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1.
Pediatr Diabetes ; 11(7): 471-8, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20144181

ABSTRACT

OBJECTIVE: This study investigates the therapeutic potential of hyperbaric oxygen therapy (HBO) in reducing hypoxia and improving engraftment of intraportal islet transplants by promoting angiogenesis. METHODS: Diabetic BALB/c mice were transplanted with 500 syngeneic islets intraportally and received six consecutive twice-daily HBO treatments (n = 9; 100% oxygen for 1 h at 2.5 atmospheres absolute) after transplantation. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) was used to assess new vessel formation at postoperative days (POD) 3, 7, and 14. Liver tissue was recovered at the same time points for correlative histology, including: hematoxylin and eosin, hypoxia-inducible factor (HIF1α), Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), vascular endothelial growth factor (VEGF), and von Willebrand Factor immunohistochemistry. RESULTS: HBO therapy significantly reduced HIF-1α, TUNEL and VEGF expression in islets at POD 7. In the non-HBO transplants, liver enhancement on DCE MRI peaked at POD 7 consistent with less mature vasculature but this enhancement was suppressed at POD 7 in the HBO-treated group. The number of new peri-islet vessels at POD 7 was not significantly different between HBO and control groups. CONCLUSION: These results are consistent with a hyperbaric oxygen-mediated decrease in hypoxia that appeared to enhance vessel maturation in the critical days following intraportal islet transplantation.


Subject(s)
Diabetes Mellitus, Experimental/therapy , Hyperbaric Oxygenation , Islets of Langerhans Transplantation/methods , Neovascularization, Physiologic/drug effects , Animals , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , In Situ Nick-End Labeling , Islets of Langerhans/blood supply , Islets of Langerhans/physiology , Magnetic Resonance Imaging , Mice , Mice, Inbred BALB C , Vascular Endothelial Growth Factor A/metabolism
2.
Sci Total Environ ; 673: 165-176, 2019 Jul 10.
Article in English | MEDLINE | ID: mdl-30986676

ABSTRACT

Many of the world's major freshwater aquifers are being exploited unsustainably, with some projected to approach environmentally unsafe drawdown limits within the 21st century. Given that aquifer depletion tends to occur in important crop producing regions, the prospect of running dry poses a significant threat to global food security. Here we use the Global Change Assessment Model (GCAM) to explore the response of land use and agriculture sectors to severe constraints on global water resources. We simulate a scenario in which a number of important groundwater aquifers become depleted to the point where further water withdrawal is unviable, either due to excessive extraction costs or environmental limits being reached. Results are then benchmarked against a scenario that neglects constraints on water withdrawals. We find that groundwater depletion and associated water price increases drive two distinct responses in the agriculture sector: an expansion of rain fed agriculture, and a shift in irrigated crop production toward regions with cheaper water resources. Losses in crop production are most pronounced in water stressed regions where groundwater is being depleted unsustainably to meet irrigation demands-namely northwest India, Pakistan, the Middle East, western United States, Mexico, and Central Asia. While these results highlight substantial risks for the affected regional agricultural economies, we show that modest changes in irrigation and location of crop growth, in a world with frictionless trade, could ensure global food demands are met despite severe water constraints.

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