Differing time courses between Δlactate and mitochondrial respiration during coronary occlusion and after reperfusion in canine hearts

Summary The present study was designed to clarify whether or not a difference between arterial and venous lactate (gif" alt="Delta" align="BASELINE" BORDER="0">lactate) levels is useful for evaluation of mitochondrial function in ischemia-reperfused myocardium. In the first experiment, 12 dogs were divided into 2 groups: 10-min occlusion of the left anterior descending coronary artery (LAD) followed by 10-min reperfusion, or 30-min occlusion followed by 40-min reperfusion, were performed. The lactate levels in the femoral artery and the great cardiac vein were measured enzymatically. gif" alt="Delta" align="BASELINE" BORDER="0">Lactate was reversed immediately after occlusion. Ten min and 20 min were required for the recovery of gif" alt="Delta" align="BASELINE" BORDER="0">lactate in the 10-min-occlusion with 10-min-reperfusion, and 30-min-occlusion with 40-min-reperfusion groups, respectively. In the second experiment, 36 dogs were divided into 6 groups: 10-min occlusion of LAD; 10-min occlusion with 10-min reperfusion; 30-min occlusion; and 30-min occlusion with 10-, 20-, or 40-min reperfusion were performed. Mitochondria from normal and occluded or reperfused areas were prepared, and the respiratory function of the mitochondria was measured polarographically. No significant decreases in the mitochondrial function were observed in the 10-min-occlusion, and 10-min-occlusion with 10-min-reperfusion groups. On the other hand, respiratory function of mitochondria was impaired by 30-min occlusion and was not improved by 10- or 20-min reperfusion. Significant recovery in the mitochondrial function was observed after 40-min reperfusion. That is, differing recovery time courses between gif" alt="Delta" align="BASELINE" BORDER="0">lactate and the mitochondrial function were observed.     

Antiserotonergic inhibition of calcitonin-induced increase of β-endorphin,ACTH, and cortisol secretion

Summary In a previous study we observed that calcitonin increases gif" alt="beta" align="MIDDLE" BORDER="0">-endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma gif" alt="beta" align="MIDDLE" BORDER="0">-endorphin, ACTH and cortisol were estimated every 30min from – 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at – 30 min and calcitonin i.v. at time 0. gif" alt="beta" align="MIDDLE" BORDER="0">-endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 gif" alt="mgr" align="MIDDLE" BORDER="0">g/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time – 30 did not alter the response of gif" alt="beta" align="MIDDLE" BORDER="0">-endorphin, ACTH and cortisol to calcitonin (infused at time 0).Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion.     

Comparison of the size of neuronal and non-neuronal histamine pools in the brain of different rat strains

Summary The size of the neuronal and non-neuronal histamine pools in the brain of three different strains of rats was measured by assuming that the gif" alt="agr" align="BASELINE" BORDER="0">-fluoromethylhistidine-induced maximal decrement of histamine represents the size of the neuronal pool. Although the total histamine levels in the brain showed a considerable interstrain variation, no significant interstrain difference was observed in the neuronal histamine level. These results suggest that the size of the neuronal histamine pool in the brain is relatively stable, whereas the size of the non-neuronal histamine pool is variable.     

Monoamine oxidase-B inhibition: a comparison of in vivo and ex vivo measures of reversible effects

Summary A behavioural test involving potentiation of the effects of an acute injection of gif" alt="beta" align="MIDDLE" BORDER="0">-phenylethylamine (10 mg kg^–1 i.p.) was used to assess the time-course of type-B MAO inhibition after administration of (–)deprenyl (5 mg kg^–1 i.p.) and of MD 240928 (20 mg kg^–1 i.p.) respectively. Potentiation of the effects of gif" alt="beta" align="MIDDLE" BORDER="0">-phenylethylamine was observed 1 h after injection of (–)deprenyl or MD 240928. This effect was still evident 120 h after administration of (–)deprenyl but not 24 h after administration of MD 240928. Comparisons of ex vivo estimates of MAO activity yielded a corresponding time-course for the recovery of this enzyme. The extent of MAO inhibition required for potentiation of the effects of gif" alt="beta" align="MIDDLE" BORDER="0">-phenylethylamine was inferred from a comparison of the behavioural test results and the ex vivo MAO activity observed after (–)deprenyl administration. These comparisons indicate a significant underestimation of MD 240928-induced MAO inhibition using ex vivo measures. This underestimation is interpreted as evidence fordilution effects in the ex vivo assay of MAO inhibition. The potentiation of effects of gif" alt="beta" align="MIDDLE" BORDER="0">-phenylethylamine under the present conditions is proposed as a useful and simple test for effects of reversible type-B MAO inhibitors.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid gif" alt="agr" align="BASELINE" BORDER="0">-glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral gif" alt="agr" align="BASELINE" BORDER="0">-glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a gif" alt="ldquo" align="MIDDLE" BORDER="0">high-uptakegif" alt="rdquo" align="MIDDLE" BORDER="0"> form of acid gif" alt="agr" align="BASELINE" BORDER="0">-glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

Adult-onset rod disease with abundant intranuclear rods

Summary The third case of adult-onset rod disease (nemaline myopathy) with abundant myofibrillar as well as intranuclear rods is described. The 61-year-old woman suffered from progressive weakness of proximal extremities and of the neck, mimicking polymyositis. Muscle biopsy revealed a striking myopathic pattern, with intranuclear rods occurring in 31% of the fibres. On light and electron microscopy and by immunohistochemical study, the rods differed from myofibrillar rods. The absence of gif" alt="agr" align="BASELINE" BORDER="0">-actinin in intranuclear rods suggests an enhanced readiness of actin filaments to bind to diverse proteins, instead of overproduction of gif" alt="agr" align="BASELINE" BORDER="0">-actinin as the pathogenetic basis of the rod formation.     

