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Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose–response relationship. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate whether sleep deprivation can induce degenerative changes in rat sublingual glands. Methods: For this purpose, a total of 24 males were distributed into three groups: control (n = 8), in which the animals were not subjected to any procedure; sleep deprivation (n = 8) in which the animals were submitted to sleep deprivation for 96 h; recovery (n = 8), in which the animals were subjected to paradoxical sleep deprivation for 96 consecutive hours followed by 96 h without intervention. Morphological changes in sublingual glands as well as the immunoexpressions of some proteins, such as Ki-67, p16, cleaved caspase-3 and BCL-2 were investigated in this setting. Results: The results showed that paradoxical sleep deprivation induced tissue degeneration as a result of the presence of pyknosis, vacuoles and areas of salivary retention, in the experimental groups. Expression of cleaved caspase 3 and BCL-2 were increased in both sleep deprivation and recovery groups. The analysis of Ki-67 showed an increase in expression only in the recovery group, associated with a decrease in p16 levels. Conclusion: Sleep deprivation can induce a degenerative process in the parenchyma of sublingual gland by means of dysregulation of apoptosis associated with proliferative activity. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate if paradoxical sleep deprivation induces some tissue changes in the parotid gland of rats. Methods: A total of 24 male Wistar rats were distributed into the following groups, as follows: Group 1-Control (CTRL; n = 8); Group 2-Sleep deprivation (PS; n = 8): the animals were submitted to Paradoxical Sleep deprivation for 96 h and Group 3-Recovery (R; n = 8): the animals were submitted to sleep loss for 96 h, followed by a period of 96 h without any intervention. The following parameters were evaluated: microscopic analysis, immunohistochemistry for Caspase-3, Ki-67, and COX-2 and gene expression of cytochrome C, TNF-α, and Interleukins 6, 10. Results: The results pointed out acinar atrophy, and the presence of cytoplasmic vacuoles in the parenchyma of the experimental groups. In the same groups, there was differential expression of interleukins 6, 10 and TNF-α. Apoptosis was also increased by means of cleaved caspase 3 expression. The cellular proliferation (ki-67 expression) was increased the R group. Conclusion: Taken together, sleep deprivation induces tissue degeneration, inflammatory process, as well as activate apoptosis in the parotid gland of rats. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate cytogenotoxicity in mammalian cells induced by ingestion of superficial water from SESS. For this purpose, surface water was collected from two points of SESS: São Vicente Channel (SVC) and Piaçaguera Channel (PIC). Four groups (n = 5) of adult male Wistar (8 weeks old) received for 5 days: (a) filtered tap water (water control), (b) tap water with 2.4% of NaCl (saline control), (c) estuarine water from PIC and (d) estuarine water from SVC. Results demonstrated that Ki67 immunoexpression was higher in hepatocytes exposed to both sampling site, while caspase-3 demonstrated downregulation in rat liver exposed to estuarine water. There was also significant increase in micronuclei frequency in bone marrow cells and hepatocytes, and DNA damage in blood and liver of rats exposed to estuarine water from SVC and PIC. In summary, studies with complex mixtures, such as contaminated estuarine water are important since this work confirmed by experiments using in vivo mammalian cells of rats that SESS water are genotoxic, mutagenic and cytotoxic, denoting concern for environmental health. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the therapeutic properties of Mimosa caesalpiniifolia in liver of rats exposed to cadmium under morphological, oxidative, inflammatory, and mutagenic parameters. A total of 40 Wistar rats (90 days, ~ 250 g) were distributed into eight groups (n = 5) as follows: (i) control; (ii) cadmium: cadmium chloride injection at 1.2 mg/kg; (iii) Mimosa extract: treatment with Mimosa extract at 250 mg/kg; (iv) Mimosa fraction: treatment with Mimosa acetate fraction at 62.5 mg/kg; (v) cadmium and Mimosa extract 62.5: submitted to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 62.5 mg/kg; (vi) cadmium and Mimosa extract 125: subjected to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 125 mg/kg; (vii) cadmium and Mimosa 250 extract: submitted to cadmium chloride 1.2 mg/kg injection and treatment with Mimosa extract at 250 mg/kg; (viii) cadmium treated with fraction of Mimosa acetate: submitted to cadmium chloride 1.2 mg/kg injection and treatment with acetate fraction of Mimosa extract at 62.5 mg/kg. In the animals intoxicated with cadmium and treated with fraction [62.5], increased expression of SOD-Mn reduced frequency of binucleated hepatocytes, karyolysis, and karyorrhexis, besides the antimutagenic and antioxidant action. The extract [62.5] was cytoprotective, antimutagenic, and reduced karyolysis. The extract [125] was cytoprotective, antioxidant, antifibrotic, anti-inflammatory, and reduced frequency of binucleated hepatocytes, while extract [250] was cytotoxic and mutagenic. In summary, the extract of Mimosa exerts some therapeutic properties in hepatic tissue after Cd intoxication, but only when it is administrated at intermediate doses. Probably, a high content of polyphenols in the EHM [250] and Fr-EtOAc groups exert pro-oxidant activities in the liver particularly when associated with Cd. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate whether sleep deprivation (SD) induces inflammation, autophagy and myogenesis in the following masticatory muscles: masseter and temporal. Methods: In this study, 18 animals were randomly distributed into three groups: control group (CTL, n = 6), SD for 96 hours (SD96, n = 6), and SD for 96 hours and more 96 hours of sleep recovery (SD96 + R, n = 6). Results: In the histopathological analysis, SD 96 was able to induce inflammation in masseter and temporal. Nevertheless, the lack of inflammatory process was evidenced to the masseter in the group SD96 + R. Upregulation of TNF‐alpha production was detected in the SD96 group, while SD96 + R decreased TNF immunoexpression for both skeletal muscles evaluated. MyoD and myogenin increased in rats submitted to SD96. By contrast, the levels of MyoD decreased in the group SD96 + R. Myogenin pointed out high immunoexpression in SD96 + R groups. In temporal, pAkt decreased in animals submitted to SD96, but it increased in the group SD96 + R. The levels of LC3 protein increased in both skeletal muscles studied, and masseter decreased LC3 protein expression in the SD96 + R. Conclusion: In summary, our results demonstrate that SD is able to induce inflammation, atrophy and myogenesis in rat masticatory muscles, being more intense in temporal when compared to masseter. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the effects of intake of Brazil nut extract (BN) or sodium selenite solution on reproductive parameters of male diabetic animals. Methods: A total of 48 Wistar rats were distributed into six groups: diabetes (n = 8); diabetes and Brazil nut extract (n = 8); diabetes and sodium selenite (Na2SeO3) (n = 8); Brazil nut extract (n = 8); sodium selenite (n = 8) and control (n = 8). A single dose of streptozotocin (65 mg/kg) was injected intravenously to the rats to induce diabetes. BN or Na2SeO3 were administered by gavage for 56 days. Results: The diabetes caused critical alterations on body mass gain, reproductive parameters and antioxidant capacity. Treatments with both BN or Na2SeO3 were able to increase significantly the glutathione peroxidase and the daily sperm production, both in diabetic (p < 0.01 and p < 0.05) and in healthy animals (p < 0.01 and p < 0.05). Conclusion: The Brazil nut extract and sodium selenite were able to improve some reproductive parameters of diabetic rats. Moreover, we could infer that this effect is probably due to the natural selenium content of the BN. [ABSTRACT FROM AUTHOR]

