Analysis of inflammation and bone remodeling of atmospheric plasma therapy in experimental periodontitis.

BACKGROUND AND OBJECTIVE: The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. METHODS: Fifty-six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. RESULTS: Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p < .05). The MPO and NAG levels were higher in the P + AP group compared to P group (p < .05). At 4 weeks, the TNF-α level was lower and the IL-10 level was higher in the P + AP group compared to P group (p < .05). In the P + AP group, the IL-1ß level increased in the second week and decreased in the fourth week (p < .05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p < .05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p < .05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p < .05). The OPG level did not differ between the P and P + AP groups (p > .05), but decreased from the second to the fourth experimental week in P + AP group (p < .05). CONCLUSIONS: The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease.

The combined treatment of gold nanoparticles associated with photobiomodulation accelerate the healing of dermonecrotic lesion.

Introduction: The search for fast and efficient treatment for dermonecrotic lesions caused by the venom of the spider from the Loxosceles simillis, is a demand in health. Prednisolone is one of the most used drugs, however it has side effects. In this context, addictionally gold nanoparticles (GNPs) have anti-inflammatory, antioxidant, and antibacterial properties. The use of photobiomodulation has show to be efficient in the process of tissue repair. Therefore, the purpose of this study was to investigate the anti-inflammatory effect of photobiomodulation and GNPs associated or not with a low concentration of prednisolone in animal models of dermonecrotic lesion.Methodology: For this, rabbits with venon-induced dermonecrotic lesion were subjected to topical treatment with prednisolone + laser or GNPs + laser or Pred-GNPs + laser. The area of edema, necrosis and erythema were measured. On the last day of treatment, the animals were euthanized to remove the organs for histopathological and biochemical analysis.Results: All treatments combinations were effective in promoting the reduction of necrotic tissue and erythema.Conclusion: With this results, we suggest that the use of laser and nanoparticles, associated or not with prednisolone, should be considered for the treatment of dermonecrotic injury.

Caloric restriction improves inflammation in different tissues of the Wistar rats with obesity and 2K1C renovascular hypertension.

Renovascular hypertension (RHV) is the cause of high blood pressure due to left renal ischemia, and obesity and hypertension cause an inflammatory response. This work analyzed the inflammatory and tissue repair profile in renal, hepatic, and cardiac tissues in an animal model of RVH associated with a high-fat diet and caloric restriction. The expressions of RORγ-t, IL-17, T-bet, and TNF-α decreased and IFN-γ increased in the right kidney. In relation to the left kidney, caloric restriction decreased the expression of IFN-γ. In the liver, caloric restriction decreased RORγ-t, IL-17, and T-bet. Hypertension associated with obesity decreased the expression of IFN-γ, while caloric restriction increased. In the right kidney, hypertension and obesity, associated or not with caloric restriction, increased the area of collagen fibers. In the heart and liver, caloric restriction reduced the area of collagen fibers. Caloric restriction increased vascular endothelial growth factor, reduced levels of growth transformation factor-ß1 (TGF-ß), and increased collagen I in the left kidney. Hypertension/obesity, submitted or not having caloric restriction, increased TGF-ß in liver. The results suggest that caloric restriction has beneficial effects in lowering blood pressure and regulating tissue proinflammatory cytokines. However, there was no change in the structure and composition of tissue repair markers.

The effectiveness of treadmill and swimming exercise in an animal model of osteoarthritis.

Introduction: Osteoarthritis (OA) is considered an inflammatory and degenerative joint disease, characterized by loss of hyaline joint cartilage and adjacent bone remodeling with the formation of osteophytes, accompanied by various degrees of functional limitation and reduction in the quality of life of individuals. The objective of this work was to investigate the effects of treatment with physical exercise on the treadmill and swimming in an animal model of osteoarthritis. Methods: Forty-eight male Wistar rats were divided (n=12 per group): Sham (S); Osteoarthritis (OA); Osteoarthritis + Treadmill (OA + T); Osteoarthritis + Swimming (OA + S). The mechanical model of OA was induced by median meniscectomy. Thirty days later, the animals started the physical exercise protocols. Both protocols were performed at moderate intensity. Forty-eight hours after the end of the exercise protocols, all animals were anesthetized and euthanized for histological, molecular, and biochemical parameters analysis. Results: Physical exercise performed on a treadmill was more effective in attenuating the action of pro-inflammatory cytokines (IFN-γ, TNF-α, IL1-ß, and IL6) and positively regulating anti-inflammatories such as IL4, IL10, and TGF-ß in relation to other groups. Discussion: In addition to maintaining a more balanced oxi-reductive environment within the joint, treadmill exercise provided a more satisfactory morphological outcome regarding the number of chondrocytes in the histological evaluation. As an outcome, better results were found in groups submitted to exercise, mostly treadmill exercise.

