Role of cytokines (TNF-alpha, IL-1 beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide

Introduction Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Purpose Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11. Materials and methods Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and KC ELISA. Results CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1 beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1 beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea. Conclusion These results suggest an important role of TNF-alpha, IL-1 beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

Effect of image analysis software on neurofunctional activation during processing of emotional human faces

Functional brain imaging techniques such as functional MRI (fMRI) that allow the in vivo investigation of the human brain have been exponentially employed to address the neurophysiological substrates of emotional processing. Despite the growing number of fMRI studies in the field, when taken separately these individual imaging studies demonstrate contrasting findings and variable pictures, and are unable to definitively characterize the neural networks underlying each specific emotional condition. Different imaging packages, as well as the statistical approaches for image processing and analysis, probably have a detrimental role by increasing the heterogeneity of findings. In particular, it is unclear to what extent the observed neurofunctional response of the brain cortex during emotional processing depends on the fMRI package used in the analysis. In this pilot study, we performed a double analysis of an fMRI dataset using emotional faces. The Statistical Parametric Mapping (SPM) version 2.6 (Wellcome Department of Cognitive Neurology, London, UK) and the XBAM 3.4 (Brain Imaging Analysis Unit, Institute of Psychiatry, Kings College London, UK) programs, which use parametric and non-parametric analysis, respectively, were used to assess our results. Both packages revealed that processing of emotional faces was associated with an increased activation in the brain`s visual areas (occipital, fusiform and lingual gyri), in the cerebellum, in the parietal cortex, in the cingulate cortex (anterior and posterior cingulate), and in the dorsolateral and ventrolateral prefrontal cortex. However, blood oxygenation level-dependent (BOLD) response in the temporal regions, insula and putamen was evident in the XBAM analysis but not in the SPM analysis. Overall, SPM and XBAM analyses revealed comparable whole-group brain responses. Further Studies are needed to explore the between-group compatibility of the different imaging packages in other cognitive and emotional processing domains. (C) 2009 Elsevier Ltd. All rights reserved.

Effect of remifentanil hydrochloride administered via constant rate infusion on the minimum alveolar concentration of isoflurane in cats

Objective-To evaluate the effects of increasing doses of remifentanil hydrochloride administered via constant rate infusion (CRI) on the minimum alveolar concentration (MAC) of isoflurane in cats. Animals-6 healthy adult cats. Procedures-For each cat, 2 experiments were performed (2-week interval). On each study day, anesthesia was induced and maintained with isoflurane; a catheter was placed in a cephalic vein for the administration of lactated Ringer`s solution or remifentanil CRIs, and a catheter was placed in the jugular vein for collection of blood samples for blood gas analyses. On the first study day, individual basal MAC (MAC(Basal)) was determined for each cat. On the second study day, 3 remifentanil CRIs (0.25, 0.5, and 1.0 mu g/kg/min) were administered (in ascending order); for each infusion, at least 30 minutes elapsed before determination of MAC (designated as MAC(R0.25`) MAC(R0.5`) and MACR(R1.0`) respectively). A 15-minute washout period was allowed between CRIs. A control MAC (MAC Control) was determined after the last remifentanil infusion. Results-Mean +/- SD MAC(Basal) and MAC(Control) values at sea level did not differ significantly (1.66 +/- 0.08% and 1.52 +/- 0.21%, respectively). The MAC values determined for each remifentanil CRI did not differ significantly. However, MACR(0.25`) MAC(R0.5`) and MAC(R1.0) were significantly decreased, compared with MAC(Basal`) by 23.4 +/- 79%, 29.8 +/- 8.3%, and 26.0 +/- 9.4%, respectively. Conclusions and Clinical Relevance-The 3 doses of remifentanil administered via CRI resulted in a similar degree of isoflurane MAC reduction in adult cats, indicating that a ceiling effect was achieved following administration of the lowest dose. (Am J Vet Res 2009;70:581-588)

Effect of laser phototherapy on recurring herpes labialis prevention: an in vivo study

