Linoleic and palmitoleic acid block streptokinase-mediated plasminogen activation and reduce severity of invasive group A streptococcal infection

Abstract In contrast to mild infections of Group A Streptococcus (GAS) invasive infections of GAS still pose a serious health hazard: GAS disseminates from sterile sites into the blood stream or deep tissues and causes sepsis or necrotizing fasciitis. In this case antibiotics do not provide an effective cure as the bacteria are capable to hide from them very quickly. Therefore, new remedies are urgently needed. Starting from a myxobacterial natural products screening campaign, we identified two fatty acids isolated from myxobacteria, linoleic and palmitoleic acid, specifically blocking streptokinase-mediated activation of plasminogen and thereby preventing streptococci from hijacking the host’s plasminogen/plasmin system. This activity is not inherited by other fatty acids such as oleic acid and is not attributable to the killing of streptococci. Moreover, both fatty acids are superior in their inhibitory properties compared to two clinically used drugs (tranexamic or ε-amino caproic acid) as they show 500–1000 fold lower IC50 values. Using a humanized plasminogen mouse model mimicking the clinical situation of a local GAS infection that becomes systemic, we demonstrate that these fatty acids ameliorate invasive GAS infection significantly. Consequently, linoleic and palmitoleic acid are possible new options to combat GAS invasive diseases

Minimum prey and area requirements of the vulnerable cheetah acinonyx jubatus : implications for reintroduction and management of the species in South Africa

In South Africa there are efforts to manage reintroduced subpopulations of the vulnerable cheetah Acinonyx jubatus in small reserves (10–1,000 km2) as a managed metapopulation. We estimated areas required to support cheetahs given varying prey densities, prey profiles and presence/absence of competing predators. A recent population and habitat viability assessment indicated that 20 subpopulations of 10 cheetahs or 10 subpopulations of 15 cheetahs are required to retain 90% of the heterozygosity of free-ranging cheetahs and to overcome stochastic events in the absence or presence of lions Panthera leo, respectively. We estimate that 203 SE 42 km2 (range 48–466 km2) is required to support 10 cheetahs in the absence of lions, whereas 703 SE 311 km2 (166–2,806 km2) is required to support 15 cheetahs given equal numbers of lions, and 2,424 SE 890 km2 (727–3,739 km2) given equal numbers of leopards Panthera pardus, spotted hyaenas Crocuta crocuta, wild dogs Lycaon pictus and lions. Existing subpopulations of cheetahs generally occur at densities higher than our mean predicted densities but usually within the range of predicted densities. The large area requirements of cheetahs have implications for the development of the managed metapopulation. Sourcing reintroduction sites of the sizes required to support recommended subpopulation sizes will be difficult. Consequently, innovative measures to increase the carrying capacity of reserves for cheetahs and/or to enlarge reserves will be required. Managers may be forced to stock cheetahs close to or beyond the carrying capacity of their reserves. Consequently, careful management of reintroduced subpopulations will be required to prevent declines in prey populations.http://journals.cambridge.org/action/displayJournal?jid=ORXnf201

Polarization-Sensitive Optical Coherence Tomography Imaging of Benign and Malignant Laryngeal Lesions: An In Vivo Study

Objective. Optical coherence tomography (OCT), an imaging technology that provides cross-sectional subsurface tissue structure images using back-scattered light, is a promising noninvasive imaging modality for in vivo assessment of vocal fold layered microstructure. Polarization-sensitive OCT (PS-OCT) augments conventional OCT by detecting changes in the polarization state of reflected light. This study imaged various benign and malignant laryngeal pathologies in patients undergoing direct laryngoscopy under general anesthesia to determine whether PS-OCT would provide useful additional information about vocal fold microstructure and glottic surface pathology. Study Design. Prospective clinical trial. Setting. Tertiary care center. Subjects and Methods. Twenty-three patients who were undergoing microlaryngoscopy under general anesthesia for benign (n = 18) and malignant (n = 5) glottic disease were imaged bilaterally with OCT and PS-OCT (n = 46 vocal folds). Intraoperative microphotography guided placement of the imaging probe. Normal-appearing glottic tissue was also imaged if present. When clinically indicated, biopsy or complete removal of the lesion established histologic confirmation. Results. PS-OCT provided high-quality, vertical, cross-sectional images up to 1.2-mm deep that complemented microlaryngoscopy and conventional OCT for vocal fold pathologies. Scar tissue was visualized by PS-OCT, characterized by a birefringence pattern more intense than that of normal glottic tissue. Cancer typically showed disruption or absence of both layered structure and birefringence. Conclusion. Combining PS-OCT with OCT during human vocal cord imaging provides useful information in characterizing vocal cord lesions, particularly scar tissue. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2011