Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute lung injury in mice

Lipopolysaccharides from gram-negative bacteria are amongst the most common causative agents of acute lung injury, which is characterized by an inflammatory response, with cellular infiltration and the release of mediators/cytokines. There is evidence that bradykinin plays a role in lung inflammation in asthma but in other types of lung inflammation its role is less clear. In the present study we evaluated the role of the bradykinin B(1) receptor in acute lung injury caused by lipopolysaccharide inhalation and the mechanisms behind bradykinin actions participating in the inflammatory response. We found that in C57BI/6 mice, the bradykinin B(1) receptor expression was up-regulated 24 h after lipopolysaccharide inhalation. At this time, the number of cells and protein concentration were significantly increased in the bronchoalveolar lavage fluid and the mice developed airway hyperreactivity to methacholine. In addition, there was an increased expression of tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma and chemokines (monocytes chemotactic protein-1 and KC) in the bronchoalveolar lavage fluid and in the lung tissue. We then treated the mice with a bradykinin B, receptor antagonist, R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8)]desArg(9)-bradykinin), 30 min after lipopolysaccharide administration. We observed that this treatment prevented the airway hyperreactivity as well as the increased cellular infiltration and protein content in the bronchoalveolar lavage fluid. Moreover, R-954 inhibited the expression of cytokines/chemokines. These results implicate bradykinin, acting through B(1) receptor, in the development of acute lung injury caused by lipopolysaccharide inhalation. (C) 2010 Elsevier B.V. All rights reserved.

SIGNALING PATHWAYS AND MEDIATORS IN LPS-INDUCED LUNG INFLAMMATION IN DIABETIC RATS: ROLE OF INSULIN

Diabetic patients are more susceptible to infections, and their inflammatory response is impaired. This is restored by insulin treatment. In the present study, we investigated the effect of insulin on LPS-induced signaling pathways and mediators in the lung of diabetic rats. Diabetic male Wistar rats (alloxan, 42 mg/kg i.v., 10 days) and control rats received intratracheal instillation of LPS (750 mu g/0.4 mL) or saline. Some diabetic rats were given neutral protamine Hagedorn insulin (4 IU s.c.) 2 h before LPS. After 6 h, bronchoalveolar lavage was performed for the release of mediators, and lung tissue was homogenized for analysis of LPS-induced signaling pathways. Relative to control rats, diabetic rats exhibited a significant reduction in the LPS-induced phosphorylation of extracellular signal-regulated kinase (64%), p38 (70%), protein kinase B (67%), and protein kinase C alpha (57%) and delta (65%) and in the expression of iNOS (32%) and cyclooxygenase 2 (67%) in the lung homogenates. The bronchoalveolar lavage fluid concentrations of NO (47%) and IL-6 (49%) were also reduced in diabetic rats, whereas the cytokine-induced neutrophil chemoattractant 2 (CINC-2) levels were increased 23%, and CINC-1 was not different from control animals. Treatment of diabetic rats with insulin completely or partially restored all these parameters. In conclusion, data presented show that insulin regulates mitogen-activated protein kinase, phosphatidylinositol 3`-kinase, protein kinase C pathways, expression of the inducible enzymes, cyclooxygenase 2 and iNOS, and levels of IL-6 and CINC-2 in LPS-induced lung inflammation in diabetic rats. These results suggest that the protective effect of insulin in sepsis could be due to modulation of cellular signal transduction factors.

Stress distribution in orthodontic mini-implants

The objective of this study was to evaluate the stress distribution in the resin in contact with the spirals of cylindrical and conical mini-implants, when submitted to lateral load and insertion torsion. A photoelastic model was fabricated using transparent gelatin to simulate the alveolar bone. The model was observed with a plane polariscope and photographically recorded before and after activation of the two screws with a lateral force and torsion. The lateral force application caused bending moments on both mini-implants, with the uprising of fringes or isochromatics, characteristics of stresses, along the threads of the mini-implants and in the apex. When the torsion was exerted in the mini-implants, a great concentration of stress upraised close to the apex. The conclusion was that, comparing conical with cylindrical mini-implants under lateral load, the stresses were similar on the traction sides. The differences appear (1) on the apex, where the cylindrical mini-implant showed a greater concentration of stress, and (2) along the spirals, in the compression side, where the conical mini-implant showed a greater concentration of stress. The greater part of the stress produced by both mini-implants, after torsion load in insertion, were concentrated on the apex. With the cylindrical mini-implant, the greater concentration of tension was close to the apex, while with the conical one, the stresses were distributed along a greater amount of apical threads.

