Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular function and leukocyte recruitment: role of VEGF-receptor 2 and host VEGF-A.

Unlike vascular endothelial growth factor (VEGF)-A, the effect of VEGF-C on tumor angiogenesis, vascular permeability, and leukocyte recruitment is not known. To this end, we quantified in vivo growth and vascular function in tumors derived from two VEGF-C-overexpressing (VC+) and mock-transfected cell lines (T241 fibrosarcoma and VEGF-A-/- embryonic stem cells) grown in murine dorsal skinfold chambers. VC+ tumors grew more rapidly than mock-transfected tumors and exhibited parallel increases in tumor angiogenesis. Furthermore, VEGF-C overexpression elevated vascular permeability in T241 tumors, but not in VEGF-A-/- tumors. Surprisingly, unlike VEGF-A, VEGF-C did not increase leukocyte rolling or adhesion in tumor vessels. Administration of VEGF receptor (VEGFR)-2 neutralizing antibody DC101 reduced vascular density and permeability of both VC+ and mock-transduced T241 tumors. These data suggest that VEGFR-2 signaling is critical for tumor angiogenesis and vascular permeability and that VEGFR-3 signaling does not compensate for VEGFR-2 blockade. An alternate VEGFR, VEGFR-1 or neuropilin-1, may modulate adhesion of leukocytes to tumor vessels.

The spectrum of respiratory disease associated with exposure to metal working fluids.

Occupational respiratory diseases have been reported following exposure to metal working fluids. We report a spectrum of respiratory illnesses occurring in an outbreak in 30 workers of an automobile parts engine manufacturing plant. Workers presented with respiratory complaints and, after clinical and laboratory evaluations, were classified as those having hypersensitivity pneumonitis, occupational asthma, or industrial bronchitis, or those without occupational lung disease. Hypersensitivity pneumonitis affected seven workers, with six exhibiting serum precipitins to Acinetobacter Iwoffii. Occupational asthma and industrial bronchitis affected 12 and six workers, respectively. Oil-mist exposures were below current recommendations. Gram-negative bacteria, but no fungi, Thermophiles, or Legionella, were identified. Although specific agents responsible for each individual case could not be identified, probably both specific sensitizing agents and non-specific irritants from metal working fluids, additives, or contaminants contributed to this spectrum of occupational respiratory illness.

A customised portable LogMAR chart with adjustable chart illumination for use as a mass screening device in the rural population.

AIM: To develop a customised, portable, cost-effective (logarithmic minimal angle resolution) LogMAR chart with adjustable illumination for use as a mass vision-screening device in the rural population. MATERIALS AND METHODS: Visual acuity of 100 individuals was evaluated with a customised chart and compared with the standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart and Snellen's Chart. Bland and Altman analytical techniques were used for analysis. RESULTS: Test-retest variability of the customised chart was just a one-line difference (95% CI for agreement), and so were the results with the standard ETDRS charts; a variability of 3-line was noted with Snellen's chart. Two-line differences were observed when comparison was made with Standard ETDRS chart and 2 to 3-line differences with Snellen's chart. CONCLUSION: The customised portable LogMAR chart with adjustable illumination shows less test-retest variability and better agreement with standard ETDRS chart; therefore, it can be used as a mass vision-screening device in rural settings.

Role of leukocytes and tissue-derived oxidants in short-term skeletal muscle ischemia-reperfusion injury.

The relative contribution of xanthine oxidase (XO) and leukocytes to tissue injury after short-term ischemia is unknown. In this study, we subjected three groups of rat spinotrapezius muscles to 30-min ischemia and 1-h reperfusion: 1) ischemia-reperfusion (I/R) + 0.9% saline, 2) I/R + superoxide dismutase, and 3) I/R + oxypurinol. A fourth group served as nonischemic control. We quantified the increase in resistance (%DeltaR) caused by leukocyte-capillary plugging concurrently with myocyte uptake of propidium iodide (PI) [expressed as no. of PI spots per total volume of perfused tissue (N(PI)/V)] and performed assays to quantify XO activity, thiobarbituric acid-reactive substances (TBARS), and myeloperoxidase (MPO). Groups 2 and 3 exhibited significant decreases in N(PI)/V relative to group 1. MPO levels and TBARS were similar among all groups, and mean %DeltaR was significantly reduced in groups 2 and 3 relative to group 1. However, elevated XO was observed in groups 1 and 2 relative to group 3 and nonischemic controls. These data are consistent with the hypothesis that XO, rather than toxic species produced by plugging or venule-adherent leukocytes, is responsible for postischemic damage in this model.

Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability.

Nitric oxide (NO) plays a critical role in vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability. However, the relative contribution of different NO synthase (NOS) isoforms to these processes is not known. Here, we evaluated the relative contributions of endothelial and inducible NOS (eNOS and iNOS, respectively) to angiogenesis and permeability of VEGF-induced angiogenic vessels. The contribution of eNOS was assessed by using an eNOS-deficient mouse, and iNOS contribution was assessed by using a selective inhibitor [l-N(6)-(1-iminoethyl) lysine, l-NIL] and an iNOS-deficient mouse. Angiogenesis was induced by VEGF in type I collagen gels placed in the mouse cranial window. Angiogenesis, vessel diameter, blood flow rate, and vascular permeability were proportional to NO levels measured with microelectrodes: Wild-type (WT) > or = WT with l-NIL or iNOS(-/-) > eNOS(-/-) > or = eNOS(-/-) with l-NIL. The role of NOS in VEGF-induced acute vascular permeability increase in quiescent vessels also was determined by using eNOS- and iNOS-deficient mice. VEGF superfusion significantly increased permeability in both WT and iNOS(-/-) mice but not in eNOS(-/-) mice. These findings suggest that eNOS plays a predominant role in VEGF-induced angiogenesis and vascular permeability. Thus, selective modulation of eNOS activity is a promising strategy for altering angiogenesis and vascular permeability in vivo.