S P Andrade

Federal University of Minas Gerais, Cidade de Minas, Minas Gerais, Brazil

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Publications (77)179.79 Total impact

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    ABSTRACT: Subcutaneous implantation of synthetic materials and biomedical devices often induces abnormal tissue healing - the foreign body reaction - which impairs their function. Here we investigated the role of the chemokine receptor CCR2 in this reaction to subcutaneous implants in mice. We measured angiogenesis, inflammation and fibrogenesis induced by implantation, for 1, 4, 7 and 14days, of polyether-polyurethane sponges in mice with genetic deletion of CCR2 (KO) and WT mice. Blood flow was determined by dye diffusion and laser Doppler perfusion techniques. Cytokines (VEGF, TNF-α, CCL2, TGF-β1) were measured by ELISA. Histochemical methods were used to assess collagen deposition and macrophage-derived giant cells in the implants. Skin and implant blood flow were lower in CCR2 KO than in WT mice, as were other aspects of neo-vascularization of the implants. Neutrophil accumulation was increased in KO implants but macrophage accumulation was decreased. Implant content of CCL2 was higher in KO implants, but TGF-β1, collagen deposition and the number of foreign body giant cells were lower than in WT implants. Deletion of CCR2 decreased blood flow in normal skin and inhibited neo-vascularization, chronic inflammation and fibrogenesis in subcutaneous implants. The chemokine receptor CCR2 plays an important role in both normal skin and in the reaction elicited by subcutaneous implantation of a foreign body.
    Microvascular Research 07/2014; · 2.93 Impact Factor
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    ABSTRACT: Natriuretic peptide receptor-C (NPR-C) activation by C-ANP4-23, a specific agonist for this receptor, has been shown to inhibit key events of the angiogenic cascade (migration, proliferation, and vascular endothelial growth factor—VEGF—production). We investigated whether C-ANP4-23 could also inhibit angiogenesis in the sponge model in vivo. In this study, we evaluated the effects of this peptide on inflammatory and angiogenic components of the fibrovascular tissue induced by polyether polyurethane sponge implants in mice. The hemoglobin content (μg/mg wet tissue) and blood flow measurements (laser Doppler perfusion imaging) of the implants, used as an index of vascularization, showed that single or multiple doses of C-ANP4-23 reduced angiogenesis in the implants relative to the PBS-treated group. The peptide exerted an inhibitory effect on nitric oxide production (nitrite levels) and a dual effect on VEGF levels, depending on the number of doses. Histological analysis corroborated the biochemical and functional parameters indicative of neovascularization inhibition (decreased vessel number). The peptide failed to modulate inflammation in our system. The inhibitory effect of C-ANP4-23 on the angiogenic component of the fibrovascular tissue induced by the synthetic matrix extends the range of the peptide's actions and may indicate its therapeutic potential in controlling angiogenesis in fibroproliferative diseases.This article is protected by copyright. All rights reserved.
    Clinical and Experimental Pharmacology and Physiology 05/2014; · 2.41 Impact Factor
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    ABSTRACT: Fibroproliferative processes are regulated by a wide variety of tissue components and genetic factors. However, whether there are genetic differences in peritoneal fibroproliferative tissue formation, with consequent differences in response to drug treatment, is unclear. We characterize the influence of the genetic background on peritoneal fibroproliferative tissue induced by sponge implants in DBA/1, Swiss, C57BL/6, and BALB/c mouse strains. In addition, responses to dipyridamole in the implants were evaluated. Angiogenesis, assessed by intra-implant hemoglobin content, was highest in Swiss mice, whereas levels of vascular endothelial growth factor were highest in C57BL/6 mice. The levels of pro-inflammatory cytokines and of inflammatory enzymes (myeloperoxidase- and N-acetyl-β-D-glucosaminidase) were also strain-related. The pro-fibrogenic markers transforming growth factor beta-1 and collagen were lowest in implants placed in DBA/1 mice, whereas those in C57BL/6 mice had the highest levels. Differential sensitivity to dipyridamole was also observed, with this compound being pro-angiogenic in implants placed in DBA/1 mice but antiangiogenic in implants placed in Swiss. An overall anti-inflammatory response was observed in the inbred strains. Antifibrogenic effects were observed only in implants placed in C57BL/6 mice. These important strain-related differences in the development of peritoneal fibrosis and in response to dipyridamole must be considered in the design and analysis of studies on fibrogenesis in mice.
