12 research outputs found
DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes
Abstract\ud
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Background\ud
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Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases.\ud
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Methods\ud
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In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ.\ud
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Results\ud
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DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete.\ud
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Conclusion\ud
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The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases.The authors are grateful to Mrs. Izaíra T Brandão and Mrs. Ana Paula Masson for technical assistance. This study was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of São Paulo), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development) and the Rede Brasileira de Pesquisa em TB (REDETB, Brazilian Tuberculosis Research Network).The authors are grateful to Mrs. Izaíra T Brandão and Mrs. Ana Paula Masson for technical assistance. This study was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of São Paulo), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development) and the Rede Brasileira de Pesquisa em TB (REDE-TB, Brazilian Tuberculosis Research Network)
High methylmercury in Arctic and subarctic ponds is related to nutrient levels in the warming eastern Canadian Arctic
Permafrost thaw ponds are ubiquitous in the eastern
Canadian Arctic, yet little information exists on their potential as
sources of methylmercury (MeHg) to freshwaters. They are
microbially active and conducive to methylation of inorganic
mercury, and are also affected by Arctic warming. This multiyear
study investigated thaw ponds in a discontinuous permafrost region
in the Subarctic taiga (Kuujjuarapik-Whapmagoostui, QC) and a
continuous permafrost region in the Arctic tundra (Bylot Island,
NU). MeHg concentrations in thaw ponds were well above levels
measured in most freshwater ecosystems in the Canadian Arctic
(>0.1 ng L−1). On Bylot, ice-wedge trough ponds showed
significantly higher MeHg (0.3−2.2 ng L−1) than polygonal
ponds (0.1−0.3 ng L−1) or lakes (<0.1 ng L−1). High MeHg was
measured in the bottom waters of Subarctic thaw ponds near
Kuujjuarapik (0.1−3.1 ng L−1). High water MeHg concentrations in thaw ponds were strongly correlated with variables
associated with high inputs of organic matter (DOC, a320, Fe), nutrients (TP, TN), and microbial activity (dissolved CO2 and
CH4). Thawing permafrost due to Arctic warming will continue to release nutrients and organic carbon into these systems and
increase ponding in some regions, likely stimulating higher water concentrations of MeHg. Greater hydrological connectivity
from permafrost thawing may potentially increase transport of MeHg from thaw ponds to neighboring aquatic ecosystems
DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes
Abstract
Background
Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases.
Methods
In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ.
Results
DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete.
Conclusion
The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases
Spatial and Temporal Assessment of Mercury and Organic Matter in Thermokarst Affected Lakes of the Mackenzie Delta Uplands, NT, Canada
We examined dated sediment cores from 14 thermokarst
affected lakes
in the Mackenzie Delta uplands, NT, Arctic Canada, using a case-control
analysis to determine how retrogressive thaw slump development from
degrading permafrost affected the delivery of mercury (Hg) and organic
carbon (OC) to lakes. We show that sediments from the lakes with retrogressive
thaw slump development on their shorelines (slump-affected lakes)
had higher sedimentation rates and lower total Hg (THg), methyl mercury
(MeHg), and lower organic carbon concentrations compared to lakes
where thaw slumps were absent (reference lakes). There was no difference
in focus-corrected Hg flux to sediments between reference lakes and
slump-affected lakes, indicating that the lower sediment Hg concentration
in slump-affected lakes was due to dilution by rapid inorganic sedimentation
in the slump-affected lakes. Sedimentation rates were inversely correlated
with THg concentrations in sediments among the 14 lakes considered,
and explained 68% of the variance in THg concentration in surface
sediment, further supporting the dilution hypothesis. We observed
higher S2 (algal-derived carbon) and particulate organic carbon (POC)
concentrations in sediment profiles from reference lakes than in slump
lakes, likely because of dilution by inorganic siliciclastic matter
in cores from slump-affected lakes. We conclude that retrogressive
thaw slump development increases inorganic sedimentation in lakes,
and decreases concentrations of organic carbon and associated Hg and
MeHg in sediments
Protective efficacy of different strategies employing Mycobacterium leprae heat-shock protein 65 against tuberculosis
Tuberculosis is a major threat to human health. The high disease burden remains unaffected and the appearance of extremely drug-resistant strains in different parts of the world argues in favor of the urgent need for a new effective vaccine. One of the promising candidates is heat-shock protein 65 when used as a genetic vaccine (DNAhsp65). Nonetheless, there are substantial data indicating that BCG, the only available anti-TB vaccine for clinical use, provides other important beneficial effects in immunized infants. Methods: We compared the protective efficacy of BCG and Hsp65 antigens in mice using different strategies: i) BCG, single dose subcutaneously; ii) naked DNAhsp65, four doses, intramuscularly; iii) liposomes containing DNAhsp65, single dose, intranasally; iv) microspheres containing DNAhsp65 or rHsp65, single dose, intramuscularly; and v) prime–boost with subcutaneous BCG and intramuscular DNAhsp65. Results: All the immunization protocols were able to protect mice against infection, with special benefits provided by DNAhsp65 in liposomes and prime–boost strategies. Conclusion: Among the immunization protocols tested, liposomes containing DNAhsp65 represent the most promising strategy for the development of a new anti-TB vaccine8912551264sem informaçãosem informaçã
Protective efficacy of different strategies employing Mycobacterium leprae heat-shock protein 65 against tuberculosis
Background: Tuberculosis is a major threat to human health. The high disease burden remains unaffected and the appearance of extremely drug-resistant strains in different parts of the world argues in favor of the urgent need for a new effective vaccine. One of the promising candidates is heat-shock protein 65 when used as a genetic vaccine (DNAhsp65). Nonetheless, there are substantial data indicating that BCG, the only available anti-TB vaccine for clinical use, provides other important beneficial effects in immunized infants. Methods: We compared the protective efficacy of BCG and Hsp65 antigens in mice using different strategies: i) BCG, single dose subcutaneously; ii) naked DNAhsp65, four doses, intramuscularly; iii) liposomes containing DNAhsp65, single dose, intranasally; iv) microspheres containing DNAhsp65 or rHsp65, single dose, intramuscularly; and v) prime-boost with subcutaneous BCG and intramuscular DNAhsp65. Results: All the immunization protocols were able to protect mice against infection, with special benefits provided by DNAhsp65 in liposomes and prime-boost strategies. Conclusion: Among the immunization protocols tested, liposomes containing DNAhsp65 represent the most promising strategy for the development of a new anti-TB vaccine