Allergic nephritis prevention by prostaglandins E2 and F2 alpha.

The effects of prostaglandins E2 and F2 alpha on renal lesions induced by an anti-rat serum were investigated in rats. It was found that these prostaglandins, administered concomitantly with the antiserum, were able to prevent or remarkably attenuate these lesions. A very interesting finding is that, after prostaglandin administration, no or insignificant morphological alterations of the kidney occurred, in spite of the fact that its mononuclear cell infiltration was somewhat persistent. Hence, in addition to the known effects of these prostaglandins on the immune response components, the blockade of cellular receptors for immunoglobulins is to be considered as a main mechanism in explaining their preventive action in allergic nephritis.

Endocrine mechanisms in the pathogenesis of essential hypertension. II. Interference of prostaglandins with the blood pressure elevating and lowering systems.

Beside exerting an impressive variety of physiological and pharmacological actions on different systems of the organism, prostaglandins (PGs) may also be main factors in the pathogenesis of essential hypertension. Their role in this process is mostly explained by their multivalent interference with the tissue hormones which regulate the vascular tone and the water-sodium balance. In this paper a discussion regarding the results of a widespread research and the growing literature dealing with this interference is made on the basis of a personal point of view. The present paper is a continuation of a previous one on this topic.

The metabolism of the preserved heart. I. Does lactate properly reflect the functional state of the preserved heart? Part one.

Since there are controversial data and opinions on the use of lactate as a viability test for preserved hearts, investigations were carried out of the variations of lactate and pyruvate amounts in the perfusion fluid during hypothermic preservation of canine hearts by means of a perfusion fluid containing amino acids in "cytoplasmic" concentrations. These variations were interpreted in connection with the changes in the coronary perfusion flow during storage and the functional performances of the preserved hearts during long periods of subsequent ex vivo functional testing. Likewise, investigations of the ability of the myocardial mitochondria to oxidize in vitro lactate and pyruvate at low temperature levels were performed in order to explain the nature of the impairment in using these metabolic substrates during preservation and of the functional cardiac disturbances after resuscitation. The investigations have led to the conclusion that lactate should not be used as the sole index of heart storage efficiency and that it gains in significance only when a high myocardial lactate production is associated with a progressively increasing resistance in the coronary vasculature during preservation. The possible metabolic significance of the results obtained in these investigations are amply discussed.

Endocrine mechanisms in the pathogenesis of essential hypertension. III. Special reference on the interrelations between the prostaglandin and kallikrein-kinin systems.

In the present paper, the involvement of the renal kallikrein-kinin system in the pathogenic mechanism of essential hypertension is discussed in the larger framework of the complex hormonal actions of prostaglandins (PGs), catecholamines, renin and angiotensins in the long-term control of arterial blood pressure and sodium metabolism. An attempt is also made to emphasize the role of the cerebral renin-angiotensin system in this pathogenic mechanism. To better understand the problems raised in this paper, the concomitant consultation of two previously published papers [88], [89] is recommended.

Changes in the activities of blood and tissue adenosinetriphosphatase and lactate dehydrogenase after exposure to 60Co gamma-rays in association with some drug treatments.

Experiments in rats exposed to a moderate dose of 60Co gamma-radiation and treated with either cystamine, AET, complamin or alpha-methyldopa suggested that the efficiency of a radioprotective drug might be related to its ability to maintain low levels of ATP-ase activity in blood and tissues after irradiation.

Heart preservation by means of a complex artificial perfusion fluid.

Heart storage for different time intervals of up to 72 hours was carried out using a complex perfusion fluid elaborated according to a personal new theoretical concept. The recovery of the hearts stored by means of this fluid was practically integral as shown by the measurements and recordings of several cardiac functional parameters within a period of 5-7 hours of ex vivo functional testing subsequent to the storage. This fluid was also found to allow repeated heart storages for 24 hours alternating with efficient ex vivo functional testing for periods of 5-7 hours. Such performances in heart preservation were not yet reported elsewhere. This fluid was thought to allow an efficient ex vivo heart conditioning before transplantation by immunological or pharmacological treatments throughout repeated short-term or long-term alternating storages and recoveries.

Dynamics of the changes in the cerebral amounts of cyclic AMP and some prostaglandins during cobalt-60 gamma-radiation-induced brain edema.