    Wound Repair and Regeneration 05/2014; 22(3). · 2.76 Impact Factor
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    ABSTRACT: The increased prevalence of diabetes worldwide is associated with increasing numbers of diabetic individuals receiving synthetic matrices and biomedical implants to repair and/or replace biological tissues. This therapeutic procedure invariably leads to adverse tissue healing (foreign body reaction), thus impairing the biomedical device function of subcutaneous implants. However, the influence of diabetes on abnormal tissue healing in intraperitoneal implants is unclear. We investigated key components of foreign body reactions in diabetic rats. Polyether-polyurethane sponge discs were placed intraperitoneally in rats previously injected with streptozotocin for induction of diabetes and in non-diabetic rats. Implants removed 10 days after implantation were assessed by determining of the components of the fibrovascular tissue (angiogenesis, inflammation, and fibrogenesis). In implants from diabetic rats, fibrous capsule thickness and fibrovascular tissue infiltration (hematoxilin & eosin and picrossirius staining) were reduced in comparison with implants from non-diabetic rats. Hemoglobin (Hb) content (vascular index) and VEGF levels (pro-angiogenic cytokine) were increased after diabetes. However, the number of vessels (H&E and CD31-immunostaining) in the fibrovascular tissue from diabetic rats was decreased when compared with vessel numbers in implants from non-diabetic animals. Overall, all inflammatory parameters (macrophage accumulation-NAG activity; TNF-α and MCP-1 levels) increased in intraperitoneal implants after diabetes induction. The pro-fibrogenic cytokine (TGFβ-1) increased after diabetes, but collagen deposition remained unaltered in the implants from diabetic rats. These important diabetes-related changes (increased levels of pro-inflammatory and angiogenic and fibrogenic cytokines) in peritoneal implant healing provide an insight into the mechanisms of the foreign body response in the diabetic environment in rats.
    Microvascular Research 01/2014; · 2.93 Impact Factor
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    ABSTRACT: Envenomation by the Loxosceles spider causes loxoscelism, a pattern of signs and symptoms that primarily manifests in the dermonecrotic form. Our studies have shown that a mouse subcutaneous sponge implantation model may be useful in evaluating the effects of Loxosceles similis venom. This model provides an ideal microenvironment in which to study loxoscelism; however, it is still important to evaluate its pathogenesis and to observe the effects of L. similis venom for longer time periods than those in previous studies of this model. The aims of this study are: (1) to histologically characterize the effects of L. similis crude venom in a subcutaneous sponge implant; (2) to quantify the mast cells present in the implant and to measure their degranulation activity; (3) to quantify collagen subtypes I and III; and (4) to verify, quantify, and evaluate the effects of apoptosis in the implant on the pathogenesis of loxoscelism at 1h, 4h, and 24 h after injecting the venom. Thirty Swiss mice (6-8 weeks old, male) were subcutaneously implanted with polyester-polyurethane sponge discs. Fourteen days post-implantation, the animals were divided into six groups (5 animals per group): three control groups (C1h, C4h, and C24h), in which the mice received 30 μl injections of intra-implant saline, and three treated groups (T1h, T4h, and T24h), in which the mice received 30 μL (0.5 μg) injections of L. similis crude venom at 1h, 4h, and 24 h intervals. After each time interval, the animals were euthanized, and the implants were harvested and processed for light and electron microscopic analyses. The following results were observed in the implants harvested from the treated groups: acute inflammation with marked edema, thrombus, and vasculitis, as well as increased levels of mast cells and mast cell degranulation, and apoptosis in giant cells. Furthermore, degradation of collagen types I and III was observed. An analysis of the ultrastructure revealed apoptosis in various cell types. The present results suggest that apoptosis in some cell types associated with an increase in mast cell degranulation and the degradation of collagen fibers are important in the pathogenesis of loxoscelism therefore may explain the difficulty in repairing the ulcer is commonly observed in severe cases of loxoscelism cutaneous in humans.
