scholarly journals EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM

1962 ◽  
Vol 116 (6) ◽  
pp. 897-911 ◽  
Author(s):  
L. Joe Berry ◽  
Dorothy S. Smythe ◽  
Susannah McC. Kolbye

The greater susceptibility to the lethal effects of bacterial endotoxin (heat-killed Salmonella typhimurium or Escherichia coli lipopolysaccharide, in mice infected with an attenuated strain of Mycobacterium tuberculosis (BCG) was confirmed. It reached a maximum at 2 weeks postinfection and gradually diminished for an additional 6 weeks. At the time of maximum susceptibility several metabolic and physiological differences became apparent. BCG-infected mice die sooner (4 to 12 hours) and without the diarrhea, conjunctivitis, and general symptomatology associated with endotoxin deaths of normal animals. Reticuloendothelial blockade results in only a small change in reactivity to endotoxin, in contrast to normal mice. Subcutaneous injection of 2 units of ACTH is followed by no significant increase in urinary nitrogen excretion while in control animals it more than doubles. Plasma clearance of intravenously administered inulin is approximately normal in BCG-infected mice 17 hours after an LD50 dose of endotoxin but control mice similarly treated show renal impairment. In line with this result is the absence of elevated carcass non-protein nitrogen (NPN) following endotoxin poisoning or at the moment of death from endotoxemia in the hyperreactive animals in contrast to the two- to threefold increase in carcass NPN in normal mice under similar conditions. Body carbohydrate is at a minimum and becomes depleted to a level approximating that found at death more rapidly in BCG-infected mice given endotoxin than in controls. There is also a lower ratio of carbohydrate anabolized to protein catabolized following cortisone administration to BCG-infected mice than in control mice. This is found in adrenalectomized mice and in stressed animals and is reported elsewhere. Some of the differences just described can be attributed to a refractory adrenal cortex. There is less depletion of adrenal cholesterol in vivo and lower corticoid synthesis in vitro than in normal mice yet this is not fundamentally responsible for the greater susceptibility of BCG-infected animals to endotoxin since adrenalectomized mice, which are even more susceptible, are metabolically and physiologically more comparable to normal mice than to BCG-infected mice. One can conclude, therefore, that the hyperreactivity of BCG-infected mice is more than an intensification of the normal response to endotoxin.

1961 ◽  
Vol 114 (5) ◽  
pp. 761-778 ◽  
Author(s):  
L. Joe Berry ◽  
Dorothy S. Smythe

In vitro secretion of glycocorticoids by adrenal glands pooled from several control mice was compared with that of glands removed from animals following injections of either ACTH or endotoxin. Both substances prevent glycocorticoid synthesis stimulated in vitro with ACTH. Cholesterol content of adrenal glands under these conditions was nearly depleted, indicating maximal response to ACTH or endotoxin prior to their removal for the in vitro tests. In an effort to account physiologically for the manner in which endotoxin suppresses or prevents the rise in urinary nitrogen excreted in response to ACTH, blood non-protein nitrogen levels (NPN) were determined. The following experimental conditions resulted in increased urinary nitrogen excretion but did not alter blood NPN: cortisone given alone or at the same time as endotoxin; ACTH alone; dichloroisoproterenol (DCI) given concurrently with endotoxin; and lactalbumin digest injected intraperitoneally. Increases (2- to 3-fold) in blood NPN were observed when endotoxin was given alone, concurrently with ACTH, or 3 hours prior to cortisone, DCI, or lactalbumin digest. Urinary nitrogen excretion showed no change under these conditions. The elevation in blood NPN in endotoxin-poisoned mice was found to be due almost entirely to urea nitrogen and not to amino acid nitrogen or to other nitrogenous wastes. Blood clearance of mulin, phenol red excretion, and urea elimination were each determined in control and in endotoxin-poisoned mice. The latter mice showed impaired renal function. Treatment with diuretics (diuril and aminophylline) failed to alter oliguria or elevated blood NPN. Hydergine treatment was also without effect. Total carcass NPN and urinary nitrogen excretion data were combined to give a picture of total protein catabolized by mice under different experimental conditions. Cortisone injected at the same time as endotoxin or 3 hours later resulted in the same increase in total NPN. However, in the former case all the extra nitrogen appeared in the urine while in the latter it remained in the carcass. ACTH given alone or concurrently with endotoxin produced large increases in total NPN but less in poisoned mice. This suggests that endotoxin suppresses adrenal response to ACTH. Urea injected into normal mice was recovered quantitatively in urine while in endotoxin-poisoned mice it was partitioned between carcass and urine. Elevation of carcass NPN by means of urea injections failed to alter the lethality of an LD70 dose of endotoxin.


