Titration of human brain monoamine oxidase-A and-B by clorgyline andl-deprenil

Summary The interaction of clorgyline andl-deprenil with the-A and-B forms of human brain monoamine oxidase (MAO) has been studied. Both compounds inhibit cerebrocortical MAO in a manner consistent with a suicide inactivation of the enzyme. The interaction of clorgyline with the-A form of the enzyme appears to take place almost entirely at specific binding sites, and the conditions required for this inhibitor to titrate the concentrations of MAO-A have been elucidated.l-Deprenil has also been used to titrate the concentration of the-B form of MAO in cerebrocortical homogenates, but there is a considerable degree of non-specific binding of this compound. The two inhibitors have been used to titrate the concentrations of the two enzyme forms in frontal cortex homogenates from different age groups. There was a significantly higher MAO-B activity for the age range 73–95 years than for the age range 2–63 years. No significant differences between the two age groups were found for MAO-A. The activity of MAO-A in the samples correlated very well with the concentration of this enzyme form. Titration of the B-form of the enzyme withl-deprenil indicated an increased enzyme concentration with age, although other factors, such as the non-specific binding of this compound, could contribute to this effect.     

Effects of enkephalins and two enzyme resistant analogues on monoamine synthesis and metabolism in rat brain

Summary Methionine-enkephalin and leucineenkephalin, administered into the lateral ventricle of intact rats, increased the accumulation of DOPA by a naloxone-sensitive mechanism in different brain regions after inhibition of the aromatic l-amino acid decarboxylase. Because of the rapid enzymatic degradation of both enkephalins large doses (500 g) were required to enhance brain catecholamine synthesis. The two enzyme resistant enkephalin analogues d-Ala²-methionine enkephalin amide (DALA (4–256 g) and FK 33-824 (0.003–1 g) also increased the synthesis of DOPA, dose-dependently and by naloxone-sensitive mechanisms, but at much lower dosage level. The enkephalins markedly enhanced the brain tyrosine concentration but this effect was not antagonized by naloxone, probably because the enzymatic cleavage releases tyrosine from the administered peptides. In contrast, neither DALA nor FK 33-824 increased the brain tyrosine concentration. The formation of 5-HTP and the brain tryptophan concentration were also increased by the enkephalins, although these effects were not blocked by naloxone. The enkephalin analogues, however, enhanced the formation of 5-HTP and the brain tryptophan concentration by naloxonesensitive mechanisms. All four peptides accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine after inhibition of monoamine synthesis. The results suggest that endogenous enkephalins, through the activation of opiate receptors, are involved in the short-term regulation of central monoaminergic systems.Preliminary data were presented at the Nobel Symposium 42, Principles for the Central Regulation of the Endocrine System, Stockholm, June 8–10, 1978, and at the 4th International Catecholamine Symposium, Asilomar Conference Center, Pacific Grove, California, September 17–22, 1978     

The adjuvant effect of tuberculin in experimental sensitization to merthiolate

Summary When guinea pigs were sensitized to tuberculin by exposure to complete Freund's adjuvant the size of the intradermal PPD test was positively correlated to the body weigth of the animal. Old Tuberculin showed stimulating effect in a subsequent sensitization to merthiolate (thimerosal). The high frequency of delayed cutaneous allergy to merthiolate in the Swedish population is probably explained by sensitization through intradermal testing with tuberculin containing merthiolatc as a preservative.

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Zusammenfassung Bei Meerschweinen, die mit Hilfe von Freunds Adjuvant gegen Tuberculin sensibilisiert wurden, konnte eine Korrelation zwischen der Größe des Intracutantests und dem Körpergewicht der Tiere festgestellt werden. Old Tuberculin zeigte in einem darauffolgenden Sensibilisierungsversuch mit Merthiolat einen stimulierenden Effekt auf die allergische Reaktion gegen Merthiolat. Die hohe Frequenz von allergischen cutanen Spätreaktionen gegen Merthiolat in der schwedischen Bevölkerung ist wahrscheinlich als Sensibilisierung durch Intracutantest mit Tuberculin, das als Konservierungsmittel Merthiolat enthält, zu erklären.

