Modulation of peritoneal macrophage activity by the saturation state of the fatty acid moiety of phosphatidylcholine

To determine the effects of saturated and unsaturated fatty acids in phosphatidylcholine (PC) on macrophage activity, peritoneal lavage cells were cultured in the presence of phosphatidylcholine rich in saturated or unsaturated fatty acids (sat PC and unsat PC, respectively), both used at concentrations of 32 and 64 µM. The treatment of peritoneal macrophages with 64 µM unsat PC increased the production of hydrogen peroxide by 48.3% compared to control (148.3 ± 16.3 vs 100.0 ± 1.8%, N = 15), and both doses of unsat PC increased adhesion capacity by nearly 50%. Moreover, 64 µM unsat PC decreased neutral red uptake by lysosomes by 32.5% compared to the untreated group (67.5 ± 6.8 vs 100.0 ± 5.5%, N = 15), while both 32 and 64 µM unsat PC decreased the production of lipopolysaccharide-elicited nitric oxide by 30.4% (13.5 ± 2.6 vs 19.4 ± 2.5 µM) and 46.4% (10.4 ± 3.1 vs 19.4 ± 2.5 µM), respectively. Unsat PC did not affect anion production in non-stimulated cells or phagocytosis of unopsonized zymosan particles. A different result pattern was obtained for macrophages treated with sat PC. Phorbol 12-miristate 13-acetate-elicited superoxide production and neutral red uptake were decreased by nearly 25% by 32 and 64 µM sat PC, respectively. Sat PC did not affect nitric oxide or hydrogen peroxide production, adhesion capacity or zymosan phagocytosis. Thus, PC modifies macrophage activity, but this effect depends on cell activation state, fatty acid saturation and esterification to PC molecule and PC concentration. Taken together, these results indicate that the fatty acid moiety of PC modulates macrophage activity and, consequently, is likely to affect immune system regulation in vivo.

STM probing of local oscillations of the Fano-Kondo effect: a Doniach-Sunjic approach for the Kondo peak

The use of the scanning tunneling microscope (STM) for the investigation of Kondo adatoms on normal metallic surfaces reveals a Fano-Kondo behavior of the conductance as a function of the tip bias. In this work, the Doniach-Sunjic expression is used to describe the Kondo peak and we analyze the effect of a complex Fano phase, arising from an external magnetic field, on the conductance pattern. It is demonstrated that such phase generates local oscillations of the Fano-Kondo line shape and can lead to the suppression of anti-resonances.

Mechanical, thermal and morphological properties of glutaraldehyde crosslinked bovine pericardium followed by glutamic acid treatment

Major problems with valve bioprostheses are associated with progressive structural deterioration and calcification, directly associated with the use of glutaraldehyde (GA). This work describes the effects of GA processing and borate/glutamic acid buffer treatment on the mechanical, thermal and morphological properties of 0.5% GA crosslinked bovine pericardium (BP). The results showed that while the treatment of 0.5% GA crosslinked BP with borate/glutamic acid significantly improves the mechanical properties, it had no visible effect on surface morphology. Better surface preservation was only achieved for BP pre-treated with a lower GA concentration followed by the conventional treatment (0.5% GA). Improvements in mechanical properties probably arises from structural changes probably involving the depolymerization of polymeric GA crosslinks and an increase electrostatic interaction due to covalent binding of glutamic acid to free carbonyl groups (Schiff base).The results indicate that the treatment GA crosslinked BP with borate/glutamic acid buffer may be an attractive procedure for the manufacture of heart valve bioprostheses.

Photodynamic antimicrobial chemotherapy (PACT) for the treatment of malaria, leishmaniasis and trypanosomiasis

A photodynamic effect occurs when photosensitiser molecules absorb light and dissipate the absorbed energy by transferring it to biological acceptors (usually oxygen), generating an excess of reactive species that are able to force cells into death pathways. Several tropical diseases present physiopathological aspects that are accessible to the application of a photosensitiser and local illumination. In addition, disease may be transmitted through infected blood donations, and many of the aetiological agents associated with tropical diseases have been shown to be susceptible to the photodynamic approach. However, there has been no systematic investigation of the application of photoantimicrobial agents in the various presentations, whether to human disease or to the disinfection of blood products or even as photo-insecticides. We aim in this review to report the advances in the photoantimicrobial approach that are beneficial to the field of anti-parasite therapy and also have the potential to facilitate the development of low-cost/high-efficiency protocols for underserved populations.

