Gonadal Hormones Modulate The Responsiveness To Local β-blocker-induced Antinociception In The Temporomandibular Joint Of Male And Female Rats.

We have previously demonstrated that blockade of β-adrenoreceptors (β-AR) located in the temporomandibular joint (TMJ) of rats suppresses formalin-induced TMJ nociceptive behaviour in both male and female rats, but female rats are more responsive. In this study, we investigated whether gonadal hormones modulate the responsiveness to local β-blocker-induced antinociception in the TMJ of rats. Co-administration of each of the selective β1 (atenolol), β2 (ICI 118.551) and β3 (SR59230A)-AR antagonists with equi-nociceptive concentrations of formalin in the TMJ of intact, gonadectomized and hormone-treated gonadectomized male and female rats. Atenolol, ICI 118.551 and SR59230A significantly reduced formalin-induced TMJ nociception in a dose response fashion in all groups tested. However, a lower dose of each β-AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and testosterone-treated gonadectomized male rats. In the female groups, a lower dose of β1 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact or gonadectomized rats treated with progesterone or a high dose of oestradiol; a lower dose of β2 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and gonadectomized rats treated with low or high dose of oestradiol. Gonadal hormones may reduce the responsiveness to local β-blocker-induced antinociception in the TMJ of male and female rats. However, their effect depends upon their plasma level, the subtype of β-AR and the dose of β-blockers used.

Morphological Aspects And Cox-2 Expression After Exposure To 780-nm Laser Therapy In Injured Skeletal Muscle: An In Vivo Study.

The effectiveness of low-level laser therapy in muscle regeneration is still not well known. To investigate the effects of laser irradiation during muscle healing. For this purpose, 63 rats were distributed to 3 groups: non-irradiated control group (CG); group irradiated at 10 J/cm(2) (G10); and group irradiated at 50 J/cm(2) (G50). Each group was divided into 3 different subgroups (n=7), and on days 7, 14 and 21 post-injury the rats were sacrificed. Seven days post-surgery, the CG showed destroyed zones and extensive myofibrillar degeneration. For both treated groups, the necrosis area was smaller compared to the CG. On day 14 post-injury, treated groups demonstrated better tissue organization, with newly formed muscle fibers compared to the CG. On the 21(st) day, the irradiated groups showed similar patterns of tissue repair, with improved muscle structure at the site of the injury, resembling uninjured muscle tissue organization. Regarding collagen deposition, the G10 showed an increase in collagen synthesis. In the last period evaluated, both treated groups showed statistically higher values in comparison with the CG. Furthermore, laser irradiation at 10 J/cm(2) produced a down-regulation of cyclooxygenase 2 (Cox-2) immunoexpression on day 7 post-injury. Moreover, Cox-2 immunoexpression was decreased in both treated groups on day 14. Laser therapy at both fluencies stimulated muscle repair through the formation of new muscle fiber, increase in collagen synthesis, and down-regulation of Cox-2 expression.

S-nitrosoglutathione Accelerates Recovery From 5-fluorouracil-induced Oral Mucositis.

Mucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side-effect of cancer therapy. To evaluate the effect of the topical application of S-nitrosoglutathione (GSNO), a nitric oxide donor, on 5-fluorouracil (5-FU)-induced oral mucositis in hamsters. Oral mucositis was induced in male hamsters by two intraperitoneal administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) followed by mechanical trauma on the fourth day. Animals received saline, HPMC or HPMC/GSNO (0.1, 0.5 or 2.0 mM) 1 h prior to the 5-FU injection and twice a day for 10 or 14 days. Samples of cheek pouches were harvested for: histopathological analysis, TNF-α and IL-1β levels, immunohistochemical staining for iNOS, TNF-α, IL-1β, Ki67 and TGF-β RII and a TUNEL assay. The presence and levels of 39 bacterial taxa were analyzed using the Checkerboard DNA-DNA hybridization method. The profiles of NO released from the HPMC/GSNO formulations were characterized using chemiluminescence. The HPMC/GSNO formulations were found to provide sustained release of NO for more than 4 h at concentration-dependent rates of 14 to 80 nmol/mL/h. Treatment with HPMC/GSNO (0.5 mM) significantly reduced mucosal damage, inflammatory alterations and cell death associated with 5-FU-induced oral mucositis on day 14 but not on day 10. HPMC/GSNO administration also reversed the inhibitory effect of 5-FU on cell proliferation on day 14. In addition, we observed that the chemotherapy significantly increased the levels and/or prevalence of several bacterial species. Topical HPMC/GSNO accelerates mucosal recovery, reduces inflammatory parameters, speeds up re-epithelization and decreases levels of periodontopathic species in mucosal ulcers.

