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1.
J Trace Elem Med Biol ; 62: 126572, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32512477

ABSTRACT

AIM: This study aims to determine the changes induced by a maximal exercise test until exhaustion on the serum and urinary concentrations of Magnesium (Mg), Phosphorous (P), Rubidium (Rb) and Strontium (Sr) in athletes (AG) and sedentary students (SG). METHODS: Fifty subjects participated in the study divided into two groups. In AG there were twenty-five male athletes and in SG there were twenty-five male sedentary students. Both groups performed an exercise test until exhaustion, starting at 8 or 10 km/h respectively, and increasing the speed at 1 km/h every 400 m. Serum and urine samples were obtained from all participants before and after the test. RESULTS: Regarding the basal status, AG showed lower values of Mg in serum (p < 0.05) and urine (p < 0.01), but higher concentrations of serum P (p < 0.05) in comparison to SG. Comparing the pre and post-test values, corrected or non-corrected for hemoconcentration in serum and for creatinine in urine, AG showed a decrease in serum Mg (p < 0.05), in serum P (p < 0.01) and in urinary Sr (p < 0.01) while an increase was observed in urinary P (p < 0.05) and in urinary Rb (p < 0.05). CONCLUSIONS: It can be concluded that a treadmill test until exhaustion leads to changes in serum and urinary concentrations of minerals in both AG and SG males. This may reflect an adaptive response of the body to overcome the physical stress and, in some cases, to avoid loss of these elements.


Subject(s)
Exercise Test , Magnesium , Phosphorus , Rubidium , Strontium , Adult , Athletes , Creatinine/urine , Hematocrit , Humans , Magnesium/blood , Magnesium/urine , Male , Nontherapeutic Human Experimentation , Phosphorus/blood , Phosphorus/urine , Rubidium/blood , Rubidium/urine , Strontium/blood , Strontium/urine , Young Adult
2.
Biol Trace Elem Res ; 189(2): 379-386, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30171597

ABSTRACT

A considerable attention has been focused on the possible association between ultra-trace elements (UTEs) status and pathogenesis of many diseases including rheumatoid arthritis (RA). UTEs have important roles in numerous metabolic processes. Serum Cs, Rb, and Re levels in RA are not studied previously. The correlation of serum Cs, Rb, and Re levels with the well-known serological parameters, anticyclic citrullinated protein antibody (ACPA), C-reactive protein (CRP), ESR, and rheumatoid factor (RF) is also not studied previously. The present study aimed to measure the level and the correlation between serum UTEs with various blood tests results in RA patients. Serum Cs, Rb, Re, ACPA, CRP, RF, and ESR were measured in Iraqi RA patients who have a positive ACPA (ACPA > 25 U/ml) and compared with healthy individuals. There were significant elevations (p < 0.05) in serum levels of all the measured parameters as compared with those of the healthy control group except Rb and uric acid which have not been changed. Subgrouping of patients according to the results of CRP and RF leads to different results. In the low-CRP group, the high-RF subgroup showed an elevation of ACPA, Cs, and ESR in comparison with the low-RF patients. In the high-CRP group, the patients with high RF showed an increase in the levels of Cs, Rb, ESR, and ACPA. The patient group with high RF and high CRP showed more significant correlations between serum UTEs and serological tests. Serum levels of UTEs were significantly altered in RA patients. The variations in the serum levels of the measured parameters in RA need more investigation to explore the possible association between these UTEs and RA. RA subgroups, according to the results of CRP and CPA, produce more and various information than taking RA as a whole group in the estimation of UTEs.


Subject(s)
Arthritis, Rheumatoid/blood , Cesium/blood , Rhenium/blood , Rheumatoid Factor/blood , Rubidium/blood , Adult , Autoantibodies/blood , C-Reactive Protein/metabolism , Case-Control Studies , Female , Humans , Male , Middle Aged
3.
J Int Soc Sports Nutr ; 14: 19, 2017.
Article in English | MEDLINE | ID: mdl-28615997

ABSTRACT

BACKGROUND: The aim of this study was to observe the concentrations of trace metals boron, lithium, rubidium, antimony, tin and strontium in the serum of athletes from different modalities and sedentary subjects and the possible influence that different energy sports training modalities can have on their concentration. METHODS: Eighty professional athletes and 31 sedentary males participated in the present survey. All of them were living in Cáceres (Spain). Serum boron, lithium, rubidium, antimony, tin and strontium analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The results show higher concentrations in athletes on tin (p < 0.01), rubidium and antimony (p < 0.001) than the control group. In the case of tin, this item had the highest concentrations only in aerobic sports modalities. Regarding rubidium and antimony, the highest concentrations are found in athletes with lower oxygen consumption (aerobic-anaerobic) (p < 0.001), followed by anaerobic group (p < 0.001). CONCLUSION: Our research shows that, probably due to increased water and air intake, especially, trace elements rubidium, antimony and tin reveal major differences in serum concentration of athletes in relation to sedentary subjects. On the other hand, physical training does not change the serum concentration of Boron, Lithium and strontium.


