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Biomedical subjects

A M Roza

Publications and source records attributed to A M Roza.

At least 37 records · Page 2Linked to original sources
PubMed1997

Management of severe pancreatitis in renal transplant recipients.

OBJECTIVE: The authors determine if any aspects of the treatment of renal transplant patients with pancreatitis were of particular benefit with regard to graft and patient survival. BACKGROUND: The incidence of pancreatitis in renal transplant patients is low (1%-2%), but the mortality of the disease approaches 100%. Although several descriptive reports have been published, there is no consensus-regarding management. METHODS: The authors conduct a retrospective chart review. RESULTS: Twenty-one patients were identified with posttransplant pancreatitis (1.3% incidence). The cause of pancreatitis was presumed to be maintenance immunosuppression in all cases. Patients were classified by dynamic computed tomography (CT) scans having 1) mild/edematous disease (4 patients), 2) localized abscess or pseudocyst (6 patients), or 3) severe disease (11 patients). Patients with mild/edematous pancreatitis did well with medical management. The six patients with localized abscess or pseudocyst were successfully treated with standard operative intervention. Of the 11 patients with severe disease, 6 had several days of intensive medical management before operation, and all died. The other five patients underwent early operative intervention based principally on CT scan findings, and all survived. The latter group had multiple operations and four of five had functioning renal allografts at discharge. CONCLUSION: The severity of pancreatitis in the posttranplant patients may be difficult to assess by clinical criteria. Dynamic CT scanning is, therefore, essential in defining the extent of disease. Early, and perhaps repeated, operations may be lifesaving in those patients having CT scan findings of severe pancreatitis.

Adult↗
PubMed1996

Evaluation of the mechanism of endothelial dysfunction in the genetically-diabetic BB rat.

Endothelial dysfunction is known to occur in chemically-induced animal models of diabetes. The BB diabetic rat is a genetic diabetes-prone model which more closely resembles Type I diabetes mellitus. In this study, we examined the role of superoxide anion radical and cyclooxygenase activity on endothelial dysfunction in aorta of the spontaneous diabetic BB rat. Vascular endothelial function was studied in vitro in aortic rings from 8-wk diabetic rats and age-matched nondiabetic littermates. There was no alteration in reactivity to norepinephrine as a result of diabetes. Relaxation to acetylcholine (but not nitroglycerin) was impaired in diabetic rings. Relaxation to acetylcholine was abolished by 100 microM L-nitroarginine but unaltered by an equimolar concentration of aminoguanidine (an inducible nitric oxide synthase inhibitor) in both control and diabetic rings. Incubation with 10 microM indomethacin did not alter relaxation to acetylcholine in either control or diabetic rings. In contrast, addition of 20 U/ml superoxide dismutase enhanced relaxation to acetylcholine in diabetic rings but had no effect on relaxation to acetylcholine in control rings. Thus, nitric oxide-mediated, endothelium-dependent relaxation is diminished in aortic rings of the genetic diabetic BB rat. Furthermore, superoxide anion radicals but not cyclooxygenase products play an important role in endothelial dysfunction in this genetic diabetic model.

Acetylcholine↗
PubMed1996

Restoration of vascular endothelial function in diabetes.

Nitric oxide (NO) is believed to mediate the phenomenon known as endothelium-dependent relaxation (EDR). NO synthase produces NO from its precursor, arginine (ARG). We have previously demonstrated impaired EDR in diabetic blood vessels. In this study, we investigated a possible mechanism for defective EDR in experimental diabetes and whether pancreatic islet transplantation could reverse established endothelial dysfunction. Streptozotocin-induced diabetic rats were maintained for 8 or 12 weeks. NO-mediated EDR was assessed in isolated thoracic rings ex vivo. A group of untreated diabetic rats received syngeneic islet transplantation at 8 weeks of diabetes and were tested for EDR after 4 weeks of euglycemia. EDR to acetylcholine was impaired in untreated diabetic rings. Endothelium-independent relaxation to nitroglycerin was unaltered. In vitro incubation of diabetic rings with 3 mM L-ARG (but not D-ARG) improved EDR to acetylcholine in rings from 8-week but not 12-week diabetic rats. L-ARG did not alter EDR in control rings nor relaxation to nitroglycerin in control or diabetic rings. Islet transplantation at 8 weeks of diabetes normalized blood glucose, plasma arginine and total glycosylated hemoglobin while restoring normal EDR. In conclusion, a defect in substrate/supply for NO synthesis is acutely reversed by ARG supplementation at early but not at later stages of diabetes. Also, preemptive surgical intervention with islet transplantation prior to the ARG-insensitive phase is an effective strategy to reverse established endothelial dysfunction in diabetes mellitus.

