Background: The role of nitric oxide synthase (NOS) in the pathophysiology of coeliac disease (CD) was investigated.
Methods: We examined mRNA (reverse transcription multiplex polymerase chain reaction) and protein expression (Western blotting) of i,e and nNOS in enterocytes isolated from the duodenum of patients with untreated CD (n=22) and iron deficiency anaemia (IDA, n=22). Expression of IL1beta and TNFalpha, two pivotal "NOS-controlling" cytokines, was also studied.
Objective: The presence, in patients with primary and secondary Sjogren's syndrome (SS), of autoantibodies that acutely inhibit M(3) muscarinic receptor (M3R)-mediated bladder contractions is difficult to reconcile with the fact that symptoms of detrusor overactivity and other features of cholinergic hyperresponsiveness occur in this disease. This study was undertaken to examine the in vivo effects of these autoantibodies on bladder function by examining bladder responsiveness and compliance following passive transfer of patient IgG to mice.
Methods: Contractile responses of isolated bladder strips both to the muscarinic agonist carbachol and to electrically evoked acetylcholine release were measured 48 hours after injection of mice with patient or control IgG.
Functional antimuscarinic M3 receptor (M3R) autoantibodies have been shown to inhibit cholinergic neurotransmission at the postsynaptic level and appear to mediate parasympathetic dysfunction, including sicca symptoms in Sjögren's syndrome (SS). The precise epitope(s) involved in the inhibition of M3R-mediated cholinergic neurotransmission has not been defined. In this study, an active immunization approach to raise antibodies with functional activity against the second extracellular loop of the M3R was used and their functional properties were compared with those of human autoantibodies.
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