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Introduction: Bone healing depends on inflammation control and tissue repair time. Low-level laser therapy (LLLT) has been investigated to accelerate this process. Methylene blue (MB), together with LLLT, has been investigated for its antioxidant and anti-inflammatory potential; however, the effects of photosensitizers (photodynamic therapy, PDT) are controversial. This study aimed to verify whether the combination of MB and LLLT changes the course of the consolidation of experimental bone defects. Methods: Sixteen Wistar rats underwent femoral bone defects. In the control group (n=4), LLLT simulations were performed without MB. The MB group (n=4) received MB and simulation of LLLT. The LLLT group (n=4) was exposed to LLLT. The PDT+LLLT group (n=4) received MB and LLLT. At the end of 7 or 14 days, the animals were euthanized, and samples were collected. Results: PDT and LLLT induced osteogenic formation with cellularity (after seven days) and union of bony edges (14 days). On the seventh day, LLLT combined with PDT induced an increase (P

Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous disease. In most cases, the initial manifestation occurs in the mouth as multiple ulcerations preceded by blisters that rupture and later spread to other mucous membranes and the skin. Esophageal impairment is rare. We report a case of PV with esophageal involvement in a 53-year-old woman who sought medical care, complaining of diffuse painful lesions in the oral cavity for approximately 1 month, with no improvement with nystatin. Upper digestive endoscopy (UDE) was performed with findings of vesiculobullous lesions in the proximal and middle esophagus, which were biopsied and for which histopathology confirmed PV in the esophageal mucosa. We draw attention to UDE as important for the diagnosis, and it should be indicated in patients with vesiculobullous lesions of the mouth, especially if there are esophageal complaints.

Background Phenol peeling is considered an important agent in the treatment of facial rejuvenation; however, its use has limitations due to its high potential for side effects. Objective This article proposes a new peeling application technique for the treatment of photoaging, aiming to evaluate, clinically and histopathologically, the efficacy of a new way of applying 88% phenol, using a punctuated pattern. Methods The procedure was performed in an outpatient setting, with female patients, on static wrinkles and high flaccidity areas of the face. Accompanying photographs and skin samples were taken for histopathological analysis before and after treatment. Results It was shown that 88% phenol applied topically using a punctuated technique is effective in skin rejuvenation. Conclusion The authors thus suggest, based on this new proposal, that further studies be conducted with a larger group of patients to better elucidate the action mechanisms of 88% phenol. This new form of application considerably reduced patients' withdrawal from their regular activities, besides reducing the cost, compared with the conventional procedure.

Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. β-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40μM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50mg/kg/day) orally administered on EAE-mice. The clinical course, body weight, cytokines and oxygen radicals production were investigated in C57BL/6 EAE-mice. In vitro and in vivo immunological responses were evaluated by ELISA, and CNS sections were stained by hematoxylin and eosin methods The in vitro production of H2O2, NO, IFN-γ, and TNF- α was inhibited by BCP (20 and 40μM) in cultured cells from EAE-mice. BCP (25 and 50mg/kg/day) reduced clinical score and severity of EAE and inhibited H2O2, NO, TNF-α, IFN-γ and, IL-17 production. EAE-mice, orally treated with BCP (mainly at 50mg/kg/day), displayed levels of cytokines and clinical signs similar to animals with no EAE disease, demonstrating the therapeutic action of BCP on EAE animals. Histopathological and histomorphometric analysis confirmed that BCP treatment significantly reduced the numbers of inflammatory infiltrates and attenuated neurological damages in the CNS of EAE-mice.

Selective IgA deficiency is the most common type of primary immunodeficiency, but there is not yet a specific effective treatment. The most prevalent clinical manifestations are infectious diseases of the respiratory system. We report herein the case of an 11-year-old female with selective IgA deficiency and recurring episodes of respiratory infections associated with rhinitis and asthma. We evaluated the efficacy of sublingual immunotherapy combined with inactivated whole-cell bacterial extract and Der p1-specific immunotherapy. After 18 months of clinical follow-up, we observed a significant reduction in the number of episodes of respiratory infections associated with control of atopic diseases. We also observed a 3-fold increase in serum IgA levels compared to treatment initiation. This case demonstrates the potential utility of the concurrent use of sublingual immunotherapy with inactivated whole-cell bacterial extract and Der p1 for successful control of allergy and infection in partial selective IgA deficiency.

