At birth, release of endogenous vasodilators such as nitric oxide and prostacyclin facilitate pulmonary vasodilation via the cyclic nucleotides, cGMP and cAMP. Interaction of cyclic nucleotides and platelet-activating factor (PAF)-mediated responses in pulmonary vascular smooth muscle is not known. We studied the effects of cGMP and cAMP on PAF-mediated responses in ovine fetal intrapulmonary venous smooth muscle cells. Studies were done in hypoxia or normoxia with buffer with 8-Br-cGMP (BGMP) and 8-Br-cAMP (BAMP), as well as cGMPdependent protein kinase (PKG) and cAMP-dependent protein kinase (PKA) inhibitors. All groups were treated with 1 nM PAF and incubated for 30 min for the binding assay or 20 min for measurement of inositol 1,4,5-phosphate (IP 3 ) production. BGMP and BAMP decreased PAF binding in normoxia by 63 and 14%, respectively. Incubations with the PKG inhibitor Rp-8-(4-chlorophenylthio)-guanosine-3Ј,5Ј-cyclic monophosphorothioate sodium and the PKA inhibitor Rp-adenosine-3Ј,5Ј-cyclic monophosphorothioate abrogated the inhibitory effects of BGMP and BAMP. PAF-stimulated IP 3 production was 8565 Ϯ 314 dpm/10 6 cells in hypoxia and 5418 Ϯ 118 dpm/10 6 cells in normoxia, a 40% decrease. BGMP attenuated PAFstimulated IP 3 production by 67 and 37% in hypoxia and normoxia, respectively; the value for BAMP was 44% under both conditions. Pretreatment with PKG or PKA inhibitor abrogated BGMP and BAMP inhibition of IP 3 release. PAF receptor (PAFr) protein expression decreased in normoxia, but pretreatment with 10 nM PAF up-regulated PAFr expression. Pretreatment with PAF decreased expression and activities of PKG or PKA proteins in normoxia and hypoxia. Our data demonstrate the existence of cGMP/cAMP-PAF cross-talk in pulmonary vascular smooth muscle cells, which may be one mechanism by which PAFr-mediated vasoconstriction is down-regulated at birth.
Background/AimsThe Central California Valley has a diverse population with significant proportions of Hispanics and Asians. This cross-sectional study was conducted to evaluate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in healthy blood donors in the Valley.MethodsA total of 217,738 voluntary blood donors were identified between 2006 and 2010 (36,795 first-time donors; 180,943 repeat donors).ResultsAmong the first-time donors, the HBV and HCV prevalence was 0.28% and 0.52%, respectively. Higher HBV prevalence seen in Asians (3%) followed by Caucasians (0.05%), African Americans (0.15%), and Hispanics (0.05%). Hmong had a HBV prevalence of 7.63% with a peak prevalence of 8.76% among the 16- to 35-year-old age group. Highest HCV prevalence in Native Americans (2.8) followed by Caucasians (0.59%), Hispanics (0.45%), African Americans (0.38%), and Asians (0.2%).ConclusionsEthnic disparities persist with regard to the prevalence of HBV and HCV in the Central California Valley. The reported prevalence may be an underestimate because our study enrolled healthy volunteer blood donors only. The development of aggressive public health measures to evaluate the true prevalence of HBV and HCV and to identify those in need of HBV and HCV prevention measures and therapy is critically important.
Immunoglobulin G subclass 4 (IgG-4)-related disease (IgG4-RD) is an uncommon immune-mediated, fibro-inflammatory disease which has garnered recognition as a systemic condition. One manifestation of the disease in the hepatobiliary system is the development of hepatic inflammatory pseudotumors. These benign tumors are often misdiagnosed as malignant tumors and undergo unnecessary hepatic resections. We present a case of IgG4-related hepatic inflammatory pseudotumor (IPT) mimicking a Klatskin tumor. A high degree of clinical suspicion and extensive workup is imperative in reaching the correct diagnosis. IgG4-related inflammatory pseudotumor is a rare entity, but an important consideration in evaluating hepatic tumors.
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