José Antônio Silva

Universidade Nove de Julho, San Paulo, São Paulo, Brazil

Publications (28)70.69 Total impact

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    ABSTRACT: Low-level laser therapy (LLLT) has been shown to increase the proliferation of several cell types. We evaluated the effects of LLLT on adhesion, proliferation, and gene expression of vascular endothelial growth factor (VEGF) and type 2 receptor of VEGF (VEGFR2) at mesenchymal stem cells (MSCs) from human (hMSCs) and rat (rMSCs) adipose tissues on nutritional deficiencies. A dose-response curve was performed with cells treated with laser Ga-Al-As (660 nm, 30 mW) at energy of 0.7 to 9 J. Cell adhesion and proliferation were quantified 20, 40, and 60 min after LLLT and 24, 72, and 120 h after cultivation. Gene expression was verified by RT-PCR after 2 h of LLLT. A minor nutritional support caused a significant decrease in proliferation and adhesion of hMSCs and rMSCs. However, at the lowest LLLT dose (0.7 J), we observed a higher proliferation in hMSCs at standard condition shortly after irradiation (24 h). Adhesion was higher in hMSCs cultivated in controlled conditions at higher LLLT doses (3 and 9 J), and rMSCs show a reduction in the adhesion on 1.5 to 9 J. On nutritional deprivation, a 9 J dose was shown to reduce proliferation with 24 h and adhesion to all culture times in rMSCs. VEGF and VEGFR2 were increased after LLLT in both cell types. However, hMSCs under nutritional deprivation showed higher expression of VEGF and its receptor after irradiation with other laser doses. In conclusion, LLLT on human and rat MSCs might upregulate VEGF messenger RNA (mRNA) expression and modulate cell adhesion and proliferation distinctively.
    Lasers in Medical Science 09/2014; · 2.40 Impact Factor
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    ABSTRACT: The increase in PGE2 production by microsomal PGE synthase-1 (mPGES-1) in CNS contributes to the severity of the inflammatory and pain responses in the model of edema formation and hyperalgesia induced by carrageenan. PGI2, alike to PGE2, plays an important role in the inflammation. Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and the acute inflammatory process. In this work, we studied the effect of LLLT on the expression of both mPGES-1 and IP messenger RNA (mRNA), in either subplantar or total brain tissues obtained from rats submitted to model of edema formation and hyperalgesia induced by carrageenan administration. The test sample consisted of 30 rats divided into five groups: A1 (control-saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). The animals from groups A3 and A5 were irradiated 1 h after induction of inflammation by carrageenan injection. Continuous-wave red laser with wavelengths of 660 nm and dose of 7.5 J/cm(2) was used. Six hours after carrageenan-induced inflammation, mPGES-1 and prostacyclin receptor (IP) mRNA expression were significantly increased both in subplantar and brain tissues. LLLT was able to reduce both mPGES-1 and IP mRNA expression in subplantar and brain tissues. We suggest that LLLT is able to reduce both inflammation and hyperalgesia observed in the model of edema formation and hyperalgesia induced by carrageenan, by a mechanism involving the decrease in the expression of both mPGES-1 and IP.
    Lasers in Medical Science 06/2014; · 2.40 Impact Factor
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    ABSTRACT: In the classical model of edema formation and hyperalgesia induced by carrageenan administration in rat paw, the increase in prostaglandin E2 (PGE2) production in the central nervous system (CNS) contributes to the severity of the inflammatory and pain responses. Prostaglandins are generated by the cyclooxygenase (COX). There are two distinct COX isoforms, COX-1 and COX-2. In inflammatory tissues, COX-2 is greatly expressed producing proinflammatory prostaglandins (PGs). Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and acute inflammatory process. Herein we studied the effect of LLLT on both COX-2 and COX-1 messenger RNA (mRNA) expression in either subplantar or brain tissues taken from rats treated with carrageenan. The experiment was designed as follows: A1 (saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). Animals from the A3 and A5 groups were irradiated at 1 h after carrageenan administration, using a diode laser with an output power of 30 mW and a wavelength of 660 nm. The laser beam covered an area of 0.785 cm(2), resulting in an energy dosage of 7.5 J/cm(2). Both COX-2 and COX-1 mRNAs were measured by RT-PCR. Six hours after carrageenan administration, COX-2 mRNA expression was significantly increased both in the subplantar (2.2-4.1-fold) and total brain (8.65-13.79-fold) tissues. COX-1 mRNA expression was not changed. LLLT (7.5 J/cm(2)) reduced significantly the COX-2 mRNA expression both in the subplantar (~2.5-fold) and brain (4.84-9.67-fold) tissues. The results show that LLLT is able to reduce COX-2 mRNA expression. It is possible that the mechanism of LLLT decreasing hyperalgesia is also related to its effect in reducing the COX-2 expression in the CNS.
