Glucose homoeostasis in rats exposed to acute intermittent hypoxia

Aim: Chronic exposure to intermittent hypoxia commonly induces the activation of sympathetic tonus and the disruption of glucose homoeostasis. However, the effects of exposure to acute intermittent hypoxia (AIH) on glucose homoeostasis are not yet fully elucidated. Herein, we evaluated parameters related to glucose metabolism in rats exposed to AIH. Methods: Male adult rats were submitted to 10 episodes of hypoxia (6% O2, for 45 s) interspersed with 5-min intervals of normoxia (21%), while the control (CTL) group was kept in normoxia. Results: Acute intermittent hypoxia rats presented higher fasting glycaemia, normal insulinaemia, increased lactataemia and similar serum lipid levels, compared to controls (n = 10, P < 0.05). Additionally, AIH rats exhibited increased glucose tolerance (GT) (n = 10, P < 0.05) and augmented insulin sensitivity (IS) (n = 10, P < 0.05). The p-Akt/Akt protein ratio was increased in the muscle, but not in the liver and adipose tissue of AIH rats (n = 6, P < 0.05). The elevated glycaemia in AIH rats was associated with a reduction in the hepatic glycogen content (n = 10, P < 0.05). Moreover, the AIH-induced increase in blood glucose concentration, as well as reduced hepatic glycogen content, was prevented by prior systemic administration of the β-adrenergic antagonist (P < 0.05). The effects of AIH on glycaemia and Akt phosphorylation were transient and not observed after 60 min. Conclusions: We suggest that AIH induces an increase in blood glucose concentration as a result of hepatic glycogenolysis recruitment through sympathetic activation. The augmentation of GT and IS might be attributed, at least in part, to increased β-adrenergic sympathetic stimulation and Akt protein activation in skeletal muscles, leading to a higher glucose availability and utilization. © 2013 Scandinavian Physiological Society.

Dynamics of bone healing after osteotomy with piezosurgery or conventional drilling - histomorphometrical, immunohistochemical, and molecular analysis

Background: Piezosurgery is an osteotomy system used in medical and dental surgery. Many studies have proven clinical advantages of piezosurgery in terms of quality of cut, maneuverability, ease of use, and safety. However, few investigations have tested its superiority over the traditional osteotomy systems in terms of dynamics of bone healing. Therefore, the aim of this study was to evaluate the dynamics of bone healing after osteotomies with piezosurgery and to compare them with those associated to traditional bone drilling.Methods: One hundred and ten rats were divided into two groups with 55 animals each. The animals were anesthetized and the tibiae were surgically exposed to create defects 2 mm in diameter by using piezosurgery (Piezo group) and conventional drilling (Drill group). Animals were sacrificed at 3, 7, 14, 30 and 60 days post-surgery. Bone samples were collected and processed for histological, histomorphometrical, immunohistochemical, and molecular analysis. The histological analysis was performed at all time points (n = 8) whereas the histomorphometrical analysis was performed at 7, 14, 30 and 60 days post-surgery (n = 8). The immunolabeling was performed to detect Vascular Endothelial Growth Factor (VEGF), Caspase-3 (CAS-3), Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), and Osteocalcin (OC) at 3, 7, and 14 days (n = 3). For the molecular analysis, animals were sacrificed at 3, 7 and 14 days, total RNA was collected, and quantification of the expression of 21 genes related to BMP signaling, Wnt signaling, inflammation, osteogenenic and apoptotic pathways was performed by qRT-PCR (n = 5).Results: Histologically and histomorphometrically, bone healing was similar in both groups with the exception of a slightly higher amount of newly formed bone observed at 30 days after piezosurgery (p < 0.05). Immunohistochemical and qRT-PCR analyses didn't detect significant differences in expression of all the proteins and most of the genes tested.Conclusions: Based on the results of our study we conclude that in a rat tibial bone defect model the bone healing dynamics after piezosurgery are comparable to those observed with conventional drilling. © 2013 Esteves et al.; licensee BioMed Central Ltd.

Novo gene cry8 de Bacillus thuringiensis: caracterização e avaliação da patogenicidade ao bicudo da cana-de-açúcar, Sphenophorus levis Vaurie, 1978 (Coleoptera: Curculionidae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência da ovariectomia associada à dieta deficiente em cálcio na periodontite experimental

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Papel das proteínas intracelulares Nod e da proteína adaptadora MyD88 na regulação de espressão de RANKL e modulação da resposta inflamatória induzidos por antígenos bacterianos in vitro: estudo em células relevantes de periodonto

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Biomechanical and Microstructural Benefits of Physical Exercise Associated With Risedronate in Bones of Ovariectomized Rats

