scholarly journals Inhibition of Hen Brain Acetylcholinesterase and Neurotoxic Esterase by Chlorpyrifos in Vivo and Kinetics of Inhibition by Chlorpyrifos Oxon in Vitro: Application to Assessment of Neuropathic Risk

1993 ◽  
Vol 20 (3) ◽  
pp. 273-279 ◽  
Author(s):  
RUDY J. RICHARDSON ◽  
THOMAS B. MOORE ◽  
USAMAH S. KAYYALI ◽  
JAY H. FOWKE ◽  
JOSEPH C. RANDALL
Keyword(s):  
Kinetics Of ◽  
Kinetics Of Inhibition ◽  
Neurotoxic Esterase ◽  
Brain Acetylcholinesterase

scholarly journals In vitro antibacterial activity and in vivo efficacy of sulbactam-durlobactam against pathogenic Burkholderia species

2020 ◽  
pp. AAC.01930-20
Author(s):  
Krisztina M. Papp-Wallace ◽  
Adam B. Shapiro ◽  
Scott A. Becka ◽  
Elise T. Zeiser ◽  
John J. LiPuma ◽  
...  
Keyword(s):  
Human Pathogens ◽  
Minimal Inhibitory Concentrations ◽  
Class A ◽  
In Vitro Antibacterial Activity ◽  
Lung Infections ◽  
Kinetics Of ◽  
Kinetics Of Inhibition ◽  
Inhibitor Combination

The Gram-negative bacterial genus Burkholderia includes several hard-to-treat human pathogens: two biothreat species, B. mallei (causing glanders) and B. pseudomallei (causing melioidosis), and the B. cepacia complex (BCC) and B. gladioli, which cause chronic lung infections in persons with cystic fibrosis. All Burkholderia spp. possess an Ambler class A Pen β-lactamase, which confers resistance to β-lactams. The β-lactam-β-lactamase inhibitor combination sulbactam-durlobactam (SUL-DUR) is in clinical development for the treatment of Acinetobacter infections. Herein, we evaluated SUL-DUR for in vitro and in vivo activity against Burkholderia clinical isolates. We measured minimal inhibitory concentrations (MICs) of SUL-DUR against BCC and B. gladioli (N = 150), B. mallei (N = 30) and B. pseudomallei (N = 28); studied the kinetics of inhibition of the PenA1 β-lactamase from B. multivorans and the PenI β-lactamase from B. pseudomallei by durlobactam; tested for blaPenA1 induction by SUL-DUR; and evaluated in vivo efficacy in a mouse model of melioidosis. SUL-DUR inhibited growth of 87.3% of the BCC and B. gladioli strains and 100% of the B. mallei and B. pseudomallei strains at 4/4 μg/mL. Durlobactam potently inhibited PenA1 and PenI with k2/K values of 3.9 x 106 M−1s−1 and 2.6 x 103 M−1s−1 and Ki app of 15 nM and 241 nM, respectively, by forming highly stable covalent complexes. Neither sulbactam, durlobactam, nor SUL-DUR increased production of PenA1. SUL-DUR demonstrated activity in vivo in a murine melioidosis model. Taken together, these data suggest SUL-DUR may be useful as a treatment for Burkholderia infections.

scholarly journals Adenine nucleotides and magnesium ions in relation to control of mammalian cerebral-cortex hexokinase

1969 ◽  
Vol 112 (5) ◽  
pp. 579-586 ◽  
Author(s):  
H S Bachelard ◽  
P. S. G. Goldfarb
Keyword(s):  
Mixed Type ◽  
Competitive Inhibition ◽  
Adenine Nucleotides ◽  
Effective Control ◽  
Magnesium Ions ◽  
Soluble Enzyme ◽  
Kinetics Of ◽  
Kinetics Of Inhibition

1. The kinetics of inhibition of brain soluble cytoplasmic hexokinase by ADP were examined in relation to variations in the concentrations of Mg2+ and ATP. The type of inhibition observed was dependent on the Mg2+/ATP ratio. 2. ADP at Mg2+/ATP ratios 2:1 exhibited inhibition of the ‘mixed’ type; at Mg2+/ATP ratios 1:1 the inhibition appeared to be competitive with regard to ATP. 3. Inhibition by free ATP was observed when the Mg2+/ATP ratio was less than 1:1. The inhibition was also of the ‘mixed’ type with respect to MgATP2−. 4. The inhibitions due to ADP and to free ATP were not additive. The results suggested that there may be up to four sites in the soluble enzyme: for glucose, glucose 6-phosphate, ADP and MgATP2−. 5. The ‘free’ non-particulate intracellular Mg2+ concentration was measured and concluded to be about 1·5mm. 6. The concentrations in vivo of Mg2+ and ATP likely to be accessible to a cytoplasmic enzyme are suggested to be below those that yield maximum hexokinase rates in vitro. The enzymic rates were measured at relevant suboptimum concentrations of Mg2+ and ATP in the presence of ADP. Calculations that included non-competitive inhibition due to glucose 6-phosphate (56–65% at 0·25mm) resulted in net rates very similar to the measured rates for overall glycolysis. This system may therefore provide a basis for effective control of cerebral hexokinase.

