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1.
J Vasc Interv Radiol ; 12(8): 969-77, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11487678

ABSTRACT

PURPOSE: To create a porcine hemodialysis access model that reliably reproduces intimal hyperplasia (IH) of the outflow vein similar to that which causes access failure in human patients undergoing dialysis treatments. MATERIALS AND METHODS: Surgical technique for creation of side-to-side iliac-artery-to-ipsilateral-iliac-vein (IAV) native fistulas and IAV conduits was optimized in three standard-bred pigs. Persistent patency of fistulas and conduits was demonstrated in two additional pigs allowed to survive for 1 week. IAV fistulas and contralateral 2-cm polytetrafluoroethylene IAV conduits were created in five additional pigs. Venous outflow from these fistulas and conduits was evaluated with venography and intravascular ultrasound (IVUS) immediately after creation (day 0) and at 2-week intervals for as long as 64 days. Animals were killed at 30 days (n = 1), 42 days (n = 2), or 64 days (n = 2), and the arteries, veins, and conduits were evaluated histologically. RESULTS: IAV native fistulas remained patent until the animals' death and conduits remained patent for at least 14 days in four of five pigs; both the fistula and conduit likely occluded before 16-day follow-up in the fifth pig. At 42-64 days, venography demonstrated maximum fistula outflow vein diameter stenoses of 53%-76% and maximum conduit outflow vein stenoses of 44%-84%, and IVUS demonstrated maximum area stenoses of 64%-86% and 43%-82%, respectively. Three of five conduits occluded, one before 16-day follow-up, one between 14 and 28 days, and the other after 42 days. Histologic sections demonstrated IH predominantly affecting the veins at the anastomoses and central (cephalad) to the anastomoses in all pigs. CONCLUSION: This porcine model reproduces IH in the fistula or conduit outflow vein with measurable stenosis. Such a model might allow relevant preclinical evaluation of interventional devices and techniques intended to reduce the effects of IH in human patients undergoing dialysis treatments.


Subject(s)
Arteriovenous Shunt, Surgical , Disease Models, Animal , Renal Dialysis/adverse effects , Swine , Tunica Intima/pathology , Animals , Female , Hyperplasia/etiology , Hyperplasia/pathology , Iliac Artery/surgery , Iliac Vein/diagnostic imaging , Iliac Vein/surgery , Radiography , Renal Dialysis/instrumentation , Reproducibility of Results , Ultrasonography, Interventional
2.
J Clin Endocrinol Metab ; 85(10): 3551-6, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11061500

ABSTRACT

The hexosamine biosynthetic pathway has recently been proposed as a mechanism through which cells "sense" nutrient flux to regulate leptin release. This study was undertaken to examine the regulation of leptin production by hexosamines in human adipocytes. Adipose tissue UDP-N-acetylglucosamine, an end product of hexosamine biosynthesis, was elevated 3.2-fold, and ob messenger ribonucleic acid was elevated 2-fold in the sc adipose tissue of 17 obese [body mass index (BMI), 41.3+/-12.0 kg/m2; age, 31+/-5 yr] subjects compared to 14 lean (BMI, 23.4+/-1.6 kg/m2; age, 33+/-11 yr) subjects. Serum leptin was increased 2.7-fold in the obese subjects. A significant positive relationship was found between adipose tissue UDP-N-acetylglucosamine and BMI (Spearman correlation = 0.576; P = 0.0007) and between UDP-N-acetylglucosamine and serum leptin (Spearman correlation = 0.4650; P = 0.0145). Treatment of isolated sc adipocytes with 1 mmol/L glucosamine, an intermediate product in UDP-N-acetylglucosamine biosynthesis, increased leptin release 21.4+/-17.6% (mean +/- SD) over control (P = 0.0365) and 74.5+/-82.8% over control (P = 0.0271) in adipocytes from lean (BMI, 23.2+/-1.6 kg/m2; n = 6) and obese (BMI, 55.4+/-13.0 kg/m2,; n = 9) subjects, respectively, by 48 h of culture. Inhibition of UDP-N-acetylglucosamine biosynthesis with 6-diazo-5-oxo-norleucine reduced glucose-stimulated leptin release from cultured adipocytes 21.8+/-32.4% (P = 0.0395; n = 12) and ob gene expression 19.9+/-18.9% (P = 0.0208; n = 8) by 48 h of treatment. These findings suggest that hexosamine biosynthesis regulates leptin production in human adipose tissue.