Alternative treatment for recurrent labial infection by herpes simplex virus (HSV) have been considered. The aim of this study was to evaluate the effectiveness of laser phototherapy in prevention and reduction of severity of labial manifestations of herpes labialis virus. Seventy-one patients, divided into experimental (n = 41) and control (n = 30) groups were followed up for 16 months. Patients in the control group were treated topically with aciclovir and patients in the experimental group were subjected to laser phototherapy (one session per week, 10 weeks): 780 nm, 60 mW, 3.0 J/cm(2) or 4.5 J/cm(2) on healthy (no HSV-1 infection) and affected (with HSV-1 infection) tissues. Patients in the experimental group presented a significant decrease in dimension of herpes labialis lesions (P = 0.013) and inflammatory edema (P = 0.031). The reduction in pain level (P = 0.051) and monthly recurrences (P = 0.076) did not reach statistical significance. This study represents an in vivo indication that this treatment should be further considered as an effective alternative to therapeutic regimens for herpes labialis lesions.

Effect of defocused infrared diode laser on salivary flow rate and some salivary parameters of rats

This study aims to investigate whether infrared diode low-level laser therapy (LLLT) increased salivary flow rate and altered pH value, protein concentration, and peroxidase and amylase activities in saliva of rats. Wistar rats were used and divided into three groups. Experimental groups (A and 13) had their parotid, submandibular and sublingual glands submitted to diode laser, 808-nm wavelength, on two consecutive days. The dose results were 4 and 8 J/cm(2), respectively. A red guide light was used to visualize the irradiated area. Group C was irradiated only with red pilot beam and served as control. The saliva samples were collected after each irradiation step (first and second collection days) and 1 week after the first irradiation (seventh day). Statistical analysis was performed, and differences were observed according to different days of salivary collection. The results showed that salivary flow rate for groups A and B was higher on the seventh day if it is compared to data obtained for the first day (p<0.05). LLLT applications on salivary glands are a therapy procedure that requires further studies.

Effect of argon purity on mechanical properties, microstructure and fracture mode of commercially pure (cp) Ti and Ti-6Al-4V alloys for ceramometal dental prostheses

Provision of an inert gas atmosphere with high-purity argon gas is recommended for preventing titanium castings from contamination although the effects of the level of argon purity on the mechanical properties and the clinical performance of Ti castings have not yet been investigated. The purpose of this study was to evaluate the effect of argon purity on the mechanical properties and microstructure of commercially pure (cp) Ti and Ti-6Al-4V alloys. The castings were made using either high-purity and/or industrial argon gas. The ultimate tensile strength (UTS), proportional limit (PL), elongation (EL) and microhardness (VHN) at different depths were evaluated. The microstructure of the alloys was also revealed and the fracture mode was analyzed by scanning electron microscopy. The data from the mechanical tests and hardness were subjected to a two-and three-way ANOVA and Tukey`s test (alpha = 0.05). The mean values of mechanical properties were not affected by the argon gas purity. Higher UTS, PL and VHN, and lower EL were observed for Ti-6Al-4V. The microhardness was not influenced by the argon gas purity. The industrial argon gas can be used to cast cp Ti and Ti-6Al-4V.

Pharmacokinetics of ingested fluoride: Lack of effect of chemical compound

Fluoride in drinking water may be present from natural sources or added as sodium fluoride (NaF), sodium silicofluoride (Na2SiF6) or fluorosilicic acid (H2SiF6). Results from an early study with rats suggested that, when ingested as Na2SiF6, the absorption and excretion of fluoride were greater than when ingested as NaF. Objective: The present single-blind, crossover study with 10 adults was done to determine three key pharmacokinetic parameters: the maximum plasma fluoride concentrations (C-max), the elapsed time to reach the maximum concentrations (T-max) and the 6-h areas under the time-plasma concentration curves (AUCs) after ingestion of 500 ml, of water containing 0.67 or 5.45 mg F/L present naturally or added as NaF or H2SiF6. Design: Blood was collected prior to and at nine time points during 6 h after ingestion of the test solutions. Plasma was analysed by electrode after HMDS-facilitated diffusion and the data were analysed for statistically significant differences using repeated measures ANOVA. Results: The C-max, T-max and AUC values after ingestion of the solutions containing natural fluoride, NaF or H2SiF6 did not differ significantly at either dose level. Further, the Tmax values associated with the 0.67 and SAS mg/L solutions did not differ significantly indicating that the absorption, distribution and elimination rates were not affected by the dose size. Conclusions: Considered together with published reports, the present findings support the conclusion that the major features of fluoride metabolism are not affected differently by the chemical compounds commonly used to fluoridate water nor are they affected by whether the fluoride is present naturally or added artificially. (C) 2008 Elsevier Ltd. All rights reserved.