Study of metals transfer from environment using teeth as biomonitor

We investigated chronic incorporation of metals in individuals from poor families, living in a small, restrict and allegedly contaminated area in Sao Paulo city, the surroundings of the Guarapiranga dam, responsible for water supply to 25% of the city population. A total of 59 teeth from individuals 7 to 60 years old were collected. The average concentrations of Pb, Cd, Fe, Zn, Mn, Ni and Cr were determined with an Atomic Absorption Spectrophotometer. The concentrations of all metals as function of the individuals` age exhibited a remarkable similarity: peaks between 7 and 10 years and sharply decreasing at higher ages, which could be attributed to alimentary habits and persistence to metals exposure all along the individuals` life span. From all the measured metals, lead and cadmium were a matter of much more concern since their measured values are close to the upper limits of the world wide averages. (C) 2009 Elsevier Ltd. All rights reserved.

Study of environmental burden of lead in children using teeth as bioindicator

The south region of Sao Paulo city hosts the Guarapiranga dam, responsible for water supply to 25% of the city population. Their surroundings have been subject to intense and irregular occupation by people from very low socioeconomics classes. Measurements undertaken on sediment and particulate materials in the dam revealed concentrations of lead. copper, zinc and cadmium above internationally accepted limits. Epidemiological and toxicological studies undertaken by the World Health Organization in individuals exhibiting lead concentrations in blood, near or below the maximum recommended (10 mu g dl(-1)), surprisingly revealed that toxic effects are more intense in individuals belonging to low socioeconomics classes. Motivated by these facts, we aimed at the investigation of chronic incorporation of lead. as well as the use of our BIOKINETICS code, which is based on an accepted ICRP biokinetics model for lead, in order to extrapolate the results from teeth to other organs. The focus of our data taking was children from poor families, living in a small, restrict and allegedly contaminated area in Sao Paulo city. Thus, a total of 74 human teeth were collected. The average concentration of lead in teeth of children 5 to 10 years old was determined by means of a high-resolution inductively coupled plasma mass spectrometer (ICP-MS). For standardization of the measurements, an animal bone certified material (H-Animal Bone), from the International Atomic Energy Agency, was analyzed. The amount of lead in children living in the surroundings of the dam, was approximately 40% higher than those from the control region, and the average lead concentration was equal to 1.3 mu g g(-1) approximately. Grouping the results in terms of gender, tooth type and condition, it was concluded that a carious molar of boys is a much more efficient contamination pathway for lead, resulting in concentrations 70% higher than in the control region. We also inferred the average concentrations of lead in other organs of these children, by making use of our BIOKINETIC code. (C) 2008 Elsevier Ltd. All rights reserved.

Evaluation of uranium incorporation from contaminated areas using teeth as bioindicators - a case study

The Southwest region of the Bahia state in Brazil hosts the largest uranium reserve of the country (100 kton in uranium, only), plus the cities of Caetite, Lagoa Real and Igapora. In this work, aim was at the investigation of uranium burdens on residents of these cities by using teeth as bioindicators, as a contribution for possible radiation protection measures. Thus, a total of 41 human teeth were collected, plus 50 from an allegedly uranium free area (the control region). Concentrations of uranium in teeth from residents of 5- to 87-y old were determined by means of a high-resolution inductively coupled plasma mass spectrometer (ICP-MS). The highest uranium concentration in teeth was measured from samples belonging to residents of Caetite (median equal to 16 ppb). Assuming that the uranium concentrations in teeth and bones are similar within 10-20% (for children and young adults), it concluded that uranium body levels in residents of Caetite are at least one order of magnitude higher than the worldwide average. This finding led to conclude that daily ingestion of uranium, from food and water, is equally high.

