PRODUCTION WITH SODIUM SULPHATES OF AN ELECTROLYTE–STEROID-GARDIOPATHY CHARACTERIZED BY NECROSES (ESCN), AND ITS PREVENTION BY MgCl2 AND KCl

Massive myocardial necroses and hemorrhagic necroses of the liver can be produced by combined treatment with monosodium or disodium sulphate (NaHSO4 or Na2SO4) and 2α-methyl-9α-chlorocortisol (Me-Cl-COL) in the rat. In this respect, the effect of the sulphates resembles that previously described for sodium phosphates and perchlorate. It differs from that of most other sodium salts that have been tested for this activity up to the present time.NaCl slightly inhibits the cardiotoxic and hepatotoxic effect of concurrent treatment with Na2SO4 plus Me-Cl-COL. Equimolecular amounts of MgCl2 or KCl are even considerably more effective in this respect. It is noteworthy that, under these experimental conditions, the effect of 1 mM. of Na2SO4 can be inhibited by 0.5 mM. of MgCl2 or KCl.We may conclude from these observations that, in rats conditioned by a highly active corticoid, such as Me-Cl-COL, the production of an "infarctoid cardiopathy" (as well as of the accompanying hepatic changes) does not only depend upon the sodium ion, but is largely influenced by the simultaneous presence of other anions and cations.

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Highly active Fe7S8 encapsulated in N-doped hollow carbon nanofibers for high-rate sodium-ion batteries

Journal of Energy Chemistry ◽

10.1016/j.jechem.2020.05.011 ◽

2021 ◽

Vol 53 ◽

pp. 26-35 ◽

Cited By ~ 5

Author(s):

Chengzhi Zhang ◽

Donghai Wei ◽

Fei Wang ◽

Guanhua Zhang ◽

Junfei Duan ◽

...

Keyword(s):

Carbon Nanofibers ◽

Sodium Ion ◽

High Rate ◽

Sodium Ion Batteries ◽

Highly Active ◽

Hollow Carbon

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Severity of promotion by sodium salts of succinic acid in rat urinary bladder carcinogenesis correlates with sodium ion concentration under conditions of equal urinary pH

Carcinogenesis ◽

10.1093/carcin/14.11.2277 ◽

1993 ◽

Vol 14 (11) ◽

pp. 2277-2281 ◽

Cited By ~ 8

Author(s):

Tatsuyuki Otoshi ◽

Hiroyuki Iwata ◽

Shinji Yamamoto ◽

Takashi Murai ◽

Shuji Yamaguchi ◽

...

Keyword(s):

Urinary Bladder ◽

Succinic Acid ◽

Sodium Ion ◽

Ion Concentration ◽

Urinary Ph ◽

Rat Urinary Bladder ◽

Sodium Salts ◽

Bladder Carcinogenesis

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NADPH-dependent generation of a cytosolic dithiol which activates hepatic iodothyronine 5′-deiodinase. Demonstration by alkylation with iodoacetamide

Biochemical Journal ◽

10.1042/bj2400559 ◽

1986 ◽

Vol 240 (2) ◽

pp. 559-566 ◽

Cited By ~ 4

Author(s):

A K Das ◽

B C W Hummel ◽

P G Walfish

Keyword(s):

