Polysaccharide fraction of Agaricus brasiliensis avoids tumor-induced IL-10 production and changes the microenvironment of subcutaneous Ehrlich adenocarcinoma

Subcutaneous Ehrlich tumor-bearing mice were treated with in situ inoculation of a P-glucan-rich extract of Agaricus brasiliensis (ATF), which reduced tumor growth. Histopathological analysis showed that the tumor masses of control mice (Ehr) presented giant tumor cells and many mitotic figures whereas the tumor tissue obtained from ATF-treated animals (Ehr-ATF) presented a lower frequency of both mitotic and giant cells, associated with a higher frequency of apoptotic cells than Ehr. Analysis of the lymphoproliferative activity of spleen cells showed that the treatment had a suppressive rather than a stimulatory effect. Spleen cells of the Ehr group produced higher in vitro levels of IL-10 than normal controls and this occurrence was partially avoided by treatment with ATF. Analysis of cytokine production by tumor-infiltrating cells (ELISpot) showed that ATF induced a higher number of IFN-gamma-producing cells at 7 and 14 days as well as reduction of IL-10-secreting cells at the latter time. Confocal microscopy analysis showed higher intensity of labeling of CD4+ and Mac-3+ cells in ATF-treated mice. Analysis of in situ expression of angiogenic growth factors showed a slight decrease of FGF-2 mRNA in Ehr-ATF animals (7th day) but not of VEGF-A or TGF-beta expression. This fraction could not directly lyse either lymphocytes or tumor cells and we speculate that antitumor effect of ATF could be due to induction of a selective migration of immunocompetent cells from the spleen to the tumor site and to the switch of cytokine production. (C) 2009 Elsevier Inc. All rights reserved.

Inducible nitric oxide synthase-deficient mice show exacerbated inflammatory process and high production of both Th1 and Th2 cytokines during paracoccidioidomycosis

Paracoccidioidomycosis, the major systemic mycosis in Latin America, is caused by fungus Paracoccidioides brasiliensis. To analyze the influence of inducible nitric oxide synthase (iNOS) in this disease, iNOS-deficient (iNOS(-/-)) and wild-type (WT) mice were infected intravenously with P. brasiliensis 18 isolate. We found that, unlike WT mice, iNOS(-/-) mice did not control fungal proliferation, and began to succumb to infection by day 50 after inoculation of yeast cells. Typical inflammatory granulomas were found in WT mice, while, iNOS(-/-) mice presented incipient granulomas with intense inflammatory process and necrosis. Additionally, splenocytes from iNOS(-/-) mice did not produce nitric oxide, however, their proliferative response to Con-A was impaired, just like infected WT mice. Moreover, infected iNOS(-/-) mice presented a mixed pattern of immune response, releasing high levels of both Th1 (IL-12, IFN-gamma and TNF-alpha) and Th2 (IL-4 and IL-10) cytokines. These data suggest that the enzyme iNOS is a resistance factor during paracoccidioidomycosis by controlling fungal proliferation, by influencing cytokines production, and by appeasing the development of a high inflammatory response and consequently formation of necrosis. However, iNOS-derived nitric oxide seems not being the unique factor responsible for immunosuppression observed in infections caused by P. brasiliensis. (c) 2008 Elsevier Masson SAS. All rights reserved.

Crocodile farms and management of saltwater crocodiles in Northern Territory: Results of a survey of NT crocodile farmers plus analysis of secondary information

After outlining some relevant background information about the NT crocodile farming industry and explaining the purpose of our survey of NT crocodile farmers conducted in the first half of 2005, this paper reports the results of the survey. The information received from the survey is supplemented by secondary data and by information from secondary sources. This report covers the location of respondents; the size of crocodile farms; farmers’ stated knowledge of and attitudes towards the NT Crocodile Management Plan; the involvement of farms in the harvesting of crocodile eggs and the costs involved; views of crocodile farmers about whether the NT Crocodile Management Plan encourages landholders to conserve crocodiles and their perceptions of the benefits to landholders; predicted production trends and trends in the number of farms operating in NT; economic characteristics of crocodile farms producing in NT including the economic advantages and disadvantages of crocodile farming in NT. Concluding comments provide, amongst other things, an overview of the structure of the crocodile farming industry in the NT gleaned from a consideration of data available from the NT Government’s Department of Business, Industry and Resource Development.

