Early Effects on T lymphocyte Response to Iron Deficiency in Mice. Short Communication

Iron deficiency is a common nutritional disorder, affecting about 30% of the world population. Deficits in iron functional compartments have suppressive effects on the immune system. Environmental problems, age, and other nutrient deficiencies are some of the situations which make human studies difficult and warrant the use of animal models. This study aimed to investigate alterations in the immune system by inducing iron deficiency and promoting recuperation in a mouse model. Hemoglobin concentration, hematocrit, liver iron store, and flow cytometry analyses of cell-surface transferrin receptor (CD71) on peripheral blood and spleen CD4+ and CD8+ T lymphocyte were performed in the control (C) and the iron-deficient (ID) groups of animals at the beginning and end of the experiment. Hematological indices of C and ID mice were not different but the iron stores of ID mice were significantly reduced. Although T cell subsets were not altered, the percentage of T cells expressing CD71 was significantly increased by ID. The results suggest that iron deficiency induced by our experimental model would mimic the early events in the onset of anemia, where thymus atrophy is not enough to influence subset composition of T cells, which can still respond to iron deficiency by upregulating the expression of transferrin receptor.

The Effects of Different Loading Times on the Bone Response Around Dental Implants: A Histomorphometric Study in Dogs

Purpose: The aim of this study was to evaluate, through histomorphometric analysis, the effect that different loading times would have on the bone response around implants. Materials and Methods: Three Replace Select implants were placed on each side of the mandible in eight dogs (n = 48 implants). One pair of implants was selected for an immediate loading protocol (IL). After 7 days, the second pair of implants received prostheses for an early loading protocol (EL). Fourteen days after implant placement, the third pair of implants received prostheses for advanced early loading (AEL). Following 12 weeks of prosthetics, counted following the positioning of the metallic crowns for the AEL group, the animals were sacrificed and the specimens were prepared for histomorphometric analysis. The differences between loading time in the following parameters were evaluated through analysis of variance: bone-to-implant contact, bone density, and crestal bone loss. Results: The mean percentage of bone-to-implant contact for IL was 77.9% +/- 1.71%, for EL it was 79.25% +/- 2.11%, and for AEL it was 79.42% +/- 1.49%. The mean percentage of bone density for IL was 69.97% +/- 3.81%, for EL it was 69.23% +/- 5.68%, and for AEL it was 69.19% +/- 2.90%. Mean crestal bone loss was 1.57 +/- 0.22 mm for IL, 1.23 +/- 0.19 mm for EL, and 1.17 +/- 0.32 mm for AEL. There was no statistical difference for any of the parameters evaluated (P > .05). Conclusion: Different early loading times did not seem to significantly affect the bone response around dental implants. INT J ORAL MAXILLOFAC IMPLANTS 2010;25:473-481

The Immune-Pineal Axis Stress as a Modulator of Pineal Gland Function

The temporal organization of mammals presents a daily adjustment to the environmental light/dark cycle. The environmental light detected by the retina adjusts the central clock in the suprachiasmatic nuclei, which innervate the pineal gland through a polysynaptic pathway. During the night, this gland produces and releases the nocturnal hormone melatonin, which circulates throughout the whole body and adjusts several bodily functions according to the existence and duration of darkness. We have previously shown that during the time frame of an inflammatory response, pro-inflammatory cytokines, such as tumor necrosis factor-a, inhibit while anti-inflammatory mediators, such as glucocorticoids, enhance the synthesis of melatonin, interfering in the daily adjustment of the light/dark cycle. Therefore, injury disconnects the organism from environmental cycling, while recovery restores the light/dark information to the whole organism. Here, we extend these observations by evaluating the effect of a mild restraint stress, which did not induce macroscopic gastric lesions. After 2 h of restraint, there was an increase in circulating corticosterone, indicating activation of the hypothalamus-pituitary-adrenal (HPA) axis. In parallel, an increase in melatonin production was observed. Taking into account the data obtained with models of inflammation and stress, we reinforce the hypothesis that the activity of the pineal gland is modulated by the state of the immune system and the HPA axis, implicating the darkness hormone melatonin as a modulator of defense responses.