Severe novel influenza A (H1N1) infection in cancer patients

Patients and methods: Clinical data from all patients admitted with acute respiratory failure due to novel viral H1N1 infection were reviewed. Lung tissue was submitted for viral and bacteriological analyses by real-time RT-PCR, and autopsy was conducted on all patients who died. Results: Eight patients were admitted, with ages ranging from 55 to 65 years old. There were five patients with solid organ tumors (62.5%) and three with hematological malignancies (37.5%). Five patients required mechanical ventilation and all died. Four patients had bacterial bronchopneumonia. All deaths occurred due to multiple organ failure. A milder form of lung disease was present in the three cases who survived. Lung tissue analysis was performed in all patients and showed diffuse alveolar damage in most patients. Other lung findings were necrotizing bronchiolitis or extensive hemorrhage. Conclusions: H1N1 viral infection in patients with cancer can cause severe illness, resulting in acute respiratory distress syndrome and death. More data are needed to identify predictors of unfavorable evolution in these patients.

Modularity and robustness of bone networks

Cortical bones, essential for mechanical support and structure in many animals, involve a large number of canals organized in intricate fashion. By using state-of-the art image analysis and computer graphics, the 3D reconstruction of a whole bone (phalange) of a young chicken was obtained and represented in terms of a complex network where each canal was associated to an edge and every confluence of three or more canals yielded a respective node. The representation of the bone canal structure as a complex network has allowed several methods to be applied in order to characterize and analyze the canal system organization and the robustness. First, the distribution of the node degrees (i.e. the number of canals connected to each node) confirmed previous indications that bone canal networks follow a power law, and therefore present some highly connected nodes (hubs). The bone network was also found to be partitioned into communities or modules, i.e. groups of nodes which are more intensely connected to one another than with the rest of the network. We verified that each community exhibited distinct topological properties that are possibly linked with their specific function. In order to better understand the organization of the bone network, its resilience to two types of failures (random attack and cascaded failures) was also quantified comparatively to randomized and regular counterparts. The results indicate that the modular structure improves the robustness of the bone network when compared to a regular network with the same average degree and number of nodes. The effects of disease processes (e. g., osteoporosis) and mutations in genes (e.g., BMP4) that occur at the molecular level can now be investigated at the mesoscopic level by using network based approaches.

Development of secondary palate requires strict regulation of ECM remodeling: sequential distribution of RECK, MMP-2, MMP-3, and MMP-9

We have evaluated RECK (reversion-inducing-cysteine-rich protein with Kazal motifs), MMP-2 (matrix metalloproteinase-2), MMP-3, and MMP-9 involvement during palate development in mice by using various techniques. Immunohistochemical features revealed the distribution of RECK, MMP-2, and MMP-3 in the mesenchymal tissue and in the midline epithelial seam at embryonic day 13 (E13), MMPs-2, -3, and -9 being particularly expressed at E14 and E14.5. In contrast, RECK was weakly immunostained at these times. Involvement of MMPs was validated by measuring not only their protein expression, but also their activity (zymograms). In situ hybridization signal (ISH) for RECK transcript was distributed in mesenchymal and epithelial regions within palatal shelves at all periods evaluated. Importantly, the results from ISH analysis were in accord with those obtained by real-time polymerase chain reaction. The expression of RECK was found to be temporally regulated, which suggested possible roles in palatal ontogeny. Taken together, our results clearly show that remodeling of the extracellular matrix is finely modulated during secondary palate development and occurs in a sequential manner.

Prescribing exercise for Osteoporosis

Osteoporosis is a major public health problem because of the morbidity and mortality associated with fracture. Minimizing the risk of fracture is the primary objective of osteoporosis management. The role of exercise in osteoporosis management is to increase and maintain peak bone density and reduce the rate of bone loss and the risk of falling. This article provides recommendations focusing on a life-span approach to minimizing the risk of fracture associated with osteoporosis. Osteoporosis prevention begins in childhood, when exercise can increase peak bone strength. In young adults, it can maintain peak bone mineral density. In elderly individuals, physical activity can slow bone loss and improve fitness and muscle strength, helping prevent falls and lower the risk of fracture. Exercise goals for individuals with osteoporosis should include reducing pain, increasing mobility, and improving muscle endurance, balance, and stability in order to improve the quality of life and reduce the risk of falling. Thus, exercise plays a significant part in reducing fractures in later life.