Effect of Fluoridated Water on Plasma Insulin Levels and Glucose Homeostasis in Rats with Renal Deficiency

Glucose intolerance in fluorosis areas and when fluoride is administered for the treatment of osteoporosis has been reported. Controlled fluoridation of drinking water is regarded as a safe and effective measure to control dental caries. However, the effect on glucose homeostasis was not studied so far. The aim of this study was to evaluate the effect of the intake of fluoridated water supply on glucose metabolism in rats with normal and deficient renal function. Male Sprague-Dawley rats were divided into eight groups of four rats. Renal insufficiency was induced in four groups (NX) which received drinking water containing 0, 1, 5, and 15 ppm F (NaF) for 60 days. Four groups with simulated surgery acted as controls. There were no differences in plasma glucose concentration after a glucose tolerance test between controls and NX rats and among rats with different intakes of fluoride. However, plasma insulin level increased as a function of fluoride concentration in drinking water, both in controls and in NX rats. It is concluded that the consumption of fluoridated water from water supply did not affect plasma glucose levels even in cases of animals with renal disease. However, a resistance to insulin action was demonstrated.

The Effect of TAK-778 on Gene Expression of Osteoblastic Cells Is Mediated Through Estrogen Receptor

This study evaluated the effect of TAK-778 [(2R, 4S)-(-)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide)] on in vitro osteogenic events and on gene expression of osteoblastic cells derived from human alveolar bone and the participation of estrogen receptors (ERs) on such effect. Osteoblastic cells were subcultured, with or without TAK-778 (10(-5) M), to evaluate cell growth and viability, total protein content, and alkaline phosphatase (ALP) activity at 7, 14, and 21 days; bone-like formation at 21 days; and gene expression, using cDNA microarray, at 7 days. Also, osteoblastic cells were exposed to TAK-778 (10-5 M) combined to ICI182,780, a nonspecific ER antagonist (10(-6) M), and gene expression was evaluated by real-time polymerase chain reaction (PCR) at 7 days. TAK-778 induced a reduction in culture growth and an increase in cell synthesis, ALP activity, and bone-like formation. The cDNA microarray showed genes associated with cell adhesion and differentiation, skeletal development, ossification, and transforming growth factor-P receptor signaling pathway, with a tendency to be higher expressed in cells exposed to TAK-778. The gene expression of ALP, osteocalcin, Msh homeobox 2, receptor activator of NF-kappa B ligand, and intercellular adhesion molecule 1 was increased by TAK-778 as demonstrated by real-time PCR, and this effect was antagonized by ICI182,780. The present results demonstrated that TAK-778 acts at a transcriptional level to enhance the in vitro osteogenic process and that its effect on gene expression of osteoblastic cells is mediated, at least partially, through ERs. Based on these findings, TAK-778 could be considered in the treatment of bone metabolic disorders. Exp Biol Med 234:190-199, 2009

Low Level Laser Effects On Pain to Palpation and Electromyographic Activity in TMD Patients: A Double-Blind, Randomized, Placebo-Controlled Study