Animals↗
PubMed1996

Delayed gastroduodenal emptying is an important mechanism for control of intestinal transit in short-gut syndrome.

PURPOSE: To understand the relative importance of changes in ileal smooth muscle contractility versus alteration of intestinal flow rate as control mechanisms for regulating intestinal transit in a surgical model of short-gut syndrome. METHODS: A model of short-gut syndrome was created by performing a 70% proximal small-bowel resection in dogs. Ten control and 6 animals with short-gut syndrome were instrumented with strain gauge transducers, steel collection cannulas, and a Silastic intraluminal infusion catheter in the midileum. Motor activity was analyzed by computer programs that determine frequency, amplitude, and propagation behavior of postprandial contractions. Perfusions of 14C-polyethylene glycol and bolus injection of 3H-polyethylene glycol were used to determine intestinal flow and transit rates. Total gastroduodenal emptying was determined using a 14C-polyethylene glycol-labelled meal. RESULTS: Postprandial contraction frequency was decreased in animals with short-gut syndrome, but other significant changes in amplitude, mean area, and propagation behavior of postprandial ileal contractions were not seen. Gastroduodenal emptying and mean intestinal flow rates were markedly slower in animals with short-gut syndrome, as were intestinal transit rates. CONCLUSIONS: In this model of short-gut syndrome, the major adaptive change is decreased intestinal flow rate, related to delayed gastroduodenal emptying. The spatial organization of ileal contractions does not change substantially aside from a change in frequency which can be accounted for by transection of the intestinal wall.

Animals↗
PubMed1996

Chronic treatment in vivo with dimethylthiourea, a hydroxyl radical scavenger, prevents diabetes-induced endothelial dysfunction.

Oxidative stress is believed to play a role in diabetes-induced vascular complications. In this study, we tested whether chronic treatment with a known hydroxyl radical scavenger, dimethylthiourea (DMTU), could prevent endothelial dysfunction in diabetes. Lewis strain rats were made diabetic by an intravenous injection of streptozotocin. A subgroup of diabetic animals received daily intraperitoneal injections of 50 mg/kg DMTU beginning at 72 h after streptozotocin and throughout 8 weeks of diabetes. Diabetes caused an increase in aortic catalase activity (an index of compensatory in vivo oxidative stress) that was not prevented by long-term DMTU treatment. Long-term treatment of diabetic animals with DMTU did not alter serum insulin levels, blood glucose concentrations, or total glycosylated hemoglobin. Descending thoracic aortas were isolated, sectioned into rings and suspended in isolated tissue baths, and contracted with a submaximal concentration of norepinephrine. Relaxation to the endothelium-dependent vasodilator, acetylcholine, was impaired in diabetic aortas, whereas relaxation to A23187 and nitroglycerin was unaltered. DMTU treatment prevented the diabetes-induced impairment in endothelium-dependent relaxation to acetylcholine but had no effect on relaxations induced by either A23187 or nitroglycerin. These data suggest that chronic exposure to increased levels of hydroxyl radicals in vivo likely play a significant role in the origin of diabetes-associated endothelial dysfunction.

Acetylcholine↗
PubMed1995

Detection by ESR of DMPO hydroxyl adduct formation from islets of Langerhans.