15890404 3 da Silva RCB, de Barros Viana M, Ribeiro DA (2022) The impact of stress on rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide: some theoretical concepts for scientific debate. Furthermore, in the same cages of the control group, there were cancer and leukoplakia (non-cancer) rats, which makes it even more difficult to evaluate the relationship between 4NQO consumption and oral cancer development. [Extracted from the article]

The aim of this study was to evaluate the protective effect of grape skin or purple carrot extracts against cadmium-induced intoxication in rats' kidneys. For this purpose, 30 male Wistar rats were distributed into six groups (n = 5), as follows: control group; cadmium group and groups treated with grape skin at 175 or 350 mg / L doses; or purple carrot extract at 400 mg / L or 800 mg / L doses, by drinking water. In the group exposed to cadmium, histopathological analysis revealed severe tissue injury as a result of coagulation necrosis, congested vessels and inflammatory infiltrate. Animals treated with grape skin or purple carrot extracts improved the histopathological changes induced by cadmium. 8-OHdG immunoexpression and catalase gene expression decreased in rats treated with purple carrot or grape skin extracts. Grape skin extract was able to increase SOD-CuZn gene expression as well. Toll-like signaling pathway (TLR2, PIKK and TRAF6) and cytochrome c expressions were not altered after the treatment with grape skin or purple carrot extracts. Taken together, we conclude that grape skin and purple carrot extracts had a protective effect on the rats' kidneys after cadmium intoxication, by means of tissue regenerating tissue regeneration and antioxidant properties, grape skin extract being more effective for this purpose. [ABSTRACT FROM AUTHOR]