The aim of the present study was to investigate the preventive potential of pentoxifylline, atorvastatin and trans-caryophyllene in oral mucositis through histopathological analysis of wounds in the oral mucosa of Wistar rats treated with 5-FU, and to evaluate the immunomodulatory effect of these drugs on serum nitrite production, in situ IFN-γ, TNF-α and TGF-β, and TNF-α in tissues. A total of 32 male Wistar rats with an average age of 9 weeks and an average body weight of 250 g were divided into four treatment groups: Saline, trans-caryophyllene, pentoxifylline and atorvastatin. Oral mucositis was then induced. On days 3 and 4, the mucosa of the mouth of eight pre-treated animals in each group was bilaterally scarified twice with the tip of a sterile needle, with an anesthetic solution. Mucosal samples from animals treated with trans-caryophyllene preserved a thin epithelial lining associated with focal perivascular inflammatory infiltrates. Pentoxifylline-treated animals exhibited total epithelial loss in oral wounds with severe inflammatory infiltrates and mild re-epithelialization associated with mild and diffuse inflammatory infiltrates. Samples from atorvastatin-treated animals exhibited no epithelial dissolution, with preserved thin lining and mild diffuse inflammatory infiltrates. The analysis of TNF-α expression revealed improved results in trans-caryophyllene animals. The analysis of TGF-β expression revealed positive mononuclear cells. Preventive treatment with atorvastatin was demonstrated to modulate the serum expression levels of TNF-α during all stages of the experiment. Treatment with trans-caryophyllene modulated serum IFN-γ levels negatively, whereas treatment with atorvastatin and trans-caryophyllene maintained lower levels of IFN-γ compared with the control group.

Sublingual immunotherapy (SLIT) has been used for more than three decades as a therapeutic strategy for the treatment of allergic diseases. Studies have demonstrated its efficacy and safety, and numerous clinical trials have evaluated these parameters. In the present study, through patient perception, we investigated the patient satisfaction with the use of house dust mite SLIT treatment. “Satisfaction Scale for Patients Receiving Allergen Immunotherapy” (ESPIA) questionnaire, a standardized and validated instrument for clinical studies evaluating allergen immunotherapy, was applied to allergic patients ( N = 136). Children and adults of both sexes who received SLIT for Dermatophagoides pteronyssinus and/or Blomia tropicalis, according to the results of an immediate reading puncture test, were included. Data analysis showed that the perception of treatment effectiveness was 92%, performance improvement in the daily activities was 91%, a satisfactory cost-benefit balance was 84%, and the perception of general satisfaction was 97%. The results showed a high perception of satisfaction in allergic patients undergoing house dust mite SLIT.

Asthma is a chronic inflammatory disease that represents high hospitalizations and deaths in world. Copaiba oil (CO) is popularly used for relieving asthma symptoms and has already been shown to be effective in many inflammation models. This study aimed to investigate the immunomodulatory relationship of CO in ovalbumin (OVA)-induced allergic asthma. The composition of CO sample analyzed by GC and GC–MS and the toxicity test was performed in mice at doses of 50 or 100 mg/kg (by gavage). After, the experimental model of allergic asthma was induced with OVA and mice were orally treated with CO in two pre-established doses. The inflammatory infiltrate was evaluated in bronchoalveolar lavage fluid (BALF), while cytokines (IL-4, IL-5, IL-17, IFN-γ, TNF-α), IgE antibody and nitric oxide (NO) production was evaluated in BALF and lung homogenate (LH) of mice, together with the histology and histomorphometry of the lung tissue. CO significantly attenuated the number of inflammatory cells in BALF, suppressing NO production and reducing the response mediated by TH2 and TH17 (T helper) cells in both BALF and LH. Histopathological and histomorphometric analysis confirmed that CO significantly reduced the numbers of inflammatory infiltrate in the lung tissue, including in the parenchyma area. Our results indicate that CO has an effective in vivo antiasthmatic effect.

