Therapeutic ultrasound stimulates MC3T3-E1 cell proliferation through the activation of NF-κB1, p38α, and mTOR.

BACKGROUND AND OBJECTIVES: As the population ages, osteometabolic diseases and osteoporotic fractures emerge, resulting in substantial healthcare resource utilization and impaired quality of life. Many types of mechanical stimulation have the potential of being recognized by bone cells after a mechanical sign is transformed into a biological one (a process called mechanotransduction). The therapeutic ultrasound (TU) is one of several resources capable of promoting bone cell mechanical stimulation. Therefore, the main purpose of present study was to evaluate the effect of TU on the proliferation of pre-osteoblasts using in vitro bioassays. STUDY DESIGN/MATERIALS AND METHODS: We used MC3T3-E1 pre-osteoblast lineage cells kept in Alpha medium. Cells were treated using pulsed mode therapeutic ultrasound, with frequency of 1 MHz, intensity of 0.2 W/cm(2) (SATA), duty cycle of 20%, for 30 minutes. Nifedipine and rapamycin were used to further investigate the role of L-type Ca(2+) channels and mTOR pathway. Intracellular calcium, TGF-ß1, magnesium, and the mRNA levels of osteopontin, osteonectin, NF-κB1, p38α were evaluated. RESULTS: The results show that TU stimulates the growth of MC3T3-E1 cells and decreases the supernatant calcium and magnesium content. Also, it increases intracellular calcium, activates NF-κB1 and mTOR complex via p38α. Moreover, TU promoted a decrease in the TGF-ß1 synthesis, which is a cell growth inhibitor. CONCLUSIONS: Therapeutic ultrasound, with frequency of 1 MHz, intensity of 0.2 W/cm(2) (SATA) and pulsed mode, for 30 minutes, was able to increase the proliferation of preosteoblast-like bone cells. This effect was mediated by a calcium influx, with a consequent activation of the mTOR pathway, through increased NF-κB1 and p38α.

Antioxidant, analgesic and anti-inflammatory effects of lavender essential oil.

Several studies have investigated the antinociceptive, immunomodulatory and anti-inflammatory properties of compounds found in the lavender essential oil (LEO), however to date, there is still lack of substantial data. The objective of this study was to assess the antioxidant, anti-inflammatory and antinociceptive effects of lavender essential oil. The 1,1-diphenyl-2-picrylhydrazyl radical decolorization assay was used for antioxidant activity evaluation. The anti-inflammatory activity was tested using two models of acute inflammation: carrageenan-induced pleurisy and croton oil-induced ear edema. The antinociceptive activity was tested using the pain model induced by formalin. LEO has antioxidant activity, which is dose-dependent response. The inflammatory response evoked by carrageenan and by croton oil was reduced through the pre-treatment of animals with LEO. In the pleurisy model, the drug used as positive control, dexamethasone, was more efficacious. However, in the ear swelling, the antiedematogenic effect of the oil was similar to that observed for dexamethasone. In the formalin test, LEO consistently inhibited spontaneous nociception and presented a similar effect to that of tramadol. The results of this study reveal (in vivo) the analgesic and anti-inflammatory activities of LEO and demonstrates its important therapeutic potential.

Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model.

OBJECTIVE AND DESIGN: Mesenchymal stem cells (MSCs) are potent modulators of immune responses. Sepsis is the association of a systemic inflammatory response with an infection. The aim of this study was to test the ability of MSCs derived from adipose tissue, which have immunomodulatory effects, and to inhibit the septic process in an experimental model of mice. METHODS: Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10(6) cells/animal). RESULTS: In the control group, there were no deaths; in the untreated septic group, the mortality rate was 100 % within 26 h; in the septic group treated with MSCs, the mortality rate reached 40 % within 26 h. The group treated with MSCs was able to reduce the markers of tissue damage in the liver and pancreas. The treated group had a reduction of inflammatory markers. Furthermore, the MSCs-treated group was able to inhibit the increase of apoptosis in splenocytes observed in the untreated septic group. CONCLUSIONS: Our data showed that MSCs ameliorated the immune response with decrease of inflammatory cytokines and increase anti-inflammatory IL-10; moreover, inhibited splenocytes apoptosis and, consequently, inhibited tissue damage during sepsis.

Phenolic enriched extract of Baccharis trimera presents anti-inflammatory and antioxidant activities.

