Short-Term Effects of Duodenocecostomy on Body Weight, Glucose Absorption, Serum Components, and Intestinal Histopathology in Four Normal Horses

The objective of this study was to evaluate duodenocecostomy in horses performed through a ventral midline laparotomy and report its influence oil body weight, glucose absorption, serum components, and characteristics of jejunum, cecum, and large colon histology. Four horses were submitted to the duodenocecostomy technique through a ventral midline laparotomy with animals in dorsal recumbency under inhalation anesthesia, followed by abdominal exploration. A side-to-side anastomosis was performed between the duodenojejunal flexure and the base of the cecum with two simple continuous suture lines of the serosal and muscular layers. The size of the opening created was approximately 2 cm in diameter. The mucosa layer was not Sutured. After 30 days, animals were submitted to a second laparotomy to check the patency of the duodenocaecal fistula. During both laparotomy procedures, excisional biopsies of different segments of the gastrointestinal tract were performed. Information on physical examination findings, results of hematologic and histopathologic evaluations, and oral glucose absorption test were recorded. The horses did not have significant weight loss from baseline, and absorption curve of glucose did not significantly vary from baseline. Only triglycerides had significant alterations. Histologic evaluation of jejunum, cecum, and large colon did not show alterations of intestinal structure and morphology. We concluded that the proposed technique, principally in relation to the fistula size and not suturing the mucosa layer, allowed partial or total Occlusion of the fistulae without the necessity of a second surgery and avoided the permanent bypass of ingesta and weight loss.

Comparison of the effects of tramadol, codeine, and ketoprofen alone or in combination on postoperative pain and on concentrations of blood glucose, serum cortisol, and serum interleukin-6 in dogs undergoing maxillectomy or mandibulectomy

Objective-To compare analgesic effects of tramadol, codeine, and ketoprofen administered alone and in combination and their effects on concentrations of blood glucose, serum cortisol, and serum interleukin (IL)-6 in dogs undergoing maxillectomy or mandibulectomy. Animals-42 dogs with oral neoplasms. Procedures-30 minutes before the end of surgery, dogs received SC injections of tramadol (2 mg/kg), codeine (2 mg/kg), ketoprofen (2 mg/kg), tramadol + ketoprofen, or codeine + ketoprofen (at the aforementioned dosages). Physiologic variables, analgesia, and sedation were measured before (baseline) and 1, 2, 3, 4, 5, and 24 hours after surgery. Blood glucose, serum cortisol, and serum IL-6 concentrations were measured 1, 3, 5, and 24 hours after administration of analgesics. Results-All treatments provided adequate postoperative analgesia. Significant increases in mean +/- SD blood glucose concentrations were detected in dogs receiving tramadol (96 +/- 14 mg/dL), codeine (120 +/- 66 mg/dL and 96 +/- 21 mg/dL), ketoprofen (105 +/- 22 mg/dL), and codeine + ketoprofen (104 +/- 16 mg/dL) at 5, 1 and 3, 5, and 3 hours after analgesic administration, respectively, compared with preoperative (baseline) values. There were no significant changes in physiologic variables, serum IL-6 concentrations, or serum cortisol concentrations. Dogs administered codeine + ketoprofen had light but significant sedation at 4, 5, and 24 hours. Conclusions and Clinical Relevance-Opioids alone or in combination with an NSAID promoted analgesia without adverse effects during the 24-hour postoperative period in dogs undergoing maxillectomy or mandibulectomy for removal of oral neoplasms. (Am J Vet Res 2010;71:1019-1026)

Effects of six carbohydrate sources on dog diet digestibility and post-prandial glucose and insulin response

The effects of six extruded diets with different starch sources (cassava flour, brewer`s rice, corn, sorghum, peas or lentils) on dog total tract apparent digestibility and glycemic and insulinemic response were investigated. The experiment was carried out on thirty-six dogs with six dogs per diet in a completely randomized design. The diets containing brewer`s rice and cassava flour presented the greatest digestibility of dry matter, organic matter and gross energy (p < 0.05), followed by corn and sorghum; pea and lentil diets had the lowest. Starch digestibility was greater than 98% in all diets and was greater for brewer`s rice and cassava flour than for lentils and peas diets (p < 0.05). Dogs` immediate post-prandial glucose and insulin responses (AUC <= 30 min) were greater for brewer`s rice, corn, and cassava flour diets (p < 0.05), and later meal responses (AUC >= 30 min) were greater for sorghum, lentil and pea diets (p < 0.05). Variations in diet digestibility and post-prandial response can be explained by differences in chemical composition of each starch source including fibre content and starch granule structure. The nutritional particularities of each starch ingredient can be explored through diet formulations designed to modulate glycemic response. However, more studies are required to support these.