BACKGROUND: Gastritis is a very common disorder that is widely distributed worldwide, representing one of the most prevalent pathological entities in Gastroenterology and Digestive Endoscopy. OBJECTIVE: This study aims to analyze the correlation between the endoscopic findings and the histological diagnosis of antral gastritis. METHODS: In this study, 92 reports of upper digestive endoscopy were performed between November 2014 and January 2015, including biopsy of the antral gastric mucosa, comparing the endoscopic and histological findings, which were classified according to the Sidney System. The 92 exams included 35 men and 57 women, ranging in age from 15 to 84 years. The most frequent indication was epigastric pain. RESULTS: Of the 92 examinations analyzed, the histological diagnosis of antral gastritis appeared in 75 exams, 59 endoscopic reports contained the diagnosis of antral gastritis, and 33 endoscopic findings were normal. The kappa coefficient was 0.212 (P

Malignant neoplasia represents the second cause of disease-related mortality and, among all patients diagnosed with cancer, 70% will receive chemotherapy during the course of treatment. As a consequence, an increasing number of researchers have focused their attention on the search for more specific anticancer therapies associated with fewer side effects. Leukopenia is an important adverse effect associated with chemotherapy. Secondary infection is very common among leukopenic patients, directly affecting the continuity of the chemotherapeutic treatment and leading to possible complications in tumor immune defense. Atorvastatin, a type of statin, is a known agent used to control hypercholesterolemia. Trans-caryophyllene, isolated from a resinous oil extracted from the copaiba tree, possesses anti-inflammatory and analgesic properties. The AIM of the present study was to evaluate, through a complete leukocyte count, the systemic immunomodulation potential of pentoxifylline (PTX), atorvastatin and trans-caryophyllene, as well as the possible prophylactic role of these drugs against secondary leukopenia, in an experimental chemotherapy model induced by 5-fluorouracil (5-FU) in wistar rats. A total of 32 male wistar rats were used, 24 of which were submitted to treatment with atorvastatin, PTX and trans-caryophyllene prior to the administration of chemotherapy. The Shapiro-Wilk test was used to verify normality and the Kruskal-Wallis test was used for negative data in the normality test. Among the drugs selected, atorvastatin exhibited the best preventive potential in regards to leukopenia secondary to experimental chemotherapy induced by 5-FU, in comparison to the group receiving saline solution, while PTX amplified such alterations in the leukograms of the animals in this trial.

Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL) on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL) inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35–55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.

IntroductionThe antiphospholipid syndrome (APS) is an autoimmune condition characterized by recurrent arterial and venous thrombosis, besides obstetric complications. The pathogenesis is associated with the presence of antiphospholipid and/or anti-b2-glicoprotein I (anti-b2GPI) antibodies that appear to change the anticoagulant activity of b2GPI. Antibody-induced dimerization of b2GPI seems to be related to the induction of platelet aggregation, contributing to the development of thrombosis in APS.ObjectiveThe objective of the present study is to demonstrate the influence of antiphospholipid antibodies in platelet aggregation tests with different agonists (ADP, collagen, and adrenaline).MethodsWe analyzed platelet aggregation tests with different agonists (ADP, collagen, adrenalin) when normal platelets were exposed to serum with different concentrations of antiphospholipid antibodies.ResultsResults demonstrated a significant inhibition in adrenalin- and ADP-induced platelet aggregation curves (P

BACKGROUND: Our objective was to evaluate changes in serum leptin levels during pregnancy in overweight/obese and non-obese women and to assess total and percent weight gain during pregnancy as possible factors that influence leptin levels. MATERIAL AND METHODS: In a prospective study of 42 low-risk pregnant women receiving prenatal care, we assessed serum leptin levels at gestational weeks 9-12, 25-28, and 34-37. Based on their pre-pregnancy body mass indices (BMIs), the cohort was divided into: non-overweight (BMI