Subject(s)
Exercise , Trace Elements/blood , Adolescent , Adult , Anthropometry , Antimony/blood , Athletes , Boron/blood , Case-Control Studies , Humans , Lithium/blood , Male , Rubidium/blood , Spain , Strontium/blood , Tin/blood , Young Adult
4.
Acta Anaesthesiol Scand ; 61(6): 650-659, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28573653

ABSTRACT

PURPOSE: Intensive care patients with acute kidney injury (AKI), treated with continuous renal replacement therapy (CRRT) are at great risk for disturbances in plasma levels of trace elements due to the underlying illness, AKI, and dialysis. This study was performed to increase our knowledge regarding eight different trace elements during CRRT. METHODS: Thirty one stable patients with AKI, treated with CRRT, were included in the study. Blood, plasma and effluent samples were taken at the start of the study and 36 ± 12 h later. A group of 48 healthy volunteers were included as controls and exposed to one fasting blood sample. Samples were analysed for trace elements (Cr, Cu, Mn, Co, Zn, Rb, Mo, Se) and standard blood chemistry. RESULTS: Blood and plasma levels of selenium and rubidium were significantly reduced while the levels of chromium, cobalt, and molybdenum were significantly increased in the study group vs. healthy volunteers. There was an uptake of chromium, manganese, and zinc. Molybdenum mass balance was around zero. For selenium, copper, and rubidium there were a marked loss. CONCLUSIONS: The low levels of selenium and rubidium in blood and plasma from CRRT patients, together with the loss via CRRT effluent, raises the possibility of the need for selenium supplementation in this group of patients, despite the unchanged levels during the short study period. Further investigations on the effect of additional administration of trace elements to CRRT patients would be of interest.


Subject(s)
Renal Replacement Therapy , Trace Elements/blood , Acute Kidney Injury/blood , Acute Kidney Injury/therapy , Adult , Aged , Aged, 80 and over , Critical Illness , Female , Healthy Volunteers , Humans , Male , Middle Aged , Nutritional Support , Renal Dialysis , Rubidium/blood , Rubidium/deficiency , Selenium/blood , Selenium/deficiency , Trace Elements/deficiency , Young Adult
5.
Biometals ; 28(4): 733-43, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26041486

ABSTRACT

Iron is reported to interact with other metals. In addition, it has been shown that genetic background may impact iron metabolism. Our objective was to characterize, in mice of three genetic backgrounds, the links between iron and several non-iron metals. Thirty normal mice (C57BL/6, Balb/c and DBA/2; n = 10 for each group), fed with the same diet, were studied. Quantification of iron, zinc, cobalt, copper, manganese, magnesium and rubidium was performed by ICP/MS in plasma, erythrocytes, liver and spleen. Transferrin saturation was determined. Hepatic hepcidin1 mRNA level was evaluated by quantitative RT-PCR. As previously reported, iron parameters were modulated by genetic background with significantly higher values for plasma iron parameters and liver iron concentration in DBA/2 and Balb/c strains. Hepatic hepcidin1 mRNA level was lower in DBA/2 mice. No iron parameter was correlated with hepcidin1 mRNA levels. Principal component analysis of the data obtained for non-iron metals indicated that metals parameters stratified the mice according to their genetic background. Plasma and tissue metals parameters that are dependent or independent of genetic background were identified. Moreover, relationships were found between plasma and tissue content of iron and some other metals parameters. Our data: (i) confirms the impact of the genetic background on iron parameters, (ii) shows that genetic background may also play a role in the metabolism of non-iron metals, (iii) identifies links between iron and other metals parameters which may have implications in the understanding and, potentially, the modulation of iron metabolism.


Subject(s)
Genetic Background , Iron/metabolism , Animals , Cobalt/blood , Cobalt/metabolism , Copper/blood , Copper/metabolism , Hepcidins/blood , Hepcidins/genetics , Hepcidins/metabolism , Iron/blood , Magnesium/blood , Magnesium/metabolism , Male , Manganese/blood , Manganese/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred DBA , Principal Component Analysis , RNA, Messenger/blood , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rubidium/blood , Rubidium/metabolism , Zinc/blood , Zinc/metabolism
6.
Article in Chinese | MEDLINE | ID: mdl-27122328

