Lack of effect of clinical doses of cyclosporin A on erythrocyte Na+/K+-ATPase activity

1999 ◽  
Vol 97 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Andreu FERRER-MARTÍNEZ ◽  
Antonio FELIPE ◽  
Pedro BARCELÓ ◽  
Francisco J. CASADO ◽  
José BALLARÍN ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Cyclosporin A ◽  
Sodium Concentration ◽  
Transport Processes ◽  
Transport Systems ◽  
Transplant Patients ◽  
Group I ◽  
Significant Linear Correlation ◽  
Group Ii

Cyclosporin A (CsA) may exert its cytotoxic effects by altering the activity of different plasma membrane transport systems. Although CsA may act at the gene level, it has been also suggested that it can directly alter transport processes at the plasma membrane. To examine this possibility in a physiological context, we determined Na+/K+-ATPase activity in erythrocytes from two groups of subjects receiving CsA treatment: group I consisted of kidney transplant patients, and group II comprised patients with steroid-resistant idiopathic nephrotic syndrome. Group I patients showed a marked decrease (35%) in the activity of the Na+/K+-ATPase in erythrocytes immediately after surgery, before the initiation of CsA treatment. The activity remained low 2 days after the introduction of CsA, but had recovered to the original (pre-surgery) value 1 month later. Group II patients showed the same pattern of erythrocyte Na+/K+-ATPase activity as those in group I. When the blood CsA levels from all patients were plotted against the corresponding erythrocyte Na+/K+-ATPase transport activity, a significant linear correlation was found. Higher levels of CsA in the blood were correlated significantly with increased Na+/K+-ATPase activities. The blood sodium concentration was also correlated positively with both erythrocyte Na+/K+-ATPase activity and blood CsA concentration. Thus CsA treatment is not associated with inhibition of the Na+/K+-ATPase in erythrocytes.

scholarly journals Trafficking of Na-K-ATPase and dopamine receptor molecules induced by changes in intracellular sodium concentration of renal epithelial cells

2008 ◽  
Vol 295 (4) ◽  
pp. F1117-F1125 ◽  
Author(s):  
Angel R. Cinelli ◽  
Riad Efendiev ◽  
Carlos H. Pedemonte
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Atpase Activity ◽  
Proximal Tubule ◽  
Dopamine Receptors ◽  
Sodium Concentration ◽  
Intracellular Sodium ◽  
Proximal Tubules ◽  
Sodium Reabsorption ◽  
Intracellular Sodium Concentration

Most of the transepithelial transport of sodium in proximal tubules occurs through the coordinated action of the apical sodium/proton exchanger and the basolateral Na-K-ATPase. Hormones that regulate proximal tubule sodium excretion regulate the activities of these proteins. We have previously demonstrated that the level of intracellular sodium concentration modulates the regulation of Na-K-ATPase activity by angiotensin II and dopamine. An increase of a few millimolars in intracellular sodium concentration leads to increased Na-K-ATPase activity without a statistically significant increase in the number of plasma membrane Na-K-ATPase molecules, as determined by cell surface protein biotinylation. Using total internal reflection fluorescence, we detected an increased number of Na-K-ATPase molecules in cytosolic compartments adjacent to the plasma membrane, suggesting that the increased intracellular sodium concentration induces a movement of Na-K-ATPase molecules toward the plasma membrane. While intracellular compartments containing Na-K-ATPase molecules are very close to the plasma membrane, compartments containing type 1 dopamine receptors (D1Rs) are distributed in different parts of the cell cytosol. Fluorescence determinations indicate that an increased intracellular sodium concentration induces the increased colocalization of dopamine receptors with Na-K-ATPase molecules in the region of the plasma membrane. We propose that under in vivo conditions, in response to a sodium load in the lumen of proximal tubules, an increased level of intracellular sodium in epithelial cells is an early event that triggers the cellular response that leads to dopamine inhibition of proximal tubule sodium reabsorption.