Antonio Carlos Maneira Godinho Netto,1,2 Túlio Gonçalves dos Reis,1,2 Cássia Franco Matheus,1,2 Beatriz Julião Vieira Aarestrup,3,4 Fernando Monteiro Aarestrup1,2,4 1School of Medical and Health Sciences – SUPREMA, 2Maternity Hospital Terezinha de Jesus, 3Morphology Department, Federal University of Juiz de Fora, Institute of Biological Sciences, 4Laboratory of Immunopathology and Experimental Pathology, Federal University of Juiz de Fora, Reproductive Biology Center (CBR), Juiz de Fora, Brazil Objective: To assess the value of fraction of exhaled nitric oxide (FeNO) measurements in the diagnosis of asthma in elderly patients. Methods: The clinical symptoms of 202 elderly patients were assessed with the asthma module of the International Study of Asthma and Allergies in Childhood test, which had been modified for the elderly patients, and the diagnostic routine for chronic obstructive pulmonary disease (COPD), which was based on the Global initiative for chronic Obstructive Lung Disease criteria. Of the 202 patients assessed, 43 were subjected to pulmonary function evaluations (spirometry) and FeNO measurements. Results: Of the 202 elderly patients, 34 had asthma (23 definite and eleven probable), 20 met COPD criteria, 13 presented with an overlap of asthma and COPD, and 135 did not fit the criteria for obstructive pulmonary disease. Among the 43 elderly patients who were subjected to FeNO measurements, ten showed altered results (23.2%) and 33 had normal results (76.7%). The average value of FeNO in patients with definite and probable asthma undergoing this procedure was 29.2 parts per billion whereas that in nonasthmatic patients was 17.5 parts per billion (P=0.0002). Conclusion: We show a clear relationship between FeNO levels and asthma symptoms and previous asthma diagnoses in elderly patients. Keywords: asthma, chronic obstructive pulmonary disease, elderly patients, nitric oxide

The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) in an experimental model of delayed hypersensitivity reaction (DTH). LLLT has been used clinically to treat numerous diseases and has been tested in different experimental models, but some of its effects have yet to be explained. We assessed the effects of LLLT on DTH to ovalbumin (OVA), a protein that has commonly been used as an antigen to sensitize laboratory animals. This experimental model is broadly used to assess the effects of substances that can potentially modulate the immune system and inflammatory reactions. Balb/C mice were randomly divided into four groups: (I) immunized, untreated, and challenged (n = 6); (II) not immunized, untreated, and challenged (n = 6); (III) immunized, treated with azathioprine (AZA), and challenged (n = 6); and (IV) immunized, treated with LLLT, and challenged (n = 6). Forty-eight hours after the challenge, the animals were submitted to a paw edema test and euthanized for histopathology analysis of their plantar pads. The results obtained in DTH units were as follows: Group I, 19.6 ± 8.9; Group II, 5.8 ± 2.6; Group III, 5.6 ± 2.5; and Group IV, 5.2 ± 2.6. DTH was less intense for the groups treated with AZA and laser compared with Group I (p 0.05). We observed no statistical difference between the AZA- and LLLT-treated groups. The slides obtained from the footpad specimens showed that AZA and laser acted similarly on the normal pattern of DTH triggering. Our results suggest that treatment with LLLT has an immunomodulatory effect on DTH to OVA.

Low-level laser therapy (LLLT) has been reported to modulate the healing of wounds by inducing an increase in mitotic activity, fibroblast number, synthesis of collagen, and neovascularization.In the present study we evaluated the effect of LLLT on expression of TGF-beta(2), an immunosuppressive cytokine, at the site of tissue repair, using an experimental rat model to study cutaneous wound healing. In addition, we also investigated the presence of apoptotic cells in epithelial and connective tissue.Thirty male Wistar rats were divided into two groups: group 1, which was subjected to surgical skin wounds only (n = 15), and group 2, which was subjected to surgical skin wounds followed by LLLT (n = 15). In group 2, the LLLT was given with these parameters: 15 mW of power, a dose of 3.8 J/cm(2), for 15 sec for three applications. At 10 d post-surgery and laser application the animals were sacrificed with an overdose of anesthetic and tissue samples from the wounds were submitted to immunohistochemistry and in-situ detection of apoptosis.Most of the inflammatory cells and fibroblasts were TGF-beta(2)-positive, and many apoptotic epithelial cells and fibroblasts were seen in the tissue samples from the LLLT-treated animals. However, a few apoptotic epithelial cells and fibroblasts were also seen in the samples obtained from control animals.Our results indicate that LLLT may be an important inducer of apoptosis during the process of tissue repair. In addition, we demonstrated that LLTT has an immunomodulatory effect on TGF-beta(2) expression at sites of wound healing.

Gingival overgrowth (GO) is a common side effect of chronic cyclosporine use. The average prevalence of GO is about 30%, ranging from 10% to 85% in various series, due to diverse aggravating risk factors: drug interactions with calcium channel blockers, age, cyclosporine dose, bacterial plaque, and genetic predisposition. Recent studies have demonstrated elevated levels of specific cytokines particularly transforming growth factor-beta (TGF-beta) in hyperplastic gingival tissue, suggesting that this growth factor plays a role in the accumulation of the extracellular matrix. Until recently treatment for this complication was only surgical. Nowadays, several studies have been performed to evaluate the effects of antibiotic treatment on the regression of GO. In the present study, we used roxithromycin, a macrolide antibiotic that has inhibitory effect on TGF-beta production by inflammatory cells. The results suggested that roxithromycin may be an important therapeutic tool to reduce cyclosporine-induced GO.