    Lasers in Medical Science 02/2014; · 2.40 Impact Factor
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    ABSTRACT: Sympathetic hyperactivity induces adverse effects in myocardial. Recent studies have shown that exercise training induces cardioprotection against sympathetic overload; however, relevant mechanisms of this issue remain unclear. We analyzed whether exercise can prevent pathological hypertrophy induced by sympathetic hyperactivity with modulation of the kallikrein-kinin and angiogenesis pathways. Male Wistar rats were assigned to non-trained group that received vehicle; non-trained isoproterenol treated group (Iso, 0.3 mg kg-1 day-1); and trained group (Iso+Exe) which was subjected to sympathetic hyperactivity with isoproterenol. The Iso rats showed hypertrophy and myocardial dysfunction with reduced force development and relaxation of muscle. The isoproterenol induced severe fibrosis, apoptosis and reduced myocardial capillary. Interestingly, exercise blunted hypertrophy, myocardial dysfunction, fibrosis, apoptosis and capillary decreases. The sympathetic hyperactivity was associated with high abundance of ANF mRNA and β-MHC mRNA, which was significantly attenuated by exercise. The tissue kallikrein was augmented in the Iso+Exe group, and kinin B1 receptor mRNA was increased in the Iso group. Moreover, exercise induced an increase of kinin B2 receptor mRNA in myocardial. The myocardial content of eNOS, VEGF, VEGF receptor 2, pAkt and Bcl-2 were increased in the Iso+Exe group. Likewise, increased expression of pro-apoptotic Bad in the Iso rats was prevented by prior exercise. Our results represent the first demonstration that exercise can modulate kallikrein-kinin and angiogenesis pathways in the myocardial on sympathetic hyperactivity. These findings suggest that kallikrein-kinin and angiogenesis may have a key role in protecting the heart.
    PLoS ONE 01/2014; 9(3):e91017. · 3.53 Impact Factor
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    ABSTRACT: Osteoarthritis (OA) resulting from injury or disease is associated with increased levels of several matrix metalloproteinases (MMPs), which degrade all components of the complex extracellular matrix in the cartilage. The objective of this study is to investigate the effect of low-level laser therapy (LLLT) on papain-induced joint damage in rats by histopathology and analysis of metalloproteinase 2 and 9 production. Sixty male Wistar rats were randomly distributed into four groups of 15 animals: (1) non-injury negative control, (2) injury positive control, (3) treated with LLLT at 50 mW, and (4) treated with LLLT at 100 mW. OA was induced in animals using papain (4 % solution) followed by treatment with LLLT. After 7, 14, and 21 days, the animals were euthanized. The articular lavage was collected and centrifuged; then, the supernatant was stored prior to protein analysis by western blot. The material was stained with hematoxylin and eosin for histopathological analysis, and Picrosirius Red was used to estimate the percentage of collagen fibers. To determine normal distribution, ANOVA and Tukey's post hoc test were used for comparison between and within each group at each time period. All data are expressed as mean and standard deviation values, with the null hypothesis considered as p < 0.05. Both laser groups (50 and 100 mW) were effective in tissue repair, decreasing collagen type III expression and increasing type I expression in all experimental periods; however, LLLT at 50 mW reduced metalloproteinase 9 more than at 100 mW in 21 days. LLLT at 50 mW was more efficient in the modulation of matrix MMPs and tissue repair.
