Thalidomide modulates renal inflammation induced by brain death experimental model.

BACKGROUND: Brain death (BD) is characterized by a complex inflammatory response, resulting in dysfunction of potentially transplantable organs. This process is modulated by cytokines, which amplify graft immunogenicity. We have investigated the inflammatory response in an animal model of BD and analyzed the effects of thalidomide, a drug with powerful immunomodulatory properties. METHODS: BD was induced in male Lewis rats. We studied three groups: Control (sham-operated rats) (n = 6), BD (rats subjected to brain death) (n = 6) and BD + Thalid (BD rats treated with one dose of thalidomide (200 mg/Kg), administered by gavage) (n = 6). Six hours after BD, serum levels of urea and creatinine, as well as systemic and renal tissue protein levels of TNF-α and IL-6, were analyzed. We also determined the mRNA expression of ET-1, and macrophage infiltration by immunohistochemistry. RESULTS: BD induced a striking inflammatory status, demonstrated by a significant increase of plasma cytokines: TNF-α (2.8 ± 4.3 pg/mL [BD] vs. 9.4 ± 2.8 pg/mL [Control]), and IL-6 (6219.5 ± 1380.6 pg/mL [BD] vs. 1854.7 ± 822.6 pg/mL [Control]), and in the renal tissue: TNF-α (2.5 ± 0.3 relative expression [BD] vs. 1.0 ± 0.4 relative expression [Control]; p < 0.05), and IL-6 (4.0 ± 0.4 relative expression [BD] vs. 1.0 ± 0.3 relative expression [Control]; p < 0.05). Moreover, BD increased macrophages infiltration (2.47 ± 0.07 cells/field [BD] vs. 1.20 ± 0.05 cells/field [Control]; p < 0.05), and ET-1 gene expression (2.5 ± 0.3 relative expression [BD] vs. 1.0 ± 0.2 relative expression [Control]; p < 0.05). In addition, we have observed deterioration in renal function, characterized by an increase of urea (194.7 ± 25.0 mg/dL [BD] vs. 108.0 ± 14.2 mg/dL [Control]; p < 0.05) and creatinine (1.4 ± 0.04 mg/dL [BD] vs. 1.0 ± 0.07 mg/dL [Control]; p < 0.05) levels. Thalidomide administration significantly reduced plasma cytokines: TNF-α (5.1 ± 1.4 pg/mL [BD + Thalid] vs. BD; p < 0.05), and IL-6 (1056.5 ± 488.3 pg/mL [BD + Thalid] vs. BD; p < 0.05), as well as in the renal tissue: TNF-α (1.5 ± 0.2 relative expression [BD + Thalid] vs. BD; p < 0.05), and IL-6 (2.1 ± 0.3 relative expression [BD + Thalid] vs. BD; p < 0.05). Thalidomide treatment also induced a significant decrease in the expression of ET-1 (1.4 ± 0.3 relative expression [BD + Thalid] vs. BD; p < 0.05), and macrophages infiltration (1.17 ± 0.06 cells/field [BD + Thalid] vs. BD; p < 0.05). Also thalidomide prevented kidney function failure by reduced urea (148.3 ± 4.4 mg/dL [BD + Thalid] vs. BD; p < 0.05), and creatinine (1.1 ± 0.14 mg/dL [BD + Thalid] vs. BD; p < 0.05). CONCLUSIONS: The immunomodulatory properties of thalidomide were effective in decreasing systemic and local immunologic response, leading to diminished renal damage, as reflected in the decrease of urea and creatinine levels. These results suggest that use of thalidomide may represent a potential strategy for treating in BD kidney organ donors.

Proprioceptive neuromuscular facilitation in the functionality and lymphatic circulation of the upper limb of women undergoing breast cancer treatment.

