Effect of noradrenalin on endogenous prostaglandin E and F2α production in cerebral and extracranial vessels of cats

The production of prostaglandins (PG) E and F₂ in the isolated cerebral and extracranial vessels of cats was determined quantitatively. Basal PG production was found to be greater in the cerebral vessels, and PGF₂ exceeded PGE. On incubation of isolated vessels with noradrenalin, production of vasopressor PGF₂ was reduced, and this was accompanied by a considerable increase in the content of vasopressor PGE. The difference was particularly marked in the cerebral vessels. The level of endogenous PG production by the cerebral vessels, it can tentatively be suggested, has an important role for the local regulation of vascular tone, and a disturbance of their dynamic ratio may be one cause of the development of cerebrovascular pathology.Problem Laboratory on Pharmacology of the Cardiovascular System, Department of Pharmacology, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 422–423, October, 1979.     

Blocking factor of normal animal serum inhibiting immunological responses in vitro

The sera of Wistar and noninbred rats of different ages and sexes were found to contain an extremely thermostable factor, resistant to various chemicals, which inhibits the action of normal and immune antibodies against the red blood cells and serum antigens of rats. The blocking factor is relatively species specific and is more active in respect of the action of normal than of immune antibodies. The activity of the blocking factor is connected with ₁-globulin.Research Laboratory of Experimental Immunobiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 80, No. 11, pp. 70–73, November, 1975.     

α-Fetoprotein production in regenerating mouse liver synchronizedin vivo

Liver cells regenerating after CCl₄ poisoning were synchronizedin vivo by continuous administration of hydroxyurea. Accumulation of hepatocytes at the G₁-S phase boundary or in the S-phase did not affect the course of changes in the blood -fetoprotein (-FP) levels or the characteristic location of -FP for regenerating liver for 2 or 3 days after poisoning. -FP production began in the hepatocytes before their entry into the S-phase, and -FP was found in the cells also at different times after they had ended their mitotic cycle. No dependence of -FP synthesis on any particular phase of the mitotic cycle could be observed.Laboratory of Immunochemistry and Diagnosis of Tumors, Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR L. M. Shabad.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 346–349, March, 1980.     

Synthesis and localization of α-fetoprotein during regeneration of the liver in mice

The main site of localization of -fetoprotein (FP) in mouse liver regenerating after CCl₄ poisoning or partial hepatectomy was in the typical mature hepatocytes that account for not more than a few per cent of the total number of residual hepatocytes. Morphologically they were indistinguishable from the main mass of hepatocytes and they retained on their surface bile capillary antigen. The change in their number and in the brightness of their fluorescence in liver sections corresponded to the dynamics of the FP level in the animals' serum. During regeneration of the liver in mice FP is evidently produced mainly by mature hepatocytes.Laboratory of Immunochemistry and Diagnosis of Tumors, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR. Laboratory of Clinical Immunology, Institute of Experimental and Clinical Oncology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. V. Baroyan.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 10, pp. 1251–1254, October, 1976.     

Effect of prostaglandin F2α on lysosomal membranes of the eye tissues

Both in experimentsin vitro and after intravenous injection of prostaglandin (PG) F₂ labilization of the lysosomal membranes takes place in the sclera and ciliary body but not in the cornea of the rabbit eye. Under the influence of PG, glycosidase activity appears in the vitreous body, where it cannot be found normally.Moscow Helmholtz Research Institute of Eye Diseases. (Presented by Academician of the Academy of Medical Sciences of the USSR S. S. Debov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 6, pp. 679–681, June, 1976.     

Characteristics of hepatocytes containing α-fetoprotein in regenerating mouse liver

After poisoning SWR mice of different ages with single or repeated doses of CCl₄ vapor the synthesis of the embryo-specific protein -fetoprotein (-FP) was induced. The greatest rise in the -FP level was observed in mice under 1 month old. In sections through the liver regenerating after CCl₄ poisoning, -FP was found in hepatocytes indistinguishable from the main population: in small cells in young animals and in large, polyploid hepatocytes in the repeatedly poisoned mice. The only distinguishing feature of the -FP-containing cells after poisoning of the mice with different doses of CCl₄ was that most of them were on the boundary with the necrotic zone. A similar localization of -FP-containing hepatocytes was observed when two other hepatotoxins were used: paracetamol and allyl alcohol.Laboratory of Immunochemistry and Diagnosis of Tumors, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 7, pp. 97–101, July, 1977.     