Arnica montana L. associated with microcurrent accelerates the dermis reorganisation of skin lesions.

The aim of this study was to test the effect of electrical stimulation in association with topical Arnica montana gel on organisational changes in the dermis during tissue repair. An experimental rat incisional skin lesion was used for the study. This involved making an incisional lesion on the dorsum of the animals using a scalpel. Ninety-six animals were used divided into the following groups: control (C), microcurrent (MC); topical treatment with Arnica montana gel (ARN); the ARN + microcurrent (ARN + MC). Treatments were administered daily, and injured tissue samples were collected and processed on Days 2, 6 and 10 for dermis analyses. Myeloperoxidase levels were greater in control than in treatment groups on Days 2 and 6. F4/80 expression was similar among all treatment groups and greater than that in control on Day 2. On Day 6, the expression of vascular endothelial growth factor was higher in the MC group than that in other groups, whereas transforming growth factor-ß expression increased in the MC and ARN + MC groups on Day 10. The expression of matrix metalloproteinase-2 was higher in the ARN + MC group when compared with other groups on Day 10. Expression levels of collagen I were increased in the ARN and ARN + MC groups when compared with control and MC groups on Day 6, while expression of collagen III was enhanced in MC, ARN, and ARN + MC groups when compared with the control. The protocol combining microcurrent with topical application of ARN reduces the inflammatory process, increases myofibroblasts proliferation and decreases the presence of macrophages in the dermis during skin repair in rats.

Electrical stimulation therapy and rotary jet-spinning scaffold to treat bone defects.

The combination of electrical stimulation (ES) and bone tissue engineering (BTE) has been successful in treatments of bone regeneration. This study evaluated the effects of ES combined with PCL + ß-TCP 5% scaffolds obtained by rotary jet spinning (RJS) in the regeneration of bone defects in the calvaria of Wistar rats. We used 120 animals with induced bone defects divided into 4 groups (n = 30): (C) without treatment; (S) with PCL+ ß-TCP 5% scaffold; (ES) treated with ES (10 µA/5 min); (ES + S) with PCL + ß-TCP 5% scaffold. The ES occurred twice a week during the entire experimental period. Cell viability (in vitro: Days 3 and 7) and histomorphometric, histochemical, and immunohistochemical (in vivo; Days 30, 60, and 90) analysis were performed. In vitro, ES + S increased cell viability after Day 7 of incubation. In vivo, it was observed modulation of inflammatory cells in ES therapy, which also promoted blood vessels proliferation, and increase of collagen. Moreover, ES therapy played a role in osteogenesis by decreasing ligand kappa B nuclear factor-TNFSF11 (RANKL), increasing alkaline phosphatase (ALP), and decreasing the tartarate-resistant acid phosphatase. The combination of ES with RJS scaffolds may be a promising strategy for bone defects regeneration, since the therapy controlled inflammation, favored blood vessels proliferation, and osteogenesis, which are important processes in bone remodeling.

Intra-articular Treatment with Triamcinolone Hexacetonide Associated with Gold Nanoparticles Reduces Cartilage Degeneration in an Animal Model of Osteoarthritis.

