Inflammation is one of the primary processes underlying respiratory distress syndrome (RDS) and its evolution into bronchopulmonary dysplasia (BPD). Recruitment and subsequent activation of macrophages in the lung are mediated by CC chemokines. The role of CC chemokines has not been extensively studied in the course of RDS. Serial tracheal aspirates (TA) were obtained from 56 mechanically ventilated infants with birth weights less than 1,500 g during intervals in the first 21 days of life. Tracheal aspirate concentrations of monocyte chemoattractant proteins-1,2,3 (MCP-1,2,3) and macrophage inflammatory proteins-1alpha and -1beta (MIP-1alpha, MIP-1beta) were determined by enzyme-linked immunosorbent assay (ELISA). Tracheal aspirate concentrations of MCP-1, MCP-2, MCP-3, and MIP-1beta increased during the first week of life in infants with RDS, whereas MIP-1alpha concentrations did not increase appreciably. Increased TA cytokine concentrations were associated with the development of BPD. Maximal TA concentrations of MCP-1, MCP-2, MCP-3, MIP-1alpha, and MIP-1beta were significantly higher in infants who were oxygen-dependent at 28 postnatal days compared to infant who were not. Similarly, maximal TA MCP-1, MCP-2, and MCP-3 but not MIP-1alpha and MIP-1beta concentrations were significantly higher in infants who were oxygen-dependent at 36 weeks of postconceptional age (PCA) than those who were not oxygen-dependent at 36 weeks PCA. Histologic chorioamnionitis and isolation of Ureaplasma urealyticum from the airways were associated with higher maximal TA concentrations of MIP-1alpha and MIP-1beta. Pulmonary hemorrhage was associated with increased maximal concentrations of MCP-1, MCP-2, and MCP-3. These data suggest a role for CC chemokines in the development of BPD in the newborn infant.
Koetjapic acid is a naturally occurring ichthyotoxic compound which can be isolated from the stem bark of Sandricum keotjape. This is a large tree species that can be found widely in Malaysia and other tropical countries in Southeast Asia. In our studies, we found koetjapic acid to be strongly antiangiogenic causing significant inhibition in endothelial tube formation. The compound inhibited VEGFA expression and caused retardation in cell migration. Keotjapic acid also suppressed the activity of Hif-1a and up regulates TGFβ and NFκB activity. This suggests the potential use of Keotjapic acid to target ailments that is angiogenesis dependent.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A52.
Background: Chemotherapy consisting of Adriamycin, Bleomycin, Vinblastine, and Doxorubicin (ABVD), which is the mainstay of treatment in Hodgkin's Lymphoma (HL), is associated with both acute and long-term pulmonary toxicity primarily due to Bleomycin. Bleomycin induced pulmonary toxicity (BPT) is clinically detected using diffusing lung capacity for carbon monoxide (DLCO). The objective of this study was to evaluate changes in DLCO in HL patients before and after ABVD chemotherapy. Methods: Medical records of all adult HL patients treated with ABVD chemotherapy at a single centre in Lahore, Pakistan during the entire calendar year 2012 were analysed. Patients with pre-existing pulmonary dysfunction, history of thoracic surgery and smokers were excluded. Results: A total of 179 HL patients were identified during the study period who received ABVD chemotherapy. Out of these, 93 (51.95%) patients had undergone both a pre-and post-chemotherapy DLCO measurements. The remaining patients had only one DLCO reading available and were not included in the analysis. The mean percentage difference between pre-and post-chemotherapy values for DLCO (5.49%; 95% confidence interval [CI] 1.56-9.43%) and for Haemoglobin-adjusted DLCO (8.24%; 95% CI 3.90-12.57%) were statistically significant at p<0.01. Diffusing lung capacity for carbon (DLCO) values declined from pre-treatment to post-treatment by 1-10% in 23 (24.7%) patients, by 10-20% in 19 (20.4%) patients, by 20-30% in 10 (10.8%) patients and >30% in 10 (10.8%) patients. After adjusting for age, a 1mg/m 2 increase in dose of Bleomycin was significantly associated with 0.14% (95% CI: 0.03-0.25%) decline in DLCO and 0.13% (95% CI: 0.10-0.26%) decline in haemoglobin-adjusted DLCO from pre-treatment value. Conclusions: Mild to moderate dysfunction in diffusion lung capacity is common after ABVD chemotherapy. DLCO and haemoglobin-adjusted DLCO value decreased with increasing age and increasing dose of Bleomycin.
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