Diminution of the temperature effect on the oxygen affinity of hemoglobin after prolonged hypothermia

The influence of temperature on the oxygen affinity of hemoglobin, expressed as half saturation tension, P₅₀, was investigated in male Sprague Dawley rats, which had been exposed to a cold environment for about 12 h. P₅₀-values were determined by equilibrating blood samples to a knownP _{O 2} at different temperatures. The well known increase in oxygen affinity at low temperatures was observed, but after a longer hypothermic period this effect was diminished. This reduction of the temperature effect is manifested in a change of the ratio log P₅₀/T from 0.022 in control experiments to 0.0115 in hypothermia. In cold adapted rats such an effect means a better oxygen supply to tissue at low body temperatures than in control animals. These changes in oxygen delivery after cold acclimatisation may partially be interpreted as the result of the decreased intraerythrocytic pH and elevated concentration of ATP found in the present study.Part of this work was presented at the 50th Meeting of the German Physiological Society in Göttinge, 1978 [13] and at the 16th Centraleuropean Anaesthesia Congress in Innsbruck, 1979     

Enzymatic and Metabolic Studies on Carbohydrate and Amino Acid Metabolism in Rat Liver during Acute Uraemia

Abstract. Enzyme activities of the glycolytic, gluconeogenic, and hexose monophosphate pathways were measured in the liver of starved rats 12 and 48 hours after bilateral nephrectomy. Control experiments (sham operated rats) revealed that alterations of enzyme activities were not due to uraemia but to starvation. Alanine-aminotransferase and aspartate- aminotransferase activities, however, were significantly elevated in rat liver 48 hours after nephrectomy when compared with sham operated controls. Concentrations of some of the gluconeogenic intermediates (3-phosphoglyceric acid, pyruvate, phosphoenolpyruvate and glucose-6-phosphate) were significantly higher in the liver of uraemic animals. Amino acid analysis showed an increase in only L-alanine concentration. It is suggested that the elevated content of pyruvate in the liver during acute uraemia is due to an inhibition of pyruvate degradation. Together with the elevated pyruvate concentration the increase in L-alanine could be explained as a consequence of the equilibrium of the alanine-aminotransferase reaction; K_app. of the reaction is not changed by uraemia. Increased activities of the transaminases and the elevated concentrations of the other metabolites measured might indicate that in the liver of nephrectomized rats there is enhanced gluconeogenesis from substrates other than pyruvate.     

Randomized controlled study of in-hospital exercise training programs in children with cystic fibrosis

The aim of this study was to compare aerobic and resistance training in children with cystic fibrosis (CF) admitted to hospital with an intercurrent pulmonary infection with a control group. The subjects were randomized into three groups on the first day of admission. The fat-free mass (FFM) was calculated, using the skin fold thickness from four sites (biceps, triceps, subscapular, and iliac crest). Pulmonary function tests were performed within 36 hr of admission and repeated on discharge from the hospital, and again at 1 month after discharge. All subjects performed an incremental treadmill exercise test, using a modified Bruce protocol. Lower limb strength was measured using a Cybex dynamometer. An assessment of quality of life was made using the Quality of Well Being Scale, as previously reported. Activity levels were measured using a 7-day activity diary, and subjects also wore an accelerometer on their hips. There were no significant differences between the three groups in terms of disease severity, and length of stay in hospital. Subjects in all three groups received intravenous antibiotics and nutritional supplementation as determined by the physician. Children randomized to the aerobic training group participated in aerobic activities for five sessions, each of 30-min duration, a week. The children randomized to the resistance training group exercised both upper and lower limbs against a graded resistance machine. Subjects in the control group received standard chest physiotherapy. Our study demonstrated that children who received aerobic training had significantly better peak aerobic capacity, activity levels, and quality of life than children who received the resistance training program. Children who received resistance training had better weight gain (total mass, as well as fat-free mass), lung function, and leg strength than children who received aerobic training. A combination of aerobic and resistance training may be the best training program, and future studies to assess optimal training programs for CF patients are indicated.     