Endurance training activates AMP-activated protein kinase, increases expression of uncoupling protein 2 and reduces insulin secretion from rat pancreatic islets

Endurance exercise is known to enhance peripheral insulin sensitivity and reduce insulin secretion. However, it is unknown whether the latter effect is due to the reduction in plasma substrate availability or alterations in beta-cell secretory machinery. Here, we tested the hypothesis that endurance exercise reduces insulin secretion by altering the intracellular energy-sensitive AMP-activated kinase (AMPK) signaling pathway. Male Wistar rats were submitted to endurance protocol training one, three, or five times per week, over 8 weeks. After that, pancreatic islets were isolated, and glucose-induced insulin secretion (GIIS), glucose transporter 2 (GLUT2) protein content, total and phosphorylated calmodulin kinase kinase (CaMKII), and AMPK levels as well as peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC-1 alpha) and uncoupling protein 2 (UCP2) content were measured. After 8 weeks, chronic endurance exercise reduced GIIS in a dose-response manner proportionally to weekly exercise frequency. Contrariwise, increases in GLUT2 protein content, CaMKII and AMPK phosphorylation levels were observed. These alterations were accompanied by an increase in UCP2 content, probably mediated by an enhancement in PGC-1 alpha protein expression. In conclusion, chronic endurance exercise induces adaptations in beta-cells leading to a reduction in GIIS, probably by activating the AMPK signaling pathway. Journal of Endocrinology (2011) 208, 257-264

BASS CYCLIC UNITS AS FACTORS IN A FREE GROUP IN INTEGRAL GROUP RING UNITS

Marciniak and Sehgal showed that if u is a non-trivial bicyclic unit of an integral group ring then there is a bicyclic unit v such that u and v generate a non-abelian free group. A similar result does not hold for Bass cyclic units of infinite order based on non-central elements as some of them have finite order modulo the center. We prove a theorem that suggests that this is the only limitation to obtain a non-abelian free group from a given Bass cyclic unit. More precisely, we prove that if u is a Bass cyclic unit of an integral group ring ZG of a solvable and finite group G, such that u has infinite order modulo the center of U(ZG) and it is based on an element of prime order, then there is a non-abelian free group generated by a power of u and a power of a unit in ZG which is either a Bass cyclic unit or a bicyclic unit.

Nanogravimetric study of the complex voltammetric response in the electro-oxidation of methanol on platinum

Instead of a time-invariant voltammetric profile, many electrochemical systems display a cycle-dependent current-potential response. This phenomenon has been referred to as complex voltammetric response and it has been observed during the electro-oxidation of several molecules such as methanol, ethanol, propanol and hydrogen. There are currently two explanations for the surface mechanism underlying this behavior. In one scenario, the complex voltammogram would result from the specific kinetic pathway taken during the forward sweep. In the other explanation, the phenomenon is discussed in terms of the interplay among the surface roughening and subsequent relaxation, and the ohmic drop coupled to a negative differential resistance. We report in this paper a nanogravimetric investigation of the complex voltammetric response in the electro-oxidation of methanol on platinum electrode in both acidic and alkaline media. Different periodic patterns composed of intercalated small and large hysteresis cycles were observed as a function of the applied voltage and the series resistance between the working electrode and the potentiostat. Independently, nanogravimetric results indicated no detectable difference in the delta-frequency versus voltage profile between small and large hysteresis cycles. These findings were interpreted as experimental evidence of the secondary, if any, role played by the very electrochemical reaction on the emergence of complex voltammetric response. (C) 2009 Elsevier Ltd. All rights reserved.

