Drugs online research references
Pediatr Res. 1998 Jul;44(1):119-24.
The effect of antioxidative combination therapy on post hypoxic-ischemic perfusion, metabolism, and electrical activity of the newborn brain.
Shadid M, Moison R, Steendijk P, Hiltermann L, Berger HM, van Bel F.
Department of Pediatrics, Leiden University Hospital, The Netherlands.
Reoxygenation and reperfusion after severe hypoxia and ischemia (HI) contribute substantially to birth asphyxia-related brain injury. Excess production of free radicals via metabolization of arachidonic acid, xanthine oxidase, and non-protein-bound iron play an important role. Cerebral reperfusion injury is characterized by a decrease in perfusion, oxygen consumption, and electrical activity of the brain. Reduction of free radical production may attenuate these features. We therefore induced severe HI in 35 newborn lambs, and upon reperfusion the lambs received a placebo [control (CONT), n = 7], the cyclooxygenase inhibitor indomethacin (INDO, 0.3 mg/kg/i.v., n = 7), the xanthine oxidase inhibitor allopurinol (ALLO, 20 mg/kg/i.v., n = 7), the iron chelator deferoxamine (DFO, 2.5 mg/kg/i.v., n = 7), or a combination of these drugs (COMB, n = 7). In each group changes (%) from pre-HI values were investigated for brain perfusion [measured by carotid artery flow (Qcar, mL/min)], (relative) cerebral O2 metabolism (CMR(O2)), and electrocortical brain activity (ECBA, microV) at 15, 60, 120, and 180 min post-HI. Qcar decreased significantly at 120 and 180 min post-HI in CONT (p < 0.05), but not in INDO, ALLO, DFO, and COMB groups. CMR(O2) decreased significantly in CONT at 60 min post-HI (p < 0.05), remained stable in DFO and INDO, and was significantly higher in ALLO and COMB (p < 0.05) at 120 and 180 min post-HI. ECBA was significantly lower in CONT during the whole post-HI period (p < 0.05), ECBA in INDO and COMB were significantly decreased at 60 and 120 min post-HI (p < 0.05), but recovered afterward, whereas DFO and ALLO remained stable during the post-HI period. In conclusion preservation of Qcar and CMR(O2), and recovery of ECBA occurred after treatment with INDO, ALLO, and DFO; combination of these drugs did not have an additional positive effect.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9667381&dopt=Abstract
J Vasc Surg. 1998 Dec;28(6):1094-103.
Thrombogenesis of different cell types seeded on vascular grafts and studied under blood-flow conditions.
Hedeman Joosten PP, Verhagen HJ, Heijnen-Snyder GJ, van Vroonhoven TJ, Sixma JJ, de Groot PG, Eikelboom BC.
Departments of Surgery and Haematology, University Hospital Utrecht, Utrecht, The Netherlands.
BACKGROUND: Small-diameter vascular grafts tend to have an early and high occlusion rate. Cell seeding on the luminal surfaces of small-diameter vascular prostheses may provide an antithrombotic lining and improve both the short-term and the long-term patency rates. We studied the net results of procoagulant and anticoagulant properties of seeded grafts under blood-flow conditions, and we compared the different available types of donor cells. METHODS: Monolayers of liposuction-derived cultured human microvascular endothelial cells (MVECs), human adult endothelial cells (HAECs), human umbilical vein endothelial cells (HUVECs), and human mesothelial cells (MCs) that had been seeded on expanded polytetrafluoroethylene (ePTFE) grafts were perfused with marginally anticoagulated blood (20 U/mL low molecular weight heparin; shear rate, 400/s, 10 minutes) or with non-anticoagulated blood (shear rate, 100/s, 5 minutes). The thrombin and fibrin generation in time was studied with the measurement of the plasma levels of prothrombin fragment 1 and 2 (F 1+2) and of fibrinopeptide A (FPA). The plain ePTFE graft was taken as a control. RESULTS: When the seeded MCs were perfused with recirculating anticoagulated blood, a linear generation of F 1+2 in time was seen, with high levels of F 1+2 and FPA after 10 minutes (4.38 nmol/L and 362 ng/mL, respectively). Allopurinol was added, and the MCs generated less F 1+2 than the HAECs (0.7 nmol/L vs 1.86 nmol/L; P <.05). No fibrin formation was seen. The MVECs generated low amounts of F 1+2 (0.7 nmol/L; 10 minutes), and the HUVECs and the plain ePTFE graft generated the lowest amounts of F 1+2 (0.26 and 0.25 nmol/L, respectively). When the MCs were perfused with non-anticoagulated blood, high amounts of thrombin and fibrin were generated immediately and constantly and could not be decreased with allopurinol. The perfusion of the plain ePTFE graft showed a dramatic increase in F 1+2 and FPA levels towards the end of the experiments. The seeded HAECs, HUVECs, and MVECs inhibited this increase. These results were confirmed by means of scanning electron microscopy. CONCLUSION: Vascular prostheses that are seeded with cultured MCs are highly procoagulant. Standard ePTFE graft prostheses also initiate coagulation, which supports the idea of cell seeding. The endothelial cells, of which the MVECs are the most readily available, seem to preserve their anticoagulant properties after being seeded on vascular grafts.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9845661&dopt=Abstract
Alcohol Alcohol. 1991;26(3):303-7.
Disturbances in myocardial creatine kinase following ethanol administration to rats--trials of prevention by allopurinol, desferrioxamine and propranolol.
Hininger I, Ribiere C, Nordmann R.
Department of Biomedical Research on Alcoholism, Universite Rene Descartes, Paris, France.
A significant decrease in myocardial creatine kinase (CK) activity is apparent 2 hr after an acute ethanol load (2.3 g/kg, i.p.) in the rat. A lower dose (1.15 g/kg, i.p.), as well as ethanol addition in vitro up to 50 mM, do not affect this activity. Pretreatment with allopurinol (146 mumols/kg, i.p.) given at 16 hr and at 30 min before ethanol (2.3 g/kg) or with desferrioxamine (152 mumols/kg, i.p.) 30 min before ethanol failed to prevent the ethanol-induced decrease in CK activity. By contrast, propranolol (17 mumols/kg, i.p.), administered 30 min before ethanol elicited an enhanced CK activity in both control and ethanol-treated rats. This finding is likely related to the beta-blocking action and/or antioxidant properties of propranolol. Chronic ethanol intake (18% in calories) for 4 weeks also induced a decrease in myocardial CK activity, which could play a role in the pathogenesis of alcoholic cardiomyopathy.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1930362&dopt=Abstract
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