scholarly journals Studies on Antimicrobial Activity and Kinetics of Inhibition by Plant Products in India (1990–2016)

2018 ◽  
Vol 101 (4) ◽  
pp. 948-955
Author(s):  
Ramesh Kumar Sharma ◽  
Bhupendra Kumar Rana
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Herbal Extracts ◽  
Analytical Approaches ◽  
Kinetics Of ◽  
Kinetics Of Inhibition ◽  
Regression Correlation

Abstract The antimicrobial activity of herbal extracts or plant isolates has usually been evaluated in India using different antimicrobial susceptibility testing methods generally based on diffusion and dilution. There are different analytical approaches for the reliable evaluation of antimicrobial activity ascribed to medicinal plants against selected pathogenic microorganisms. Obtained results may provide scientific bases for the selective use of these natural plants as healing drugs, crop-protecting pesticides, or shelf-life-extending solutions. In general, antimicrobial susceptibility methodologies involve in vivo and in vitro studies; at present, the in vitro evaluation of antibacterial activity appears more popular. Diffusion methods have some limitations, although they are extensively used to determine the susceptibility of organisms isolated from specimen samples to applied antimicrobials and vice versa. Dilution methods are preferred in the case of more precise antimicrobial activity estimation, in terms of minimum inhibitory concentration. With regard to the inherent antimicrobial nature of herbal compositions, herbs, and herbal extracts, Indian researchers have evaluated the reliability of these antimicrobial agents against selected pathogens and have shown them to be effective. Researchers have also tried to establish linear regression correlation analyses on the basis of available inhibition results. This research is still evolving, and interesting results may be expected in the future.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

Acquired Haemophilia: Functional Study of Antibodies to Factor VIII

1981 ◽  
Vol 45 (03) ◽  
pp. 285-289 ◽  
Author(s):  
J P Allain ◽  
A Gaillandre ◽  
D Frommel
Keyword(s):  
Factor Viii ◽  
Functional Study ◽  
Factor Viii Inhibitor ◽  
Acquired Haemophilia ◽  
Viii Inhibitor ◽  
Kinetics Of ◽  
Antibody Function ◽  
Native Plasma

SummaryFactor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.

In vitro/in vivo correlations in the kinetics of poly (lactide-co-glycolide) (PLG) delivery systems of GnRH peptides

1992 ◽  
Vol 21 (1-3) ◽  
pp. 213
Author(s):  
H. Berger ◽  
K. Fechner ◽  
N. Heinrich ◽  
D. Lorenz ◽  
E. Albrecht ◽  
...  
Keyword(s):  
Delivery Systems ◽  
Kinetics Of

scholarly journals SIMILARITY OF THE KINETICS OF INVERTASE ACTION IN VIVO AND IN VITRO. II

1932 ◽  
Vol 16 (2) ◽  
pp. 233-242 ◽  
Author(s):  
B. G. Wilkes ◽  
Elizabeth T. Palmer
Keyword(s):  
Physiological Activity ◽  
Outer Region ◽  
Living Cells ◽  
Yeast Cells ◽  
Live Cells ◽  
Intracellular Enzyme ◽  
Relationship Of ◽  
Kinetics Of

1. The pH-activity relationship of invertase has been studied in vivo and in vitro under identical external environmental conditions. 2. The effect of changing (H+) upon the sucroclastic activity of living cells of S. cerevisiae and of invertase solutions obtained therefrom has been found, within experimental error, to be identical. 3. The region of living yeast cells in which invertase exerts its physiological activity changes its pH freely and to the same extent as that of the suspending medium. It is suggested that this may indicate that this intracellular enzyme may perform its work somewhere in the outer region of the cell. 4. In using live cells containing maltase, no evidence of increased sucroclastic activity around pH 6.9, due to the action of Weidenhagen's α-glucosidase (maltase), was found.

Sign in / Sign up

Export Citation Format

Share Document