Glucocorticoid-induced osteoporosis (GIO) has emerged as a challenge after long-term glucocorticoids (GCs) administration. Exercise has been an important non-pharmacological option, while medications ...modulate bone remodeling despite adverse effects. In this way, milk Kefir (MK) therapy stands out as a safe alternative to improve bone metabolism. Our study aimed to investigate the effect of MK associated to resistance exercise on bone loss in rats with GIO. For this, sixty male Wistar rats were divided into 2 groups: normal (N) and subjected to GIO, which was subdivided into 4 groups: control (C), milk kefir therapy (K), Exercise (Ex), and Exercise+K (ExK). GIO was induced by dexamethasone (7 mg/kg – i.m.; 1×/wk, 5 wk). MK was administered daily (1×/day; 0.7 ml/animal) and the climb exercise with load was performed 3×/wk; both for 16 wk. Femur was collected for assessment of bone microarchitecture, quality and metabolism. GIO markedly reduced trabecular bone volume density (BV/TV) (−35 %), trabecular thickness (Tb.Th) (−33 %), mineral content of femur (−26 %) as well as bone collagen content (−56 %). Bone strength and its biomechanical properties given by flexural strength (−81 %), fracture load (−80 %), and the number of osteocytes (−84 %) were lowered after GIO. GCs reduced osteoblast number and function while increased osteoclast number, altering bone remodeling (p < 0.05). On the other hand, ExK significantly improved bone microarchitecture and quality, marked by fractal dimension increase (+38 %), cortical volume (+34 %), BV/TV (+34 %), Tb.Th (+33 %), mineral content and collagen maturity, while reduced the space between trabecula (−34 %). The Ex and ExK increased the number of osteocytes (p < 0.05) and they were able to reverse the lower osteoblast number. Both treatments used alone significantly enhanced bone biomechanical properties, but the ExK showed a more significant improvement. ExK ameliorated bone strength and biomechanics (p < 0.05) and stimulated bone formation and modulated bone remodeling (p < 0.05). MK and exercise administered isolated or in association increased the percentage of collagen bone filling after GIO (p < 0.05), but only ExK improved collagen maturity. Our results showed that MK associated to resistance exercise enhanced bone microarchitecture, quality and metabolism, being therefore an interesting tool to improve skeletal response during GIO.
•GIO model promoted a negative impact on bone tissue, mainly in trabecular bone.•Kefir and exercise treatment reversed many of the deleterious effects of GC on bone.•Kefir and exercise are an interesting tool to improve skeletal response during GIO.•First time that evaluation of exercise+Kefir on bone of rats with GIO was performed.
Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Cashew gum (CG) has been reported as a potent ...anti-inflammatory agent. In the present study, we aimed to evaluate the effect of CG extracted from the exudate of
L. on experimental intestinal mucositis induced by 5-FU. Swiss mice were randomly divided into seven groups: Saline, 5-FU, CG 30, CG 60, CG 90, Celecoxib (CLX), and CLX + CG 90 groups. The weight of mice was measured daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis), levels of malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH), and immunohistochemical analysis of interleukin 1 beta (IL-1β) and cyclooxygenase-2 (COX-2). 5-FU induced intense weight loss and reduction in villus height compared to the saline group. CG 90 prevented 5-FU-induced histopathological changes and decreased oxidative stress through decrease of MDA levels and increase of GSH concentration. CG attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. Our findings suggest that CG at a concentration of 90 mg/kg reverses the effects of 5-FU-induced intestinal mucositis.
To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic ...Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.
The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model.
Periodontal inflammation was induced by LPS/
. Maxillae, femur, and vertebra ...were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR.
The vertebra showed decreased BMD in AT1 H compared with WT H (
< 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H,
< 0.01 and
< 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H:
< 0.05; WT H-AT2 H:
< 0.05) and in the femur (WT H-AT1 H:
< 0.01; WT H-AT2 H:
< 0.05). AT1 PD increased linear bone loss (
< 0.05) and decreased osteoblast cells (
< 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (
< 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (
< 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (
< 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (
< 0.01).
AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.
The aim of this study was to evaluate the bone regenerative effect of glutaraldehyde (GA) cross-linking on mineralized polyanionic collagen membranes in critical-sized defects on rat calvarias. Bone ...calvarial defects were induced in Wistar rats, which were then divided into five groups: a sham group; a control group, which received a commercial membrane; and GA, 25GA, and 75GA groups, which received one of three different polyanionic collagen membranes mineralized by 0, 25, or 75 hydroxyapatite cycles and then cross-linked by GA. Bone formation was evaluated based on digital radiography and computerized tomography. Histological analyses were performed 4 and 12 weeks after the surgical procedure to observe bone formation, membrane resorption, and fibrous tissue surrounding the membranes. Measurement of myeloperoxidase activity, tumor necrosis factor alpha, and interleukin 1beta production was performed 24 h after surgery. The percentage of new bone formation in the GA, 25GA, and 75GA groups was higher compared with the control and sham groups. In the GA and 25 GA groups, the membranes were still in place and were contained in a thick fibrous capsule after 12 weeks. No significant difference was found among the groups regarding myeloperoxidase activity and interleukin 1beta levels, although the GA, 25GA, and 75GA groups presented decreased levels of tumor necrosis factor alpha compared with the control group. These new GA cross-linked membranes accelerated bone healing of the calvarium defects and did not induce inflammation. In addition, unlike the control membrane, the experimental membranes were not absorbed during the analyzed period, so they may offer advantages in large bone defects where prolonged membrane barrier functions are desirable.
To evaluate the relationship between the volume and weight of the buccal fat pad removed in the perioperative period and the body mass index (BMI) of patients subjected to buccal fat pad excision as ...well as to compare the facial dimensions and the level of satisfaction of these patients before and after the surgical procedure. Fifty‐seven patients were included in this study. All were included in the dimensional analysis (weight and volume) and anthropometric correlation (BMI). To evaluate the facial dimensions, 20 volunteers were included and subjected to bilateral measurement at four specific points on the face before and after surgery. Thirty‐five patients were also evaluated regarding the occurrence of peri‐ and post‐operative complications and their level of satisfaction through a specific questionnaire. There was no statistically significant correlation between the dimensions of the buccal fat pad and the anthropometric measurements of the individuals involved in the analysis. There was also no significant alteration of the facial measurements assessed after buccal fat pad excision. The descriptive analysis showed that self‐perception regarding aesthetic need was the predominant factor indicating surgery and that most patients were satisfied with the results, which were close to expected, according to their self‐assessment. Post‐operative complications were limited to trismus and oedema. The weight and volume of the buccal fat pad showed no significant correlation with the anthropometric variables of weight, height and BMI. There were no significant differences in the facial measurements analysed after buccal fat pad excision. The patient satisfaction questionnaire showed that surgical indication was generally motivated by aesthetic factors of individual perception and obtaining results consistent with personal expectations. The frequency of complications arising from buccal fat pad excision included patient discomfort.
One of the challenges in treating
infection (CDI) is that the bacterium forms biofilms, a critical virulence mechanism known to promote antibiotic resistance and, as a result, consequently, a higher ...recurrence of the disease. The goal of this study was to compare the ability of three MLST Clade 2 strains to form a biofilm in vitro: ICC-45 (ribotype SLO231/UKCE821), a ST41 toxinotype IXb isolated in Brazil; and two epidemic NAP1/027/ST01 strains: NAP1/027/ST01 (LIBA5756), isolated during a 2010 outbreak in Costa Rica and the reference epidemic strain NAP1/027/ST01 (R20291); and ATCC700057, a non-toxigenic strain.
The ability of strains to form biofilm was evaluated using crystal violet staining. In addition, samples were stained with the Film Tracer biofilm matrix (Invitrogen®) and the biofilm matrix thickness was measured using confocal microscopy. The matrix architecture was determined using Scanning electron microscop. Confocal microscopy was used to detect the presence of toxin A (tcdA) using an anti-
TcdA antibody. The expression of virulence genes (
,
,
,
,
,
,
and
) was examined, as well as the effect of antibiotics metronidazole (MTZ) and vancomycin (VAN) on biofilm growth.