1983 ◽  
Vol 55 (2) ◽  
pp. 628-634 ◽  
Author(s):  
K. N. Frayn

This paper reviews the assumptions involved in calculating rates of carbohydrate and fat oxidation from measurements of O2 consumption, CO2 production, and urinary nitrogen excretion. It is shown that erroneous results are obtained in the presence of metabolic processes such as lipogenesis and gluconeogenesis. The apparent rates calculated under these conditions can, however, be interpreted as net rates of “utilization.” Thus the apparent rate of carbohydrate oxidation is the sum of the rates of utilization for oxidation and for lipogenesis minus the rate at which carbohydrate is formed from amino acids. The apparent rate of fat oxidation is the difference between the rates of oxidation and synthesis from carbohydrate, so that the apparently negative rates encountered in patients infused with glucose do quantitatively represent net rates of synthesis. Other processes such as synthesis of ketone bodies or lactate at rates greater than their utilization can also disturb the calculations, but the magnitude of the effect can be estimated from appropriate measurements. Methods of correcting the observed gaseous exchange in these circumstances are given.


1961 ◽  
Vol 113 (1) ◽  
pp. 83-94 ◽  
Author(s):  
L. Joe Berry ◽  
Dorothy S. Smythe

There exists an inverse proportionality between number of heat-killed cells of Salmonella typhimurium injected intraperitoneally into mice and the quantity of urinary nitrogen the animals excrete during a 17 hour period following the subcutaneous administration of 2 units of ACTH. This relationship has been developed into an assay for bacterial endotoxin. Mice immunized against S. typhimurium require 10 to 20 times the number of cells needed by control animals to suppress urinary nitrogen excretion to the same extent. Intravenous saccharated iron oxide sensitizes animals so that fewer heat-killed salmonellae can be detected. Heat-killed cells of Staphylococcus aureus are without effect in the assay. Several lipopolysaccharides derived from Gram-negative bacteria are effective in preventing the rise of urinary nitrogen excreted in response to ACTH and the amount required, compared to the LD50, is in the same ratio for all of them. Citrated mouse serum partially inactivates the endotoxin during in vitro incubation for 1 hour at 37°C. while normal serum does not. Dichloroisoproterenol protects mice against the lethal effects of lipopolysaccharide and it lowers its effectiveness in the assay. The minimum amount of endotoxin reliably determined by the test is 0.25 µg. of an E. coli preparation that was given intravenously in mice in which the reticuloendothelial system had been "blocked" with saccharated iron oxide.


1974 ◽  
Vol 11 (5) ◽  
pp. 190-193 ◽  
Author(s):  
Yoshio NAKAHIRO ◽  
Yutaka ISSHIKI ◽  
Jun-ichi OKUMURA

1969 ◽  
Vol 17 (2) ◽  
pp. 187 ◽  
Author(s):  
GD Brown

Macropod marsupials, the kangaroos and wallabies, are characterized by a ruminant-like digestive physiology. One feature of digestion in eutherian species of ruminants is the ability of these animals to utilize non-protein nitrogen through the conversion of such nitrogen to microbial protein by the microorganisms in the rumen. In the present experiments with the euro or hill kangaroo (M. robustus), the utilization of dietary protein (casein) and non-protein nitrogen (urea) has been compared by means of nitrogen balance feeding trials. No consistent differences between the levels of nitrogen retention and urinary nitrogen excretion were observed for euros fed rations supplemented with either casein or urea. It is suggested that the digestion of nitrogen by the ruminant-like macropod marsupials is similar to that of eutherian species of ruminant herbivores.