Synthesis of α-fetoproteinin vitro by human hepatocytes,singly and in microcolonies

By a combination of microelectrophoresis and precipitation in polyacrylamide gel, -fetoprotein (-FP) produced by single hepatocytes and by microcolonies of hepatocytes was determined. Liver cells from 6–13-week-old human fetuses were cultivatedin vitro for 2–5 days. -FP was found to be produced in amounts of between 70 and 800 pg per cell by 23 of 28 single hepatocytes and by 89 of 91 microcolonies consisting of 2 to 35 cellsLaboratory of Immunochemistry and Diagnosis of Tumors, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR. Laboratory of Human Cytogenetics, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR L. M. Shabad.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 481–484, April, 1977.     

Action of prostaglandin F2α on the course of pregnancy and plasma 17β-estradiol concentration in mice

The effect of prostaglandin F₂ (2 mg/kg at each stage of development) on the preimplantation development of mice and on their plasma 17-estradiol concentration was investigated. Prostaglandin F₂ inhibited mitotic division in the embryo and reduced the percentage of embryos shedding the zona pellucida. Meanwhile the 17-estradiol concentration in the peripheral blood plasma fell. Under physiological conditions there was a significant increase in the 17-estradiol concentration at the blastocyst stage after shedding of the zona pellucida.Department of Histology and Embryology, Pediatric Faculty, N. I. Pirogov Second Moscow Medical Institute. Laboratory of Endocrinology, Moscow University. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupriyanov.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 468–470, October, 1979.     

Effect of α1-protease inhibitor (α1-antitrypsin on the intensity of transformation of phytohemagglutinin-stimulated lymphocytes

₁-Antitrypsin (₁-AT) reduces the intensity of transformation of human peripheral blood lymphocytes stimulated by phytohemagglutinin. The degree of inhibition is determined by the antiprotease activity of the ₁-AT. Maximal inhibition of transformation was shown to be 50%. Participation of ₁-AT in the control of activity of lymphoid tissue cells is postulated.Laboratory of Immunogenetics, Research Institute of Transplantology and Artificial Organs, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Orekhovich.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 1, pp. 35–36, January, 1980.     

Thermostable antigens of malignant tumors and normal tissues of experimental animals

Thermostable antigens (TA) were found by the gel precipitation test and by immunoelectrophoresis in malignant tumors of muscle tissue induced by dimethylbenzanthracene, and in the amniotic fluid of 8–12-day embryos and certain normal organs of adult Wistar rats. Relative tissue specificity of these antigens was demonstrated, on the one hand, for tumors, amniotic fluid, and the uterus, and on the other hand for the lung, spleen, and serum. TA detected in tumors and amniotic fluid by immunoelectrophoresis are located in the zones of - and ₁-globulins.Research Laboratory of Experimental Immunobiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 6, pp. 726–728, June, 1978.     

Effect of proquazone and indomethacin on gastric prostaglandin synthesisin vitro andin vivo

Although proquazone is less ulcerogenic than indomethacin in rat and man, it inhibits more effectively than indomethacin gastric mucosal synthesis of 6-keto-prostaglandin (PG) F₁ in both species during incubationin vitro. The more pronounced inhibitory activity of proquazone can be observed on formation of 6-keto-PGF₁ from endogenous substrate by fragments of gastric mucosa as well as on conversion of exogenous arachidonic acid by a microsomal fraction of mucosal homogenates indicating high affinity of proquazone for gastric mucosal cyclo-oxygenase. After oral administration, however, both drugs exhibit equal inhibitory potency on gastric formation of 6-keto-PGF₁ in the rat. These findings indicate that pharmacokinetic properties of non-steroidal anti-inflammatory drugs (NSAID) contribute significantly to their inhibitory action on gastric PG formationin vivo. The comparable reduction of gastric 6-keto-PGF₁ synthesis observed after oral administration of proquazone and indomethacin in the rat suggests that the ulcerogenic effects of NSAID result not only from inhibition of the gastric PG system. Effects on other processes and other enzyme systems, e.g. the lipoxygenase pathway of arachidonic acid metabolism, may modulate drug-induced ulcerogenicity and deserve further investigation.     