    Lasers in Medical Science 08/2013; · 2.40 Impact Factor
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    ABSTRACT: The present study investigated the effects of low-level light-emitting diode (LED) therapy (880 ± 10 nm) on interleukin (IL)-10 and type I and III collagen in an experimental model of Achilles tendinitis. Thirty male Wistar rats were separated into six groups (n = 5), three groups in the experimental period of 7 days, control group, tendinitis-induced group, and LED therapy group, and three groups in the experimental period of 14 days, tendinitis group, LED therapy group, and LED group with the therapy starting at the 7th day after tendinitis induction (LEDT delay). Tendinitis was induced in the right Achilles tendon using an intratendinous injection of 100 μL of collagenase. The LED parameters were: optical power of 22 mW, spot area size of 0.5 cm(2), and irradiation time of 170 s, corresponding to 7.5 J/cm(2) of energy density. The therapy was initiated 12 h after the tendinitis induction, with a 48-h interval between irradiations. The IL-10 and type I and III collagen mRNA expression were evaluated by real-time polymerase chain reaction at the 7th and 14th days after tendinitis induction. The results showed that LED irradiation increased IL-10 (p < 0.001) in treated group on 7-day experimental period and increased type I and III collagen mRNA expression in both treated groups of 7- and 14-day experimental periods (p < 0.05), except by type I collagen mRNA expression in LEDT delay group. LED (880 nm) was effective in increasing mRNA expression of IL-10 and type I and III collagen. Therefore, LED therapy may have potentially therapeutic effects on Achilles tendon injuries.
    Lasers in Medical Science 02/2013; · 2.40 Impact Factor
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    ABSTRACT: Muscle repair is regulated by growth factors and cytokines. Low-level laser therapy (LLLT) seems to influence acute inflammation and accelerate skeletal muscle repair. This study verifies the effect of LLLT on the expression of IL-1β in the tibialis anterior (TA) muscle of rats following acute injury. Wistar rats (n = 35) were allocated into three groups: control (without lesion and LLLT, n = 5), injury group (n = 15), and injury + LLLT group (n = 15). The acute injury was induced by the contact with a cooled metal probe (3 mm in diameter) during 10 s, twice, in the same muscle area. LLLT was used three times a week using the InGaAlP laser (660 nm; beam spot of 0.04 cm(2), output power of 20 mW, power density of 500 mW/cm(2), and energy density of 5 J/cm(2) during 10 s). The animals were analyzed at 1, 7, and 14 days following injury. TA muscles samples were used for obtaining total RNA and performing cDNA synthesis. Real-time polymerase chain reactions were realized using IL-1β primer. There was a decrease in IL-1β expression after 7 days in LLLT group in comparison with the no treated group. In conclusion, LLLT was able to decrease IL-1β expression during the skeletal muscle repair following an acute injury.
    Lasers in Medical Science 11/2012; · 2.40 Impact Factor
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    ABSTRACT: A variety of treatments for tendinopathies is currently used or has been trialed. However, in fact, there is a remarkably little evidence that any conventional therapies are effective. In the last years, low-level laser therapy (LLLT) has been showing interesting results in inflammatory modulation in different musculoskeletal disorders, but the optimal parameters and mechanisms behind these effects are not fully understood. The aim of this study is to investigate if the LLLT modulates the acute and chronic phase of collagenase-induced tendinitis in rat by interfering in mRNA expression for matrix metalloproteinases (MMP13 and MMP1), vascular endothelial growth factor (VEGF), and anti-inflammatory mediator (interleukin (IL)-10). For such, tendinitis was induced by collagenase injection in male Wistar rats. Animals were treated with LLLT (780 nm, potency of 22 mW, 107 mW/cm(2), energy density of 7.5 J/cm(2), and energy delivered of 1.54 J) with different number of treatments in accordance with the inflammatory phase analyzed. LLLT was able to modulate mRNA gene expression of IL-10, VGEF, MMP1, and MMP13 both in acute than in chronic inflammatory phase (p < 0.05). Our results suggest that LLLT with parameters employed in the present study was able to modulate IL-10, VEGF, MMP1, and MMP13 mRNA gene expression both in acute than in chronic tendon inflammation. However, further studies are needed to establish optimal parameters for LLLT.