Effects of six carbohydrate sources on diet digestibility and postprandial glucose and insulin responses in cats

The effects of diets with different starch sources on the total tract apparent digestibility and glucose and insulin responses in cats were investigated. Six experimental diets consisting of 35% starch were extruded, each containing one of the following ingredients: cassava flour, brewers rice, corn, sorghum, peas, or lentils. The experiment was carried out on 36 cats with 6 replications per diet in a completely randomized block design. The brewers rice diet offered greater DM, OM, and GE digestibility than the sorghum, corn, lentil, and pea diets (P < 0.05). For starch digestibility, the brewers rice diet had greater values (98.6%) than the sorghum (93.9%), lentil (95.2%), and pea (96.3%) diets (P < 0.05); however, starch digestibility was > 93% for all the diets, proving that despite the low carbohydrate content of carnivorous diets, cats can efficiently digest this nutrient when it is properly processed into kibble. Mean and maximum glucose concentration and area under the glucose curve were greater for the corn-based diet than the cassava flour, sorghum, lentil, and pea diets (P < 0.05). The corn-based diets led to greater values for the mean glucose incremental concentration (10.2 mg/dL), maximum glucose incremental concentration (24.8 mg/dL), and area under the incremental glucose curve (185.5 mg.dL(-1).h(-1)) than the lentil diet (2.9 mg/dL, 3.1 mg/dL, and -40.4 mg.dL(-1).h(-1), respectively; P < 0.05). When compared with baseline values, only the corn diet stimulated an increase in the glucose response, occurring at 4 and 10 h postmeal (P < 0.05). The corn-based diet resulted in greater values for maximum incremental insulin concentration and area under the incremental insulin curve than the lentil-based diet (P < 0.05). However, plasma insulin concentrations rose in relation to the basal values for cats fed corn, sorghum, pea, and brewers rice diets (P < 0.05). Variations in diet digestibility and postprandial response can be explained by differences in the chemical composition of the starch source, including fiber content and granule structure, and also differences in the chemical compositions of the diets. The data suggest that starch has less of an effect on the cat postprandial glucose and insulin responses than on those of dogs and humans. This can be explained by the metabolic peculiarities of felines, which may slow and prolong starch digestion and absorption, leading to the delayed, less pronounced effects on their blood responses.

Glucose transporter protein 1 expression in mucoepidermoid carcinoma of salivary gland: correlation with grade of malignancy

P>Mucoepidermoid carcinoma (MEC), the most common primary salivary malignancy, shows great variability in clinical behaviour, thus demanding investigation to identify of prognostic markers. Since Warburg`s studies, unrestricted cell growth during tumorigenesis has been linked to altered metabolism, implying hypoxic stimulation of glycolysis and diminished contribution of mitochondrial oxidative phosphorylation to cellular ATP supply. Hypothesizing that the study of MEC metabolic status could lead to the discovery of prognostic markers, we investigated by immunohistochemistry the expression of glucose transporter 1 (Glut-1), mitochondrial antigen and peroxiredoxin I (Prx I) in samples of MEC from different histological grades. Our results showed that mitochondrial antigen and Prx I were expressed in the majority of the MEC cases independent of the histological grade. In contrast Glut-1 expression increased significantly as the tumours became more aggressive. These results suggested that oxidative phosphorylation may contribute to ATP supply in all stages of MEC progression, and that the relative contribution of glycolysis over mitochondria for cellular ATP supply increases during MEC progression, favouring growth under low oxygen concentration. In addition, the observed high Prx I protein levels could provide protection to tumour cells against reactive oxygen species generated as a consequence of mitochondrial function and hypoxia-reoxygenation cycling. Altogether our findings suggest that upregulation of Glut-1 and Prx I constitute successful adaptive strategies of MEC cells conferring a growth advantage over normal salivary gland cells in the unstable oxygenation tumour environment.

