scholarly journals The metabolism in vitro and hepatic microsomal interactions of some enantiomeric drug substrates

1970 ◽  
Vol 117 (5) ◽  
pp. 833-841 ◽  
Author(s):  
David S. Hewick ◽  
James R. Fouts
Keyword(s):  
Type I ◽  
Type Ii ◽  
Difference Spectra ◽  
Microsomal Cytochrome ◽  
Hepatic Microsomes ◽  
Michaelis Constants ◽  
Nadph Oxidation ◽  
Identical Type ◽  
Cytochrome P 450

1. The metabolism in vitro and microsomal interactions of (+)-amphetamine, (−)-amphetamine, (+)-benzphetamine and (−)-benzphetamine were studied with hepatic microsomes from phenobarbitone-pretreated male rabbits. 2. (+)-Benzphetamine was N-demethylated 30–35% faster than (−)-benzphetamine, but the apparent Michaelis constants for the two enantiomers were similar. 3. (−)-Amphetamine was deaminated about 200% faster than (+)-amphetamine. 4. The benzphetamine enantiomers gave qualitatively and quantitatively identical type I microsomal difference spectra (peak, 390nm; trough, 425nm) indicating identical apparent binding affinities for microsomes and identical spectral changes at maxima (ΔEmax. values). 5. The amphetamine enantiomers gave qualitatively identical type II microsomal difference spectra (peak, 433nm; trough, 395nm). However, the type II spectral data indicated that (+)-amphetamine had a markedly higher apparent binding affinity than (−)-amphetamine for microsomes. The amphetamine enantiomers gave identical ΔEmax. values. 6. The benzphetamine enantiomers (0.5mm) enhanced the rate of microsomal cytochrome P-450 reduction by NADPH by 400–500%, (+)-benzphetamine enhancing the rate 20–25% more than (−)-benzphetamine. 7. The amphetamine enantiomers decreased the rate of microsomal cytochrome P-450 reduction by NADPH. At a concentration of 2mm, (+)-amphetamine decreased the rate more than (−)-amphetamine. 7. All four enantiomers enhanced microsomal NADPH oxidation.

Alterations of Hepatic Microsomal Drug Metabolism by Glucagon

1975 ◽  
Vol 53 (5) ◽  
pp. 873-879 ◽  
Author(s):  
Jacob V. Aranda ◽  
Kenneth W. Renton
Keyword(s):  
Substrate Oxidation ◽  
Type I ◽  
Nadph Cytochrome ◽  
Transport Chain ◽  
Hexobarbital Sleeping Time ◽  
Nadph Oxidation ◽  
In Vivo Effects ◽  
Cytochrome P 450

The effect of glucagon on the components of the hepatic microsomal electron transport chain (NADPH oxidase, NADPH cytochrome c reductase (EC 1.6.2.4), cytochrome P-450, and NADPH cytochrome P-450 reductase), and on two representative oxidative pathways (aminopyrine N-demethylation, a type I substrate oxidation; and aniline p-hydroxylation, a type II substrate oxidation) was determined. Microsomes from rats pretreated with glucagon (300 μg/kg per day for 3 days) showed a significant decrease in NADPH oxidation and in aminopyrine N-demethylation with a prolonged hexobarbital sleeping time, and a significant increase in aniline p-hydroxylation. Microsomes from rats pretreated with a lower dose of glucagon (30 μg/kg per day for 3 days) showed a significant decrease in the microsomal N-demethylation of aminopyrine. Glucagon had no effect when added in vitro to microsomes, suggesting that the in vivo effects of glucagon are mediated indirectly in the intact animal.