Baccharis trimera is a plant popularly used as a tea and to treat gastrointestinal diseases and inflammatory processes as well. The total phenolic content was determined and the antioxidant and anti-inflammatory activities of six extracts (dichloromethane, ethyl acetate, butanol, aqueous, saponin and phenolic) from B. trimera were evaluated. Using carrageenan-induced pleurisy as a model of acute inflammation, the phenolic extract at 15 mg/kg decreased significantly the analyzed parameters when compared to the carrageenan group ( p < 0.05), thus showing potential anti-inflammatory activity. The total phenolic content and antioxidant activity were evaluated by the Folin-Ciocalteau and DPPH methods, respectively. Phenolic and ethyl acetate extracts presented higher antioxidant activity ( p < 0.05) than ascorbic acid. The phenolic extract also showed the highest antioxidant potential in relation to the other extracts, thus suggesting that the antioxidant and anti-inflammatory activities were due to the presence of phenolic compounds.

Anti-inflammatory and immunomodulatory effects of RDV-8 [C18H22N2O2S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] in a rat model of induced pleurisy and in vitro lymphoproliferation.

RDV-8 [C(18)H(22)N(2)O(2)S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] is derived from the 4-thioxopyrimidine, and presents important clinical effects. The present study explored the RDV-8 effects in the proliferation of human peripheral blood mononuclear cells (PBMCs), as well as in a pleurisy-induced rat model. PBMCs were directly plated in four different RDV-8 concentrations (0.0125, 0.025, 0.05 and 0.1 mg/mL). RDV-8 decreased cell proliferation and monocyte chemotactic protein 1 synthesis. The interleukin 1 levels and the cytotoxic effect were not significantly affected by RDV-8 treatment. In the carrageenan-induced pleurisy model, the RDV-8 (3 mg/kg) treatment induced a significant reduction in the exudate volume, in the polymorphonuclear leukocyte migration and in the pleural exudate NO levels. The results indicate that RDV-8 may have an immunomodulatory effect, as well as anti-inflammatory actions suggesting that it could represent a new strategy in the inflammatory response modulation.

Anti-inflammatory effects of red pepper (Capsicum baccatum) on carrageenan- and antigen-induced inflammation.

Inflammation is a pivotal component of a variety of diseases, such as atherosclerosis and tumour progression. Various naturally occurring phytochemicals exhibit anti-inflammatory activity and are considered to be potential drug candidates against inflammation-related pathological processes. Capsicum baccatum L. var. pendulum (Willd.) Eshbaugh (Solanaceae) is the most consumed species in Brazil, and its compounds, such as capsaicinoids, have been found to inhibit the inflammatory process. However, the anti-inflammatory effects of C. baccatum have not been characterized. Thus, this study was designed to evaluate the effects of C. baccatum juice in animal models of acute inflammation induced by carrageenan and immune inflammation induced by methylated bovine serum albumin. Pretreatment (30 min) of rats with pepper juice (0.25-2.0 g kg(-1)) significantly decreased leucocyte and neutrophil migration, exudate volume and protein and LDH concentration in pleural exudates of a pleurisy model. This juice also inhibited neutrophil migration and reduced the vascular permeability on carrageenan-induced peritonitis in mice. C. baccatum juice also reduced neutrophil recruitment and exudate levels of pro-inflammatory cytokines TNF-alpha and IL-1beta in mouse inflammatory immune peritonitis. Furthermore, we demonstrated that the main constituent of C. baccatum juice, as extracted with chloroform, is capsaicin. In agreement with this, capsaicin was able to inhibit the neutrophil migration towards the inflammatory focus. To our knowledge, this is the first demonstration of the anti-inflammatory effect of C. baccatum juice and our data suggest that this effect may be induced by capsaicin. Moreover, the anti-inflammatory effect induced by red pepper may be by inhibition of pro-inflammatory cytokine production at the inflammatory site.

Anti-Inflammatory effects of low-level laser therapy (660 nm) in the early phase in carrageenan-induced pleurisy in rat.