Subject(s)
Adipocytes/metabolism , Hexosamines/physiology , Leptin/biosynthesis , Adipocytes/drug effects , Body Mass Index , Cells, Cultured , Diazooxonorleucine/pharmacology , Glucosamine/pharmacology , Hexosamines/biosynthesis , Humans , In Vitro Techniques , Leptin/blood , Obesity/metabolism , Stimulation, Chemical , Uridine Diphosphate N-Acetylglucosamine/metabolism
3.
Alcohol Clin Exp Res ; 21(1): 122-7, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9046384

ABSTRACT

Therapeutic observations suggest that azidothymidine (AZT)-resistant HIV+/AIDS patients are frequently offered AZT/dideoxycytidine (DDC) or dideoxyinosine (DDI) therapy. The latter therapies have been associated with the development of acute pancreatitis. During the initial portion of this study, when patients reported limiting ethanol consumption, an increase in CD4+, a decrease in amylase, and a decrease in lipase was observed in patients on DDI monotherapy. Marinol/marijuana usage was associated with depressed CD4+ counts and elevated amylase levels within the DDI subgroup. The purpose of this study was to follow these patients over 1 year and compare clinical indicators of pancreatitis and HIV progression. After 1 year, the remaining 56 patients were reexamined in the follow-up portion for clinical indicators of HIV disease progression and pancreatoxic/hepatotoxic effects. Those in the AZT group, who remained on this therapy throughout the year, had significantly increased amylase values from 55.3 to 69.3 IU/liter (p < 0.05). In the AZT/DDC group, those who remained on combination therapy throughout the year, 4 of the 5 clinical indicators of disease progression changed. Amylase, ALT, and AST all increased significantly from 55.2 to 77.8 IU/liter (p < 0.01), from 38.0 to 92.3 IU/liter (p < 0.05), and from 55.2 to 97.0 IU/liter (p < 0.05), respectively. Lipase levels decreased significantly (106.0 to 74.6 IU/liter, p < 0.05). The most remarkable changes occurred in the AZT/DDC group (who reduced ethanol consumption), wherein clinical indicators of pancreatitis and liver dysfunction declined, including amylase (65.0 to 20.0 IU/liter, p < 0.05), ALT (350.0 to 100.0 IU/liter, p < 0.01), and AST (240.0 to 95.0 IU/liter, p < 0.01). No significant changes were noted in the DDI or AZT groups. Marinol/marijuana use was associated with declining health status in both the AZT and AZT/DDC groups. In contrast, all clinical indicators of pancreatitis improved in the DDI patients who utilized Marinol/marijuana, including amylase (-34%), lipase (-30.8%), ALT (-21.4%), and AST (-20.1%). This paired follow-up study suggests that HIV+/AIDS patients on antiretroviral therapies should restrict their ethanol consumption. In HIV+/AIDS patients with the lowest CD4+ counts (those on DDI monotherapy), utilization of Marinol/marijuana does not seem to have a deleterious impact.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Alcohol Drinking/adverse effects , Anti-HIV Agents/adverse effects , Appetite Stimulants/adverse effects , Didanosine/adverse effects , Dronabinol/adverse effects , HIV Seropositivity/drug therapy , Marijuana Smoking/adverse effects , Pancreatitis, Alcoholic/etiology , Zalcitabine/adverse effects , Zidovudine/adverse effects , Acquired Immunodeficiency Syndrome/immunology , Adult , Aged , Alcohol Drinking/immunology , Amylases/blood , Anti-HIV Agents/administration & dosage , Appetite Stimulants/administration & dosage , CD4 Lymphocyte Count/drug effects , Didanosine/administration & dosage , Dronabinol/administration & dosage , Drug Therapy, Combination , Female , Follow-Up Studies , HIV Seropositivity/immunology , Humans , Liver Function Tests , Male , Marijuana Smoking/immunology , Middle Aged , Pancreatitis, Alcoholic/immunology , Zalcitabine/administration & dosage , Zidovudine/administration & dosage
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