Relations between resistance to chloroquine and acidification of endocytic vesicle of Plasmodium berghei

Parasitology ◽  
1989 ◽  
Vol 98 (1) ◽  
pp. 1-6 ◽  
Author(s):  
J. Mahmalgi ◽  
E. Veignie ◽  
G. Prensier ◽  
S. Moreau
Keyword(s):  
Plasmodium Berghei ◽  
Resistant Strain ◽  
Low Ph ◽  
Chloroquine Resistance ◽  
Acidic Ph ◽  
Endocytic Vesicle ◽  
Complementary Method ◽  
Endocytic Vesicles ◽  
Acidic Compartments

SummaryIn order to visualize low-pH compartments of Plasmodium berghei strains we have used a basic congener of dinitrophenol, 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine (DAMP) which concentrates in acidic compartments, and can be detected by immunocytochemistry with anti-dinitrophenol antibodies. We have demonstrated that in a P. berghei chloroquine-sensitive strain (N strain), DAMP accumulates in the endocytic vacuoles where haemoglobin degradation is occurring. These compartments which have recently been shown to concentrate 4-aminoquinoline drugs (Moreau, Prensier, Maalla & Fortier, 1986) have an acidic pH. Conversely DAMP was found scattered all over the cytoplasm in a P. berghei chloroquine-resistant strain; the same phenomenon was previously observed (Moreau et al. 1986) in the localization of a 4-aminoquinoline on this same strain. Monensin-induced swelling of acidic compartments (Boss & Morre, 1984) was used as a complementary method for the determination of low-pH compartments on P. berghei strains. All the data reported here suggest that chloroquine resistance in P. berghei RC may be related to an impairment in the acidification of endocytic vesicles.

Visualization of acidic compartments in cultured osteoclasts by use of an acidotrophic amine as a marker for low pH

1999 ◽  
Vol 298 (3) ◽  
pp. 527-537 ◽  
Author(s):  
Megumi Inoue ◽  
Hisaho Yoshida ◽  
Toshitaka Akisaka
Keyword(s):  
Low Ph ◽  
Acidic Compartments

scholarly journals Impact of the acidic environment on gene expression and functional parameters of tumors in vitro and in vivo

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mandy Rauschner ◽  
Luisa Lange ◽  
Thea Hüsing ◽  
Sarah Reime ◽  
Alexander Nolze ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Western Blot ◽  
Tumor Cell ◽  
Low Ph ◽  
Strong Increase ◽  
Acidic Ph ◽  
The Impact

Abstract Background The low extracellular pH (pHe) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pHe on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia. Methods Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed. Results NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O2 consumption increased gradually with decreasing pH. Conclusions These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.

Loss of Chloroquine Resistance on Transfer of Plasmodium berghei from Mouse to Hamster

1967 ◽  
Vol 53 (5) ◽  
pp. 1111 ◽  
Author(s):  
William Trager ◽  
Renata Klatt ◽  
Sharon Smith
Keyword(s):  
Plasmodium Berghei ◽  
Chloroquine Resistance

scholarly journals Modelling of pH-dependence to develop a strategy for stabilising mAbs at acidic steps in production

2019 ◽  
Author(s):  
Max Hebditch ◽  
Ryan Kean ◽  
Jim Warwicker
Keyword(s):  
Experimental Data ◽  
Design Principle ◽  
Ph Dependence ◽  
Low Ph ◽  
Viral Clearance ◽  
Acidic Ph ◽  
Antibody Therapeutics ◽  
Acid Environment ◽  
Pass Through ◽  
Acid Stable

AbstractEngineered proteins are increasingly being required to function or pass through environmental stresses for which the underlying protein has not evolved. A major example in health are antibody therapeutics, where a low pH step is used for purification and viral clearance. In order to develop a computational model for analysis of pH-stability, predictions are compared with experimental data for the relative pH-sensitivities of antibody domains. The model is then applied to proteases that have evolved to be functional in an acid environment, showing a clear signature for low pH-dependence of stability in the neutral to acidic pH region, largely through reduction of saltbridges. Interestingly, an extensively acidic protein surface can maintain contribution to structural stabilisation at acidic pH through replacement of basic sidechains with polar, hydrogen-bonding groups. These observations form a design principle for engineering acid-stable proteins.

Low pH reduces the activity of ceftolozane/tazobactam in human urine, but confirms current breakpoints for urinary tract infections

2019 ◽  
Vol 75 (3) ◽  
pp. 593-599 ◽  
Author(s):  
Alina Karoline Nussbaumer-Pröll ◽  
Sabine Eberl ◽  
Birgit Reiter ◽  
Thomas Stimpfl ◽  
Christoph Dorn ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Human Urine ◽  
Negative Impact ◽  
Low Ph ◽  
Antibiotic Activity ◽  
Clinical Isolates ◽  
Acidic Ph ◽  
Bacterial Strains ◽  
Tract Infections

Abstract Background Acidic pH has been shown to impact the antibiotic activity of non-β-lactams in urine. Objectives To investigate the in vitro activity of ceftolozane/tazobactam compared with meropenem at different pH settings in urine. Methods We determined the MICs for 30 clinical isolates of Escherichia coli, 25 clinical isolates of Klebsiella pneumoniae and 24 clinical isolates of Proteus mirabilis in pooled human urine and standard growth medium at pH 5 and 7. Time–kill curves were produced for one representative clinical isolate of tested bacterial strains in urine at pH 5, 6 and 7 for both antibiotics at concentrations above and below the MIC. HPLC analysis of the stability of ceftolozane/tazobactam and meropenem was performed at different pH values. Results The median MICs of both antibiotics were up to 8-fold higher at pH 5 than at pH 7. Bacterial growth of E. coli was not impacted by pH, while for K. pneumoniae and P. mirabilis low pH slightly reduced growth. Compared with pH 7, pH 5 resulted in a significant decrease in antibiotic activity with a delta of up to 3 log10 bacterial counts after 24 h. Impact of acidic pH was lowest for P. mirabilis; however, this strain metabolically increased the pH during experiments. Stability was not impacted by low pH. Conclusions Acidic pH had a significant negative impact on the activity of ceftolozane/tazobactam and meropenem in urine. Considering concentrations achieved in urine, our results confirm existing breakpoints and do not advocate increasing ceftolozane/tazobactam breakpoints for urinary tract infections.