    Toxicon 01/2014; · 2.92 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the presence of myeloperoxidase (MPO), N-acetyl-β-D-glucosaminidase (NAG), tumor necrosis factor alpha (TNF-α) and vascular endothelial growth factor (VEGF) in peripheral and menstrual blood in women with (n = 10) and without (n = 7) endometriosis. NAG and MPO activities were evaluated by enzymatic methods, whereas TNF-α and VEGF by immunoassay. No significant differences were found for these markers, neither in menstrual nor in peripheral blood between groups. Menstrual blood NAG (P = 0.039) and MPO (P = 0.0117) activities in the endometriosis group were significantly higher than in peripheral blood. NAG and MPO presented positive linear correlation in peripheral (P = 0.07; r = 0.641) and menstrual blood (P = 0.01; r = 0.603). These findings point to the existence of an increased local inflammatory activity in women with endometriosis.
    Biomedicine & Pharmacotherapy. 01/2014;
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    ABSTRACT: Inflammatory cells surround breast carcinomas and may act promoting tumor development or stimulating anti-tumor immunity. N-acetylglucosaminidase (NAG) has been employed to detect macrophage accumulation/activation. Myeloperoxidase (MPO) is considered a marker for neutrophils activity/accumulation. Vascular Endothelial Growth Factor (VEGF) is as strong pro-angiogenic cytokine. The aim of this study was to measure the systemic inflammatory response by measuring serum levels of NAG, MPO and VEGF in women diagnosed with breast cancer and associate this response to the peritumoral inflammatory infiltrate and to prognostic factors. Serum samples obtained from women with no evidence of disease (n=31) and with breast cancer (n=68) were analyzed for the activities of NAG, MPO and VEGF by enzymatic assay. Serum levels of NAG and VEGF were higher in healthy volunteers (P<0.0001) and serum levels of MPO were higher in patients with breast cancer (P=0.002). Serum levels of NAG were positively correlated to serum levels of MPO and VEGF (P<0.0001 and P=0.0012, respectively) and MPO and VEGF serum levels had also a positive correlation (P=0.0018). The inflammatory infiltrate was not associated to serum levels of the inflammatory markers, and higher levels of MPO were associated to lymphovascular invasion negativity (P=0.0175).
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11/2013; · 2.24 Impact Factor
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    ABSTRACT: Carboplatin, efficient cytostatics for cancer therapy, could induce apoptosis and inhibit the growth of vascular endothelium in several tumor cell lines and xenograft models. It has been suggested that the antitumor effect of chemotherapy could be increased by combining it with an antiangiogenesis agent in anticancer strategy. The present study explored the potential to increase the antitumor effect of carboplatin by combining it with thalidomide in mouse 4T1 breast cancer models, and the underlining mechanism was investigated. The systemic administration of carboplatin and thalidomide significantly decreased tumor growth through increased tumor cell apoptosis compared with either control group. Collectively, these findings suggest that combined treatment has shown synergistic suppression in tumor progression according to the analysis. Furthermore, also was observed reduction in number of lung metastases as compared to isolated treatments and increased survival of the animals. The present study may be important in future exploration of the potential application of the combined approach in the treatment of breast cancer.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 08/2013; · 2.24 Impact Factor
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    ABSTRACT: Introduction: The aim of this study was to investigate the value of placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PLGF ratio, in predicting symptomatic preeclampsia (PE). Methods: A prospective longitudinal study was carried out on 71 high risk preeclamptic women cohort. All of them had normal blood pressure level (≤140/90 mmHg) at the time of enrolment, 26.8 ± 1.5 weeks. Maternal blood was collected and plasma was stored in a freezer at -80 °C. PE was defined according to the National High Blood Pressure Education Program Working Group Criteria. Accuracy of angiogenic factors in predicting PE was evaluated using Receiver-operating characteristics. Results: Maternal plasma concentrations of PLGF and sFlt-1 were able to predict PE (0.90, p < 001; 0.78, p = 0.003, area under the curve, respectively) but the sFlt-1/PLGF ratio presented the best prediction potential over the others (0.95, area under the curve, p < 0.001). Conclusion: All angiogenesis factors were effective biomarkers in predicting PE during the second trimester, before the clinical onset of PE.
