Publications by authors named "Sérgio Britto Garcia"

56 Publications

Experimental Model of Rectal Carcinogenesis Induced by N-Methyl-N-Nitrosoguanidine in Mice with Endoscopic Evaluation.

Int J Med Sci 2020 10;17(16):2505-2510. Epub 2020 Sep 10.

Department of Surgery and Anatomy, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.

The discovery of chemical substances with carcinogenic properties has allowed the development of several experimental models of colorectal cancer (CRC). Classically, experimental models of CRC in mice have been evaluated through clinical or serial euthanasia. The present study aims to investigate the role of low endoscopy in the analysis of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Thirty C57BL6 mice were divided into two groups: a control group with fifteen animals that underwent rectal instillation of saline solution on day 0 and a carcinogen group with fifteen animals that underwent a 100 mg/kg MNNG rectal instillation on day 0. In both groups, low endoscopies were performed on weeks 4 and 8. We used a validated endoscopic scoring system to evaluate the severity of colitis and colorectal tumor. Euthanasia was carried out at week 12. We observed higher inflammation scores (p <0.001) and a higher number of tumors (p <0.05) in the MNNG group than the control group, both at weeks 4 and 8. A worsening of inflammation scores from the first to the second endoscopy was also noticeable in the MNNG group. There were no bowel perforations related to the procedure, and there was one death in the control group. Low endoscopy in experimental animals allows safe macroscopic evaluation of colorectal carcinogenesis without the need for euthanasia.
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http://dx.doi.org/10.7150/ijms.48231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532479PMC
September 2020

Thalidomide Reduces Cell Proliferation in Endometriosis Experimentally Induced in Rats.

Rev Bras Ginecol Obstet 2019 Nov 19;41(11):668-672. Epub 2019 Nov 19.

Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Objective:  To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium.

Methods:  Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells.

Results:  Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland ( < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma ( < 0.001), respectively. Also, the mean lesion area of Group I was 69.2 mm2, a significantly higher value compared with Group II (49.4 mm2,  = 0.023) and Group III (48.6 mm2,  = 0.006). No significant difference was observed between Groups II and III.

Conclusion:  Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1 mg/kg/day and at the dose of 10 mg/kg/day.
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http://dx.doi.org/10.1055/s-0039-3399551DOI Listing
November 2019

Botulinum toxin as a treatment for short bowel syndrome in rats.

Acta Cir Bras 2019 Sep 16;34(7):e201900705. Epub 2019 Sep 16.

PhD, Full Professor, Department of Pathology and Legal Medicine, School of Medicine of Ribeirao Preto, USP, Sao Paulo-SP, Brazil. Conception, design, intellectual and scientific content of the study; critical revision; final approval.

Purpose: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine.

Methods: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C - control).

Results: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection.

Conclusion: This may provide a new promising approach to the surgical treatment of SBS.
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http://dx.doi.org/10.1590/s0102-865020190070000005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756011PMC
September 2019

Effect of High Voltage Pulsed Current on the integration of total skin grafts in rats submitted to nicotine action.

J Tissue Viability 2019 Aug 20;28(3):161-166. Epub 2019 May 20.

Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School - FMRP/USP, Brazil. Electronic address:

Objective: The aim of this study was to evaluate the impact of High Voltage Pulsed Current (HVPC) on the integration of total skin grafts in rats submitted to nicotine action.

Materials And Methods: For this purpose, 60 adult Wistar rats randomly distributed in 6 groups of 10 animals were analyzed. The electrical stimulation (anodic and cathodic stimulation, motor level, 30 min at 10 Hz; minimum voltage 20 μs and 100 μs pulse interval) was applied for seven days, starting on the third day after surgery and after the dressing was removed from the graft.

Results: Anodic HVPC promoted greater graft integration, demonstrating a lower percentage of tissue contraction, a lower number of inflammatory infiltrates and a greater amount of vascular endothelial growth factor (VEGF), as well as a higher number of newly formed blood vessels.

Conclusions: HVPC can positively influence the integration of skin grafts in nicotine-treated rats. anodic HVPC is shown to promote greater integration in relation to a lower percentage of tissue contraction, a lower number of inflammatory infiltrates and a greater amount of vascular endothelial growth factor and newformed blood vessels. Whereas, the cathodic polarity has presented smaller amount of tissue gap.
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http://dx.doi.org/10.1016/j.jtv.2019.05.001DOI Listing
August 2019

Myenteric Denervation of the Gut with Benzalkonium Chloride: A Review of Forty Years of an Experimental Model.

Can J Gastroenterol Hepatol 2019 3;2019:3562492. Epub 2019 Feb 3.

Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Av. Bandeirantes 3900, 14, Ribeirão Preto 049-900, Brazil.

Experimental denervation of organs plays a key role in understanding the functional aspects of the normal innervation as well as the diseases related to them. In 1978 the experimental model of myenteric denervation of the rat gut by serosal application of benzalkonium chloride (BAC) was proposed. BAC is a positively charged surface-active alkylamine and is a powerful cationic detergent, which destroys bacteria after ionic attraction and for this reason is largely used as a surgical antiseptic. Since its initial report, the BAC-induced myenteric denervation model has been used to study many functional and pathological aspects of the enteric nervous system. So far this is the only pure method of myenteric denervation available for research in this area. Promising reports in the literature have shed light on the possibilities for the development of new uses of the BAC-denervation experimental model as a therapeutic tool in some pathological situations. This review aims to shed light on the main historical and recent findings provided by this experimental model.
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http://dx.doi.org/10.1155/2019/3562492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378025PMC
June 2019

Increased Expression Levels of Metalloprotease, Tissue Inhibitor of Metalloprotease, Metallothionein, and p63 in Ectopic Endometrium: An Animal Experimental Study.