Effect of cyclic load on vertical misfit of prefabricated and cast implant single abutment

OBJECTIVES: The purpose of this in vitro study was to evaluate misfit alterations at the implant/abutment interface of external and internal connection implant systems when subjected to cyclic loading. MATERIAL AND METHODS: Standard metal crowns were fabricated for 5 groups (n=10) of implant/abutment assemblies: Group 1, external hexagon implant and UCLA cast-on premachined abutment; Group 2, internal hexagon implant and premachined abutment; Group 3, internal octagon implant and prefabricated abutment; Group 4, external hexagon implant and UCLA cast-on premachined abutment; and Group 5, external hexagon implant and Ceraone abutment. For groups 1, 2, 3 and 5, the crowns were cemented on the abutments and in group 4 crowns were screwed directly on the implant. The specimens were subjected to 500,000 cycles at 19.1 Hz of frequency and non-axial load of 133 N in a MTS 810 machine. The vertical misfit (μm) at the implant/abutment interface was evaluated before (B) and after (A) application of the cyclic loading. Data were analyzed statistically by using two-away ANOVA and Tukey's post-hoc test (p<0.05). RESULTS: Before loading values showed no difference among groups 2 (4.33±3.13), 3 (4.79±3.43) and 5 (3.86±4.60); between groups 1 (12.88±6.43) and 4 (9.67±3.08), and among groups 2, 3 and 4. However, groups 1 and 4 were significantly different from groups 2, 3 and 5. After loading values of groups 1 (17.28±8.77) and 4 (17.78±10.99) were significantly different from those of groups 2 (4.83±4.50), 3 (8.07±4.31) and 5 (3.81±4.84). There was a significant increase in misfit values of groups 1, 3 and 4 after cyclic loading, but not for groups 2 and 5. CONCLUSIONS: The cyclic loading and type of implant/abutment connection may develop a role on the vertical misfit at the implant/abutment interface.

Bone response to biosilicates® with different crystal phases

The aim of this study was to investigate the histological and histomorphometrical bone response to three Biosilicates with different crystal phases comparing them to Bioglass®45S5 implants used as control. Ceramic glass Biosilicate and Bioglass®45S5 implants were bilaterally inserted in rabbit femurs and harvested after 8 and 12 weeks. Histological examination did not revealed persistent inflammation or foreign body reaction at implantation sites. Bone and a layer of soft tissue were observed in close contact with the implant surfaces in the medullary canal. The connective tissue presented few elongated cells and collagen fibers located parallel to implant surface. Cortical portion after 8 weeks was the only area that demonstrated significant difference between all tested materials, with Biosilicate 1F and Biosilicate 2F presenting higher bone formation than Bioglass®45S5 and Biosilicate® vitreo (p=0.02). All other areas and periods were statistically non-significant (p>0.05). In conclusion, all tested materials were considered biocompatible, demonstrating surface bone formation and a satisfactory behavior at biological environment.

Subcutaneous connective tissue response to primary root canal filling materials

This study evaluated the response of the subcutaneous connective tissue of BALB/c mice to root filling materials indicated for primary teeth: zinc oxide/eugenol cement (ZOE), Calen paste thickened with zinc oxide (Calen/ZO) and Sealapex sealer. The mice (n=102) received polyethylene tube implants with the materials, thereby forming 11 groups, as follows: I, II, III: Calen/ZO for 7, 21 and 63 days, respectively; IV, V, VI: Sealapex for 7, 21 and 63 days, respectively; VII, VIII, IX: ZOE for 7, 21 and 63 days, respectively; X and XI: empty tube for 7 and 21 days, respectively. The biopsied tissues were submitted to histological analysis (descriptive analysis and semi-quantitative analysis using a scoring system for collagen fiber formation, tissue thickness and inflammatory infiltrate). A quantitative analysis was performed by measuring the area and thickness of the granulomatous reactionary tissue (GRT). Data were analyzed by Kruskal-Wallis, ANOVA and Tukey's post-hoc tests (?=0.05). There was no significant difference (p>0.05) among the materials with respect to collagen fiber formation or GRT thickness. However, Calen/ZO produced the least severe inflammatory infiltrate (p<0.05). The area of the GRT was significantly smaller (p<0.05) for Calen/ZO and Sealapex. In conclusion, Calen/ZO presented the best tissue reaction, followed by Sealapex and ZOE.