Effects of variations in food intake on renal sodium pump activity and its gene expression in Psammomys kidney

2000 ◽  
Vol 279 (6) ◽  
pp. F1124-F1131 ◽  
Author(s):  
P. Scherzer ◽  
I. Nachliel ◽  
E. Ziv ◽  
H. Bar-On ◽  
M. M. Popovtzer
Keyword(s):  
Atpase Activity ◽  
G Protein ◽  
Group Iv ◽  
Osmotic Gradient ◽  
Urine Osmolarity ◽  
Outer Medulla ◽  
Solute Content ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Psammomys obesus lives in an arid environment and feeds on saltbush. When animals are fed a laboratory diet, urine osmolarity drops. To explore the mechanism(s) of water conservation, we measured renal function, kidney solute content, Na-K-ATPase activity, and mRNA in several groups: group I (saltbush diet, 18 g/day, 4.2 g protein); group II (laboratory diet, 10 g/day, 1.8 g protein); and group III, the same as group I, and group IV, the same as group II, both plus a 1-day fast. Urine osmolarity was 2,223 ± 160, 941 ± 144, 1,122 ± 169 and 648 ± 70.9 mosM in groups I, II, III, and IV, respectively. Tissue osmolarities in cortex, outer medulla, and inner medulla, respectively, were 349 ± 14, 644 ± 63, and 1,152 ± 34 μosM/mg tissue in group I; 317 ± 24, 493 ± 17, and 766 ± 60 μosM/mg tissue in group II; 335 ± 6, 582 ± 15, 707 ± 35 μosM/mg tissue in group III; and 314 ± 18, 490 ± 22, and 597 ± 29 μosM/mg tissue in group IV. There were no differences in Na-K-ATPase activity and mRNA in cortex and in medulla between groups I and II, whereas in group III Na-K-ATPase activity and mRNA increased in cortex and outer medulla. These results suggest a key role for urea in corticomedullary osmotic gradient of Psammomys. The absence of differences in Na-K-ATPase activity and mRNA between groups I and II despite differences in tissue sodium concentrations is consistent with Na-K-ATPase-independent Na absorption. Increased Na-K-ATPase activity and mRNA in fasting suggest transition to Na-K-ATPase- dependent Na transport.

The behavior of ATPase in cotyledon tissue during germination

1972 ◽  
Vol 50 (2) ◽  
pp. 327-332 ◽  
Author(s):  
Y. F. Lai ◽  
J. E. Thompson
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Phaseolus Vulgaris ◽  
Atpase Activity ◽  
Major Part ◽  
Protein Body ◽  
Transport Processes ◽  
Assay Mixture ◽  
Storage Cells ◽  
Soluble Fractions

The behavior of ATPase in cotyledon tissue of Phaseolus vulgaris during germination has been examined with a view to assessing the feasibility of its involvement in transport processes. Both basal ATPase activity (no cations added to the assay mixture) and Na+–K+ stimulated activity were routinely present in homogenates of the tissue but decreased during germination in a manner that corresponded very closely with the pattern of protein attenuation for the same period. Since the decreased levels of protein primarily reflect protein body digestion, this parallel behavior suggests that as the need for transport of metabolites out of the storage cells becomes less, there is a corresponding decrease in the levels of basal and cation-stimulated ATPases.Fractionation of the tissue revealed that ATPase activity is present in isolated soluble fractions, but throughout the germination period the major proportions of both basal and Na+–K+ stimulated activities proved to be particulate and were distributed among nuclear, mitochondrial, and microsomal fractions. Since both types of ATPase are present in purified cell wall and plasma membrane from this tissue, this distribution is thought to reflect in large part fragmentation of cell wall and plasma membrane incurred during homogenization. Thus the subcellular distributions of the enzymes as well as their patterns of change during germination are consistent with the involvement of a major part of the cotyledon ATPase activity in transport phenomena.

scholarly journals Effect of Cyclosporin A on Hearing Status in Children with Difficult to Treat Idiopathic Nephrotic Syndrome

2021 ◽  
pp. 17-28
Author(s):  
Mohammed Tawfik Ramadan Rageh ◽  
Shimaa Basyony El-Nemr ◽  
Amani Mohamed El- Gharib ◽  
Hend Hassan Abdelnabi
Keyword(s):  
Nephrotic Syndrome ◽  
Cyclosporin A ◽  
High Frequency ◽  
Idiopathic Nephrotic Syndrome ◽  
Hearing Threshold ◽  
Positive Correlation ◽  
Hearing Status ◽  
Group I ◽  
High Frequency Audiometry ◽  
Group Ii

