Dominant-Negative Tumor Necrosis Factor Protects from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and Endotoxin-Induced Liver Injury without Compromising Host Immunity to BCG and Mycobacterium tuberculosis

BackgroundTumor necrosis factor (TNF) is associated with the development of inflammatory pathologies. Antibodies and soluble TNF (solTNF) receptors that neutralize excessive TNF are effective therapies for inflammatory and autoimmune diseases. However, clinical use of TNF inhibitors is associated with an increased risk of infections MethodsA novel dominant-negative (DN) strategy of selective TNF neutralization, consisting of blocking solTNF while sparing transmembrane TNF (tmTNF), was tested in mouse models of mycobacterial infection and acute liver inflammation. XENP1595, a DN-TNF biologic, was compared with etanercept, a TNF receptor 2 (TNFR2)-IgG1 Fc fusion protein that inhibits murine solTNF and tmTNF ResultsXENP1595 protected mice from acute liver inflammation induced by endotoxin challenge in Mycobacterium bovis bacillus Calmette-Guérin (BCG)-infected mice, but, in contrast to etanercept, it did not compromise host immunity to acute M. bovis BCG and Mycobacterium tuberculosis infections in terms of bacterial burden, granuloma formation, and innate immune responses ConclusionsA selective inhibitor of solTNF efficiently protected mice from acute liver inflammation yet maintained immunity to mycobacterial infections. In contrast, nonselective inhibition of solTNF and tmTNF suppressed immunity to M. bovis BCG and M. tuberculosis. Therefore, selective inhibition of solTNF by DN-TNF biologics may represent a new therapeutic strategy for the treatment of inflammatory diseases without compromising host immunit

Distribution of Phytoplankton in Nebraska Lakes

Protection of the environment requires effective regulatory actions which are based on ssound technical and scientific information. This information must include the quantitative description and linking of pollutant sources, transport mechanisms, interactions, and resulting effects on man and his environment. Because of the complexities involved, assessment of specific pollutants in the environment requires a total systems approach which transcends the media of air, water, and land. The Environmental Monitoring and Support Laboratory-Las Vegas contributes to the formation and enhancement of a sound monitoring data base for exposure assessment through programs designed to: develop and optimize systems and strategies for monitoring pollutants and their impact on the environment demonstrate new monitoring systems and technologies by applying them to fulfill special monitoring needs of the Agency\u27s operating programs This report presents the species and abundance of phytoplankton in the 9 lakes sampled by the National Eutrophication Survey in the State of Nebraska, along with results from the calculation of several commonly used biological indices of water quality and community structure. These data can be used to biologically characterize the study lakes, and as baseline data for future investigations. This report was written for use by Federal, State, and local governmental agencies concerned with water quality analysis, monitoring, and or regulation. Private industry and individuals similarly involved with the biological aspects of water quality will find the document useful. For further information contact the Water and Land Quality Branch, Monitoring Operations Division

Distribution of Phytoplankton in Nebraska lakes

The National Eutrophication Survey was initiated in 1972 in response to an Administration commitment to investigate the nationwide threat of accelerated eutrophication to freshwater lakes and reservoirs. The Survey was designed to develop, in conjunction with State environmental agencies, information on nutrient sources, concentrations, and impact on selected freshwater lakes as a basis for formulating comprehensive and coordinated national, regional, and State management practices relating to point source discharge reduction and nonpoint source pollution abatement in lake watershed. The Survey collected physical, chemical, and biological data from 815 lakes and reservoirs throughout the contiguous United States. To date, the Survey has yielded more than two million data points. In-depth analyses are being made to advance the rationale and data base for refinement of nutrient water quality criteria for the Nation\u27s freshwater lakes

Prevalence of viral and non-viral hepatitis in Menoua Division, West Region, Cameroon: a retrospective hospital-based study

Introduction: the paucity of data on hepatitis' epidemiology in Menoua Division, west region, Cameroon, prompted us to assess the prevalence of viral and non-viral hepatitis in this area. Methods: a retrospective exhaustive study based on records of patients from January 2008 to June 2014 was conducted in 9 health centres in Menoua Division. Targeted subjects were patients who did not receive hepatitis vaccines for the past year and have been screened for hepatitis B virus (HBV), hepatitis C virus (HCV) and/or a blood transaminase. Associations between variables were quantified with odd ratios (OR) and 95% confidence interval (CI). Cochran-Armitage test of linear trend was used for testing proportions of ordinal variables. Fisher's exact test was used for testing the association between 2 qualitative variables when expected counts were less than 5. Results: the overall prevalence were 9.6% and 6.7% for HBV and HCV respectively. HBV mostly infected people aged 21-30 (12.4%) while the prevalence of HCV increased with age up to 35.4% (p=0.03). A 0.6% co-infection was observed. Thirty percent of positive HBV or HCV had high transaminase while 13% of patients with elevated transaminase showed negative viral serology. Conclusion: these results show that hospital-based prevalence of HCV and HBV in Menoua Division is under the Cameroon's national range but point out the fact that non-viral hepatitis might be a serious case of concern in this area. There is therefore, a need to identify the risk-factors of non-viral hepatitis