Rev Bras Ginecol Obstet 2018 Nov 28;40(11):705-712. Epub 2018 Nov 28.

Faculty of Medicine, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Objective:  To characterize the patterns of cell differentiation, proliferation, and tissue invasion in eutopic and ectopic endometrium of rabbits with induced endometriotic lesions via a well- known experimental model, 4 and 8 weeks after the endometrial implantation procedure.

Methods:  Twenty-nine female New Zealand rabbits underwent laparotomy for endometriosis induction through the resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of animals (one with 14 animals, and the other with15) were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised along with the opposite uterine horn for endometrial gland and stroma determination. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissues for analysis of the following markers: metalloprotease (MMP-9) and tissue inhibitor of metalloprotease (TIMP-2), which are involved in the invasive capacity of the endometrial tissue; and metallothionein (MT) and p63, which are involved in cell differentiation and proliferation.

Results:  The intensity of the immunostaining for MMP9, TIMP-2, MT, and p63 was higher in ectopic endometria than in eutopic endometria. However, when the ectopic lesions were compared at 4 and 8 weeks, no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue.

Conclusion:  Ectopic endometrial lesions seem to express greater power for cell differentiation and tissue invasion, compared with eutopic endometria, demonstrating a potentially invasive, progressive, and heterogeneous presentation of endometriosis.
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http://dx.doi.org/10.1055/s-0038-1675612DOI Listing
November 2018

Coffee, but Neither Decaffeinated Coffee nor Caffeine, Elicits Chemoprotection Against a Direct Carcinogen in the Colon of Wistar Rats.

Nutr Cancer 2019 26;71(4):615-623. Epub 2018 Oct 26.

a Department of Pathology , University of Sao Paulo , Ribeirao Preto , Brazil.

Colorectal cancer (CRC) is the third most frequent malignancy worldwide. Coffee is the second most consumed drink in the globe and suggested to decrease the CRC risk. Here, we explored whether coffee, decaffeinated coffee, or caffeine impact on the development of colorectal carcinogenesis induced by the direct carcinogen N-methyl-N-nitro-N-nitrosoguanidine (MNNG) in rats. To this end, sixty-four young male Wistar rats were divided into eight groups of eight animals each. We analyzed the frequency of dysplastic crypts and expression of metallothionein as a biomarker of the cancer risk, as well the expression of phosphorylated H2A histone family/member X (γH2AX) for DNA damage and cyclooxygenase-2 (COX-2) for inflammatory response. We also studied the oxidative stress profile in hepatic and colonic frozen samples (malondialdehyde [MDA], glutathione [GSH], and α-tocopherol). We found that coffee but neither decaffeinated coffee nor caffeine decreased the development of dysplastic crypts in MNNG-exposed rats. All treatments reduced DNA damage intensity in colonocytes. Only decaffeinated coffee increased the numbers of metallothionein positive crypts in comparison with coffee-treated rats. Coffee and caffeine inhibited COX-2 expression in the colon. Both decaffeinated coffee and caffeine decreased hepatic α-tocopherol levels. We suggest that coffee may have other compounds that elicit greater chemoprotective effects than caffeine reducing the CRC risk.
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http://dx.doi.org/10.1080/01635581.2018.1506489DOI Listing
May 2020

Increased exposure to pesticides and colon cancer: Early evidence in Brazil.

Chemosphere 2018 Oct 20;209:623-631. Epub 2018 Jun 20.

Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address:

Environmental factors may increase colon cancer (CC) risk. It has been suggested that pesticides could play a significant role in the etiology of this malignancy. As agriculture is one of the mainstays of the Brazilian economy, this country has become the largest pesticides consumer worldwide. The CC burden is also increasing in Brazil. Herein, we examined data from the Brazilian Federal Government to determine whether CC mortality and pesticide consumption may be associated. Database of the Ministry of Health provided CC mortality data in Brazil, while pesticide usage was accessed at the website of Brazilian Institute of Environment and Renewable Natural Resources. The CC mortality in the Brazilian states was calculated as standard mortality rates (SMR). All Bayesian analysis was performed using a Markov chain Monte Carlo method in WinBUGS software. We observed that CC mortality has exhibited a steady increase for more than a decade, which correlated with the amount of sold pesticides in the country. Both observations are concentrated in the Southern and the Southeast regions of Brazil. Although ecological studies like ours have methodological limitations, the current dataset suggests the possibility that pesticide exposure may be a risk factor for CC. It warrants further investigation.
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http://dx.doi.org/10.1016/j.chemosphere.2018.06.118DOI Listing
October 2018

Chemopreventive effects of a Tamarindus indica fruit extract against colon carcinogenesis depends on the dietary cholesterol levels in hamsters.

Food Chem Toxicol 2017 Sep 4;107(Pt A):261-269. Epub 2017 Jul 4.

Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil.

