The Measurement of Transmembrane Cation Transportin vivoin Acute Manic Illness

1989 ◽  
Vol 155 (4) ◽  
pp. 501-504 ◽  
Author(s):  
A. J. Wood ◽  
J. K. Aronson ◽  
P. J. Cowen ◽  
D. G. Grahame-Smith

We have used a novel technique to assess the transport of cations across the erythrocyte membranein vivoin unmedicated patients suffering an acute manic illness. The results show that erythrocyte cation transport via the sodium-pump enzyme Na+,K+-ATPase is increased in manic patients compared with healthy controls.

1992 ◽  
Vol 82 (1) ◽  
pp. 99-104 ◽  
Author(s):  
J. F. St. J. Dwight ◽  
A. C. Mendes Ribeiro ◽  
B. M. Hendry

1. Sodium pump function has been assessed by measurement of ouabain-sensitive 86Rb uptake in human erythrocytes after incorporation of palmitic, stearic, oleic and linoleic acids into the erythrocyte membrane. 14C-labelled fatty acids were used to measure membrane uptake of these substances. 2. For palmitic, oleic and linoleic acids, up to 1000 nmol of the fatty acid/ml of packed cells can be incorporated without causing significant haemolysis. For stearic acid, 270 nmol/ml of packed cells was incorporated in similar conditions. More than 88% of the fatty acid incorporated could be extracted with a 50 μmol/l fatty-acid-free albumin solution and was, therefore, in a non-esterified form in the erythrocyte membrane. The concentrations of palmitic, stearic, oleic and linoleic acids incorporated in these experiments represent a five- to ten-fold increase above the normal concentrations of these fatty acids in the membrane. 3. Up to 1000 nmol of palmitic, oleic and linoleic acids/ ml of packed cells and up to 270 nmol of stearic acid/ml of packed cells could be incorporated without a significant change in mean ouabain-sensitive 86Rb uptake with respect to control cells. Mean percentage changes in ouabain-sensitive 86Rb uptake for all these experiments were: palmitic acid, 3.7% (sd 11.4, n = 15); stearic acid, 4.0% (sd 5.7, n = 7); oleic acid, −4.8% (sd 19, n = 17); linoleic acid, 2.2% (sd 15.6, n = 19). 4. The demonstration of near-normal sodium pump activity in the presence of greatly elevated membrane levels of these fatty acids makes it extremely unlikely that they act as modulators of sodium pump function in vivo.


1989 ◽  
Vol 77 (4) ◽  
pp. 375-381 ◽  
Author(s):  
S. Balzan ◽  
U. Montali ◽  
A. Genovesi-Ebert ◽  
P. Biver ◽  
M. Fantoni ◽  
...  

1. To investigate endogenous cardiac glycoside-like compounds in plasma and their ability to inhibit the sodium pump, digoxin-like immunoreactivity [digoxin-like immunoreactive substance(s), DL1S] and 86Rb uptake by erythrocytes were measured in plasma extracts from normal adults, hypertensive adults and neonates. 2. DLIS levels in neonate plasma extracts were significantly higher than those found for normotensive or hypertensive adults. No difference was observed between normotensive and hypertensive subjects. DLIS was significantly increased when boiled plasma was extracted. 3. Extracts of boiled neonate and adult plasma inhibited 86Rb uptake. Instead, when boiling was omitted, no detectable inhibition was found in extracts of plasma from normotensive or hypertensive adult subjects. When present, the inhibition resulted from a depression of the ouabain-sensitive (sodium-pump-mediated) component, and, for the boiled neonate plasma only, also of the ouabain-resistant component. When the data from the different groups were pooled, a statistically significant inverse relationship between DLIS and erythrocyte 86Rb uptake was observed. Furthermore, in a subgroup of samples in which determinations were made before and after boiling in the same samples, an inverse correlation was found between changes in DLIS and changes in ouabain-sensitive (but not ouabain-resistant) 86Rb uptake. 4. Plasma extracts incubated with albumin at a physiological concentration significantly decreased (by approximately 20%) the inhibition of 86Rb uptake observed. 5. These findings support the existence of one or more endogenous compounds which both bind to antidigoxin antibodies and inhibit transmembrane cation transport. Part of this inhibition may, however, not involve the sodium pump. Furthermore, this chemically unidentified substance(s) may be bound to plasma proteins which partly reduce its action in vivo.


1989 ◽  
Vol 155 (4) ◽  
pp. 504-510 ◽  
Author(s):  
A. J. Wood ◽  
M. Elphick ◽  
J. K. Aronson ◽  
D. G. Grahame-Smith

We have investigated cation transportin vivoin patients being treated with lithium for bipolar affective illness by studying the disposition of rubidium after an oral load of rubidium chloride. The rate of erythrocyte cation transport was increased in the patients when compared with matched healthy volunteers. However, the rate ofin-vivoerythrocyte rubidium accumulation in the euthymic treated patients was significantly lower than in a matched group of unmedicated manic patients. The regulation of specific pathways for cation transport may be altered in individuals predisposed to affective illness.