INTRODUCTION: The association between triamcinolone hexacetonide (TH) and gold nanoparticles (GNPs) represents a promising treatment due to the potential anti-inflammatory and antioxidant effects of these compounds. In this study, we evaluated the effects of intra-articular treatment of TH associated with GNPs in a mechanical model of osteoarthritis (OA). METHODS: Fifty Wistar rats were divided into five groups: Sham; OA; OA+TH; OA+GNPs; OA+TH-GNPs. Both applications were performed 30 and 60 days after the model was induced. After 30 days of the last application, the animals were euthanized. RESULTS: Only the combined treatment with TH and GNPs promoted a reduction in proinflammatory cytokines and an increase in anti-inflammatory cytokines. The OA+TH-GNPs group obtained a significant reduction in the production of oxidants and oxidative damage markers while an increase in antioxidants. Histologically, all treated groups showed results of a significant increase in cartilage thickness and chondrocyte count, the OA+TH-GNPs group had similar behavior to the group without osteoarthritis, with significantly smaller amounts of chondrocytes than the OA group. CONCLUSION: The intra-articular use of TH associated with GNPs may be able to prevent the progression of the pathology and minimize joint degradation.

Effects of the Application of Decellularized Amniotic Membrane Solubilized with Hyaluronic Acid on Wound Healing.

A perfect graft for wound care must be readily available without affecting the immune response, covering and protecting the wound bed. Considering previous studies have already established the use of hyaluronic acid (HA) for the treatment of wounds but the data presented on the amniotic membrane (AM) and its promising effects on healing still requires further investigation, this study aimed to evaluate the effects of the application of a decellularized amniotic membrane solubilized with hyaluronic acid on the healing process of cutaneous wounds on the 7th and 14th day, to evaluate the evolution of the wound and the inflammatory phases in these two times. Cutaneous lesions were excised from the dorsal region and 96 Wistar rats were divided into four groups: I-Excisional wound (EW); II-EW + AM; III-EW + HA; IV-EW + AM + HA. The present study demonstrated that the proposed combined therapy favors the tissue repair process of the epithelial lesion. Results showed a reduction in pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, an increase in TGF-ß, and attenuation of oxidative stress, reducing the acute inflammatory response and promoting the beginning of tissue repair. We concluded that the proposed therapies accelerated the inflammatory process with anticipation of the repair phase.

Photobiomodulation and photodynamic therapy applied after electrocauterization for skin healing optimization in rats.

Photobiomodulation-PBM and Photodynamic Therapy-PDT have been used to induce healing. However, the effects of these therapies on skin-lesions induced by electrocautery are unknown, aiming at more favorable clinical and esthetic results. Electrocauterization was done in 78-female Wistar-rats using a system that includes an electrocautery and red-LED. The groups were: No injury, Injury, Injury + ALA (topical 5-aminolevulinic acid application), Injury + LED and Injury + ALA + LED (topical ALA application followed by photoactivation with LED). After 2nd, 7th and 14th days post-injury, immuno-histomorphometric analyses (inflammatory infiltrate, blood vessels, fibroblasts, eschar/epidermal thickness, IL-10 and VEGF) and biochemical assays of MPO (neutrophil), NAG (macrophage), nitrite, DCF (H2 O2 ), carbonyl (membrane's damage), sulfhydryl (membrane's integrity), SOD, GSH, hydroxyproline and re-epithelialization area were performed. The Injury + LED and Injury + ALA + LED groups controlled inflammation and oxidative stress, favoring angiogenesis, fibroblasts proliferation and collagen formation. Therefore, the PBM or PDT was effective in tissue formation with thinner eschar and epidermis, resulting in less scarring after electrocauterization.

Intra-articular treatment with hyaluronic acid associated with gold nanoparticles in a mechanical osteoarthritis model in Wistar rats.

This study aimed to evaluate the effects of intra-articular treatment with hyaluronic acid (HA) associated with GNPs in a mechanical model of osteoarthritis induced by median meniscectomy (MM). Fifty Wistar rats (2 months weighing between 250 and 300 g) were used, divided into five groups of 10 animals each: Sham, osteoarthritis (OA), OA + HA, OA + gold nanoparticles (GNPs), and OA + HA + GNPs. Intra-articular treatment was started 30 days after the model was induced, with a frequency of 2 weeks for 60 days. Fifteen days after the last application, the animals were euthanized with the removal of the joint tissue for biochemical and histological analysis. The model used was able to mimic osteoarthritis, characterized by the presence of high levels of proinflammatory cytokines, oxidative stress, and degeneration of joint surfaces (Grade III, according to SCORE OARSI). The isolated use of HA or GNPs provided beneficial results to the joint; however, only the group subjected to the association between HA and GNPs showed the attenuation of oxidative stress and reduced proinflammatory markers, with a simultaneous increase in levels of anti-inflammatory cytokines and growth factors. Upon histological analysis, only the OA + HA + GNPs group achieved the restoration of the thickness of the joint cartilage with reduced damage and return to the intact joint surface. The results found demonstrated that the association of GNPs with HA was able to reverse the deleterious effects caused by the model by inhibiting the progressive degeneration of joint surfaces, representing a promising treatment for osteoarthritis.