Tamarind has significant antioxidant potential. We showed that tamarind protects hypercholesterolemic hamsters from atherosclerosis. Hypercholesterolemia might increase the risk of colon cancer. We investigated whether tamarind extract modulates the risk of colon cancer in hypercholesterolemic hamsters. Hamsters (n = 64) were given tamarind and a hypercholesterolemic diet for 8 weeks. The groups were the control, tamarind treatment, hypercholesterolemic, and hypercholesterolemic treated with tamarind groups. Half of each group was exposed to the carcinogen dimethylhydrazine (DMH) at the 8th week. All hamsters were euthanatized at the 10th week. In carcinogen-exposed hypercholesterolemic hamsters, tamarind did not alter the cholesterol or triglyceride serum levels, but it reduced biomarkers of liver damage (alanine transaminase [ALT], and aspartate aminotransferase [AST]). Tamarind decreased DNA damage in hepatocytes, as demonstrated by analysis with an anti-γH2A.X antibody. In liver and serum samples, we found that this fruit extract reduced lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) and increased endogenous antioxidant mechanisms (glutathione peroxidase [GPx] and superoxide dismutase [SOD]). However, tamarind did not alter either lipid peroxidation or antioxidant defenses in the colon, which contrasts with DMH exposure. Moreover, tamarind significantly increased the stool content of cholesterol. Although tamarind reduced the risk of colon cancer in hypercholesterolemic hamsters that were carcinogenically exposed to DMH by 63.8% (Metallothionein), it was still ∼51% higher than for animals fed a regular diet. Staining colon samples with an anti-γH2A.X antibody confirmed these findings. We suggest that tamarind has chemoprotective activity against the development of colon carcinogenesis, although a hypercholesterolemic diet might impair this protection.
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http://dx.doi.org/10.1016/j.fct.2017.07.005DOI Listing
September 2017

Jacalin Has Chemopreventive Effects on Colon Cancer Development.

Biomed Res Int 2017 6;2017:4614357. Epub 2017 Jun 6.

Postgraduate Program in Basic and Applied Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.

Colorectal cancer, which is one of the most common causes of cancer-related deaths worldwide, has a slow natural history that provides a great opportunity for prevention strategies. Plant-derived natural products have received considerable attention because of their inherent colorectal cancer chemopreventive effects. The plant lectin jacalin specifically recognizes the tumor-associated Thomsen-Friedenreich antigen and has antiproliferative effects on human colon cancer cells, highlighting its potential antitumor activity. To evaluate jacalin's potential application in colorectal cancer chemoprevention, we studied its effects on the early stages of carcinogenesis. Balb/c mice were given 4 intrarectal deposits of 0.1 ml solution of Methyl-N'-Nitro-N-Nitroso-Guanidine (5 mg/ml) twice a week (with a 3-day interval) for 2 weeks. Starting 2 weeks before carcinogen administration, animals were treated orally with jacalin (0.5 and 25 g) three times a week (on alternate weekdays) for 10 weeks. We show that jacalin treatment reduced the number of preneoplastic lesions in carcinogen-exposed mice. This anticarcinogenic activity was associated with decreased colonic epithelial cell proliferation and stromal COX-2 expression and with increased intestinal production of TNF-. Our results demonstrate that jacalin is able to modulate the early stages of colon carcinogenesis and emphasize its promising chemopreventive activity in colorectal cancer.
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http://dx.doi.org/10.1155/2017/4614357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476885PMC
March 2018

High-Fat and Fat-Enriched Diets Impair the Benefits of Moderate Physical Training in the Aorta and the Heart in Rats.

Front Nutr 2017 18;4:21. Epub 2017 May 18.

Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.

Aim: Millions of people die each year due to cardiovascular disease (CVD). A Western lifestyle not only fuses a significant intake of fat with physical inactivity and obesity but also promotes CVD. Recent evidence suggests that dietary fat intake impairs the benefits of physical training. We investigated whether aerobic training could reverse the adverse effects of a high-fat diet (HFD) on the aorta. Then, we explored whether this type of exercise could reverse the damage to the heart that is imposed by fat-enriched diet (FED).

Methods: Rats were randomly assigned to two experiments, which lasted 8 weeks each. First, rats swam for 60 min and were fed either a regular diet [standard diet (STD)] or an HFD. After aortic samples had been collected, the rats underwent a histopathological analysis for different biomarkers. Another experiment subjected rats that were fed either an STD or an FED to swimming for 20 or 90 min.

Results: The first experiment revealed that rats that were subjected to an HFD-endured increased oxidative damage in the aorta that exercises could not counteract. Together with increased cyclooxygenase 2 expression, an HFD in combination with physical training increased the number of macrophages. A reduction in collagen fibers with an increased number of positive α-actin cells and expression of matrix metalloproteinase-2 occurred concomitantly. Upon analyzing the second experiment, we found that physically training rats that were given an FED for 90 min/day decreased the cardiac adipose tissue density, although it did not protect the heart from fat-induced oxidative damage. Even though the physical training lowered cholesterol levels that were promoted by the FED, the levels were still higher than those in the animals that were given an STD. Feeding rats an FED impaired the swimming protocol's effects on lowering triglyceride concentration. Additionally, exercise was unable to reverse the fat-induced deregulation in hepatic antioxidant and lipid peroxidation activities.

Conclusion: Our findings reveal that an increased intake of fat undermines the potential benefits of physical exercise on the heart and the aorta.
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http://dx.doi.org/10.3389/fnut.2017.00021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435813PMC
May 2017

Photobiomodulation laser and pulsed electrical field increase the viability of the musculocutaneous flap in diabetic rats.

Lasers Med Sci 2017 Apr 2;32(3):641-648. Epub 2017 Feb 2.

Post-Graduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School-FMRP/USP, Ribeirão Preto, Brazil.