ABSTRACT

OBJECTIVE: To investigate the distribution of rubidium (Rb), cesium (Cs), beryllium (Be), strontium (Sr), and barium (Ba) in blood and urine in general Chinese population. METHODS: A total of 18 120 subjects aged 6~60 years were enrolled from 24 regions in 8 provinces in Eastern, Central, and Western China from 2009 to 2010 based on the method of cluster random sampling. Questionnaire survey was conducted to collect the data on living environment and health status. Blood and urine samples were collected from these subjects, and the levels of Rb, Cs, Be, Sr, and Ba in these samples were determined by inductively coupled plasma mass spectrometry. The distribution of these elements in blood and urine in male or female subjects living in different regions was analyzed statistically. RESULTS: In the general Chinese population, the concentration of Be in the whole blood was below the detection limit (0.06 µg/L); the geometric mean (GM) of Ba in the whole blood was below the detection limit (0.45 µg/L), with the 95th percentile (P95)of 1.37 µg/L; the GMs (95% CI)of Rb, Cs, and Sr in the whole blood were 2 374(2 357~2 392) µg/L, 2.01 (1.98~2.05) µg/L, and 23.5 (23.3~23.7) µg/L, respectively; in males and females, the GMs (95%CI)of blood Rb, Cs, and Sr were 2 506 (2 478~2 533) µg/L and 2 248 (2 227~2 270) µg/L, 1.88 (1.83~1.94) µg/L and 2.16 (2.11~2.20) µg/L, and 23.4 (23.1~23.7) µg/L and 23.6 (23.3~23.9) µg/L, respectively(P<0.01, P>0.05, and P>0.05). In the general Chinese population, the GM of urine Be was below the detection limit (0.06 µg/L), while the GMs (95%CI)of urine Rb, Cs, Sr, and Ba were 854 (836~873) µg/L, 3.65 (3.56~3.74) µg/L, 39.5 (38.4~40.6) µg/L, and 1.10 (1.07~1.12) µg/L, respectively; in males and females, the GMs (95%CI)of urine Rb, Cs, Sr, and Ba were 876 (849~904) µg/L and 832 (807~858) µg/L, 3.83 (3.70~3.96) µg/L and 3.47 (3.35~3.60) µg/L, 42.5 (40.9~44.2) µg/L and 36.6 (35.1~38.0) µg/L, and 1.15 (1.12~1.19) µg/L and 1.04 (1.01~1.07) µg/L, respectively (all P< 0.01). Correlation analyses showed that there were weak correlations between blood Rb and urine Rb (r=0.197)and between blood Sr and urine Sr (r=0.180), but a good correlation between blood Cs and urine Cs (r=0.487). CONCLUSION: The levels of Rb, Cs, Be, Sr, and Ba in the general Chinese population are similar to those reported in other countries, and there is a significant difference in the concentration of each element among the populations living in different regions, as well as significant differences in blood Rb, urine Rb, urine Cs, urine Sr, and urine Ba between males and females.


Subject(s)
Barium , Beryllium , Cesium , Rubidium , Strontium , Adolescent , Adult , Barium/blood , Barium/urine , Beryllium/blood , Beryllium/urine , Cesium/blood , Cesium/urine , Child , China , Female , Humans , Limit of Detection , Male , Middle Aged , Rubidium/blood , Rubidium/urine , Strontium/blood , Strontium/urine , Young Adult
7.
Health Phys ; 99(6): 811-3, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21068600

ABSTRACT

Three models for the biodistribution and dosimetry of 82Rb-chloride were reviewed and a proposal is made for the best dosimetry for this agent to be adopted. Data from three proposed biokinetic models for 82Rb-chloride were used to calculate dose estimates for the compound, and the results were compared. The blood content-based model was found to produce dose estimates that were considered to be overly conservative, and a blood flow-based model, which showed good agreement with available measured data, was considered to be more reasonable. A new set of dose estimates for 82Rb-chloride, based on the blood flow-based kinetic model are suggested for general use.


Subject(s)
Chlorides , Radiation Dosage , Radiometry/methods , Rubidium , Algorithms , Chlorides/blood , Chlorides/pharmacokinetics , Humans , Models, Biological , Radiometry/standards , Rubidium/blood , Rubidium/pharmacokinetics , Tissue Distribution
8.
Biopharm Drug Dispos ; 31(8-9): 455-63, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20848389

ABSTRACT

The altered electrolyte handling of the choroid plexus was investigated in rats with acute renal failure (ARF) using lithium and rubidium as surrogate markers for sodium and potassium, respectively. Firstly, the transport of these two markers from the plasma to cerebrospinal fluid (CSF) was evaluated after they were concurrently injected into the femoral vein. As a result, their disposition from the plasma to CSF was shown to decrease in ARF rats, but the relationship profile between those two markers was not different from that observed in normal rats, indicating that the decreased disposition of lithium and rubidium occurs without affecting the stoichiometric balance. To clarify the mechanisms accounting for the decreased disposition, an inhibition study was then performed. When bumetanide, an inhibitor of the Na(+) /K(+) /2Cl(-) co-transporter, was directly introduced into the cerebroventricle prior to lithium and rubidium being intravenously administered, a marked increase in the markers' disposition was observed. However, such an increased disposition did not occur when bumetanide was injected into the femoral vein. Other inhibitors, such as amiloride for the Na(+) /H(+) exchanger and ouabain for Na(+) /K(+) -ATPase, did not show any effects on marker disposition regardless of the inhibitor being administered into either the cerebroventricle or femoral vein. These findings suggest that the decreased marker disposition in ARF rats is due to an increased efflux process of the choroid plexus mediated by the Na(+) /K(+) /2Cl(-) co-transporter. That is, electrolyte efflux from the CSF to plasma increases, and thereby the electrolyte influx from the plasma to CSF is counteracted.


