Pterostilbene and Probiotic Complex in Chemoprevention of Putative Precursor Lesions for Colorectal Cancer in an Experimental Model of Intestinal Carcinogenesis with 1,2-Dimethylhydrazine.

Dietary supplementation with pterostilbene (PS) and/or a probiotic (PRO) may ameliorate the intestinal microbiota in disease conditions. This study aims to evaluate PS and PRO for the chemoprevention of putative precursor lesions for colorectal cancer (CRC) in an experimental model of intestinal carcinogenesis with 1,2-dimethylhydrazine (1,2-DMH). Sixty male Wistar rats were equally divided into five groups: Sham, 1,2-DMH, 1,2-DMH + PS, 1,2-DMH + PRO, and 1,2-DMH + PS + PRO. PRO (5 × 107/mL) was offered in water, and PS (300 ppm) was provided in the diet ad libitum. 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. PRO alone and PRO combined with PS were the best intervention strategies to improve experimental 1,2-DMH-induced CRC regarding several parameters of carcinogenesis. Our findings may contribute to the development of novel preventive strategies for CRC and may help to identify novel modulators of colon carcinogenesis.

Endosuture trainer box simulator as a tool for training and teaching in bariatric laparoscopic surgery.

BACKGROUND: Video surgery requires acquisition of psychomotor skills that are different from those required for open surgery. The aim of this study was to assess the EndoSuture Trainer Box Simulator (ESTBS), a new bariatric laparoscopic skills simulator, as a tool for surgical education, comparing it with a standard laparoscopic trainer (SLT). METHODS: A randomized prospective crossover study was designed to compare ESTBS versus SLT as a tool for training bariatric laparoscopic skills. Participants were assigned to perform a task simulating Nissen fundoplication operation. All subjects evaluated the simulators concerning to their performance on simulating laparoscopic procedures by the use of a questionnaire comparing: triangulation, resistance and resilience, spatial perception (stereotaxy), ergonomics and positioning, inverted movements, visibility, design, technical and technological resources for training and education. The overall score was defined as the median value obtained. A total of 37 participants were enrolled in the study, including 29 experienced surgeons (78.37%) and 08 surgical residents (21.63%). RESULTS: A superior performance was observed with ESTBS as compared to SLT upon 7 of the 10 items evaluated in the questionnaire. Additionally, the overall score of ESTBS (median of 4, very good) was significantly higher (P < 0.0001) than that of SLT (median of 3, good). For the items, triangulation, resistance and resilience, ergonomics, design, training, technology and teaching, the evaluation for the ESTBS was very good and excellent, which was significantly higher than obtained by SLT. Also, ESTBS was cheaper. CONCLUSIONS: The ESTBS was shown to present excellent technical and technological performances and appears to constitute a useful cost-effective promising instrument for teaching and training bariatric surgical laparoscopic skills.

Presence of new mutations in the TP53 gene in patients with low-risk myelodysplastic syndrome: two case reports.

BACKGROUND: Myelodysplastic syndromes are heterogeneous disorders. Patients with myelodysplastic syndrome disease often have ineffective hematopoiesis, cytopenias, blood cell dysplasia in one or more cell types, and are at high risk for developing acute myeloid leukemia. In myelodysplastic syndrome, mutations of TP53 gene are usually associated with complex karyotype and confer a worse prognosis. In the present study, two mutations in this gene are presented and discussed with the clinical evolution of the patients. CASE PRESENTATION: The first case is a 77-year-old Brazilian woman diagnosed as having multiple lineage dysplasia myelodysplastic syndrome according to World Health Organization 2016 and classified as very low-risk by Revised International Prognostic Scoring. The second case is an 80-year-old Brazilian man also diagnosed as having multiple lineage dysplasia myelodysplastic syndrome and classified as low risk. The mutation described in the first case was already identified in some neoplasias and it is associated with a poor prognosis, but it had never been reported before in myelodysplastic syndrome. The second mutation has never been described. CONCLUSIONS: This is a novel report for the scientific community and may be very helpful as we can better understand the disease and the impact of mutations through the follow-up of these patients and others in the future. Both patients are in a good clinical condition, suggesting that these mutations may not alter the clinical course of the disease or may be associated with a good prognosis, but their role in the disease must be investigated more deeply in a larger population.

Tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome.

BACKGROUND: At the time of diagnosis, more than 50% of patients with myelodysplastic syndrome have a normal karyotype and are classified as having a favorable prognosis. However, these patients often show very variable clinical outcomes. Furthermore, current diagnostic tools lack the ability to look at genetic factors beyond karyotyping in order to determine the cause of this variability. OBJECTIVE: To evaluate the impact of p53 protein expression at diagnosis in patients with low-risk myelodysplastic syndrome. METHODS: This study enrolled 38 patients diagnosed with low-risk myelodysplastic syndrome. Clinical data were collected by reviewing medical records, and immunohistochemical p53 staining was performed on bone marrow biopsies. RESULTS: Of the 38 participants, 13 (34.21%) showed p53 expression in their bone marrow. At diagnosis, this group of patients also presented clinical features characteristic of a poor prognosis more often than patients who did not express p53. Furthermore, patients expressing p53 had a shorter median survival time compared to those without p53 expression. CONCLUSION: This study shows that the expression of p53 at diagnosis is a useful indicator of distinct clinical characteristics and laboratory profiles found in low-risk myelodysplastic syndrome patients. These data indicate that the immunohistochemical analysis of p53 may be a prognostic tool for myelodysplastic syndrome and should be used as an auxiliary test to help determine the best therapeutic choice.

Electroacupuncture attenuates oxidative stress in random skin flaps in rats.

BACKGROUND: Skin flaps may be damaged by free radicals produced during blood reflow and oxygen return to ischemic tissues. Considering that published studies have demonstrated the effects of manual acupuncture (MA) and electroacupuncture (EA) in attenuating the oxidative stress in different tissues and organs, this study aimed to investigate the possible protective effects of MA and EA in randomized skin flaps in rats. METHODS: Thirty-two rats were subjected to dorsal skin flap (8 × 2.5 cm) construction and randomly divided into four groups of eight rats each: G1, surgical trauma; G2, MA; G3, EA 3 Hz; and G4, EA 100 Hz. All rats were anesthetized with ketamine (90 mg/kg) + xylazine (10 mg/kg) intraperitoneally on days 1, 3, and 7. MA (G2) and EA (G3/G4) were applied on days 3 and 7 of the experiment. G3 and G4 rats were treated with EA 3 and 100 Hz, respectively. Needles were inserted in GV-14 (Dazhui), GV-2 (Yaoshu), and L-13 (Zhangmen) acupoints and retained for 30 min. Blood and skin samples were collected at the end of the last procedure. The ANOVA/Dunnett test was used for group comparison. Values of p < 0.05 were considered significant. RESULTS: Skin myeloperoxidase (MPO) activity decreased significantly in G2, G3, and G4 rats. Plasma and skin levels of reduced glutathione (GSH) increased significantly in G3 and G4 rats (p < 0.001) compared with G1 control. Malondialdehyde (MDA) plasma and skin levels increased significantly in G4 compared with G1 rats. CONCLUSIONS: MA/EA decreased MPO activity in the graft, consistent with attenuated inflammation, and increased plasma and tissue GSH, indicative of reduced systemic and local oxidative stress. EA at 100 Hz enhances lipid peroxidation in plasma and skin of rats subjected to surgical stress. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article.

Enteral nutrition supplemented with L-glutamine in patients with systemic inflammatory response syndrome due to pulmonary infection.