Heat Treatment ◽

Strong Evidence ◽

Sodium Arsenite ◽

Complete Loss ◽

Partial Reduction ◽

Simultaneous Presence ◽

Experimental Conditions

We have assessed a previously proposed mechanism mediating 5′-deiodinase activation involving enzymic reduction of disulphides to thiols in non-glutathione cytosolic components of Mr approx. 13,000 (Fraction B) catalysed by NADPH in the presence of other cytosolic components of Mr greater than 60,000 (Fraction A). The extent of Fraction B reduction under various experimental conditions was monitored by determining the amount of 14C incorporated into chromatographically isolated Fractions B and A after their alkylation with iodo[14C]acetamide. Incorporation of 14C into B was found to require the simultaneous presence of NADPH and A, to be directly proportional to the concentration of NADPH added, and to be unaffected by either propylthiouracil or iopanoate. Activation of 5′-deiodinase attainable using B after its partial reduction by various concentrations of NADPH and subsequent alkylation with non-radioactive iodoacetamide was inversely proportional to the previously added concentration of NADPH. Fraction B was stable at 100 degrees C for 5 min, while similar heat treatment of Fraction A or omission of NADPH resulted in a complete loss of 14C incorporation. A greater than 90% reduction in iodo[14C]acetamide incorporation was revealed when 0.2 mM-sodium arsenite was added after enzymic reduction of B, as well as when NADPH was replaced by NADH. Fraction B could be labelled more extensively after reduction non-specifically, with dithiothreitol or NaBH4, but not by GSH. These observations provide strong evidence for the presence in vivo of a cytosolic disulphide (DFBS2) in Fraction B which can be reduced enzymically to a dithiol [DFB(SH)2] by NADPH and cytosolic components in Fraction A. The degree of activation of hepatic 5′-deiodinase correlated with the amount of available (unalkylated) Fraction B.

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Differences in the vigilance performance of highly active and normal second-grade males under four experimental conditions.

Journal of Educational Psychology ◽

10.1037/0022-0663.68.6.696 ◽

1976 ◽

Vol 68 (6) ◽

pp. 696-701 ◽

Cited By ~ 3

Author(s):

Grace L. Kirchner

Keyword(s):

Second Grade ◽

Vigilance Performance ◽

Experimental Conditions ◽

Highly Active

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Co-Treatment with the hsp90 Inhibitor 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (DMAG) and Histone Deacetylase Inhibitor (HDI) Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA): A Highly Active Combination Against Human Mantle Cell Lymphoma (MCL) Cells.

Blood ◽

10.1182/blood.v106.11.2418.2418 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2418-2418 ◽

Cited By ~ 1

Author(s):

Angela Hatter ◽

Purva Bali ◽

Maria Balasis ◽

Warren Fiskus ◽

Sandhya Boyapalle ◽

...

Keyword(s):

Cyclin D1 ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Combined Treatment ◽

Atp Binding ◽

Dependent Manner ◽

Chaperone Function ◽

Highly Active ◽

Deacetylase Inhibitor ◽

Dose Dependent

Abstract We have previously reported that agents that inhibit ATP binding and chaperone function of hsp90 are highly active against wild type and mutant Bcr-Abl and mutant FLT-3 containing human acute leukemia cells. In the present studies, we determined the effects of a more soluble and potent geldanamycin analogue, DMAG (Kosan Biosciences Inc.), and/or hydroxamate histone deacetylase inhibitor (HHDI), vorinostat (Merck & Co., Inc.), against human MCL Jeko1 and MO2058 cells. These cells contain the characteristic MCL-associated chromosomal translocation t(11; 14)(q13;q32), which results in the overexpression of cyclin D1. Recently, HHDIs, such as vorinostat, have been shown to inhibit HDAC6, which results in the acetylation of hsp90 and inhibition of its ATP binding and chaperone function. Treatment with vorinostat (0.5 to 2.0 μM) induced the accumulation of the cells in the G1 and DMAG (0.1 to 0.5 μM) in the G2/M phase of the cell cycle. Both agents induced apoptosis in a dose-dependent manner (up to 50%). While vorinostat induced both p21 and p27 levels, DMAG only increased the intracellular levels of p21. Treatment with either agent depleted the intracellular levels of c-Myc, c-Raf, Akt and cdk4 in a dose dependent manner. It is well established that the chaperone association with hsp90 maintains Akt, c-Raf, cyclin D1 and cdk4 in the native and active conformation, and inhibition of hsp90 promotes their polyubiquitylation and proteasomal degradation. Notably, co-treatment with DMAG (e.g., 0.25 μM) and vorinostat (e.g., 2.0 μM), more than either agent alone, markedly attenuated the levels of cyclin D1 and cdk4, as well as the levels of c-Myc, c-Raf and Akt. The combination of DMAG and vorinostat also induced significantly more apoptosis of Jeko1 and MO2058 cells, as compared to the treatment with either agent alone (p < 0.01). These findings demonstrate that the combined treatment with vorinostat and DMAG is highly active against human MCL cells, and support the rationale to determine the in vivo efficacy and safety of the combination against human MCL.

