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Biomedical subjects

O E Akwari

Publications and source records attributed to O E Akwari.

At least 19 recordsLinked to original sources
PubMed1996

Effect of L-glutamine supplementation on impaired glucose regulation during intravenous lipid administration.

In contrast to L-glutamine, lipid emulsions are routinely administered to patients receiving nutritional support. The provision of fat during intravenous feeding is essential, but the potentially toxic byproducts of fatty acid oxidation may have adverse metabolic consequences. In the present study, we have examined the effect of L-glutamine, an inhibitor of fatty acid oxidation, on the development of defective blood glucose regulation caused by a 48-hour infusion of 10% intralipid in rats. Male Sprague-Dawley rats (200-290 g) were anesthetized with sodium pentobarbital, the right femoral vein cannulated, and baseline blood samples were taken. Each rat was placed in a metabolic cage with access to water, in the presence or absence of rodent chow. Two hours after waking, the rats were infused with 10% intralipid with either saline (control), 2% L-glutamine, or 2% L-alanine. After 48 hours, all animals were sacrificed and blood samples were again obtained. The mean +/- SEM plasma glucose levels before and after lipid infusion at the rate of 1 mL/hr in control rats fed ad libitum, were 125 +/- 13 and 170 +/- 5 mg/dL (p < 0.01, n = 7). Similarly, plasma free fatty acids (FFA) in these animals rose from 0.74 +/- 0.11 to 1.34 +/- 0.32 mmol/L (p < 0.05). Plasma insulin levels also increased from 337 +/- 44 to 1278 +/- 88 pg/mL (p < 0.01). Reduction of intralipid dose infusion did not prevent insulin resistance characterized by hyperglycemia and hyperinsulinemia. However, addition of L-glutamine to the high-dose lipid infusion with chow feeding prevented changes in plasma glucose, insulin levels, and FFA but not triglyceride levels. Also, glutamine but not alanine supplementation in intralipid infused rats without chow feeding prevented changes in plasma glucose, insulin, and malondialdehyde levels. In conclusion, these data show that glutamine supplementation during intravenous lipid administration in rats prevents the development of impaired glucose regulation associated with hyperlipidemia.

Alanine↗
PubMed1995

Glutathione-mediated preservation and enhancement of isolated perifused islet function.

It has been shown that myocardial tissue function may be better preserved if antioxidants are incorporated into the reoxygenation medium at the end of the ischemic period following isolation of the organ. Although isolated pancreatic islets are prone to ischemic-reperfusion injury, it is not clear if antioxidants have a role in the preservation of their function. The purpose of the present study, therefore, was to examine the effect of the addition of glutathione (GSH) to a physiologic incubation medium on pancreatic islet response to glucose stimulation. Islets isolated by microdissection were preperifused at the rate of 1 ml/min for 1 hr at 37 degrees C, with Krebs-Ringer bicarbonate (KRB) buffer containing 1% albumin, 5.5 mM (basal) glucose without (control) or with 10 mM glutamine or 10 mN GSH and maintained at pH 7.4 by continuous gassing with 95/5% O2/CO2. After preperifusion, basal effluent samples were taken on ice for 20 min. The perifusion was then continued for 20 min with the KRB containing 27.7 mM glucose alone, followed by another 20 min of basal glucose washout. Solutions were changed using a stopcock and all effluent perifusate samples obtained were stored frozen at -20 degrees C until radioimmunoassay for insulin. Total insulin output in the control group increased from a basal 11.45 +/- 3.18 to 29.23 +/- 7.08 ng/6 islets/20 min (P < 0.001, n = 5) when the glucose concentration was raised to 27.7 mM. During a 20-min washout, insulin secretion was still significantly raised and did not return to the prestimulation basal rate. In the glutamine-treated islets, insulin output increased from 7.23 +/- 0.94 to 16.83 +/- 2.25 ng/6 islets/20 min (P < 0.001, n = 5) with 27.7 mM glucose stimulation and the significantly raised washout basal rate of secretion did not return to the prestimulation level. GSH treatment not only caused an enhanced 27.7 mM glucose stimulation (8.46 +/- 1.99 to 38.72 +/- 11.51 ng/6 islets/20 min, P < 0.001, n = 6) of insulin output but also completely restored the basal rate of insulin secretion to the prestimulation level within the 20-min washout perifusion. In conclusion, these data show that incubation of isolated islets with GSH enhanced their secretory response to glucose stimulation and preserved their functional integrity.