Education's role in economic development and in assisting the poor

Much faith has been put in the increased supply of education as a means to promote national economic development and as a way to assist the poor and the disadvantaged. However, the benefits that nations can obtain by increasing the level of education of their workforce depends on the availability of other forms of capital to complement the use of its educated workforce in production. Generally, less developed nations are lacking in complementary capital compared to more developed ones and it is appropriate for less developed countries to spend relatively less on education. The contribution of education to economic growth depends on a nation’s stage of economic development. It is only when a nation becomes relatively developed that education becomes a major contributor to economic growth. It is possible for less developed nations to retard their economic growth by favouring investment in educational capital rather than other forms of capital. Easy access to education is often portrayed as a powerful force for assisting the poor and the disadvantaged. Several reasons are given here as to why it may not be so effective in assisting the poor and in promoting greater income equality even though the aim is a worthy one. Also, an economic argument is presented in favour of special education for the physically and mentally handicapped. This paper is not intended to belittle the contribution of education to economic development nor to devalue the ideal of making basic education available to all. Instead, it is intended as an antidote to inflated claims about the ability of greater investment in education to promote economic growth and about the ability of more widespread access to education to reduce poverty and decrease income inequality.

Resource entitlements of indigenous minorities, their poverty and conservation of nature: Status of Australian Aborigines, comparisons with India's tribals, theory and changing policies globally

Considers the relevance of A.K. Sen’s theory of entitlements to the situation facing indigenous tribal people, its relationship to institutionalism, and to theories of property rights. Changing world views about the resource entitlements that should be given to local communities are outlined concentrating on the views expressed by the World Conservation Union (IUCN). These changing views have relevance for the resource entitlements of indigenous tribal communities and are reflected in differences in the policy approaches inherent in the Convention on International Trade in Endangered Species (CITES) and the more recent Convention on Biological Diversity. The latter embodies the view that provision of greater resource entitlements to local communities can provide economic incentives for nature conservation. There is a case for Indigenous Australians to be given greater rights to market the natural produce from their lands. Despite progress with land rights, they are not entitled to market much of the natural produce from their land. The socioeconomic status of Australian Aborigines is outlined. Their standard of living and their life expectancy are low by world standards and in comparison to other Australians. This is partly a result of historical events that have restricted their rights. These events are outlined briefly. Views differ about the appropriate development paths for Indigenous Australians and these are assessed. Concern on environmental and economic grounds is expressed about the view that the economic development of Australian Aboriginal communities would be accelerated by replacing their communal land titles by private land titles and encouraging Western-style agriculture and commercial development of their lands. Some comparisons are also made with the situation of India’s Tribals.

Sustainable agriculture

This paper provides an overview of concepts of sustainable agriculture and possible methods of attaining sustainability of agricultural yields and production. Reasons are given as to why modern industrialised agriculture might be less sustainable in terms of yields than traditional agriculture. The question of whether organic agriculture is likely to be more sustainable than non-organic agriculture is considered as well as organic agriculture’s likely impact on wild biodiversity. The impact of the development of agriculture on wild biodiversity is assessed because some environmentalists see the conservation of wild biodiversity as an important ingredient of sustainable development. However, there is a policy conflict between conservationist groups. Some see intensive agriculture (including silviculture) as favourable to the conservation of wild biodiversity whereas others oppose such production methods as being unfavourable to wild biodiversity conservation. Reasons why modern industrialised agricultural systems are so widely adopted (and continue to be adopted) despite their apparent lack of sustainability are suggested. Market systems may tend to lock producers into unsustainable production methods.

Heat-killed Enterococcus faecalis Alters Nitric Oxide and CXCL12 Production but not CXCL8 and CCL3 Production by Cultured Human Dental Pulp Fibroblasts

Introduction: Fibroblasts are the most abundant cells in dental pulp. To investigate their capacity to produce the chemokines CCL3, CXCL8, and CXCL12 as well as nitric oxide (NO), we evaluated the production of these mediators in supernatants of cultured human dental pulp fibroblasts (HDPF) stimulated by heat-killed Enterococcus faecalis (HKEF). Methods: Primary cultures of HDPF were stimulated with medium alone or HKEF (1:1, 10:1, or 100:1 bacteria:fibroblast) for 1, 6, and 24 hours. Chemokines and NO were assessed through enzyme-linked immunosorbent assay and Griess reaction, respectively. Statistical analysis was performed by using analysis of variance and Tukey post test. Results: CCL3 was not detected, whereas constitutive CXCL8 was not affected. Production of CXCL12 was increased at 1 and 6 hours, and NO was increased at the concentration of 1:1 bacteria:fibroblast at 24 hours. Viability and proliferation assays did not reveal cell number differences. Conclusions: These findings demonstrate that heat-killed E. faecalis is able to increase production of CXCL12 and NO by HDPF. (J Endod 2010;36:91-94)

Effect of lipopolysaccharide from periodontal pathogens on the production of tissue plasminogen activator and plasminogen activator inhibitor 2 by human gingival fibroblasts

Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) are important proteolysis factors present in inflamed human periodontal tissues. The aim of the present study was to investigate the effect of lipopolysaccharide (LPS) on the synthesis: of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum were extracted by the hot phenol water method. The levels of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT-PCR. The results showed t-PA synthesis was increased in response to all types of LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was greater following exposure of the cells to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P. gingivalis. These results indicate that LPS derived from periodontal pathogens may cause unbalanced regulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodontal connective tissue through dysregulated pericellular proteolysis.

