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Effects of maternal diet during late pregnancy and lactation on the development of IgE and egg- and milk-specific IgE and IgG antibodies in infants.

The IgE levels and food-allergen-specific IgE- and IgG-antibodies (Ab) to ovalbumin (OA), ovomucoid (OVO) and beta-lactoglobulin (BLG) were determined up to 18 months of age in 163 infants born to women who were atopic. A high (HIGH group) or a low (REDUCED group) intake of hen's egg and cow's milk by the mother during the third trimester gave no significant differences in the concentrations of IgE or in IgE-Ab (OVO, BLG) and IgG-Ab (OA, OVO, BLG). Similarly, a prolongation of the abstention diet to the early lactation period did not influence the immune response. The IgG-Ab levels to all three food allergens decreased significantly (P less than 0.001) in both study groups between birth and 2 months of age, but then increased significantly (P less than 0.001) between 6 and 18 months of age. The presence in serum of IgE-Ab to OVO (greater than or equal to 0.15 PRU/ml) was associated with significantly higher IgG-Ab levels to OVO at 6 months (P less than 0.001) and at 18 months (P less than 0.05). Infants with positive skin-prick tests (SPT) to OA and OVO showed higher IgG-Ab levels at 6 and 18 months of age than did infants with negative SPT reactions to the two egg allergens. This indicates a relation between the IgE- and IgG-Ab response and it also suggests that some individuals are 'high responders' to both types of immunoglobulin isotypes while others are 'low responders'.

Allergens↗

Somatosensory evoked potentials and cerebral metabolism during cardiopulmonary bypass with special reference to hypotension induced by prostacyclin infusion.

Somatosensory evoked potentials and cerebral metabolism were studied during cardiopulmonary bypass in 41 patients undergoing coronary bypass. Twenty-two patients received prostacyclin 50 ng/kg/min during cardiopulmonary bypass for platelet protection and 19 patients served as controls. Mean arterial blood pressure in the prostacyclin group was below 30 mm Hg during the first 30 minutes of bypass, but it remained above 50 mm Hg in the control group. Central conduction time, a measure of the electrical conduction time in the central nervous system, was prolonged in both groups during bypass up to 30 minutes of rewarming. The prolongation was greater in the control group early during bypass. At 20 minutes of cardiopulmonary bypass, central conduction time was increased by 81% (standard deviation 38) of the prebypass value in the control group and by 44% (standard deviation 17) in the prostacyclin group (p less than 0.001). Arteriovenous oxygen difference across the brain was greater in the prostacyclin group early during bypass. It was 36 ml/L (standard deviation 9) in the control group and 60 ml/L (standard deviation 18) in the prostacyclin group (p less than 0.001) at 10 minutes of bypass. There was no difference between the groups in regard to glucose and lactate. We conclude that cardiopulmonary bypass with hypothermia prolongs central conduction time. The hypotension induced by prostacyclin (50 ng/kg/min) did not further impair conduction in the central nervous system.

Blood Platelets↗

Myocardial metabolic changes during reperfusion of ventricular fibrillation: a 31P nuclear magnetic resonance study in swine.

OBJECTIVE: Myocardial metabolic requirements during reperfusion of ventricular fibrillation are poorly understood. The objective of this study was to determine if controlled reperfusion after a clinically relevant global ischemia period of 10 mins was sufficient to prevent or reverse myocardial ischemia as indicated by changes in myocardial high energy phosphates, myocardial intracellular pH, and great cardiac vein lactate. DESIGN: Prospective laboratory study with controlled reperfusion. SETTING: Research laboratory at a university medical center. SUBJECTS: Five swine weighing 19 +/- 3 kg. INTERVENTIONS: Ten minutes of nonperfused ventricular fibrillation followed by reperfusion with cardiopulmonary bypass (flow 30 mL/kg/min) for 50 mins. MEASUREMENTS AND MAIN RESULTS: Myocardial adenosine triphosphate (ATP), phosphocreatine, and intracellular pH were determined using in vivo 31P nuclear magnetic resonance. Myocardial blood flow, measured by 15-mu radiolabeled microspheres, was significantly increased above baseline during reperfusion. Phosphocreatine was depleted during the 10 mins of nonperfused ventricular fibrillation, but recovered to 122 +/- 18% of baseline with reperfusion and was 112 +/- 18% at 60 mins (p < .005). ATP concentrations decreased to 51 +/- 16% of baseline after 10 mins of nonperfused ventricular fibrillation, improved to 67 +/- 9% of baseline with early reperfusion, and were 65 +/- 9% of baseline at 60 mins (p < .02). Myocardial intracellular pH improved from 6.11 +/- 0.18 after 10 mins of nonperfused ventricular fibrillation, to 6.89 +/- 0.20 with early reperfusion, and then decreased to 6.85 +/- 0.35 at 60 mins ventricular fibrillation (p < .001). Despite myocardial blood flows higher than baseline during the reperfusion period, great cardiac vein/aortic lactate gradient increased over the reperfusion period. CONCLUSION: Prolonged reperfusion with supranormal myocardial blood flow does not restore normal myocardial aerobic metabolism in the fibrillating myocardium after a 10-min nonperfused ventricular fibrillation period.