Effect of Fluoridated Water on Plasma Insulin Levels and Glucose Homeostasis in Rats with Renal Deficiency

Glucose intolerance in fluorosis areas and when fluoride is administered for the treatment of osteoporosis has been reported. Controlled fluoridation of drinking water is regarded as a safe and effective measure to control dental caries. However, the effect on glucose homeostasis was not studied so far. The aim of this study was to evaluate the effect of the intake of fluoridated water supply on glucose metabolism in rats with normal and deficient renal function. Male Sprague-Dawley rats were divided into eight groups of four rats. Renal insufficiency was induced in four groups (NX) which received drinking water containing 0, 1, 5, and 15 ppm F (NaF) for 60 days. Four groups with simulated surgery acted as controls. There were no differences in plasma glucose concentration after a glucose tolerance test between controls and NX rats and among rats with different intakes of fluoride. However, plasma insulin level increased as a function of fluoride concentration in drinking water, both in controls and in NX rats. It is concluded that the consumption of fluoridated water from water supply did not affect plasma glucose levels even in cases of animals with renal disease. However, a resistance to insulin action was demonstrated.

Arachidonic acid stimulates glucose uptake in 3T3-L1 adipocytes by increasing GLUT1 and GLUT4 levels at the plasma membrane: Evidence for involvement of lipoxygenase metabolites and peroxisome proliferator-activated receptor

Exposure of insulin-sensitive tissues to free fatty acids can impair glucose disposal through inhibition of carbohydrate oxidation and glucose transport. However, certain fatty acids and their derivatives can also act as endogenous ligands for peroxisome proliferator-activated receptor gamma (PPARgamma ), a nuclear receptor that positively modulates insulin sensitivity. To clarify the effects of externally delivered fatty acids on glucose uptake in an insulin-responsive cell type, we systematically examined the effects of a range of fatty acids on glucose uptake in 3T3-L1 adipocytes. Of the fatty acids examined, arachidonic acid (AA) had the greatest positive effects, significantly increasing basal and insulin-stimulated glucose uptake by 1.8- and 2-fold, respectively, with effects being maximal at 4 h at which time membrane phospholipid content of AA was markedly increased. The effects of AA were sensitive to the inhibition of protein synthesis but were unrelated to changes in membrane fluidity. AA had no effect on total cellular levels of glucose transporters, but significantly increased levels of GLUT1 and GLUT4 at the plasma membrane. While the effects of AA were insensitive to cyclooxygenase inhibition, the lipoxygenase inhibitor, nordihydroguaiaretic acid, substantially blocked the AA effect on basal glucose uptake. Furthermore, adenoviral expression of a dominant-negative PPARgamma mutant attenuated the AA potentiation of basal glucose uptake. Thus, AA potentiates basal and insulin-stimulated glucose uptake in 3T3-L1 adipocytes by a cyclooxygenase-independent mechanism that increases the levels of both GLUT1 and GLUT4 at the plasma membrane. These effects are at least partly dependent on de novo protein synthesis, an intact lipoxygenase pathway and the activation of PPARgamma with these pathways having a greater role in the absence than in the presence of insulin.

Glucose induced IEG expression in the thiamin-deficient rat brain

Glucose loading of rats made thiamin deficient by dietary deprivation of thiamin and the administration of pyrithiamin (40 mug/100 g, i.p.) precipitates an acute neuropathy, a model of Wernicke's encephalopathy in man (Zimitat and Nixon, Metab. Brain Dis. 1999;14:1-20). Immunohistochemical detection of Fos proteins was used as a marker to identify neuronal populations in the thiamin-deficient rat brain affected by glucose loading. As thiamin deficiency progressed, the extent and intensity of Fos-Like immunoreactivity (FLI) in brain structures typically affected by thiamin deficiency (the thalamus, mammillary bodies, inferior colliculus, vestibular nucleus and inferior olives) were markedly increased when compared to thiamin-replete controls. Glucose loading for 1-3 days further increased the intensity of FLI in these same regions, consistent with a dependence of Fos expression on carbohydrate metabolism as well as on thiamin deficiency. The timed acute changes that follow a bolus glucose load administered to thiamin-deficient animals may provide a sequential account of events in the pathogenesis of brain damage in this model of Wernicke's encephalopathy. (C) 2001 Elsevier Science B.V. All rights reserved.

