Effects of the stimulus phase on the air-conducted ocular vestibular evoked myogenic potential in healthy subjects

Objective

The study aimed to examine the effect of the stimulus phase of air-conducted sound on ocular vestibular evoked myogenic potentials (oVEMPs).

Brown Bears (Ursus arctos) Seem Resistant to Atherosclerosis -Despite Highly Elevated Plasma Lipids during Hibernation and Active State

Hibernation is an extreme physiological challenge for the brown bear (Ursus arctos) in which metabolism is based mainly on lipids. The study objective was to compare plasma lipids in hibernating and active free‐ranging brown bears and relate them to arterial histopathology. Blood was drawn from seven immobilized free‐ranging brown bears (three females, 2–3 years old) during hibernation in February and from the same bears while active in June and analyzed by enzymatic and automated hematology methods within 48 hours of sampling. Left anterior descending coronary arteries and aortic arches from 12 bears (six females, 1.5–12 years old) killed in hunting were examined by histopathology. Total plasma cholesterol decreased from hibernation to the active period (11.08 ± 1.04 mmol/L vs. 7.89 ± 1.96 mmol/L, P= 0.0028) as did triglyceride (3.16 ± 0.62 mmol/L vs. 1.44 ± 0.27 mmol/L, P= 0.00012) and LDL cholesterol (4.30 ± 0.71 mmol/L vs. 2.02 ± 1.03 mmol/L, P= 0.0075), whereas HDL cholesterol was unchanged. No atherosclerosis, fatty streaks, foam cell infiltration, or inflammation were seen in any arterial samples. Brown bears tolerate elevated cholesterol levels, obesity, physical inactivity, and circulatory slow flow during hibernation without signs of ­atherosclerosis. This species might serve as a reverse translational model for atherosclerosis resistance. Clin Trans Sci 2012; Volume 5: 269–272     

Brown bears (Ursus arctos) seem resistant to atherosclerosis despite highly elevated plasma lipids during hibernation and active state

Hibernation is an extreme physiological challenge for the brown bear (Ursus arctos) in which metabolism is based mainly on lipids. The study objective was to compare plasma lipids in hibernating and active free-ranging brown bears and relate them to arterial histopathology. Blood was drawn from seven immobilized free-ranging brown bears (three females, 2-3 years old) during hibernation in February and from the same bears while active in June and analyzed by enzymatic and automated hematology methods within 48 hours of sampling. Left anterior descending coronary arteries and aortic arches from 12 bears (six females, 1.5-12 years old) killed in hunting were examined by histopathology. Total plasma cholesterol decreased from hibernation to the active period (11.08 ± 1.04 mmol/L vs. 7.89 ± 1.96 mmol/L, P= 0.0028) as did triglyceride (3.16 ± 0.62 mmol/L vs. 1.44 ± 0.27 mmol/L, P= 0.00012) and LDL cholesterol (4.30 ± 0.71 mmol/L vs. 2.02 ± 1.03 mmol/L, P= 0.0075), whereas HDL cholesterol was unchanged. No atherosclerosis, fatty streaks, foam cell infiltration, or inflammation were seen in any arterial samples. Brown bears tolerate elevated cholesterol levels, obesity, physical inactivity, and circulatory slow flow during hibernation without signs of -atherosclerosis. This species might serve as a reverse translational model for atherosclerosis resistance.     

Two adult siblings with atypical cryopyrin‐associated periodic syndrome due to a novel M299V mutation in NLRP3

Objective

The NALP3 inflammasome is a multiprotein complex that triggers caspase 1–mediated interleukin‐1β (IL‐1β) release. Mutations in the gene encoding NALP3 (NLRP3) underlie the cryopyrin‐associated periodic syndrome (CAPS). The aim of this study was to report a novel NLRP3 mutation in 2 siblings of Swedish descent in whom symptoms first presented in adulthood.

Methods

Mutation analysis of NLRP3 was performed on DNA from patients with CAPS and 100 control subjects. For assessment of caspase 1 and IL‐1β, blood was collected from patients and age‐ and sex‐matched healthy control subjects. Genetic constructs containing mutant or wild‐type NLRP3 were transduced into THP‐1 cells, followed by assessment of IL‐1β levels in cell supernatant.

Results

Both siblings carried a novel M299V mutation in NLRP3, which was not present in the control population. The samples obtained from the patients displayed increased caspase 1 activity and elevated IL‐1β levels at basal conditions as compared with healthy control subjects. THP‐1 cells expressing mutated M299V revealed almost 10‐fold higher IL‐1β production compared with the wild‐type construct.

Conclusion

M299V is an activating mutation in NLRP3 resulting in elevated spontaneous caspase 1 activity and IL‐1β levels. The classic CAPS phenotype was lacking in these adult siblings. Whereas one sibling displayed a milder phenotype that has so far responded satisfactorily to oral nonsteroidal antiinflammatory drugs in combination with low‐dose corticosteroids, the inflammatory symptoms in the sibling with the more severe case responded well to IL‐1β blockade. Understanding the pathogenic mechanism underlying such disorders can be helpful for the physician. Our study reinforces the importance of genetic testing and laboratory investigations in combination with careful phenotypic evaluation for the diagnosis of such patients.

     

Propionibacterium acnes activates caspase‐1 in human neutrophils

Propionibacterium acnes is a Gram‐positive, slow‐growing, anaerobic bacillus, predominantly found as a commensal on the skin and mucous membranes of adults. It is, however, also considered an opportunistic pathogen; mostly associated with acne vulgaris, but rarely also with severe infections such as infective endocarditis, prosthetic joint infections, and deep sternal wound infections following cardiothoracic surgery. In addition, P. acnes has recently been found in high frequency in prostate tissue from patients with prostatitis and prostate cancer. The NOD‐like receptors (NLR) act as intracellular sensors of microbial components, and a number of various bacteria have been found to induce assembling and activation of NLR‐inflammasomes; leading to a pro‐inflammatory response. The inflammasome‐mediated formation of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β) and IL‐18 involves the auto‐proteolytic maturation of caspase‐1. This study investigated if P. acnes activates inflammasomes. Propionibacterium acnes isolates (n = 29) with diverse origin were used as stimuli for peripheral leukocytes obtained from blood donors (BDs). The activity of inflammasomes was determined by measuring caspase‐1 by flow cytometry and cytokine production by ELISA. A significant amount of caspase‐1 was found in neutrophils upon P. acnes stimulation, whereas only a modest activation was seen in monocytes. The activation was mainly produced by components of the bacterial cell and no exo‐products, because heat‐killed and live bacteria caused high activation of caspase‐1 as well as cytokine production, whereas the bacterial supernatant elicited minor effect. The response among different BDs varied significantly, almost fivefold. In addition, P. acnes of various origins showed considerable variation, however, the commensal isolates showed a stronger response compared with the invasive. In conclusion, although regarded as a harmless commensal of the skin, P. acnes strongly activates the inflammasome of human peripheral neutrophils.