    Lasers in Medical Science 08/2012; · 2.40 Impact Factor
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    ABSTRACT: We previously showed that patients with temporal lobe epilepsy (TLE) present an increased expression of angiotensin II (AngII) AT1 and AT2 receptors in the hippocampus, supporting the idea of an upregulation of renin-angiotensin system (RAS) in this disease. This study aimed to verify the relationship between the RAS and TLE during epileptogenesis. Levels of the peptides angiotensin I (AngI), angiotensin II (AngII) and angiotensin 1-7 (Ang 1-7), were detected by HPLC assay. Angiotensin AT1 and AT2 receptors, Mas mRNA receptors and angiotensin converting enzyme (ACE), tonin and neutral endopeptidase (NEP) mRNA were also quantified at the hippocampus of Wistar rats by real time PCR, during acute (n=10), silent (n=10) and chronic (n=10) phases of pilocarpine-induced epilepsy. We observed an increased peptide level of Ang1-7 into acute and silent phases, decreasing importantly (p≤0.05) in the chronic phase, suggesting that AngI may be converted into Ang 1-7 by NEP, which is present in high levels in these periods. Our results also showed increased peptide level of AngII in the chronic phase of this model. In contraposition, the ACE expression is reduced in all periods. These data suggest that angiotensinogen or AngI may be cleaved to AngII by tonin, which showed increased expression in all phases. We found changes in AT1, AT2 and Mas mRNA receptors levels suggesting that Ang1-7 could act at Mas receptor during the silent period. Herein, we demonstrated for the first time, changes in angiotensin-related peptides, their receptors as well as the releasing enzymes in the hippocampus of rats during pilocarpine-induced epilepsy.
    Neurochemistry International 04/2012; 61(1):54-62. · 2.66 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the impact of circuit-based exercise on the body composition in obese older women by focusing on physical exercise and body weight (BW) gain control in older people. Seventy older women (>60 years old) voluntarily took part in the study. Participants were randomized into six different groups according to body mass index (BMI): appropriate weight (AW) control (AWC) and trained (AWT) groups, overweight (OW) control (OWC) and trained (OWT) groups, and obesity (O) control (OC) and trained (OT) groups. The exercise program consisted of 50 minutes of exercise three times per week for 12 weeks. The exercises were alternated between upper and lower body using rest between sets for 40 seconds with intensity controlled by heart rate (70% of work). The contraction time established was 5 seconds to eccentric and concentric muscular action phase. The following anthropometric parameters were evaluated: height (m), body weight (BW, kg), body fat (BF, %), fat mass (FM, kg), lean mass (LM, kg), and BMI (kg/m(2)). The values (mean ± standard deviation [SD]) of relative changes to BW (-8.0% ± 0.8%), BF (-21.4% ± 2.1%), LM (3.0% ± 0.3%), and FM (-31.2% ± 3.0%) to the OT group were higher (P < 0.05) than in the AWT (BW: -2.0% ± 1.1%; BF: -4.6% ± 1.8%; FM: -7.0% ± 2.8%; LM: 0.2% ± 1.1%) and OWT (BW: -4.5% ± 1.0%; BF: -11.0% ± 2.2%; FM: -16.1% ± 3.2%; LM: -0.2% ± 1.0%) groups; additionally, no differences were found for C groups. While reduction (P < 0.03) in BMI according to absolute values was observed for all trained groups (AWT: 22 ± 1 versus 21 ± 1; OWT: 27 ± 1 versus 25 ± 1, OT: 34 ± 1 versus 30 ± 1) after training, no differences were found for C groups. In summary, circuit-based exercise is an effective method for promoting reduction in anthropometrics parameters in obese older women.