Influence of microcurrent on the modulation of remodelling genes in a wound healing assay.

The literature has shown the beneficial effects of microcurrent (MC) therapy on tissue repair. We investigated if the application of MC at 10 µA/90 s could modulate the expression of remodeling genes transforming growth factor beta (Tgfb), connective tissue growth factor (Ctgf), insulin-like growth factor 1 (Igf1), tenascin C (Tnc), Fibronectin (Fn1), Scleraxis (Scx), Fibromodulin (Fmod) and tenomodulin in NIH/3T3 fibroblasts in a wound healing assay. The cell migration was analyzed between days 0 and 4 in both fibroblasts (F) and fibroblasts + MC (F+MC) groups. On the 4th day, cell viability and gene expression were also analyzed after daily MC application. Higher expression of Ctgf and lower expression of Tnc and Fmod, respectively, were observed in the F+MC group in relation to F group (p < 0.05), and no difference was observed between the groups for the genes Tgfb, Fn1 and Scx. In cell migration, a higher number of cells in the scratch region was observed in group F+MC (p < 0.05) compared to group F on the 4th day, and the cell viability assay showed no difference between the groups. In conclusion, MC therapy at an intensity/time of 10 µA/90 s with 4 daily applications did not affect cell viability, stimulated fibroblasts migration with the involvement of Ctgf, and reduced the Tnc and Fmod expression.

Anti-inflammatory and antimicrobial effects of Zingiber officinale mouthwash on patients with fixed orthodontic appliances.

INTRODUCTION: This study aimed to assess the anti-inflammatory and antimicrobial effects of mouthwashes with 0.12% chlorhexidine (CLX) and 0.5% Zingiber officinale essential oil (ZOEO). METHODS: The gas chromatography-mass spectrometry of ZOEO was developed, and the mouthwash was prepared. Thirty-one adult subjects of both sexes with fixed orthodontic appliances were selected. For 7 days, the mouthwashes with CLX, ZOEO, and flavored sterile water placebo were used randomly, with a 15-day interval between each solution. Saliva was collected before the first mouthwash, 1 minute and 15 minutes after it, and on the seventh day. The patients were subjected to clinical examinations of the bonded bracket index proposed by Ciancio, bleeding on probing, and sensory analysis (flavor). Generalized linear models were used to assess in vitro cell viability. The GENMOD procedure was used to assess the changes of bleeding on probing, and Friedman and Wilcoxon tests were used for data on colony-forming units per milliliter (CFU/mL), bonded bracket index, and flavor, at the 5% significance level. RESULTS: In the microbiologic analysis, the ZOEO mouthwash presented antimicrobial effectiveness for Streptococcus mutans as well as the CLX mouthwash, but it did not show the same substantivity. The ZOEO was efficient in controlling dental biofilm and reducing gingival bleeding. The sensory analyses showed that the flavor for ZOEO and CLX solutions presented low acceptability. CONCLUSIONS: The ZOEO mouthwash has an anti-inflammatory property with an effect on reducing gingival bleeding. However, it requires adjustments to the formulation to improve flavor quality.

Effects of Percutaneous Collagen Induction Therapy Associated with Hyaluronic Acid on Inflammatory Response, Oxidative Stress, and Collagen Production.

