Avaliação clínico-laboratorial e da expressão de metaloproteinases 2 e 9 de equinos com obstrução experimental do cólon menor

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Duloxetina para melhoria na qualidade de recuperação anestésica em histerectomia abdominal

Pós-graduação em Anestesiologia - FMB

Acidose láctica ruminal aguda induzida experimentalmente em ovinos: estudo clínico e laboratorial

Pós-graduação em Medicina Veterinária - FCAV

Acute phase response following ovariohysterectomy in female dogs

The concentrations of acute phase proteins are correlated with the severity of the surgical trauma, being elevated when severe tissue injury is produced. The aim of this study was to evaluate the leukogram and the acute phase proteins concentrations in healthy female dogs submitted to minimally invasive ovariohysterectomy, with the use of nylon cable ties (G1), and conventional (laparotomy) ovariohysterectomy, with the use of nylon suture (G2), as methods to ligate the ovarian pedicles and uterine body, respectively. Blood samples from 30 adult healthy female dogs (15 for each group) were obtained before surgery, and at 24 and 48 h and 7 days after surgery. Serum protein fractions were determined by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis. Neutrophilia was observed 24 h after both surgical procedures but did not differ (P ≥ 0.05) between the groups. In G1, the estimated concentration of ceruloplasmin increased (P ≤ 0.05) 48 h after the surgical procedure. The estimated ceruloplasmin concentration was significantly higher in G1 (P ≤ 0.05) when compared to G2 48 h postoperatively, and the estimated haptoglobin concentration was also significantly greater in G1 (P ≤ 0.05) than in G2 from 24 h to 7 days after surgery. Through the ceruloplasmin and haptoglobin estimated concentrations, we conclude that the minimally invasive ovariohysterectomy caused a more intense inflammatory response, which was not reflected in the white blood cell count.

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.

Fatores de risco nutricionais associados à mortalidade em pacientes com lesão renal aguda de acordo com os critérios do Acute Kidney Injury Network (AKIN)

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Fatores de risco nutricionais associados à mortalidade em pacientes com lesão renal aguda de acordo com os critérios do Acute Kidney Injury Network (AKIN)

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Relationship Between Oral Health-Related Quality of Life, Oral Health, Socioeconomic, and General Health Factors in Elderly Brazilians

Objectives To assess the impact of oral health on quality of life in elderly Brazilians and to evaluate its association with clinical oral health measures and socioeconomic and general health factors. Design Cross-sectional study. Setting Population-based cohort study on health, well-being, and aging. Participants Eight hundred fifty-seven participants representing 588,384 community-dwelling elderly adults from the city of Sao Paulo, Brazil. MeasurementS Self-perceived impact of oral health on quality of life was measured using the Geriatric Oral Health Assessment Index (GOHAI), with scores categorized as good, moderate, or poor, indicating low, moderate, and high degrees of negative impact on quality of life, respectively. Results Nearly half of the individuals had good GOHAI scores (44.7% of overall sample, 45.9% of dentate participants, and 43.4% of edentulous participants). In the overall sample, those with poor self-rated general health and a need for dental prostheses were more likely to have poor and moderate GOHAI scores. Individuals with depression were significantly more likely to have poor GOHAI scores. No socioeconomic variables were related to the outcome, except self-perception of sufficient income, which was a protective factor against a poor GOHAI score in dentate participants. Conclusion Moderate and high degrees of negative impact of oral health on quality of life were associated with general health and clinical oral health measures, independent of socioeconomic factors.

Oral Contraceptive Containing Chlormadinone Acetate and Ethinylestradiol Reduces Plasma Concentrations of Matrix Metalloproteinase-2 in Women with Polycystic Ovary Syndrome

Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first-line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti-androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 20 ovulatory women who wanted non-hormonal contraception (non-OC-control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 mu g ethinylestradiol for 6 months. Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by gelatin zymography or enzyme-linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control and OC-PCOS groups and TIMP-2 and TIMP-1 concentrations levels in the OC-control group (all p < 0.05), but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in any group (all p > 0.05). These findings indicated that long-term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP-2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.

