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PURPOSE: To explore the mechanism of resistance to IKKβ inhibitor in multiple myeloma (MM) cells and uncover novel therapeutic targets for MM. METHODS: We downloaded the microarray data (GSE8476) from GEO (Gene Expression Omnibus) database. The data were derived from the human MM cells lines (L363 cells) treated with IKKβ inhibitor MLN120b (MLN) for eight, 12 and 24 hours. Furthermore, we applied the Search Tool for the Retrieval of Interacting Genes (STRING) and Expression Analysis Systematic Explorer (EASE) database to construct protein-protein interaction networks and identified over-represented pathway among DEGs (differentially expressed genes). RESULTS: We obtained 108 DGEs in 8h vs. 12h group and 101 ones in 8h vs. 24h group. Most of DGEs were found to be involved in biological regulation. The significant pathways were Ig A pathway and the CAMs pathways. In addition, 24 common DGEs were found in the networks of the two groups such as ICAM 3 and SELL. CONCLUSION: Intercellular adhesion molecule 3 and SELL may be potential targets in multiple myeloma treatment in the future.

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PURPOSE: To verify the effects of different catecholamines on volemic expansion and on the autonomic nervous system in rabbits that were subjected to hemorrhage. METHODS: Twenty four rabbits subjected to hemorrhage (with a 25% loss of blood volume) and were randomly divided into four experimental groups: 1) HEMO Group underwent replacement with their own blood in an equal volume; 2) SS Group underwent replacement with saline solution (SS) in a volume that corresponded to three times the removed blood volume; 3) ISP Group underwent replacement with SS and isoprenaline; 4) FNL Group underwent replacement with SS and phenylephrine. Spectral Analysis of the heart rate and heart rate variability were performed from the recorded data. Hematocrit was measured throughout the experiment. RESULTS: Replacement with SS and an α- or β-agonist did not produce differences in the intravascular retention compared to replacement with SS alone. An analysis of HRV showed that the FNL group maintained the LF/HF ratio better than ISP and SS. CONCLUSIONS: No difference in vascular retention when α- or β- agonists were added to SS during post-hemorrhagic recovery. The animals in the FNL group maintained the integrity of the autonomic response within normal physiological standards during hemorrhagic stress.

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PURPOSE: To create in vitro a model to generate acidosis by CO2bubbling "organ chambers", which would be useful for researchers that aim to study the effects of acid-base disturbs on the endothelium-dependent vascular reactivity. METHODS: Eighteen male Wistar rats (230-280g) were housed, before the experiments, under standard laboratory conditions (12h light/dark cycle at 21°C), with free access to food and water. The protocol for promoting in vitro respiratory acidosis was carried out by bubbling increased concentrations of CO2. The target was to achieve an ideal way to decrease the pH gradually to a value of approximately 6.6.It was used, initially, a gas blender varying concentrations of the carbogenic mixture (95% O2 + 5% CO2) and pure CO2. RESULTS: 1) 100% CO2, pH variation very fast, pH minimum 6.0; 2) 90%CO2 pH variation bit slower, pH minimum6.31; 3) 70%CO2, pH variation slower, pH minimum 6.32; 4) 50% CO2, pH variation slower, pH minimum 6:42; 5) 40 %CO2, Adequate record, pH minimum 6.61, and; 6) 30 %CO2 could not reach values below pH minimum 7.03. Based on these data the gas mixture (O2 60% + CO2 40%) was adopted, CONCLUSION: This gas mixture (O2 60% + CO2 40%) was effective in inducing respiratory acidosis at a speed that made, possible the recording of isometric force.

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PURPOSE: To investigate the development of a laparoscopy technique for local injection into the X-linked muscular dystrophy (mdx) diaphragm. METHODS: It was used 10 mice Balb/C57 and 5 mdx mice and three differents decubitus type were tested: the right lateral, supine, and supine decubitus with 20 degrees elevation of the forelimb. Abdominal caudal face and the 10 intercostal space were tested as spot to introduce the needle into the diaphragm. RESULTS: Supine position with elevation of 20 degrees forelimb and the 10th intercostal space are the beneficial position to apply a local injection. CONCLUSION: It was proved to be possible to perform the laparoscopy technique in the X-linked muscular dystrophy diaphragm and this requires a specific position and technique during the surgery.