OBJECTIVE: To evaluate the effect of enteral nutrition (EN) supplemented with l-glutamine on glycolytic parameters, inflammation, immune function, and oxidative stress in moderately ill intensive care patients with sepsis. METHODS: Thirty patients received EN. Fifteen patients received EN supplemented with glutamine (30 g; GLN group) for 2 d followed by EN supplemented with calcium caseinate (30 g, CAS group), also over 2 d. The other 15 patients received EN with calcium caseinate (30 g; CAS group) for 2 d followed by EN with glutamine (30 g; GLN group), also over 2 days. One washout day with only EN was provided between every 2-d period of EN plus supplementation to all patients. Blood samples were taken before and after supplementation. RESULTS: There were no changes in glycolytic parameters in either group. Leukocytes decreased in the two groups (from 13 650 to 11 500 in the CAS group, P = 0.019; from 12.850 to 11.000 in the GLN group, P = 0.046). Lymphocytes increased in the GLN group (from 954 to 1916, P < 0.0001) and were more numerous after glutamine supplementation (from 1916 to 1085, P < 0.0001, GLN versus CAS). No significant changes were observed in interleukin levels, but urea levels were higher in the GLN compared with the CAS group (50.0-47.0, P = 0.030). Glutathione plasma concentrations did not differ significantly between the groups. No significant changes were observed in the plasma glutamine and glutamate concentrations. CONCLUSIONS: The EN supplemented with glutamine increased the lymphocyte count and helped to decrease lipid peroxidation but presented no effect on the antioxidant glutathione capacity and on cytokine concentrations or glycolytic parameters.

Oxidative stress in follicular units during hair transplantation surgery.

BACKGROUND: Hair transplantation surgery currently is a well-established procedure in plastic surgery. It consists of harvesting a strip of scalp from the back of the head, then obtaining grafts called follicular units (FUs) from this strip and implanting them in the bald area. The FUs undergo oxidative stress during cold ischemia and after their implantation. METHODS: Surgery was performed for 18 patients between April and July 2008. Follicular units were preserved in solutions containing different growth-stimulating hormone (GSH) concentrations (5, 10, and 20 mmol). Saline solution was used as a control condition. Spectrophotometry was used to measure the thiobarbituric acid-reactive substance (TBARS) and GSH concentrations before ischemia (control group) in the FUs preserved in the four proposed solutions, then after 30 min of cold ischemia and 30 min after grafting. The data obtained were submitted to analysis of variance, t test, and linear regression analysis. RESULTS: The TBARS (µmol of malondialdehyde [MDA]/g) and GSH (µmol/g) concentrations were not significantly different between the four solutions in either the ischemia or grafting group. The GSH concentration did not differ significantly between the control (59.801 ± 30.639 µmol/g) and ischemia (56.284 ± 28.404 µmol/g) groups. The GSH concentrations were significantly greater (p < 0.05) in the postgrafting group (63.815 ± 28.404 µmol/g) than in the group subjected to ischemia. CONCLUSION: Increasing the GSH concentrations used in FU preservation solutions does not reduce the oxidative effects of cold ischemia and reperfusion injury during hair transplantation surgery.

L-alanyl-glutamine preoperative infusion in patients with critical limb ischemia subjected to distal revascularization reduces tissue damage and protects from oxidative stress.

BACKGROUND: Critical limb ischemia (CLI) is the most severe form of peripheral vascular disease where there is inadequate blood flow to a limb. Our aim was to examine the effects of preoperative infusion of l-alanyl-glutamine (l-Ala-Gln) during the ischemic period and during the first 30 minutes following blood reflow in patients with CLI who are undergoing distal femoral artery bypass surgery. METHODS: Thirty-two patients with CLI were alternately allocated to group 1 (saline) or group 2 (l-Ala-Gln). Saline (1000 mL) or L-Ala-Gln 250 mL plus 750 mL of saline were infused intravenously over a 3-hour period prior to surgery. Samples (muscle and blood) were collected at the beginning of the surgical procedure, at the end of ischemia, and at 15 and 30 minutes after reperfusion. RESULTS: l-Ala-Gln induced elevation in glutathione (GSH) muscle concentrations while promoting reduction in thiobarbituric acid reactive substance concentrations, demonstrating enhancement of antioxidant capacity and protection from lipid peroxidation. Decreases in LDH, lactate, and glucose blood concentrations in l-Ala-Gln-treated patients suggest increased glucose utilization by muscle and peripheral tissues. Reduction in creatine phosphokinase blood concentrations may reflect smaller muscle cell damage in l-Ala-Gln-treated patients. CONCLUSION: l-Ala-Gln pretreatment reduces muscle cell damage and enhances antioxidant capacity in patients with CLI.