Blocking of Connexin-Mediated Communication Promotes Neuroprotection during Acute Degeneration Induced by Mechanical Trauma

Accruing evidence indicates that connexin (Cx) channels in the gap junctions (GJ) are involved in neurodegeneration after injury. However, studies using KO animal models endowed apparently contradictory results in relation to the role of coupling in neuroprotection. We analyzed the role of Cx-mediated communication in a focal lesion induced by mechanical trauma of the retina, a model that allows spatial and temporal definition of the lesion with high reproducibility, permitting visualization of the focus, penumbra and adjacent areas. Cx36 and Cx43 exhibited distinct gene expression and protein levels throughout the neurodegeneration progress. Cx36 was observed close to TUNEL-positive nuclei, revealing the presence of this protein surrounding apoptotic cells. The functional role of cell coupling was assessed employing GJ blockers and openers combined with lactate dehydrogenase (LDH) assay, a direct method for evaluating cell death/viability. Carbenoxolone (CBX), a broad-spectrum GJ blocker, reduced LDH release after 4 hours, whereas quinine, a Cx36-channel specific blocker, decreased LDH release as early as 1 hour after lesion. Furthermore, analysis of dying cell distribution confirmed that the use of GJ blockers reduced apoptosis spread. Accordingly, blockade of GJ communication during neurodegeneration with quinine, but not CBX, caused downregulation of initial and effector caspases. To summarize, we observed specific changes in Cx gene expression and protein distribution during the progress of retinal degeneration, indicating the participation of these elements in acute neurodegeneration processes. More importantly, our results revealed that direct control of GJ channels permeability may take part in reliable neuroprotection strategies aimed to rapid, fast treatment of mechanical trauma in the retina.

Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer

Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. Patients and Methods Patients were randomly assigned to first-or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand-foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

Antioxidant treatment protects against matrix metalloproteinase activation and cardiomyocyte injury during acute pulmonary thromboembolism

Increased reactive oxygen species (ROS) promote matrix metalloproteinase (MMP) activities and may underlie cardiomyocyte injury and the degradation of cardiac troponin I (cTI) during acute pulmonary thromboembolism (APT). We examined whether pretreatment or therapy with tempol (a ROS scavenger) prevents MMP activation and cardiomyocyte injury of APT. Anesthetized sheep received tempol infusion (1.0 mg kg(-1) min(-1), i.v.) or saline starting 30 min before or 30 min after APT (autologous blood clots). Control animals received saline. Hemodynamic measurements were performed. MMPs were studied in the right ventricle (RV) by gelatin zymography, fluorimetric activity assay, and in situ zymography. The ROS levels were determined in the RV and cTI were measured in serum samples. APT increased the pulmonary arterial pressure and pulmonary vascular resistance by 146 and 164 %, respectively. Pretreatment or therapy with tempol attenuated these increases. While APT increased RV + dP/dt (max), tempol infusions had no effects. APT increased RV MMP-9 (but not MMP-2) levels. In line with these findings, APT increased RV MMP activities, and this finding was confirmed by in situ zymography. APT increased the RV ROS levels and tempol infusion, before or after APT, and blunted APT-induced increases in MMP-9 levels, MMP activities, in situ MMP activities, and ROS levels in the RV. cTI concentrations increased after APT, and tempol attenuated these increases. RV oxidative stress after APT increases the RV MMP activities, leading to the degradation of sarcomeric proteins, including cTI. Antioxidant treatment may prevent MMP activation and protect against cardiomyocyte injury after APT.

Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis

Purpose Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. Patients and Methods We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning. Results Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 x 10(9)/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; +/- standard deviation) was higher (30% +/- 5% v 16% +/- 5%; P = .006) and leukemia-free survival (LFS) lower (58% +/- 5% v 71% +/- 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. Conclusion FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.