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PURPOSE: To determine the behavior of intraocular pressure and its relationship with infusion pressure in vitrectomy, phacofragmentation and phacoemulsification surgeries in rabbits. METHODS: Intraocular pressure fluctuation was measured in 24 eyes of 12 rabbits submitted to vitrectomy, phacofragmentation and phacoemulsification procedures (eight eyes per group). The procedures were divided according to the force of aspiration of the instrument. Intraocular pressure was monitored with a computerized polygraph by means of a cannula introduced into the vitreous chamber. RESULTS: Intraocular pressure showed a mean variation from 33 mmHg (maximum) to 6 mmHg (minimum). Vitrectomy showed the greatest difference between weak and strong aspiration. The greatest fluctuations occurred during procedures with strong aspiration, with phacoemulsification showing the widest variation, with maximum peaks almost reaching 50 mmHg. The infusion pressure varied less than the intraocular pressure, especially at the lowest pressures. CONCLUSIONS: The fluctuation of intraocular pressure during ocular surgeries was not great. The higher the aspiration pressure, the higher the intraocular pressure. The infusion pressure did not show a good correlation with intraocular pressure.

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PURPOSE: To evaluate the effect of curcumin in the acute phase of zymosan-induced arthritis. METHODS: Twenty-eight male rats were subjected to intra-articular infiltration of zymosan of both knees and, in four the infiltration was made with saline. The animals were divided into five groups second received every six hours by gavage: corn oil by (positive and negative control); curcumin (100 mg/kg); prednisone 1 mg/kg/day; prednisone 8 mg/kg. All animals were sacrificed after six, 12, 24 and 48 hours of the infiltration. The knees were removed for evaluation of neutrophil infiltration. The number of neutrophils was counted by computer-assisted analysis of the images. The neutrophil infiltrate was stratified into four grades: 0 = normal; + = mild; ++/+++ = moderate; > ++++ = severe. The results were compared using the Mann-Whitney test and the variance by Kruskal-Wallis test adopting a significance level of 5% (p<0.05). RESULTS: Curcumin reduces inflammatory activity in the first six hours after zymosan-induced arthritis when compared to saline (p<0.01). This was also observed in animals subjected to administration of prednisone (1 mg/kg) and those treated with prednisone (8 mg/kg). Curcumin was more effective than lower doses of prednisone in the first six hours after induction of the arthritis. After 12, 24 and 48 hours, curcumin does not have the same anti-inflammatory effects when compared to prednisone. After 48 hours, prednisone is more effective than curcumin in reducing the inflammatory infiltrate regardless of the dose of prednisone used. CONCLUSION: Oral administration of curcumin reduces inflammation in the first six hours after experimentally zymosan-induced arthritis.

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PURPOSE: To evaluate intestinal inflammatory and apoptotic processes after intestinal ischemia/reperfusion injury, modulated by pentoxifylline and hypertonic saline. METHODS: It was allocated into four groups (n=6), 24 male Wistar rats (200 to 250g) and submitted to intestinal ischemia for 40 min and reperfusion for 80 min: IR (did not receive any treatment); HS group (Hypertonic Saline, 4ml/kg-IV); PTX group (Pentoxifylline, 30mg/kg-IV); HS+PTX group (Hypertonic Saline and Pentoxifylline). All animals were heparinized (100U/kg). At the end of reperfusion, ileal fragments were removed and stained on hematoxylin-eosin and histochemical studies for COX-2, Bcl-2 and cleaved caspase-3. RESULTS: The values of sO2 were higher on treated groups at 40 minutes of reperfusion (p=0.0081) and 80 minutes of reperfusion (p=0.0072). Serum lactate values were lower on treated groups after 40 minutes of reperfusion (p=0.0003) and 80 minutes of reperfusion (p=0.0098). Morphologic tissue injuries showed higher grades on IR group versus other groups: HS (p=0.0006), PTX (p=0.0433) and HS+PTX (p=0.0040). The histochemical study showed lesser expression of COX-2 (p=0.0015) and Bcl-2 (p=0.0012) on HS+PTX group. A lower expression of cleaved caspase-3 was demonstrated in PTX (p=0.0090; PTXvsIR). CONCLUSION: The combined use of pentoxifylline and hypertonic saline offers best results on inflammatory and apoptotic inhibitory aspects after intestinal ischemia/reperfusion.

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PURPOSE: We evaluated the hypothesis that induced perioperative hypothermia (32 ± 1ºC) affects the redox balance in the tissue of colonic anastomosis in rats by modifying biochemical enzymatic and non-enzymatic markers related to oxidative stress. METHODS: Forty-eight male Wistar rats were randomly divided into eight experimental groups of six animals each and underwent laparotomy, sigmoid section and immediate anastomosis. Four groups were operated under normothermia (36 ± 1ºC), and the other four under hypothermia (32 ± 1ºC). The animals were reoperated on days 3, 7 and 14 postoperatively, and two groups underwent SHAM at 3 days. From the scar tissue samples, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was evaluated, and the levels of non-enzymatic markers of oxidative stress, such as reduced glutathione (GSH) and lipid peroxidation, were measured by the thiobarbituric acid reactive substances (TBARS) assay. The means were compared between groups corresponding to each day of sampling and euthanasia. RESULTS: The hypothermic groups showed a significant reduction on the activity of SOD on day 7 postoperatively, on the activity of CAT on days 7 and 14 postoperatively and on the levels of GSH on day 7 postoperatively. The level of lipid peroxidation was increased in the hypothermia group on day 7 postoperatively and decreased on day 14 compared with the normothermic groups. CONCLUSION: Perioperative hypothermia reduced the activity of the antioxidant enzymes catalase and superoxide dismutase, glutathione levels and increased lipid peroxidation in the scar tissue of colonic anastomoses in rats.

