Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms.

Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1-H4HRs. H1HR acts by Gαq activating IP(3)/Ca(2+), whereas H2HR activates Gα(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCα and protein kinase A (PKA) phosphorylation; and (3) PKCα silencing on H1HR-stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCα phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCα siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts.

Using the Alzheimer's Association web site to improve knowledge of Alzheimer's disease in health care providers.

BACKGROUND: The purpose of the current study was to investigate whether an informative Web site is effective at producing higher scores for an individual's knowledge of Alzheimer's disease (AD) relative to those who do not visit a Web site. METHODS: A total of 552 participants completed the study on Amazon's Mechanical Turk; half were randomly assigned to visit alz.org, while a control group did not. Both groups were given the AD Knowledge Scale (ADKS) to assess their knowledge of AD. RESULTS: Participants who visited alz.org scored significantly higher on the ADKS than those in the control group. Participants who were health care workers demonstrated higher scores than others in the experimental condition. Findings indicate that the Alzheimer's Association Web site is effective at producing higher scores for AD knowledge relative to no Web site at all and that it is especially helpful for health care workers compared to those who are not health care workers.