The total amounts of cyclic AMP (cAMP), prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in cerebra have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rads) or a unique lethal dose (750 rads) of cobalt-60 gamma-radiation. The experimental findings indicate that this radiation (i) results in an abrupt short-lasting increase in the amount of cerebral cAMP after a 500 rad-irradiation and a progressive long-lasting increase in its amount after a 750 rad-irradiation, and (ii) induces no change in the normally, existing correlation between cerebral PGE1 and cAMP, but affects deeply the normally existing correlation between cerebral PGF2alpha and cAMP. These biochemical alterations generally parallel the evolution of the radiation-induced brain edema.

Tissular cycli AMP levels after treatments with prostaglandins.

In this study both prostaglandin A1 (PGA1) and prostaglandin F2alpha (PGF2alpha) have been shown to be effective long-lasting stimulators of the cyclic AMP (cAMP) synthesis in the liver, intestinal mucosa and brain, whereas prostaglandin E1 (PGE1) was found to have a similar effect on the cerebral cAMP synthesis and a dissimilar effect (decrease) on the hepatic one. A lack of sensitivity of the intestinal mucosa cAMP to PGE1 was also observed.

Endogenous biochemical factors affecting the efficiency of some radioprotective or radiosensitizing drugs: sulfhydryl groups and lipid peroxides.

The changes in the amounts of blood and tissular sulfhydryl groups and lipid peroxides were investigated in lethally gamma-irradiated rats treated with cystamine, AET (radioprotectors) or alpha-methyl-dopa (a radiosensitizer). The results of experiments revealed the following findings: 1. The ionizing radiation generally causes increases in the levels of tissular sulfhydryl groups and lipid peroxides (excepting the hepatic levels of these compounds). 2. AET and, especially, cystamine are able to reverse the radiation-induced changes in the tissular amounts of sulfhydryl groups and lipid peroxides; there are close relationships between this effect (including its intensity and extension) and the radioprotective action of these drugs. 3. In spite of its radiosensitizing action, alpha-methyl-dopa induces approximately similar changes in the tissular amounts of sulfhydryl groups and lipid peroxides, suggesting that biochemical processes other than an excessive yield of free radicals are also involved in radiosensitivity.

Dynamics of the changes in the tissular levels of cyclic AMP after cobalt-60 gamma-irradiation.

The total amounts of cyclic AMP in liver, brain and intestinal mucosa have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rd) or a unique lethal dose (750 rd) of cobalt-60 gamma-radiation. This radiation, even in a lethal dose, was found to induce no significant changes in the hepatic levels of cAMP. In contrast, an abrupt short-lasting increase in the levels of cAMP was observed in brain and intestinal mucosa after a 500-rd-irradiation, and a progressive long-lasting increase in its levels in the intestinal mucosa and, especially, in the brain was found after a 750-rd-irradiation. It is concluded that these organs contain different cAMP systems, which would explain, at least in part, their dissimilar responses to the ionizing rays.

Comparative study of the gamma-radiation-induced changes in the tissular levels of acyclic and cyclic adenosine phosphates.

Periodical measurement of total adenosine phosphates and cAMP in liver, intestinal mucosa and brain carried out in rats after irradiation with either 500 rads or 750 rads generally revealed high intratissular levels of these compounds, suggesting both a stimulated cellular synthesis and an abnormal redistribution in different tissues. The most interesting findings were those regarding the brain considering their close relationships with the clinical evolution of the animals and other previously described biochemical observations.

The protective action of prostaglandins E2 and F2 alpha on antibody induced myocardial lesions: morphological studies.

Optic and electron microscopical investigations as well as histochemical investigations were performed in rats which have intraperitoneally received an anti-rat serum together with either PGE2 or PGF2 alpha, in order to study the effect of these prostaglandins on antibody-induced myocardial lesions. PGE2 and, especially, PGF2 alpha were found to considerably prevent the myocardium against these lesions (mononuclear cell infiltration, interstitial and intracellular hyperhydration, disintegration of myofibrils, vacuolization of sarcoplasmic reticulum, mitochondrial swelling and degradation, lysosomal activation and disruption of myocardial sarcolemmas and blood capillary membranes). Their protective actions were revealed in animals killed 24 h and 6 days after the administration of anti-rat immunoglobulins.