The purpose of this study is to investigate the effect of pulsed electrical field (PEF) and photobiomodulation laser (PBM) on the viability of the TRAM flap in diabetic rats. Fifty Wistar rats were divided into five homogeneous groups: Group 1-control; Group 2-diabetics; Group 3-diabetics + PEF; Group 4-diabetic + laser 660 nm, 10 J/cm, 0.27 J; Group 5-diabetic + laser 660 nm, 140 J/cm, 3.9 J. The percentage of necrotic area was evaluated using software Image J®. The peripheral circulation of the flap was evaluated by infrared thermography FLIR T450sc (FLIR® Systems-Oregon USA). The thickness of the epidermis (haematoxylin-eosin), mast cell (toluidine blue), leukocytes, vascular endothelial growth factor, fibroblast and newly formed blood vessels were evaluated. For the statistical analysis, the Kruskal-Wallis test was applied followed by Dunn and ANOVA test followed by Tukey with critical level of 5% (p < 0.05). The PEF reduced the area of necrosis, decreased the leukocytes, increased the mast cells, increased the thickness of epidermis and increased newly formed blood vessels when it was compared to the untreated diabetic group of animals. Laser 660 nm, fluence 140 J/cm (3.9 J) showed better results than the 10 J/cm (0.27 J) related to reduction of the area of necrosis and the number of leukocytes, increased mast cells, increased thickness of the epidermis, increased vascular endothelial growth factor, increased fibroblast growth factor and increase of newly formed blood vessels in diabetic animals. The laser and pulsed electrical field increase the viability of the musculocutaneous flap in diabetic rats.
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http://dx.doi.org/10.1007/s10103-017-2160-7DOI Listing
April 2017

Digital de-waxing on FTIR images.

Analyst 2017 Apr;142(8):1358-1370

Universidade de São Paulo, Avenida dos Bandeirantes, 3900, Ribeirão Preto, SP, Brazil.

This paper presents a procedure that digitally neutralizes the contribution of paraffin to FTIR hyperspectral images. A brief mathematical derivation of the procedure is demonstrated and applied on one normal human colon sample to exemplify the de-waxing procedure. The proposed method includes construction of a paraffin model based on PCA, EMSC normalization and application of two techniques for spectral quality control. We discuss every step in which the researcher needs to take a subjective decision during the de-waxing procedure, and we explain how to make an adequate choice of parameters involved. Application of this procedure to 71 hyperspectral images collected from 55 human colon biopsies (20 normal, 17 ulcerative colitis, and 18 adenocarcinoma) showed that paraffin was appropriately neutralized, which made the de-waxed images adequate for analysis by pattern-recognition techniques such as k-means clustering or PCA-LDA.
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http://dx.doi.org/10.1039/c6an01975gDOI Listing
April 2017

Laser photobiomodulation (830 and 660 nm) in mast cells, VEGF, FGF, and CD34 of the musculocutaneous flap in rats submitted to nicotine.

Lasers Med Sci 2017 Feb 2;32(2):335-341. Epub 2016 Dec 2.

Post-Graduate Program in Rehabilitation and Functional Performance of Ribeirão Preto Medical School of the University of São Paulo (FMRP/USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil.

The aim of this study was to investigate the effect of laser photobiomodulation (PBM) on the viability of the transverse rectus abdominis musculocutaneous (TRAM) flap in rats subjected to the action of nicotine. We evaluated 60 albino Wistar rats, divided into six groups of ten animals. Group 1 (saline) underwent the surgical technique to obtain a TRAM flap; group 2 (laser 830 nm) underwent the surgical technique and was irradiated with a laser 830 nm; group 3 (laser 660 nm) underwent the surgical technique and was irradiated with a laser 660 nm; group 4 was treated with nicotine subcutaneously (2 mg/kg/2×/day/4 weeks) and underwent surgery; group 5 (nicotine + laser 830 nm) was exposed to nicotine, underwent the surgical technique, and was irradiated with a laser 830 nm; group 6 (nicotine + laser 660 nm) was exposed to nicotine, underwent the surgical technique, and was irradiated with a laser 660 nm. The application of PBM occurred immediately after surgery and on the two following days. The percentage of necrosis was assessed using the AxioVision® software. The number of mast cells (toluidine blue staining) was evaluated, and immunohistochemistry was performed to detect vascular endothelial growth factor expression (anti-VEGF-A), fibroblasts (anti-basic FGF), and neoformed vessels (anti-CD34). PBM with a wavelength of 830 nm increased the viability of the TRAM flap, with a smaller area of necrosis, increased number of mast cells, and higher expression of VEGF and CD34. PBM increases the viability of musculocutaneous flaps treated with to nicotine.
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http://dx.doi.org/10.1007/s10103-016-2118-1DOI Listing
February 2017

A critical discussion on diet, genomic mutations and repair mechanisms in colon carcinogenesis.

Toxicol Lett 2017 Jan 28;265:106-116. Epub 2016 Nov 28.

Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address:

Colon cancer is one of the most common malignancies and its etiology closely tied to dietary habits. Recent epidemiological data shows that colon cancer incidence is shifting to a much younger population. In this regard, some dietary components from a regular human meal might have various DNA-damaging compounds. Given that not every person endure cancer, the colonic malignancy develops throughout decades, and persistent DNA damage promotes cancer when induced at the proper intensity, a critical discussion of possible novel mechanisms by which carcinogens promote these tumors is urgently needed. Robust genomic sequencing analyses showed that low and late cell cycle expressed genes are prone to undergo mutation. Moreover, detection and repair mechanisms have a particular threshold to be activated throughout the G2/M phase, and reactivation of these devices during the M phase promotes genomic instability. Conditions of combined exposure to non-genotoxic concentrations of various carcinogens seem to act effectively through these weaknesses in genomic repair mechanisms. Therefore, we suggest that the natural tolerance of body defence mechanisms eventually become overwhelmed by the chronic exposure to different combinations and intensities of dietary mutagens leading to the high incidence of colon cancer in modern society.
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http://dx.doi.org/10.1016/j.toxlet.2016.11.020DOI Listing
January 2017

KRAS mutation associated with CD44/CD166 immunoexpression as predictors of worse outcome in metastatic colon cancer.