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PURPOSE: To perform a cost analysis of simultaneous pancreas-kidney transplantation (SPKT) in a Brazilian hospital. METHODS: Between January 2008 and December 2011, 105 consecutive SPKTs at the Hospital of Kidney and Hypertension in Sao Paulo were evaluated. We evaluated the patient demographics, payment source (public health system or supplementary system), and the impact of each hospital cost component. The evaluated costs were corrected to December 2011 values and converted to US dollars. RESULTS: Of the 105 SPKT patients, 61.9% were men, and 38.1% were women. Eight patients died, and 97 were discharged (92.4%). Eighty-nine procedures were funded by the public health system. The cost for the patients who were discharged was $18.352.27; the cost for the deceased patients was $18.449.96 (p = 0.79). The FOR for SPKT during this period was positive at $5,620.65. The costs were distributed as follows: supplies, 36%; administrative costs, 20%; physician fees, 15%; intensive care unit, 10%; surgical center, 10%; ward, 9%. CONCLUSION: Mortality did not affect costs, and supplies were the largest cost component.

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PURPOSE: To evaluate the efficacy and side-effects of fentanyl and sufentanil combined with hyperbaric spinal bupivacaine in elective cesarean section. METHODS: A prospective, randomized, double-blind study with 64 term parturients, distributed into 2 groups according to the opioid combined with hyperbaric bupivacaine 0.5% (10mg): GF - fentanyl (25µg) and GS - sufentanil (5.0µg). The latency and maximum sensory block level; degree and duration of motor block; duration and quality of analgesia; maternal-fetal repercussions were evaluated. This was an intention-to-treat analysis with a 5% significance level. RESULTS: The latency period, maximum sensory block level, motor block degree and perioperative analgesia were similar in both groups. Motor block and analgesia had a longer duration in the sufentanil group. Maternal adverse effects and neonatal repercussions were similar. The incidence of hypotension was higher in the fentanyl group. In both groups, there was a predominance of patients who were awake and either calm or sleepy. CONCLUSIONS: The addition of fentanyl and sufentanil to hyperbaric subarachnoid bupivacaine was shown to be effective for the performance of cesarean section, and safe for the mother and fetus. Analgesia was more prolonged with sufentanil.

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PURPOSE: To characterize the comorbidities associated with hospitalizations for obesity and the relationship of these co-morbidities with bariatric surgery and hospitalization costs during the period between 2000 and 2010 in Sao Paulo that were financed by the Brazilian Public Health System (SUS). METHODS: We used data from the Hospital Information System of the Unified Health System (SIH-SUS) for selected individuals hospitalized for obesity according to International Classification of Diseases (ICD10). RESULTS: The total cost of hospitalizations was approximately two million dollars, with 67% of the total cost for bariatric and reconstructive surgery. Women accounted for 87% of hospitalizations, and 77% of subjects were aged between 30 and 59 years; the main comorbidity found was hypertension, and the procedures performed were bariatric surgery and reconstructive surgery (post-bariatric surgery). CONCLUSION: Obesity is a major public health problem that affects people of productive age, causing high costs of hospitalization, which reinforces the requirement for preventive interventions beginning from childhood.

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PURPOSE: To investigate the accelerating effects of low-intensity pulse ultrasound stimulation (LIPUS) on the fracture healing of distal radius. METHODS: A total of 81 patients with distal radius fracture were randomly divided into two groups: the ultrasound treatment group and the control group. Patients in the ultrasound treatment group were immobilized in a below-elbow cast and received LIPUS treatment 15 min/day, while the control group were immobilized by a plaster support and cast. The patients were followed up every week and took X-ray films. The initial and healed X-ray films and the gray value of fracture site were analyzed by Photoshop software. The effect of reposition was evaluated based upon Steward recommended by Dienst, combining with Aro's measuring method. RESULTS: Clinical fracture healing time in ultrasound group was significantly shorter than that in the control group (32.04 ± 2.58d vs. 40.75 ± 5.12d, p <0.01). In addition, the grey value changes of fracture sites of the ultrasound group were much higher than that of the control group. The reposition effects of fracture healing had no difference between the two groups (p >0.05). CONCLUSION: Low-intensity pulse ultrasound stimulation could accelerate fracture healing of the distal radius and promote local bone formation.