    Hypertension in Pregnancy 08/2013; 32(3):312-20. · 0.93 Impact Factor
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    ABSTRACT: OBJECTIVE: Angiogenesis depends on a complex interaction between cellular networks and mediators. The endocannabinoid system and its receptors have been shown to play a role in models of inflammation. Here, we investigated whether blockade of cannabinoid receptors may interfere with inflammatory angiogenesis. MATERIALS AND METHODS: Polyester-polyurethane sponges were implanted in C57Bl/6j mice. Animals received doses (3 and 10 mg/kg/daily, s.c.) of the cannabinoid receptor antagonists SR141716A (CB1) or SR144528 (CB2). Implants were collected at days 7 and 14 for cytokines, hemoglobin, myeloperoxidase, and N-acetylglucosaminidase measurements, as indices of inflammation, angiogenesis, neutrophil and macrophage accumulation, respectively. Histological and morphometric analysis were also performed. RESULTS: Cannabinoid receptors expression in implants was detected from day 4 after implantation. Treatment with CB1 or CB2 receptor antagonists reduced cellular influx into sponges at days 7 and 14 after implantation, although CB1 receptor antagonist were more effective at blocking leukocyte accumulation. There was a reduction in TNF-α, VEGF, CXCL1/KC, CCL2/JE, and CCL3/MIP-1α levels, with increase in CCL5/RANTES. Both treatments reduced neovascularization. Dual blockade of cannabinoid receptors resulted in maximum inhibition of inflammatory angiogenesis. CONCLUSIONS: Blockade of cannabinoid receptors reduced leukocyte accumulation, inflammation and neovascularization, suggesting an important role of endocannabinoids in sponge-induced inflammatory angiogenesis both via CB1 and CB2 receptors.
    Inflammation Research 05/2013; · 1.96 Impact Factor
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    ABSTRACT: Inflammation, angiogenesis and cytokine production are common features of almost, if not all tumors. However, the extent of these processes induced by different types of tumors has not been evaluated. We investigated the growth pattern of the experimental metastatic tumors, B16F10 melanoma, CT26.WT colon and 4T1 mammary cells inoculated in the flank of syngeneic mice and determined the degree of inflammation, angiogenesis, and production level of pro-inflammatory and pro-angiogenic cytokines within the tumors. In addition, we have analyzed vascular changes in the interface between the tumors and the adjacent cutaneous tissue and levels of relevant pro-inflammatory and pro-angiogenic cytokines systemically. The weight of tumors 15 days post-inoculation of 10(6) cells was markedly different. Melanomas were 2 and 10-fold heavier than colon and mammary tumors, respectively. Locally, CT26.WT tumor cells induced more vessels in cutaneous tissue adjacent to the tumors but systemically, the plasma levels of VEGF were higher (approximately 2-fold) in 4T1 tumor-bearing mice compared with the other two tumors. Mammary tumors presented the most prominent inflammatory content as assessed by a range of markers (inflammatory enzymes and cytokines). The vascular index, as determined by the intra-tumor amount of hemoglobin and number of vessels in hot spot areas, was also higher (approximately 2-fold) in melanomas compared with the other two tumors. These findings showing that distinct tumor types determine differential grade of inflammation, angiogenesis and host interaction in mice may provide new insights to tailor differential therapeutic approach based on the status of tumor biomarkers.
    Microvascular Research 12/2012; · 2.93 Impact Factor
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    ABSTRACT: Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been shown to ameliorate a number of vascular diseases. We evaluated the inflammatory and angiogenic components of the fibrovascular tissue induced by subcutaneous implants in mice and their modulation by fluvastatin. Our results showed that the statin (0.6 and 6 mg/kg/day) inhibited hemoglobin (Hb) content (51%) and vascular endothelial growth factor (VEGF) levels (71%) in the treated group compared with the control group. The inflammatory component, as assessed by N-acetyl-β-D-glucosaminidase activity and tumor necrosis factor-α (TNF-α) level was also decreased by the compound. In the treated group; the inhibition of the enzyme activity was 33% and the cytokine was 67% relative to the control. In these implants the statin was also able to decrease nitric oxide (NO) production, detected with an NO-sensitive electrode. To our knowledge this is the first study demonstrating an inhibitory role of fluvastatin on the production of NO in inflammatory angiogenesis of newly formed fibrovascular tissue.