Urinary prostaglandins in human neonates: Relationship to kidney function and blood pressure

Summary We studied the excretion of prostaglandin (PG) E₂ and of PGF₂ in 172 healthy newborns during the first week of life to detect possible biochemical markers for the individual susceptibility to hypertension. PG excretion was compared to urinary electrolytes, urinary osmolality, and blood pressure. In addition, blood pressure of the newborns was related to the blood pressure of the mothers and to the history of hypertension in parents and/or grandparents.PGE₂-excretion increased from 0.7 ng/mg creatinine on the third day to 1.5 ng on the fifth day of life (p<0.001) while PGF₂ excretion remained unchanged at 2 ng/mg creatinine. PGE₂ (but not PGF₂) was inversely correlated to urinary osmolality (p<0.001) while urinary potassium was positively correlated to PGF₂ (p<0.001). On the fifth day of life systolic blood pressure of the newborns was correlated to PGF₂-excretion and to systolic blood pressure of the mother (p<0.05). Blood pressure was significantly higher in newborns with a history of hypertension in parents or grandparents than in those without hypertension in relatives (p<0.02).The data suggest that renal PG:s are involved in the regulation of urinary osmolality and potassium excretion in the neonate. The positive correlation between PGF₂ excretion and blood pressure may indicate a genetically determined PG-related renal influence on the level of systemic blood pressure.Supported by the Deutsche Forschungsgemeinschaft (Sche 118/3–5)     

Immunochemical study of the CBA mouse kidney

Seven antigens, one of which (with a relative electrophoretic mobility of 0.35) is specific for the kidney, were detected in the CBA mouse kidney by immunoelectrophoresis and the agar precipitation test. The remaining kidney antigens were common to the kidney and other mouse organs and tissues. Antigens with the mobility of albumin and globulin were serum in origin; an antigen with close to zero mobility was common to the kidney and liver; an antigen with the mobility of ₂ globulin was evidently not homogeneous and, besides wide interorgan specificity, most closely resembled lung antigen.Laboratory of Immunoembryology, Research Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 6, pp. 566–569, June, 1979.     

Mechanism of changes in lymphocytic dehydrogenase activity during transplantation of the heart

Succinate dehydrogenase (SD) and -glycerophosphate dehydrogenase (-GPD) activity were studied in the peripheral blood lymphocytes and grafted myocardium in CBA mice after transplantation of the heart from newborn C57BL/6 mice subcutaneously into the concha auriculae. The ratio SD/-GPD was shown to be greater than 1 in the myocardium and lymphocytes of intact animals and in recipients of a transplanted isolinear heart. After allogeneic (heterolinear) transplantation the ratio between the activities was reversed (SD/-GPD less than 1) on account of activation of -GPD in the blood lymphocytes, and this was preceded by inversion in the myocardium of the graft. This phenomenon is assumed to be connected with the development of immunological conflict.A. N. Bakulev Institute of Cardiovascular Surgery, Academy of Medical Sciences of the USSR. Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 4, pp. 423–425, April, 1976.     

Immunochemical identification of organ-specific human placentalαin2-globulin and its content in the amniotic fluid

An organ-specific human placental ₂, differing immunologically from previously known ₂ and ₁-globulins of pregnancy, -fetoprotein, placental lactogen, and chorionic gonadotropin, was identified by immunochemical analysis. The antigen thus discovered is present in large quantities in the placental tissue and amniotic fluid in the early stages of pregnancy, but at parturition its concentration is sharply reduced.Presented by Academician of the Academy of Medical Sciences of the USSR Yu. M. Lopukhin.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 803–804, July, 1976.     

Prostaglandins,cyclic nucleotides,and adaptation of the heart to acute and chronic pressure overloading

The concentration of prostaglandins (PG) and cyclic nucleotides was determined in the rat heart at different times after coarctation of the abdominal aorta. The animals were divided into three types depending on the rate of development and degree of hypertrophy. Rats best adapted to pressure overloading of the heart (with the greatest degree of hypertrophy) had the highest PG level in the myocardium. Correlation was found between the increase in weight of the heart and the PGE/PGF₂ ratio. A connection was demonstrated between PG and cyclic nucleotides in the myocardium in the course of its adaptation to pressure overloading. It is suggested that PG may be an important component of the system of adaptation of the heart to pressure overloading.All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 525–528, November, 1979.     

Species differences in the pattern of eicosanoids produced by inflamed and non-inflamed tissue

The synthesis of¹⁴C labelled arachidonic acid metabolites was measured in colonic tissues obtained from mice, rats, guinea pigs, rabbits, piglets and in colonic biopsies from humans during colonoscopy. The main eicosanoids formed after stimulation with calcium ionophore A23187 were: in humans, 15-hydroxy-eicosatetraenoic acid (15-HETE); in mice, 12-HETE; in rats, 12-HETE, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandine F₁ (6kPGF₁); in guinea pigs, PGD₂; in rabbits, 6kPGF₁, PGE₂ and 15-HETE; and in pigs PGE₂ and 12-HETE. In inflamed 15-HETE production was increased in man, HHT and 12-HETE production in rats and overall eicosanoid production in mice.     