BACKGROUND AND OBJECTIVE: In the classic model of pleurisy there is little evidence about the anti-inflammatory effects of low-level laser therapy (LLLT) as well the dosage characteristics, such as wavelength, total energy, number and pattern of treatment. In this study we investigated the potential effects of LLLT on modulating the pro-inflammatory and anti-inflammatory mediators of acute inflammation in a rat pleurisy model. STUDY DESIGN/MATERIALS AND METHODS: A sample of 48 female Wistar rats were divided into control and experiential groups. An inflammation was induced by carrageenan (0.2 ml) injected into the pleural cavity. At 1, 2, and 3 hours after induction a continuous wave (20 mW) diode laser of the InGaAlP (660 nm) type was used in the four laser groups with different doses and treatment patterns. One group received a single dose of 2.1 J and the other three groups received a total energy of 0.9, 2.1, and 4.2 J. Four hours later the exudate volume, total and differential leukocytes, protein concentration, NO, IL-6, IL-10, TNF-alpha, and MCP-1 were measured from the aspirated liquid. RESULTS: All the treatment patterns and quantity of energy studied show significant reduction of the exudate volume (P<0.05). Using energy of 0.9 J only NO, IL-6, MCP-1 and IL-10 are significantly reduced (P<0.05). On the other hand, higher energies (2.1 and 4.2 J) significantly reduce all variables independently of the treatment pattern. The neutrophil migration has a straight correlation with the TNF-alpha (r = 0.551) and NO (r = 0.549) concentration. CONCLUSIONS: LLLT-660 nm induced an anti-inflammatory effect characterized by inhibition of either total or differential leukocyte influx, exudation, total protein, NO, IL-6, MCP-1, IL-10, and TNF-alpha, in a dose-dependent manner. Under these conditions, laser treatment with 2.1 J was more effective than 0.9 and 4.2 J.

Low-intensity pulsed ultrasound (LIPUS) stimulates mineralization of MC3T3-E1 cells through calcium and phosphate uptake.

The present study aimed to evaluate the effect of low-intensity pulsed ultrasound (LIPUS) on pre-osteoblast mineralization using in vitro bioassays. Pre-osteoblastic MC3T3-E1 cells were exposed to LIPUS at 1 MHz frequency, 0.2 W/cm2 intensity and 20% duty cycle for 30 min. The analyses were carried out up to 336 h (14 days) after exposure. The concentration of collagen, phosphate, alkaline phosphatase, calcium and transforming growth factor beta 1 (TGF-ß1) in cell supernatant and the presence of calcium deposits in the cells were analyzed. Our results showed that LIPUS promotes mineralized nodules formation. Collagen, phosphate, and calcium levels were decreased in cell supernatant at 192 h after LIPUS exposure. However, alkaline phosphatase and TGF-ß1 concentrations remained unchanged. Therapeutic pulsed ultrasound is capable of stimulating differentiation and mineralization of pre-osteoblastic MC3T3-E1 cells by calcium and phosphate uptake with consequent hydroxyapatite formation.

Safety and patient subjective efficacy of using galvanopuncture for the treatment of striae distensae.

BACKGROUND: Striae distensae are linear atrophic dermal scars with associated epidermal atrophy. This recurrent skin disorder causes a significant cosmetic and psychologic concern and remains a therapeutic challenge, especially when they are mature and hypopigmented (striae alba). AIMS: In this prospective single-center study, we evaluated the efficacy, safety, and patient's satisfaction of galvanopuncture for the treatment of striae alba. PATIENTS/METHODS: Thirty-two female subjects with striae alba present on the buttocks were treated with galvanopuncture once a week over a period of 10 weeks. Photographs and a percentage category scale were used to assess striae improvement and patient's satisfaction. Biochemical analyses were performed to assess possible systemic inflammatory effects or oxidative stress induction by the treatment. RESULTS: All patients achieved a substantial increase in clinical improvement in their striae within 10 treatment sessions. Galvanopuncture did not induce any inflammatory effect; however, it reduced oxidative injury. CONCLUSION: The use of galvanopuncture for the treatment of striae alba demonstrated a significant improvement in the lesions with visible results. This study supports the high degree of patient's satisfaction and demonstrate the safe and effective use of galvanopuncture in the treatment of striae alba on several skin types.

Effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life.

The present study aimed to evaluate the long-term effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life. Neonatal Balb/c mice received different treatments on day 10: LPS i.p. injection (100g/kg) (nLPS) or saline i.p. injection (nSal). As adults, fear/anxiety behavior was evaluated in the elevated plus maze. The following week, saline solution or LPS was administered and, after 12h, serum (inflammatory cytokines), liver (mitochondrial complexes and oxidative stress) and adrenal gland samples (angiotensin II type 1 and 2 receptors) were collected. There was an increase in the fear/anxiety behavior in the nLPS group. Neonatal administration of LPS increased the mRNA expression of the AT1 receptor and decreased the mRNA expression of the AT2 receptor in the adrenal glands of males. The complexes II and II-III increased in the nLPS saline male group when compared to control. The LPS administration in adult females, regardless of the neonatal treatment, induced a decrease of the glutathione enzyme activity. There were no differences in the inflammatory cytokines. The results showed that neonatal inflammation influenced mitochondrial respiratory chain metabolism and angiotensin II receptors in a sex-dependent manner. Balb/c mice fear and anxiety behaviors in adulthood were programmed by early life inflammatory stress.