Bacterial superinfection in human tungiasis

Tungiasis is caused by penetration of the female sand flea Tunga penetrans into the epidermis of its host. It is endemic in many countries in Latin America, the Caribbean and sub-Saharan Africa. Although superinfection is a common clinical observation, the frequency and the pattern of bacterial pathogens associated with tungiasis have never been investigated systematically. We conducted a prospective clinico-bacteriological study with patients living in a shantytown in Fortaleza, capital of Ceará State (Northeast Brazil), where tungiasis is hyperendemic. Swabs were taken from 78 patients with multiple lesions after surgical extraction of the parasite, and the specimens were cultured for aerobic and anaerobic microorganisms. Ninety-nine specimens were investigated for aerobic bacteria, from which 146 pathogens were identified. The most common species were Staphyloccous aureus (35.5%) and various enterobacteriaceae (29.5%). Bacillus sp., Enteroccous faecalis, Streptococcus pyogenes and Pseudomonas sp. were also isolated. Eighty-four anaerobic cultures yielded 20 pathogens: in eight cases we detected Peptostreptococcus sp., in seven cases Clostridium sp., and in five cases non-identifiable gram-negative bacilli. These results show that secondary infection is very common in tungiasis, and caused by a variety of highly pathogenic microorganisms. It is proposed that T. penetrans acts as a foreign body facilitating biofilm formation within the epidermis. To prevent spreading of pathogens to the surrounding tissue and/or the systemic circulation, sand fleas should be surgically extracted immediately after penetration.     

Absence of phosphoglucose isomerase-1 in retinal photoreceptor, pigment epithelium and Muller cells

Macroarray analysis was used to compare equal amounts of cDNA from wild-type and rd/rd (retinal degeneration) mice, collected at P90 when photoreceptor degeneration is virtually complete. A stronger signal for the glycolytic enzyme phosphoglucose isomerase (Gpi1) was observed in the rd/rd sample. Extracellularly, Gpi1 may act as a cytokine, independently described as neuroleukin and autocrine motility factor. Retinal Gpi1 expression was investigated by Northern and Western blot analysis and immunohistochemistry. Double-labelling was performed with antibodies against Gpi1 and calbindin-D, glutamine synthetase, RPE65, calretinin and ultraviolet opsin in order to provide positive cell type identification. Northern and Western blots showed double expression levels per microgram of RNA and protein, respectively, in the rd/rd retina compared with wild-type. However, the total amount of Gpi1 protein per retina was indistinguishable. Gpi1 immunoreactivity was found in ganglion, amacrine, horizontal and bipolar cells, but not in rods, cones, pigment epithelium and Muller cells. This distribution explains why the absolute amounts of Gpi1 protein were not appreciably different between wild-type and the rd/rd phenotype, where rods and cones are absent, whilst the relative contribution of Gpi1 to the total protein and RNA pools differed. Some extracellular immunoreactivity was observed in the photoreceptor matrix around cones in freshly fixed tissue only, which could possibly reflect a role as a cytokine. We propose that glycolysis in Gpi1-negative cells proceeds entirely through the pentose phosphate pathway, creating NADPH at the cost of organic carbon. We hypothesize that the unique metabolic needs of photoreceptors justify this trade-off.     

