Efficacy evaluation of combination vaccine of recombinant C-terminal fragments of ApxIA, ApxIIA and ApxIIIA in piglets

The efficacy of the combination vaccine of the individual C-terminal fragments of ApxIA, ApxIIA and ApxIIIA of Actinobacillus pleuropneumoniae (APP) was evaluated in piglets. Twenty piglets were divided equally into 2 groups (n=10). All piglets were intramuscularly primed at 4 week-of-age (0 week post prime inoculation (WPPI)) and were intramuscularly boosted at 6 week-of-age (2 WPPI). Group A piglets were inoculated with sterile PBS and group B piglets were inoculated with the combination vaccine. Concentrations of each of the C-terminal fragment-specific IgG as determined by ELISA were significantly higher in group B than in group A from 2 WPPI until the end of this study. Clinical signs were observed from only 10% of group B piglets after the challenge with the mixture of APP serotypes 1, 2 and 5 at 4 WPPI, while 50% of group A piglets were protected against APP infections. Overall, intramuscular inoculation with the vaccine candidate can efficiently protect piglets against APP infection

Junctional membrane inositol 1,4,5-trisphosphate receptor complex coordinates sensitization of the silent EGF-induced Ca2+ signaling

Ca2+ is a highly versatile intracellular signal that regulates many different cellular processes, and cells have developed mechanisms to have exquisite control over Ca2+ signaling. Epidermal growth factor (EGF), which fails to mobilize intracellular Ca2+ when administrated alone, becomes capable of evoking [Ca2+]i increase and exocytosis after bradykinin (BK) stimulation in chromaffin cells. Here, we provide evidence that this sensitization process is coordinated by a macromolecular signaling complex comprised of inositol 1,4,5-trisphosphate receptor type I (IP3R1), cAMP-dependent protein kinase (PKA), EGF receptor (EGFR), and an A-kinase anchoring protein, yotiao. The IP3R complex functions as a focal point to promote Ca2+ release in two ways: (1) it facilitates PKA-dependent phosphorylation of IP3R1 in response to BK-induced elevation of cAMP, and (2) it couples the plasmalemmal EGFR with IP3R1 at the Ca2+ store located juxtaposed to the plasma membrane. Our study illustrates how the junctional membrane IP3R complex connects different signaling pathways to define the fidelity and specificity of Ca2+ signaling

Prognostic Value of Postoperative CEA Clearance in Rectal Cancer Patients with High Preoperative CEA Levels

PURPOSE: We determined the prognostic value of carcinoembryonic antigen (CEA) clearance after tumor resection with serial evaluation of postoperative CEA levels in rectal cancer. METHODS: Between 1994 and 2004, we retrospectively reviewed 122 patients with rectal cancer whose serum CEA levels were measured on the preoperative day and postoperative days 7 and 30. Patients with preoperative CEA levels <5.0 ng/ml were excluded. An exponential trend line was drawn using the three CEA values. Patients were categorized into three groups based on R(2) values calculated through trend line, which indicates the correlation coefficient between exponential graph and measured CEA values: exponential decrease group (group 1: 0.9 < R(2) < or = 1.0), nearly exponential decrease group (group 2: 0.5 < R(2) < or = 0.9), and randomized clearance group (group 3: 0.5 < or = R(2)). We then analyzed the CEA clearance pattern as a prognostic indicator. RESULTS: With a median follow-up of 57 months, the 5-year overall survival was 62.3% vs. 48.1% vs. 25% and the 5-year disease-free survival was 58.6% vs. 52.7% vs. 25% among groups 1, 2, and 3 (P = 0.014, P = 0.027, respectively) in patients with stage III rectal cancer. For those with stage II rectal cancer, the 5-year overall survival rate of group 1 was significantly better than groups 2 and 3 (88.8% vs. 74.1%, respectively, P = 0.021). CONCLUSIONS: the postoperative pattern of CEA clearance is a useful prognostic determinant in patients with rectal cancer. Patients with a randomized pattern of CEA clearance after tumor resection should be regarded as having the possibility of a persistent CEA source and may require consideration of intensive follow-up or adjuvant therapy.ope

Tetrahydroabietic Acid, a Reduced Abietic Acid, Inhibits the Production of Inflammatory Mediators in RAW264.7 Macrophages Activated with Lipopolysaccharide

Abietic acid (AA), the main component of the rosin fraction of oleoresin synthesized by conifer species, has been reported to have anti-inflammatory effects. AA is a weak contact allergen; however, compounds resulting from its oxidation by air elicit stronger allergic response. Hydrogenation of the conjugated double bonds of AA, as in tetrahydroabietic acid (THAA), decreases its susceptibility to air oxidation and would thus reduce the allergenicity of AA. The aim of this study was to investigate whether THAA could exert anti-inflammatory effects to the same extent as AA in RAW264.7 macrophages activated with the endotoxin lipopolysaccharide (LPS). THAA and AA inhibited the production of nitric oxide (NO) and prostaglandin E2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively, in LPS-activated RAW264.7 macrophages. They also inhibited the LPS-induced production of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Both THAA and AA prevented the LPS-induced nuclear translocation of the nuclear factor-κB/p65 subunit, suggesting that THAA may inhibit the production of pro-inflammatory mediators through the same mechanism as AA. In comparison, the anti-inflammatory effects of THAA and AA were almost identical, indicating that THAA retains the anti-inflammatory activity of AA at least in LPS-activated RAW264.7 macrophages

Efficacy Evaluation of Combination Vaccine of Recombinant C-Terminal Fragments of ApxIA, ApxIIA and ApxIIIA in Piglets (Penilaian Kemujaraban Gabungan Vaksin Rekombinan Terminal-C Serpihan ApxIA, ApxIIA dan ApxIIIA pada Anak Babi)

ABSTRACT The efficacy of the combination vaccine of the individual C-terminal fragments o