Animals↗
PubMed1995

Defective glucose-stimulated insulin release from perifused islets of C57BL/6J mice.

Previous work has shown that the C57BL/6J (BL/6) mouse strain develops type 2 diabetes after being fed a high-fat, high-simple carbohydrate (HFHSC) diet. In contrast, the AJ mouse strain does not. The aim of the present study was to determine if differences in the insulin secretory characteristics of isolated perifused islets of these animals could help explain why the BL/6 mouse develops diet-induced diabetes. Insulin secretion was assessed as mean integrated area under the curve during 20 min of stimulation with 27.7 mM glucose or 5 mM lauric acid. We found that both glucose- and laurate-stimulated insulin secretions were significantly less in euglycemic BL/6 mice than in the euglycemic AJ mice. The defect in insulin response to glucose, but not laurate, in islets from the BL/6 mouse was exacerbated when the animals were fed the HFHSC diet. These data suggest that the BL/6 mouse has a defective insulin response to glucose, which is exacerbated by a diabetogenic diet.

Animals↗
PubMed1994

Effect of fatty acids on insulin release: role of chain length and degree of unsaturation.

The purpose of the present study was to examine the role played by structural differences among fatty acids in their effect on insulin secretion by isolated perifused murine islets. Insulin secretion measured by radioimmunoassay was assessed either as total insulin output (ng.6 islets-1.20 min-1) or as percent of basal insulin secretion. Raising the glucose concentration from a basal 5.5 to 27.7 mM caused an increase of insulin output from 6.69 +/- 1.59 to 19.92 +/- 4.99 ng.6 islets-1.20 min-1 (P < 0.05) in control (untreated) islets. However, after 20-min exposure of islets to 5 mM 16:0 or 18:2, the effect of 27.7 mM glucose was enhanced or diminished, respectively. Basal insulin output (100% basal) changed to 44 +/- 10% basal (P < 0.005) with the addition of 5 mM 4:0 but was not altered when 4:0 was replaced by 6:0. Insulin output increased modestly with 5 mM 8:0 but significantly (P < 0.05) with 10:0 until a maximal of 280 +/- 24% basal with 12:0 (P < 0.01), then fell to 110 +/- 18 and 93 +/- 15% basal (P < 0.05) with 14:0 and 16:0, respectively. The addition of 5 mM 18:0 inhibited insulin secretion to 30 +/- 10% of basal (P < 0.003), and this effect was not caused by fatty acid interference with insulin assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

An experimental model of neonatal testicular torsion: evidence against an exclusively extravaginal etiology.

The present study was designed to determine whether extravaginal torsion of the spermatic cord (EVT) can be distinguished from intravaginal torsion (IVT) on the basis of gross and histologic examination of the testis. It is traditionally believed that EVT, postulated to occur only in neonates, can be grossly distinguished from IVT, which occurs in older patients, on the basis of adherence between testis and tunica vaginalis. Such adherence is felt to be present in EVT but not IVT. This concept that the two types of torsion can be distinguished in the operating room has important clinical ramifications. In cases of EVT, contralateral orchidopexy theoretically need not be performed, since adhesions develop between tunica vaginalis and dartos by a few weeks of age. This is in contrast to IVT, in which contralateral orchidopexy is necessary due to the bilateral nature of the bell clapper deformity. Using a rat model, we first demonstrated that IVT could produce adherence of the tunica vaginalis to testis. Then, eight rats were operated on, producing right IVT and left EVT. Animals were then sacrificed at intervals of up to one month. Gross and histologic examination showed involvement of the tunica vaginalis in an ischemic and inflammatory response in a majority of testes, regardless of the type of torsion. Attempts to distinguish EVT from IVT on the basis of grossly evident adhesions between tunica vaginalis and testis are of questionable validity. Early contralateral orchidopexy is therefore recommended in all cases of neonatal torsion.