Low-level laser therapy is an important method for the treatment of healing processes, and several experimental studies have been carried out in search of a greater understanding of its therapeutic possibilities. The objective of this study was to review pathogenetic aspects of soft tissue repair to better understand skin lesion healing and the role of low-intensity laser in the progression of tissue healing. This study consists of a concise review of scientific literature data on the use of low-level laser and its influence on wound healing. Many studies have extensively covered the effects of using laser radiation in tissues, describing its beneficial aspects in tissue healing. However, many unanswered questions demand research on the mechanism of action and on parameters of low-level laser use in different stages of wound repair to clarify how this method acts at a cell level in healing processes.

Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-β expression. Together, IL-6 and TGF-β have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin-induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin-induced airway inflammation, whereas the number of neutrophils increased after ovalbumin-induced airway inflammation. The results showed that expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin-induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF-α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced acute airway inflammation is relevant to preventing or treating asthmatic patients that require oxygen supplementation to reverse the hypoxemia.

The development of deformities during the course of leprosy disease is a major public health concern worldwide. It is possible that cytokine production and apoptosis of Schwann cells (SCs) directly affect nerve degeneration and regeneration leading to injury of the myelin sheath and axon. In the present study, the expression of TNFalpha, TGFbeta, and their receptors, in addition to cell death triggered by cytokines or whole Mycobacterium leprae were investigated in a human SC line. The results showed the presence of TNF-Rs and TGF-RII on the SC membrane and the shedding of TNF-Rs during the culture period. Evaluation of cell death was performed through TUNEL and flow cytometry techniques. TNFalpha/TGFbeta combination as well as M. leprae infection triggered an increase in the apoptosis rate in the cultured SC. Moreover, reverse transcriptase-polymerase chain reaction assay revealed that M. leprae upregulated the expression of such cytokines and their receptors on the SC line. Despite the detection of TNFalpha mRNA, no protein was found in the culture supernatants. The data indicate that induction of SC death after cell interaction with M. leprae may, in fact, be implicated in the pathogenesis of nerve damage, which can most likely be modulated by in vivo cytokine production.

In this work we investigated the in vivo protective effects of Baccharis dracunculifolia leaves extract (BdE) against carbon tetrachloride (CCl4)- and acetaminophen (APAP)-induced hepatotoxicity. Total phenolic content, total flavonoid content, antioxidant DPPH radical scavenging activity, and HPLC analysis were performed. Our results showed that pretreatment with BdE significantly reduced the damage caused by CCl4 and APAP on the serum markers of hepatic injury, AST, ALT, and ALP. Results were confirmed by histopathological analysis. Phytochemical analysis, performed by HPLC, showed that BdE was rich in p-coumaric acid derivatives, caffeoylquinic acids and flavonoids. BdE also showed DPPH antioxidant activity (EC50 of 15.75 ± 0.43 μg/mL), and high total phenolic (142.90 ± 0.77 mg GAE/g) and flavonoid (51.47 ± 0.60 mg RE/g) contents. This study indicated that B. dracunculifolia leaves extract has relevant in vivo hepatoprotective properties.

Oral mucositis is a condition that is characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy. Oral mucositis is currently considered to be the most severe complication of anticancer therapy, affecting 40-80% of patients undergoing chemotherapy and almost all those undergoing radiotherapy of the head and neck. Although they do not prevent lesions from appearing, drugs for the treatment of oral mucositis are required to minimize its clinical aggressiveness and improve the nutritional status, hydration and quality of life of the affected patients. Furthermore, the prevention and control of oral ulcers is crucial for cancer prognosis, since the establishment of severe lesions may lead to temporary or permanent treatment discontinuation and compromise cancer control. The objective of this study was to present a review on this condition, its causes and its treatment to professional clinical dentists, in order to help minimize patient suffering. A search was conducted through PubMed, Lilacs and MedLine, to retrieve related articles published between 1994 and 2013.