Differential Production of Macrophage Inflammatory Protein-1 alpha, Stromal-Derived Factor-1, and IL-6 by Human Cultured Periodontal Ligament and Gingival Fibroblasts Challenged With Lipopolysaccharide From P. gingivalis

Background: Fibroblasts are considered important cells in periodontitis. When challenged by different agents, they respond through the release of cytokines that participate in the inflammatory process. The aim of this study is to evaluate and compare the expression and production of macrophage inflammatory protein (MIP)-1 alpha, stromal-derived factor (SDF)-1, and interleukin (IL)-6 by human cultured periodontal ligament and gingival fibroblasts challenged with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Methods: Fibroblasts were cultured from biopsies of gingival tissue and periodontal ligament of the same donors and used on the fourth passage. After confluence in 24-well plates, the culture medium alone (control) or with 0.1 to 10 mu g/ml of LPS from P. gingivalis was added to the wells, and after 1, 6, and 24 hours, the supernatant and the cells were collected and analyzed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction, respectively. Results: MIP-1 alpha, SDF-1, and IL-6 protein production was significantly greater in gingival fibroblasts compared to periodontal ligament fibroblasts. IL-6 was upregulated in a time-dependent manner, mainly in gingival fibroblasts (P<0.05), which secreted more MIP-1 alpha in the lowest concentration of LPS used (0.1 mu g/ml). In contrast, a basal production of SDF-1 that was inhibited with the increase of LPS concentration was detected, especially after 24 hours (P<0.05). Conclusion: The distinct ability of the gingival and periodontal ligament fibroblasts to secrete MIP-1 alpha, SDF-1, and IL-6 emphasizes that these cells may differently contribute to the balance of cytokines in the LPS-challenged periodontium. J Periodontol 2010;81:310-317.

Differential inclusions and robust control theory

Uncontrolled systems (x) over dot is an element of Ax, where A is a non-empty compact set of matrices, and controlled systems (x) over dot is an element of Ax + Bu are considered. Higher-order systems 0 is an element of Px - Du, where and are sets of differential polynomials, are also studied. It is shown that, under natural conditions commonly occurring in robust control theory, with some mild additional restrictions, asymptotic stability of differential inclusions is guaranteed. The main results are variants of small-gain theorems and the principal technique used is the Krasnosel'skii-Pokrovskii principle of absence of bounded solutions.

Should optional properties be used in conceptual modelling? A theory and three empirical tests

An important feature of some conceptual modelling grammars is the features they provide to allow database designers to show real-world things may or may not possess a particular attribute or relationship. In the entity-relationship model, for example, the fact that a thing may not possess an attribute can be represented by using a special symbol to indicate that the attribute is optional. Similarly, the fact that a thing may or may not be involved in a relationship can be represented by showing the minimum cardinality of the relationship as zero. Whether these practices should be followed, however, is a contentious issue. An alternative approach is to eliminate optional attributes and relationships from conceptual schema diagrams by using subtypes that have only mandatory attributes and relationships. In this paper, we first present a theory that led us to predict that optional attributes and relationships should be used in conceptual schema diagrams only when users of the diagrams require a surface-level understanding of the domain being represented by the diagrams. When users require a deep-level understanding, however, optional attributes and relationships should not be used because they undermine users' abilities to grasp important domain semantics. We describe three experiments which we then undertook to test our predictions. The results of the experiments support our predictions.

Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis

In a previous study, we concluded that overproduction of nitric oxide (NO) by inducible nitric Oxide synthase (iNOS) in the late phase of sepsis prevents hypothalamic activation, blunts vasopressin secretion and contributes to hypotension, irreversible shock and death. The aim of this follow-up study was to evaluate if the same neuronal activation pattern happens in brain structures related to cardiovascular functions. Male Wistar rats received intraperitoneal injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before cecal ligation and puncture (CLP) or sham surgeries. The animals were perfused 6 or 24 h after the surgeries and the brains were removed and processed for Fos immunocytochemistry We observed an increase (P < 0.001) in c-fos expression 6 h after CLP in the area postrema (AP), nucleus of he tractus solitarius (NTS), ventral lateral medulla (VLM), locus coeruleus (LC) and parabrachial nucleus (PB). At 24 h after CLP, however, c-fos expression was strongly decreased in all these nuclei (P < 0.05), except for the VLM. Aminoguanidine reduced c-fos expression in the AP and NTS at 6 h after CLR but showed an opposite effect at 24 h, with an increase in the AP, NTS, and also in the VLM. No such effect was observed in the LC and PB at 6 or 24 h. In all control animals, c-fos expression was minimal or absent. We conclude that in the early phase of sepsis iNOS-derived NO may be partially responsible for the activation of brain structures related to cardiovascular regulation. During the late phase, however, this activation is reduced or abolished. (C) 2009 Elsevier Ireland Ltd. All rights reserved.