    Clinical Interventions in Aging 01/2012; 7:551-6. · 2.65 Impact Factor
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    ABSTRACT: We tested if modulation in mRNA expression of cyclooxygenase isoforms (COX-1 and COX-2) can be related to protective effects of phototherapy in skeletal muscle. Thirty male Wistar rats were divided into five groups receiving either one of four laser doses (0.1, 0.3, 1.0 and 3.0 J) or a no-treatment control group. Laser irradiation (904 nm, 15 mW average power) was performed immediately before the first contraction for treated groups. Electrical stimulation was used to induce six tetanic tibial anterior muscle contractions. Immediately after sixth contraction, blood samples were collected to evaluate creatine kinase activity and muscles were dissected and frozen in liquid nitrogen to evaluate mRNA expression of COX-1 and COX-2. The 1.0 and 3.0 J groups showed significant enhancement (P < 0.01) in total work performed in six tetanic contractions compared with control group. All laser groups, except the 3.0 J group, presented significantly lower post-exercise CK activity than control group. Additionally, 1.0 J group showed increased COX-1 and decreased COX-2 mRNA expression compared with control group and 0.1, 0.3 and 3.0 J laser groups (P < 0.01). We conclude that pre-exercise infrared laser irradiation with dose of 1.0 J enhances skeletal muscle performance and decreases post-exercise skeletal muscle damage and inflammation.
    Photochemistry and Photobiology 07/2011; 87(5):1159-63. · 2.29 Impact Factor
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    ABSTRACT: Kallikrein 1 (hK1) is a tissue enzyme responsible for kinin release in inflammatory cascade. This study was delineated to study the distribution and the co-localization of hK1 and kinin B1 and B2 receptors with glial and/or neuronal proteins markers, in the hippocampus of patients with refractory temporal lobe epilepsy, associated with hippocampal sclerosis (TLE-HS), comparing with control tissues. Hippocampal levels of KLK1 mRNA were also measured. hK1, kinin B1 and B2 receptors, NeuN and GFAP were analyzed using immunohistochemistry and confocal microscopy and KLK1 mRNA was quantified with real time PCR. Increased expression of hK1 by astrocytes co-localized with GFAP was found, contrasting with kinin B1 and B2 receptors, which were co-localized with NeuN in the sclerotic hippocampus. In addition, KLK1 mRNA was also up-regulated in same tissues. These data suggest an overexpression of kallikrein-kinin system and a neuron-glia interaction in the inflammatory process present in refractory TLE-HS.
    Neurochemistry International 01/2011; 58(4):477-82. · 2.66 Impact Factor
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    ABSTRACT: Low-level laser therapy (LLLT) has been found to produce anti-inflammatory effects in a variety of disorders. Tendinopathies are directly related to unbalance in expression of pro- and anti-inflammatory cytokines which are responsible by degeneration process of tendinocytes. In the current study, we decided to investigate if LLLT could reduce mRNA expression for TNF-α, IL-1β, IL-6, TGF-β cytokines, and COX-2 enzyme. Forty-two male Wistar rats were divided randomly in seven groups, and tendinitis was induced with a collagenase intratendinea injection. The mRNA expression was evaluated by real-time PCR in 7th and 14th days after tendinitis. LLLT irradiation with wavelength of 780 nm required for 75 s with a dose of 7.7 J/cm(2) was administered in distinct moments: 12 h and 7 days post tendinitis. At the 12 h after tendinitis, the animals were irradiated once in intercalate days until the 7th or 14th day in and them the animals were killed, respectively. In other series, 7 days after tendinitis, the animals were irradiated once in intercalated days until the 14th day and then the animals were killed. LLLT in both acute and chronic phases decreased IL-6, COX-2, and TGF-β expression after tendinitis, respectively, when compared to tendinitis groups: IL-6, COX-2, and TGF-β. The LLLT not altered IL-1β expression in any time, but reduced the TNF-α expression; however, only at chronic phase. We conclude that LLLT administered with this protocol reduces one of features of tendinopathies that is mRNA expression for pro-inflammatory mediators.