Animals↗
PubMed1992

Insulinotropic potency of lauric acid: a metabolic rationale for medium chain fatty acids (MCF) in TPN formulation.

The need for a better lipid system to satisfy the fuel requirements of patients while avoiding the adverse effects of current systems has led to suggestions that medium chain fatty acids (MCFs) be incorporated into TPN-lipid emulsions. Since clinical situations requiring TPN are associated with metabolic processes mediated by insulin, in the present study we have therefore examined the effects of a variety of medium chain fatty acids on insulin release. Using an isolated perifused mouse islet model, various doses of medium chain fatty acids and the essential fatty acid, linoleic acid, were tested and compared. The possibility of an additive effect of an insulinotropic MCF and linoleate when both are provided together was also examined. Effluent perifusate samples collected on ice during these experiments were assayed for insulin by radioimmunoassay. It was found that the ability of 5 mM of a given MCF to stimulate insulin secretion was dependent upon its chain length. Thus, while adipic acid (C6) had no effect, Caprylic acid (C8) had a minimal effect that was not statistically significant, but capric acid (C10) and lauric acid had very potent effects that were of the same magnitude to the effect of linoleate on insulin secretion. When insulin output was assessed as the mean integrated area under the curve during a 20-min perifusion, 5 mM lauric acid enhanced insulin secretion from a basal 7351 +/- 666 pg to 15,756 +/- 1680 pg (P less than 0.01, n = 5). In the same experiments, 5 mM linoleic acid stimulated insulin release to 11,260 +/- 867 pg (P less than 0.05). When C12 and linoleate were added together, each at a submaximally effective concentration of 2.5 mM, insulin output was 12,712 +/- 1011 pg (P less than 0.05, n = 5), which was not statistically different from the values obtained when the islets were perifused with 5 mM of each fatty acid alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Characterization of the insulinotropic potency of polyunsaturated fatty acids.

In this study we have assessed the individual abilities of the essential fatty acids, linoleic and linolenic acids, to release insulin and compared their insulinotropic potencies with those of the more established nutrient insulin secretagogues, glucose and arginine. In each experiment, a total of six islets microdissected from three mice were preperifused at the rate of 1 ml/min with Krebs-Ringer bicarbonate buffer, pH 7.4, containing 2% bovine albumin and 5.5 mM glucose (basal) with a continuous supply of 95% O2-5% CO2 at 37 C for 1 h. After collecting basal samples, the effects of 27.7 mM glucose, 20 mM arginine, 10 mM linoleic acid (18:2, omega 6), and 5 mM linolenic acid (18:3, omega 3) were tested using a sandwich protocol that entails 20-min alternating periods of stimulation with a secretagogue and a washout with basal perifusion. These nutrient concentrations were selected from initial experiments performed to characterize their dose-response effects on insulin secretion. Effluent samples were collected throughout each experiment for measurement of insulin by RIA. In one series of experiments, islets were challenged three times with 27.7 mM glucose, 10 mM linoleic acid, and 5 mM linolenic acid. In another set of experiments, islets were perifused with 20 mM arginine, 27.7 mM glucose, and 10 mM linoleic acid. All of these nutrients stimulated insulin release in a dose-dependent manner. In comparing the insulinotropic potencies of these secretagogues, we assessed insulin secretion as the integrated areas under the curve during 20 min of perifusion with a given nutrient. Thus, the mean integrated area under the curve per 20 min above basal in the presence of 27.7 mM glucose was 6,516 +/- 1,435 pg, which was not significantly different from the value of 4,772 +/- 866 pg obtained during arginine perifusion. However, the area under the curve during 20 min above basal obtained in the presence of linoleate and linolenic acid (8,712 +/- 1,949 and 10,506 +/- 1,490 pg, respectively) were significantly different (P less than 0.05) from those calculated during arginine and glucose perifusions. There was no statistically significant difference between the effects of these two fatty acids at the concentrations tested. In conclusion, our data suggest that linoleic acid and linolenic acid may be, at least in this murine islet preparation, as effective in stimulating insulin release as glucose and arginine, hitherto used to assess the abilities of nutrients to stimulate insulin secretion. However, it remains to be seen whether the efficacy of these polyunsaturated fatty acids in insulin release by murine islets will be obtained in experiments performed on human islets.