In this study, the authors have demonstrated that stress as a result of social isolation contributes to rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide. Prior cold water swim stress alters immobility in the forced swim test and associated activation of serotonergic neurons in the rat dorsal raphe nucleus. [Extracted from the article]

The aim of the present study was to investigate the effects of long-term grape juice concentrate (GJC) consumption, in two dosages, on the reproductive parameters of cadmium-exposed male rats. The effects of the concentrate on body mass gain, plasma testosterone levels, reproductive organ weights, daily sperm production, sperm morphology, testis histopathological and histomorphometrical parameters, and testicular antioxidant markers were investigated. Wistar rats (n 54) were distributed into six groups: CdCl2; cadmium and grape juice I (1·18 g/kg per d); cadmium and grape juice II (2·36 g/kg per d); grape juice I (1·18 g/kg per d); grape juice II (2·36 g/kg per d); control. A single dose of CdCl2 (1·2 mg/kg body weight (BW)) was injected intraperitoneally and the grape juice was administered orally for 56 d. The results indicated that cadmium changed all reproductive and antioxidant parameters. At dosage I (1·18 g/kg BW), GJC consumption did not show the effects against cadmium-induced damages. In contrast, at dosage II (2·36 g/kg BW), the GJC improved the gonadosomatic index (P= 0·003), serum testosterone levels (P= 0·001), the relative weight of epididymis (P= 0·013) and ventral prostate (P= 0·052), the percentage of normal sperm (P= 0·001), and histopathological and histomorphometrical parameters. In addition, at this dosage, normalisation of the enzymatic activity of superoxide dismutase (P= 0·001) and of testicular levels of glutathione (P= 0·03) were observed. The parameters of the non-exposed rats did not depict significant alterations. In conclusion, the product was able to act as a protector of reproductive function against cadmium-induced damage. Such a property was expressed in a dose-dependent manner as the more effective dose was dosage II. The GJC acted possibly by antioxidant mechanisms. [ABSTRACT FROM PUBLISHER]

Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2 % grape juice control group; 1 % grape juice 24 h after TNBS colitis induction; 1 % grape juice on day 7 after colitis induction; 2 % grape juice 24 h after colitis induction; 2 % grape juice on day 7 after colitis induction. The 1 % grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1 % grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (P< 0·05) of TNF-α and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1 % dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1 % dose. [ABSTRACT FROM PUBLISHER]

