F. Teixeira

Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-α levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy.

Background  Several cross‐sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis.

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index, severity and therapy

Background  Psoriasis vulgaris is associated with overweight/obesity and with increased C‐reactive protein (CRP), tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, leptin and resistin levels and decreased adiponectin levels.

Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty rats

OBJECTIVE In the present study we evaluated the effect of exercise on the plasma levels of proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory molecule uric acid in the Zucker diabetic fatty (ZDF) rats that are more prone to develop type 2 diabetes mellitus. METHODS Sixteen obese ZDF (Gmi fa/fa) rats (8 wk old, 228.40 +/- 4.05 g) were randomly assigned to one of two groups (n = 8 each): an exercise-trained group and a sedentary one. In addition, 16 lean ZDF (Gmi +/+) rats (8 wk old, 199.00 +/- 3.50 g) were subjected to identical sedentary and exercise conditioning (n = 8 each). Initially, rats swam 15 min/d (5 d/wk) in a 36 degrees C bath. The exercise protocol was gradually increased by 15 min/d until a swimming period of 1 h/d (1 wk) was attained. Thereafter, rats swam 1 h/d, 3 d/wk, for an additional period of 11 wk. Rats were sacrificed 48 h after the last training period and the blood and pancreas were collected. Circulating levels of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, insulin, uric acid, IL-6, and TNF-alpha were assessed. The concentrations of proinflammatory cytokines in the pancreas were also evaluated. RESULTS In the diabetic ZDF (fa/fa) rats, exercise decreased hyperuricemia (-37.3%) and IL-6 and TNF-alpha levels (-16.9% and -12.7% respectively) and maintained the weight of the pancreas at near normal. Immunohistochemistry revealed a marked decrease in the expression of TNF-alpha and IL-6 in the pancreatic islet cells of ZDF (fa/fa) rats. CONCLUSION These results indicate that aerobic exercise is anti-inflammatory in nature.

Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood–retinal barrier in a type 2 diabetes animal model

Aim: The aim of this study was to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV inhibitor (DPP‐IV), in preventing the deleterious effects of diabetes on the blood–retinal barrier in male Zucker Diabetic Fatty (ZDF) rats.

Hypertension induced by immunosuppressive drugs: a comparative analysis between sirolimus and cyclosporine

The purpose of this study was to compare the effects of sirolimus (SRL) vs cyclosporine (CsA) concerning the cardiovascular mechanisms hypothetically contributing to hypertension development. Three rat groups were studied: control (vehicle), CsA (5 mg/kg/d), and SRL (1 mg/kg/d). The following parameters were evaluated after 7 weeks of treatment: blood pressured (BP) and heart rate (HR; tail cuff), lipid profile, hematology, plasma and platelet 5-HT and catecholamines (HPLC-ECD), and oxidative equilibrium (serum malondialdehyde [MDA] and total antioxidant status [TAS]). Systolic (SBP) and diastolic blood pressure (DBP) values were higher (P < .001) in both the CsA (146.2 +/- 4.5 and 124.9 +/- 4.5 mm Hg) and SRL (148.9 +/- 4.8 and 126.4 +/- 6.0 mm Hg) groups vs the controls (115.9 +/- 3.3 and 99.1 +/- 2.0 mm Hg). However, HR values were elevated in CsA but not SRL animals. The dyslipidemic pattern of CsA was even more enhanced in the SRL group, with significantly higher low-density lipoprotein cholesterol (LDL-c) and triglyceride (TG) levels vs CsA (P < .05); red blood cells, hematocrit, hemoglobin concentration, mean platelet volume, and platelet distribution width were significantly (P < .05) higher in the SRL vs CsA group. The pro-oxidative profile (increased MDA/TAS) in the CsA group was not reproduced in the SRL cohort. While plasma and platelet 5-HT were elevated in SRL rats, catecholamine content was higher in CsA animals. In conclusion, this study demonstrated that CsA and SRL produce identical hypertensive effects. However, while CsA promotes oxidative stress and sympathetic activation, SRL mainly interferes with lipid profile and hematological parameters. Thus, the hypertensive effects of CsA, a calcineurin inhibitor, and of SRL, an mTOR inhibitor, are associated with impairment of distinct cardiovascular pathways.

Treadmill running and swimming imposes distinct cardiovascular physiological adaptations in the rat: Focus on serotonergic and sympathetic nervous systems modulation

Physical exercise may improve the metabolic and haemodynamic responses, but the beneficial effects seem to depend on intensity, duration and muscular mass recruitment, which may vary between different types of protocols. This study was performed to evaluate the effects of two distinct moderate/long-term aerobic training protocols in the normal Wistar rat, the treadmill running and the swimming, on several important parameters related to cardiovascular (CV) physiological adaptations, namely: lipid profile, haemorheological measures, lipid peroxidation, peripheral serotonergic system (SS) modulation and sympathetic nervous system (SNS) activation. In both groups under training an HDL-c increment versus the sedentary control was demonstrated. There was a noticeable increase in ADP-induced platelet aggregation in the exercised rats, together with higher PDW and MPV values. The RBC patterns were altered in both groups under training; in the swimming one, however, significantly higher RBC and HCT and lower MCH and MCHC values were found, suggesting renovation of the RBCs. Plasma and platelet SS measures were generally higher in both groups under training, being noticeably relevant the 5-HT and 5-HIAA increment in the treadmill. In opposition, concerning the plasma and platelet NE and E concentrations, the rise was remarkably higher in the rats under a swimming protocol. In conclusion, this study demonstrates that, despite the similar beneficial effects on lipid profile, different aerobic exercise protocols may produce distinct CV physiological adaptations. Therefore, treadmill running was more influent than swimming concerning peripheral SS modulation while swimming was more important on SNS activation, thus recommending a judicious choice of the protocol to be tested in works which make use of rat models of exercise to study physiological or pathophysiological conditions.