Marked anemic hypoxia deteriorates cerebral hemodynamics and brain metabolism during massive intracerebral hemorrhage

The present study was undertaken to investigate the influence of imposed anemic hypoxia on cerebral hemodynamics and metabolism in a condition of massive ICH. Two groups of eight dogs, with a target hemoglobin concentration of 12 g/dl in nonanemic and 6 g/dl in anemic group, were included. Before the onset of the insult, anemic group had a significant reduction (p<0.05) in cerebral arteriovenous oxygen content difference (AVDO₂), accompanied with a significant rise (p<0.05) in flow velocity (FV) of the basilar artery and cerebral extraction fraction of oxygen (CEO₂) and a lower brain-tissue lactate clearance than did nonanemic group. Shortly after ICH, both groups displayed significant reductions (p<0.05) in FV, CEO₂ and AVDO₂, and simultaneous rises in arteriovenous lactate concentrations. In nonanemic group, the CEO₂ and AVDO₂ gradually returned after an initial decrease, and then the arteriovenous lactate concentrations slowly decreased. In contrast, anemic group showed progressive reductions in CEO₂ and AVDO₂ associated with persistent rises in arteriovenous lactate concentrations. Consequently, anemic group exhibited significantly greater brain-tissue lactate clearances (p<0.05), occurring at 10 min and 5 h postinjury, than did nonanemic group, although the former had relatively higher levels of CEO₂ up to 3 h postinjury. We conclude that anemic hypoxia modulates a favorable change in cerebral hemodynamics and oxygenation, while it progressively deteriorates after an initial reduction during massive ICH, thus facilitating cerebral anaerobic glycolysis in biphasic periods. These results point to a complex interaction between cerebral hemodynamics, oxygen supply and glycolysis homeostasis upon the addition of anemic hypoxia in severe stress conditions of the brain.     

Determinants of Aerobic Capacity During Exercise Following Complete Repair of Tetralogy of Fallot with a Transannular Patch

Exercise capacity and the causes of its limitation following repair of tetralogy of Fallot have been studied in heterogeneous populations. Study populations have been grouped together regardless of the type of repair and residual hemodynamic abnormalities. To better understand the factors limiting aerobic exercise capacity in patients repaired with a transannular patch, 37 patients with a transannular patch and no residual pulmonary stenosis underwent resting spirometry and treadmill exercise testing. Maximal oxygen consumption and oxygen consumption at anaerobic threshold were measured in all patients to assess aerobic capacity. Patients were subdivided by gender. Resting spirometry measurements tended to be lower in both genders compared to healthy controls but did not correlate with any measurement of aerobic capacity. Maximal oxygen consumption and anaerobic threshold were significantly less in the female than the male population. A quadratic relation between maximal oxygen consumption and age at exercise testing existed for both genders but peaked at an earlier age and was significantly less in the female population. There was a significant negative correlation between maximal oxygen consumption and echocardiographically estimated right ventricular inflow volume index in the female population only. These data suggest that in patients with tetralogy of Fallot repaired with a transannular patch aerobic capacity is limited primarily by cardiac function, but that gender differences are due to noncardiac causes.     

Response of the lens to oxidative-osmotic stress

Both aldose reductase and glutathione reductase share a common cofactor, NADPH. Glutathione reductase is preferentially activated due to its higher affinity for the cofactor. Since NADPH is primarily consumed by glutathione reductase, which in conjunction with glutathione peroxidase detoxifies H₂O₂ present in the aqueous humor, the cataractogenic role of sorbitol-induced osmotic pressure must therefore depend on the availability of NADPH for aldose reductase activity.We examined the response of the lens to an oxidative-osmotic double stress and found that the lens indeed produced 79% less sorbitol and 45% less fructose than a lens subjected to the osmotic stress alone. Morphological studies showed that photo-oxidation damaged the epithelium where the cation pump resided. However, with additional osmotic stress, the swelling of lens fibers in the posterior pole region became more pronounced, and cell nuclei deep in the lens nuclear bow were dislodged to the posterior pole. This could be explained by the slight but significant loss of K⁺ in the lenses under the double stress. Apparently, the slightly decreased ⁸⁶Rb uptake (26% loss), caused by photooxidation could not maintain adequate ionic balance even though the stress from accumulation of sorbitol + fructose was sub-maximal. No disturbance in the glycolytic activity or to the ⁸⁶Rb efflux was found in these lenses, however.     

