In vivo and in vitro effects of a new hypoglycemic agent, 2-(3-methylcinnamylhydrazono)-propionate (BM 42.304) on glucose metabolism in guinea pigs

SummaryIn vitro, concentration-dependent effects of rt-PA on a range of coagulation and fibrinolytic assays in thawed plasma samples were investigated. In absence of a fibrinolytic inhibitor, 2 μg rt-PA/ml blood (3.4 μg/ml plasma) caused prolongation of clotting time assays and decreases of plasminogen (to 44% of the control value), fibrinogen (to 27%), α2-antiplasmin (to 5%), FV (to 67%), FVIII (to 41%) and FXIII (to 16%).Of three inhibitors tested, a specific polyclonal anti-rt-PA antibody prevented interferences in all fibrinolytic and most clotting assays. D-Phe-Pro-Arg-CH2Cl (PPACK) enabled correct assays of fibrinogen and fibrinolytic parameters but interfered with coagulometric assays dependent on endogenous thrombin generation. Aprotinin was suitable only for a restricted range of both assay types.Most in vitro effects were observed only with rt-PA plasma concentrations in excess of therapeutic values. Nevertheless it is concluded that for clinical application, collection of blood samples on either specific antibody or PPACK is essential for a correct assessment of in vivo effects of rt-PA on the haemostatic system in patients undergoing fibrinolytic therapy.

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Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648055 ◽

1976 ◽

Vol 36 (02) ◽

pp. 401-410 ◽

Cited By ~ 6

Author(s):

Buichi Fujttani ◽

Toshimichi Tsuboi ◽

Kazuko Takeno ◽

Kouichi Yoshida ◽

Masanao Shimizu

Keyword(s):

Guinea Pig ◽

Acetylsalicylic Acid ◽

Guinea Pigs ◽

Glass Bead ◽

Animal Species ◽

Inhibitory Effect ◽

Rabbit Platelet ◽

Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

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Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

Melatonin Research ◽

10.32794/mr11250042 ◽

2019 ◽

Vol 2 (4) ◽

pp. 83-98 ◽

Cited By ~ 2

Author(s):

André De Lima Mota ◽

Bruna Vitorasso Jardim-Perassi ◽

Tialfi Bergamin De Castro ◽

Jucimara Colombo ◽

Nathália Martins Sonehara ◽

...

Keyword(s):

Breast Cancer ◽

Glucose Metabolism ◽

Tumor Growth ◽

Tumor Cells ◽

Carbonic Anhydrases ◽

In Vivo Models ◽

Ca Ix ◽

Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression.

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In Vitro Effects of Sulforaphane on Interferon-Driven Inflammation and Exploratory Evaluation in Two Healthy Volunteers

Molecules ◽

10.3390/molecules26123602 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3602

Author(s):

Elena Genova ◽

Maura Apollonio ◽

Giuliana Decorti ◽

Alessandra Tesser ◽

Alberto Tommasini ◽

...

Keyword(s):

Healthy Volunteers ◽

Supportive Therapy ◽

P Value ◽

Type I ◽

Interferon Signature ◽

Interferon Stimulated Genes ◽

Immune System Activation ◽

In Vitro Effects

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value < 0.0001; cGAMP 6 h vs. SFN+cGAMP 6 h p < 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy.

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A Detailed Examination of the in vivo and in vitro Effects of ACTH on Gonadotropin Secretion in the Adult Rat

Neuroendocrinology ◽

10.1159/000124090 ◽

1985 ◽

Vol 40 (4) ◽

pp. 297-302 ◽

Cited By ~ 18

Author(s):

David R. Mann ◽

Diane Evans ◽

Festus Edoimioya ◽

Freja Kamel ◽

George M. Butterstein

Keyword(s):

Detailed Examination ◽

Gonadotropin Secretion ◽

Adult Rat ◽

In Vitro Effects

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Contamination of erythropoietin by endotoxin: in vivo and in vitro effects on murine erythropoiesis

Blood ◽

10.1182/blood.v54.1.146.146 ◽

1979 ◽

Vol 54 (1) ◽

pp. 146-158 ◽

Cited By ~ 8

Author(s):

KS Zuckerman ◽

PJ Quesenberry ◽

J Levin ◽

R Sullivan

Keyword(s):

Significant Inhibition ◽

Erythropoietic Activity ◽

Limulus Amebocyte Lysate ◽

Endogenous Erythropoietin ◽

Significant Change ◽

In Vitro Effects ◽

Stimulation Of

Abstract Endotoxin was detected in all erythropoietin preparations tested and was removed from four lots, without loss of erythropoietic activity, by adsorption with limulus amebocyte lysate. Comparison of adsorbed (endotoxin-depleted) and nonadsorbed (endotoxin-containing) erythropoietin preparations demonstrated significant inhibition of CFU- e and BFU-e in vitro by nonadsorbed erythropoietin at concentrations higher than 0.25 U/ml and 2.0 U/ml, respectively. CFU-e and BFU-e were inhibited significantly by readdition in vitro of 10(-5)-10(-3) mug of endotoxin per unit of limulus-adsorbed erythropoietin. Administration of saline or 6 U of nonadsorbed or adsorbed erythropoietin twice a day for 4 days of CF1 mice resulted in reticulocyte counts of 2.1%, 9.9%, and 15.9%, respectively. Nonadsorbed erythropoietin resulted in a 29% decrease in erythropoiesis, a 42% decrease in CFU-e, and a 16% increase in granulopoiesis in the marrow, whereas adsorbed erythropoietin caused a 28% increase in erythropoiesis, no significant change in CFU-e and a 19% decrease in granulopoiesis in the marrow. Both preparations resulted in marked increases in splenic erythropoiesis and granulopoiesis. The effects of adsorbed erythropoietin are similar to those produced following stimulation of hematopoiesis by endogenous erythropoietin. Hemopoietic changes induced by nonadsorbed erythropoietin in vivo and in vitro are affected substantially by contamination of the erythropoietin preparations with endotoxin.

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Comparative studies on Salmonella typhi grown in vivo and in vitro III. The immunizing potencies of acetone-killed vaccines prepared from in vivo and in vitro grown bacteria and the immunizing potency of substances isolated from infected organs

Journal of Hygiene ◽

10.1017/s0022172400039644 ◽

1963 ◽

Vol 61 (3) ◽

pp. 353-363 ◽

Cited By ~ 1

Author(s):

A. L. Olitzki ◽

Dina Godinger

Keyword(s):

Comparative Studies ◽

Guinea Pigs ◽

Peritoneal Fluid ◽

Parent Strain ◽

Salmonella Typhi ◽

Challenge Strain

1. Salmonella typhi, strain Ty2, grown in vivo and employed as acetone-dried vaccine possessed a higher immunizing potency than the descendants of the same parent strain grown in vitro and employed as vaccine.2. When 2 × 108in vitro-grown bacteria were employed as challenge, the immunizing effects of both types of vaccine were more marked than after administration of 2 × 108in vivo-grown bacteria as challenge.3. The higher potency of the in vivo-grown vaccine was apparent in all experiments, whether the challenge strain was grown in vivo or in vitro.4. Immunogenic substances were isolated from infected organs of mice and guinea-pigs, and an immunogenic substance from the peritoneal fluid of the infected guinea-pigs was concentrated by precipitation with ethanol.

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