Animals↗
PubMed1991

Pancreatic hormone response to neuropeptide Y (NPY) perifusion in vitro.

Available data on the effect of neuropeptide Y (NPY) on insulin release are conflicting and little data exist regarding the effect of NPY on glucagon secretion. The purpose of the present study, therefore, was to characterize the direct effect of NPY on the release of these pancreatic hormones and to examine the role of glucose on these interactions. Using a perifused mouse islet system, we found that NPY suppressed both basal and glucose-stimulated insulin secretion. Thus, basal insulin release assessed as mean integrated area under the curve/20 min (AUC/20 min) decreased from 1446 +/- 143 pg to 651 +/- 112 pg (P less than 0.05) with the addition of 2 x 10(-8) M NPY and the AUC/20 min for glucose stimulated insulin output decreased from 1973 +/- 248 pg to 1426 +/- 199 pg (P less than 0.05). In both cases, this inhibitory effect was followed after removing NPY by a stimulation of insulin secretion which was typical of a 'rebound off-response'. In contrast, NPY exerted a stimulatory effect on basal glucagon release and significantly reversed the suppressive effect of high glucose on glucagon output. The basal glucagon AUC/20 min increased from 212 +/- 103 pg to 579 +/- 316 pg (P less than 0.05), while glucagon secretion in the presence of 27.7 mM glucose increased from 75 +/- 26 pg to 255 +/- 28 pg (P less than 0.01). In conclusion, we have shown that the direct effect of NPY on the endocrine pancreas is to suppress insulin but stimulate glucagon secretion. These data are compatible with a role for NPY in the regulation of pancreatic hormone output.

Animals↗
PubMed1990

Enhancement of endocrine pancreatic secretions by essential fatty acids.

Recent studies have suggested the beneficial effects of essential fatty acids in postoperative patients receiving total parenteral nutrition. While there is abundant information on the role of glucose and amino acids on insulin release, the effect of essential fatty acids on endocrine pancreatic secretions is not clear. Since linoleic and linolenic acids are constituents of TPN solutions as well as dietary fat, our aim was to examine their effect on the endocrine pancreatic function, using isolated islets. In each experiment, six islets microdissected from three mice were preperifused at the rate of 1 ml/min with Krebs-Ringer bicarbonate (KRB) buffer pH 7.4 containing 2% bovine albumin and 5.5 mM glucose (basal) with continuous supply of 95%/5%, O2/CO2 for 1 hr, after which basal samples were collected on ice every minute. The perifusion was continued for 20 min after the addition of a mixture of 10 mM linoleic acid and 5 mM linolenic acid to the KRB. During each perifusion phase, effluent samples were also collected for insulin and glucagon assay. The mean integrated area under the curve/20 min showed an increase in both insulin and glucagon secretions with the addition of fatty acids. Hence insulin increased from a basal 3154.8 +/- 953.7 to 8393.0 +/- 2073.1 pg (P less than 0.025, n = 6) and glucagon increased from 193.7 +/- 46.9 to 1566.1 +/- 411.2 pg (P less than 0.0025, n = 5). The fatty-acid-induced insulin but not glucagon secretion was blocked by the addition of 2 mM palmoxirate an inhibitor of fatty acid oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hepatobiliary cystadenoma with mesenchymal stroma.