All of the strains tested formed a moderate biofilm with 1.1 3.5. After 72h, biofilm biomass of the NAP1/027/ST01 epidemic strains (LIBA5756 and R20291) was significantly higher than ICC-45 and ATCC 700057 biofilms, as confirmed by electron and confocal microscopy. At 120h, the LIBA5756 biofilm biomass decreased compared to other strains. The toxigenic strains R20291 or LIBA 5756 had higher expression of genes
,
,
,
,
and
than ICC-45, but there were no significant differences in the expression levels of
,
and
. In epidemic strains, VAN and MTZ inhibited biofilm formation; however, in the ICC-45 strain, MIC concentrations of VAN and MIC and 4MIC of MTZ did not inhibit biofilm formation.
The three MLST Clade 2 isolated from different rybotipes, two of which were isolated from Latin America, are competent biofilm-forming bacteria, indicating their ability to induce
infection recurrence, making treatment difficult.
The treatment of chronic wounds is considered a public health problem. When the condition affects at-risk groups such as those with diabetics, it becomes a great clinical challenge. In this work, we ...evaluated the healing effects of a new zinc complex, Zn(phen)(van)
, identified as ZPV, which was synthesized, characterized and associated with chitosan (CS) membranes and tested on cutaneous wounds of diabetic rats. Chitosan membranes were modified by Schiff base reaction with the complex under two experimental conditions (14 and 21 days), resulting in membranes with concentrations of complex equal to 0.736 μmol cm
(CS-ZPV1) and 1.22 μmol cm
(CS-ZPV2). Release assays in aqueous medium indicated that the membranes release the complex gradually when exposed to an aqueous medium. Diabetes was inducted in
rats using 40 mg/kg (i.v.) streptozotocin. On the 7th day after diabetic induction, a circular excision on the skin (1.0 cm) was performed with a punch. The lesions were treated with the pure chitosan membrane and the membrane associated with the zinc-vanillin complex in two different doses. Skin samples were subjected to macroscopic and histopathological analyses, cytokine (TNF-α, IL-1β, and IL-10) quantification and reverse transcriptase polymerase chain reaction (TGF-β and VEGF) assays. The analyses showed a decrease in wound size, reepithelialization, angiogenic stimulus, collagen deposition, and reduced levels of TNF-α and IL-1β as well as increased IL-10 and gene expression of TGF-β and VEGF. The evaluated parameters suggest that CS-ZPV in the two concentrations tested may be effective in the treatment of chronic wounds.
Abstract Background There is a spectrum of possibilities for analyzing muscle O2 resaturation parameters for measurement of reactive hyperemia in microvasculature. However, there is no consensus with ...respect to the responsiveness of these O2 resaturation parameters for assessing reactive hyperemia. Objectives This study investigates the responsiveness of the most utilized muscle O2 resaturation parameters to assess reactive hyperemia in the microvasculature of a clinical group known to exhibit impairments of tissue O2 saturation (StO2). Methods Twenty-three healthy young adults, twenty-nine healthy older adults, and thirty-five older adults at risk of cardiovascular disease (CVD) were recruited. Near-infrared spectroscopy (NIRS) was used to assess StO2 after a 5-min arterial occlusion challenge and the following parameters were analyzed: StO2slope_10s, StO2slope_30s, and StO2slope_until_baseline (upslope of StO2 over 10s and 30s and until StO2 reaches the baseline value); time to StO2baseline and time to StO2max (time taken for StO2 to reach baseline and peak values, respectively); ∆StO2reperfusion (the difference between minimum and maximum StO2 values); total area under the curve (StO2AUCt); and AUC above the baseline value (StO2AUC_above_base). Results Only StO2slope_10s was significantly slower in older adults at risk for CVD compared to healthy young individuals (p < 0.001) and to healthy older adults (p < 0.001). Conversely, time to StO2max was significantly longer in healthy young individuals than in older adult at CVD risk. Conclusions Our findings suggest that StO2slope_10s may be a measure of reactive hyperemia, which provides clinical insight into microvascular function assessment.