    Lasers in Medical Science 01/2011; 26(1):85-94. · 2.40 Impact Factor
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    ABSTRACT: Statins may act on inflammatory responses, decreasing oxidative stress and also reducing temperature after a brain ischemic insult. Previous data have indicated that statins protect neurons from death during long-lasting status epilepticus (SE) and attenuate seizure behaviors in animals treated with kainic acid. In this context, the study described here aimed to investigate the effect of lovastatin on body temperature and on mRNA expression levels of hippocampal cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 and B2 receptors of rats submitted to pilocarpine-induced SE. Quantitative real-time polymerase chain reaction showed a significant decrease in mRNA expression of interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 receptor in animals with SE treated with lovastatin, compared with untreated animals with SE (P<0.001). Lovastatin also reduced SE-induced hyperthermia, indicating that mechanisms related to brain protection are triggered by this drug under conditions associated with acute excitotoxicity or long-lasting SE.
    Epilepsy & Behavior 01/2011; 20(1):1-5. · 2.06 Impact Factor
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    ABSTRACT: The aim of the present study was to determine the effect of low-level laser therapy (LLLT) on the expression of TNF-α and TGF-β in the tibialis anterior muscle of rats following cryoinjury. Muscle regeneration involves cell proliferation, migration and differentiation and is regulated by growth factors and cytokines. A growing body of evidence suggests that LLLT promotes skeletal muscle regeneration by reducing the duration of acute inflammation and accelerating tissue repair. Adult male Wistar rats (n = 35) were randomly divided into three groups: control group (no lesion, untreated, n = 5), cryoinjury without LLLT group (n = 15), and cryoinjury with LLLT group (n = 15). The injured region was irradiated three times a week using an AlGaInP laser (660 nm; beam spot 0.04 cm(2), output power 20 mW, power density 500 mW/cm(2), energy density 5 J/cm(2), exposure time 10 s). Muscle remodeling was evaluated at 1, 7 and 14 days (long-term) following injury. The muscles were removed and total RNA was isolated using TRIzol reagent and cDNA synthesis. Real-time polymerase chain reactions were performed using TNF-α and TGF-β primers; GAPDH was used to normalize the data. LLLT caused a decrease in TNF-α mRNA expression at 1 and 7 days following injury and in TGF-β mRNA expression at 7 days following cryoinjury in comparison to the control group. LLLT modulated cytokine expression during short-term muscle remodeling, inducing a decrease in TNF-α and TGF-β.
    Lasers in Medical Science 11/2010; 26(3):335-40. · 2.40 Impact Factor
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    ABSTRACT: The present study investigated the effects of low-level light emitting diode (LED) therapy (880 +/- 10 nm) on inflammatory process in a experimental model of Achilles tendinitis induced by collagenase. Fifty-six male Wistar were separated into seven groups (n = 8), three groups in the experimental period of 7 days and four groups in the experimental period of 14 days, the control group (CONT), tendinitis group (TEND), LED therapy group (LEDT) for both experimental periods, and LED therapy group 7th to 14th day (LEDT delay) for 14 days experimental period. The LED parameters was 22 mW CW of optical output power, distributed in an irradiation area of 0.5 cm(2), with an irradiation time of 170 seconds, the applied energy density was 7.5 J/cm(2) in contact. The therapy was initiated 12 hours after the tendinitis induction, with a 48-hour interval between the irradiations. The histological analysis and inflammatory mediators were quantified. Our results showed that LED decreases the inflammatory cells influx and mRNA expression to IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) in both phase, and cyclooxygenase-2 (COX-2) just in initial phase (P < 0.05). Our results suggest that the anti-inflammatory therapy with low-power LED (880 nm) enhanced the tissue response in all groups. We can conclude that the LED was able to reduce signs of inflammation in collagenase-induced tendinitis in rats by reducing the number of inflammatory cells and decrease mRNA expression of cytokines.