Electron spin resonance (ESR) spectroscopy together with spin trapping techniques and the application of state-of-the-art loop gap resonators was used to provide a direct measure of spontaneous oxygen radical production by homogenates of freshly isolated and cultured rat pancreatic islets. Using the spin trap agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), we were able to detect production by islets of an ESR-sensitive radical signal consisting of a quartet with intensity ratio of 1:2:2:1 and hyperfine splitting of aN = aH = 14.9 Gauss, which is consistent with the DMPO-OH adduct. The amplitude of the signal was decreased by decreasing amount of islets and not detected in the absence of islets. Formation of the DMPO-OH adduct was diminished by the hydroxyl radical scavengers (e.g., ethanol, dimethylsulfoxide, and dimethylthiourea). Only partial attenuation of signal was produced by incubation with an iron chelator or using chelex-treated buffers. The ESR signal was insensitive to the xanthine oxidase inhibitor, oxypurinol, or to superoxide dismutase, but was eliminated in a concentration-dependent manner by either potassium cyanide or catalase (but not heat-inactivated catalase). These observations suggest that the origin of the DMPO-OH arose not from free hydroxyl radicals but primarily from endogenous hydrogen peroxide production perhaps of mitochondrial origin. The development of this technology has implications for the potential measure of oxygen radical production in islet homogenates under pathologic conditions as well as to the application of other cell culture systems.

Animals↗
PubMed1995

Effects of transection and reanastomosis on postprandial jejunal transit and contractile activity.

BACKGROUND: The purpose of this study was to determine how transection and reanastomosis of the intestinal wall influences postprandial motor activity and transit in the small intestine. METHODS: Six dogs were each instrumented with 12 strain gauge transducers, two collection cannulas, and an infusion catheter defining a 100 cm study segment in the midjejunum. The animals underwent baseline measurements of postprandial motor activity and transit rate after 650 kcal solid and liquid meals. Postprandial motor activity was analyzed by computer methods that identify frequency, duration, amplitude, and propagation behavior of smooth muscle contractions. After the baseline measurements were performed, each animal underwent transection and reanastomosis of the intestinal wall at sites marked during the initial laparotomy. Measurements of postprandial motor activity and transit were repeated and compared with control values. RESULTS: Transection decreased frequency, amplitude, and percent propagation for postprandial contractions. Total propagating area per minute significantly decreased from 382 +/- 20 gram-seconds/minute to 190 +/- 66 gram-seconds/minute after transection (p < 0.05). Intestinal transit decreased from 13.5 +/- 1.5 cm/min to 8.5 +/- 2.4 cm/min (p < 0.05). The change in transit was related primarily to a change in frequency of propagating contractions (r = 0.767; p = 0.004). CONCLUSIONS: Transection and reanastomosis of the intestinal wall changes the temporal and spatial organization of contractions distal to the transection site. The net result is fewer distally propagating contractions and slower intestinal transit.

Anastomosis, Surgical↗
PubMed1995

Pancreatic antioxidant enzyme activity in normoglycemic diabetic prone BB rats.

Free radicals have been implicated in beta-cell destruction. pancreatic antioxidant enzymatic defenses provide significant endogenous protection from these highly cytotoxic effector molecules. In our colony of BB rats, the reliability of peripheral blood lymphocyte count (PBLC) as a predictor of diabetes onset was assessed in 99 male and 110 female BB rats. In rats with a PBLC < 4,200 mm3, 90% of males and 86% of females developed diabetes by 120 days of age and are designated "lymphopenic" or BBL. Rats with a PBLC > 4,200 mm3 have a much lower incidence of insulin-dependent diabetes mellitus (IDDM) and are designated "nonlymphopenic" or BBNL. In separate cohorts of normoglycemic (prediabetic) BBL rats (high risk for developing diabetes) and BBNL rats (low risk for developing diabetes), the activities of pancreatic cytosolic antioxidant enzymes, copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), and glutathione peroxidase (GPX) were determined. Alterations in CuZnSOD and CAT were noted in BBL males only as compared to BBNL males and BBL and BBNL females. CuZnSOD and CAT activities were significantly lower in BBL males. GPX showed a similar trend. The changes in pancreatic antioxidant enzymes precede overt hyperglycemia in male rats at risk for development of diabetes and may result in increased beta-cell vulnerability to oxygen-derived free radical destruction.

Animals↗
PubMed1995

Highly variable gastric emptying in patients with insulin dependent diabetes mellitus.