Adenosine Triphosphate↗

Metabolic changes associated with the slowing of relaxation in fatigued mouse muscle.

1. The biochemical basis of the slowing of relaxation seen in fatigue has been examined using an isolated mouse soleus preparation. 2. Slowing of relaxation occurred during prolonged tetani under anaerobic conditions when ATP and PC fell and lactate accumulated. 3. Slowing of relaxation was also demonstrated with muscles poisoned with cyanide and iodoacetic acid when there was a fall in ATP and PC but no accumulation of lactate. During a period of anaerobic recovery following a fatiguing tetanus, relaxation became faster at a time when lactate was accumulating in the muscle. 4. It is concluded that the slowing of relaxation in fatigue is not a consequence of lactate accumulation, and a relationship is demonstrated between the ATP content of the muscle and the rate of relaxation in muscles fatigued by prolonged stimulation, 5. Rates of ATP turn-over in fresh muscle, and at intervals throughout a tetanus are consistent with the suggestion that the rate limiting step for myofibrillar ATPase may be directly related to the rate limiting step for the decay of tension during relaxation.

Adenosine Triphosphate↗

Monitoring high-intensity endurance exercise with heart rate and thresholds.

Ventilatory and lactate thresholds have been proposed as tools to establish the highest steady-state intensity sustainable during prolonged physical exercise. The purposes of this study were to clarify whether the intensity at the ventilatory threshold could be sustained during prolonged high-intensity exercise and if the corresponding work rate, pulmonary ventilation, and blood lactate concentration could also be maintained. Fifteen young and healthy male subjects were submitted to a VO2max test on ergocycle and a 90-min high-intensity ergocycle endurance exercise test. During the 90-min exercise test, subjects were able to maintain an intensity corresponding to a heart rate 5 beats.min-1 lower than that predetermined from the ventilatory threshold. Heart rate, FeO2, and FeCO2 were stable during the period from 20 to 80 min, VO2 was constant from 30 to 80 min, while work output, pulmonary ventilation, blood lactate, and VCO2 decreased significantly over the 90-min performance. These results show that physiological parameters near the ventilatory threshold are not interchangeable and that some cannot be used to monitor high-intensity long term exercise. Moreover, they clearly demonstrate that the blood lactate concentration fluctuates substantially during a 90-min endurance performance and cannot predict the highest work intensity that can be sustained during prolonged exercise without fatigue. However, heart rate and VO2 at the ventilatory threshold seem to be more suitable markers for that purpose.

Adult↗

[The cardioprotective effect of verapamil in acute percutaneous transluminal coronary angioplasty].