Effect of cold fronts on the benthic macrofauna of exposed sandy beaches with contrasting morphodynamics

The aim of this study was to determine the short-term environmental changes caused by the simultaneous passage of a high energy event on two sandy beaches with different morphodynamic states and their influence on the richness, abundance and distribution of the benthic macrofauna. Two microtidal exposed sandy beaches with contrasting morphodynamics were simultaneously sampled before, during and after the passage of two cold fronts in Santa Catarina. The reflective beach showed a higher susceptibility to the increase in wave energy produced by the passage of cold fronts and was characterized by rapid and intense erosive processes in addition to a capacity for rapid restoration of the beach profile. As regards the dissipative beach, erosive processes operated more slowly and progressively, and it was characterized further by a reduced capacity for the recovery of its sub-aerial profile. Although the intensity of the environmental changes was distinct as between the morphodynamic extremes, changes in the composition, richness and abundance of macrobenthos induced by cold fronts were not evident for either of the beaches studied. On the other hand, alterations in the distribution pattern of the macrofauna were observed on the two beaches and were related to variations in sea level, position of the swash zone and moisture gradient, suggesting that short-term accommodations in the spatial structure of the macrobenthos occur in response to changes in environmental conditions in accordance with the temporal dynamics characteristic of each morphodynamic state.

Effect of protein intake on bone and muscle mass in the elderly

The aging process is frequently characterized by an involuntary loss of muscle (sarcopenia) and bone (osteoporosis) mass. Both chronic diseases are associated with decreased metabolic rate, increased risk of falls fracture, and, as a result, increased morbidity and loss of independence in the elderly. The quality and quantity of protein intake affects bone and muscle mass in several ways and there is evidence that increased essential amino acid or protein availability can enhance muscle protein synthesis and anabolism, as well as improve bone homeostasis in older subjects. A thorough evaluation of renal function is important, since renal function decreases with age. Finally, protein and calcium intake should be considered in the prevention or treatment of the chronic diseases osteoporosis and sarcopenia

The Effect of Spatial Scale on Predicting Time Series: A Study on Epidemiological System Identification

A susceptible-infective-recovered (SIR) epidemiological model based on probabilistic cellular automaton (PCA) is employed for simulating the temporal evolution of the registered cases of chickenpox in Arizona, USA, between 1994 and 2004. At each time step, every individual is in one of the states S, I, or R. The parameters of this model are the probabilities of each individual (each cell forming the PCA lattice ) passing from a state to another state. Here, the values of these probabilities are identified by using a genetic algorithm. If nonrealistic values are allowed to the parameters, the predictions present better agreement with the historical series than if they are forced to present realistic values. A discussion about how the size of the PCA lattice affects the quality of the model predictions is presented. Copyright (C) 2009 L. H. A. Monteiro et al.

Helminth Coinfection Does Not Affect Therapeutic Effect of a DNA Vaccine in Mice Harboring Tuberculosis

Background: Helminthiasis and tuberculosis (TB) coincide geographically and there is much interest in exploring how concurrent worm infections might alter immune responses against bacilli and might necessitate altered therapeutic approaches. A DNA vaccine that codifies heat shock protein Hsp65 from M. leprae (DNAhsp65) has been used in therapy during experimental tuberculosis. This study focused on the impact of the co-existence of worms and TB on the therapeutic effects of DNAhsp65. Methodology/Principal Findings: Mice were infected with Toxocara canis or with Schistosoma mansoni, followed by coinfection with M. tuberculosis and treatment with DNAhsp65. While T. canis infection did not increase vulnerability to pulmonary TB, S. mansoni enhanced susceptibility to TB as shown by higher numbers of bacteria in the lungs and spleen, which was associated with an increase in Th2 and regulatory cytokines. However, in coinfected mice, the therapeutic effect of DNAhsp65 was not abrogated, as indicated by colony forming units and analysis of histopathological changes. In vitro studies indicated that Hsp65-specific IFN-gamma production was correlated with vaccine-induced protection in coinfected mice. Moreover, in S. mansoni-coinfected mice, DNA treatment inhibited in vivo TGF-beta and IL-10 production, which could be associated with long-term protection. Conclusions/Significance: We have demonstrated that the therapeutic effects of DNAhsp65 in experimental TB infection are persistent in the presence of an unrelated Th2 immune response induced by helminth infections.