Neural Mechanisms And Delayed Gastric Emptying Of Liquid Induced Through Acute Myocardial Infarction In Rats.

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos.

Inhibition Of Tumor Necrosis Factor-alpha And Cyclooxigenase-2 By Isatin: A Molecular Mechanism Of Protection Against Tnbs-induced Colitis In Rats.

Isatin, an indole alkaloid has been shown to have anti-microbial, anti-tumor and anti-inflammatory effects. Due to its findings, we evaluated whether this alkaloid would have any effect on TNBS-induced colitis. Animals (male Unib:WH rats, aged 8 weeks old) were induced colitis through a rectal administration of 2,4,6-trinitrobenzene sulphonic acid using a catheter inserted 8 cm into the rectum of the animals. The rats were divided into two major groups: non-colitic and colitic. The colitic group was sub-divided into 6 groups (10 animals per group): colitic non-treated, Isatin 3; 6; 12.5; 18.75 and 25 mg/kg. Our main results showed that the oral treatment with Isatin 6 and 25 mg/kg were capable of avoiding the increase in TNF-α, COX-2 and PGE₂ levels when compared to the colitic non-treated group. Interestingly, the same doses (6 and 25 mg/kg) were also capable of preventing the decrease in IL-10 levels comparing with the colitic non-treated group. The levels of MPO, (an indirect indicator of neutrophil presence), were also maintained lower than those of the colitic non-treated group. Isatin also prevented the decrease of SOD activity and increase of GSH-Px and GSH-Rd activity as well as the depletion of GSH levels. In conclusion, both pre-treatments (6 and 25 mg/kg) were capable of protecting the gut mucosa against the injury caused by TNBS, through the combination of antioxidant and anti-inflammatory properties, which, together, showed a protective activity of the indole alkaloid Isatin.

Evaluation Of Photodynamic Therapy Using A Diode Laser And Different Photosensitizers Against Enterococcus Faecalis.

Photodynamic therapy (PDT) has been proven to be effective in disinfecting root canals. The aim of this present study was to evaluate the effects of PDT on the viability of Enterococcus faecalis using methylene blue (MB) and malachite green (MG) as photosensitizers. Solutions containing E. faecalis (ATCC 29212) were prepared and harvested by centrifugation to obtain cell suspensions, which were mixed with MB and MG. Samples were individually irradiated by the diode laser at a distance of 1mm for 30, 60, or 120 seconds. Colonyforming units (CFU) were determined for each treatment. PDT for 60 and 120 seconds with MG reduced E. faecalis viability significantly. Similar results were obtained when MB was used as photosensitizer. PDT using MB and MG have antibacterial effect against E. faecalis, showing potential to be used as an adjunctive antimicrobial procedure in endodontic therapy.

Orthognathic Surgery With Or Without Induced Hypotension.

This study involved a retrospective evaluation of patients subjected to surgery for dentofacial deformities treated without induced controlled hypotension (group I, n=50) and a prospective evaluation of patients who were subjected to surgery under hypotensive general anaesthesia (group II, n=50). No statistical differences were found between the study groups with regard to the duration of surgery. However, there were statistically significant differences in the need for blood transfusion and the occurrence of bradycardia during the maxillary down-fracture. Hypotensive anaesthesia decreased the need for a blood transfusion and the occurrence of bradycardia, and is therefore considered highly beneficial for patients undergoing orthognathic surgery.

Laser Printer Attribution: Exploring New Features And Beyond.