Subject(s)
Acute Kidney Injury/metabolism , Chlorides/metabolism , Choroid Plexus/metabolism , Electrolytes/metabolism , Lithium Chloride/metabolism , Rubidium/metabolism , Acute Kidney Injury/chemically induced , Animals , Area Under Curve , Bumetanide/pharmacology , Chlorides/blood , Chlorides/cerebrospinal fluid , Electrolytes/blood , Electrolytes/cerebrospinal fluid , Glycerol , Ion Transport , Lithium Chloride/blood , Lithium Chloride/cerebrospinal fluid , Male , Potassium/metabolism , Rats , Rats, Wistar , Rubidium/blood , Rubidium/cerebrospinal fluid , Sodium/metabolism , Sodium-Potassium-Chloride Symporters/metabolism , Solute Carrier Family 12, Member 2
9.
Environ Pollut ; 158(1): 98-107, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19713018

ABSTRACT

We investigated the concentrations of 22 essential and non-essential elements among a community of Procellariiformes (and their prey) to identify the extent to which trophic position and foraging range governed element accumulation. Stable isotope analysis (SIA) was used to characterise trophic (delta(15)N) and spatial patterns (delta(13)C) among species. Few consistent patterns were observed in element distributions among species and diet appeared to be highly influential in some instances. Arsenic levels in seabird red blood cells correlated with delta(15)N and delta(13)C, demonstrating the importance of trophic position and foraging range for arsenic distribution. Arsenic concentrations in prey varied significantly across taxa, and in the strength of association with delta(15)N values (trophic level). In most instances, element patterns in Procellariiformes showed the clearest separation among species, indicating that a combination of prey selection and other complex species-specific characteristics (e.g. moult patterns) were generally more important determining factors than trophic level per se.


Subject(s)
Birds/blood , Animals , Arsenic/analysis , Arsenic/blood , Cadmium/analysis , Cadmium/blood , Carbon Isotopes/analysis , Carbon Isotopes/blood , Georgia , Molybdenum/analysis , Molybdenum/blood , Nitrogen Isotopes/analysis , Nitrogen Isotopes/blood , Rubidium/analysis , Rubidium/blood , Selenium/analysis , Selenium/blood
10.
Neurobiol Aging ; 30(8): 1265-71, 2009 Aug.
Article in English | MEDLINE | ID: mdl-18191875

ABSTRACT

Accumulating evidence implicates a role for altered metal homeostasis in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, few investigations have addressed this issue in dementia with Lewy bodies (DLB). The aim of the present study was to investigate metal concentrations in cerebrospinal fluid (CSF) and plasma from patients with DLB and other neurodegenerative disorders. To that end, CSF and plasma samples were collected from 29 patients with DLB, 174 patients with AD, 90 patients with AD with minor vascular components, and 51 healthy volunteers. Total concentrations of Mg, Ca, Mn, Fe, Cu, Zn, Rb, Sr, and Cs were determined using mass spectrometry. Patients with DLB had elevated Ca and Mg levels in CSF and Mg levels in plasma as compared to all other groups (p<0.001). Furthermore, a combination of CSF-Mg and CSF-Ca could distinguish DLB from AD with a sensitivity of 93% and a specificity of 85%. Cu levels in both CSF and plasma tended to be higher in DLB compared to the other groups, but these trends failed to reach significance after correction for multiple comparisons. Mn, Fe, Zn, Rb, and Sr concentration in CSF or plasma were similar in all groups. The observed elevations of CSF-Mg, CSF-Ca and CSF-Cu may contribute to or be associated with the neurodegenerative process in DLB. Furthermore, determination of CSF-Mg and CSF-Ca concentration may be a valuable tool in distinguishing DLB from AD.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Calcium/cerebrospinal fluid , Lewy Body Disease/cerebrospinal fluid , Magnesium/cerebrospinal fluid , Aged , Aged, 80 and over , Alzheimer Disease/blood , Analysis of Variance , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Calcium/blood , Cesium/blood , Cesium/cerebrospinal fluid , Copper/blood , Copper/cerebrospinal fluid , Female , Humans , Iron/blood , Iron/cerebrospinal fluid , Lewy Body Disease/blood , Magnesium/blood , Male , Manganese/blood , Manganese/cerebrospinal fluid , Mass Spectrometry , Middle Aged , ROC Curve , Rubidium/blood , Rubidium/cerebrospinal fluid , Sensitivity and Specificity , Strontium/blood , Strontium/cerebrospinal fluid , Zinc/blood , Zinc/cerebrospinal fluid
11.
Am J Physiol Regul Integr Comp Physiol ; 293(5): R2090-8, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17761513