Percutaneous collagen induction (PCI) is an alternative treatment for skin dysfunctions, it aims to stimulate collagen production by encouraging normal wound healing that occurs after any trauma by inducing microlesions; also it may be potentiated with the association with drugs such as hyaluronic acid (HA). Our objective was to evaluate the effects of PCI associated with hyaluronic acid (0.9%) on inflammatory process, oxidative stress, and collagen production in rat epidermis. For the study, 36 adult Wistar rats were randomly divided into 6 groups (n = 6): Control; PCI 0.5; PCI 1.0; HA; PCI 0.5 + HA; and PCI 1.0 + HA. The animals were anesthetized, trichotomized, and the application of therapies was performed once; After 7 days, the animals were euthanized for removal of the skin region. Levels of pro-inflammatory (IL1, IL6, TNFα), anti-inflammatory (IL4 and IL10) cytokines and growth factors (FGF, TGFß) were evaluated, besides oxidative stress parameters and histological analysis. In combination groups, there is a decrease in TNFα compared with the control and PCI groups in contrast to a significant increase in anti-inflammatory cytokines and growth factors. Oxidant and oxidative damage levels showed a significant decrease in PCI + HA groups in relation to PCI groups while antioxidant defense increased in PCI + HA groups compared with the control group. The number of fibroblasts was increased in the PCI 1.0 group in relation to the control, HA, and PCI 0.5. The number of blood vessels and collagen area was increased in groups PCI and PCI + HA compared with the HA group. We conclude that the combination of PCI with HA is able to accelerate the acute inflammatory process, reducing its deleterious effects and anticipating the chronic response, contributing to tissue repair.

Inhibitory effect of red LED irradiation on fibroblasts and co-culture of adipose-derived mesenchymal stem cells.

The objective of this study was to evaluate the effects of red Light Emiting Diode (red LED) irradiation on fibroblasts in adipose-derived mesenchymal stem cells (ASC) co-culture on the scratch assay. We hypothesized that red LED irradiation could stimulate paracrine secretion of ASC, contributing to the activation of genes and molecules involved in cell migration and tissue repair. ASC were co-cultured with NIH/3T3 fibroblasts through direct contact and subjected to red LED irradiation (1.45 J/cm2/5min6s) after the scratch assay, during 4 days. Four groups were established: fibroblasts (F), fibroblasts + LED (FL), fibroblasts + ASC (FC) and fibroblasts + LED + ASC (FLC). The analyzes were based on Ctgf and Reck expression, quantification of collagen types I and III, tenomodulin, VEGF, TGF-ß1, MMP-2 and MMP-9, as well as viability analysis and cell migration. Higher Ctgf expression was observed in FC compared to F. Group FC presented higher amount of tenomodulin and VEGF in relation to the other groups. In the cell migration analysis, a higher number of cells was observed in the scratched area of the FC group on the 4th day. There were no differences between groups considering cell viability, Reck expression, amount of collagen types I and III, MMP-2 and TGF-ß1, whereas TGF-ß1 was not detected in the FC group and the MMP-9 in none of the groups. Our hypothesis was not supported by the results because the red LED irradiation decreased the healing response of ASC. An inhibitory effect of the LED irradiation associated with ASC co-culture was observed with reduction of the amount of TGF-ß1, VEGF and tenomodulin, possibly involved in the reduced cell migration. In turn, the ASC alone seem to have modulated fibroblast behavior by increasing Ctgf, VEGF and tenomodulin, leading to greater cell migration. In conclusion, red LED and ASC therapy can have independent effects on fibroblast wound healing, but the combination of both does not have a synergistic effect. Therefore, future studies with other parameters of red LED associated with ASC should be tested aiming clinical application for tissue repair.

Effects of the Association between Photobiomodulation and Hyaluronic Acid Linked Gold Nanoparticles in Wound Healing.