Some diabetic patients--particularly those with nausea and vomiting--frequently have evidence of delayed gastric emptying while other diabetic patients may in fact exhibit accelerated gastric emptying. Whether the presence or absence of symptoms of upper gastrointestinal dysfunction correlated with objective measures of gastric emptying in insulin dependent diabetic subjects was investigated. Twenty one insulin dependent diabetic patients underwent a solid phase gastric emptying scintiscan using in vivo labelled chicken liver. Thirteen patients had symptoms suggestive of gastrointestinal dysfunction (nausea, vomiting, early satiety, or constipation), while eight patients had no gastrointestinal symptoms. Eleven patients had orthostatic hypotension. All patients had been diabetic since childhood or adolescence. As a group, the diabetic patients showed a half time (T50) of gastric emptying (mean (SD) 150.0 min (163.7) that was not significantly different from that of 12 healthy control subjects (148.1 min (62.4)). Those diabetic patients without gastrointestinal symptoms and without orthostatic hypotension, however, showed a gastric emptying half time (70.1 min (41.6)) that was significantly faster than that of the control subjects. Conversely, those diabetic patients with nausea, vomiting, and early satiety (or early satiety alone) showed T50 values that were significantly greater than those of the diabetic patients without these symptoms. No correlation was found between the T50 value and the duration of diabetes, the fasting blood glucose at the time of study, or the respiratory variation in heart rate (E:I ratio). These observations indicate that highly variable rates of gastric emptying occur in insulin dependent diabetic patients, and that accelerated gastric emptying may occur in diabetic patients who have no symptoms of gastrointestinal dysfunction.

Adult↗
PubMed1995

Peroxidative stress in diabetic blood vessels. Reversal by pancreatic islet transplantation.

Diabetic complications are believed to arise, in part, through an increase in oxidative stress. We characterized antioxidant status in vascular tissue in untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) were measured. Sprague-Dawley rats with streptozotocin-induced diabetes were killed after 8 weeks of untreated hyperglycemia and compared with age-matched controls. Eight weeks of untreated diabetes resulted in a significant increase of tissue catalase in aorta, iliac artery, and femoral artery as compared with controls. No significant changes in either superoxide dismutase or glutathione peroxidase were observed in aorta, iliac artery, or femoral artery of diabetic animals. This increase in catalase in diabetic vascular tissue suggests increased oxidative stress due to chronic exposure to H2O2 in vivo. To assess the impact of islet transplantation on oxidative stress in vascular tissue, inbred Lewis strain rats were rendered diabetic with streptozotocin. After 8 weeks of untreated diabetes, rats received an intraportal islet isograft and were monitored for 4 subsequent weeks of euglycemia. Islet transplantation improved weight gain and normalized blood glucose and total glycosylated hemoglobin. While catalase was significantly increased in aorta and iliac artery at 8 and 12 weeks of diabetes, vascular catalase was restored to normal by islet transplantation. These data suggest that islet transplantation is an effective treatment strategy to minimize increased oxidative stress in diabetic vasculature.

Animals↗
PubMed1995

Syngeneic pancreatic islet transplantation reverses endothelial dysfunction in experimental diabetes.

Diabetes is known to cause impaired endothelium-dependent relaxation of blood vessels. The purpose of this study was to determine whether this endothelial dysfunction is a permanent defect or is reversible after acute arginine supplementation in vitro or by surgical intervention in vivo using syngeneic pancreatic islet transplantation. Lewis rats were injected with streptozotocin to induce diabetes and were studied either 8 or 12 weeks later. Another group received syngeneic islets via intraportal injection at 8 weeks of diabetes and were allowed to become euglycemic for 4 weeks before study. Thoracic aortic rings were tethered in isolated muscle baths, contracted with a submaximal concentration of norepinephrine, and challenged with either the endothelium-dependent vasodilator acetylcholine or the endothelium-independent vasodilator nitroglycerin. Relaxation to acetylcholine (but not nitroglycerin) was reduced in both 8- and 12-week diabetic rings compared with age-matched control rings. Preincubation of diabetic rings in vitro with L-arginine (but not D-arginine) restored relaxation to acetylcholine to normal to rings from 8-week but not 12-week diabetic animals. Plasma basic amino acids (arginine, lysine, and histidine) were reduced by diabetes, whereas other neutral or acidic amino acids were unchanged (phenylalanine, proline, and glutamate), reduced (serine, cysteine, threonine, tyrosine, tryptophan, and aspartate), or elevated (isoleucine, leucine, and valine). Islet transplantation restored to normal the changes in plasma amino acids. Elevation in blood glucose and total glycosylated hemoglobin in diabetic animals was normalized after islet transplantation. Furthermore, islet transplantation completely restored the defective endothelium-dependent relaxation to acetylcholine in diabetic rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Motor activity and transit in the autonomically denervated jejunum.

