UNTERSUCHUNGEN ÜBER DEN STOFFWECHSEL VON 17α-HYDROXY-19-NOR-PROGESTERON-CAPRONAT BEIM MENSCHEN IN VIVO UND VON 17α-HYDROXY-19-NOR-PROGESTERON BEI DER RATTE IN VITRO

1966 ◽  
Vol 51 (1) ◽  
pp. 114-130 ◽  
Author(s):  
H. Breuer ◽  
B. P. Lisboa
Keyword(s):  
Urinary Excretion ◽  
Comparative Studies ◽  
Intramuscular Injection ◽  
Pregnant Patient ◽  
Main Metabolite ◽  
Postmenopausal Patient ◽  
Enzyme Preparations ◽  
Single Intramuscular Injection

ABSTRACT The effect of a single intramuscular injection of 300 mg of 17α-hydroxy-19-nor-progesterone caproate on the urinary excretion of oestrogens, 17-ketosteroids, 17-hydroxycorticosteroids and the »pregnanetriol«-fraction has been studied in two pregnant patients and in two postmenopausal patients. In one postmenopausal patient, small and irregular increases in the excretion of oestrogens, 17-hydroxycorticosteroids and »pregnanetriol«-fraction were observed; in one pregnant patient, there was also an increase in the excretion of oestrone and 17β-oestradiol. Apart from these instances, the excretion of the steroid fractions investigated remained unchanged after administration of 17α-hydroxy-19-nor-progesterone caproate. In addition to a 19-nor-pregnanetriol isomer, a 19-nor-pregnanediol-20-one was found as main metabolite in the »pregnanetriol«-fraction. In comparative studies, the metabolism of 17α-hydroxyprogesterone and 17α-hydroxy-19-nor-progesterone was investigated, using the cytoplasmic and microsomal fractions of rat liver as enzyme preparations. With NADPH2 as cofactor the two steroids yielded predominantly ring A saturated compounds, whereas with NADH2 only 20α- and 20β-hydroxysteroids were formed. After incubation of 17α-hydroxyprogesterone with the microsomal and/or cytoplasmic fractions, the following metabolites were identified: 17α-hydroxy-5α-pregnane-3,20-dione; 17α,20β-dihydroxy-pregn-4-en-3-one; 17α,20α-dihydroxy-pregn-4-en-3-one; 3β,17α-dihydroxy-5α-pregnan-20-one; 3β,17α-dihydroxy-5β-pregnan-20-one; 3α, 17α-dihydroxy-5β-pregnan-20-one. After incubation of 17α-hydroxy-19-nor-progesterone the following metabolites were characterized: 17α-hydroxy-19-nor-5α-pregnane-3,20-dione; 17α,20β-dihydroxy-19-nor-pregn4-en-3-one; 17α,20α-dihydroxy-19-nor-pregn-4-en-3-one; 3β,17α-dihydroxy-19-nor-5α-pregnan-20-one; 3α,17α-dihydroxy-19-nor-5β-pregnan-20-one. These results shows that no qualitative differences exist in the metabolism of 17α-hydroxyprogesterone and 17α-hydroxy-19-nor-progesterone.

scholarly journals THER-05. GENETICALLY STABLE POLIOVIRUS VECTOR CARRYING H3.3K27M ANTIGEN FOR TREATMENT OF DIFFUSE MIDLINE GLIOMA BY INTRAMUSCULAR INJECTION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii472-iii472
Author(s):  
Mubeen Mosaheb ◽  
Daniel Landi ◽  
Elena Dobrikova ◽  
Michael Brown ◽  
Yuanfan Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Intramuscular Injection ◽  
Cd8 T Cell ◽  
Cytokine Profiles ◽  
Cell Immunity ◽  
Novel Approach ◽  
Diffuse Midline Glioma

Abstract BACKGROUND H3 K27M-mutant diffuse midline glioma (DMG) is invariably lethal. Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses, in particular, are uniquely tropic for dendritic cells (DC) and potently activate DC, inducing Th1-dominant cytokine profiles, CD8 T cell immunity, and enhanced epitope presentation. Thus, poliovirus is ideally suited for vectored delivery of signature tumor neoantigens, e.g. the H3 K27M feature of DMG. However, poliovirus vector design is inherently limited by genetic instability and the underlying neuropathogenicity of poliovirus. METHODS We created a genetically stable, polio:rhinovirus chimera vector devoid of neuropathogenicity and modified for stable expression of the HLA-A2 restricted H3.3 K27M antigen (RIPO (H3.3)). RESULTS RIPO(H3.3) infects, activates, and induces H3.3K27M antigen presentation in DCs in vitro. Given intramuscularly in vivo, RIPO(H3.3) recruits and activates DCs with Th1-dominant cytokine profiles, efficiently primes H3.3K27M-specific CD8 T cells, induces antigen-specific CD8 T cell migration to the tumor site, delays tumor growth, and enhances survival in murine tumor models. CONCLUSION This novel approach leverages the unique ability of polioviruses to activate DCs while simultaneously introducing the H3.3 K27M antigen. In this way, DCs are activated optimally in situ, while being simultaneously infected to express/present tumor antigen. RIPO(H3.3), given by intramuscular injection, will be evaluated in a clinical trial for children with H3 K27M-mutant diffuse midline glioma.

scholarly journals 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

1963 ◽  
Vol 61 (3) ◽  
pp. 353-363 ◽  
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.