Verapamil improved the ischemic tolerance of the myocardium in experiments in animals. Therefore, 20 patients were examined during percutaneous transluminal coronary angioplasty (PTCA) of a proximal LAD stenosis in order to evaluate the ability of verapamil to improve the ischemic tolerance in man. Before the second dilatation, 1 mg verapamil was given intracoronarily to 10 patients, the other 10 patients received placebo ic. Before and after each of the three inflations, blood samples were obtained from the coronary sinus in five patients of each group to analyze the contents of lactate, pyruvate, and pH. Verapamil caused a significant prolongation of the inflation from 58 +/- 12 s to 83 +/- 20 s. This effect was persistent also during the following inflation (96 +/- 19 s). The onset of angina was delayed (p less than 0.05). ST-wave elevations and T-wave amplitudes were smaller after verapamil, in spite of the increased duration of inflation, as compared with the control group. The time until ST elevations of 0.1 mV occurred was increased from 17 +/- 3 s to 57 +/- 18 s (p less than 0.05). The increase in lactate in coronary sinus blood was less pronounced after verapamil (48% of control; p less than 0.05). Intracoronary verapamil before PTCA of the LAD improved the ischemic tolerance of the poststenotic myocardium significantly as evaluated by measurements of electrocardiographic and metabolic parameters. No side effects occurred during the injection of verapamil into the left coronary artery.

Adult↗

Evaluation of surfactant cytotoxicity potential by primary cultures of ocular tissues: I. Characterization of rabbit corneal epithelial cells and initial injury and delayed toxicity studies.

This investigation was undertaken to develop cytotoxicity assay systems using primary cultures of rabbit corneal epithelial cells as an experimental model to evaluate oculotoxic agents and the ability of these in vitro assay systems to predict irritancy potential and delayed toxicity. We have characterized the epithelial nature of the cultures by identifying keratins with antikeratin antibodies (AE1/AE3) and by demonstrating metabolic enzymes important to the integrity of the cells: lactate dehydrogenase, glucose 6-phosphate dehydrogenase and aldolase. Eight surfactants were compared and ranked according to their cytotoxic potential. We evaluated cytotoxicity by measuring leakage of the cytosolic enzyme, lactate dehydrogenase, into the medium, by making morphological observations and by assessing lysosomal neutral red uptake and mitochondrial 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction. The cells were treated for 1 h with the surfactants and the possibility of delayed toxicity was evaluated 24 h after removal of the surfactant. The cytotoxicity of the different types of surfactants as shown by all the tests was cationic > anionic = amphoteric > non-ionic. Triton X-100, a non-ionic surfactant but a severe irritant, had a ranking similar to anionic surfactants. The in vitro rankings corresponded well to reported in vivo Draize rabbit eye test data. The 24-h test for lactate dehydrogenase leakage showed that mild and non-irritating surfactants did not demonstrate any subsequent damage after a 1-h exposure, but the extreme and severe surfactants continued to show further damage after the 1-h exposure. These in vitro findings were similar to reported in vivo results. The neutral red and MTT tests did not adequately predict the prolonged toxicity of the more irritating surfactants, as was demonstrated by the lactate dehydrogenase leakage test. We conclude that in vitro cytotoxicity assays using primary cultures of rabbit corneal epithelial cells may be used to rank the cytotoxic potential of surfactants, but only the lactate dehydrogenase leakage test was able to assess prolonged cell injury.

Animal Testing Alternatives↗

Body weight loss during lactation in relation to energy and protein metabolism in standard-fed primiparous sows.

After 5 weeks of lactation 14 standard-fed primiparous sows were divided into a low weight-loss group (L-gr, loss < 25 kg, n = 7) and a high weight-loss group (H-gr, loss > or = 25 kg, n = 7). Body weights of the sows and their litters were recorded on days 2, 7, 14, 21, 28 and 35 of lactation. Blood samples were collected before the morning feeding on each weighing day. Samples were analysed to determine concentrations of insulin, glucagon, glucose, triglycerides, non-esterified fatty acids (NEFA), urea and creatinine. The H-gr sows lost weight throughout lactation, whereas the L-gr sows gained weight during the last week. Weight loss was higher in the H-gr than in the L-gr during weeks 2, 3 and 5 of lactation. Litter size and litter weight gain were higher in the H-gr than in the L-gr. Significant changes in levels of insulin, glucagon, glucose, triglycerides and creatinine were observed over lactation. No significant differences in concentrations of any of the parameters were found between the two groups, except for insulin and cholesterol which were higher in the L-gr. Catabolism of adipose tissue and muscle protein was observed in both groups during the first week of lactation. This catabolic state was more pronounced and tended to be prolonged in the H-gr. Concentrations of all parameters seemed to be stable in both groups during the last two weeks of lactation.

Animals↗

Metabolic adaptation to prolonged exercise in severely obese subjects.