    Lasers in Surgery and Medicine 08/2010; 42(6):553-8. · 2.46 Impact Factor
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    ABSTRACT: The inhibitors of apoptosis proteins (IAPs) act by directly blocking cleaved caspase-3 (XIAP) or the protein SMAC/DIABLO, an antagonist. The inhibition of XIAP activity or the increase of SMAC activity might improve the therapeutic response of the patients. This work evaluated the immunoexpression of IAPs and SMAC in colorectal carcinoma and their correlation with apoptotic index (AI), cellular proliferation, p53 protein immunoexpression and patient survival rate. TMA paraffin blocks were made with colorectal cancer tissue and adjacent non-tumorous mucosa of 130 patients, not submitted to radio or chemotherapy. Sections of 4 microm were processed by immunohistochemistry for survivin, XIAP, cIAP-1, cIAP-2 and SMAC, and the immunoexpression scores were obtained. They were correlated between each other and with the AI obtained by anti-cleaved caspase-3 and M30 (cleaved cytokeratin-18) antibodies, the cellular proliferation index, p53 protein immunoexpression and patient survival data. Direct correlation occurred between the four IAPs studied in tumor and non-tumorous mucosa tissues. SMAC, survivin, cIAP-1 and cIAP-2 were positively correlated with tumoral tissue AI. Cellular proliferation and p53 immunoexpression was positively correlated with XIAP, SMAC and cIAP-1 scores. Low cIAP-1 immunoexpression showed a tendency for correlation with shorter patient survival. Equilibrium between the activities of IAPs and SMAC was demonstrated by the direct correlation between their immunoexpression. Correlation between SMAC and AI confirmed the pro-apoptotic activity of this protein. XIAP showed no inverse correlation with AI. XIAP, SMAC and cIAP-1 play a role in colorectal tumorigenesis, as demonstrated by their direct correlation with cellular proliferation and p53 protein. The tendency for correlation between low cIAP-1 immunoexpression and survival might indicate a role for this protein as a prognostic marker in colorectal cancer.
    Oncology Reports 09/2009; 22(2):295-303. · 2.30 Impact Factor
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    ABSTRACT: We determined if cutaneous hyperalgesia and pain-induced c-Fos overexpression in the spinal cord produced by repeated forced swimming (FS) stress in the rat were related to changes in GABA neurotransmission by studying spinal release of GABA and the effect of positive modulation of GABA-A receptors with diazepam. Male rats were daily submitted to 10-20 min of either forced swimming or sham swimming (SS) for 3 consecutive days. Two days later, spinal GABA release was estimated by in vivo microdialysis. In other set of rats, either diazepam (2 mg/kg, i.p.) or saline was administered 1h before either SS or FS and inflammatory nociception was assessed with the formalin test; it was followed by removal of lumbar spinal cords for c-Fos immunocytochemistry. Basal and pain-evoked release of GABA in the spinal cord was lower in FS rats than in SS rats. In contrast, pain scores during formalin test late phase and pain-induced c-Fos expression in laminae I-VI of ipsilateral dorsal horn were significantly higher in FS rats than in SS rats. In FS rats, diazepam did not have effect on GABA release but reduced pain scores and overexpression of c-Fos whereas flumazenil (0.1 mg/kg, i.p.), an antagonist of the benzodiazepine binding site, reversed these effects. When diazepam was given only 1h before the formalin test, it slightly but significantly reduced pain scores during late phase in FS rats but not in SS rats. In conclusion, stress-induced reduction in GABA-A receptor activation is involved in the development of FS stress-induced hyperalgesia.
    Behavioural Brain Research 06/2008; 189(1):159-69. · 3.33 Impact Factor

Institutions

  • 2012
    • Universidade Nove de Julho
      San Paulo, São Paulo, Brazil
  • 2004–2012
    • Universidade Federal de São Paulo
      • • School of Medicine
      • • Departamento de Neurologia e Neurocirurgia
      São Paulo, Estado de Sao Paulo, Brazil
  • 2010
    • Universidade do Vale do Paraíba
      • Instituto de Pesquisa e Desenvolvimento
      São José dos Campos, São Paulo, Brazil