Background: Cyclosporin A (CsA) is an important drug regimen for difficult to treat nephrotic syndrome (NS) with few information known about its ototoxicity. Aims: Assessment the hearing status in children with difficult to treat idiopathic NS on CsA treatment. Material and Methods: This prospective cohort study included 2 groups: Group I: 15 children with steroid sensitive idiopathic nephrotic syndrome on steroids only as a line of treatment was used as comparing group to group II which included 15 children recently diagnosed difficult to treat NS starting CsA as steroids sparing drug, hearing functions were assessed using standard, high-frequency audiometry and transient otoacoustic emissions (TOAEs) at base line for both groups and after 6 months of CsA treatment for group II. Results: There was significant elevation of hearing threshold in extended high frequency (> 8 KHz) (subclinical hearing loss) after six months of CsA. There was positive correlation between Cyclosporin A trough level and elevated hearing threshold in pure tone audiometry and extended high frequency (> 8 KHz). There was insignificant difference between groups according to TOAEs. There was statistically significant positive correlation between extended high frequency range and serum trough CsA level in group II. Conclusions: CsA is a potential cause of hearing impairment in children with difficult to treat NS so all patients on CsA need routine audiological assessment especially with high serum CsA level and long duration.

scholarly journals CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Yilei Yang ◽  
Xin Huang ◽  
Yinping Shi ◽  
Rui Yang ◽  
Haiyan Shi ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Renal Transplant ◽  
High Performance ◽  
Therapeutic Drug ◽  
Transplant Patients ◽  
Cyp3a5 Genotype ◽  
Group I ◽  
Trough Concentrations ◽  
Renal Transplant Patients ◽  
Group Ii

Purpose: The drug-drug interactions (DDIs) of tacrolimus greatly contributed to pharmacokinetic variability. Nifedipine, frequently prescribed for hypertension, is a competitive CYP3A5 inhibitor which can inhibit tacrolimus metabolism. The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-nifedipine DDI in Chinese renal transplant patients.Method: All renal transplant patients were divided into CYP3A5*3/*3 homozygotes (group I) and CYP3A5*1 allele carriers (CYP3A5*1/*1 + CYP3A5*1/*3) (group II). Each group was subdivided into patients taking tacrolimus co-administered with nifedipine (CONF) and that administrated with tacrolimus alone (Controls). Tacrolimus trough concentrations (C0) were measured using high performance liquid chromatography. A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C0) (C0/D) between CONF and Controls in group I and II, respectively. At the same time, a multivariate line regression analysis was made to evaluate the effect of variates on C0/D.Results: In this study, a significant DDI between tacrolimus and nifedipine with respect to the CYP3A5*3 polymorphism was confirmed. In group I (n = 43), the C0/D of CONF was significantly higher than in Controls [225.2 ± 66.3 vs. 155.1 ± 34.6 ng/ml/(mg/kg); p = 0.002]. However, this difference was not detected in group II (n = 27) (p = 0.216). The co-administrated nifedipine and CYP3A5*3/*3 homozygotes significantly increased tacrolimus concentrations in multivariate line regression analysis.Discussion: A CYP3A5 genotype-dependent DDI was found between tacrolimus and nifedipine. Therefore, personalized therapy accounting for CYP3A5 genotype detection as well as therapeutic drug monitoring are necessary for renal transplant patients when treating with tacrolimus and nifedipine.

Is there a Cl- pump?

1988 ◽  
Vol 255 (5) ◽  
pp. R677-R692
Author(s):  
G. A. Gerencser ◽  
J. F. White ◽  
D. Gradmann ◽  
S. L. Bonting
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Membrane Fraction ◽  
Plasma Membranes ◽  
Direct Evidence ◽  
Objective Evaluation ◽  
Chemical Processes ◽  
Transport Processes ◽  
Cl Transport ◽  
Active Ion Transport

Three universally accepted mechanisms of Cl- transport across plasma membranes exist and they are 1) anion-coupled antiport, 2) cation-coupled symport, and 3) coupling to primary active ion transport through electrical and/or chemical processes. No unequivocal direct evidence has been provided for primary active Cl- transport (Cl- pump) despite numerous reports of cellular Cl- -stimulated adenosinetriphosphatase (ATPases) and of Cl- transport that cannot be accounted for by the three well-documented Cl- transport processes. It has been demonstrated that Cl- -stimulated ATPase activity is localized to both mitochondrial and microsomal aspects of the cellular apparatus. However, one group ascribes microsomal localization of Cl- -stimulated ATPase activity to mitochondrial contamination of that membrane fraction. Therefore, no Cl- pump could ever exist naturally in any plasma membrane. The other group simply states that there is plasma membrane localization of Cl- -stimulated ATPase activity that could function as a Cl- pump. Both arguments are logically advanced and their conclusions are consistent with their respective premises. Resolution to the question Is there a Cl- pump? rests with each reader's critique and objective evaluation.

scholarly journals Comparison between 200 ml and 1 liter packages of oral rehydration solution prepared by mothers of patients with diarrhea in the oral rehydration room