The relationship between muscle size and bone geometry during growth and in response to exercise

As muscles become larger and stronger during growth and in response to increased loading, bones should adapt by adding mass, size, and strength. In this unilateral model, we tested the hypothesis that (1) the relationship between muscle size and bone mass and geometry (nonplaying arm) would not change during different stages of puberty and (2) exercise would not alter the relationship between muscle and bone, that is, additional loading would result in a similar unit increment in both muscle and bone mass, bone size, and bending strength during growth. We studied 47 competitive female tennis players aged 8–17 years. Total, cortical, and medullary cross-sectional areas, muscle area, and the polar second moment of area (Ip) were calculated in the playing and nonplaying arms using magnetic resonance imaging (MRI); BMC was assessed by DXA. Growth effects: In the nonplaying arm in pre-, peri- and post-pubertal players, muscle area was linearly associated BMC, total and cortical area, and Ip (r = 0.56–0.81, P < 0.09 to < 0.001), independent of age. No detectable differences were found between pubertal groups for the slope of the relationship between muscle and bone traits. Post-pubertal players, however, had a higher BMC and cortical area relative to muscle area (i.e., higher intercept) than pre- and peri-pubertal players (P < 0.05 to < 0.01), independent of age; pre- and peri-pubertal players had a greater medullary area relative to muscle area than post-pubertal players (P < 0.05 to < 0.01). Exercise effects: Comparison of the side-to-side differences revealed that muscle and bone traits were 6–13% greater in the playing arm in pre-pubertal players, and did not increase with advancing maturation. In all players, the percent (and absolute) side-to-side differences in muscle area were positively correlated with the percent (and absolute) differences in BMC, total and cortical area, and Ip (r = 0.36–0.40, P < 0.05 to < 0.001). However, the side-to-side differences in muscle area only accounted for 11.8–15.9% of the variance of the differences in bone mass, bone size, and bending strength. This suggests that other factors associated with loading distinct from muscle size itself contributed to the bones adaptive response during growth. Therefore, the unifying hypothesis that larger muscles induced by exercise led to a proportional increase in bone mass, bone size, and bending strength appears to be simplistic and denies the influence of other factors in the development of bone mass and bone shape.

Fabrication of novel metal alloy foams for biomedical applications

Degeneration of the weight bearing bones of the ageing population often requires the inception of metallic biomaterials. Research in this area is receiving increased attention globally. However, most of today's artificial bone materials are dense and suffer from problems of adverse reaction, biomechanical mismatch and lack of appropriate space for the regeneration of new bone tissues. In the present study, novel ZrTi alloy foams with a porous structure and mechanical properties that are very close to those of bone were fabricated. These ZrTi alloy foams are biocompatible, and display a porous structure permitting the ingrowth of new bone tissues.

Nano- and macro-scale characterisation of the mechanical properties of bovine bone

In the present study, nano- and macro-scale characterisations on the mechanical properties of bovine cortical bones have been performed by using nanoindentation and conventional compressive tests. Nanoindentation results showed that the elastic modulus for the osteons and the interstitial lamellae in the longitude direction were 24.7 ± 2.5 GPa and 30.1 ± 2.4 GPa. As it’s difficult to distinguish osteons from interstitial lamellae in the transverse direction, the average elastic modulus for cortical bovine bone in the transverse direction was 19.8 ± 1.6 GPa. Significant differences were found in the modulus values between different microstructures of bone tissue and in different testing direction. It was found that the elastic modulus of bone bovine material in nano-level was higher than that in macro-level. The elastic modulus and
ultimate stress of large bone samples were 12.5 ± 1.9 GPa and 195 ± 19 MPa respectively from the compression test.