Clinical outcomes of long-acting injectable risperidone in patients with schizophrenia: six-month follow-up from the Electronic Schizophrenia Treatment Adherence Registry in Latin America

Background: Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. The aim of this work was to determine the effect of RLAI on clinical outcome and hospitalization rate in patients with schizophrenia or schizoaffective disorder enrolled in the electronic Schizophrenia Treatment Adherence Registry in Latin America. Methods: Data were collected at baseline, retrospectively for the 12 months prior to baseline, and prospectively every three months for 24 months. Hospitalization prior to therapy was assessed by a retrospective chart review. Efficacy and functioning were evaluated using Clinical Global Impression of Illness Severity (CGI-S), Personal and Social Performance (PSP), and Global Assessment of Functioning (GAF) scores. Relapse and treatment were also registered. Results: Patients were recruited in Mexico (n = 53), Brazil (n = 11), and Colombia (n = 15). Sixty-five percent (n = 52) were male, and mean age was 32.9 years. Patients were classified as having schizophrenia (n = 73) or schizoaffective disorder (n = 6). The mean dose of RLAI at six months was 34.1 mg (standard deviation = 10.2 mg). The percentage of hospitalized patients before treatment was 28.2% and 5.1% at six months after initiating RLAI (P < 0.001). Significant changes were registered on CGI-S, GAF, and PSP scores. Conclusions: RLAI was associated with an improvement in clinical symptoms and functioning, and a greater reduction in hospitalization.

Effect of GaAlAs Laser Irradiation on the Epiphyseal Cartilage of Rats

Objective: To study the effect of an 830-nm gallium-aluminum-arsenic (GaAlAs) diode laser at two different energy densities (5 and 15 J/cm(2)) on the epiphyseal cartilage of rats by evaluating bone length and the number of chondrocytes and thickness of each zone of the epiphyseal cartilage. Background Data: Few studies have been conducted on the effects of low-level laser therapy on the epiphyseal cartilage at different irradiation doses. Materials and Methods: A total of 30 male Wistar rats with 23 days of age and weighing 90 g on average were randomly divided into 3 groups: control group (CG, no stimulation), G5 group (energy density, 5 J/cm(2)), and G15 group (energy density, 15 J/cm(2)). Laser treatment sessions were administered every other day for a total of 10 sessions. The animals were killed 24 h after the last treatment session. Histological slides of the epiphyseal cartilage were stained with hematoxylin-eosin (HE), photographed with a Zeiss photomicroscope, and subjected to histometric and histological analyses. Statistical analysis was performed using one-way analysis of variance followed by Tukey's post hoc test. All statistical tests were performed at a significance level of 0.05. Results: Histological analysis and x-ray radiographs revealed an increase in thickness of the epiphyseal cartilage and in the number of chondrocytes in the G5 and G15 groups. Conclusion: The 830-nm GaAlAs diode laser, within the parameters used in this study, induced changes in the thickness of the epiphyseal cartilage and increased the number of chondrocytes, but this was not sufficient to induce changes in bone length.

Effect of Laser (670 nm) on Healing of Wounds Covered with Occlusive Dressing: A Histologic and Biomechanical Analysis

Objectives: To analyze the effects of low-level laser therapy (LLLT), 670 nm, with doses of 4 and 7 J/cm(2), on the repair of surgical wounds covered by occlusive dressings. Background Data: The effect of LLLT on the healing process of covered wounds is not well defined. Materials and Methods: For the histologic analysis with HE staining, 50 male Wistar rats were submitted to surgical incisions and divided into 10 groups (n=5): control; stimulated with 4 and 7 J/cm(2) daily, for 7 and 14 days, with or without occlusion. Reepithelization and the number of leukocytes, fibroblasts, and fibrocytes were obtained with an image processor. For the biomechanical analysis, 25 rats were submitted to a surgical incision and divided into five groups (n=5): treated for 14 days with and without occlusive dressing, and the sham group. Samples of the lesions were collected and submitted to the tensile test. One-way analysis of variance was performed, followed by post hoc analysis. A Tukey test was used on the biomechanical data, and the Tamhane test on the histologic data. A significance level of 5% was chosen (p <= 0.05). Results: The 4 and 7J/cm(2) laser with and without occlusive dressing did not alter significantly the reepithelization rate of the wounds. The 7 J/cm(2) laser reduced the number of leukocytes significantly. The number of fibroblasts was higher in the groups treated with laser for 7 days, and was significant in the covered 4 J/cm(2) laser group. Conclusions: Greater interference of the laser-treatment procedure was noted with 7 days of stimulation, and the occlusive dressing did not alter its biostimulatory effects.