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Hormone dependency of splenic iron stores in the rat: effect of oestrogens on the recuperation of reserves in ferrodeficient subjects

Laboratory Animals ◽

10.1258/002367798780559275 ◽

1998 ◽

Vol 32 (3) ◽

pp. 290-297 ◽

Cited By ~ 5

Author(s):

Miquel Borràs

Keyword(s):

Single Dose ◽

Regression Model ◽

Hormone Replacement ◽

Combined Treatment ◽

Iron Dextran ◽

Experimental Conditions ◽

Iron Stores ◽

Hormone Dependency ◽

Positive Effect

Splenic iron stores are negligible in prepuberal rats, increasing quickly from the age of 2 months (at which moment sexual differences become apparent) and stabilizing around 3 months, when females show values approximately two-fold greater than males. Castration, adrenalectomy and hormone replacement studies show that the amount of iron stored depends directly on circulating oestrogens and is slightly but not significantly decreased, in our experimental conditions, by testosterone. The role of oestrogens is emphasized by the high correlation obtained, according to a hyperbolic regression model, between splenic iron values and doses of hormone administered to ovariectomized females. In ferrodeficient females (chronic phlebotomy), oestradiol had a positive effect on the replenishment of the stores, superior to that of iron dextran, and improved by combined treatment. However, iron levels found after a single dose were less than those found in non-phlebotomized animals.

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Treatment of biologically treated leachate by oxidation and coagulation

Water Science & Technology ◽

10.2166/wst.2011.377 ◽

2011 ◽

Vol 64 (7) ◽

pp. 1413-1418

Author(s):

H. Y. Zhang ◽

Y. C. Zhao ◽

J. Y. Qi

Keyword(s):

Removal Efficiency ◽

Combined Treatment ◽

Ferric Sulfate ◽

Oxidation Time ◽

Advanced Treatment ◽

Experimental Conditions ◽

Combined Process ◽

Effective Removal

This work aims to investigate removal efficiency of oxidation and coagulation/flocculation processes, to provide an effective method for the treatment of biologically pre-treated leachate. Leachate containing 985 mg L−1 COD was treated by using three treatment schemes, i.e. oxidation, coagulation/flocculation and the combined process of coagulation/flocculation followed by oxidation. The application of single oxidation resulted in the effective removal of COD and color up to 80.4 and 83.2%, respectively. However, residual COD values lower than 200 mg L−1 could only be achieved under intensive experimental conditions (high dosage of Ca(ClO)2 and prolonged oxidation time). Coagulation/flocculation yielded residual COD values higher than 200 mg L−1 even at the optimum coagulation conditions. The combined treatment by coagulation/flocculation followed by oxidation yielded final COD lower than 100 mg L−1 at the following conditions: pre-coagulation with 250 mg L−1 PFS (poly-ferric sulfate) and over 30-min post-oxidation, or pre-coagulation with 300 mg L−1 PFS and over 20-min post-oxidation. Hence, pre-coagulation with PFS followed by oxidation with Ca(ClO)2 was recommended for advanced treatment of biologically treated leachate.

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Identification of BCL-XL as highly active survival factor and promising therapeutic target in colorectal cancer

Cell Death and Disease ◽

10.1038/s41419-020-03092-7 ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Anna-Lena Scherr ◽

Andreas Mock ◽

Georg Gdynia ◽

Nathalie Schmitt ◽

Christoph E. Heilig ◽

...