ABSTRACT

Over three decades ago, Parker and Snow (Am J Physiol 223: 888-893, 1972) demonstrated that canine erythrocytes undergo an increase in cation permeability when incubated with extracellular ATP. In this study we examined the expression and function of the channel/pore-forming P2X(7) receptor on canine erythrocytes. P2X(7) receptors were detected on canine erythrocytes by immunocytochemistry and immunoblotting. Extracellular ATP induced (86)Rb(+) (K(+)) efflux from canine erythrocytes that was 20 times greater than that from human erythrocytes. The P2X(7) agonist 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-trisphosphate (BzATP) was more potent than ATP, and both stimulated (86)Rb(+) efflux from erythrocytes in a dose-dependent fashion with EC(50) values of approximately 7 and approximately 309 microM, respectively. 2-Methylthioadenosine 5'-triphosphate and adenosine 5'-O-(3-thiotriphosphate) induced a smaller (86)Rb(+) efflux from erythrocytes, whereas ADP, AMP, UTP, or adenosine had no effect. ATP-induced (86)Rb(+) efflux from erythrocytes was inhibited by oxidized ATP, KN-62, and Brilliant blue G, known P2X(7) antagonists. ATP also induced uptake of choline(+) into canine erythrocytes that was 60 times greater than that into human erythrocytes. Overnight incubation of canine erythrocytes with ATP and BzATP induced phosphatidylserine exposure in >80% of cells and caused up to 20% hemolysis. In contrast, <30% of human erythrocytes showed phosphatidylserine exposure after overnight incubation with ATP and BzATP, and hemolysis was negligible. Flow cytometric measurements of ATP-induced ethidium(+) uptake showed that P2X(7) function was three times lower in canine monocytes than in human monocytes. These data show that the massive cation permeability increase induced by extracellular ATP in canine erythrocytes results from activation and opening of the P2X(7) receptor channel/pore.


Subject(s)
Erythrocytes/metabolism , Receptors, Purinergic P2/blood , Adenosine Triphosphate/pharmacology , Animals , Blotting, Western , Choline/blood , Dogs , Ethidium/blood , Flow Cytometry , Fluorescent Antibody Technique , Hemoglobins/metabolism , Hemolysis , Humans , In Vitro Techniques , Microscopy, Confocal , Monocytes/drug effects , Monocytes/metabolism , Phosphatidylserines/pharmacology , Receptors, Purinergic P2/genetics , Receptors, Purinergic P2X7 , Rubidium/blood , Species Specificity
12.
N Z Med J ; 118(1210): U1319, 2005 Feb 25.
Article in English | MEDLINE | ID: mdl-15776095

ABSTRACT

AIMS: This pilot study tested the hypothesis that aluminium (Al), rubidium (Rb), arsenic (As), lead (Pb), mercury (Hg), fluorine (F), and chlorine (Cl), which are all known to be present in volcanic emissions, may be useful biological markers for occupational gas exposure in volcanologists. METHODS: Ten human subjects were exposed to fumarole gases on White Island, New Zealand, for approximately 20 minutes. Sulphur dioxide (SO2) exposure was recorded by personal monitoring tubes. Pre- and post-exposure urine, blood and serum samples (collected using standard protocols) were analysed in the pathology laboratory for trace element and halogen content. RESULTS: Average personal exposure was measured at <75 ppm SO2 and calculated at approximately 25 ppm HCl, approximately 8 ppm hydrogen fluoride (HF), approximately 1 ppm Al, approximately 0.1 ppb Rb and approximately 4 ppb Pb. These concentrations almost certainly exceed those usually found in occupational exposure settings. Advanced levels of urinary Al and Rb were found following gas exposure and were statistically significant in the population at p<0.005 and p<0.001, respectively. The other chemical elements that were analysed (urinary Cl, F, and Hg; blood Pb, and serum Al) did not show such patterns. CONCLUSIONS: It is possible that urinary Al and Rb may be useful markers for exposure, a hypothesis which should be followed up in future work.


Subject(s)
Air Pollutants/blood , Air Pollutants/urine , Inhalation Exposure , Metals/blood , Metals/urine , Volcanic Eruptions , Adult , Aluminum/blood , Aluminum/urine , Arsenic/blood , Arsenic/urine , Biomarkers/blood , Biomarkers/urine , Chlorine/blood , Chlorine/urine , Environmental Monitoring , Fluorine/blood , Fluorine/urine , Humans , Lead/blood , Lead/urine , Mercury/blood , Mercury/urine , Pilot Projects , Rubidium/blood , Rubidium/urine
13.
Eur J Neurosci ; 20(7): 1761-8, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15379997