The effect of laparoscopy access and antibiotics on the outcome of severe bacterial peritonitis in rats

Introduction: Treatment of severe bacterial peritonitis, especially by videolaparoscopy, is still a matter of investigation. The aim of the present study was to evaluate the effect of videolaparoscopy and laparotomy access with or without antibiotics on the outcome of severe bacterial peritonitis in rats. Materials and Methods: Sixty-four male Wistar rats were equally assigned to 8 groups: Sham surgery (SHAM), SHAM+antibiotics (SHAM+AB), cecal ligation and puncture (CLP), CLP+AB, CLP+videolaparoscopy (VLAP), CLP+laparotomy (LAP), VLAP+AB, and LAP+AB. All treated animals were submitted to an evaluation of bacteremia, white cell counts, and cytokine determinations: interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha). The groups treated with antibiotics received gentamicin and metronidazole. Survival was monitored over a period of 7 days. Results: Peritonitis induced by CLP was severe, with IL-1, IL-6, and TNF-alpha levels and lethality being significantly higher compared to the SHAM group. The IL-6 levels in the VLAP group were significantly higher compared to the CLP and VLAP+AB groups, and the TNF-alpha levels in the VLAP and LAP+AB groups were significantly higher compared to the LAP group. The survival time was significantly higher in the CLP+AB and VLAP+AB groups, when compared to the CLP group. There was no significant difference in bacteremia and lethality rates between the resources employed for treatment of peritonitis. Conclusions: Although the use of laparoscopic access itself exacerbates the inflammatory response, the combination with antibiotics minimizes this effect and increases the survival time. However, all of the resources used for treating severe peritonitis, when applied alone or in combination, have an equivalent influence on bacteremia and lethality rates.

Acute reversible inactivation of the bed nucleus of stria terminalis induces antidepressant-like effect in the rat forced swimming test

Background: The bed nucleus of stria terminalis (BNST) is a limbic forebrain structure involved in hypothalamo-pituitary-adrenal axis regulation and stress adaptation. Inappropriate adaptation to stress is thought to compromise the organism's coping mechanisms, which have been implicated in the neurobiology of depression. However, the studies aimed at investigating BNST involvement in depression pathophysiology have yielded contradictory results. Therefore, the objective of the present study was to investigate the effects of temporary acute inactivation of synaptic transmission in the BNST by local microinjection of cobalt chloride (CoCl(2)) in rats subjected to the forced swimming test (FST). Methods: Rats implanted with cannulae aimed at the BNST were submitted to 15 min of forced swimming (pretest). Twenty- four hours later immobility time was registered in a new 5 min forced swimming session (test). Independent groups of rats received bilateral microinjections of CoCl(2) (1 mM/100 nL) before or immediately after pretest or before the test session. Additional groups received the same treatment and were submitted to the open field test to control for unspecific effects on locomotor behavior. Results: CoCl(2) injection into the BNST before either the pretest or test sessions reduced immobility in the FST, suggesting an antidepressant-like effect. No significant effect of CoCl(2) was observed when it was injected into the BNST immediately after pretest. In addition, no effect of BNST inactivation was observed in the open field test. Conclusion: These results suggest that acute reversible inactivation of synaptic transmission in the BNST facilitates adaptation to stress and induces antidepressant-like effects.

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Background Minimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and Methods We analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. Results At least one marker was detected by polymerase chain reaction in 96.4%, of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%,, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor. Conclusions This simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.

Effect of Laser Phototherapy on the Release of TNF-alpha and MMP-1 by Endodontic Sealer-Stimulated Macrophages

Objective: Our aim was to analyze the effect of laser phototherapy on the secretory activity of macrophages activated by interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS), and stimulated by substances leached from an epoxy resin-based sealer (AH-Plus) and a calcium hydroxide-based sealer (Sealapex). Background Data: Laser phototherapy can modulate the inflammatory process, improving wound healing. This type of therapy could be useful for modulating postoperative symptoms seen after endodontic treatment. Materials and Methods: Cytotoxicity was indirectly assessed by measuring mitochondrial activity. Macrophages were stimulated by the leached substances or not (controls), and the groups were then irradiated or not. The secretion of pro-inflammatory cytokines (TNF-alpha and MMP-1) was analyzed using ELISA. Two irradiations at 6-h intervals were done with an As-Ga-Al diode laser (780 nm, 70 mW, spot size 4.0 mm(2), 3 J/cm(2), for 1.5 sec) in contact mode. Results: The sealers were non-cytotoxic to macrophages. The production of TNF-alpha was significantly decreased by laser phototherapy, regardless of experimental group. The level of secretion of MMP-1 was similar in all groups. Conclusion: Based on the conditions of this study we concluded that in activated macrophages, laser phototherapy impairs the secretion of the pro-inflammatory cytokine TNF-alpha, but has no influence on MMP-1 secretion.