BACKGROUND: With the increase in survival of women treated for breast cancer, it is necessary to evaluate the effect of therapeutic resources on co-morbidities resulting from the surgical treatment of the disease. The aim of this study was to evaluate the effects of proprioceptive neuromuscular facilitation on the functionality and lymphatic circulation of the upper limb involved in the treatment of breast cancer. METHODS: The study was conducted according to randomized clinical trial design. Thirty-two women at a mean age of 52.20 (±8.32) years, submitted to breast cancer treatment, divided into two groups, control - women submitted to standard breast cancer treatment, and treated group, composed of women who underwent breast cancer treatment and rehabilitation with the proprioceptive neuromuscular facilitation technique. Palmar grip strength with dynamometer and shoulder range of motion with goniometer were evaluated. Lymphatic circulation analysis was performed in a computerized scintillation chamber, before and after therapeutic intervention. FINDINGS: In the results obtained, a significant increase (p < 0.05) of palmar grip strength was observed, a significant increase in range of motion of flexion (p < 0.001), extension (p < 0.0012), abduction (p < 0.0001), external rotation (p < 0.0001), internal rotation (p < 0.0001), and not significant for lymphatic flow (p > 0.05). INTERPRETATION: The results obtained in this study allow us to conclude that proprioceptive neuromuscular facilitation favors an increase in muscle strength, range of motion, but not in lymphatic flow, in women undergoing surgical treatment for breast cancer.

Assessment of late anthracycline-induced cardiotoxicity by 123I-mIBG cardiac scintigraphy in patients treated during childhood and adolescence.

PURPOSE: The goal of this study was to evaluate late cardiotoxic effects of anthracyclines (ATC) by evaluating cardiac sympathetic activity in a cohort of asymptomatic patients previously treated with ATC for childhood cancers. METHODS: We studied 89 asymptomatic patients previously treated with ATC with a normal echocardiogram (49 men and 40 women) and a control group of 40 healthy individuals (26 men and 14 women). Both groups underwent planar myocardial 123I-meta-iodobenzylguanidine scintigraphy (123I-mIBG). From these images, the early and late heart-to-mediastinum (H/M) ratio and washout rate (WR) were assessed. RESULTS: The mean survival at the time of the 123I-mIBG scintigraphy was 5.3 ± 3.4 years. Patients treated with ATC had a lower but clinical normal left ventricular ejection fraction (LVEF) compared to controls (60.44 ± 6.5 vs 64.1 ± 6.0%, P < 0.01). Both the late H/M ratio and WR were not able to discriminate ATC treated patients from controls. The cumulative ATC dose was the only independent predictor of the LVEF, explaining approximately 12% of the variation in LVEF (P = 0.01). CONCLUSIONS: Although the pathophysiology behind ATC cardiotoxicity is most likely multifactorial, myocardial sympathetic activity is not associated with a reduction in LVEF 5-years after completion of chemotherapy.

Physiotherapeutic stimulation: Early prevention of lymphedema following axillary lymph node dissection for breast cancer treatment.

The aim of this study was to confirm the effectiveness of early physiotherapeutic stimulation for lymphatic flow progression in patients with breast cancer undergoing axillary dissection. This was a randomized experimental study on 22 patients who underwent lymphoscintigraphy in their arms on two different occasions, firstly without stimulation and secondly after randomization into two groups: without physiotherapeutic stimulation (WOPS; n=10) and with physiotherapeutic stimulation (WPS; n=12). The lymphoscintigraphy scan was performed with (99m)Tc-phytate administered into the second interdigital space of the hand, ipsilaterally to the dissected axilla, in three phases: dynamic, static, and delayed whole body imaging. Physiotherapeutic stimulation was carried out using Földi's technique. In both groups, images from the two examinations of each patient were compared. Flow progression was considered positive when, on the second examination, the radiopharmaceutical reached areas more distant from the injection site. Statistical analysis was used to evaluate frequencies, percentages and central trend measurements, and non-parametric tests were conducted. Descriptive analysis showed that the WPS and WOPS groups were similar in terms of mean age, weight, height, body mass index and number of lymph nodes removed. There were statistically significant associations between physiotherapeutic stimulation and radiopharmaceutical progression at all three phases of the study (p<0.0001). Early physiotherapeutic stimulation in breast cancer patients undergoing radical axillary dissection is effective, and can therefore be indicated as a preventive measure against lymphedema.