With a huge amount of printed documents nowadays, identifying their source is useful for criminal investigations and also to authenticate digital copies of a document. In this paper, we propose novel techniques for laser printer attribution. Our solutions do not need very high resolution scanning of the investigated document and explore the multidirectional, multiscale and low-level gradient texture patterns yielded by printing devices. The main contributions of this work are: (1) the description of printed areas using multidirectional and multiscale co-occurring texture patterns; (2) description of texture on low-level gradient areas by a convolution texture gradient filter that emphasizes textures in specific transition areas and (3) the analysis of printer patterns in segments of interest, which we call frames, instead of whole documents or only printed letters. We show by experiments in a well documented dataset that the proposed methods outperform techniques described in the literature and present near-perfect classification accuracy being very promising for deployment in real-world forensic investigations.

Gut Bacteria Products Prevent Aki Induced By Ischemia-reperfusion.

Short-chain fatty acids (SCFAs) are fermentation end products produced by the intestinal microbiota and have anti-inflammatory and histone deacetylase-inhibiting properties. Recently, a dual relationship between the intestine and kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI model in which the inflammatory process has a detrimental role. We observed that therapy with the three main SCFAs (acetate, propionate, and butyrate) improved renal dysfunction caused by injury. This protection was associated with low levels of local and systemic inflammation, oxidative cellular stress, cell infiltration/activation, and apoptosis. However, it was also associated with an increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and modulated the expression levels of enzymes involved in chromatin modification. In vitro analyses showed that SCFAs modulated the inflammatory process, decreasing the maturation of dendritic cells and inhibiting the capacity of these cells to induce CD4(+) and CD8(+) T cell proliferation. Furthermore, SCFAs ameliorated the effects of hypoxia in kidney epithelial cells by improving mitochondrial biogenesis. Notably, mice treated with acetate-producing bacteria also had better outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and viability after an injury through modulation of the inflammatory process, most likely via epigenetic modification.

A Metabolomic Protocol For Plant Systematics By Matrix-assisted Laser-desorption/ionization Time-of Flight Mass Spectrometry.

Matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOF MS) has been widely used for the identification and classification of microorganisms based on their proteomic fingerprints. However, the use of MALDI-TOF MS in plant research has been very limited. In the present study, a first protocol is proposed for metabolic fingerprinting by MALDI-TOF MS using three different MALDI matrices with subsequent multivariate data analysis by in-house algorithms implemented in the R environment for the taxonomic classification of plants from different genera, families and orders. By merging the data acquired with different matrices, different ionization modes and using careful algorithms and parameter selection, we demonstrate that a close taxonomic classification can be achieved based on plant metabolic fingerprints, with 92% similarity to the taxonomic classifications found in literature. The present work therefore highlights the great potential of applying MALDI-TOF MS for the taxonomic classification of plants and, furthermore, provides a preliminary foundation for future research.

Enhanced Glucose-induced Intracellular Signaling Promotes Insulin Hypersecretion: Pancreatic Beta-cell Functional Adaptations In A Model Of Genetic Obesity And Prediabetes.

Obesity is associated with insulin resistance and is known to be a risk factor for type-2 diabetes. In obese individuals, pancreatic beta-cells try to compensate for the increased insulin demand in order to maintain euglycemia. Most studies have reported that this adaptation is due to morphological changes. However, the involvement of beta-cell functional adaptations in this process needs to be clarified. For this purpose, we evaluated different key steps in the glucose-stimulated insulin secretion (GSIS) in intact islets from female ob/ob obese mice and lean controls. Obese mice showed increased body weight, insulin resistance, hyperinsulinemia, glucose intolerance and fed hyperglycemia. Islets from ob/ob mice exhibited increased glucose-induced mitochondrial activity, reflected by enhanced NAD(P)H production and mitochondrial membrane potential hyperpolarization. Perforated patch-clamp examination of beta-cells within intact islets revealed several alterations in the electrical activity such as increased firing frequency and higher sensitivity to low glucose concentrations. A higher intracellular Ca(2+) mobilization in response to glucose was also found in ob/ob islets. Additionally, they displayed a change in the oscillatory pattern and Ca(2+) signals at low glucose levels. Capacitance experiments in intact islets revealed increased exocytosis in individual ob/ob beta-cells. All these up-regulated processes led to increased GSIS. In contrast, we found a lack of beta-cell Ca(2+) signal coupling, which could be a manifestation of early defects that lead to beta-cell malfunction in the progression to diabetes. These findings indicate that beta-cell functional adaptations are an important process in the compensatory response to obesity.