Cancer Biomark 2016 Mar;16(4):513-21

Internal Medicine Department, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.

Introduction: Multiple stages of carcinogenesis in colon cancer encompass subpopulations of cancer stem cells (CSC), responsible for tumor cell transformation, growth and proliferation. CD44 and CD166 proteins are CSC markers associated with cell signaling, adhesion, migration, metastasis and lymphocytic response. The expression of CSC may be modulated by some factors, such as the KRAS gene mutation.

Objective: Correlate the expression of CD44 and CD166 markers in metastatic colon adenocarcinoma and KRAS mutation status (wild-type/mutated) with clinical pathological features and patients' outcome.

Material And Methods: Fifty-eight samples of tumor tissue samples of metastatic colon adenocarcinoma were collected from patients treated with CapeOx at the HCFMRP-USP Clinical Oncology Service. Clinical and survival data were collected from medical records. KRAS status was determined by the polymerase chain reaction (PCR) technique, and analysis of immunohistochemical expression of CD44 and CD166 proteins was performed by tissue microarray.

Results: The expression of CD44 and CD166 were positive in 41% and 43% of patients, respectively, and mutated KRAS was detected in 48% of patients. A significant association was found between CD166 and CD44 expression (p= 0.016), mainly in the wild-type KRAS group (p= 0.042) and patients over 65 years (p= 0.001). CD44-positive patients had 3.7-fold and 5.3-fold greater risk of liver metastasis and lung metastasis, respectively (p< 0.01), compared with CD44-negative patients. CD166-negative patients had 2.7 greater risk of lymph node involvement (0.03), compared with CD166-positive patients. KRAS mutation increased the risk of liver metastasis by 8 times (p< 0.01), and the risk of lung metastasis by 5 times (p= 0.04) in CD44-positive patients. KRAS mutation increased the risk of lymph node involvement by 8 times in CD166-negative patients (p= 0.0007).

Conclusion: An association between CD44 and CD166 expression was demonstrated in this study. Analysis of KRAS mutation combined with immunohistochemical expression of CD44 and CD166 identified subgroups of patients with colon adenocarcinoma at higher risk of lymph node involvement by the tumor and development of liver and lung metastasis.
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http://dx.doi.org/10.3233/CBM-160592DOI Listing
March 2016

Oncostatic effects of fluoxetine in experimental colon cancer models.

Cell Signal 2015 Sep 22;27(9):1781-8. Epub 2015 May 22.

Department of Toxicology, University of Wuerzburg, Germany.

Colon cancer is one of the most common tumors in the human population. Recent studies have shown a reduced risk for colon cancer in patients given the antidepressant fluoxetine (FLX). The exact mechanism by which FLX might protect from colon cancer remains however controversial. Here, FLX reduced the development of different colon tumor xenografts, as well as proliferation in hypoxic tumor areas within them. FLX treatment also decreased microvessel numbers in tumors. Although FLX did not increase serum and tumor glucose levels as much as the colon chemotherapy gold standard Fluorouracil did, lactate levels were significantly augmented within tumors by FLX treatment. The gene expression of the MCT4 lactate transporter was significantly downregulated. Total protein amounts from the third and fifth mitochondrial complexes were significantly decreased by FLX in tumors. Cell culture experiments revealed that FLX reduced the mitochondrial membrane potential significantly and disabled the reactive oxygen species production of the third mitochondrial complex. Furthermore, FLX arrested hypoxic colon tumor cells in the G0/G1 phase of the cell-cycle. The expression of key cell-cycle-related checkpoint proteins was enhanced in cell culture and in vivo experiments. Therefore, we suggest FLX impairs energy generation, cell cycle progression and proliferation in tumor cells, especially under condition of hypoxia. This then leads to reduced microvessel formation and tumor shrinkage in xenograft models.
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http://dx.doi.org/10.1016/j.cellsig.2015.05.008DOI Listing
September 2015

Effects of taurine supplementation on adipose tissue of obese trained rats.

Adv Exp Med Biol 2015 ;803:707-14

Department of Foods and Nutrition, School of Pharmaceutical Science, State University of São Paulo "Júlio de Mesquita Filho", Araraquara, SP, Brazil.

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http://dx.doi.org/10.1007/978-3-319-15126-7_56DOI Listing
August 2015

Aerobic Training Activates Interleukin 10 for Colon Anticarcinogenic Effects.

Med Sci Sports Exerc 2015 09;47(9):1806-13

1Department of Pathology, University of São Paulo, Ribeirão Preto, BRAZIL; 2Nutrition Division, University of São Paulo, Ribeirão Preto, BRAZIL; 3Department of Maternal-Infant Nursing and Public Health, University of São Paulo, Ribeirão Preto, BRAZIL; and 4Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BRAZIL.

Purpose: Physical exercise has been shown to be protective against colon carcinogenesis. Physical exercise, however, covers a wide range of modalities, from which different effects on the human body have been reported. We sought to clarify whether aerobic and resistance trainings would differently affect the development of early carcinogenic events in the colon.