Keyword(s):

Colorectal Cancer ◽

Ex Vivo ◽

Combined Treatment ◽

Therapy Resistance ◽

Sequencing Analysis ◽

Protein Activity ◽

Highly Active ◽

Promising Therapeutic Target ◽

Induced Apoptosis

Abstract Since metastatic colorectal cancer (CRC) is a leading cause of cancer-related death, therapeutic approaches overcoming primary and acquired therapy resistance are an urgent medical need. In this study, the efficacy and toxicity of high-affinity inhibitors targeting antiapoptotic BCL-2 proteins (BCL-2, BCL-XL, and MCL-1) were evaluated. By RNA sequencing analysis of a pan-cancer cohort comprising >1500 patients and subsequent prediction of protein activity, BCL-XL was identified as the only antiapoptotic BCL-2 protein that is overactivated in CRC. Consistently, pharmacologic and genetic inhibition of BCL-XL induced apoptosis in human CRC cell lines. In a combined treatment approach, targeting BCL-XL augmented the efficacy of chemotherapy in vitro, in a murine CRC model, and in human ex vivo derived CRC tissue cultures. Collectively, these data show that targeting of BCL-XL is efficient and safe in preclinical CRC models, observations that pave the way for clinical translation.

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258 IMPACT OF MILRINONE AND FORSKOLIN ON THE EFFICIENCY AND QUALITY OF BOVINE OOCYTE IN VITRO MATURATION

Reproduction Fertility and Development ◽

10.1071/rdv25n1ab258 ◽

2013 ◽

Vol 25 (1) ◽

pp. 277

Author(s):

E. Stachowiak ◽

K. Papis ◽

J. Karasiewicz ◽

J. A. Modlinski

Keyword(s):

In Vitro Maturation ◽

Combined Treatment ◽

Phosphodiesterase Inhibitor ◽

Microscopic Analysis ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Experimental Conditions ◽

Oocyte Meiosis

The efficiency of in vitro maturation (IVM) of bovine oocytes remains inferior compared with maturation in vivo. Recently, some modifications of in vitro maturation (IVM) procedures have been proposed, such as simulated physiological maturation (Gilchrist 2011 Reprod. Fertil. Dev. 23, 23–31). In our experiment, a comparison of the traditional IVM efficiency with maturation after oocyte meiosis inhibition using roscovitine or with a modified two-step maturation using forskolin (cyclic adenosine monophosphate stimulator) and milrinone (type-3 phosphodiesterase inhibitor) was performed. Control oocytes obtained from slaughterhouse-derived ovaries were subjected to the traditional 24-h maturation in TCM-199 medium supplemented with sodium pyruvate, l-glutamine, gentamicin, 10% FCS, and hormones (pregnant mare’s serum gonadotropin and hCG, PG 600, Intervet, Kenilworth, NJ, USA). The roscovitine (50 µM, 24 h) inhibitory treatment was accomplished in the same medium (without hormones) and subsequently, traditional 24-h IVM was performed. The same TCM-199 medium (with hormones) supplemented with forskolin (100 µM) and milrinone (50 µM) was used for the first step (17 h) of the two-step maturation, whereas the second step (7 h) was performed in the same TCM-199 medium devoid of forskolin and milrinone. Fertilization with frozen sperm processed using TALP media was performed in TALP supplemented with heparin, penicillamine, hypotaurine, epinephrine, and BSA. In vitro culture of presumptive zygotes was performed in CR1aa medium. Portions of oocytes from all treatments after maturation and after fertilization procedures were stained and subjected to microscopic analysis. There were no differences in terms of maturation and fertilization rates between treatments. However, roscovitine-mediated inhibition of maturation performed in our experimental conditions was efficient and reversible, but harmful for subsequent embryo development. On the other hand, two-step maturation was equally as efficient as (but not better than) traditional IVM in all aspects examined in the present study (Table 1). In conclusion, the forskolin and milrinone combined treatment during the IVM procedure gives hope for fully efficient IVM. However, to achieve this goal, more research is necessary. Table 1.Development of embryos after different oocyte maturation procedures1

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