Healing is the process responsible for restoring the integrity of the body's internal or external structures when they rupture. Photobiomodulation (PBM) stands out as one of the most efficient resources in the treatment of epithelial lesions, as well as hyaluronic acid (HA), which has been emerging as a new molecule for the treatment of dermal and epidermal lesions. The biological application of gold nanoparticles (GNPs) shows promising results. This study aimed to investigate the possible anti-inflammatory and antioxidant effects of the association between PBM and GNPs-linked HA in an epithelial lesion model. Fifty Wistar rats were randomly distributed in the Control Group (CG); (PBM); (PBM + HA); (PBM + GNPs); (PBM + GNPs-HA). The animals were anesthetized, trichotomized, and induced to a surgical incision in the dorsal region. Topical treatment with HA (0.9%) and/or GNPs (30 mg/kg) occurred daily associated with 904 nm laser irradiation, dose of 5 J/cm2, which started 24 h after the lesion and was performed daily until the seventh day. The levels of proinflammatory (IL1 and TNFα), anti-inflammatory (IL10 and IL4) and growth factors (FGF and TGFß) cytokines and oxidative stress parameters were evaluated, besides histological analysis through inflammatory infiltrate, fibroblasts, new vessels, and collagen production area. Finally, for the analysis of wound size reduction, digital images were performed and subsequently analyzed by the IMAGEJ software. The treated groups showed a decrease in proinflammatory cytokine levels and an increase in anti-inflammatory cytokines. TGFß and FGF levels also increased in the treated groups, especially in the combination therapy group (PBM + GNPs-HA). Regarding the oxidative stress parameters, MPO, DCF, and Nitrite levels decreased in the treated groups, as well as the oxidative damage (Carbonyl and Thiol groups). In contrast, antioxidant defense increased in the groups with the appropriate therapies proposed compared to the control group. Histological sections were analyzed where the inflammatory infiltrate was lower in the PBM + GNPs-HA group. The number of fibroblasts was higher in the PBM and PBM + HA treated groups, whereas collagen production was higher in all treated groups. Finally, in the analysis of the wound area contraction, the injury group presented a larger area in cm2 compared to the other groups. Taken together, these results allow us to observe that the combination of PBM + GNPs-HA optimized the secretion of anti-inflammatory cytokines, proliferation and cell differentiation growth factors, and made an earlier transition to the chronic phase, contributing to the repair process.

Effects of phonophoresis with ibuprofen associated with gold nanoparticles in animal model of traumatic muscle injury.

The repair process consists of molecular and cellular events that can be accelerated by specific therapies. Considering this, the objective of this study was to evaluate the effects of ibuprofen phonophoresis associated with gold nanoparticles in the animal model of traumatic muscle injury. Was used 80 male wistar rats divided into eight groups: Sham; Muscle injury (MI); MI + therapeutic pulsed ultrasound (TPU); MI + Ibuprofen (IBU); MI + GNPs; MI + TPU+ IBU; MI + TPU + GNPs and MI + TPU + IBU + GNPs. The lesion in the gastrocnemius was performed by a single direct trauma impact on the injured press. The animals were treated with pulsed ultrasound and the gel with gold nanoparticles and/or ibuprofen. The treatment was applied daily for 5 days and the first session was 12 h after the muscle injury. The gastrocnemius muscle was surgically removed for analyzes biochemical, molecular and histological. In the analyzes only the MI + TPU + IBU + GNPs group showed a reduction in TNF-a and IL-1 levels, with a concomitant increase in the levels of anti-inflammatory cytokines. In the analysis of oxidative stress, only the MI + TPU + IBU + GNPs group presented a reversal of the condition when compared to the MI group. In the histological analysis, the MI group presented a large cell infiltrate and a centralized nucleus and only the MI + TPU + IBU + GNPs group showed a structural improvement, also in the pain results the MI + TPU + IBU + GNPs showed a significant difference in comparison to the MI group (p<0.01). We believe that the effects of phonophoresis with anti-inflammatory drugs associated with gold nanoparticles may potentiate the reduction of the inflammatory response and regulate the cellular redox state.

Do electrical current and laser therapies improve bone remodeling during an orthodontic treatment with corticotomy?