Analysis of Piezoelectric sensor to detect flexural waves

The electromechanical transfer characteristics of adhesively bonded piezoelectric sensors are investigated. By the use of dynamic piezoelectricity theory, Mindlin plate theory for flexural wave propagation, and a multiple integral transform method, the frequency-response functions of piezoelectric sensors with and without backing materials are developed and the pressure-voltage transduction functions of the sensors calculated. The corresponding simulation results show that the sensitivity of the sensors is not only dependent on the sensors' inherent features, such as piezoelectric properties and geometry, but also on local characteristics of the tested structures and the admittance and impedance of the attached electrical circuit. It is also demonstrated that the simplified rigid mass sensor model can be used to analyze successfully the sensitivity of the sensor at low frequencies, but that the dynamic piezoelectric continuum model has to be used for higher frequencies, especially around the resonance frequency of the coupled sensor-structure vibration system.

Lipophilic methotrexate conjugates with glucose-lipoamino acid moieties: Synthesis and in vitro antitumor activity

To obtain methotrexate (MTX) derivatives with a balanced hydrolipophilic character, we synthesized a series of conjugates in which the drug was linked to lipoamino acid (LAA)-glucose residues (LAAG-MTX). These conjugates displayed increased solubility in polar media compared with the corresponding LAA-MTX conjugates previously described. In vitro biological testing of LAAG-MTX indicated that the introduction of the sugar moiety decreased the biological activity of these MTX conjugates. The tetradecyl derivative 6b, however, was effective in inhibiting the dihydrofolate reductase activity in vitro and showed an inhibitory effect on human lymphoblastoid cell growth. (C) 2001 Wiley-Liss, Inc.

A titrimetric respirometer measuring the nitrifiable nitrogen in wastewater using in-sensor-experiment

Measurement of nitrifiable nitrogen contained in wastewater by combining the existing respirometric and titrimetric principles is reported. During an in-sensor-experiment using nitrifying activated sludge. both the dissolved oxygen (DO) and pH in the mixed liquor were measured, and the FH was controlled at a set-point through titration of base or acid. A combination of the oxygen uptake rate (OUR), which was obtained from the measured DO signal, and the titration data allowed calculation of the nitrifiable nitrogen and the short-term biological oxygen demand (BOD) of the wastewater sample that was initially added to the sludge. The calculation was based solely on stoichiometric relationships. The approach was preliminarily tested with two types of wastewaters using a prototype sensor. Good correlation was obtained. (C) 2000 Elsevier Science Ltd. All rights reserved.

Determination of reference values for glucose tolerance, insulin tolerance, and insulin sensitivity tests in clinically normal cats

Objective-To determine reference values and test variability for glucose tolerance tests (GTT), insulin tolerance tests (ITT), and insulin sensitivity tests (IST) in cats, Animals-32 clinically normal cats. Procedure-GTT, ITT, and IST were performed on consecutive days. Tolerance intervals tie, reference values) were calculated as means +/- 2.397 SD for plasma glucose and insulin concentrations, half-life of glucose (T-1/2glucose), rate constants for glucose disappearance (K-glucose and K-itt), and insulin sensitivity index (S-l). Tests were repeated after 6 weeks in 8 cats to determine test variability. Results-Reference values for T-1/2glucose, K-glucose, and fasting plasma glucose and insulin concentrations during GTT were 45 to 74 minutes, 0.93 to 1.54 %/min, 37 to 104 mg/dl, and 2.8 to 20.6 muU/ml, respectively. Mean values did not differ between the 2 tests. Coefficients of variation for T-1/2glucose, K-glucose, and fasting plasma glucose and insulin concentrations were 20, 20, 11, and 23%, respectively. Reference values for K-itt were 1.14 to 7.3%/min, and for S-l were 0.57 to 10.99 x 10(-4) min/muU/ml. Mean values did not differ between the 2 tests performed 6 weeks apart, Coefficients of variation for K-itt and S-l were 60 and 47%, respectively. Conclusions and Clinical Relevance-GTT, ITT, and IST can be performed in cats, using standard protocols. Knowledge of reference values and test variability will enable researchers to better interpret test results for assessment of glucose tolerance, pancreatic beta -cell function, and insulin sensitivity in cats.

