ABSTRACT
Objectives: In May 2018, a laboratory network for antimicrobial resistance (AMR) surveillance in Tamil Nadu, India, detected a cluster of Salmonella enterica serotype Typhi (S. Typhi) isolates resistant to ceftriaxone. We investigated to describe the epidemiology and identify risk factors for the outbreak. Methods: We conducted unmatched case-control studies. We defined a case as illness (fever with abdominal pain, diarrhea or vomiting) in a person with blood culture-confirmed ceftriaxone-resistant S. Typhi isolated between January 1 and July 4, 2018 in Tiruchirappalli, Tamil Nadu. We interviewed cases using a semi-structured questionnaire to identify common exposures to food, water and places visited. Results: We identified 7 cases (5 men) during March 25-June 8, 2018, median age 23 years (range: 12-42); all were hospitalized, none died. Eating at Restaurant A (odds ratio [OR]=22) and chicken gravy (OR=16) was associated with illness. Of the 10 workers at Restaurant A, stool culture from 8 did not detect S. Typhi; 2 did not consent to provide samples. Five water samples around the restaurant showed low or no residual chlorine content. Conclusions: The investigation highlights the value of AMR surveillance in detecting emerging pathogens and the need for timely investigations, along with strengthening food safety.
ABSTRACT
The mechanism of cell-cell contact dependent regulation of pericellular proteolysis in angiogenesis was examined by studying the expression of MMPs using isolated HUVECs in culture. Zymography, Immunoblot and RT-PCR analysis showed that the production and secretion of matrixmetalloproteinase-2 and matrixmetalloproteinase-9 by HUVECs in culture were high when they remain as individual cells and significantly decreased during later stages of culture when cells developed cell-cell contact and tubular network-like structure. As MMPs decreased there was significant upregulation of VE-cadherin in cells undergoing angiogenic transition. Investigations to understand the signaling pathways downstream of VE-cadherin showed a relatively high level of ß-catenin in the nucleus of endothelial cells in culture during initial stages and decrease in its levels in the nucleus, associated with an increase in the cytosol during later stages of culture. The distribution of ß-catenin was found to be regulated by Tyr/Ser phosphorylation status of this protein. Cell-cell contact dependent downregulation of MMPs during angiogenesis was also observed in experiments using proangiogenic substances which caused a rapid rate of downregulation of MMP-2 and MMP-9 and absence of downregulation of MMPs when treated with anti-angiogenic agents.
ABSTRACT
The molecular mechanism of the angiogenic effect of laminin (Ln) was studied using human umbilical vein endothelial cells (HUVECs) maintained in culture on Ln-1 substratum. High-pressure liquid chromatography analysis showed that in cells maintained on Ln, the levels of proangiogenic prostaglandin E(2) (PGE(2)) increased and that of antiangiogenic PGD(2) decreased. The angiogenic effect of PGE(2) and PGD(2) was confirmed by assessing the expression of CD31 and E-selectin in HUVECs. Immunoblot analysis, reverse transcription-polymerase chain reaction and cyclooxygenase (COX) assay showed increase in the expression and activity of COX-2 in cells maintained on Ln. Use of pharmacological inhibitors suggested that the modulation in the expression of COX-2 and thereby the levels of PGE(2) and PGD(2) in endothelial cells by Ln is mediated through the α(6)ß(4) integrin-p38MAPK (mitogen-activated protein kinase)-NF-κB signaling pathway.