Methods: Male BALB/c, C57/BL6, and interleukin 10 knockout (IL-10; on C57/BL6 background) mice were exposed to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. BALB/c mice were subjected to either aerobic (swimming) or resistance trainings (climbing a ladder with load attached to the tail). C57/BL6 and IL-10 mice only swam.

Results: In BALB/c carcinogen-exposed mice, aerobic and resistance trainings decreased serum creatine kinase levels (P < 0.001). Although aerobic and resistance trainings reduced the generation of lipid thiobarbituric reactive species (P < 0.01 and P < 0.001), only aerobic exercises enhanced serum glutathione levels aside from carcinogenic exposure (P < 0.05). Carcinogen-exposed and aerobic-trained mice developed 36% less colon preneoplastic lesions than its control group (P < 0.05). Aerobic training reduced colonic subepithelial cyclooxygenase-2 expression in carcinogen-exposed mice (P < 0.001). Interestingly, in this same group, colonic IL-10 expression was upregulated sevenfold (P < 0.001). Current findings were confirmed in C57/BL6 carcinogen-exposed mice, in which aerobic training promoted antipreneoplastic effects (P < 0.05). Knocking IL-10 out of C57/BL6 mice abrogated antipreneoplastic effects of aerobic training on the colon tissue (P > 0.05).

Conclusions: IL-10 is a pivotal element for antipreneoplastic effects of aerobic training on the colon.
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http://dx.doi.org/10.1249/MSS.0000000000000623DOI Listing
September 2015

Vitamin E supplementation in chemical colorectal carcinogenesis: a two-edged knife.

Nutrients 2014 Aug 13;6(8):3214-29. Epub 2014 Aug 13.

Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto14049-900, Brazil.

This work investigated the effects of Vitamin E (VE) on aberrant crypt foci (ACF) incidence, oxidative stress parameters (serum and hepatic VE concentration, and homocysteine, glutathione (GSH), and malondialdehyde (MDA) levels), and expression of both cyclooxygenase-2 (COX2) and proliferating cellular nuclear antigen (PCNA) in experimental colorectal carcinogenesis. Male Wistar rats received subcutaneous injections of 1,2-dimethylhydrazine (DMH) twice a week, for two weeks (40 mg/kg), except for the Control group. Animals were separated into groups that received different amounts of VE in the diet: 0 IU (0×), 75 IU (recommended daily intake, RDI), 225 IU (3× RDI), or 1500 IU (20× RDI), during (dDMH) or after (aDMH) administration of carcinogen. The 0×dDMH and 3×dDMH groups showed decreased serum VE levels. Hepatic VE concentration was higher in 3×aDMH as compared with the other groups. All the groups, except the Control and the 0×aDMH groups, had reduced GSH levels. The 0×dDMH, 0×aDMH, and 20×aDMH groups exhibited increased MDA levels. The aDMH groups had higher ACF incidence and PCNA expression. The 0×aDMH group presented higher ACF rate, followed by 20×aDMH. Moreover, the 3×aDMH group displayed reduced ACF incidence and COX2 expression. Multivariate analysis revealed that GSH modulated homocysteine levels and COX2. These results suggested that 1500 IU of VE is hazardous, whereas 225 IU of VE has beneficial effects on chemical colorectal carcinogenesis.
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http://dx.doi.org/10.3390/nu6083214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145304PMC
August 2014

Endplates changes related to age and vertebral segment.

Biomed Res Int 2014 12;2014:545017. Epub 2014 Jun 12.

Department of Biomechanics, Medicine, and Rehabilitation of the Locomotor Apparatus, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Bandeirantes Avenue 3900, 14049-900 Ribeirão Preto, SP, Brazil.

Endplate separations are defined as the presence of a space between the hyaline cartilage and the cortical bone of the adjacent vertebral body. This study evaluates endplate separations from the vertebral body and intervertebral discs and verifies if endplate separation is related to age and the spinal level. Groups were formed based on age (20-40 and 41-85 years old) and the vertebral segment (T7-T8 and L4-L5 segments). Histological analysis included assessment of the length of the vertebral endplates, the number and dimensions of the separations, and orientation of the collagen fibers, in the mid-sagittal slice. Two indexes were created: the separation index (number of separations/vertebral length) and separation extension index (sum of all separations/vertebral length). The results of the study demonstrated a direct relationship between the density of separations in the endplate and two variables: age and spinal level.
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http://dx.doi.org/10.1155/2014/545017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075072PMC
March 2015

The contribution of neuronal-glial-endothelial-epithelial interactions to colon carcinogenesis.

Cell Mol Life Sci 2014 Sep 22;71(17):3191-7. Epub 2014 May 22.

Department of Pathology, Medical School of Ribeirão Preto, University of Sao Paulo, Av. Bandeirantes 3900, 14, Ribeirão Preto, 049-900, Brazil.

Several different cell types constitute the intestinal wall and interact in different manners to maintain tissue homeostasis. Elegant reports have explored these physiological cellular interactions revealing that glial cells and neurons not only modulate peristalsis and mechanical stimulus in the intestines but also control epithelial proliferation and sub-epithelial angiogenesis. Although colon carcinoma arises from epithelial cells, different sub-epithelial cell phenotypes are known to support the manifestation and development of tumors from their early steps on. Therefore, new perspectives in cancer research have been proposed, in which neurons and glial cells not only lead to higher cancer cell proliferation at the tumor invasion front but also further enhance angiogenesis and neurogenesis in tumors. Transformation of physiological neural activity into a pro-cancer event is thus discussed for colon carcinogenesis herein.
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http://dx.doi.org/10.1007/s00018-014-1642-zDOI Listing
September 2014

Antidepressant fluoxetine and its potential against colon tumors.