Fatal intoxications in Denmark following intake of morphine from opium poppies

Summary In Denmark it is legal to grow opium poppies for the production of poppy seeds and until 1986 for decoration purposes, too. Danish poppy capsules contain 0.3–5 mg morphine per capsule and the content of morphine in opium exuded from the capsules may amount to 24%. This has resulted in misuse as both fresh and dried poppy capsules have been used for the production of gif" alt="ldquo" align="MIDDLE" BORDER="0">opium teagif" alt="rdquo" align="MIDDLE" BORDER="0">. During the period 1982–1985, seven casualties occurred among drug addicts in Denmark which were solely or partly caused by these opium poppies.     

Decreased antibody-dependent cellular cytotoxicity in minimal change nephrotic syndrome

Secondary IgG response to a tetanus toxoid booster and in vitro measurement of immunoglobulin synthesis, antibody-dependent cellular cytotoxicity (ADCC) and gif" alt="gamma" align="MIDDLE" BORDER="0">-interferon (IFN-gif" alt="gamma" align="MIDDLE" BORDER="0">) production were evaluated in 20 healthy controls and in 17 children with minimal change nephrotic syndrome (MCNS), during the acute nephrotic phase and 6 months after remission. Defective responses were observed in all but IFN-gif" alt="gamma" align="MIDDLE" BORDER="0"> production during the acute nephrotic phase; these improved with disease remission. There was a significant correlation between decreases in vitro IgG production and ADCC reaction. These data indicate that defective antibody production is associated with decreased ADCC during the acute nephrotic phase of MCNS.     

Only activated but not non-activated presynaptic α2-autoreceptors interfere with neighbouring presynaptic receptor mechanisms

Summary Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic gif" alt="agr" align="BASELINE" BORDER="0">₂-autoreceptors of effects mediated by presynaptic opioid gif" alt="kappa" align="BASELINE" BORDER="0">- and adenosine A₁-receptors requires activation of the gif" alt="agr" align="BASELINE" BORDER="0">₂-receptors. The slices were preincubated with ³H-noradrenaline and then superfused with medium containing desipramine 1 gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz.The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca²⁺-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l or yohimbine 0.3 gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l. Ethylketocyclazocine (EK; 0.1–10 nmol/l) and R-(–)-N⁶-phenylisopropyladenosine (PIA; 1–1,000 nmol/1) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. — The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca²⁺ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine.The results demonstrate that there is no gif" alt="agr" align="BASELINE" BORDER="0">₂-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic gif" alt="agr" align="BASELINE" BORDER="0">₂-adrenoceptor does not interfere with presynaptic opioid gif" alt="kappa" align="BASELINE" BORDER="0">- and adenosine A₁-receptor mechanisms. It is only when the autoreceptor is activated by released noradrenaline that it attenuates neighbouring presynaptic receptor mechanisms, and this attenuation is removed by gif" alt="agr" align="BASELINE" BORDER="0">₂-adrenoceptor antagonists.Send offprint requests to N. Limberger at the above address     

Characteristics of β-endorphin-induced histamine release from rat serosal mast cells Comparison with neurotensin,dynorphin and compound 48/80

Summary Rat peritoneal mast cells were exposed to the neurohormone and basic opioid peptide gif" alt="beta" align="MIDDLE" BORDER="0">-endorphin. gif" alt="beta" align="MIDDLE" BORDER="0">-Endorphin induced a dose-dependent release of histamine from the mast cells. A significant histamine release was found at 5 gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l of gif" alt="beta" align="MIDDLE" BORDER="0">-endorphin and maximal release (35% of total) at 20 gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l. The histamine release process was very rapid and terminated within 30 s at 37°C, and in this sense is very similar to the histamine release induced by compound 48/80 or neurotensin. The histamine release was temperature-dependent showing an optimum release around 30°C, and it was independent of available extracellular calcium, but was inhibited in the presence of high extracellular calcium concentrations. Naloxone, only in very high concentrations (10 mmol/l), inhibited the release, and the very same concentration also inhibited the neurotensin — as well as the compound 48/80-induced histamine release. Cromoglycate and benzalkoniumchloride, a 48/80 antagonist, both produced a progressive dose-dependent inhibition of gif" alt="beta" align="MIDDLE" BORDER="0">-endorphin-, neurotensin- as well as compound 48/80-induced histamine release. Taken together, the findings indicate that the opioid peptide gif" alt="beta" align="MIDDLE" BORDER="0">-endorphin induces a selective, energy-dependent release of histamine from peritoneal rat mast cells. The pattern of release has much in common with that of compound 48/80 and other basic peptides, such as neurotensin and substance P. In addition this pattern of release is similar to that induced by dynorphin. Send offprint requests to Anita Sydbom at the above address