ABSTRACT

Early deterioration and death after brain injury is often the result of oedema in the injured and peri-lesional tissue. So far, no pharmacotherapy is available that exhibits significant brain oedema-reducing efficacy in patients. We selected two low molecular weight compounds from different chemical classes, a triazole (1-[(2-chlorophenyl)diphenylmethyl]-1,2,3-triazole) and a cyclohexadiene (methyl 4-[4-chloro-3-(trifluoromethyl)phenyl]-6-methyl-3-oxo-1,4,7-tetrahydroisobenzofuran-5-carboxylate) to characterize their pharmacological properties on KCNN4 channels (intermediate/small conductance calcium-activated potassium channel, subfamily N, member 4) in vitro as well as in vivo. In vitro we replaced potassium by rubidium (Rb+) and determined Rb+ fluxes evoked by 10 micro m of the calcium ionophore A23187 on C6BU1 rat glioma cells. Compared with known KCNN4 blockers, such as clotrimazole (IC50=360 +/- 12 nm) and charybdotoxin (IC50=3.3 +/- 1.9 nm), the triazole and cyclohexadiene were considerably more potent than clotrimazole and displayed similar potencies (IC50=12.1 +/- 8.8 and 13.3 +/- 4.7 nm, respectively). In the rat acute subdural haematoma model, both the triazole and cyclohexadiene displayed reduction of brain water content (-26% at 0.3 mg/kg and -24% at 0.01 mg/kg) and reduction of the intracranial pressure (-46% at 0.1 mg/kg and -60% at 0.003 mg/kg) after 24 h when administered as a 4-h infusion immediately after brain injury. When infarct volumes were determined after 7 days, the triazole as well as the cyclohexadiene displayed strong neuroprotective efficacy (-52% infarct volume reduction at 1.2 mg/kg and -43% at 0.04 mg/kg, respectively). It is concluded that blockade of KCNN4 channels is a new pharmacological approach to attenuate acute brain damage caused by traumatic brain injury.


Subject(s)
Brain Edema/therapy , Brain Injuries/therapy , Clotrimazole/therapeutic use , Hematoma, Subdural/therapy , Potassium Channel Blockers/therapeutic use , Animals , Brain Chemistry , Calcimycin/pharmacology , Cell Line, Tumor , Cerebral Infarction/pathology , Charybdotoxin/therapeutic use , DNA Primers , Erythrocytes/physiology , Glioma/genetics , Humans , Intermediate-Conductance Calcium-Activated Potassium Channels , Potassium Channels, Calcium-Activated , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Rubidium/blood , Water/analysis
14.
Biol Trace Elem Res ; 98(1): 27-43, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15051898

ABSTRACT

Intestinal permeability has been suggested to be closely linked with the etiology or activity of Crohn's disease. However, current methods for measurement of intestinal permeability are too laborious for routine examination, as they require urine collection and/or use of radioisotopes. The present study was performed to develop a more convenient and safer method for assessing intestinal permeability using blood samples rather than urine. Rats with indomethacin-induced enteritis were orally administered Rb, Mn, and Zn as tracers. Intestinal permeability was determined by assaying the levels of Rb, Mn, and Zn in blood samples by particle-induced X-ray emission (PIXE). The distributions of Rb, Mn, and Zn in the small intestine after administration were analyzed by micro-PIXE. The conventional PIXE analysis showed that the levels of Rb and Zn in the blood in the enteritis group were correlated with the grade of enteritis. The micro-PIXE analysis showed that Rb, Mn, and Zn were translocated into the wall of the proximal small intestine 5 min after administration, and this effect was more conspicuous in the enteritis group than in controls. Analysis of blood or small intestine tissue samples using the PIXE allows determination of both intestinal permeability and the route of permeation.


Subject(s)
Intestinal Absorption , Intestine, Small/metabolism , Manganese/metabolism , Rubidium/metabolism , Spectrometry, X-Ray Emission/methods , Zinc/metabolism , Animals , Crohn Disease/metabolism , Crohn Disease/pathology , Enteritis/chemically induced , Enteritis/metabolism , Enteritis/pathology , Indomethacin/pharmacology , Inflammation/metabolism , Inflammation/pathology , Intestine, Small/pathology , Male , Manganese/administration & dosage , Manganese/blood , Permeability , Rats , Rats, Sprague-Dawley , Rubidium/administration & dosage , Rubidium/blood , Zinc/administration & dosage , Zinc/blood
15.
Eur J Biochem ; 270(12): 2605-11, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12787026

ABSTRACT

Alpha-crystallin, a molecular chaperone and lens structural protein protects soluble enzymes against heat-induced aggregation and inactivation by a variety of molecules. In this study we investigated the chaperone function of alpha-crystallin in a more physiological system in which alpha-crystallin was incorporated into red cell 'ghosts'. Its ability to protect the intrinsic membrane protein Na/K-ATPase from external stresses was studied. Red cell ghosts were created by lysing the red cells and removing cytoplasmic contents by size-exclusion chromatography. The resulting ghost cells retain Na/K-ATPase activity. alpha-Crystallin was incorporated in the cells on resealing and the activity of Na/K-ATPase assessed by ouabain-sensitive 86Rb uptake. Incubation with fructose, hydrogen peroxide and methylglyoxal (compounds that have been implicated in diabetes and cataract formation) were used to test inactivation of the Na/K pump. Intracellular alpha-crystallin protected against the decrease in ouabain sensitive 86Rb uptake, and therefore against inactivation induced by all external modifiers, in a dose-dependent manner.