World J Gastrointest Oncol 2014 Jan;6(1):11-21

Helga Stopper, Vinicius Kannen, Department of Toxicology, University of Wuerzburg, D-97078 Wurzburg, Germany.

Colon cancer is one of the most common tumors worldwide, with increasing incidence in developing countries. Patients treated with fluoxetine (FLX) have a reduced incidence of colon cancer, although there still remains great controversy about the nature of its effects. Here we explore the latest achievements related to FLX treatment and colon cancer. Moreover, we discuss new ideas about the mechanisms of the effects of FLX treatment in colon cancer. This leads to the hypothesis of FLX arresting colon tumor cells at the at G1 cell-cycle phase through a control of the tumor-related energy generation machinery. We believe that the potential of FLX to act against tumor metabolism warrants further investigation.
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http://dx.doi.org/10.4251/wjgo.v6.i1.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936192PMC
January 2014

Biomechanical adaptations of mice cortical bone submitted to three different exercise modalities.

Acta Ortop Bras 2013 ;21(6):328-32

Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, Faculdade de Medicina de Ribeirão Preto, USP.

Objective: To compare the adaptive effects of three non-weight bearing exercise on bone mechanical properties.

Methods: 24 male Balb/c mice (22-25g), were randomly divided into four groups (n=6): sedentary group (S); swimming group (N) which performed sessions five times per week for 60 min progressively; resistance group (R), which performed climbing exercise with progressive load, three times per week; and combined group (C), which performed the same protocols aforementioned being three times a week according to N protocol and two times a week the R protocol during eight weeks. Biomechanical tests, load until failure and stiffness evaluation of shinbone was performed after animals have been sacrificed.

Results: Stiffness values were statistically higher only in the isolated modalities groups (N and R, 41.68 ± 10.43 and 41.21 ± 11.38 N/mm, respectively) compared with the S group (28.48 ± 7.34 N/mm). However, taking into consideration the final body mass, relative values, there was no difference in the biomechanical tests among the groups.

Conclusion: Data from the present investigation demonstrated a favorable influence of muscle contraction in lower impact isolated exercise modalities on absolute stiffness values, i.e.groups N and R, whereas the combined group (C) did not present any statistical significant difference compared to sedentary group. Level of Evidence II, Prospective Comparative Study .
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http://dx.doi.org/10.1590/S1413-78522013000600006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874991PMC
January 2014

Topical Brazilian propolis improves corneal wound healing and inflammation in rats following alkali burns.

BMC Complement Altern Med 2013 Nov 27;13:337. Epub 2013 Nov 27.

Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirão Preto - University of São Paulo, Av, Bandeirantes, 3900 - 12°, Andar, Ribeirão Preto, São Paulo, Brazil.

Background: The objective of this study was to investigate the effects of the Brazilian Scaptotrigona sp propolis, a widely used folk medicine, in corneal wound healing and inflammation.

Methods: Corneal epithelial defects of 1 mm in diameter were made in the right eyes of Wistar male adult rats by cauterization with silver nitrate sticks. Subsequently, they were divided in two groups (n = 40 rats/group): Brazilian propolis (BP) group was topically treated with a microemulsion containing 1% Brazilian propolis; vehicle (VH) group received the same formulation without propolis. The epithelial defect area was photographed and measured at t = 0 (wound induction), and after 12, 24, 48 and 120 h of treatment. The inflammatory response was evaluated based on counting of neutrophils. Epithelial regeneration rates were determined based on Ki-67 expression in basal epithelial cells. Comparisons were made using the Kruskal-Wallis and the Mann-Whitney U test.

Results: The BP group presented both smaller epithelial defect areas at 12, 24 and 48 h and fewer corneal infiltrating neutrophils at 24 and 48 h (P < 0.01) than the VH group. These effects were associated with more pervasive Ki-67 staining in the BP group at 12 and 24 h (P < 0.05).

Conclusions: Topically applied BP accelerated wound healing and reduced the inflammatory response to silver nitrate-induced corneal alkali burns in rats.
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http://dx.doi.org/10.1186/1472-6882-13-337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224050PMC
November 2013

Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma.

World J Oncol 2013 Oct 27;4(4-5):179-187. Epub 2013 Sep 27.

Clinical Oncology, FMRP-USP (SP), Clinical Oncology Service, FMRP-USP (SP), Brazil.

Background: KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes.

Methods: Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status.

Results: KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients.

Conclusion: The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.
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http://dx.doi.org/10.4021/wjon719wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5649925PMC
October 2013

Glucagon-like peptide 2 in colon carcinogenesis: possible target for anti-cancer therapy?

Pharmacol Ther 2013 Jul 11;139(1):87-94. Epub 2013 Apr 11.

Department of Toxicology, University of Wuerzburg, Germany.

The role of glucagon-like peptide 2 (GLP2) in colon tissue has been studied extensively, from the time it was discovered that GLP2 promotes intestinal growth. A large number of studies have shown potential applications for GLP2 in human therapy. However, recent data have suggested the notion that GLP2 plays a key role in colon carcinogenesis. Questions have been arisen regarding the pro-proliferative effects of GLP2 and whether they might promote intestinal healing or advance colon tumor growth. Here, we provide striking evidence to show that the physiological activities of GLP2 are closely related to cancer-related molecular pathways that have been shown to circumvent drug desensitization. We further explore the different pathways of GLP2-signaling to suggest suitable GLP2-based therapeutic strategies in colon cancer.
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http://dx.doi.org/10.1016/j.pharmthera.2013.04.007DOI Listing
July 2013

Clinical and immunohistopathological aspects of venous ulcers treatment by Low-Intensity Pulsed Ultrasound (LIPUS).