1987 ◽  
Vol 253 (2) ◽  
pp. E208-E213 ◽  
Author(s):  
K. S. Nair ◽  
D. Halliday ◽  
D. E. Matthews ◽  
S. L. Welle

Hyperglucagonemia coexists with insulin deficiency or insulin resistance in many conditions where urinary nitrogen excretion is increased, but the precise role of glucagon in these conditions is controversial. The purpose of this study was to evaluate the effect of hyperglucagonemia on protein metabolism in insulin-deficient subjects. We used the stable isotope of an essential amino acid (L-[1-13C]leucine) as a tracer of in vivo protein metabolism. A combined deficiency of insulin and glucagon was induced by intravenous infusion of somatostatin. Hyperglucagonemia and hypoinsulinemia were induced by infusions of somatostatin and glucagon. When somatostatin alone was infused leucine flux increased, indicating a 6-17% increase in proteolysis. When somatostatin and glucagon were infused, leucine flux increased, indicating a 12-32% increase in proteolysis. The increase in leucine flux during the infusion of somatostatin and glucagon was higher than the increase during infusion of somatostatin alone. Somatostatin alone did not change leucine oxidation, whereas the somatostatin plus glucagon increased leucine oxidation 100%. We conclude that hyperglucagonemia accelerates proteolysis and leucine oxidation in insulin-deficient humans.


Author(s):  
B N Harsh ◽  
B J Klatt ◽  
M J Volk ◽  
A R Green-Miller ◽  
J C McCann

Abstract The objective was to quantify the effects of the beta-adrenergic agonist (β-AA) ractopamine hydrochloride (Actogain, Zoetis, Parsippany, NJ) on nitrogen excretion and nutrient digestibility in feedlot cattle. In experiment 1, twelve Simmental × Angus steers were blocked by bodyweight (531 ± 16 kg) and used in a randomized complete block design. Dietary treatments included: 1) a control without β-AA (CON) or 2) 400 mg/steer/d ractopamine hydrochloride (RAC) for 35 d before slaughter. Diets contained (DM basis) 55% dry rolled corn, 20% corn silage, 15% modified wet distillers grains with solubles, and 10% supplement. For each block, total collection of feed, orts, feces and urine were conducted for two 5 d sampling periods during week 2 and 4 of RAC supplementation. No interaction (P > 0.21) between treatment and collection period was observed for any parameter evaluated. Dietary treatment had no effect (P = 0.51) on DMI, but RAC had decreased fecal DM output (P = 0.04) compared with CON. Thus, RAC had greater apparent total tract DM digestibility (77.2 vs. 73.5%; P < 0.01), N digestibility (72.4 vs. 69.4%; P = 0.01), and NDF digestibility (65.6 vs. 60.2%; P < 0.01) than CON. Although treatment did not affect nitrogen intake (P = 0.52), RAC tended to reduce total nitrogen excretion (113.3 vs. 126.7 g/d; P = 0.10) compared with CON due to a tendency for decreased fecal nitrogen output (53.9 vs. 61.3 g/d; P = 0.10). However, dietary treatment had no effect (P = 0.53) on urinary nitrogen output or percentage of urinary nitrogen excreted as urea (P = 0.28). Experiment 2 was an in vitro experiment conducted to validate the effects of RAC on nutrient digestibility using Simmental × Angus heifers (451 ± 50 kg). Rumen fluid was collected individually by stomach tube from CON- (n = 9) and RAC-fed (n = 10) heifers to inoculate bottles containing a CON or RAC-containing substrate in a split-plot design. No interaction between rumen fluid source and in vitro substrate was observed. Greater IVDMD (P = 0.01) was observed in rumen fluid from RAC-fed heifers compared with rumen fluid from CON-fed heifers. Inclusion of RAC in the in vitro substrate increased IVDMD (P < 0.01). Overall, feeding RAC increased microbial digestion of the dry-rolled corn-based finishing diet to increase total tract dry mater digestion by 5% and reduce nitrogen excretion by 10.6% in the 35 d period prior to slaughter.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Pierre Singer ◽  
Itai Bendavid ◽  
Ilana BenArie ◽  
Liran Stadlander ◽  
Ilya Kagan