2019 ◽  
Vol 28 (11-12) ◽  
pp. 231-7
Author(s):  
Muhammad Suryanto ◽  
Renny Hariati ◽  
Yati Soenarto ◽  
Moenginah P. A.
Keyword(s):  
Oral Rehydration Solution ◽  
Sodium Concentration ◽  
Children Under Five ◽  
Oral Rehydration ◽  
Under Five ◽  
Group I ◽  
Significant Difference ◽  
Rehydration Solution ◽  
Group Ii ◽  
Hospital Group

To have a comparison between the preparation of oral rehydration solution (ORS) of 200 ml and 1 liter packages, a study had been done in 30 mothers of children under five years of age suffering from diarrhea who treated their children in oral rehydration room (group I) and 30 mothers of non diarrheal children under five years sampled in the out-patient Department of Child Health, Dr. Sardjito General Hospital (group II). No significant difference was found (p <0.05) concerning the sodium concentration in th ORS of 200 ml and in the 1 liter package (group I: 85.95 ± 16.07, and 81.52 ± 16.21, group II 98.11 ± 24.67 and 97.02 ± 21.87) (mEq/L, Mean ± SD). Of 30 mothers group 11, 5 mothers (19.23%) made mistakes in preparing the I liter packages of ORS and the sodium concentration in this package was higher compared to the concentration in the 200 ml package. There was no significant difference concerning diluted volume and the sodium concentration between group I and the recommended method, but there was a significant difference (p < 0.005) between group II and recommended method. A significant difference was also found (p ( 0.001) between group I and group 11 about the mothers knowledge of the effect of diarrhea, the use of ORS, the amount of ORS that must be given lo !he patients and !he indications to refer the patients to !he health center or hospital.

scholarly journals H+-ATPase ACTIVITY IN CRUDE HOMOGENATES OF FISH GILL TISSUE: INHIBITOR SENSITIVITY AND ENVIRONMENTAL AND HORMONAL REGULATION

1993 ◽  
Vol 180 (1) ◽  
pp. 163-174 ◽  
Author(s):  
H. Lin ◽  
D. J. Randall
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Hormonal Regulation ◽  
Gill Tissue ◽  
Sodium Concentration ◽  
Plasma Membrane Atpase ◽  
Atpase Inhibitor ◽  
Fish Gills ◽  
Fish Gill ◽  
Membrane Type

N-ethymaleimide-sensitive ATPase activity was measured in crude homogenates of gill tissue from rainbow trout using a coupled-enzyme ATPase assay in the presence of EGTA, ouabain and azide. This NEM-sensitive ATPase activity, determined to be about 1.5 micromole mg-1 protein h-1 at 15 °C for freshwater trout, is also inhibited by other H+-ATPase blockers such as DCCD, DES, PCMBS and bafilomycin. It is concluded, therefore, that the NEM-sensitive ATPase activity was generated by a proton-translocating ATPase. Since this NEM-sensitive ATPase was also sensitive to the plasma membrane ATPase inhibitor vanadate, we conclude that the H+-ATPase in fish gill is of the plasma membrane type. The major role of the H+-ATPase in the gill epithelium is to facilitate Na+ uptake from fresh water. Sodium concentration in the external medium was the primary regulator of the H+-ATPase in fish gills, with low sodium levels being associated with high H+-ATPase activity. High external calcium concentration had a marked stimulatory effect on H+-ATPase activity in fish gills when the sodium level was low. Environmental hypercapnia induced a 70 % increase in the H+-ATPase activity in fish gills. H+-ATPase activity was also elevated in freshwater fish after chronic cortisol infusion.

scholarly journals Hyperhomocyst(e)inemia in chronic stable renal transplant patients

2000 ◽  
Vol 55 (5) ◽  
pp. 161-168 ◽  
Author(s):  
David José de Barros Machado ◽  
Flávio Jota de Paula ◽  
Emil Sabbaga ◽  
Luiz Estevan Ianhez
Keyword(s):  
Folic Acid ◽  
Renal Transplant ◽  
Serum Creatinine ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Group Iii ◽  
Transplant Patients ◽  
Group I ◽  
Renal Transplant Patients ◽  
Group Ii