In a detailed review of cystic hepatobiliary neoplasms, we identified a subset of 50 cases in which tumors were characterized by the presence of a mesenchymal cell layer interposed between an inner epithelial lining and an outer connective tissue layer. We have recently seen three such patients, making a total of 53 patients reported in the English literature. All of the patients were female, 44 of whom, with an average age of 41 years, had benign tumors. The average age of the remaining nine patients was 57 years and these patients had malignant tumors. In seven patients, the malignancy arose from the epithelial layer, but in two patients sarcomatous changes were identified in the mesenchymal tissues. The older age of the patients with malignant tumors with adequate serial biopsies in two cases supported the thesis that malignant transformation may occur in the benign tumors. Moreover the location of the tumor in one of our patients in whom the resected tumor was associated with anomalous right hepatic ducts and portal veins supported the theory that these tumors develop embryologically from nests of primitive hepatobiliary endodermal and mesodermal cells. Although surgical treatment was performed in all patients, 25% of the patients with benign hepatobiliary cystadenoma with mesenchymal stroma (CMS), and 33% of the patients with malignant CMS had tumor recurrence after primary resection. Ninety per cent of these patients had an incomplete resection at the time of their initial operations. Forty-four per cent of the patients with malignant CMS died after a mean follow-up of 17 months. We conclude that CMS (Edmonson's tumor) occurs uniquely in young female patients, develops from nests of primitive embryonal cells, has the potential for malignant transformation, and should be completely resected at primary operation to avoid recurrence.

Adult↗
PubMed1987

Gastric emptying, glucose tolerance, and insulin response after duodenojejunostomy.

We investigated the impact of direct jejunal delivery of various meals on gastric emptying, glucose tolerance, and insulin response in a chronic dog model following duodenojejunostomy. Ten beagle dogs underwent duodenal transection 2 cm distal to the pylorus and end-to-side duodenojejunostomy 20 cm distal to the ligament of Treitz. Three months after operation each dog underwent gastric emptying studies using radiolabeled normal saline, 20% glucose solution, and standardized mixed solid meal. Glucose tolerance tests with plasma insulin determinations were obtained using the glucose meal. After duodenojejunostomy both the rapid exponential pattern of emptying of normal saline and the slower linear pattern of glucose emptying seen in intact dogs were preserved. The linear gastric emptying of the solid meal which was slower than gastric emptying of either of the liquid meals was also preserved. Although integrated plasma glucose levels over 2 hr were 484.8 +/- 40.4 and 456.6 +/- 30.4 mg X hr/dl in intact and duodenojejunostomy dogs, respectively (P greater than 0.05), the initial rate of rise of plasma glucose was significantly delayed in the duodenojejunostomy dogs. But integrated plasma insulin levels over 2 hr differed significantly (P less than 0.05) between the intact (71.6 +/- 9.2 microU X hr/nl) and duodenojejunostomy (48.3 +/- 6.2 microU X hr/nl) dogs. We conclude that duodenojejunostomy (jejunal delivery) preserved the patterns of gastric emptying of saline, glucose, and mixed solid meals; retarded initial plasma glucose response to the glucose meal; and blunted plasma insulin response to the glucose load.

Animals↗
PubMed1987

Splenectomy for primary and recurrent immune thrombocytopenic purpura (ITP). Current criteria for patient selection and results.

Of 565 patients with thrombocytopenia admitted to Duke University Hospital between 1975 and 1985, 100 had splenectomy. Ninety-eight patients had failed chronic immunosuppressive therapy and three patients had acute intracranial bleeding or total absence of platelets in the peripheral blood smear, and had urgent splenectomy. At primary splenectomy, accessory spleens were identified and resected in 18% of patients. There was no operative mortality. Fifty-eight patients had an excellent response to splenectomy and their steroids were tapered off within 3 weeks. Thirteen patients had a poor response to primary splenectomy of whom eight remitted spontaneously and five required accessory splenectomy resulting in complete remission in three patients. Twenty-nine patients were considered nonresponders, 25 of whom had radionuclide scanning for accessory spleens. Seven of these patients had accessory spleens identified but only four consented to accessory splenectomy. In three of the four patients, a complete remission was achieved. Neither platelet antibody titers nor measurements of platelet survival or turnover predicted platelet response to splenectomy. However, immune thrombocytopenic purpura (ITP) in older patients was significantly less likely to respond to splenectomy. These data support continuing use of splenectomy in selected patients with ITP and an aggressive search for accessory spleens in patients who relapse since they are easily localized at operation by hand-held isotope detector probe.

Adolescent↗
PubMed1987

Painful palmar and plantar erythema associated with hepatic artery infusion of 5-fluoro-2'deoxyuridine.