Abstract Background and aims Combining energy and protein targets during the acute phase of critical illness is challenging. Energy should be provided progressively to reach targets while avoiding overfeeding and ensuring sufficient protein provision. This prospective observational study evaluated the feasibility of achieving protein targets guided by 24-h urinary nitrogen excretion while avoiding overfeeding when administering a high protein-to-energy ratio enteral nutrition (EN) formula. Methods Critically ill adult mechanically ventilated patients with an APACHE II score > 15, SOFA > 4 and without gastrointestinal dysfunction received EN with hypocaloric content for 7 days. Protein need was determined by 24-h urinary nitrogen excretion, up to 1.2 g/kg (Group A, N = 10) or up to 1.5 g/kg (Group B, N = 22). Variables assessed included nitrogen intake, excretion, balance; resting energy expenditure (REE); phase angle (PhA); gastrointestinal tolerance of EN. Results Demographic characteristics of groups were similar. Protein target was achieved using urinary nitrogen excretion measurements. Nitrogen balance worsened in Group A but improved in Group B. Daily protein and calorie intake and balance were significantly increased in Group B compared to Group A. REE was correlated to PhA measurements. Gastric tolerance of EN was good. Conclusions Achieving the protein target using urinary nitrogen loss up to 1.5 g/kg/day was feasible in this hypercatabolic population. Reaching a higher protein and calorie target did not induce higher nitrogen excretion and was associated with improved nitrogen balance and a better energy intake without overfeeding. PhA appears to be related to REE and may reflect metabolism level, suggestive of a new phenotype for nutritional status. Trial registration 0795-18-RMC.


1976 ◽  
Vol 27 (1) ◽  
pp. 139 ◽  
Author(s):  
JG Mulholland ◽  
JB Coombe ◽  
WR McManus

Individually penned Border Leicester x Merino wethers, aged 11 months, were fed ad lib. for 16 weeks on a basal ration of ground, pelleted oat straw, urea and minerals, supplemented with 0, 5, 10, 15, 20, 30 or 40% starch. The diets contained equal percentages of nitrogen and minerals. Dry matter intake reached a maximum of 2000 g/day with 30% starch; above this starch level, digestive disturbances were observed. Organic matter digestibility was increased by the addition of starch, but cellulose digestibility was depressed by as much as 18 units with the addition of 30% starch. Up to 10% the starch level had little effect on cellulose digestibility. Liveweight change was significantly correlated with digestible organic matter intake, mean daily weight gains varying from 22 g with no starch to 104 g with 30% starch. However, a large percentage of the liveweight gain was as total body water, and body energy storage increased appreciably only when the diet contained at least 20% starch. The inclusion of 5% starch slightly depressed both intake and liveweight gain. Daily clean wool production was significantly increased at starch levels higher than 20% and ranged from 5.3 to 7.5 g/day with 0 and 40% starch respectively. Increasing levels of starch had little effect on apparent nitrogen digestibility, but resulted in a substantial increase in nitrogen retention through a reduction in urinary nitrogen excretion. Serum urea levels fell from a mean of 42 mg/100 ml during the first week to 31 mg/100 ml during subsequent periods, with no significant differences between diets. With the general exception of potassium, mineral balances were positive or close to zero throughout the experiment.


1969 ◽  
Vol 49 (2) ◽  
pp. 135-141 ◽  
Author(s):  
L. P. Milligan ◽  
A. R. Robblee ◽  
J. C. Wood ◽  
W. C. Kay ◽  
S. K. Chakrabartty

The preparation of a polymer of urea and furfural containing 23.2% nitrogen is described. This product was converted by rumen microorganisms in vitro to ammonia at a rate approximately one-seventh that of conversion of urea to ammonia. Use of the polymer as a dietary supplement in a feeding trial with lambs improved nitrogen retention over that of unsupplemented controls by 3.45 g of nitrogen retained per day, while an isonitrogenous quantity of supplemental urea improved nitrogen retention by 0.51 g of nitrogen retained per day. The blood urea pattern, throughout the day, of lambs adapted to control, urea-supplemented and urea–furfural polymer-supplemented rations indicated a slow, prolonged production of ammonia from the latter supplement and very rapid, short-term degradation of urea in vivo.


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