Modeling Endoleaks and Collateral Reperfusion following Endovascular AAA Exclusion

2003 ◽  
Vol 10 (3) ◽  
pp. 424-432 ◽  
Author(s):  
Chuh K. Chong ◽  
Thien V. How ◽  
Geoffrey L. Gilling-Smith ◽  
Peter L. Harris
Keyword(s):  
Stent Graft ◽  
Aortic Pressure ◽  
Type I ◽  
Type Ii ◽  
Pump System ◽  
Type Ii Endoleak ◽  
Type I Endoleak ◽  
The Impact ◽  
Mean Aortic Pressure

Purpose: To investigate the effect on intrasac pressure of stent-graft deployment within a life-size silicone rubber model of an abdominal aortic aneurysm (AAA) maintained under physiological conditions of pressure and flow. Methods: A commercial bifurcated device with the polyester fabric preclotted with gelatin was deployed in the AAA model. A pump system generated physiological flow. Mean and pulse aortic and intrasac pressures were measured simultaneously using pressure transducers. To simulate a type I endoleak, plastic tubing was placed between the aortic wall and the stent-graft at the proximal anchoring site. Type II endoleak was simulated by means of side branches with set inflow and outflow pressures and perfusion rates. Type IV endoleak was replicated by removal of gelatin from the graft fabric. Results: With no endoleak, the coated graft reduced the mean and pulse sac pressures to negligible values. When a type I endoleak was present, mean sac pressure reached a value similar to mean aortic pressure. When net flow through the sac due to a type II endoleak was present, mean sac pressure was a function of the inlet pressure, while pulse pressure in the sac was dependent on both inlet and outlet pressures. As perfusion rates increased, both mean and pulse sac pressures decreased. When there was no outflow, mean sac pressure was similar to mean aortic pressure. In the presence of both type I and type II endoleaks, mean sac pressure reached mean aortic pressure when the net perfusion rate was low. Conclusions: In vitro studies are useful in gaining an understanding of the impact of different types of endoleaks, in isolation and in combination, on intrasac pressure after aortic stent-graft deployment.

Type VI collagen expression is upregulated in the early events of chondrocyte differentiation

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 245-251
Author(s):  
R. Quarto ◽  
B. Dozin ◽  
P. Bonaldo ◽  
R. Cancedda ◽  
A. Colombatti
Keyword(s):  
Suspension Culture ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Type I ◽  
Type Ii ◽  
Type Vi Collagen ◽  
Full Spectrum ◽  
Collagen Expression ◽  
Hypertrophic Chondrocyte

Dedifferentiated chondrocytes cultured adherent to the substratum proliferate and synthesize large amounts of type I collagen but when transferred to suspension culture they decrease proliferation, resume the chondrogenic phenotype and the synthesis of type II collagen, and continue their maturation to hypertrophic chondrocyte (Castagnola et al., 1986, J. Cell Biol. 102, 2310–2317). In this report, we describe the developmentally regulated expression of type VI collagen in vitro in differentiating avian chondrocytes. Type VI collagen mRNA is barely detectable in dedifferentiated chondrocytes as long as the attachment to the substratum is maintained, but increases very rapidly upon passage of the cells into suspension culture reaching a peak after 48 hours and declining after 5–6 days of suspension culture. The first evidence of a rise in the mRNA steady-state levels is obtained already at 6 hours for the alpha 3(VI) chain. Immunoprecipitation of metabolically labeled cells with type VI collagen antibodies reveals that the early mRNA rise is paralleled by an increased secretion of type VI collagen in cell media. Induction of type VI collagen is not the consequence of trypsin treatment of dedifferentiated cells since exposure to the actin-disrupting drug cytochalasin or detachment of the cells by mechanical procedures has similar effects. In 13-day-old chicken embryo tibiae, where the full spectrum of the chondrogenic differentiation process is represented, expression of type VI collagen is restricted to the articular cartilage where chondrocytes developmental stage is comparable to stage I (high levels of type II collagen expression).(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital Dyserythropoietic Anemia

PEDIATRICS ◽  
1973 ◽  
Vol 51 (5) ◽  
pp. 957-958
Author(s):  
G. Bennett Humphrey ◽  
Bahaod-Din Mojab ◽  
Ingomar Mutz
Keyword(s):  
Carbohydrate Metabolism ◽  
Morphological Characteristics ◽  
Type I ◽  
Type Ii ◽  
Congenital Dyserythropoietic Anemia ◽  
The 1950S ◽  
Deja Vu ◽  
Déjà Vu ◽  
Excellent Article

Reading the excellent article by Drs. Murphy and Oski, "Congenital Dyserythropoietic Anemia (CDA)",1 which further defines type II, produced a sense of deja vu. In the 1950s, nonspherocytic, hemolytic anemias (HNHA) were categorized as type I and II based on the in vitro autohemolysis test.2 This group of anemias has subsequently been demonstrated to be due to a series of enzymatic abnormalities in carbohydrate metabolism.3 In CDA, the morphological characteristics which define types I, II, and III probably reflect nuclear rather than cytoplasmic abnormalities.

