Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation

Acknowledgments: We thank Dr. Robert Barkley and Charis Uhlson for mass spectrometry analysis. Funding: This work was supported by grants from the National Institutes of Health HL34303 (to C.C.L., R.C.M. and D.L.B), DK54741 (to J.V.B.), GM5322 (to D.L.W.) and the Wellcome Trust (to N.A.R.G. and G.D.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

PROPRANOLOL HYDROCHLORIDE TOPICAL GEL FOR THE TREATMENT OF INFANTILE HEMANGIOMA

Objective: To formulate and evaluate propranolol hydrochloride topical gel for overcoming the limitations and low oral bioavailability associated with conventional therapy. Methods: The propranolol hydrochloride topical gels were prepared by the cold mechanical method. The preliminary evaluation and further characterisation studies was conducted to find the optimised formulation. The in vitro release and ex vivo permeation studies were investigated. The histopathological studies and stability studies was also assessed. Results: The propranolol hydrochloride topical gel was successfully prepared. The in vitro release of optimized topical propranolol hydrochloride gel formulation (G2) showed the highest cumulative percentage drug release that is, 95.55%±0.15 after 7.5 h. (G2) the formulation showed a higher flux value of 4.61μg/cm2/h. The histopathological study using pig skin revealed that the optimized formulation was found to be safe for topical application. Conclusion: The formulated topical gel containing propranolol Hydrochloride seems to be a promising dosage form for enhanced skin delivery of propranolol hydrochloride in treating Infantile Hemangioma

Pathways Regulating Cytosolic Phospholipase a\u3csub\u3e2\u3c/sub\u3e Activation and Eicosanoid Production in Macrophages by Candida Albicans

Resident tissue macrophages are activated by the fungal pathogen Candida albicans to release eicosanoids, which are important modulators of inflammation and immune responses. Our objective was to identify the macrophage receptors engaged by C. albicans that mediate activation of group IVA cytosolic phospholipase A2 (cPLA2α), a regulatory enzyme that releases arachidonic acid (AA) for production of prostaglandins and leukotrienes. A comparison of peritoneal macrophages from wild type and knock-out mice demonstrates that the β-glucan receptor Dectin-1 and MyD88 regulate early release of AA and eicosanoids in response to C. albicans. However, cyclooxygenase 2 (COX2) expression and later phase eicosanoid production are defective in MyD88-/- but not Dectin-1-/- macrophages. Furthermore, C. albicans-stimulated activation of MAPK and phosphorylation of cPLA2α on Ser-505 are regulated by MyD88 and not Dectin-1. In contrast, Dectin-1 mediates MAPK activation, cPLA 2α phosphorylation, and COX2 expression in response to particulate β-glucan suggesting that other receptors engaged by C. albicans preferentially mediate these responses. Results also implicate the mannan-binding receptor Dectin-2 in regulating cPLA2α. C. albicans-stimulated MAPK activation and AA release are blocked by D-mannose and Dectin-2-specific antibody, and overexpression of Dectin-2 in RAW264.7 macrophages enhances C. albicans-stimulated MAPK activation, AA release, and COX2 expression. In addition, calcium mobilization is enhanced in RAW264.7 macrophages overexpressing Dectin-1 or -2. The results demonstrate that C. albicans engages both β-glucan and mannan-binding receptors on macrophages that act with MyD88 to regulate the activation of cPLA2α and eicosanoid production

Genetic Variability for Downy Mildew Disease Incidence in Mapping Population Parents of Pearl Millet

Downy mildew caused by Sclerospora graminicola (Sacc.) Shroet. is a major biotic constraint to pearl millet production in the semi-arid tropics. The pathogen is heterothallic and frequent recombination leads to evolution of new virulent populations. Identification of resistance to new virulent isolates is a prerequisite for resistance breeding. In the present investigation, forty parents along with five control entries were screened against three Indian populations of Sclerospora graminicola under greenhouse conditions. Among the parental lines under study, ICMP 85410-P7, LGD-1-B-10, Tift 23DB-P1-P5, H77/833-2-P5, H77/833-2, Tift 238D1, ICMB 89111-P6, 81B-P13, ICMB 01222-P1, ICMB 95333-P1, ICMB 95333-P5 and IPC 804-P4 were found to be highly susceptible (>80 % DMI) in screening against three Indigenous pathogen isolates from Gujarat (Sg445), Haryana (Sg519) and Rajasthan (Sg526), while 863B-P2, AIMP 92901-S1-183-2-2-B-P08 and AIMP 92901-S1-15-1-2-B-P03 were resistant (<10% DMI) to test isolates. Some parents exhibited different levels of DM incidence to pathogen - isolates

Breeding tomato (Solanum lycopersicum L.) for resistance to biotic and abiotic stresses

Tomato (Solanum lycopersicum L.) is an important vegetable crop cultivated in the tropical and sub-tropical regions of the world. Low productivity in India is due to occurrence of both biotic and abiotic stresses. Among the biotic stresses, tomato leaf curl disease, bacterial wilt, early blight and Groundnut Bud Necrosis Virus disease have become serious production constraints causing considerable yield loss in the major tomato growing areas of the country. Adoption of multiple disease resistant varieties or F1 hybrids would be the most appropriate way to address these diseases. At ICAR-IIHR, Bengaluru systematic breeding strategies were employed to pyramid genes for resistance to early blight, bacterial wilt and tomato leaf curl diseases and to develop advanced breeding lines&amp; F1 hybrids with triple disease resistance. Stable source of resistance to early blight and bi-partite begomo-virus (Tomato Leaf Curl New Delhi Virus) has been identified in Solanum habrochaites LA-1777. Validation with molecular markers linked to tomato leaf curl virus resistance revealed that LA-1777 carryTy2 and other putative resistant genes. Several high yielding dual purpose hybrids were also developed for fresh market and processing with high level of resistance to multiple diseases. Cherry tomato lines have also been bred for high TSS, total carotenoids, total phenols, flavonoids, vitamin C, acidity and lycopene content. IIHR-249-1, IIHR-2101 (Solanum habrochaites LA-1777), IIHR- 2866 and IIHR-2864 recorded high values for quality parameters like total carotenoids, lycopene, vitamin C, total phenols, flavonoids and TSS. Drought tolerant root stock has been developed by an interspecific cross between S. habrochaites LA-1777 and S. lycopersicum (15 SB SB). Resistant sources have also been identified against Tuta absoluta, a serious insect pest reported from major tomato growing areas in the country in recent time. High temperature tolerant breeding lines are in pipe line