The safety of oral use of L-glutamine in middle-aged and elderly individuals.

OBJECTIVE: To evaluate the safety of nutraceutical oral administration of L-glutamine (L-Gln) in middle-aged and elderly individuals. METHODS: In this randomized, crossover, double-blind clinical study, 30 residents of a long-term-care institution, selected according to a modified SENIEUR protocol (Working Party of the EURAGE Concerted Action Programme on Ageing of the European Community), were studied. Fourteen subjects received orally 0.5 g kg(-1) d(-1) of L-Gln and 16 received calcium caseinate for 14 d, followed by a 5-d washout. Supplements were switched for the second 14-d trial. Laboratory tests for hepatic and renal functions and ammonemia were performed and the estimated glomerular filtration rate (eGFR) was calculated. RESULTS: Of the 30 subjects, 16 were men, mean age was 69+/-8.8 y, average weight was 61.8+/-14.2 kg, and mean serum albumin was 4.0+/-0.3g/dL. Neither adverse clinical effects nor clinically significant laboratory changes were noted during L-Gln supplementation. There was no difference in ammonemia between the groups. There were statistically but not clinically significant increases in plasma urea nitrogen and creatinine concentrations. There was no significant decrease in eGFR during calcium caseinate supplementation (-2.9%). The eGFR decreased significantly after L-Gln supplementation (-13.3%) but well below the 25% limit for biologic significance. CONCLUSION: Increases in serum urea nitrogen and creatinine and decrease in eGFR are probably due to difficulties by older kidneys in metabolizing the supplemented protein sources. Although not clinically significant, those alterations impose a rigorous control on the evaluation parameters of renal function during oral L-Gln supplementation, with doses of 0.5 g kg(-1) d(-1) in middle-aged and elderly individuals.

Effects of Copaifera langsdorffii Desf. on ischemia-reperfusion of randomized skin flaps in rats.

BACKGROUND: Copaíba oil is an oleoresin obtained from the Copaiffera langsdorffii genus (Leguminoseae). It is widely used in folk medicine as an antiinflammatory, healing, and antiseptic agent. Comparative pharmacologic studies between different species of copaíba oils are scarce. METHODS: The protective effect of Copaiffera langsdorffii was evaluated on an experimental model of random skin flaps on rat dorsums. RESULTS: Seventy-two Wistar rats (average weight = 216.8 g) were divided randomly into four equal groups (saline control, vehicle control, GT200-Test 1, and GT400-Test 2). A caudally based rectangular flap, 2.5-8.0 cm in size, was elevated on the back of the rat using McFarlane's method. The flap was sutured back into its original place. Copaifera and control drugs (saline and Tween 80) were administered by gavage 24, 12, and 2 h prior to the beginning of the experiment followed by daily doses for the next 7 days. To observe the effects of Copaifera, laboratory analyses included plasma and tissue levels of tiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) and tissue levels of myeloperoxidase (MPO). CONCLUSION: The oil-resin of copaíba presents discrete antilipoperoxidation action, intense antioxidant action, and antiinflammatory activity during the ischemia and reperfusion of randomized cutaneous flaps. The effects of ischemia-reperfusion are complex and substances capable of increasing the tolerance of tissue to those effects by reducing the production or neutralizing the action of free radicals are needed.

Protective effect of alpha-lipoic acid in experimental spermatic cord torsion.