The purpose of this study was to evaluate the effect of diode laser (GaAlAs - 780 nm) on pain to palpation and electromyographic (EMG) activity of the masseter and anterior temporalis muscles. The laser was applied on the temporalis and masseter muscles twice a week (four weeks). Forty-eight (48) patients with myofascial pain were randomly assigned between actual and placebo treatments and between the energetic doses of 25 J/cm(2) and 60 J/cm(2), and were evaluated using VAS before, immediately after the final application, and 30 days after the laser treatment. Surface electromyography was performed with maximum dental clenching before and after laser therapy. The results show there were no significant statistical differences in the EMG activity between the groups before and after laser treatment. With regard to the pain at palpation, although both groups presented a significant difference in the symptoms before and after the treatment, only the active doses showed statistically significant reductions in pain level in all the regions of the palpated muscles. However, there was no significant statistical difference between groups (experimental and placebo). In conclusion, low level laser did not promote any changes in EMG activity. The treatment did, however, lessen the pain symptoms in the experimental groups.

Effect of Chelating Solutions on the Microhardness of Root Canal Lumen Dentin

Introduction: The greatest reduction in microhardness of the most superficial layer of dentin of the root canal lumen is desired. The use of chelating agents during biomechanical preparation of root canals removes smear layer, increasing the access of the irrigant into the dentin tubules to allow adequate disinfection, and also reduces dentin microhardness, facilitating the action of endodontic instruments. This study evaluated the effect of different chelating solutions on the microhardness of the most superficial dentin layer from the root canal lumen. Methods: Thirty-five recently extracted single-rooted maxillary central incisors were instrumented, and the roots were longitudinally sectioned in a mesiodistal direction to expose the entire canal extension. The specimens were distributed in seven groups according to the final irrigation: 15% EDTA, 10% citric acid, 5% malic acid, 5% acetic acid, apple vinegar, 10% sodium citrate, and control (no irrigation). A standardized volume of 50 mu L of each chelating solution was used for 5 minutes. Dentin microhardness was measured with a Knoop indenter under a 10-g load and a 15-second dwell time. Data were analyzed statistically by one-way analysis of variance and Tukey-Kramer multiple-comparison test at 5% significance level. Results: EDTA and citric acid had the greatest overall effect, causing a sharp decrease in dentin microhardness without a significant difference (p > .05) from each other. However, both chelators differed significantly from the other solutions (p < .001). Sodium citrate and deionized water were similar to each other (p > .05) and did not affect dentin microhardness. Apple vinegar, acetic acid, and malic acid were similar to each other (p > .05) and presented intermediate results. Conclusion: Except for sodium citrate, all tested chelating solutions reduced microhardness of the most superficial root canal dentin layer. EDTA and citric acid were the most efficient. (J Endod 2011;37:358-362)

Effect of a calcium hydroxide-based paste associated to chlorhexidine on RAW 264.7 macrophage cell line culture

Objective. The objective of this study was to evaluate the effect of a calcium hydroxide Ca(OH)(2)-based paste (Calen) associated or not to 0.4% chlorhexidine digluconate (CHX) on RAW 264.7 macrophage cell line culture. Study design. The cell viability (MTT assay), immunostimulating properties (NO dosage), and anti-inflammatory properties (NO, TNF-alpha, and IL-1 alpha dosage) were evaluated after cell exposure to the materials. Data were analyzed statistically by Kruskal-Wallis test at 5% significance level. Results. There was low immunostimulating activity of the Calen paste associated or not to 0.4% CHX in the different materials` concentrations evaluated (P > .05). Anti-inflammatory activity with inhibition of NO and cytokine (TNF-alpha and IL1-alpha) release was observed only with Ca(OH)(2) + CHX at the highest concentration (25 mu g/mL). Conclusion. As the Calen paste associated to 0.4% CHX did not alter cell viability or the immunostimulating and anti-inflammatory properties, the addition of CHX brought no benefits to the Ca(OH)(2)-based paste with regard to the tested parameters. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:e44-e51)

Effect of blood contamination on the shear bond strength at resin/dentin interface in primary teeth