The role of extrinsic (autonomic) innervation in postprandial contractile activity of the small intestine is unknown. Using a canine model, we investigated the effects of complete extrinsic denervation on the parameters of fasting and postprandial jejunal contractions and their relationship to intestinal transit. Individual contractions were recorded using strain gauge transducers. Spatial and temporal parameters of contractions were analyzed by computer methods. Bolus injection of 14C-polyethylene glycol was used to calculate intestinal transit rates. Statistical comparisons of control and denervated animals were made by nonparametric tests. Extrinsic denervation did not abolish fasting or fed motor activity, but the following effects were observed: (1) the frequency of migrating motor complexes (MMCs) increased; (2) the onset of fed motor activity was delayed, and the duration of fed activity was shortened; (3) frequency, mean amplitude, and mean area of postprandial contractions were decreased; (4) fewer contractions propagated distally, and mean propagation distance was shortened; and (5) intestinal transit was slower for solids, but not for liquids. In the small intestine, extrinsic nerves modulate motor activity, which is under primary control of the intrinsic (enteric) nervous system.

Animals↗
PubMed1994

Hydroxyethyl starch deferoxamine, a novel iron chelator, delays diabetes in BB rats.

Hydroxyl radicals (.OH) may contribute to beta cell death. Because iron catalyzes .OH production, we examined whether administration of a novel, long-acting iron chelator, hydroxyethyl starch-deferoxamine (HES-DFO) could prevent diabetes in spontaneously diabetic biobreeding (BB) rats. In our colony, a peripheral lymphocyte count (PBLC) < 4200 mm3 has an 88% positive predictive value for onset of diabetes mellitus (DM). Rats with PBLC < 4200 mm3 were randomized at 6 weeks of age to receive 50 mg/kg of HES-DFO (a high molecular weight hydroxyethyl starch-conjugated derivative of deferoxamine) or equimolar hydroxyethyl starch (HES) alone given intraperitoneally three times weekly until DM or 120 days of age. Administration of HES significantly decreased the incidence of IDDM to 57% as compared with the incidence of 87% in the lymphopenic unmanipulated BB rats in the colony (p < 0.01). Administration of HES-DFO further significantly decreased the incidence of IDDM to 31% as compared with the lymphopenic unmanipulated rats (p < 0.01). When analyzed by sex, 3 of 17 (18%) HES-DFO-treated males developed DM, versus 10 of 17 (58%) of HES-treated males (p < 0.05, chi square); 8 of 19 (42%) of HES-DFO-treated females developed DM, versus 11 of 20 (55%) HES-treated females (p = NS). There were no differences between the groups in (1) mean time of onset of DM, (2) serum iron levels at study entry and completion, (3) weekly hematocrits, (4) total lymphocyte counts; and (5) weekly weight gains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Accelerated gastric emptying in diabetic rodents: effect of insulin treatment and pancreas transplantation.

Gastric emptying of a suspended solid, digestible meal was examined after 30 to 90 days of diabetes in two strains of streptozotocin-treated rodents and in genetically diabetic BB/Wor rats. After a 14-hour overnight fast the animals were gavage-fed 1.0 gm of rat food suspended in water and were killed 30 minutes later. Ligatures were placed around the lower esophageal sphincter and the pylorus and the stomachs were removed intact. The stomachs were evacuated and the gastric contents and gastric remnant were separately dried and weighted. Both the streptozotocin-treated and BB/Wor rats showed significantly accelerated (1.5- to 2.2-fold) rates of gastric emptying of the meal compared with respective nondiabetic control animals. Streptozotocin-treated diabetic animals that received daily insulin supplementation or those that had undergone pancreas transplantation shortly after induction of diabetes showed a similar reduction in blood glucose levels and normal rates of gastric emptying. Diabetes had a significant but variable effect on gastric mass and body weight. This response was dependent on the strain of animal examined, whether or not insulin supplementation was administered, or whether the animal underwent pancreas transplantation. These observations indicate that early diabetes in rodents has a prokinetic effect on gastric emptying of a suspended solid digestible meal. Restoration of euglycemia by insulin treatment or pancreas transplantation is associated with return of the gastric emptying rate to normal. These changes in gastric emptying appear to be independent of the effects of diabetes on gastric mass.

Animals↗