Nocodazole inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes via a microtubule-independent mechanism

Insulin stimulates glucose transport in adipocytes and muscle cells by triggering redistribution of the GLUT4 glucose transporter from an intracellular perinuclear location to the cell surface. Recent reports have shown that the microtubule-depolymerizing agent nocodazole inhibits insulin-stimulated glucose transport, implicating an important role for microtubules in this process. In the present study we show that 2 mum nocodazole completely depolymerized microtubules in 3T3-L1 adipocytes, as determined morphologically and biochemically, resulting in dispersal of the perinuclear GLUT4 compartment and the Golgi apparatus. However, 2 mum nocodazole did not significantly effect either the kinetics or magnitude of insulin-stimulated glucose transport. Consistent with previous studies, higher concentrations of nocodazole (10-33 mum) significantly inhibited basal and insulin-stimulated glucose uptake in adi. pocytes. This effect was not likely the result of microtubule depolymerization because in the presence of taxol, which blocked nocodazole-induced depolymerization of microtubules as well as the dispersal of the perinuclear GLUT4 compartment, the inhibitory effect of 10-33 muM nocodazole on insulin-stimulated glucose uptake prevailed. Despite the decrease in insulin-stimulated glucose transport with 33 muM nocodazole we did not observe inhibition of insulin-stimulated GLUT4 translocation to the cell surface under these conditions. Consistent with a direct effect of nocodazole on glucose transporter function we observed a rapid inhibitory effect of nocodazole on glucose transport activity when added to either 3T3-L1 adipocytes or to Chinese hamster ovary cells at 4 degreesC. These studies reveal a new and unexpected effect of nocodazole in mammalian cells which appears to occur independently of its microtubule-depolymerizing effects.

The role of Ca2+ in insulin-stimulated glucose transport in 3T3-L1 cells

We have examined the requirement for Ca2+ in the signaling and trafficking pathways involved in insulin-stimulated glucose uptake in 3T3-LI adipocytes. Chelation of intracellular Ca2+, using 1,2-bis (o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM), resulted in >95% inhibition of insulin-stimulated glucose uptake. The calmodulin antagonist, W13, inhibited insulin-stimulated glucose uptake by 60%. Both BAPTA-AM and W13 inhibited Akt phosphorylation by 70-75%. However, analysis of insulin-dose response curves indicated that this inhibition was not sufficient to explain the effects of BAPTA-AM and W13 on glucose uptake. BAPTA-AM inhibited insulin-stimulated translocation of GLUT4 by 50%, as determined by plasma membrane lawn assay and subcellular fractionation. In contrast, the insulin-stimulated appearance of HA-tagged GLUT4 at the cell surface, as measured by surface binding, was blocked by BAPTA/AM.. While the ionophores A23187 or ionomycin prevented the inhibition of Akt phosphorylation and GLUT4 translocation by BAPTA-AM, they did not overcome the inhibition of glucose transport. Moreover, glucose uptake of cells pretreated with insulin followed by rapid cooling to 4 degreesC, to promote cell surface expression of GLUT4 and prevent subsequent endocytosis, was inhibited specifically by BAPTA-AM. This indicates that inhibition of glucose uptake by BAPTA-AM is independent of both trafficking and signal transduction. These data indicate that Ca2+ is involved in at least two different steps of the insulin-dependent recruitment of GLUT4 to the plasma membrane. One involves the translocation step. The second involves the fusion of GLUT4 vesicles with the plasma membrane. These data are consistent with the hypothesis that Ca2+/cahnodulin plays a fundamental role in eukaryotic vesicle docking and fusion. Finally, BAPTA-AM may inhibit the activity of the facilitative transporters by binding directly to the transporter itself.