    Apmis 11/2012; · 2.07 Impact Factor
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    ABSTRACT: Carboplatin is commonly used to treat a variety of tumors. We investigated the effects of carboplatin (100mg/kg) in the development and metastatic dissemination of the 4T1 mice mammary carcinoma. Carboplatin was able to reduce tumor volume and the number of lung metastases in 50% compared to the control animals. Mitotic and apoptotic indices were also decreased by the treatment. Assessment of the vascularization of the tumors revealed a significant decrease in blood vessel formation by carboplatin. A decrease in nuclear positivity of CDC47 and cyclin D1 was observed in the group treated with carboplatin when compared to the control group. Positivity for p53 was observed in the control group (2/28; 5%) and the treated group (5/71; 4%). Carboplatin has been demonstrated to be an efficient regulator of 4T1MMT growth and dissemination. The action of this chemotherapeutic agent seems to be related to the induction of apoptosis and inhibition of angiogenesis and cell proliferation.
    Pathology - Research and Practice 11/2012; · 1.21 Impact Factor
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    ABSTRACT: Inflammation and angiogenesis, key components of fibrovascular tissue growth, exhibit considerable variability among species and strains. We investigated whether the response of inbred and outbred mice strains to dipyridamole (DP) on these processes would present similar variability. The effects of the drug on blood vessel formation, inflammatory cell recruitment, collagen deposition and cytokine production were determined on the fibroproliferative tissue induced by sponge implants in Swiss and Balb/c mice. Angiogenesis as assessed by hemoglobin (Hb) and vascular endothelial growth factor (VEGF) concentrations differed between the strains. Swiss implants had the highest Hb content but the lowest VEGF concentrations. Systemic DP treatment exerted an antiangiogenic effect on Balb/c implants but an proangiogenic effect on Swiss implants. The inflammatory enzyme activities myeloperoxidase (six-fold higher in Balb/c implants) and N-acetyl-β-d-glucosaminidase were reduced by the treatment in Balb/c implants only. Nitrite concentrations were also higher in Balb/c implants by 40% after DP treatment. Tumor necrosis factor-alpha levels were similar in the implants of both strains and were not reduced by DP. Transforming growth factor β-1 levels and collagen deposition also varied between the strains. The inbred strain had similar levels of the cytokine but implants of Swiss mice presented more collagen. DP treatment reduced collagen deposition in Balb/c implants only. Our data showing the influence of the genetic background on marked heterogeneity of inflammatory angiogenesis components and differential sensitivity to DP may provide some answers to clinical evidence for resistance to angiogenic therapy.
    Experimental Biology and Medicine 09/2012; 237(9):1084-92. · 2.80 Impact Factor
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    ABSTRACT: Thalidomide has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on key components (blood vessel formation, inflammatory cell recruitment/activation, cytokine production) of 4T1 mammary tumor in mice. In addition, tumor growth and lung metastasis were evaluated. 4T1 cells were injected subcutaneously into Balb/c mice. After tumor engraftment (5days), thalidomide (150mg/kg) was administered to the treated group for 7days. Tumors of control (saline) and treated groups were sized regularly, removed 12days after inoculation and processed for biochemical and immunohistological parameters to assess neovascularization, inflammation and proliferative activity. Daily oral dose of thalidomide was able to reduce in 46% the tumor volume. The number of metastasis in the lungs was less in the thalidomide-treated group compared with the control animals. Assessment of tumor vascularization revealed a significant decrease in blood vessels formation by thalidomide. Likewise, the expression of FGF-1 showed weaker cytoplasmic positivity in the group treated with thalidomide compared with the control group. The levels of two cytokines, VEGF (pro-angiogenic) and TNF-α (pro-inflammatory) were decreased in tumor samples of thalidomide-treated group compared with the control group. Accumulation of neutrophils or macrophages in the 4T1 tumor measured by the activities of inflammatory enzymes, myeloperoxidase (MPO) for neutrophils and N-acetyl-β-D-glucosaminidase (NAG) for macrophages was inhibited by the treatment. By targeting key components of 4T1 tumor simultaneously, thalidomide was effective in attenuating tumor growth and metastasis. This approach, suppression of inflammation and angiogenesis may provide further insights for both prevention and treatment of cancer.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 05/2012; 66(7):491-8. · 2.24 Impact Factor