     

The use of non-invasive probes and (13)C nuclear magnetic resonance spectroscopy to assess liver metabolism in humans

Two new methods to assess liver metabolism in humans will be discussed, non-invasive probes and (13)C NMR (nuclear magnetic resonance) spectroscopy. Hepatic UDP-glucose and alpha-ketoglutarate can be sampled by non-invasive probes. This method has been used to quantitate the contribution of the indirect pathway to liver glycogen formation and to estimate relative flow rates and carbon exchange in the Krebs cycle. (13)C NMR spectroscopy has been developed to measure liver glycogen concentrations in vivo. Using this method in combination with measurements of whole body glucose production during fasting, the contribution of gluconeogenesis has been calculated.     

Quality of life: A model for evaluating Health for all. Conceptual considerations and policy implications

Summary The potential of the quality of life (QoL) concept lies in its basically positive meaning and interdisciplinary acceptance. This can be used when the Public Health sector tries to develop health into a resource concept, as is the intention of the WHO Health For All Strategy. Out of different scientific views on QoL this paper synthetises a theoretical framework of QoL and describes how this concept can be used in practice when evaluating the health resources of a population.

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Zusammenfassung Das Potential des Begriffs Lebensqualität liegt in der grundliegenden positiven Bedeutung und querwissenschaftlichen Anerkennung. Dieses kann von Nutzen sein, wenn das öffentliche Gesundheitswesen versucht, Gesundheit als einen Hilfsmittelbegriff zu entwickeln, welches das Ziel der Strategien von Gesundheit für Alle der WHO ist. Diese Abhandlung schafft einen theoretischen Rahmen aus verschiedenen wissenschaftlichen Anschauungen und beschreibt wie dieser Begriff praktisch in der Auswertung der Gesundheit der Bevölkerung angewendet werden kann.

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Résumé Le concept de qualité de vie a l'avantage de présenter à la base un sens positif et aussi une acceptation interdisciplinaire. Cela peut se révéler utile à un moment où la science de la santé publique essaie de développer la santé selon un concept de moyens et cela constitue un but parmi les directives de Santé pour Tous énoncés par l'OMS (Organisation Mondiale de la Santé). Cette présentation résume un cadre théorique concernant le concept de la qualité de vie, émanant de différentes interprétations scientifiques et montre aussi comment le concept peut être applicable à l'évaluation des ressources de santé dans une population.

     

Pre-operative and post-operative radiotherapy and rectal cancer

The appropriate role for additional radiotherapy in patients with resectable rectal cancer is not yet settled. Irradiation has been considered by surgeons and radiotherapists as superfluous since no effect on survival has been shown. However, numerous trials have demonstrated that perioperative radiotherapy decreases an often high local recurrence rate while others believe it has a definite place in routine management. Several surgeons have, on the contrary, claimed that a skilled surgeon compared to a less skilled surgeon, will get the same acceptably low local recurrence rates. Since we will probably never have a randomized trial comparing good and bad surgeons, this argument cannot be settled. A further obstacle arises in the difficulty of persuading surgeons to organize their routine work so that it is performed in an optimal way by those specializing in this field. The question also arises whether radiotherapy should be delivered pre-operatively, postoperatively or as a sandwich technique, i.e., both pre-operatively and postoperatively. According to radio-biological considerations and results from reported trials, the best effect on local tumor control has been achieved using pre-operative radiotherapy.