PURPOSE: Hyperhomocyst(e)inaemia is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients. The aim of this study was to assess the influence of immunosuppressive therapy on homocyst(e)inemia in renal transplant recipients. METHODS: Total serum homocysteine (by high performance liquid chromatography), creatinine, lipid profile, folic acid (by radioimmunoassay-RIA) and vitamin B12 (by RIA) concentrations were measured in 3 groups. Group I patients (n=20) were under treatment with cyclosporine, azathioprine, and prednisone; group II (n=9) were under treatment with azathioprine and prednisone; and group III (n=7) were composed of renal graft donors for groups I and II. Creatinine, estimated creatinine clearance, cyclosporine trough level, lipid profile, folic acid, and vitamin B12 concentrations and clinical characteristics of patients were assessed with the aim of ascertaining determinants of hyperhomocyst(e)inemia. RESULTS: Patient ages were 48.8 ± 15.1 yr (group I), 43.3 ± 11.3 yr (group II); and 46.5 ± 14.8 yr (group III). Mean serum homocyst(e)ine (tHcy) concentrations were 18.07 ± 8.29 mmol/l in renal transplant recipients; 16.55 ± 5.6 mmol/l and 21.44 ± 12.1 mmol/l respectively for group I (with cyclosporine) and group II (without cyclosporine) (NS). In renal donors, tHcy was significantly lower (9.07 ± 3.06 mmol/l; group I + group II vs. group III, p<0.008). There was an unadjusted correlation (p<0.10) between age (r=0.427; p<0.005) body weight (r=0.412; p<0.05), serum creatinine (r=0.427; p<0.05), estimated creatinine clearance (r=0.316; p<0.10), and tHcy in renal recipients (group I +II). Independent regressors (r²=0.46) identified in the multiple regression model were age (coefficient= 0.253; p=0.009) and serum creatinine (coefficient=8.07; p=0.045). We found no cases of hyperhomocyst(e)inemia in the control group. In contrast, 38% of renal recipients had hyperhomocyst(e)inemia: 7 cases (35%) on cyclosporine and 4 (45%) without cyclosporine, based on serum normal levels. CONCLUSIONS: Renal transplant recipients frequently have hyperhomocyst(e)inemia. Hyperhomocyst(e)inemia in renal transplant patients is independent of the scheme of immunosuppression they are taking. The older the patients are and the higher are their serum creatinine levels, the more susceptible they are to hyperhomocyst(e)inemia following renal transplantation.

Apoptotic-like changes of boar spermatozoa in freezing media supplemented with different antioxidants

2015 ◽  
Vol 18 (3) ◽  
pp. 473-480 ◽  
Author(s):  
M. Trzcińska ◽  
M. Bryła
Keyword(s):  
Plasma Membrane ◽  
Dna Fragmentation ◽  
Tunel Assay ◽  
Combination Group ◽  
Group Viii ◽  
Group Vi ◽  
Group V ◽  
Group I ◽  
Group Ii ◽  
Boar Spermatozoa

Abstract This study evaluated the effect of supplementing the freezing extender with exogenous anti-oxidants on apoptotic-like changes in post-thaw boar spermatozoa. A total of 36 ejaculates were resuspended in standard lactose-egg yolk-glycerol extender supplemented with antioxidant to final concentrations of 0 (as control), 2.5mM GSH (group I), 5.0 mM GSH (group II), 150 IU/mL SOD (group III), 300 IU/mL SOD (group IV), 200 IU/mL CAT (group V), 400 IU/mL CAT (group VI), 150 IU/mL SOD+200 IU/mL CAT (group VII), 300 IU/mL SOD+400 IU/mL CAT (group VIII). Sperm motility and apoptotic-like changes were determined before and after freeze-thawing. The various markers of apoptotic-like changes were measured: plasma membrane permeability by YO-PRO-1/PI assay, phosphatidylserine (PS) translocation across the plasma membrane using fluorescein-labeled Annexin-V, mitochondrial transmembrane potential detected by JC-1, and DNA fragmentation evaluated by TUNEL assay. The highest percentage of progressive motile sperm was noticed in group II (PM% 64.2±15.4) compared with control (PM% 36.8±5.5). The supplementation of 400 IU/mL CAT (group VI) revealed significant (P<0.01) reduction of apoptotic-like changes (YO-PRO-1+/PI−: 13.1±7.5%, AnV+/PI−: 9.9±4.1%) in frozen-thawed spermatozoa compared with extender supplemented with 200 IU/mL CAT (group V). Irrespective of the concentration used, SOD and CAT in combination (group VII and group VIII) significantly (P<0.01) improved post-thaw sperm survival compared with the control. Evaluation by TUNEL assay revealed that cryopreservation and thawing did not induce DNA fragmentation in boar spermatozoa.

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