Ultrasonics 2013 Apr 23;53(4):870-9. Epub 2012 Dec 23.

Bioengineering Post-Graduate Program (EESC-IQSC-FMRP-USP), Trabalhador São-carlense Avenue, 400 Arnold Schimidt, São Carlos, São Paulo 13566-590, Brazil.

The immunological mechanisms that are triggered by Low-Intensity Pulsed Ultrasound (LIPUS) in wound healing are unknown. In the present study, experimental groups were used to assess the treatment of chronic venous ulcers with 30mW/cm(2) SATA peripheral LIPUS three times per week compared to a daily treatment of 1% silver sulfadiazine (SDZ). The ulcers of the SDZ group (n=7) (G1) and LIPUS group (n=9) (G2) were photographed five times three months, and the images were analyzed using ImageJ software to quantify the total area (S), fibrin/sphacel area (yellow) and granulation area (red). The healing process was evaluated by the wound healing rate (WHR), granulation tissue rate (GTR) and fibrin/sphacel tissue rate (FTR). The ulcers were biopsied on days 1 and 45 and stained for collagen fiber quantification (picrosirius) and CD68(+) protein and VEGF (vascular endothelial growth factor) expression using HRP-streptavidin (horseradish peroxidase-streptavidin). On day 90, G2 had a mean 41% decrease in the ulcer area, while no decrease was observed in G1 (p<0.05). An increased tendency toward positive labeling of collagen fibers and VEGF (p>0.05) was observed in G2 compared to G1, and the number of CD68(+) cells was greater in G2 than in G1 (p<0.05). LIPUS presents superior activity compared to SDZ in stimulating the inflammatory and proliferative (angiogenesis and collagenesis, respectively) phases of chronic venous wound healing.
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http://dx.doi.org/10.1016/j.ultras.2012.12.009DOI Listing
April 2013

Expression of VEGF and collagen using a latex biomembrane as bladder replacement in rabbits.

Int Braz J Urol 2012 Jul-Aug;38(4):536-43

Department of Surgery, Division of Urology, Ribeirão Preto Medical School - University of Sao Paulo Ribeirão Preto, SP and Department of Experimental Surgery, Anhanguera-Uniderp University, Campo Grande, MS, Brazil.

Objective: To investigate the VEGF expression and collagen deposition using a latex biomembrane as bladder replacement in rabbits.

Materials And Methods: After partial cystectomy, a patch of a non-vulcanized latex biomembrane (2 x 2 cm) was sewn to the bladder of rabbits with 5/0 monofilament polydioxanone sulfate sutures in a watertight manner. Groups of 5 animals were killed at 15, 45 and 90 days after surgery and the bladder was removed. Sections of 5µm were cut and stained with picrosirius-red in order to estimate the amount of extracellular matrix in the graft. To confirm the presence of VEGF in tissues, protein expression was determined by immunohistochemistry.

Results: No death, urinary leakage or graft extrusion occurred in any group. All bladders showed a spherical shape. A progressive reduction in the amount of collagen occurred in the graft area and was negatively and linearly correlated with time (p < 0.001). VEGF expression was higher in grafted areas when compared to controls at 15 and 45 days after surgery and decreased with time (p < 0.001).

Conclusion: The latex biomembrane as a matrix for partial bladder replacement in rabbits promotes temporary collagen deposition and stimulates the angiogenic process.
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http://dx.doi.org/10.1590/s1677-55382012000400014DOI Listing
May 2013

Effects of 830 and 670 nm laser on viability of random skin flap in rats.

Photomed Laser Surg 2012 Aug 25;30(8):418-24. Epub 2012 Jun 25.

Department of Physiotherapy, Federal University of Goias, Campus Jataí, Goias, Brazil.

Objective: This study aimed to investigate the effect of 830 and 670 nm diode laser on the viability of random skin flaps in rats.

Background Data: Low-level laser therapy (LLLT) has been reported to be successful in stimulating the formation of new blood vessels and reducing the inflammatory process after injury. However, the efficiency of such treatment remains uncertain, and there is also some controversy regarding the efficacy of different wavelengths currently on the market.

Materials And Methods: Thirty Wistar rats were used and divided into three groups, with 10 rats in each. A random skin flap was raised on the dorsum of each animal. Group 1 was the control group, group 2 received 830 nm laser radiations, and group 3 was submitted to 670 nm laser radiation (power density=0.5 mW/cm(2)). The animals underwent laser therapy with 36 J/cm(2) energy density (total energy=2.52 J and 72 sec per session) immediately after surgery and on the 4 subsequent days. The application site of laser radiation was one point at 2.5 cm from the flap's cranial base. The percentage of skin flap necrosis area was calculated on the 7th postoperative day using the paper template method. A skin sample was collected immediately after to determine the vascular endothelial growth factor (VEGF) expression and the epidermal cell proliferation index (KiD67).

Results: Statistically significant differences were found among the percentages of necrosis, with higher values observed in group 1 compared with groups 2 and 3. No statistically significant differences were found among these groups using the paper template method. Group 3 presented the highest mean number of blood vessels expressing VEGF and of cells in the proliferative phase when compared with groups 1 and 2.

Conclusions: LLLT was effective in increasing random skin flap viability in rats. The 670 nm laser presented more satisfactory results than the 830 nm laser.
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http://dx.doi.org/10.1089/pho.2011.3042DOI Listing
August 2012