OBJECTIVES: Evaluate the bone remodeling during orthodontic movement with corticotomy when submitted to low-intensity electrical stimulation application (microcurrent-MC) and low-level laser therapy (LLLT). MATERIAL AND METHODS: One hundred and fifty Wistar rats were divided into the following 5 groups: (C) submitted to tooth movement; (Cort) tooth movement/corticotomy; (Cort-L) tooth movement/corticotomy/laser AsGaAl 808 nm (4.96J/50s); (Cort-Mc) tooth movement/corticotomy/microcurrent (10 µA/5 min); (Cort-L-Mc) tooth movement/corticotomy and laser/microcurrent alternated. Inflammation, angiogenesis, and osteogenesis were evaluated in the periodontal ligament (PDL) and alveolar bone on the 7th, 14th, and 21st days of orthodontic movement. RESULTS: The quantification of inflammatory infiltrate, angiogenesis and expression of TGF-ß1, VEGF, and collagen type I were favorably modulated by the application of therapies such as low-level laser therapy (LLLT), MC, or both combined. However, electrical stimulation increased fibroblasts, osteoclasts and RANK numbers, birefringent collagen fiber organization, and BMP-7 and IL-6 expression. CONCLUSIONS: Low-level laser therapy (LLLT) and MC application both improved the process of bone remodeling during orthodontic treatment with corticotomy. Still, electrical current therapy promoted a more effective tooth displacement but presented expected root resorption similar to all experimental treatments. CLINICAL RELEVANCE: It is important to know the effects of minimally invasive therapies on cellular and molecular elements involved in the bone remodeling of orthodontic treatment associated with corticotomy surgery, in order to reduce the adverse effects in the use of this technique and to establish a safer clinical routine.

Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo.

Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 µg crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-α, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5⁻0.6 OD/mg) and MPO (0.1⁻0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 µg crotamine resulted in serum NO (64.7 µM) and local tissue NO (58.5 µM) levels higher or equivalent to those recorded for their respective histamine controls (55.7 µM and 59.0 µM). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4⁻45.8 mg/mL), which was significantly greater than control values. Crotamine (400 µg) also caused an increase in serum TNF-α, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0⁻1.8 µM/mL) and decrease in SH levels (124.7⁻19.5 µM/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form.

Electrical stimulation: Complementary therapy to improve the performance of grafts in bone defects?

The limitations of bone reconstruction techniques have stimulated the tissue engineering for the repair of large bone defects using osteoconductive materials and osteoinductive agents. This study evaluated the effects of low intensity electric current on the inorganic bovine graft in calvaria defects. Bone defects were performed with piezoelectric system in the calvaria of Wistar rats divided into four groups (n = 24): (C) without grafting and without electrical stimulation; (E) with grafting; (MC) without grafting and submitted to electrical stimulation; (MC + E) with grafting and submitted to electrical stimulation. Inflammatory, angiogenic and osteogenic events during bone repair at the 10th, 30th, 60th, and 90th days were considered. Several inflammatory markers demonstrated the efficacy of grafting in reducing inflammation, particularly when subjected to electrical stimulation. Angiogenesis and collagen organization were more evident by electrical stimulation application on the grafts. Moreover, the osteogenic cell differentiation process indicated that the application of microcurrent on grafting modulated the homeostasis of bone remodeling. It is concluded that microcurrent favored the performance of grafts in calvarial rat model. Low-intensity electrical current might improve the osteoconductive property of grafting in bone defects. Therefore, electrical current becomes an option as complementary therapy in clinical trials involving bone surgeries and injuries. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 924-932, 2019.

Struthanthus vulgaris ointment prevents an over expression of inflammatory response and accelerates the cutaneous wound healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Struthanthus vulgaris (Vell.) Mart. (Loranthaceae) has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and to treat various skin disorders, including wounds. AIMS OF THE STUDY: To investigated the influence of 5% Struthanthus vulgaris ointment during cutaneous wound healing in rats. MATERIALS AND METHODS: Twenty Wistar rats were used in each group according the daily treatment, S. vulgaris 5% ointment (SV 5%) and vehicle control groups. Four full thicknesses wounds were punched in back side skin of each animal, and five animals were sacrificed after 2, 7, 14 and 21 days after surgery for histological, immunological and biochemical analysis. RESULTS: A significant wound closured area in the S. vulgaris 5% group of about 38% and 35% as compared to 19% and 21% in the control group was observed after 2 and 5 days, respectively. Histological and biochemical analysis of the skin biopsies showed that S. vulgaris treated wounds exhibited increased granulation tissue and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines like IL-1α, TNF-α and IL-10, nitric oxide and, growth factors like TGF-ß. Moreover, S. vulgaris showed a marked and robust increase in the deposition and organization of collagen fibers in the wounds, and improve the quality of the scar tissue. CONCLUSIONS: Altogether these data revealed that S. vulgaris seems to prevent an over expression of inflammation and accelerates wound epithelialization and might be beneficial for treating healing disorders.