In investigating the metabolic adaptation to prolonged exercise in markedly obese subjects, we compared blood glucose, plasma lactate, free fatty acids, insulin and glucagon concentrations during 3 h of treadmill exercise in nine severely obese male patients (OB) (weight excess 84 +/- 7 per cent of their ideal body weight) and in nine healthy controls (C). Speed and slope of treadmill were selected to give a similar oxygen consumption in both groups (OB: 1.61 +/- 0.08 1/min; C: 1.72 +/- 0.07 1/min). Under these conditions, heart rate was similar in both groups, whereas ventilation was significantly lower in overweight subjects. In obese patients, plasma free fatty acid (FFA) levels were higher in the basal state (OB: 740 +/- 43 mumol/l; C: 602 +/- 40 mumol/l, 2 P less than 0.05) but showed a lower increase during the exercise period (OB: + 576 +/- 135 mumol/l; C: + 1071 +/- 100 mumol/l, 2 P less than 0.02). This impaired FFA mobilization was related to significantly higher insulin (IRI) levels throughout the exercise period as shown by the regression line of exercise-induced FFA increase (y, mumol/l) vs mean plasma IRI during exercise (x, microU/ml): y = 1238 - 60 x, r = -0.709, 2 P less than 0.001. Lack of glucagon increase could also contribute to the lower rise of FFA in obese subjects. A correspondingly increased contribution of carbohydrates to the energy supply is suggested by a significant decline in blood glucose and higher lactate plasma concentrations during the second half of the exercise period in overweight patients. These abnormalities could represent a metabolic limitation for performing prolonged exercise in markedly obese patients.

Blood Glucose↗

[Lactic acidosis and hyperlactatemia].

Lactic acidosis is a relatively frequent acid-base disorder in a hospital setting. It is defined by the association of an arterial pH inferior to 7.35 and an arterial lactate level superior to 5 mmol/l. Classically, 2 types of acidosis are distinguished on the basis of their mechanisms of onset: the type A, with evident clinical signs of tissue hypoperfusion and the type B, more are, without apparent hypoxia. This last category is observed in various circumstances such as diabetes, acute liver failure, poisoning and, more rarely, inborn errors of carbohydrate metabolism. Treatment aims primarily at the correction of the cause. The efficacy of sodium bicarbonate is presently debated, considering the risk to worsen hyperlactatemia and to induce hyperosmolarity or rebound alkalosis. The administration of dichloroacetate, an activator of pyruvate dehydrogenase, permits to correct partially the lactic acidosis but is not harmless especially in case of prolonged administration. Other therapeutic modalities are evoked. Arterial lactate level is a reliable prognostic index of shock, because blood values do not depend only of the oxygen debt but also of the efficacy of hepatic and renal lactate uptake. Sequential measurements are recommended.

Acidosis, Lactic↗

Studies on the effects of growth hormone administration in vivo on the rates of glucose transport and utilization in rat skeletal muscle.

The effects of growth hormone (GH) administration to rats in vivo on the sensitivity of the rate of glucose utilization to insulin were studied in soleus muscles isolated from these rats. A single injection of GH did not increase the rate of glucose transport within 1-2 h. However, 12 h after, the rate of glucose transport was increased at 10 mU insulin l-1 and was accompanied by a similar increase in the rate of lactate formation but no change in the rate of glycogen synthesis. Prolonged treatment with GH decreased the rate of glucose transport and glycogen synthesis and increased the content of glucose 6-phosphate at physiological levels of insulin but did not affect the rate of lactate formation. These results suggest that: (a) GH does not increase the rate of glucose transport acutely; however, after several hours, the sensitivity of glucose transport and glycolysis to insulin are increased; (b) prolonged elevations of the level of GH in plasma decrease the sensitivity of the rate of glucose transport and glycogen synthesis to insulin. However, redirection of glucose residues away from the pathway of glycogen synthesis towards that of glycolysis and a possible increase in the rate of glycogenolysis maintain a normal rate of lactate formation, although the rate of glucose transport is decreased.

Animals↗

Metabolism in pedicled and free TRAM flaps: a comparison using the microdialysis technique.

