity, surface roughness and permeability characteristics. Next, the effect of the induced physicochemical attributes on the scaffold's mechanical behavior, bone bonding potential and biodegradability were evaluated. It was found that the scaffold microstructure, their inherent surface roughness, and the compression strength of the gelatin scaffolds can be modulated by the effect of the cross-linking agent and, essentially, by mimicking the nano-scale size of hydroxyapatite in natural bone. A clear effect of bioactive hydroxyapatite nano-rods on the scaffolds skills can be appreciated and it is greater than the effect of the cross-linking agent, offering a huge perspective for the upcoming progress of bone implant technology.


Assuntos
Biomimética/métodos , Durapatita/química , Gelatina/química , Alicerces Teciduais/química , Nanotubos/química , Taninos/química , Engenharia Tecidual
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