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Resumen Aún no se ha defindo la indicación apropriada para radioterapia adicional en pacientes con cáncer rectal. La irradiación ha sido considerada como superflua por cirujanos y radioterapeutas, puesto que no se ha demostrado efecto sobre la sobrevida. Sin embargo, numerosos ensayos clínicos han demostrado que la radioterapia perioperatoria disminuye la que con frecuencia es una elevada tasa de recurrencía local, mientras ostros creen que tiene un lugar definido en el manejo rutinario. Por el contrario, varios cirujanos han planteado que un cirujano hábil comparado con uno menos hábil, logra las mismas aceptables tasas de recurrencia, alg que jamás se ha decidido, puesto que nunca habremos de realizar ensayos comparando buenos cirujanos con malos cirujanos. Un obstáculo adicional surge de la dificultad en cuanto a persuadir a los cirujanos de organizar su trabajo rutinario de tal manera que sea realizado en forma óptima por aquellos que se especializan en este campo. También ha surgido el interrogante sobre si la radioterapia debe ser administrada preoperatoriamente, postoperatoriamente o como técnica de sandwich, o sea tanto pre como postoperatoriamente. Según consideraciones radio-biológicas y los resultados de los ensayos clínicos, el mejor efecto sobre el control local del tumor ha sido logrado mediante el uso de radioterapia preoperatoria.

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Résumé La place de la radiothérapie adjuvante chez les patients ayant un cancer du rectum reste discutée. La radiothérapie est estimée superflue par certains chirurgiens et radiothérapeutes car aucun bénéfice n'a eté clairement démontré en ce qui concerne la survie. De nombreux essais cliniques ont indiqué, cependant, que la radiothérapie périopératoire diminuait le taux habituellement élevé des récldives locales, et certains estiment que la radiothérapie a toujours une place dans le schéma thérapeutique. D'autres, au contraire, croient que la quialité et l'expérience de l'opérateur influencent directement le taux de récidives, et équivalent l'efficacité de la radiothérapie. Puisqu'il est peu probable qu'on réalise une étude randomisée entre les bons et les mauvais chirurgiens, on ne peut régler cette querelle. Un autre obstacle incontournable semble être de persuader les chirurgiens d'organiser leur travail de façon à ce que cette chirurgie soit faite par des spécialistes. Le meilleur moment pour réaliser la radiothérapie (préopératoire, postopératoire, ou les deux) reste à déterminer. Selon les données radiobiologiques et les résultats des essais contrôlés, il semble que le meilleur contôle sur les récidives locales soit obtenu par la radiothérapie préopératoire.

     

Evaluation of micromotion in cemented vs uncemented knee arthroplasty in osteoarthrosis and rheumatoid arthritis. Randomized study using roentgen stereophotogrammetric analysis

Twenty-four patients (25 knees) with osteoarthrosis (OA) and 19 patients (20 knees) with rheumatoid arthritis (RA) were operated with bi-tricompartmental knee arthroplasty. The patients were randomized to cemented or cementless fixation of the tibial component. The fixation of the tibial components was examined with roentgen stereophotogrammetric analysis (RSA) up to 24 months after operation. The following parameters representing tibial component micromotion were measured: (1) maximum migration of the prosthetic edge (maximum total point motion, MTPM); (2) distal migration of the prosthetic center (subsidence); (3) maximum proximal movements of the prosthetic edge ("lift-off"); and (4) prosthetic rotations, corresponding to internal/external rotation, adduction/abduction, and forward/backward tilt of the tibial component. All prostheses displayed significant micromotions, which tended to decrease 3-6 months after the operation. The average migration after 2 years, when measured as maximum single axis rotation, and MTPM were about 0.9 degrees-1.5 degrees and 1.0-1.5 mm, respectively, in all four groups. There were no statistically significant differences between cemented and cementless prostheses in either the OA or the RA group. The fixation in the RA patients did not significantly differ from that of the OA patients, perhaps because the RA patients had lower weight and were living a more sedentary life.     