The objective of this article was to evaluate the impact potential of nandrolone decanoate on DNA damage, cellular regulatory proteins and cyclooxygenase (COX)-2 in oral mucosa cells of Wistar rats. A total of 40 rats were distributed into four groups. Two experimental groups were treated with nandrolone decanoate, at 5 mg/kg doses, subcutaneously, three times a week in two periods: 15 and 30 days. The remaining groups received only 0.9% saline subcutaneously, three times a week. To evaluate genetic damage, nandrolone decanoate at 15 mg/kg dose was exposed to 24 h. In the histopathological analysis, no remarkable morphological changes were observed in tongue tissue in all groups. Significant increase in immunoexpression of Ki-67, p53, COX-2 proteins was detected in the groups treated with nandrolone decanoate during 15 and 30 days, when compared to their respective controls. A positive correlation between immunoexpression of p53 and COX-2 protein was detected following nandrolone decanoate exposure. DNA damage was induced by nandrolone decanoate in oral mucosa cells at 15 mg/kg dose. Our results suggest that nandrolone decanoate was able to alter the expression of cell cycle-related proteins, as well as to induce genetic damage and COX-2 immunoexpression in tongue cells of Wistar rats. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate whether paradoxical sleep deprivation could affects the mechanisms and pathways essentials for cancer cells in tongue cancer induced by 4-nitroquinole 1-oxide in Wistar rats. Materials and Methods: For this purpose, the animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 nitroquinoline 1 oxide (4 NQO) solution through their drinking water for 4 and 12 weeks. The animals were submitted to paradoxical sleep deprivation (PSD) for 72 h using the modified multiple platform method, which consisted of placing 5 mice in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways. Statistical analysis was performed by Kruskal-Wallis non-parametric test followed by the Dunn's test using SPSS software pack (version 1.0). P value < 0.05 was considered for statistic significance. Results: Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplasic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53 and for bcl-2 and for all immunomarkers after 12 weeks of 4NQO administration. Conclusion: Our results reveal that sleep deprivation exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of exercise in multiple organs of rats treated with doxorubicin. Male adult Wistar rats were distributed into the following groups: sedentary + NaCl; exercise + NaCl; sedentary + doxorubicin; and exercise + doxorubicin. Animals were sacrificed 2 days following injections. Central fragments from heart, liver, and kidney were collected and minced in 0.9% NaCl being cellular suspensions used for the single-cell gel (comet) assay. The results showed that exercise was able to prevent genotoxicity induced by doxorubicin in heart cells. By contrast, exercise was not able to prevent genotoxicity induced by doxorubicin in liver cells. The same occurred to kidney cells, i.e. no statistically significant differences ( p > 0.05) were found when compared with groups not exposed to doxorubicin. Taken together, our results support the idea that exercise could contribute to the protective effect against genotoxicity induced by doxorubicin in heart cells. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to investigate whether subchronic treatment with grape juice concentrate is able to protect the liver from high fat diet injury in rats. The effects of grape juice concentrate treatment on histopathological changes, and immunohistochemistry for p53, p16 and p21 were evaluated. Methods: Male Wistar rats ( n == 18) were distributed into three groups: group 1: negative control; group 2: cholesterol at 1% (w/w) in their diet, treated during 5 weeks; and group 3: cholesterol at 1% in their chow during 5 weeks, and grape juice concentrate at 222 mg per day in their drinking-water in the last week only. Results: The results pointed out that treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in the cholesterol-exposed group when compared to group 2. However, grape juice concentrate was able to modulate p16 immunoexpression when compared to high fat diet group. p53 and p21 did not show any significant statistical differences among groups. Conclusion: Taken together, our results suggest that subchronic grape juice concentrate administration was able to modulate cell cycle control by downregulation of p16 immunoexpression in high fat diet-induced liver steatosis in rats. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of 660 nm laser on the healing of burn wounds made on the backs of rats. Thirty-two Wistar male rats were used. The animals were randomly distributed into 2 groups of 16 animals each: control group (burned rats without treatment) and laser-treated group (burned rats treated with laser therapy). Each group was divided into two different subgroups, euthanized in different periods (subgroup A: 7 days post-surgery and subgroup B: 14 days post-surgery). Histopathological analysis revealed a significant decrease in the necrotic area in the laser-treated group compared to the controls at days 7 and 14 post-injury. COX-2 positive cells were found in a strong pattern in the group submitted to laser therapy after 7 days. Regarding VEGF immunomarker, a significant VEGF immunoexpression was detected in the laser-exposed group after 14 days when compared to the negative control group. Taken together, our results demonstrate that laser therapy is able to promote skin repair of burned rats as a result of decreasing necrotic area and an up-regulation of COX-2 and VEGF immunoexpression. [ABSTRACT FROM AUTHOR]

The goal of the present study was to investigate whether subchronic treatment with grape juice concentrate is able to protect liver and peripheral blood cells against cholesterol-induced injury in rats. The effects of the grape juice concentrate treatment on histopathological changes, immunohistochemistry for cyclo-oxygenase-2 (COX-2), and basal and oxidative DNA damage induced by H2O2 using a single-cell gel (comet) assay were evaluated. Male Wistar rats (n 18) were divided into three groups: group 1 – negative control; group 2 – cholesterol at 1 % (w/w) in their diet, treated for 5 weeks; group 3 – cholesterol at 1 % in their chow, treated for 5 weeks, and grape juice concentrate at 222 mg/d in their drinking-water in the final week only. The results indicated that the treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in group 3 compared with group 2. However, grape juice concentrate was able to decrease oxidative DNA damage induced by H2O2 in peripheral blood cells, as depicted by the tail moment results. COX-2 expression in the liver did not show statistically significant differences (P>0·05) between groups. Taken together, the present results suggest that the administration of subchronic grape juice concentrate prevents oxidative DNA damage in peripheral blood cells. [ABSTRACT FROM PUBLISHER]