Evaluation of the Effects of a Preoperative 2-Hour Fast With Maltodextrine and Glutamine on Insulin Resistance, Acute-Phase Response, Nitrogen Balance, and Serum Glutathione After Laparoscopic Cholecystectomy: A Controlled Randomized Trial

Background: Prolonged preoperative fasting increases insulin resistance (IR). The authors investigated whether an abbreviated preoperative fast with glutamine (GLN) plus a carbohydrate (CHO)-based beverage would improve the organic response after surgery. Methods: Forty-eight female patients (19-62 years) were randomized to either standard fasting (control group) or to fasting with 1 of 3 different beverages before video-cholecystectomy. Beverages were consumed 8 hours (400 mL; placebo group: water; GLN group: water with 50 g maltodextrine plus 40 g GLN; and CHO group: water with 50 g maltodextrine) and 2 hours (200 mL; placebo: water; GLN: water with 25 g maltodextrine plus 10 g GLN; and CHO: water with 25 g maltodextrine) before anesthesia. Blood samples were collected pre- and postoperatively. Results: The mean (SEM) postoperative homeostasis model assessment-insulin resistance was greater (P < .05) in control patients (4.3 [1.3]) than in the other groups (placebo, 1.6 [0.3]; CHO, 2.3 [0.4]; and GLN, 1.5 [0.1]). Glutathione was significantly higher (P < .01) in the GLN group than in both CHO and control groups. Interleukin-6 increased in all groups except the GLN group. The C-reactive protein/albumin ratio was higher (P < .05) in controls than in CHO and GLN groups. The nitrogen balance was less negative in GLN (-2.5 [0.8] gN) than in both placebo (-9.0 [2] gN; P = .001) and control (-6.6 [0.4] gN; P = .04) groups. Conclusions Preoperative intake of a GLN-enriched CHO beverage appears to improve IR and antioxidant defenses and decreases the inflammatory response after video-cholecystectomy. (JPEN J Parenter Enteral Nutr. 2012; 36: 43-52)

ACUTE EFFECTS OF A WARM-UP INCLUDING ACTIVE, PASSIVE, AND DYNAMIC STRETCHING ON VERTICAL JUMP PERFORMANCE

Carvalho, FLP, Carvalho, MCGA, Simao, R, Gomes, TM, Costa, PB, Neto, LB, Carvalho, RLP, and Dantas, EHM. Acute effects of a warm-up including active, passive, and dynamic stretching on vertical jump performance. J Strength Cond Res 26(9): 2447-2452, 2012-The purpose of this study was to examine the acute effects of 3 different stretching methods combined with a warm-up protocol on vertical jump performance. Sixteen young tennis players (14.5 +/- 2.8 years; 175 +/- 5.6 cm; 64.0 +/- 11.1 kg) were randomly assigned to 4 different experimental conditions on 4 successive days. Each session consisted of a general and specific warm-up, with 5 minutes of running followed by 10 jumps, accompanied by one of the subsequent conditions: (a) Control Condition (CC)-5 minutes of passive rest; (b) Passive Stretching Condition (PSC)-5 minutes of passive static stretching; (c) Active Stretching Condition (ASC)-5 minutes of active static stretching; and (d) Dynamic Stretching Condition (DC)-5 minutes of dynamic stretching. After each intervention, the subjects performed 3 squat jumps (SJs) and 3 countermovement jumps (CMJs), which were measured electronically. For the SJ, 1-way repeated measures analysis of variance (CC x PSC x ASC x DC) revealed significant decreases for ASC (28.7 +/- 4.7 cm; p = 0.01) and PSC (28.7 +/- 4.3 cm; p = 0.02) conditions when compared with CC (29.9 +/- 5.0 cm). For CMJs, there were no significant decreases (p > 0.05) when all stretching conditions were compared with the CC. Significant increases in SJ performance were observed when comparing the DC (29.6 +/- 4.9 cm; p = 0.02) with PSC (28.7 +/- 4.3 cm). Significant increases in CMJ performance were observed when comparing the conditions ASC (34.0 +/- 6.0 cm; p = 0.04) and DC (33.7 +/- 5.5 cm; p = 0.03) with PSC (32.6 +/- 5.5 cm). A dynamic stretching intervention appears to be more suitable for use as part of a warm-up in young athletes.