Derivatization and Cleanup Improvements in Determination of Residues of Glyphosate and Aminomethylphosphonic Acid in Blueberries

1982 ◽  
Vol 65 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Richard A Guinivan ◽  
Neal P Thompson ◽  
Willis B Wheeler
Keyword(s):  
Handling Time ◽  
Low Ph ◽  
Electron Capture Detection ◽  
Aqueous Environment ◽  
Sample Handling ◽  
Aminomethylphosphonic Acid ◽  
Gel Permeation ◽  
Cation Exchange Column ◽  
Derivatives Of

Abstract A new method based on development of the 2-chloroethyl N-heptafluorobutyryl derivatives of glyphosate and its major metabolite aminomethylphosphonic acid is reported for fortified blueberry samples. The concentrated aqueous extract is chromatographed on a gel permeation column in a low pH eluant. Under these conditions, sugar is eliminated by permeation and pigments are strongly adsorbed. Additional sugar is eliminated with a small cation exchange column and then the sample is easily dried and derivatized. The derivatized compounds are extracted from an aqueous environment with hexane and analyzed by gas chromatography with electron capture detection. This procedure requires significantly less sample handling time and provides greater sensitivity for glyphosate than the commonly used procedure recommended by EPA.

Improved direct specific determination of serum iron and total iron-binding capacity.

1980 ◽  
Vol 26 (2) ◽  
pp. 327-331 ◽  
Author(s):  
F Ceriotti ◽  
G Ceriotti
Keyword(s):  
Serum Iron ◽  
Binding Capacity ◽  
Low Ph ◽  
Total Iron ◽  
Total Iron Binding Capacity ◽  
Ascorbic Acid Solution ◽  
Ph Values ◽  
Specific Determination ◽  
Iron Binding Capacity

Abstract Serum iron is released from transferrin and reduced at pH 1.7 by treating serum with a 10 g/L ascorbic acid solution in 0.1 mol/L HCl. When ferrozine is added to this reagent, it forms a complex with iron that is as intensely colored as at higher pH values, and under these conditions no turbidity is produced. The second major interference, that from copper, is eliminated by adding 1 g of thiosemicarbazide per liter, which at a low pH forms a stable, uncolored complex with copper without affecting the reaction of ferrozine with iron.

The Method of Substitutive Circles Family: Application in Catia Design Environment for Gear Shaped Tool Profiling

2014 ◽  
Vol 1036 ◽  
pp. 370-375 ◽  
Author(s):  
Silviu Berbinschi ◽  
Gabriel Frumuşanu ◽  
Virgil Gabriel Teodor ◽  
Nicolae Oancea
Keyword(s):  
Numerical Data ◽  
Rolling Process ◽  
Design Environment ◽  
Complementary Method ◽  
Contact Points ◽  
Rolling Method ◽  
Graphical Algorithm

Tools which generate by enveloping using the rolling method may be profiled using various methods. The substitutive circles family method is a complementary method developed based a specifically theorem, in which is determined a family of circles associated with the blank’s centrode, family which envelop the profile to be generate. The method assumes the determination of the circles family, transposed in the rolling process between the blank and tool centrodes. In this paper is proposed an algorithm for curling surfaces in enveloping, associated with a pair of rolling circular centrodes. The graphical algorithm is based on the representation of the circles family enveloped the blank’s profile. It is generated the circles family transposed on the centrode associated with the gear shaped cutter and is determined a new position of contact points with the blank. The assembly of these points forms the profile of the gear shaped cutter. The numerical data proof the proposed method quality.

scholarly journals PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression.

1997 ◽  
Vol 17 (10) ◽  
pp. 5960-5967 ◽  
Author(s):  
F A Mühlschlegel ◽  
W A Fonzi
Keyword(s):  
Candida Albicans ◽  
Mutant Strain ◽  
Low Ph ◽  
Predicted Amino Acid Sequence ◽  
Acidic Ph ◽  
Null Mutant ◽  
Alkaline Ph ◽  
Ph Values ◽  
Functional Homolog ◽  
Morphological Defects

Deletion of PHR1, a pH-regulated gene of Candida albicans, results in pH-conditional defects in growth, morphogenesis, and virulence evident at neutral to alkaline pH but absent at acidic pH. Consequently, we searched for a functional homolog of PHR1 active at low pH. This resulted in the isolation of a second pH-regulated gene, designated PHR2. The expression of PHR2 was inversely related to that of PHR1, being repressed at pH values above 6 and progressively induced at more acidic pH values. The predicted amino acid sequence of the PHR2 protein, Phr2p, was 54% identical to that of Phr1p. A PHR2 null mutant exhibited pH-conditional defects in growth and morphogenesis analogous to those of PHR1 mutants but manifest at acid rather than alkaline pH values. Engineered expression of PHR1 at acid pH in a PHR2 mutant strain and PHR2 at alkaline pH in a PHR1 mutant strain complemented the defects in the opposing mutant. Deletion of both PHR1 and PHR2 resulted in a strain with pH-independent, constitutive growth and morphological defects. These results indicate that PHR1 and PHR2 represent a novel pH-balanced system of functional homologs required for C. albicans to adapt to environments of diverse pH.

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