Ernährungsphysiologische Untersuchungen mit Formeldiäten: Der Stoffwechsel mehrfach ungesättigter Fettsäuren und die Prostaglandinbiosynthese beim Menschen

Summary Linoleic and linolenic acids are precursors for the biosynthesis of prostaglandins (PG) and related compounds. In man augmented linoleic acid intake results in stimulation of PG-biosynthesis, for PG originating from the kidney a stimulation only is found for PGE₂. Dietary linolenic acid inhibits PG biosynthesis to a tenfold lesser degree than eicosapentaenoic acid. Renal PGE₂ is depressed by linolenic acid intake, while no effect is found for PGF₂ up to 8 energy% of linolenic acid supply.Linoleic and linolenic acids additionally display effects on fatty acid metabolism. In contrast to the results of in vitro studies the supply with the precursor linoleic acid results in a decrease of arachidonic acid in cholesterolesters of plasma and in HDL-lecithin, while the intake of linolenic acid is without effect. From these data it is concluded that in vivo the conversion of linoleic to arachidonic acid occurs preferentially to the analogous conversion of linolenic to eicosapentaenoic acid.

---

Abkürzungen -Linolensäure all-cis-9,12,15-Octadecatriensäure - Arachidonsäure all-cis-5,8,11,14 Eicosatetraensäure - Eicosapentaensäure (EPA) all-cis-5,8,11,14,17-Eicosapentaensäure - HDL Lipoproteine hoher Dichte (d>1.063) - LDL Lipoproteine niedriger Dichte (d 1.006–1.063) - LCAT Lecithin-Cholesterin- Acyl- Transferase - Linolsäure all-cis-9,12-Octadecadiensäure - PG Prostaglandin Unterstützt durch eine Sachbeihilfe der Deutschen ForschungsgemeinschaftDie Arbeit wurde anläßlich der Heinrich-Wieland-Preis-Verleihung am 26. 10. 1984 in München vorgetragen     

Differential effects of interleukin-1α and β on the arachidonic acid cascade in human synovial cells and chondrocytes in culture

The effects of interleukin-1 and were tested on the [³H]-arachidonic acid release and the prostaglandin synthesis by human cultured synovial cells and chondrocytes. Both forms of interleukin-1 stimulated the arachidonic acid release but interleukin-1 was more potent than IL-1. Human synovial cells and chondrocytes synthesized three types of prostaglandins upon stimulation with interleukin-1 or : prostaglandin E₂, F₂ and 6-keto-prostaglandin F₁. Regarding the synthesis of these prostaglandins, IL-1 was again more potent than IL-1. A comparison between interleukin-1-stimulated synovial cells and chondrocytes revealed neither significant quantitative nor qualitative differences in both the arachidonic acid release and the prostaglandin synthesis.     

Failure of anti-inflammatory steroids to inhibit prostaglandin release from the hydronephrotic rabbit kidney

The release of prostaglandins E₂, F₂, I₂ and thromboxane A₂ from isolated perfused normal and hydronephrotic rabbit kidneys was investigated by extraction and radio-immunoassay. In both types of kidneys, basal PG efflux increased with time and was not altered by co-perfusion with dexamethasone or hydrocortisone. Several vasoactive substances at 1 to 4 g (e.g., bradykinin, angiotensin II, substance P, noradrenaline and vasopressin) caused release of additional amounts of prostaglandins. PGE₂ and 6-keto PGF₁ were the major prostanoids detected, but substantial amounts of PGF₂ were also found. Thromboxane A₂ was not released from normal kidneys. In hydronephrotic kidneys there was greatly augmented release of prostaglandins E₂ and I₂, some increases in PGF₂, and the appearance of substantial amounts of thromboxane A₂ (measured as immunoreactive TXB₂) when the kidneys were challenged with angiotensin, bradykinin and vasopressin, and smaller augmentation of the response to noradrenaline and substance P. There was no evidence that these evoked increases in renal PG output could be inhibited by dexamethasone or hydrocortisone. Some explanations for the failure of steroids to alter prostanoid metabolism from arachidonate in rabbit kidney are discussed, and it is proposed that there are clear exceptions to the concept that steroids inhibit prostaglandin generation in intact tissues.