Fernando Monteiro Aarestrup

Modulação da proliferação fibroblástica e da resposta inflamatória pela terapia a laser de baixa intensidade no processo de reparo tecidual

BACKGROUND: Several studies have been performed to understand the tissue repair process as well as the possible effects of laser therapy in wound healing. OBJECTIVES: To study the behavior of skin wounds induced in the dorsal region of Wistar rats (Rattus norvegicus), which were submitted to the low-intensity laser therapy at 3.8 J/cm2 dosage, 15mW potency, during 15 seconds. MATERIAL AND METHODS: The animals (n=12) were divided into two groups - control and laser-treated. The latter comprised three applications (immediately after surgery, 48 hours and 7 days after induction of surgical wounds). Ten days after surgery samples of the wounds were collected and submitted to histopathological and histomorphometric studies. RESULTS: Neovascularization, fibroblast proliferation and reduced inflammatory infiltrate in surgical wound submitted to laser therapy were demonstrated. CONCLUSION: Taken together, the results suggest that low-intensity laser therapy is an effective method to modulate tissue repair, thus significantly contributing to a faster and more organized healing process.

Effects of low-level laser therapy on the progress of wound healing in humans: the contribution of in vitro and in vivo experimental studies

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.

Low-Level Laser Therapy Increases Transforming Growth Factor-β2 Expression and Induces Apoptosis of Epithelial Cells During the Tissue Repair Process

BACKGROUND DATA 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. OBJECTIVE 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. MATERIALS AND METHODS 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. RESULTS 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. CONCLUSION 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.

Effect of thalidomide and pentoxifylline on experimental autoimmune encephalomyelitis (EAE)

BACKGROUND Autoimmune encephalomyelitis (EAE) in Lewis rats is a classical experimental model of demyelinating inflammatory disease of the central nervous system. EAE is widely accepted for study of immune-inflammatory mechanisms in the CNS related to multiple sclerosis (MS) due to similar clinical evolution. OBJECTIVES In the present study we investigated the effects of Thalidomide and pentoxifylline during EAE development in Lewis rats. METHODS EAE was induced in Lewis rats and treatment with Thalidomide or pentoxifylline was performed. Clinical evaluation was carried out daily. Histopathological analysis of the brain tissue and spinal cord was performed. Griess method was used for determination of NO serum levels. TNF-alpha and IFN-gamma serum levels were investigated using ELISA method. RESULTS Thalidomide and pentoxifylline treatment is associated with significant reduction of neuroinflammation in CNS. Serum levels of NO, IFN-gamma and TNF-alpha showed a marked reduction. Such findings were correlated with improvement of clinical symptoms, particularly in thalidomide treated rats. CONCLUSIONS Taken together the data suggested that thalidomide and pentoxifylline may be therapeutic options for the treatment of MS, however further experiments must be performed to investigate this hypothesis.

Cellular profile of the peritumoral inflammatory infiltrate in squamous cells carcinoma of oral mucosa: Correlation with the expression of Ki67 and histologic grading

BackgroundSquamous cells carcinoma is the most important malignant tumor with primary site in the oral cavity and, given the great exposure of mucosa and lips to the etiologic factors of this neoplasm, its incidence is high. Investigation of the prognostic determinants is significant for the expectations of treatment proposal and cure of the patient. The local immune response represented by peritumoral inflammatory infiltrate is a possible prognostic factor.MethodsIn this study, oral mucosa samples of squamous cells carcinoma were analyzed, separated according to their histological classification as well as the phenotypical profile of the cells comprising the peritumoral inflammatory infiltrate was investigated by immunohistochemical method, in addiction, the cell proliferation index via protein Ki67 expression was determinated.ResultsThe T lymphocytes made up most of this inflammatory infiltrate, and among these cells, there was a predominance of T CD8 lymphocytes relative to the T CD4 lymphocytes. The B lymhocytes were the second most visualized leucocyte cell type followed by macrophages and neutrophils. The immunohistochemical assessment of Ki-67 positive cells revealed a greater expression of this protein in samples of undifferentiated squamous cells carcinoma.ConclusionThe results suggest that the cellular immune response is the main defense mechanism in squamous cells carcinoma of oral mucosa, expressed by the large number of T lymphocytes and macrophages, and that the greatest intensity of local response may be associated with the best prognosis.

Roxithromycin Reduces Cyclosporine-Induced Gingival Hyperplasia in Renal Transplant Patients

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.

Body weight gain and serum leptin levels of non-overweight and overweight/obese pregnant women

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/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 <25 kg/m2) and overweight/obese (BMI ≥25 kg/m2) subjects. Results We found a progressive increase in maternal weight gain during pregnancy in both groups. There was also a progressive increase in leptin levels in the 2 strata; however, the increase was significantly higher in the non-overweight patient group. We found that non-overweight pregnant women had a noticeably larger total weight gain. When analyzing the percent weight gain during pregnancy compared to the pre-pregnancy weight, the non-overweight group had a significantly greater percent weight gain than the overweight/obese group. Conclusions Our results suggest that the greater increase in leptin levels in non-overweight pregnant women can be explained by the higher percent weight gain in this group compared to overweight/obese women. These findings suggest that controlling the percent weight gain may be an important preventive measure when controlling leptin levels during pregnancy and subsequent medical complications.

Protective Effects of Baccharis dracunculifolia Leaves Extract against Carbon Tetrachloride- and Acetaminophen-Induced Hepatotoxicity in Experimental Animals

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.

Copaiba Oil Suppresses Inflammatory Cytokines in Splenocytes of C57Bl/6 Mice Induced with Experimental Autoimmune Encephalomyelitis (EAE)

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.

The effect of essential oil of Syzygium cumini on the development of granulomatous inflammation in mice

The anti-inflammatory and apoptotic activity of the essential oil of Syzygium cumini (L.) Skeels, Myrtaceae, leaves was investigated in vivo. The antiinflammatory action and chronic granulomatous inflammation in BALB/c mice, intravenously infected with Mycobacterium bovis, BCG, (Bacillo Calmet Guerim), was judged by measuring and classifying the granulomas formed in the hepatic parenchyma. The degree of apoptosis in the inflammatory cells was also measured. A reduction in the granulomatous area and a change in the pattern of the granulomas were found. Anti-mycobacterial activity of the essential oil against M. bovis was detected in vitro by an interferometric method in liquid culture medium. The chemical constituents of the essential oil were determined by GC/MS. Higher yields of the essential oil of S. cumini leaves were obtained by extraction in a Clevenger apparatus when the fresh leaves were previously frozen as a pre-processing step. The essential oil obtained from this plant demonstrated a statistically significant and dramatic effect in the chosen model system.