Characterization of the Metamitron Deaminating Enzyme Activity from Sugar Beet ( Beta vulgaris L.) Leaves

1979 ◽  
Vol 34 (11) ◽  
pp. 948-950 ◽  
Author(s):  
Carl Fedtke ◽  
Robert R. Schmidt
Keyword(s):  
Cytochrome C ◽  
Sugar Beet ◽  
Electron Donor ◽  
Nitrogen Atmosphere ◽  
Enzyme Preparations ◽  
Reducing Conditions ◽  
Trade Name ◽  
Membrane Bound

Abstract The enzymatic activity from sugar beet leaves which is responsible for the detoxification of the herbicide metamitron (4-amino-4,5-dihydro-3-methyl-6-phenyl-1, 2, 4-triazin-5-one, trade name Goltix®) has been characterized in vitro. The detoxification occurs by rapid deamination in vivo as well as in vitro. However, the deamination in vitro is only maximal under reducing conditions, i. e. with an electron donor and in a nitrogen atmosphere. The electron donor may be cystein, glutathione, dithionite or ascorbate. The enzymatic deamination further requires the addition of cytochrome c and a “supernatant factor”, which may be replaced by FMN, FAD or DCPIP. However, in the presence of FMN or DCPIP cytochrome c is not essential but only stimulatory. The partic­ulate as well as the soluble metamitron deaminating enzyme preparations obtained take up oxygen when supplied with cysteine and FMN. The particulate enzyme appears in the peroxysome-fraction. It is therefore suggested, that the enzymatic deamination of metamitron in sugar beet leaves is mediated by a proxisomal membrane bound electron transport system which alternatively may reduce oxygen or metamitron (deaminating).

Critical Assessment of In Vitro Screening of α-Glucosidase Inhibitors from Plants with Acarbose as a Reference Standard

Planta Medica ◽  
2021 ◽  
Author(s):  
Neil Miller ◽  
Elizabeth Joubert
Keyword(s):  
Reference Standard ◽  
Screening Assay ◽  
Enzyme Preparations ◽  
Glucosidase Inhibitor ◽  
Biological Source ◽  
Oral Antidiabetic ◽  
Glucosidase Inhibitors ◽  
Plant Sources

AbstractPostprandial hyperglycemia is treated with the oral antidiabetic drug acarbose, an intestinal α-glucosidase inhibitor. Side effects of acarbose motivated a growing number of screening studies to identify novel α-glucosidase inhibitors derived from plant extracts and other natural sources. As “gold standard”, acarbose is frequently included as the reference standard to assess the potency of these candidate α-glucosidase inhibitors, with many outperforming acarbose by several orders of magnitude. The results are subsequently used to identify suitable compounds/products with strong potential for in vivo efficacy. However, most α-glucosidase inhibitor screening studies use enzyme preparations obtained from nonmammalian sources (typically Saccharomyces cerevisiae), despite strong evidence that inhibition data obtained using nonmammalian α-glucosidase may hold limited value in terms of identifying α-glucosidase inhibitors with actual in vivo hypoglycemic potential. The aim was to critically discuss the screening of novel α-glucosidase inhibitors from plant sources, emphasizing inconsistencies and pitfalls, specifically where acarbose was included as the reference standard. An assessment of the available literature emphasized the cruciality of stating the biological source of α-glucosidase in such screening studies to allow for unambiguous and rational interpretation of the data. The review also highlights the lack of a universally adopted screening assay for novel α-glucosidase inhibitors and the commercial availability of a standardized preparation of mammalian α-glucosidase.

scholarly journals Role of ABCG2 in Secretion into Milk of the Anti-Inflammatory Flunixin and Its Main Metabolite: In Vitro-In Vivo Correlation in Mice and Cows

2019 ◽  
Vol 47 (5) ◽  
pp. 516-524 ◽  
Author(s):  
Dafne Garcia-Mateos ◽  
Alba Maria Garcia-Lino ◽  
Indira Alvarez-Fernandez ◽  
Esther Blanco-Paniagua ◽  
Alvaro de la Fuente ◽  
...  
Keyword(s):  
Main Metabolite ◽  
Anti Inflammatory
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