The physico-chemical properties of tumor cells with different metastatic potential.

Authors investigated the total and surface sialic-acid content and elpho mobility of Lewis lung lines with low (LLT-parent) and high (LLT-HH selected) metastatic capacity. They pointed out, that the total and surface sialic-acid content of LLT-HH primary tumor cells is higher than in the cells of the LLT line. Despite the increase of sialic-acid on the cell surface, the electrophoretic mobility of the cells was unchangeable. The changes in sialic acid content are the markers of the metastasizing cells, but not of the highly metastatic cell lines.

Morphine inhibits the carrageenan-induced oedema and the chemoluminescence of leucocytes stimulated by zymosan.

Morphine inhibited the oedema formation induced by carrageenan. The anti-inflammatory activity developed 120 min after carrageenan injection, suggesting that inhibition of the kinin phase might be partly responsible. This assumption is supported by the findings that morphine inhibited bradykinin oedema but did not influence oedema formation induced by histamine, 5-HT or PGE2. The anti-inflammatory activity of morphine was partially inhibited by naloxone (0.5-1 mg kg-1) in the carrageenan oedema test. Zymosan-stimulated chemoluminescence of neutrophils of the rat was inhibited both by morphine (0.1-10 microM) and naloxone (1-100 microM). When morphine and naloxone were administered simultaneously (10 microM) their inhibitory effects were additive. Naloxone also failed to antagonize the inhibitory action of morphine in lower dose (0.1 microM). These results suggest that the effect of morphine in inflammation might be mediated either by one of the opiate receptor subtypes insensitive to naloxone or a non-opiate mechanism might be involved.

Analysis of the analgesic and anti-inflammatory effects of rimazolium, a pyrido-pyrimidine derivative, compared with that of prostaglandin synthesis inhibitors and morphine.

The analgesic, anti-inflammatory and gastrointestinal effects of rimazolium, morphine and prostaglandin synthesis inhibitors were compared in a battery of tests. Rimazolium, morphine and indomethacin all inhibited carrageenin-induced inflammation; however, the onset of action was different. The first (histamine-serotonin) phase was inhibited by rimazolium, the second (kinin) phase by morphine and the third (prostaglandin) by indomethacin. The chemoluminescence of leucocytes was inhibited by morphine and indomethacin but was unaffected by rimazolium. Prostaglandin-mediated pain (ACh, ATP, acetic acid writhing) was inhibited by all three types of compound; however, pain reaction where prostaglandins (PGs) are not involved (MgSO4 writhing) was inhibited by rimazolium and morphine, but not (or only slightly) by PG synthesis inhibitors. Gastric lesions produced by indomethacin were depressed by rimazolium and aggravated by morphine. These results suggest different mechanisms of anti-inflammatory and analgesic action of rimazolium, morphine and PG synthesis inhibitors.

Antiinflammatory effect of the antioxidant MTDQ-DS.

The effects of native and oxidized forms of the new antioxidant drug MTDQ-DS (HUMAN, Hungary) on some parameters of acute inflammatory processes were studied. In short-term in vitro experiments, both forms at 10(-4) to 10(-6) g/l inhibited dose-dependently the zymosan-induced chemotaxis of the rat peritoneal polymorphonuclear (PMN) granulocytes. In short-term in vivo experiments both forms administered intraperitoneally at 450 or 600 mg/kg inhibited the formation of carrageenin oedema in the rat paw. The long-term administration for 3 weeks of native and oxidized MTDQ-DS in doses of 450 mg/kg significantly inhibited the carrageenin-induced oedema formation, the zymosan-induced chemotaxis, and the luminol-dependent light production of rat peritoneal PMN granulocytes. The results suggest that the native and oxidized forms of MTDQ-DS have an antiinflammatory effect since they inhibit several events in the local inflammatory reaction.

Study of hydroxyproline excretion in patients with prostatic cancer.

Urinary hydroxproline concentrations were measured in 36 prostatic cancer patients. Metastases were ruled out by radiography in 24, and confirmed in 12 cases.14 patients with no malignant disease served as controls. In patients with no metastases excretion was similar to that in the controls, in some of them it was higher. In the patients with higher values the studies were repeated six months later: deposits were found in all cases but one. In the group in which deposits had been present at the outset the values of the untreated patients were significantly higher than in the controls, whereas in the treated patients no consistent values were found.

Cholinesterase activity in rat liver and serum during experimentally induced inflammation.