Embryotoxicity of chromium: Distribution in pregnant mice and effects on embryonic cells in vitro

The embryonic and fetal uptake of Na₂ ⁵¹Cr₂O₇(Cr VI) was about 10 times higher than that of ⁵¹CrCl₃(Cr III) when these two were given in the same doses i. v. to pregnant C57BL mice. On day 13 of gestation, embryonic concentrations were 12% (Cr VI) and 0.4% (Cr III) of the maternal serum concentration 1 h after injection to the mother. After injection of Cr(III) radioactivity was not detectable in embryonic structures in early gestation, when autoradiographic techniques were used. In late gestation, administration of both forms of Cr resulted in an accumulation in the calcified areas of the fetal skeleton. The radioactivity after administration of Cr(VI) may represent Cr(III) after reduction in the tissues. When added to chick limb bud mesenchymal cells in vitro, Cr(VI) inhibited chondrogenesis at a concentration of about 0.1 g/ml medium, which is around 1/10 of the embryonic concentration achieved after giving teratogenic doses to pregnant mice. Cr(III) on the other hand did not show any overt cytotoxicity even at 15 g/ml ( 500 times higher than the in vivo embryonic concentrations after teratogenic doses). Especially Cr(III) accumulated strongly in the visceral yolk sac, probably after binding to and transport by maternal serum proteins. The possibilities that Cr(III) excerts its teratogenic action by inhibiting embryotrophic nutrition is discussed.     

Glutathione conjugation and DNA-binding of ({+/-})-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and ({+/-})-7{beta},8{alpha}-dihydroxy-9{alpha},10{alpha}-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in isolated rat hepatocytes

Isolated rat liver hepatocytes, previously depleted of glutathione(GSH) by treatment with diethylmaleate, were allowed to incorporate[³H]glycine into their GSH. Incubation of ³H-labelled cellswith ¹⁴C-labelled (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene((±)-BP-7,8-dihydrodiol) or (±)7ß,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]-pyrene(()-BPDE) revealed the formation of double labelled products.This together with evidence from amino acid analysis indicatesformation of GSH-conjugates of the highly carcinogenic BP-derivatives.Incubation of hepatocytes isolated from 3-methylcholanthrene(MC) treated rats with ³H-labelled (±)-BP-7,8-dihydrodiolor (±)-BPDE resulted in binding of radioactivity to DNA.Reduction of the intracellular level of GSH to 40% of the normallevel resulted in an approximate 2-fold increase in the DNA-bindingof either substrate. In addition there was a concurrent decreasein the amount of GSH-conjugates formed. These data clearly demonstratethat GSH participates in conjugation reactions with carcinogenic(±)-BP-7,8-dihydrodiol and (±)-BPDE and that theintracelluilar level of GSH is important in preventing reactiveintermediates from reacting with the DNA in intact cells.     

A COMPARISON BETWEEN AGAR GEL ELECTROPHORESIS and CSF SERUM QUOTIENTS of IgG and ALBUMIN IN NEUROLOGICAL DISEASES

CSF and serum was obtained from 216 patients with neurological or psychoneurotic symptoms and the concentrations of albumin and IgG were immunologically determined. The IgG/albumin index, calculated as the quotient of the CSF/serum ratios of IgG and albumin was compared with electrophoresis on agar gel. In "normal" cases, the IgG/albumin index was between 0.26-0.66. Pathological electrophoresis, i.e. with two or more IgG bands in the gamma globulin region was found in 85 per cent of the MS patients; in 29 per cent of the patients with a possible demyelinating disease; in 41 per cent of patients with CNS infection; and in 4 per cent of patients with other neurological disorders; whereas an increased IgG/albumin index ( greater than 0.66) was found in 88 per cent of the MS patients; in 43 per cent of the patients with a possible demyelinating disease; in 50 per cent of the patients with CNS infection; in 11 per cent of patients with immunological disorders; and in 18 per cent of patients with other neurological diseases. The increase of the IgG/albumin index was sometimes moderate (0.67-0.90), except in patients with MS, syphilis and other CNS infections, where a pathological electrophoresis combined with an IgG/albumin index above 1.0 was found to be a valuable support for the clinical diagnosis.