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    ABSTRACT: Injury of skeletal abdominal muscle wall is a common medical condition and implantation of synthetic or biological material is a procedure to repair musculofascial defects. We proposed to characterize the dynamics of inflammatory cell recruitment, newly formed blood vessels, cytokine production and fibrogenesis in the abdominal skeletal muscle in response to polyether-polyurethane sponge implants in mice. At 2, 4, 7 and 10days after implantation the muscle tissue underneath the sponge matrix was removed for the assessment of the angiogenic response (hemoglobin content, vascular endothelial growth factor and morphometric analysis of the number of vessels) and inflammation (myeloperoxidase and n-acethyl-B-d-glucosaminidase activities, cytokines). In addition, muscle fibrogenesis was determined by the levels of TGF-β1 and collagen deposition. Hemoglobin content, wash out rate of sodium fluorescein (indicative of blood flow) and the number of vessels increased in the abdominal muscle bearing the synthetic matrix in comparison with the intact muscle. Neutrophil recruitment peaked in the muscle at day 2, followed by macrophage accumulation at day 4 post-injury. The levels of the cytokines, VEGF, TNF-α, CCL-2/MCP-1 were higher in the injured muscle compared with the intact muscle and peaked soon after muscle injury (days 2 to 4). Collagen levels were higher in sponge-bearing muscle compared with the non-bearing tissue soon after injury (day 2). The implantation technique together with the inflammatory and vascular parameters used in this study revealed inflammatory, angiogenic and fibrogenic events and mechanisms associated with skeletal muscle responses to synthetic implanted materials.
    Microvascular Research 04/2012; 84(1):9-15. · 2.93 Impact Factor
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    ABSTRACT: The purpose of this study was to develop triamcinolone acetonide-loaded polyurethane implants (TA PU implants) for the local treatment of different pathologies including arthritis, ocular and neuroinflammatory disorders. The TA PU implants were characterized by FTIR, SAXS and WAXS. The in vitro and in vivo release of TA from the PU implants was evaluated. The efficacy of TA PU implants in suppressing inflammatory-angiogenesis in a murine sponge model was demonstrated. FTIR results revealed no chemical interactions between polymer and drug. SAXS results indicated that the incorporation of the drug did not disturb the polymer morphology. WAXS showed that the crystalline nature of the TA was preserved after incorporation into the PU. The TA released from the PU implants efficiently inhibited the inflammatory-angiogenesis induced by sponge discs in an experimental animal model. Finally, TA PU implants could be used as local drug delivery systems because of their controlled delivery of TA.
    Journal of Materials Science Materials in Medicine 04/2012; 23(6):1431-45. · 2.14 Impact Factor
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    ABSTRACT: Inflammation is as an important factor in ovulation with the active participation of leucocytes and their inflammatory mediators. The present study was performed to compare the activity of the inflammatory enzymes myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in patients with endometriosis-related infertility and in normally ovulating women undergoing intracytoplasmic sperm injection (ICSI). This prospective study included infertile women undergoing ICSI treatment. These women were divided into two groups: endometriosis anovulation (n = 18) and normally ovulating (n = 20). NAG and MPO activity was evaluated colorimetrically in serum and in follicular fluids obtained at the time of oocyte retrieval. There was a significant correlation between the serum and follicular fluid activities of NAG and MPO (τ = 0.256, P = 0.025; and τ = -0.234, P = 0.041; respectively). Both serum and follicular fluid NAG activities were higher in patients with endometriosis compared to the control group (P < 0.001). MPO follicular fluid activity was lower in patients with endometriosis compared to normally ovulating women (P = 0.016). Infertile patients with endometriosis show a distinct pattern of serum and follicular fluid macrophage/neutrophil activation compared to normally ovulating women undergoing ICSI, which may reflect the role of immune and inflammatory alterations in endometriosis-related infertility.