OBJECTIVE: We investigated the effect of alpha-lipoic acid (LA) in rats that were subjected to torsion/detorsion of the spermatic cord in a comparative controlled experiment. METHODS: Forty-eight male Wistar rats, randomized in two groups, received intraperitoneal injections of LA (LA group; aqueous solution at 36 mg/kg of body weight per day) or equal volume of saline (control group) 21, 9, and 1 h before torsion of the spermatic cord. Rats in each group were distributed in four subgroups, each comprising six animals. All surgical procedures were performed under inhaled ether anesthesia. Ischemia was induced by 720-degree torsion of the spermatic cord for 3 h. The right testis was assessed through longitudinal scrotal incision. After each surgical procedure, scrotal incisions were closed with 4-0 nylon monofilament. Ipsilateral testes and arterial blood samples were collected at the end of ischemia and 1, 3, and 6 h after detorsion. Thiobarbituric acid-reactive substances and reduced glutathione levels (micromoles per gram of wet tissue) were assayed in testis. Total antioxidant power was measured in blood plasma. RESULTS: LA pretreatment promoted a significant decrease in testicular concentrations of thiobarbituric acid-reactive substances and simultaneously induced an increase in reduced glutathione concentrations at all time points studied. Plasma total antioxidant power levels increased significantly during reperfusion (T-1) in LA-treated rats compared with control rats. CONCLUSION: LA administered before torsion of the spermatic cord showed significant protective effects against ischemia/reperfusion injury by decreasing lipid peroxidation and regulating testicular reduced glutathione and plasma total antioxidant power levels.

Metabolic effects of l-alanyl-glutamine in burned rats.

Burn injury elicits a sustained hypermetabolic state characterized by accelerated hepatic synthesis of amino acids and proteolysis leading to negative nitrogen balance. This paper was aimed at studying the effects l-alanyl-glutamine (Ala-Gln) exogenous offer to rats submitted to thermal burn. Twenty-four anesthetized male Wistar rats were submitted to scald burn of dorsal skin (30% body surface). Eighteen and 42-h later rats were randomized to receive (by gavage) 2ml of water (G-1) or equal volume (0.5g/kg weight/day) of Ala-Gln solution (G-2). Tissue and blood samples were collected at the end of 24 and 48-h post-burn trauma (PBT). Blood concentrations of metabolites (glucose, pyruvate, lactate and ketone bodies) were similar in all groups. There were significant differences in tissue metabolites concentrations in Ala-Gln treated rats (G-2) compared to control (G-1) following scald injury. The administration of Ala-Gln to burned rats induces a fall ATP (muscle, healthy skin), pyruvate and ketone bodies (liver) concentrations 24-h PBT. It also induces significant increase of lactate (burned skin) 24-h and glucose (liver) 28/48-h PBT. Rise of tissue lactate concentrations may be due to enhanced anaerobic glycolysis resulting from increased availability of glutamate, derived from glutamine, with possible activation of the malate-aspartate shuttle.

Capella's gastroplasty: metabolites and acute phase proteins changes in midline and bilateral arciform approaches.

BACKGROUND: Obesity has adverse health effects. Dietary reeducation does not seem to offer sustained weight loss. For appropriately selected patients, surgery may be beneficial. AIM: To evaluate early postoperative metabolic response to surgery in patients submitted to Capella's gastroplasty using two different surgical approaches to the abdominal cavity. PATIENTS/METHOD: Twenty patients (9 males and 11 females, aged 21 to 53 years) were randomized prior to submission to either one of the surgical access incisions (bilateral arciform or supra-umbilical midline incisions). Blood samples were collected at the beginning and end of the operation, 12 (T-12 h) and 24 hours (T-24 h) postoperatively. Dieresis and synthesis time, blood loss, planimetry of operative field, operative time, hospital stay, hemoglobin, hematocrit, lymphocytes, potassium, albumin, erythrocyte sedimentation rate, C-reactive protein, glucose, pyruvate, lactate and ketone bodies were analyzed. RESULTS: Dieresis time was significantly decreased when median approach was used. Total operating time, hospital stay, hematocrit, hemoglobin, lymphocyte count, potassium and albumin concentrations were similar in both groups. C-reactive protein (T-12 h), glucose and pyruvate concentrations (T-24 h) increased significantly after completion of surgical procedure. Ketone bodies concentrations were significantly decreased 24 hour following completion of surgical procedure. CONCLUSION: Capella's gastroplasty induces metabolic and inflammatory changes in blood parameters. There is no evidence of technical superiority of arciform over midline incisions in this study.