Effect Of Low-level Laser Therapy (lllt) On Peripheral Nerve Regeneration Using Fibrin Glue Derived From Snake Venom.

The purpose of this study was to assess whether the adhesive permits the collateral repair of axons originating from a vagus nerve to the interior of a sural nerve graft, and whether low-level laser therapy (LLLT) assists in the regeneration process. Study sample consisted of 32 rats randomly separated into three groups: Control Group (CG; n=8), from which the intact sural nerve was collected; Experimental Group (EG; n=12), in which one of the ends of the sural nerve graft was coapted to the vagus nerve using the fibrin glue; and Experimental Group Laser (EGL; n=12), in which the animals underwent the same procedures as those in EG with the addition of LLLT. Ten weeks after surgery, the animals were euthanized. Morphological analysis by means of optical and electron microscopy, and morphometry of the regenerated fibers were employed to evaluate the results. Collateral regeneration of axons was observed from the vagus nerve to the interior of the autologous graft in EG and EGL, and in CG all dimensions measured were greater and presented a significant difference in relation to EG and EGL, except for the area and thickness of the myelin sheath, that showed significant difference only in relation to the EG. The present study demonstrated that the fibrin glue makes axonal regeneration feasible and is an efficient method to recover injured peripheral nerves, and the use of low-level laser therapy enhances nerve regeneration.

Low-level Laser Therapy To The Mouse Femur Enhances The Fungicidal Response Of Neutrophils Against Paracoccidioides Brasiliensis.

Neutrophils (PMN) play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM), which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. The goal of the study was to use low-level laser therapy (LLLT) to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan), and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point) on alternate days at two points on each hind leg. The aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. The number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS) and their fungicidal activity. The highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. The kinetics of neutrophil protein production also correlated with a more activated state. LLLT may be a safe and non-invasive approach to deal with PCM infection.

In Vivo Evaluation Of The Genetic Toxicity Of Rubus Niveus Thunb. (rosaceae) Extract And Initial Screening Of Its Potential Chemoprevention Against Doxorubicin-induced Dna Damage.

Rubus niveus Thunb. plant belongs to Rosaceae family and have been used traditionally to treat wounds, burns, inflammation, dysentery, diarrhea and for curing excessive bleeding during menstrual cycle. The present study was undertaken to investigate the in vivo genotoxicity of Rubus niveus aerial parts extract and its possible chemoprotection on doxorubicin (DXR)-induced DNA damage. In parallel, the main phytochemicals constituents in the extract were determined. The animals were exposed to the extract for 24 and 48h, and the doses selected were 500, 1000 and 2000mg/kg b.w. administered by gavage alone or prior to DXR (30mg/kg b.w.) administered by intraperitoneal injection. The endpoints analyzed were DNA damage in bone marrow and peripheral blood cells assessed by the alkaline alkaline (pH>13) comet assay and bone marrow micronucleus test. The results of chemical analysis of the extract showed the presence of tormentic acid, stigmasterol, quercitinglucoronide (miquelianin) and niga-ichigoside F1 as main compounds. Both cytogenetic endpoints analyzed showed that there were no statistically significant differences (p>0.05) between the negative control and the treated groups with the two higher doses of Rubus niveus extract alone, demonstrating absence of genotoxic and mutagenic effects. Aneugenic/clastogenic effect was observed only at 2000mg/kg dose. On the other hand, in the both assays and all tested doses were observed a significant reduction of DNA damage and chromosomal aberrations in all groups co-treated with DXR and extract compared to those which received only DXR. These results indicate that Rubus niveus aerial parts extract did not revealed any genotoxic effect, but presented some aneugenic/clastogenic effect at higher dose; and suggest that it could be a potential adjuvant against development of second malignant neoplasms caused by the cancer chemotherapic DXR.

The Psychedelic State Induced By Ayahuasca Modulates The Activity And Connectivity Of The Default Mode Network.

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.