Cholinesterase activity of albino rats with acute local oedematous inflammation induced by turpentine, croton oil or Freund's adjuvant was elevated in the liver homogenate but decreased in the serum. Aprotinin administration prevented the decrease of serum activity. In the oedema fluid of rats treated with croton oil an enzyme with cholinester splitting activity was detected and it was shown to be identical with serum cholinesterase (EC 3. 1. 1. 8.).

The effect of alpha-melanophor-stimulating hormone on liver regeneration and incorporation of amino acid in rats' liver protein.

Following 25 mug/day synthetic alpha-MSH administration, the liver regeneration of partially hepatectomized rats proved to be increased. The hormone treatment resulted in an enhanced alanine incorporation of the liver proteins, but this effect was uncertain on partially hepatectomized rats. Due to the hormone treatment the low liver protein content of the operated rats became normal. The pseudocholinesterase activity of the liver homogenate of alpha-MSH treated rats was also elevated. On the basis of these experiments authors are supposing some protein synthesis increasing effect of synthetic alpha-MSH.

Effect of vibration on the activity of the plasma kallikrein-kinin system in the rat.

Rats were exposed to whole body vibration horizontally for four hours at 5 Hz frequency and 2 cm amplitude. Of the components of the plasma kallikrein-kinin system the free (spontaneous) and kaolin-activated kallikrein (prekallikrein) activities, the concentration of bradykinin, the bradykinin splitting total kininase activity, total kallikrein-inhibitor activity and the concentration of alpha 2-macroglobulin, a major plasma kallikrein inhibitor, were estimated. Results showed that in response to acute vibration plasma free kallikrein activity was increased significantly in association with a significant reduction of prekallikrein concentration. The concentrations of bradykinin and total kininase activity were significantly elevated, too. Neither total kallikrein-inhibitor activity nor the concentration of alpha 2-macroglobulin were changed indicating that the plasma kallikrein inhibitors did not play a role in the alterations of plasma free kallikrein and prekallikrein activities. During acute vibration the plasma kallikrein-kinin system was activated probably by the enhanced catecholamine secretion. We suggest that the biological importance of this phenomenon is in the defense against the impaired microcirculation caused by catecholamines.

The changed activity of the serum kallikrein-kinin system after ligation of the superior mesenteric artery in rats.

The aim of the experiments was to study the effect of ligation of the superior mesenteric artery on the activity of the kinin-kallikrein system in the plasma and on arterial blood pressure. Ligation of 60 minutes did not change the free kallikrein activity of the plasma, while prekallikrein activity significantly decreased. Blood pressure showed a tendency to increase but not to a significant degree. Five minutes after the release of the ligation (during the period when the functional parameters of the intestinal mucosa returned to normal) free kallikrein activity increased and the arterial blood pressure decreased significantly. A rinse of the intestine with 5 p.c. glucose solution prior to the release of ligation prevents the increase in free kallikrein activity and the fall of blood pressure. The substances absorbed from the bowel lumen and activating the kinin system are probably responsible for the circulation failure following the ligation of the superior mesenteric artery.

The role of leukocytes in the serum acute-phase reaction accompanying inflammatory reactions.

The effects of whole-body X-irradiation with a dose of (7 Gray) were studied on the time course of systemic responses (fever, leukocytosis, serum coeruloplasmin concentration) in turpentine-induced inflammation and on the acute-phase reaction (coeruloplasmin, haptoglobin and seromucoid) produced by various stressful conditions (turpentine-abscess, immobilization, restraint conditions). Results showed that in the irradiated animals the lack of the leukocytic and febrile response to turpentine administration was accompanied by a normal coeruloplasmin response. Therefore, we have concluded to the involvement of more than one mediator in the development of systemic reactions accompanying inflammation. The leukopenia induced by whole-body irradiation could not prevent the development or reduce the magnitude of the acute-phase response in any of the models analysed. This observation appears to make doubtful the exclusive role of leukocytes in the mediation of the acute-phase reaction.

Inflammatory reaction in germfree mice.

In intact germfree animals, the total leukocyte count, the number of polymorphonuclear (PMN) granulocytes, the phagocytic index of peritoneal PMN granulocytes, the serum seromucoid and coeruloplasmin levels are significantly lower than in conventional controls. As a result of treatment with turpentine, the total leukocyte count and the number of PMN granulocytes increased significantly in both groups, but the phagocytic index and the level of the two examined acute phase proteins rose significantly less in germfree animals than in conventionals. The decreased phagocytic function of PMN granulocytes in germfree animals has been explained by the lack of the stimulating effect of the normal bacterial flora.