The aim of this study was to investigate, through the single-cell gel (comet) assay, whether vitamin C is able to protect against renovascular hypertension-induced genotoxicity in multiple organs. A total of 32 male Wistar rats were divided into four groups: negative control (n = 6); animals treated with vitamin C (n = 6); hypertensive rats (n = 10) and hypertensive rats and treated with vitamin C (n = 10). Hypertension was induced as a result of partial obstruction of the left renal artery by means of a silver clip during 6 weeks. Vitamin C was administered at 150 mg/kg during 7 consecutive days before the end of the experimental period. The results showed that vitamin C was able to protect blood cells against hypertension-induced genotoxicity. Brain, liver and heart cells were also protected by vitamin C following hypertension-induced genotoxic damage. Regarding blood pressure, vitamin C reduced the hypertensive state. In conclusion, our results suggest that vitamin C can prevent hypertension-induced DNA damage in blood, liver, brain and heart cells as well as to normalize the blood pressure of rats. [ABSTRACT FROM AUTHOR]

The main purpose of the present work was to evaluate if low level laser therapy (LLLT) can improve the effects of novel fully-crystallized glass–ceramic (Biosilicate®) on bone consolidation in tibial defects of rats. Forty male Wistar rats with tibial bone defects were used. Animals were divided into four groups: group bone defect control (CG); group bone defect filled with Biosilicate® (BG); group bone defect filled with Biosilicate®, irradiated with LLLT, at 60 J cm−2 (BG 60) and group bone defect filled with Biosilicate®, irradiated with LLLT, at 120 J cm−2 (BG 120). A low-energy GaAlAs 830 nm, CW, 0.6 mm beam diameter, 100 W cm−2, 60 and 120 J cm−² was used in this study. Laser irradiation was initiated immediately after the surgery procedure and it was performed every 48 h for 14 days. Fourteen days post-surgery, the three-point bending test revealed that the structural stiffness of the groups CG and BG was higher than the values of the groups BG60 and BG120. Morphometric analysis revealed no differences between the control group and the Biosilcate® group. Interestingly, the groups treated with Biosilicate® and laser (BG 60 and BG120) showed statistically significant lower values of newly formed bone in the area of the defect when compared to negative control (CG) and bone defect group filled with Biosilicate (CB). Our findings suggest that although Biosilicate® exerts some osteogenic activity during bone repair, laser therapy is not able to modulate this process. [ABSTRACT FROM AUTHOR]

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to measure the temporal pattern of the protein expression of RUNX2, RANKL, OPG, and osteocalcin after ultrasound therapy during the process of bone healing by immunohistochemistry. The animals were randomly distributed into two groups: control or ultrasound-treated group. A non-critical size bone defects were surgically created at the upper third of the tibia. The treatments started 24h post-surgery, and they are performed for 3, 6, and 12 sessions, with an interval of 48h. A low-intensity pulsed ultrasound (1.5MHz, 1:4 duty cycle, intensity SATA 30mW/cm2, 20min/session, stationary mode application) was used. On days 7, 13, and 25 post-injury, rats were killed individually by carbon dioxide asphyxia. The tibias were removed for analysis. The histopathological analysis pointed out no remarkable differences between groups for all periods evaluated. However, immunohistochemical data revealed that ultrasound therapy produced an up-regulation of osteocalcin at day 7th and 13th post-surgery. Taken together, our results indicate that ultrasound therapy modulates osteocalcin expression during bone repair in rats as depicted by differential immunopression at the initial and intermediate stages of recovery. [Copyright &y& Elsevier]

Abstract: The aim of this study was to measure the temporal expression of osteogenic genes during the process of bone healing in low-intensity pulsed ultrasound (LIPUS) treated bone defects by means of histopathologic and real-time polymerase chain reaction (PCR) analysis. Animals were randomly distributed into two groups (n = 30): control group (bone defect without treatment) and LIPUS treated (bone defect treated with LIPUS). On days 7, 13 and 25 postinjury, 10 rats per group were sacrificed. Rats were treated with a 30 mW/cm2 LIPUS. The results pointed out intense new bone formation surrounded by highly vascularized connective tissue presenting a slight osteogenic activity, with primary bone deposition was observed in the group exposed to LIPUS in the intermediary (13 days) and late stages of repair (25 days) in the treated animals. In addition, quantitative real-time polymerase chain reaction (RT-qPCR) showed an upregulation of bone morphogenetic protein 4 (BMP4), osteocalcin and Runx2 genes 7 days after the surgery. In the intermediary period, there was no increase in the expression. The expression of alkaline phosphatase, BMP4 and Runx2 was significantly increased at the last period. Our results indicate that LIPUS therapy improves bone repair in rats and upregulated osteogenic genes, mainly at the late stages of recovery. (E-mail: a.renno@unifesp.br) [ABSTRACT FROM AUTHOR]