Resumo Contexto Existe um espectro de possibilidades na análise dos parâmetros de ressaturação de O2 muscular como uma medida de hiperemia reativa na microvasculatura. No entanto, não há consenso com relação à responsividade desses parâmetros de ressaturação de O2 para avaliação de hiperemia reativa. Objetivos Este estudo investigou a capacidade de resposta dos parâmetros de ressaturação muscular de O2 mais utilizados para avaliar a hiperemia reativa na microvasculatura de um grupo clínico conhecido por apresentar comprometimento da saturação de O2 (StO2). Métodos Foram recrutados 23 jovens saudáveis, 29 idosos saudáveis e 35 idosos com risco para doença cardiovascular. A espectroscopia no infravermelho próximo foi usada para avaliar a StO2 após um teste de oclusão arterial de 5 minutos, no qual os seguintes parâmetros foram analisados: StO2slope_10s, StO2slope_30s e StO2slope_until_baseline (inclinação da StO2 em 10 s, 30 s e até StO2 atingir valores basais); tempo para StO2baseline e tempo para StO2máx (o tempo necessário para StO2 atingir os valores da linha de base e o máximo, respectivamente); ∆StO2reperfusão (a diferença entre o valor de StO2mínimo e StO2máximo); área total sob a curva (StO2AUCt); e área sob a curva acima do valor da linha de base (StO2AUC_above_base). Resultados Apenas StO2slope_10s foi significativamente mais lento em idosos em risco de doença cardiovascular comparados com indivíduos jovens saudáveis (p < 0,001) e idosos saudáveis (p < 0,001). Por outro lado, o tempo para StO2max foi significativamente maior em indivíduos jovens saudáveis do que em idosos em risco de doença cardiovascular. Conclusões Nossos achados sugerem que StO2slope_10s pode ser uma medida de hiperemia reativa, que fornece informações clínicas sobre a avaliação da função microvascular.
Oral mucositis (OM) is one of the main side effects of the head and neck cancer treatment, particularly radiotherapy and/or chemotherapy. OM is characterized by ulcers, erythema, dysphagia, ...xerostomia, and increased susceptibility to opportunistic infections. In the perspective of finding pharmacological therapies to prevent inflammation and ulceration of OM, the investigation of the pleiotropic effect of commercial drugs is needed, among them gliclazide, an antidiabetic drug. This study aimed to evaluate the effect of gliclazide in an experimental OM model induced by 5-fluorouracil. Male hamsters were pre-treated with oral gliclazide (1, 5, or 10 mg/kg) for 10 days. Cheek pouch samples were subjected to histopathological and immunohistochemical analysis (COX
, iNOS, MMP-2, NFκB P65, GPx) and imunofluorescence (P-selectin). IL-1β and TNF-α levels, Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were investigated by ultraviolet-visible spectroscopy analysis. NFκB NLS P50 protein levels were analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg showed presence of erythema, no evidence of erosion, and absence of mucosal ulceration with a score of 1 (1-2) (
< 0.01). Histopathological data for the group treated with gliclazide 10 mg/kg showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage, edema, ulcers and abscesses with a score of 1 (1-1) (
< 0.01). Treatment with gliclazide 10 mg/kg reduced MPO activity (
< 0.001), MDA levels (
< 0.001) and NFκB NLS P50 (
< 0.05) protein levels, resulting in low immunostaining to Cox-2, iNOS (
< 0.05), NFκB P65 (
< 0.05), and negative immunoreaction to MMP-2 (
< 0.001). However, it appeared that for Gpx1, the staining was restored in the GLI 10-FUT group compared with 5FUT/saline (
< 0.05). Immunofluorescence revealed decreased levels of P-selectin (
< 0.001) after treatment with gliclazide 10 mg/kg (
< 0.05). In summary, gliclazide accelerated mucosal recovery and reduced oxidative stress and inflammation in the 5-FU-induced OM in hamsters.
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