Subject(s)
Erythrocyte Membrane/physiology , Oxidative Stress/physiology , Sodium-Potassium-Exchanging ATPase/blood , alpha-Crystallins/blood , Adenosine Triphosphate/blood , Erythrocyte Membrane/drug effects , Glycosylation , Hemolysis , Humans , Hydrogen Peroxide/pharmacology , Molecular Chaperones/blood , Ouabain/pharmacology , Rubidium/blood , Rubidium/pharmacokinetics , Sucrose/pharmacology
16.
Blood ; 101(6): 2412-8, 2003 Mar 15.
Article in English | MEDLINE | ID: mdl-12433690

ABSTRACT

A prominent feature of sickle cell anemia is the presence of dehydrated red blood cells (RBCs) in circulation. Loss of potassium (K(+)), chloride (Cl(-)), and water from RBCs is thought to contribute to the production of these dehydrated cells. One main route of K(+) loss in the RBC is the Gardos channel, a calcium (Ca(2+))-activated K(+) channel. Clotrimazole (CLT), an inhibitor of the Gardos channel, has been shown to reduce RBC dehydration in vitro and in vivo. We have developed a chemically novel compound, ICA-17043, that has greater potency and selectivity than CLT in inhibiting the Gardos channel. ICA-17043 blocked Ca(2+)-induced rubidium flux from human RBCs with an IC(50) value of 11 +/- 2 nM (CLT IC(50) = 100 +/- 12 nM) and inhibited RBC dehydration with an IC(50) of 30 +/- 20 nM. In a transgenic mouse model of sickle cell disease (SAD), treatment with ICA-17043 (10 mg/kg orally, twice a day) for 21 days showed a marked and constant inhibition of the Gardos channel activity (with an average inhibition of 90% +/- 27%, P <.005), an increase in RBC K(+) content (from 392 +/- 19.9 to 479.2 +/- 40 mmol/kg hemoglobin [Hb], P <.005), a significant increase in hematocrit (Hct) (from 0.435 +/- 0.007 to 0.509 +/- 0.022 [43.5% +/- 0.7% to 50.9% +/- 2.2%], P <.005), a decrease in mean corpuscular hemoglobin concentration (MCHC) (from 340 +/- 9.0 to 300 +/- 15 g/L [34.0 +/- 0.9 to 30 +/- 1.5 g/dL], P <.05), and a left-shift in RBC density curves. These data indicate that ICA-17043 is a potent inhibitor of the Gardos channel and ameliorates RBC dehydration in the SAD mouse.


Subject(s)
Acetamides/pharmacology , Anemia, Sickle Cell/blood , Calcium Channel Blockers/pharmacology , Erythrocytes/chemistry , Potassium Channels, Calcium-Activated/antagonists & inhibitors , Trityl Compounds/pharmacology , Acetamides/chemistry , Acetamides/therapeutic use , Anemia, Sickle Cell/drug therapy , Animals , Calcium/pharmacology , Clotrimazole/chemistry , Clotrimazole/pharmacology , Clotrimazole/therapeutic use , Erythrocytes/drug effects , Erythrocytes/physiology , Female , Humans , Hypoxia , Male , Mice , Mice, Transgenic , Potassium Channels, Calcium-Activated/metabolism , Rubidium/blood , Trityl Compounds/chemistry , Trityl Compounds/therapeutic use
17.
Am J Physiol Cell Physiol ; 281(3): C825-32, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11502559

ABSTRACT

This work was undertaken to obtain a direct measure of the stoichiometry of Na(+)-independent K(+)-Cl(-) cotransport (KCC), with rabbit red blood cells as a model system. To determine whether (86)Rb(+) can be used quantitatively as a tracer for KCC, (86)Rb(+) and K(+) effluxes were measured in parallel after activation of KCC with N-ethylmaleimide (NEM). The rate constant for NEM-stimulated K(+) efflux into isosmotic NaCl was smaller than that for (86)Rb(+) by a factor of 0.68 +/- 0.11 (SD, n = 5). This correction factor was used in all other experiments to calculate the K(+) efflux from the measured (86)Rb(+) efflux. To minimize interference from the anion exchanger, extracellular Cl(-) was replaced with SO, and 4,4'-diisothiocyanothiocyanatodihydrostilbene-2,2'-disulfonic acid was present in the flux media. The membrane potential was clamped near 0 mV with the protonophore 2,4-dinitrophenol. The Cl(-) efflux at 25 degrees C under these conditions is approximately 100,000-fold smaller than the uninhibited Cl(-)/Cl(-) exchange flux and is stimulated approximately 2-fold by NEM. The NEM-stimulated (36)Cl(-) flux is inhibited by okadaic acid and calyculin A, as expected for KCC. The ratio of the NEM-stimulated K(+) to Cl(-) efflux is 1.12 +/- 0.26 (SD, n = 5). We conclude that K(+)-Cl(-) cotransport in rabbit red blood cells has a stoichiometry of 1:1.