Cardiac antiapoptotic and proproliferative effect of recombinant human erythropoietin in a moderate stage of chronic renal failure in the rat

Objective: Recombinant human erythropoietin (rhEPO) therapy under circumstances of moderate chronic renal failure (CRF), with yet lower kidney and heart lesion, may have a protective cardiac effect beyond the correction of anemia, whose mechanism deserves better elucidation, namely by clarifying the impact on gene expression profile of markers of apoptosis, inflammation, proliferation, angiogenesis, and lesion/stress in the heart. Materials and Methods: Four groups of rats were studied over a period of 15 weeks (n=7 each): control—without surgery and without drug treatment; rhEPO—treated with 50 IU/kg/week of rhEPO—beta; CRF—submitted to partial nephrectomy (3/4); CRF + rhEPO—CRF with rhEPO treatment after the 3rd week of surgery. The heart was collected in order to evaluate the gene expression, by real-time qPCR, of markers of apoptotic machinery, inflammation/immunology, proliferation/angiogenesis, and lesion/stress. Results: The main findings obtained were (a) CRF rats have demonstrated overexpression of EPO-R in the heart without changes on EPO expression, together with overexpression of Bax/Bcl2 ratio, PCNA, and IL-2; (b) rhEPO therapy on the heart of the rats with CRF induced by partial 3/4 nephrectomy promoted nonhematopoietic protection, demonstrated by the apoptosis prevention, viewed by the Bax/Bcl2 balance, by the promotion of proliferation, due to PCNA increment, and by the immunomodulatory action, expressed by a trend to prevent the IL-2 increment. Conclusion: In this model of moderate CRF, rhEPO treatment showed important cardiac nonhematopoietic effects, expressed mainly by the antiapoptotic and the proproliferative action, suggesting that early rhEPO therapy in moderate stages of CRF might have further therapeutic benefits.

Characterization of a rat model of moderate chronic renal failure--focus on hematological, biochemical, and cardio-renal profiles.

The pathophysiological modifications underlying chronic renal failure seems to be dependent on the insufficiency degree, which will determine the moment to start therapy. As there is yet limited information about animal models of moderate chronic renal failure, we intended to perform a complete characterization of the hematological and cardio-renal alterations induced by partial nephrectomy. Blood samples from control and chronic renal failure rats were collected at 0, 3, 9, and 15 weeks in order to evaluate renal function, hematological parameters, iron metabolism, blood lipids, peripheral sympathetic nervous system, and inflammatory and redox status markers. BP, tissues trophy indexes, and kidney histomorphology were also assessed. Our data are consistent with a sustained moderate degree of chronic renal failure with a quickly compensated modest anaemia, though presenting iron metabolism disturbances. Despite the reasonable degree of functionality of the remnant kidney, as suggested by the anaemia correction and by the kidney hypertrophy and moderate lesions, several important cardiovascular modifications were developed. Our model presented hypertension, dyslipidemia, erythropoietic disturbances, sympathetic activation, and oxidative stress. This model might be a good tool to study the cellular/molecular mechanisms underlying moderate stages of chronic renal failure and to evaluate the therapeutic efficacy for prevention and treatment/correction of cardio-renal anaemia syndromes and complications in early stages.

CURATIVE ISOSORBIDE-5-MONONITRATE TREATMENT, IN OPPOSITION TO THE BENEFICIAL PREVENTIVE ONE, AGGRAVATES THE PROTHROMBOTIC AND PROCONSTRICTOR STATE IN CYCLOSPORINE-INDUCED HYPERTENSIVE RATS

1. The aim of the present study was to evaluate the effect of preventive and curative isosorbide‐5‐mononitrate (Is‐5‐Mn) treatment on the development of hypertension, cGMP content, thromboxane (TX) A2/prostaglandin (PG) I2 balance, the peripheral serotonergic system, platelet activation, lipid peroxidation and plasma lipids in cyclosporine A (CsA)‐induced hypertensive rats.

Autologous stem-cell transplantation in Hodgkin's lymphoma: analysis of a therapeutic option

OBJECTIVE To report the clinical progress of patients with Hodgkins lymphoma treated with autologous transplantation after failure or relapse of first-line treatment with chemotherapy and/or radiation therapy. METHODS The results of a retrospective analysis of 31 patients submitted to autologous transplantation as second-line treatment, between April 2000 and December 2008, were analyzed. Fourteen men and seventeen women, with a median age of 27 years, were submitted to autologous transplantation for relapsed (n = 21) or refractory (n = 10) Hodgkins lymphoma. RESULTS Mortality related to treatment in the first 100 days after transplant was 3.2%. With a mean follow-up period of 18 months (range: 1 to 88 months), the probability of global survival and progression-free survival in 18 months was 84 and 80%, respectively. The probability of global survival and progression-free survival at 18 months for patients with chemosensitive relapses (n = 21) was 95 and 90%, respectively, versus 60 and 45% for patients with relapses resistant to chemotherapy (n = 10) (p = 0.001 for global survival; p = 0.003 for progression-free survival). In the multivariate analysis, absence of disease or pretransplant disease < 5 cm were favorable factors for global survival (p= 0.02; RR: 0.072; 95%CI: 0.01-0.85) and progression-free survival (p= 0.01; RR: 0.040; 95%CI: 0.007-0.78). CONCLUSION Autologous transplantation of stem-cells is a therapeutic option for Hodgkins lymphoma patients after the first relapse. Promising results were observed in patients with a low tumor burden at transplant.