Purpose: To assess in vitro the shear bond strength at the resin/dentin interface in primary teeth after contamination with fresh human blood. Methods: 75 crowns of primary molars were embedded in acrylic resin and mechanically ground to expose a flat dentin surface. The specimens were randomly assigned to five groups (n=15), according to the surface treatment. Group I (control) had no blood contamination. The other groups were blood-contaminated and subjected to different post-contamination protocols: in Group 2, the surfaces were rinsed with water; in Group 3, the surfaces were air-dried; in Group 4, the surfaces were rinsed and air-dried; and in Group 5, no post-contamination treatment was done. In all groups, a 3-mm dentin bonding site was demarcated, Single Bond adhesive system was applied and resin composite cylinders were bonded. After 24 hours in distilled water, shear bond strength was tested at a crosshead speed of 0.5 mm/minute. Results: Means (in MPa) were: Group 1: 7.1 (+/- 4.2); Group 2: 4.0 (+/- 1.8); Group 3: 0.9 (+/- 0.7); Group 4: 3.9 (+/- 2.2) and Group 5: 1.3 (+/- 1.5). Data were analyzed statistically by the Kruskal-Wallis test at 5% significance level. Groups 2 and 4 were similar to each other (P > 0.05) and both ware similar to Group 1 (P > 0.05). These groups (2, 3 and 4) had statistically significantly higher bond strengths than Groups 3 and 5 (P < 0.05). Blood contamination negatively affected the shear bond strength to primary tooth dentin. Among the blood-contaminated groups, water-rinsed specimens had higher bond strengths than those that were exclusively air-dried or not submitted to any post-contamination protocol before adhesive application.

A prospective 12-month study of the effect of smoking cessation on periodontal clinical parameters

P>Aim The aim of this 12-month prospective study was to assess the adjunctive effect of smoking cessation in non-surgical periodontal therapy of subjects with severe chronic periodontitis. Materials and methods Of the 201 subjects enrolled from a smoking cessation clinic, 93 were eligible and received non-surgical periodontal treatment and concurrent smoking cessation treatment. Periodontal maintenance was performed every 3 months. Full-mouth periodontal examination in six sites per tooth was performed by a calibrated examiner, blinded to smoking status, at baseline, 3, 6 and 12 months after non-surgical periodontal treatment. Furthermore, expired air carbon monoxide concentration measurements and interviews based on a structured questionnaire were performed in order to collect demographic and smoking data. Results Of the 93 eligible subjects, 52 remained in the study after 1 year. Of these, 17 quit smoking and 35 continued smoking or oscillated. After 1 year, only quitters presented significant clinical attachment gain (p=0.04). However, there were no differences between the groups regarding clinical attachment level, probing depth, bleeding on probing and plaque index after 1 year (p > 0.05). Conclusion Smoking cessation promoted clinical attachment gain in chronic periodontitis subjects from a smoking cessation clinic after 1 year of follow-up.

A case study of the direct radiative effect of biomass burning aerosols on precipitation in the Eastern Amazon

Numerical experiments with the Brazilian additions to the Regional Atmospheric Modeling System were performed with two nested grids (50 and 10 km horizontal resolution, respectively) with and without the effect of biomass burning for 8 different situations for 96 h integrations. Only the direct radiative effect of aerosols is considered. The results were analyzed in large areas encompassing the BR163 road (one of the main areas of deforestation in the Amazon). mainly where most of the burning takes place. The precipitation change due to the direct radiative impact of biomass burning is generally negative (i.e., there is a decrease of precipitation). However, there are a few cases with a positive impact. Two opposite forcing mechanisms were explored: (a) the thermodynamic forcing that is generally negative in the sense that the aerosol tends to stabilize the lower atmosphere and (b) the dynamic impact associated with the low level horizontal pressure gradients produced by the aerosol plumes. In order to understand the non-linear relationship between the two effects, experiments were performed with 4-fold emissions. In these cases, the dynamic effect overcomes the stabilization produced by the radiative forcing and precipitation increase is observed in comparison with the control experiment. This study suggests that. in general, the biomass burning radiative forcing decreases the precipitation. However, very large concentrations of aerosols may lead to an increase of precipitation due to the dynamical forcing associated with the horizontal pressure gradients. (C) 2009 Elsevier B.V. All rights reserved.