Tumor Necrosis Factor-α +489G/A gene polymorphism is associated with chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory process, in which the pro-inflammatory cytokine Tumor Necrosis Factor (TNF)-α is considered to play a role. In the present study the putative involvement of TNF-α gene polymorphisms in pathogenesis of COPD was studied by analysis of four TNF-α gene polymorphisms in a Caucasian COPD population. METHODS: TNF-α gene polymorphisms at positions -376G/A, -308G/A, -238G/A, and +489G/A were examined in 169 Dutch COPD patients, who had a mean forced expiratory volume in one second (FEV1) of 37 ± 13%, and compared with a Dutch population control group of 358 subjects. RESULTS: The data showed that the TNF-α +489G/A genotype frequency tended to be different in COPD patients as compared to population controls, which was due to an enhanced frequency of the GA genotype. In line herewith, carriership of the minor allele was associated with enhanced risk of development of COPD (odds ratio = 1.9, p = 0.009). The other TNF-α gene polymorphisms studied revealed no discrimination between patients and controls. No differences in the examined four TNF-α polymorphisms were found between subtypes of COPD, which were stratified for the presence of radiological emphysema. However, comparison of the COPD subtypes with controls showed a significant difference in the TNF-α +489G/A genotype in patients without radiological emphysema (χ(2)-test: p < 0.025 [Bonferroni adjusted]), while no differences between COPD patients with radiological emphysema and controls were observed. CONCLUSION: Based on the reported data, it is concluded that COPD, and especially a subgroup of COPD patients without radiological emphysema, is associated with TNF-α +489G/A gene polymorphism

In vitro antimicrobial activity of natural toxins and animal venoms tested against Burkholderia pseudomallei

BACKGROUND: Burkholderia pseudomallei are the causative agent of melioidosis. Increasing resistance of the disease to antibiotics is a severe problem in treatment regime and has led to intensification of the search for new drugs. Antimicrobial peptides are the most ubiquitous in nature as part of the innate immune system and host defense mechanism. METHODS: Here, we investigated a group of venoms (snakes, scorpions and honey bee venoms) for antimicrobial properties against two strains of Gram-negative bacteria Burkholderia pseudomallei by using disc-diffusion assay for in vitro susceptibility testing. The antibacterial activities of the venoms were compared with that of the isolated L-amino acid oxidase (LAAO) and phospholipase A(2 )(PLA(2)s) enzymes. MICs were determined using broth dilution method. Bacterial growth was assessed by measurement of optical density at the lowest dilutions (MIC 0.25 mg/ml). The cell viability was measured using tetrazolium salts (XTT) based cytotoxic assay. RESULTS: The studied venoms showed high antimicrobial activity. The venoms of C. adamanteus, Daboia russelli russelli, A. halys, P. australis, B. candidus and P. guttata were equally as effective as Chloramphenicol and Ceftazidime (30 μg/disc). Among those tested, phospholipase A(2 )enzymes (crotoxin B and daboiatoxin) showed the most potent antibacterial activity against Gram-negative (TES) bacteria. Naturally occurring venom peptides and phospholipase A(2 )proved to possess highly potent antimicrobial activity against Burkholderia pseudomallei. The XTT-assay results showed that the cell survival decreased with increasing concentrations (0.05–10 mg/mL) of Crotalus adamanteus venom, with no effect on the cell viability evident at 0.5 mg/mL. CONCLUSION: This antibacterial profile of snake venoms reported herein will be useful in the search for potential antibacterial agents against drug resistant microorganisms like B. pseudomallei

The Epidemiology and Clinical Spectrum of Melioidosis: 540 Cases from the 20 Year Darwin Prospective Study

Melioidosis is an occupationally and recreationally acquired infection important in Southeast Asia and northern Australia. Recently cases have been reported from more diverse locations globally. The responsible bacterium, Burkholderia pseudomallei, is considered a potential biothreat agent. Risk factors predisposing to melioidosis are well recognised, most notably diabetes. The Darwin prospective melioidosis study has identified 540 cases of melioidosis over 20 years and analysis of the epidemiology and clinical findings provides important new insights into this disease. Risk factors identified in addition to diabetes, hazardous alcohol use and chronic renal disease include chronic lung disease, malignancies, rheumatic heart disease, cardiac failure and age ≥50 years. Half of patients presented with pneumonia and septic shock was common (21%). The decrease in mortality from 30% in the first 5 years of the study to 9% in the last five years is attributed to earlier diagnosis and improvements in intensive care management. Of the 77 fatal cases (14%), all had known risk factors for melioidosis. This supports the most important conclusion of the study, which is that melioidosis is very unlikely to kill a healthy person, provided the infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care where required

Glanders & Melioidosis: A Zoonosis and a Sapronosis—“Same Same, but Different”

Glanders, caused by infection with Burkholderia mallei, primarily causes infection in equines, but may be transmitted to humans, and thus qualifies as a true zoonosis. Melioidosis Melioidosis is caused by B. pseudomallei, genetically very similar to B. mallei, but which is an environmental saprophyte capable of infecting humans and a wide range of other animals. Good evidence of animal-to-human, or even human-to-human, transmission of melioidosis is lacking, and so it most appropriately referred to as a sapronosis, or at most a sapro-zoonosis. Although rare in Western countries, both micro-organisms have recently gained much interest because of their potential use as bioterrorism agents Bioterrorism. The increasing recognition of melioidosis in humans and recent outbreaks of glanders Glanders in animals have led to their description as emerging or re-emerging diseases. Laboratory-associated infections with both organisms have also occurred, resulting in their categorisation as Hazard Group 3 pathogens. In this chapter we review the epidemiology of animal and human cases of glanders and melioidosis, the evidence for different modes of transmission, pathogenesis and clinical features, diagnosis and treatment, as well as public health and disease control issues