Subject(s)
Carrier Proteins/blood , Chlorides/blood , Erythrocyte Membrane/physiology , Erythrocytes/physiology , Potassium/blood , Symporters , 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology , Animals , Carrier Proteins/drug effects , Erythrocytes/drug effects , Ethylmaleimide/pharmacology , In Vitro Techniques , Kinetics , Membrane Potentials/drug effects , Membrane Potentials/physiology , Rabbits , Rubidium/blood , K Cl- Cotransporters
18.
Biol Trace Elem Res ; 84(1-3): 37-43, 2001.
Article in English | MEDLINE | ID: mdl-11817694

ABSTRACT

The contents of elements K, Ca, Fe, Cu, Zn, Se, and Rb in erythrocytes of 78 cases with different thyroid hormone status have been measured by proton-induced X-ray emission and neutron activation analysis. According to the status of thyroid hormones T3, T4, TSH, FT3, and FT4 detected by radioimmunoassay, the experiment subjects were divided into four groups (i.e., hyperthyroid, hypothyroid, critical [one of thyroid hormones was abnormal], and normal). Elements contents and hormones levels of four groups were analyzed by one-way analysis of variance and correlation using an SPSS/PC statistical package. The results showed that the Se contents of four groups were not significantly different (p<0.05). Zn content of hypothyroid group was significantly higher than those of hyperthyroid and critical groups. The Zn content of the normal group was higher than that of the hypothyroid group and lower than that of the hyperthyroid and critical groups. In the hyperthyroid group, there were significant correlations between elements contents and thyroid hormones levels (except TSH), but not between elements contents and levels of thyroid hormones. However, in the hypothyroid group, relatively strong correlations have been found between elements contents and thyroid hormones levels, especially between Zn and the T3/T4 ratio, and between Zn and TSH.


Subject(s)
Erythrocytes/metabolism , Thyroid Hormones/blood , Trace Elements/blood , Animals , Calcium/blood , Cattle , Copper/blood , Graves Disease/blood , Humans , Iodine/blood , Iodine Radioisotopes/therapeutic use , Iron/blood , Neutrons , Ostreidae , Potassium/blood , Protons , Radioimmunoassay , Rubidium/blood , Selenium/blood , X-Rays , Zinc/blood
19.
Bioelectrochemistry ; 52(2): 127-31, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11129236

ABSTRACT

The maintenance of red blood cell volume is important in the pathophysiology of sickle cell disease. The KCl cotransporter (KCCl) is capable of mediating sickle cell dehydration. In this study, we have determined the effect of increased temperature (over the range 37-41 degrees C) on basal K+ transport and K+ transport following activation of KCCl by urea or N-ethylmaleimide (NEM). An increased temperature was found to have only a small effect (approximately a 20% increase) on basal K+ transport. In contrast, the increase was much greater (about 60%) after activation of KCCl by urea. Following activation of KCCl by NEM, the increase in K+ transport with increasing temperature was small (about 10%). This suggests that it is the signalling system rather than the transporter itself that is sensitive to temperature.


Subject(s)
Anemia, Sickle Cell/blood , Carrier Proteins/blood , Symporters , Humans , Hydrogen-Ion Concentration , Rubidium/blood , Temperature , K Cl- Cotransporters
20.
Eur Biophys J ; 29(7): 464-71, 2000.
Article in English | MEDLINE | ID: mdl-11156287

ABSTRACT

Forces that are able to transport Na+ and K+ into two compartments were investigated. A modified Nernst-Planck equation for coupled flows of electric current, water, and ions was integrated. The result shows that if alkali ions in the ion channel of the cell membrane are separated by their electric-current-induced inward flows against an electro-osmotic outward flow of water, the logarithms of the stationary cell/medium distributions of these ions should be proportional to the inverse of their diffusion mobilities. The relationship was tested in human erythrocytes. From inward and outward movements of tracer alkali ions, calculations were made to obtain their stationary distributions at infinite time. The cell/medium distributions determined in this way at 38 degrees C are Li+ = 0.59, 22Na+ = 0.044, 42K+ = 10.0, 86Rb+ = 11.9, and 137Cs+ = 3.07. The entry rates of ions into the cell at 0 degrees C are understood to represent their diffusion mobilities in the pump channel. The entry rates are Li+ = 1.44, 2Na+ = 1, 42K+ = 2.22, 86Rb+ = 2.39, and 137Cs+ = 1.72 relative to that of 22Na+. There is an expected negative correlation between the logarithms of the stationary cell/ medium distributions at 38 degrees C and the inverse of the entry rates into the cell at 0 degrees C for the five ions. It is suggested that the proposed physical forces cause the separation of alkali ions in the channel of Na,K-ATPase.


Subject(s)
Cesium/blood , Erythrocytes/metabolism , Lithium/blood , Potassium/blood , Rubidium/blood , Sodium/blood , Biological Transport, Active , Electrochemistry , Erythrocytes/chemistry , Humans , Hydrostatic Pressure , Kinetics , Models, Biological , Sodium-Potassium-Exchanging ATPase/blood , Temperature , Thermodynamics
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