Subcutaneous tissue response of isogenic mice to calcium hydroxide-based pastes with chlorhexidine

This study was evaluated the response of subcutaneous connective tissue of isogenic mice to calcium hydroxide-based pastes with chlorhexidine digluconate (CHX). Seventy isogenic male BALB/c mice aged 6-8 weeks and weighing 15-20 g were randomly assigned to 8 groups. The animals received polyethylene tube implants as follows: Groups I, II, and III (n=10) - Calen® paste mixed with 0.4% CHX (experimental paste; Calen/CHX) for 7, 21, and 63 days, respectively; Groups IV, V, and VI (n=10) - UltraCal™ paste mixed with 2% CHX (experimental paste supplied by Ultradent Products Inc.; Ultracal/CHX) for 7, 21, and 63 days, respectively; and Groups VII and VIII (n=5): empty tube for 7 and 21 days, respectively. At the end of the experimental periods, the implants were removed together with the surrounding tissues (skin and subcutaneous connective tissue). The biopsied tissues were subjected to routine processing for histological analysis. Using a descriptive analysis and a four-point (0-3) scoring system, the following criteria were considered for qualitative and quantitative analysis of the tissue around the implanted materials: collagen fiber formation, tissue thickness and inflammatory infiltrate. A quantitative analysis was performed by measuring the thickness (µm), area (µm²) and perimeter (µm) of the reactionary granulomatous tissue formed at the tube ends. Data were analyzed statistically by the Kruskal-Wallis test and Dunn's post-test (α=0.05). Calen/CHX showed biocompatibility with the subcutaneous and reactionary tissues, with areas of discrete fibrosis and normal conjunctive fibrous tissue, though without statistically significant difference (p>0.05) from the control groups. In Groups I to III, there was a predominance of score 1, while in Groups IV to VI scores 2 and 3 predominated for all analyzed parameters. UltraCal/CHX, on the other hand, induced the formation of an inflammatory infiltrate and abundant exudate, suggesting a persistent residual aggression from the material, even 63 days after implant placement. In conclusion, the Calen paste mixed with 0.4% CHX allowed an adequate tissue response, whereas the UltraCal paste mixed with 2% CHX showed unsatisfactory results.

Bone response to a Ca- and P-enriched titanium surface obtained by anodization

This study evaluated bone response to a Ca- and P- enriched titanium (Ti) surface treated by a multiphase anodic spark deposition coating (BSP-AK). Two mongrel dogs received bilateral implantation of 3 Ti cylinders (4.1 x 12 mm) in the humerus, being either BSP-AK treated or untreated (machined - control). At 8 weeks postimplantation, bone fragments containing the implants were harvested and processed for histologic and histomorphometric analyses. Bone formation was observed in cortical area and towards the medullary canal associated to approximately 1/3 of implant extension. In most cases, in the medullary area, collagen fiber bundles were detected adjacent and oriented parallel to Ti surfaces. Such connective tissue formation exhibited focal areas of mineralized matrix lined by active osteoblasts. The mean percentages of bone-to-implant contact were 2.3 (0.0-7.2 range) for BSP-AK and 0.4 (0.0-1.3 range) for control. Although the Mann-Whitney test did not detect statistically significant differences between groups, these results indicate a trend of BSP-AK treated surfaces to support contact osteogenesis in an experimental model that produces low bone-to-implant contact values.