The most common complication in flap surgery is of a circulatory nature. Impeded blood flow leads to altered metabolism in the tissue. Possible metabolic differences between different zones of the transverse rectus abdominis muscle (TRAM) flap were studied and the metabolism of pedicled and free TRAM flaps was compared intraoperatively and postoperatively. The method used was microdialysis, which is a useful technique for following local metabolic changes continuously in various tissues.Twenty-two patients with a pedicled or free TRAM flap were monitored using the microdialysis technique. Two microdialysis catheters were placed subcutaneously in the flap (zone I and zone II), and a third one was placed subcutaneously in the flank to serve as a control. The flaps were monitored intraoperatively and postoperatively for 3 days with repeated analyses of extracellular glucose, lactate, and glycerol concentrations. An additional analysis of pyruvate was performed in some patients to calculate the lactate-to-pyruvate ratio. This study showed that glucose, lactate, and glycerol change in a characteristic way when complete ischemia (i.e., complete inhibition of the blood circulation) is present. A slower stabilization with prolonged metabolic signs of ischemia, such as lower glucose and higher lactate and glycerol concentrations, was seen in zone II compared with zone I, and more pronounced metabolic signs of ischemia, but with a faster recovery, were detected in the free TRAM flap group than in the pedicled TRAM flap group. The fact that the metabolites returned to normal earlier in free flaps than in pedicled flaps may indicate that free TRAM flaps sustain less ischemic damage because of better and more vigorous perfusion.

Abdominal Muscles↗

Experiment and computer-aided simulation: complementary tools to understand exercise metabolism.

During the last two decades the concept of the MLSS (maximal lactate steady state) has been established. The MLSS detects the highest level of the BLC (blood lactate concentration) and the corresponding workload (MLSS workload) that can be maintained over time without continual BLC accumulation. In spite of a lack of experimental and/or theoretical foundation, it has been speculated that the level of the MLSS may decrease with increasing performance capacity. The potential inter-relationship between performance capacity and BLC response to prolonged constant workload will be analysed based on a recent study, which provided evidence that the MLSS is independent of performance whereas MLSS workload increases with performance capacity, and by a computer-aided simulation. The simulated model modifies and combines previous theories put forward to explain the response of BLC to exercise and incorporates a theory about limiting factors of oxygen transport to the muscle cell. Simulations consider the BLC response to selected prolonged constant workloads while paying special respect to changes in body structure and substrate utilization, which are generally accepted as limiting factors of performance capacity. This complex modulation of appearance and disappearance of lactate during constant prolonged exercise seems to support the experimental results, which indicated independence between MLSS and performance capacity.

Adult↗

Brain lactate, not glucose, fuels the recovery of synaptic function from hypoxia upon reoxygenation: an in vitro study.

Lactate has been considered for many years to be a useless, and frequently, harmful end-product of anaerobic glycolysis. In the present in vitro study, lactate-supplied rat hippocampal slices showed a significantly higher degree of recovery of synaptic function after a short hypoxic period than slices supplied with an equicaloric amount of glucose. More importantly, all slices in which anaerobic lactate production was enhanced by pre-hypoxia glucose overload exhibited functional recovery after a prolonged hypoxia. An 80% recovery of synaptic function was observed even when glucose utilization was blocked with 2-deoxy-D-glucose during the later part of the hypoxic period and during reoxygenation. In contrast, slices in which anaerobic lactate production was blocked during the initial stages of hypoxia did not recover their synaptic function upon reoxygenation despite the abundance of glucose and the removal of 2-deoxy-D-glucose. Thus, for brain tissue to show functional recovery after prolonged period of hypoxia, the aerobic utilization of lactate as an energy substrate is mandatory.

Animals↗

Simultaneous and separable flux of pathways for glucose and glycogen utilization studied by 13C-NMR.