ANTIOXIDANT PROPERTIES OF DICHROCEPHALA INTEGRIFOLIA (ASTERACEAE) IN A MOUSE MODEL OF MONOSODIUM GLUTAMATE-INDUCED NEUROTOXICITY

Background: In Africa, neurodegenerative diseases in the elderly have become a major health concern due to the increase in live expectancy. Glutamate mediated neurotoxicity is involved in neurodegenerative diseases such as Ischemia, Epilepsy, Alzheimer’s and Parkinson diseases. Plants with antioxidant properties are reported to protect vital organs against glutamate toxicity. This study aims to assess the effect of Dichrocephala integrifolia against monosodium glutamatemediated neurotoxicity and oxidative stress. Methodology: The decoction prepared from the leaves of Dichrocephala integrifolia was evaluated against monosodium glutamate-induced neurotoxicity in mice. The animals were grouped in seven groups of 6 animals each. The animals received daily; distilled water (p.o) for the distilled water and the negative control groups, one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o) for the tests groups and memantine (20 mg/kg p.o) for the positive control group. Monosodium glutamate (2.5 g/kg ip) was injected daily to animals except those of the normal control group all the seven days of the experimentation. Animals were observed for aggressiveness, locomotor and forepaws muscle grip activities 30 min after monosodium injections. Brain reduced glutathione and malondialdehyde levels were also assessed following the behavioral tests on day 8. Results: The decoction of Dichrocephala integrifolia at the doses of 87.5 and 175 mg/kg significantly (

Involvement of Sulfur in the Biosynthesis of Essential Metabolites in Pathogenic Fungi of Animals, Particularly Aspergillus spp. : Molecular and Therapeutic Implications

Fungal sulfur uptake is required for incorporation into the sidechains of the amino acids cysteine and methionine, and is also essential for the biosynthesis of the antioxidant glutathione (GSH), S-adenosylmethionine (SAM), the key source of methyl groups in cellular transmethylation reactions, and S-adenosylhomocysteine (SAH). Biosynthesis of redox-active gliotoxin in the opportunistic fungal pathogen Aspergillus fumigatus has been elucidated over the past 10 years. Some fungi which produce gliotoxin-like molecular species have undergone unexpected molecular rewiring to accommodate this high-risk biosynthetic process. Specific disruption of gliotoxin biosynthesis, via deletion of gliK, which encodes a γ-glutamyl cyclotransferase, leads to elevated intracellular antioxidant, ergothioneine (EGT), levels, and confirms crosstalk between the biosynthesis of both sulfur-containing moieties. Gliotoxin is ultimately formed by gliotoxin oxidoreductase GliT-mediated oxidation of dithiol gliotoxin (DTG). In fact, DTG is a substrate for both GliT and a bis-thiomethyltransferase, GtmA. GtmA converts DTG to bisdethiobis(methylthio)gliotoxin (BmGT), using 2 mol SAM and resultant SAH must be re-converted to SAM via the action of the Methyl/Met cycle. In the absence of GliT, DTG fluxes via GtmA to BmGT, which results in both SAM depletion and SAH overproduction. Thus, the negative regulation of gliotoxin biosynthesis via GtmA must be counter-balanced by GliT activity to avoid Methyl/Met cycle dysregulation, SAM depletion and trans consequences on global cellular biochemistry in A. fumigatus. DTG also possesses potent Zn2+ chelation properties which positions this sulfur-containing metabolite as a putative component of the Zn2+ homeostasis system within fungi. EGT plays an essential role in high-level redox homeostasis and its presence requires significant consideration in future oxidative stress studies in pathogenic filamentous fungi. In certain filamentous fungi, sulfur is additionally indirectly required for the formation of EGT and the disulfide-bridge containing non-ribosomal peptide, gliotoxin, and related epipolythiodioxopiperazines. Ultimately, interference with emerging sulfur metabolite functionality may represent a new strategy for antifungal drug development