Glycolytic and gluconeogenic enzyme activities in the hereditary obese-hyperglycemic syndrome and in acquired obesity

Summary Activities of hepatic regulatory glycolytic and gluconeogenic enzymes were assayed in obese-hyperglycemic mice and were found to be elevated over those observed in lean littermates. Qualitatively similar results were obtained when goldthioglucose-obese mice were compared with untreated controls. It therefore appears that these alterations of enzyme activity are not unique to the obese-hyperglycemic syndrome but reflect metabolic disturbances related to obesityper se. The unexpected elevation in the activities of the gluconeogenic enzymes are discussed. Glycolytic enzyme activity assayed in heart and striated muscle revealed no differences between obese-hyperglycemic mice and their lean littermates.

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Aktivität der glykolytischen und gluconeogenetichen Enzyme beim hereditären obes-hyperglyhämischen Snydrom (Mutation obob) und bei erworbener Fettsucht

Zusammenfassung Im Vergleich zu Kontrolltieren wurden in Leberextrakten vonobob-Mäusen erhöhte Aktivitäten der Schlüsselenzyme sowohl der Glykolyse als auch der Gluconeogenese gefunden. Mit Leberextrakten von nach Goldthioglucose-Injektion hyperphagisch und fettsüchtig gewordenen Mäusen wurden ähnliche Resultate erhalten. Es scheint deshalb, daß diese Veränderungen des Profils der Enzymaktivitäten nicht primärer Natur, sondern durch die Fettsucht induziert sind. In Herzund quergestreifter Muskulatur waren bezüglich der Aktivität der glykolytischen Enzymkette keine Unterschiede zwischenobob-Mäusen und deren normalgewichtigen Geschwistern festzustellen.

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Les activités enzymatiques de la glycolyse et de la gluconéogénèse dans le syndrome obésite-hyperglycémie héreditaire (mutation obob) et dans l'obésité acquise

Résumé Les activités des enzymes hépatiques régulateurs de la glycolyse et de la gluconéogénèse ont été étudiées chez la souris obèse-hyperglycémique. Celles-ci furent trouvées plus élevées que chez les animaux nono-bèse d'une même nichée. Des résultats qualitativement semblables ont été obtenus lorsqu'on compare la souris rendue obèse par l'aurothioglucose aux animaux témoins non-traites. Il semblerait donc que ces altérations de l'activité enzymatique ne se produisent pas uniquement dans le cas de syndrome obèse-hyperglycémique, mais reflètent plutôt des désequilibres métaboliques de l'obésitéper se. L'accroissement inattendu des activités des enzymes gluconéogénétiques est discuté. L'activite des enzymes glycolytiques étudiée dans les muscles cardiaque et strié n'a pas révélé de différences entre les souris obèse-hyperglycémiques et les animaux normaux d'une même nichée.

     

Inhibitory Action of Exogenous Adenosine-5′-triphosphate on Glycolysis in Isolated Rat Mast Cells: Significance for Histamine Release

Abstract: Histamine release and lactate content were concomitantly determined in samples of isolated rat mast cells. Histamine release induced by exogenous ATP or compound 48/80 was inhibited by antimycin A (0.2 μM). Glucose (0.60 mM) restored the release induced by compound 48/80 but not that induced by ATP. ATP but not compound 48/80 inhibited the accumulation of lactate in suspensions of mast cells containing glucose (0.60 mM). ATP induced inhibition of lactate accumulation and release of histamine within the same concentration range. However, the time courses for the two processes were different. Antimycin A (0.2 μM) enhanced the accumulation of lactate, an effect which was counteracted by ATP. 0.05 mM ATP or more reduced the lactate accumulation to the same values as those found in the absence of antimycin A. The inhibitory action of ATP on glycolysis may explain the observed inability of glycolytic substrates to restore the ATP-induced histamine release blocked by inhibitors of oxidative metabolism.