Glucose utilization and glycogen turnover was studied by 13C-NMR in segments of hog carotid artery smooth muscle. After superfusion of carotid segments for 8-16 h at 37 degrees C with C-1 labeled glucose. 13C-NMR spectra revealed substantial incorporation into glycogen, lactate and into resonances tentatively identified as glutamate at the C-2 and C-4 positions. The rate of net glycogen incorporation was approximately linear over 8 h in unstimulated muscle. After washing out the initial labeled glucose, carotids were contracted by 80 mM KCl in the presence of C-2 labeled glucose. During the contraction simultaneous flux of glycogenolysis and glycolysis was observed with production of lactate labeled at the C-2 position (from glucose labeled at the second carbon) and with the magnitude of the glycogen resonance decreasing. However, no lactate labeled at the C-3 position (derived from C-3 glycogen) was observed at the end of a prolonged contraction. If complete mixing of the intermediates of the two pathways occurred, lactate derived from both glucose and glycogen would have been observed. When similar experiments are performed in the presence of 5 mM NaCN to block oxidative metabolism, then lactate derived from glucose and from glycogen was clearly observed. Therefore, when oxidative metabolism was intact, the intermediates of glycogenolysis and glycolysis did not normally appear to fully mix despite simultaneous flux of the two pathways during contraction. These separable cytosolic pathways for carbohydrate utilization are proposed to be governed by a reaction-diffusion class of mechanism. Such an organization of cytosolic enzymes may represent a general feature of cell metabolism.

Animals↗

[Effect of hypoxia on the viability of rat brain astrocytes in vitro].

OBJECTIVE: To investigate the effect of hypoxia on the viability of rat brain astrocytes in vitro and determine the optimal duration of hypoxic treatment for studying the biological behavior of the in vitro cultured cells in response to hypoxia. METHODS: Rat astrocytes were cultured and identified by glial fibrillary acidic protein (GFAP) immunofluorescent staining. After incubation with 5%; CO(2)+95%; N(2) for different time to induce hypoxia, the cells were harvested and observed microscopically for morphological changes and counting of the dead cells. The culture media of the cells were also collected and pO(2), concentrations of glucose and lactate as well as lactate dehydrogenase (LDH) activity were analyzed. RESULTS: As the hypoxia prolonged, the astrocytes appeared swollen and floating in the medium with some becoming necrotic. Compared with the cells in the control group, the changes in the number of necrotic cells, concentrations of glucose and lactate, and LDH activity in the cells of the hypoxic group were significantly different after 10 h of hypoxia (P<0.05). However, the flat and polygonal morphology of the astrocytes almost remained unchanged after 8 h of hypoxia in spite of significant changes in the concentrations of glucose and lactate and LDH activity. CONCLUSION: Hypoxia induced injury and necrosis of rat brain astrocytes in vitro, and 8 h of hypoxia can be the optimal time point for studying the biological behaviors of the cells in response to hypoxia.

Animals↗

Plasma volume expansion with Haemaccel does not impair haemostasis during reduction mammaplasty.

OBJECTIVES: An in vivo study under well-controlled conditions was undertaken to determine the effect of Haemaccel, a colloidal plasma volume expander, on normal haemostasis. METHODOLOGY: Twenty patients, who were admitted for reduction mammaplasty, were included in this study. A standardised anaesthesia protocol was followed with all patients. Ten patients received 500 ml Haemaccel and 10 controls received 1,500 ml Ringer's lactate, a crystalloid solution. The solutions were administered intravenously during surgery over a period of 30-40 minutes. Standardised clinical observations and haematological tests were done at the following time intervals: after anaesthesia but before infusion of the plasma substitute, immediately after infusion was completed, and 20, 40 and 60 minutes after infusion. RESULTS: The blood pressure, pulse rate and O2 saturation levels were not influenced by the treatment given. Haemodilution was similar for the two patient groups. The platelet count and plasma levels of fibrinogen decreased in parallel with haemodilution. Thereafter the platelet count gradually increased to pre-infusion counts at 60 minutes. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT) and platelet aggregation in response to adenosine diphosphate (ADP) and collagen were not affected by the plasma volume expander given. Arachidonic acid-induced aggregation decreased significantly after Ringer's lactate was given but did not change when Haemaccel was given. The bleeding time was prolonged slightly, but not significantly, from 7.4 +/- 1.6 minutes to 8.8 +/- 1.6 minutes with Ringer's lactate and from 6.9 +/- 2.0 to 9.7 +/- 3.7 minutes with Haemaccel. CONCLUSIONS: We could not find any scientific evidence that Haemaccel affects haemostasis; neither does it increase bleeding relative to Ringer's lactate.

Adult↗