Several treatments have been developed aiming the prevention of bone loss. There are discussions about the best prophylactic and therapeutic procedures for osteoporosis. This study evaluated the effects of physical exercise associated with risedronate as a prophylactic and therapeutic procedure in osteopenic bones of rats submitted to ovariectomy. We used 48 Wistar rats divided into: ovariectomized or subjected to sham surgery. Ovariectomized rats were divided into the following sub-groups: OVX, 12 weeks sedentary; OVX-EX, treadmill training for 12 weeks; OVX-RA, 12 weeks with risedronate administration; and OVX-EX-RA, 12 weeks with risedronate administration and treadmill training. Rats subjected to sham surgery were divided into the following sub-groups: SH, 12 weeks sedentary; SH-EX, treadmill training for 12 weeks; SH-RA, 12 weeks with risedronate administration; and SH-EX-RA, 12 weeks with risedronate administration and training on the treadmill. The effectiveness of the treatment was evaluated in tibias using biomechanical, radiological, histomorphometric, and immunohistochemical analyses. Data were analyzed by statistical tests, with significance level of P < 0.05. Results of mechanical tests showed that the SH-RA group had lower values compared with OVX-RA group; densitometry showed no significant differences; according to histomorphometric methods, OVX group presented lower results than the SH-EX, OVX-RA, SH-EX-RA, and OVX-EX-RA groups, and SH-EX-RA and OVX-EX-RA groups showed values higher than SH-RA, SH, and OVX-EX groups. The SH-EX-RA and OVX-EX-RA groups had decreased immunostaining for tartrate-resistant acid phosphatase and receptor activator of nuclear factor kappa-B ligand and increased osteoprotegerin immunostaining. In this experimental model, it was concluded that the physical training associated with use of risedronate exerted positive effects on biomechanical and microstructural properties in bones of ovariectomized rats. (C) 2014 Wiley Periodicals, Inc.

Effect of Qualea multiflora on Macrophages and Tumour Cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exposure to lard-based high-fat diet during fetal and lactation periods modifies breast cancer susceptibility in adulthood in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Open-Flap Versus Flapless Esthetic Crown Lengthening: 12-Month Clinical Outcomes of a Randomized Controlled Clinical Trial

Background: Excessive gingival display (EGD) has a negative impact on a pleasant smile. Minimally invasive therapeutic modalities have become the standard treatment in many dentistry fields. Therefore, the aim of this study is to compare the clinical outcomes of open-flap (OF) and minimally invasive flapless (FL) esthetic crown lengthening (ECL) for the treatment of EGD.Methods: A split-mouth randomized controlled trial was conducted in 28 patients presenting with EGD. Contralateral quadrants received ECL using OF or FL techniques. Clinical parameters were evaluated at baseline and 3, 6, and 12 months post-surgery. The local levels of receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) were assessed by enzyme-linked immunosorbent assay at baseline and 3 months. Patients' perceptions regarding morbidity and esthetic appearance were also evaluated. Periodontal tissue dimensions were obtained by computed tomography at baseline and correlated with the changes in the gingival margin (GM).Results: Patients reported low morbidity and high satisfaction with esthetic appearance for both procedures (P > 0.05). RANKL and OPG concentrations were increased in the OF group at 3 months (P < 0.05). Probing depths were reduced for both groups at all time points, compared with baseline (P < 0.05). There were no differences between groups for GM reduction at any time point (P > 0.05).Conclusions: FL and OF surgeries produced stable and similar clinical results up to 12 months. FL ECL may be a predictable alternative approach for the treatment of EGD.

Transcriptional and Posttranscriptional Regulations of the HLA-G Gene

HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-gamma and NF-kappa B, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3' untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3' UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.

Oral squamous carcinoma cells secrete RANKL directly supporting osteolytic bone loss

Objective: Local invasion of bone is a frequent complication of oral squamous cell carcinoma (OSCC). Development of these osteolytic lesions is mediated by osteoclasts. Receptor activation of NF-kappa B ligand (RANKL) signaling, counteracted by osteoprotegerin (OPG), regulates osteoclastogenesis. Previous studies in rodent models have demonstrated that inhibition of RANKL decreases tumor growth and lesions within bone. However, the contributory role of OSCC cells to this disease process has yet to be defined.Methods: RANKL expression was assessed in a panel of OSCC cell lines by qPCR, flow cytometry, and ELISA. Induction of osteoclastogenesis was assessed by co-culture with macrophages or with OSCC-derived conditioned medium. In an animal model of bone invasion, nude mice were injected intratibially with UMSCC-11B cells expressing a RANKL luciferase promoter to detect tumor-derived RANKL activity. Osteolytic lesions were analyzed by X-ray, micro-CT, and histological methods. RANKL expression was assessed in human OSCC tissues by immunohistochemistry.Results: We demonstrated that OSCCs express varied levels of all RANKL isoforms, both membrane-bound and soluble RANKL. Both co-culture and treatment with OSCC-conditioned media induced osteoclastogenesis. In mice, we demonstrated human RANKL promoter activity during bone invasion. Over the course of the experiment, animals suffered osteolytic lesions as RANKL-driven luciferase expression increased with time. After 8 weeks, human-derived RANKL was detected in areas of bone resorption by immunohistochemistry. Similar epithelial RANKL expression was detected in human OSCC tissues.Conclusion: These data demonstrate the ability of OSCCs to produce RANKL, directly altering the tumor microenvironment to increase osteoclastogenesis and mediate local bone invasion. (C) 2012 Elsevier Ltd. All rights reserved.

Curcurnin abrogates LPS-induced pro-inflammatory cytokines in RAW 264.7 macrophages. Evidence for novel mechanisms involving SOCS-1,-3 and p38 MAPK

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Acerola (Malpighia emarginata DC.) juice intake protects against alterations to proteins involved in inflammatory and lipolysis pathways in the adipose tissue of obese mice fed a cafeteria diet

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Potent Anti-Inflammatory Activity of Pyrenocine A Isolated from the Marine-Derived Fungus Penicillium paxilli Ma(G) K

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Aerobic Exercise Training Prevents Heart Failure-Induced Skeletal Muscle Atrophy by Anti-Catabolic, but Not Anabolic Actions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)