Painful palmar and plantar erythema is an uncommon systemic complication of chemotherapy and has been reported in association with methotrexate, cystosine arabinoside, doxorubicin, and 5-fluorouracil. The authors report a case in which the syndrome was precipitated by hepatic artery infusion of 5-FUdR. The previous recommendation that treatment of patients developing painful palmar-plantar erythema from other drugs may be successfully resumed using intrahepatic arterial infusion of FUdR must be reconsidered in light of the present report.

Erythema↗
PubMed1986

Pylorus-preserving pancreatoduodenectomy. A clinical and physiologic appraisal.

Since 1978, 252 patients from different centers in the world have undergone pylorus-preserving pancreatoduodenectomy. Fifty-five per cent of the patients had malignant tumors in the region of the head of the pancreas. The overall operative mortality rate was 2.8%. Anastomotic leakage and fistulae occurred in 19% of the patients. Pancreatic, biliary, and enteric fistulae represented 11%, 4%, and 4%, respectively. Peptic ulcers were subsequently diagnosed in seven patients (3%), two of whom required vagotomy and antrectomy. Delayed recovery of gastric function was the most common complication of this operation, with an overall incidence of 30%. Although the cause of this gastric dysfunction is unknown, its transient nature in most patients makes expectant therapy with gastric tube drainage the best remedy when the problem is encountered. Pylorus-preserving pancreatoduodenectomy decreased the incidence of postgastric surgery syndromes that are commonly associated with the standard Whipple operation. The existing data support the continued use of the operation and the need for future laboratory and clinical investigation of its physiologic impact.

Adenocarcinoma↗
PubMed1985

A reversible enteropathy complicating continuous hepatic artery infusion chemotherapy with 5-fluoro-2-deoxyuridine.

This article describes two patients with hepatic metastases from colorectal cancer in whom a reversible enteropathy developed during the administration of hepatic artery infusion chemotherapy with 5-fluoro-2-deoxyuridine (5-FUdR) via an Infusaid Series 400 pump (Infusaid Corp., Sharon, MA). Both patients had severe diarrhea and signs that suggested small bowel obstruction. Barium studies revealed a distinctive radiologic appearance of severe narrowing of the ileum associated with complete loss of normal mucosal patterns. Results of an extensive evaluation for an infectious or toxin-related enterocolitis were negative. Perfusion studies confirmed the appropriate position of the catheters and revealed no extrahepatic perfusion. Systemic shunting of the 5-FUdR through the liver or tumor bed is postulated as the primary event, with the small bowel manifesting the major toxicity.

Aged↗
PubMed1983

Neural control of gastrointestinal motility: evidence for noncholinergic regulatory influences.

Although it is well known that neural control of gastric motility occurs via sympathetic, parasympathetic, noncholinergic, and nonadrenergic fibers contained in the vagus nerve, the central sites of origin of these influences are largely unknown. Recent experiments in our laboratory indicate that noncholinergic neural pathways originating in the posterior hypothalamus can markedly influence gastric motility. At least 2 weeks prior to the experiment, mongrel dogs were surgically prepared with bipolar recording electrodes fixed to the serosal surface of the stomach. This prevented violation of the abdominal cavity on the day of testing. Experiments were performed with the animals under alpha-chloralose anesthesia (100 mg kg-1) in temperature-controlled settings. Under stereotactic guidance, bipolar stimulation of the posterior periventricular hypothalamus produced profound reproducible excitatory or inhibitory effects on gastric myoelectric and motor activity. Changes in the frequency and amplitude of pacesetter potentials (PPs) and in the incidence of action potentials associated with them were observed. Stimulation of various loci in 14 dogs resulted in a 71 +/- 7.5% increase in the incidence of action potentials associated with gastric PPs in "excitatory" areas (n = 7) and a 69.1 +/- 4% decrease in this ratio in "inhibitory" areas (n = 19). In general, more lateral stimulation produced greater inhibitory effects. Responses were frequency dependent, with a threshold greater than 25 Hz in most cases. Excitatory gastric responses to hypothalamic stimulation occurred despite full systemic atropinization (0.1 mg kg-1). The physiologic significance of these noncholinergic excitatory pathways influencing distal gastric motility and the neurotransmitters they employ are as yet unknown.

Action Potentials↗