Disparate cytokine regulation of ICAM-1 in rat alveolar epithelial cells and pulmonary endothelial cells in vitro

1995 ◽  
Vol 269 (1) ◽  
pp. L127-L135 ◽  
Author(s):  
W. W. Barton ◽  
S. Wilcoxen ◽  
P. J. Christensen ◽  
R. Paine
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Alveolar Epithelial Cells ◽  
Normal Lung ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial

Intercellular adhesion molecule-1 (ICAM-1) is expressed at high levels on type I alveolar epithelial cells in the normal lung and is induced in vitro as type II cells spread in primary culture. In contrast, in most nonhematopoetic cells ICAM-1 expression is induced in response to inflammatory cytokines. We have formed the hypothesis that the signals that control ICAM-1 expression in alveolar epithelial cells are fundamentally different from those controlling expression in most other cells. To test this hypothesis, we have investigated the influence of inflammatory cytokines on ICAM-1 expression in isolated type II cells that have spread in culture and compared this response to that of rat pulmonary artery endothelial cells (RPAEC). ICAM-1 protein, determined both by a cell-based enzyme-linked immunosorbent assay and by Western blot analysis, and mRNA were minimally expressed in unstimulated RPAEC but were significantly induced in a time- and dose-dependent manner by treatment with tumor necrosis factor-alpha, interleukin-1 beta, or interferon-gamma. In contrast, these cytokines did not influence the constitutive high level ICAM-1 protein expression in alveolar epithelial cells and only minimally affected steady-state mRNA levels. ICAM-1 mRNA half-life, measured in the presence of actinomycin D, was relatively long at 7 h in alveolar epithelial cells and 4 h in RPAEC. The striking lack of response of ICAM-1 expression by alveolar epithelial cells to inflammatory cytokines is in contrast to virtually all other epithelial cells studied to date and supports the hypothesis that ICAM-1 expression by these cells is a function of cellular differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Biological Relevance of Colony Morphology and Phenotypic Switching by Burkholderia pseudomallei

2006 ◽  
Vol 189 (3) ◽  
pp. 807-817 ◽  
Author(s):  
Narisara Chantratita ◽  
Vanaporn Wuthiekanun ◽  
Khaemaporn Boonbumrung ◽  
Rachaneeporn Tiyawisutsri ◽  
Mongkol Vesaratchavest ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Vaccine Development ◽  
Colony Morphology ◽  
Phenotypic Switching ◽  
Type I ◽  
Type Ii ◽  
Altered Expression ◽  
Replication Fitness

ABSTRACT Melioidosis is a notoriously protracted illness and is difficult to cure. We hypothesize that the causative organism, Burkholderia pseudomallei, undergoes a process of adaptation involving altered expression of surface determinants which facilitates persistence in vivo and that this is reflected by changes in colony morphology. A colony morphotyping scheme and typing algorithm were developed using clinical B. pseudomallei isolates. Morphotypes were divided into seven types (denoted I to VII). Type I gave rise to other morphotypes (most commonly type II or III) by a process of switching in response to environmental stress, including starvation, iron limitation, and growth at 42°C. Switching was associated with complex shifts in phenotype, one of which (type I to type II) was associated with a marked increase in production of factors putatively associated with in vivo concealment. Isogenic types II and III, derived from type I, were examined using several experimental models. Switching between isogenic morphotypes occurred in a mouse model, where type II appeared to become adapted for persistence in a low-virulence state. Isogenic type II demonstrated a significant increase in intracellular replication fitness compared with parental type I after uptake by epithelial cells in vitro. Isogenic type III demonstrated a higher replication fitness following uptake by macrophages in vitro, which was associated with a switch to type II. Mixed B. pseudomallei morphologies were common in individual clinical specimens and were significantly more frequent in samples of blood, pus, and respiratory secretions than in urine and surface swabs. These findings have major implications for therapeutics and vaccine development.

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