Comparative experimental study of myocardial energy metabolism during ventricular workload induced by chronic stenoses of ascendent aorta and pulmonary artery.

In this paper, an attempt was made to describe the alterations of the myocardial energy metabolism following moderate stenoses of aorta or pulmonary artery. Biochemical investigations regarding the main high energy phosphates and a large series of dehydrogenases in the myocardium of the overloaded ventricles have revealed the following facts: (1) the myocardial CP-CPK system appears to be more labile than the myocardial AMP-ATP system in response to a ventricular overload; (2) the changes in the amounts of myocardial high energy phosphates seem to be more important in the right chronic cardiac overload than in the left one; (3) before the overloaded ventricle becomes insufficient, the myocardial dehydrogenase system elicits no alteration, suggesting that the oxidative phosphorylation is not affected; (4) there is a closer relationship between the coronary flow and pressure and the myocardial energy metabolism than that existing between this metabolism and the tension of the myocardial fibres following a persistent increase in the systemic arterial resistance.

Early biochemical disorders in the hindlimb muscles following femoral artery stenosis in dogs: protein and electrolyte metabolism.

Investigations regarding the metabolism of proteins and electrolytes in the hindlimb skeletal muscles were carried out in dogs with a moderate unilateral stenosis of femoral artery (reduction of almost 65% of its lumen) early after surgery. The results of these investigations were compared with those obtained by investigating the correspondent skeletal muscles of the opposite hindlimb. This comparison has revealed the following findings: (1) ischemia in a moderate form early elicites a remarkable K+ accumulation (not a K+ loss!) in the skeletal muscle without any change in the concentrations of other cations; (2) in this instance, an activation of muscle proteases and peptidases occurs meading to an important production of histamine, which is detectable in appreciable amounts in the ischemic muscle and, especially, in its effluent blood. On the basis of the findings reported in this study, as well as on the basis of our previous findings on the same experimental model, an approach to correlate and explain the early muscular metabolic disturbances induced by a moderate ischemia is discussed. In addition, it is to be pointed out that the presence of histamine in increased amounts in the effluent blood of a skeletal muscle mass could be a reliable laboratory parameter revealing an incipient muscle ischemia.

Early biochemical disorders in hindlimb muscles following femoral artery stenosis in dogs: oxidative metabolism.

An approach to explain the early metabolic disturbances induced by a moderate ischaemia on the basis of comparative biochemical investigations concerning the oxidative metabolism in the skeletal muscles, is the object of the present paper. These investigations have revealed the following findings: (i) during a slight ischaemia the skeletal muscle maintains its ability to oxidize in vitro lactate and exhibits an increased activity in oxidizing pyruvate, succinate and L-glutamate, and (ii) the stores of adenosine and ATP are depleted and an important accumulation of inorganic phosphate, accompanied by a remarkable activation of phosphatases, occurs in the ischaemic muscle, while no significant changes in the ATPase and creatine phosphokinase activities and in the amount of AMP, ADP and creatine phosphate are detectable in this muscle.

Effects of cobalt-60 gamma-irradiation in association with prostaglandin E1 treatment on the cyclic AMP levels of some radiosensitive tissues.

The amounts of cyclic AMP in brain, liver and intestinal mucosa have been measured in rats, at constant intervals, up to 18 days after whole-body exposure to either a unique moderate dose (500 rd) or a unique lethal dose (750 rd) of cobalt-60 gamma-radiation in association with a preliminary intraperitoneally treatment with prostaglandin E1 (5 microgram/100 g body weight/day) during five days. The amounts of tissular cyclic AMP in these two experimental groups were compared with those obtained from control groups identically irradiated or treated with prostaglandin E1. The effects of gamma-irradiation and prostaglandin E1 treatment on the cyclic AMP levels were found to be quite specific in these organs, suggesting that they contain different adenyl cyclase-cyclic AMP-phosphodiesterase systems: a cerebral system which is influenced by both gamma-radiation and prostaglandin E1, a hepatic system which is "radioresistant" and an intestinal system which is not influenced by prostaglandin E1. When associated with gamma-radiation, this prostaglandin is capable, on the one hand, to annul the "radioresistance" of the hepatic cyclic AMP system and, on the other hand, to annul the "radiosensitivity" of the intestinal cyclic AMP system.