    Journal of Obstetrics and Gynaecology Research 03/2012; 38(5):810-6. · 0.84 Impact Factor
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    ABSTRACT: Envenomation by Loxosceles spider bite leads to a set of signs and symptoms, called loxoscelism, which in most cases manifests through the dermonecrotic frame. The development of a smaller size animal model, of easy handling and maintenance, and lower cost is needed to study the loxoscelism pathogenesis. The inflammatory effects of the Loxosceles similis crude venom was evaluated considering neutrophil and macrophage activation, vasodilatation, hyperhaemia, edema and hemorrhage and TNF-α and VEGF production using the murine sponge implant model. Thirty two male Swiss mice (6-8 weeks old) were implanted subcutaneously with polyether-polyurethane sponge discs. Fourteen days post implantation, animals were separated into two groups: (1) control group--16 mice received 30 μL of saline intra-implant; (2) treated group-sixteen mice injected with 0.5 μg/30 μL of L. similis crude venom intra-implant. The animals were euthanized with xylazine/ketamine after 1 and 4 h post- injection. Microscopically, implants of the treated groups presented an acute inflammation characterized by: neutrophilic infiltrate, edema, vasodilatation hyperhaemia, and severe hemorrhage. Some vessels presented ruptured walls. Under morphometric analysis, vessel area was bigger in the treated groups compared with the control ones. The biochemical parameters, hemoglobin content, inflammatory enzyme activities (myeloperoxidase and n-acethyl-β-D glucosaminidase) and levels of the cytokines, TNF-α and VEGF, were also significantly higher in the venom-treated groups. The effects of Loxosceles venom in the granulation tissue of the implant in mice were similar to those observed in cutaneous loxoscelism in other species (human and rabbits). Consequently, the murine sponge implant model provides a new method to investigate cellular/molecular mechanisms associated with cutaneous loxoscelism.
    Toxicon 03/2012; 59(7-8):672-9. · 2.92 Impact Factor
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    ABSTRACT: Ovarian hormones modulate the metabolism of adipose cells and present a protective effect against hypertension. The aim of this study was to compare the effect of estradiol on adiposity markers in spontaneously hypertensive rats. Ovariectomized spontaneously hypertensive rats treated with estradiol (5 μg/100 g/day), three weeks after ovariectomy, presented decreased blood pressure and insulin levels and increased hepatic glycogen content. Periuterine or mesenteric adipocytes from treated animals were smaller as compared to vehicle treated group, whereas no differences were observed in relation to the number of cells. Basal rates of glycerol release were higher only in periuterine adipocytes of treated rats. The increment of glycerol release over basal values in response to isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated periuterine and mesenteric adipocytes, respectively. The estradiol treated group was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis than the control animals. The lipoprotein lipase activity decreased after treatment, only in periuterine adipose tissue. Estradiol administration increased basal and insulin-stimulated rates of glucose transport in adipocytes of both sites, although the values obtained by periuterine were higher than those observed for mesenteric adipocytes. Both adipose tissues from treated animals exhibited a decreased expression of the peroxisome proliferator-activated receptor-γ, but an increased expression of peroxisome proliferator-activated receptor-α in liver. These findings suggest that estrogen administration attenuates adiposity markers of spontaneously hypertensive rats as a result of the decreased expression levels of peroxisome proliferator-activated receptor-γ in adipose tissue and increased expression of peroxisome proliferator-activated receptor-α in liver.
    Metabolism: clinical and experimental 03/2012; 61(8):1100-7. · 3.10 Impact Factor

Publication Stats

903 Citations
179.79 Total Impact Points


  • 1992–2014
    • Federal University of Minas Gerais
      • • Instituto de Cîências Biológicas (ICB)
      • • Departamento de Fisiologia e Biofísica
      Cidade de Minas, Minas Gerais, Brazil
  • 2011
    • Dompé farmaceutici S.p.A.
      Milano, Lombardy, Italy
  • 2007
    • Imperial College London
      • Section of Leukocyte Biology
      Londinium, England, United Kingdom