Diabetes ◽  
1987 ◽  
Vol 36 (9) ◽  
pp. 991-995 ◽  
Author(s):  
D. Rahmani-Jourdheuil ◽  
Y. Mourayre ◽  
P. Vague ◽  
J. Boyer ◽  
I. Juhan-Vague

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hansol Lee ◽  
Myung Jun Lee ◽  
Eun-Joo Kim ◽  
Gi Yeong Huh ◽  
Jae-Hyeok Lee ◽  
...  

AbstractAbnormal iron accumulation around the substantia nigra (SN) is a diagnostic indicator of Parkinsonism. This study aimed to identify iron-related microarchitectural changes around the SN of brains with progressive supranuclear palsy (PSP) via postmortem validations and in vivo magnetic resonance imaging (MRI). 7 T high-resolution MRI was applied to two postmortem brain tissues, from one normal brain and one PSP brain. Histopathological examinations were performed to demonstrate the molecular origin of the high-resolution postmortem MRI findings, by using ferric iron staining, myelin staining, and two-dimensional laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging. In vivo iron-related MRI was performed on five healthy controls, five patients with Parkinson’s disease (PD), and five patients with PSP. In the postmortem examination, excessive iron deposition along the myelinated fiber at the anterior SN and third cranial nerve (oculomotor nerve) fascicles of the PSP brain was verified by LA-ICP-MS. This region corresponded to those with high R2* values and positive susceptibility from quantitative susceptibility mapping (QSM), but was less sensitive in Perls’ Prussian blue staining. In in vivo susceptibility-weighted imaging, hypointense pixels were observed in the region between the SN and red nucleus (RN) in patients with PSP, but not in healthy controls and patients with PD. R2* and QSM values of such region were significantly higher in patients with PSP compared to those in healthy controls and patients with PD as well (vs. healthy control: p = 0.008; vs. PD: p = 0.008). Thus, excessive iron accumulation along the myelinated fibers at the anterior SN and oculomotor nerve fascicles may be a pathological characteristic and crucial MR biomarker in a brain with PSP.


2021 ◽  
Vol 09 (06) ◽  
pp. E918-E924
Author(s):  
Tomonori Yano ◽  
Atsushi Ohata ◽  
Yuji Hiraki ◽  
Makoto Tanaka ◽  
Satoshi Shinozaki ◽  
...  

Abstract Backgrounds and study aims Gel immersion endoscopy is a novel technique to secure the visual field during endoscopy. The aim of this study was to develop a dedicated gel for this technique. Methods To identify appropriate viscoelasticity and electrical conductivity, various gels were examined. Based on these results, the dedicated gel “OPF-203” was developed. Efficacy and safety of OPF-203 were evaluated in a porcine model. Results  In vitro experiments showed that a viscosity of 230 to 1900 mPa·s, loss tangent (tanδ) ≤ 0.6, and hardness of 240 to 540 N/cm2 were suitable. Ex vivo experiments showed electrical conductivity ≤ 220 μS/cm is appropriate. In vivo experiments using gastrointestinal bleeding showed that OPF-203 provided clear visualization compared to water. After electrocoagulation of gastric mucosa in OPF-203, severe coagulative necrosis was not observed in the muscularis but limited to the mucosa. Conclusions OPF-203 is useful for gel immersion endoscopy.


2021 ◽  
Vol 22 (15) ◽  
pp. 8031
Author(s):  
Iris G. M. Schouten ◽  
Richard A. Mumford ◽  
Dirk Jan A. R. Moes ◽  
Pieter S. Hiemstra ◽  
Jan Stolk

In alpha-1-antitrypsin deficiency (AATD), neutrophil serine proteases such as elastase and proteinase 3 (PR3) are insufficiently inhibited. A previous study in AATD patients showed a higher plasma level of the specific PR3-generated fibrinogen-derived peptide AαVal541, compared with healthy controls. Here, we analyzed the course of AαVal541 plasma levels during 4 weeks after a single iv dose of 240 mg/kg AAT in ten patients with genotype Z/Rare or Rare/Rare. To this end, we developed an immunoassay to measure AαVal541 in plasma and applied population pharmacokinetic modeling for AAT. The median AαVal541 plasma level before treatment was 140.2 nM (IQR 51.5–234.8 nM)). In five patients who received AAT for the first time, AαVal541 levels decreased to 20.6 nM (IQR 5.8–88.9 nM), and in five patients who already had received multiple infusions before, it decreased to 26.2 nM (IQR 22.31–35.0 nM). In 9 of 10 patients, AαVal541 levels were reduced to the median level of healthy controls (21.4 nM; IQR 16.7–30.1 nM). At 7–14 days after treatment, AαVal541 levels started to increase again in all patients. Our results show that fibrinopeptide AαVal541 may serve as a biochemical footprint to assess the efficacy of in vivo inhibition of PR3 activity in patients receiving intravenous AAT augmentation therapy.


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