Muc5ac: a critical component mediating the rejection of enteric nematodes

De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced in the cecum of mice resistant to Trichuris muris infection. In this study, we investigated the role of Muc5ac, which is detected shortly before worm expulsion and is associated with the production of interleukin-13 (IL-13), in resistance to this nematode. Muc5ac-deficient mice were incapable of expelling T. muris from the intestine and harbored long-term chronic infections, despite developing strong T(H)2 responses. Muc5ac-deficient mice had elevated levels of IL-13 and, surprisingly, an increase in the T(H)1 cytokine IFN-γ. Because T(H)1 inflammation is thought to favor chronic nematode infection, IFN-γ was neutralized in vivo, resulting in an even stronger T(H)2-type immune response. Nevertheless, despite a more robust T(H)2 effector response, the Muc5ac-deficient mice remained highly susceptible to chronic T. muris infection. Importantly, human MUC5AC had a direct detrimental effect on nematode vitality. Moreover, the absence of Muc5ac caused a significant delay in the expulsion of two other gut-dwelling nematodes (Trichinella spiralis and Nippostrongylus brasiliensis). Thus, for the first time, we identify a single mucin, Muc5ac, as a direct and critical mediator of resistance during intestinal nematode infection.     

Detecting impairment associated with cannabis with and without alcohol on the Standardized Field Sobriety Tests

Rationale

Cannabis and alcohol are the most popular drugs amongst recreational users and most prevalent in injured and deceased drivers. The Standardized Field Sobriety Tests (SFST) are commonly used to establish impairment due to drugs and alcohol, but limited empirical evidence exists concerning the combined effects of these drugs on SFST performance.

Methods

The sample comprised 80 individuals (31 females; 49 males). Age ranged between 21 and 35?years (M?=?26.5, SD?=?5). Forty participants (15 females; 25 males) took part in the low alcohol condition (BAC, <0.05?%), and 40 participants (16 females; 24 males), took part in the high alcohol condition (BAC, >0.05?%). For each part of the study, two levels of ?9-tetrahydrocannabinol (THC) were administered (1.8 and 3?% THC) or a matching placebo cigarette (0?% THC) in combination with alcohol. Performance on the SFST was assessed 30?min post-dosing.

Results

A number of significant differences in SFST performance were identified with 28?% of the sample failing the test (when the head movement and jerks sign was included) when low alcohol and low THC were administered together. When a higher dose of alcohol was administered with a low dose of THC, 38?% of the sample failed the test, and 35?% also failed when the high dose of alcohol was combined with a higher dose of THC.

Conclusions

The current results highlight the limited ability of the SFST to identify drug consumption in the absence of any evidence of driving impairment or physiological indicators.     

Autoantibodies and Sjögren's syndrome: a physiologist's perspective

Sj?gren's syndrome is a systemic autoimmune condition centred around salivary gland dysfunction and atrophy. There are a plethora of antibodies that mark the decline of the salivary glands, most of which relate to apoptopic mediated destruction of acinar cells. The best known of these autoantibodies, anti-Ro and anti-La form part of the diagnostic criteria for the condition. An emerging viewpoint in recent years is that glandular dysfunction precedes rather than follows glandular atrophy and attention has shifted to the interface between the immune system and the secretory process. An autoantibody against the muscarinic type 3 acetylcholine receptor occupies precisely this position because it inhibits the acetylcholine receptor which controls salivary and lacrimal fluid secretion. The consequence of identifying an autoantibody that can cause rather than simply reflect the disease process are manifold and could have a huge impact on development of therapeutic treatments. Furthermore, a "functional" autoantibody directed against an important component of the autonomic nervous system could also account for some of the extraglandular features of Sj?gren's syndrome.     

Pathogens resistant to antibacterial agents

Resistance to antimicrobial drugs is increasing at an alarming rate among both gram-positive and gram-negative bacteria. Traditionally, bacteria resistant to multiple antimicrobial agents have been restricted to the nosocomial environment. A disturbing trend has been the recent emergence and spread of resistant pathogens in nursing homes, in the community, and in the hospital. This article reviews the epidemiology, molecular mechanisms of resistance, and treatment options for pathogens resistant to antimicrobial drugs.