Tissue inflammatory response to implantation of calcium hydroxide and iodoform in the back of rats

PURPOSE: This study evaluated the inflammatory reaction caused by the implantation of iodoform and calcium hydroxide in the back of rats. These drugs may be used as intracanal dressings to eliminate residual bacteria of the root canal system. METHODS: Twenty albinic rats (Rattus norvegicus, var Wistar) were divided into four groups: control group 1 (CG1) had normal skin; control group 2 (CG2) had wounded tissue without drugs; in groups 3 and 4, iodoform (IG) and calcium hydroxide (CHG) were inserted into the wounds, respectively. After 3, 5 and 11 days, slices of the implanted areas were macroscopically and microscopically observed regarding to their qualitative and quantitative aspects. RESULTS: In the macroscopical analysis, the CHG showed a large area of necrosis and swelling, which progressively decreased; in the IG the presence of iodoform surrounded by normal tissue was observed. The qualitative and quantitative histological analysis showed that IG promoted a shorter delay in the inflammatory response than the CHG. CONCLUSION: The inflammatory reaction for iodoform had a peak period five days after the drug insertion. By comparison, calcium hydroxide showed a very large area of necrosis that could only be partially eliminated after eleven days.

Cardiac response and anxiety levels in psychopathic murderers

OBJECTIVE: To compare the emotional response and level of anxiety of psychopathic murderers, non-psychopathic murderers, and nonpsychopathic non-criminals. METHOD: 110 male individuals aged over 18 years were divided into three groups: psychopathic murderers (n = 38); non-psychopathic murderers (n = 37) serving sentences for murder convictions in Maximum Security Prisons in the State of Sao Paulo; and non-criminal, non-psychopathic individuals (n = 35) according to the Psychopathy Checklist-Revised. The emotional response of subjects was assessed by heart rate variation and anxiety level (State-Trait Anxiety Inventory) after viewing standardized pictures depicting pleasant, unpleasant and neutral content from the International Affective Picture System. RESULTS: Psychopathic murderers presented lower anxiety levels and smaller heart rate variations when exposed to pleasant and unpleasant stimuli than nonpsychopathic murderers or non-psychopathic non-criminals. The results also demonstrated that the higher the score for factor 1 on the Psychopathy Checklist-Revised, the lower the heart rate variation and anxiety level. CONCLUSION: The results suggest that psychopathic murderers do not present variation in emotional response to different visual stimuli. Although the non-psychopathic murderers had committed the same type of crime as the psychopathic murderers, the former tended to respond with a higher level of anxiety and heart rate variation.

Enhanced response of the fricke solution doped with hematoporphyrin under X-rays irradiation

The vials filled with Fricke solutions were doped with increasing concentrations of Photogem®, used in photodynamic therapy. These vials were then irradiated with low-energy X-rays with doses ranging from 5 to 20 Gy. The conventional Fricke solution was also irradiated with the same doses. The concentration of ferric ions for the Fricke and doped-Fricke irradiated solutions were measured in a spectrophotometer at 220 to 340 nm. The results showed that there was an enhancement in the response of the doped-Fricke solution, which was proportional to the concentration of the photosensitizer. The use of such procedure for studying the radiosensitizing property of photosensitizers based on the production of free radicals is also discussed.

Keratoconus prediction using a finite element model of the cornea with local biomechanical properties

PURPOSE: The ability to predict and understand which biomechanical properties of the cornea are responsible for the stability or progression of keratoconus may be an important clinical and surgical tool for the eye-care professional. We have developed a finite element model of the cornea, that tries to predicts keratoconus-like behavior and its evolution based on material properties of the corneal tissue. METHODS: Corneal material properties were modeled using bibliographic data and corneal topography was based on literature values from a schematic eye model. Commercial software was used to simulate mechanical and surface properties when the cornea was subject to different local parameters, such as elasticity. RESULTS: The simulation has shown that, depending on the corneal initial surface shape, changes in local material properties and also different intraocular pressures values induce a localized protuberance and increase in curvature when compared to the remaining portion of the cornea. CONCLUSIONS: This technique provides a quantitative and accurate approach to the problem of understanding the biomechanical nature of keratoconus. The implemented model has shown that changes in local material properties of the cornea and intraocular pressure are intrinsically related to keratoconus pathology and its shape/curvature.