A new clinical score to identify children at low risk for appendicitis.

BACKGROUND: Besides clinical signs and imaging, in recent years, biomarkers have proven to be a viable diagnostic resource for acute appendicitis (AA). OBJECTIVE: The objective of this study was to develop a clinical score including clinical signs and a combination of biomarkers to identify children with abdominal pain at low risk of AA. DESIGN/METHODS: We prospectively included children 2 to 14 years of age with abdominal pain suggestive of AA who presented to the emergency department between July 2016 and September 2017. A new score, the Pediatric Appendicitis Laboratory Score (PALabS) including clinical signs, leucocyte (WBC) and neutrophil (ANC) counts and plasma C-reactive protein (CRP) and calprotectin (CP) levels was developed and validated through secondary analyses of two distinct cohorts The validation sample included visits to a single pediatric emergency department from 2012 to 2013 and 2016 to 2017. RESULTS: The derivation sample included 278 children, 35.9% of whom had AA and the validation sample included 255 children, 49% of whom had AA. Using logistic regression, we created a 6-part score that consisted of nausea (3 points), history of focal right lower quadrant pain (4 points), ANC of ≥7500/µL (7 points), WBC of ≥10,000/µL (4 points), CRP ≥ 10.0 mg/L (2 points) and CP ≥ 0.50 ≥ ng/mL (3 points). This score exhibited a high discriminatory power (area under the curve: 0.88; 95% confidence interval: 0.84 to 0.92) and outperformed the PAS and Kharbanda scores (area under the curve: 0.76; 95% confidence interval: 0.71 to 0.82 and 0.82; 95% confidence interval: 0.77 to 0.87, respectively). A PALabS ≤6 had a sensitivity of 99.2% (95% confidence interval [CI]: 95.6-99.9), negative predictive value of 97.6% (95% CI: 87.7-99.6), and negative likelihood ratio of 0.03 (95% CI: 0.00-0.18) in the validation set. CONCLUSION: In our validation cohort of patients with acute abdominal pain, the new score can accurately predict which children are at low risk of appendicitis and could be safely managed with close observation.

Usefulness of new and traditional serum biomarkers in children with suspected appendicitis.

OBJECTIVE: The objective of the study is to evaluate the usefulness of the leukocyte (white blood count [WBC]) and neutrophil (absolute neutrophil count [ANC]) counts; the values of C-reactive protein (CRP), procalcitonin, and calprotectin (CP); and the APPY1 Test panel of biomarkers, to identify children with abdominal pain at low risk for appendicitis. METHOD: Children 2 to 14 years of age with abdominal pain suggesting acute appendicitis (AA) were prospectively included. Procalcitonin, calprotectin, C-reactive protein, white blood count, ANC, and the new plasma APPY1 Test were performed. The final diagnosis was determined by histopathology in cases of AA and telephone follow-up in children discharged without AA. RESULTS: Between February 2012 and June 2013, 185 children were enrolled with an average age of 9.32±2.7 years. Eighty-nine (48.1%) were finally diagnosed with AA. The APPY1 Test panel showed the highest discriminatory power, sensitivity of 97.8 (95% confidence interval [CI], 92.2-99.4), negative predictive value of 95.1 (95% CI, 83.9-98.7), negative likelihood ratio of 0.06 (95% CI, 0.01-0.22), and specificity of 40.6 (95% CI, 31.3-50.5). A negative APPY1 Test and ANC less than 7500 per milliliter provided a sensitivity of 100 (95% CI, 95.9-100), negative predictive value of 100 (95% CI, 89.8-100), and specificity of 35.4 (95% CI, 26.6-45.4). In the multivariate analysis, only the APPY1 Test and ANC greater than 7500 per milliliter were significant risk factors for AA (odds ratio, 13.76; 95% CI, 3.02-62.57, and odds ratio, 6.37; 95% CI, 2.89-14.28, respectively). CONCLUSIONS: The APPY1 Test panel with ANC could be useful in identifying children with abdominal pain suggestive of AA who are at low risk for this disease.

[Pharmacological management of anxiety in patients suffering from schizophrenia]. / Prise en charge médicamenteuse de l'anxiété chez le patient souffrant de schizophrénie.

INTRODUCTION: Anxiety is a major and frequent symptom of schizophrenia, which is associated with an increased risk of relapse, impaired functioning, lower quality of life and increased incidence of suicide attempts. Despite its clinical relevance, anxiety in schizophrenia remains poorly understood. In the prodromic phase, anxiety indicates a progression towards psychotic decompensation. After a first episode, it is an indicator of relapse. LITERATURE FINDINGS: Two approaches have been used to investigate anxiety in schizophrenia: (i) categorical approach (comorbidity of schizophrenia and anxiety disorders) and (ii) dimensional approach (anxiety as a major symptom of the "dysphoric" dimension). Clinical categorical studies reported an increased frequency of comorbidity between schizophrenia and obsessive-compulsive disorder, panic disorder, social phobia, post-traumatic stress disorder, generalized anxiety disorder, agoraphobia, and specific phobia. The dimensional approach proposes that five different factors contribute to the structure of the Positive and Negative Syndrome Scale (PANSS), with anxiety as a major symptom of the "dysphoria" dimension. Concerning diagnosis, it is unclear whether psychotic and neurotic anxiety differs in nature or intensity. Nevertheless, both are frequently opposed. DISCUSSION: Psychotic anxiety is intense, profound and hermetic. In contrast to neurotic anxiety, it is associated with psychomotor disturbances, such as agitation and sideration. There is no specific tool to evaluate anxiety in schizophrenia. The dimensional approach usually runs an evaluation using items or factors extracted from the most widely-used scales, i.e. PANSS or Brief Psychiatric Rating Scale (BPRS) or from anxiety scales developed in non-schizophrenic populations, such as the Hamilton Anxiety Scale (HAMA). Recently, we developed a specific scale for hetero-evaluation (Échelle Anxiété Schizophrénie [EAS scale]). The EAS scale was recently validated and the study of its sensitivity is ongoing. THERAPEUTICAL ISSUES: Several studies have examined the effects of antipsychotics on the anxious/depressive cluster extracted from the PANSS, and some other studies have specifically evaluated the effect of antipsychotics on depressive symptoms using the Montgomery and Asberg Depression Rating Scale (MADRS) and Calgary Depression Scale for Schizophrenia (CDSS), but to our knowledge, no study has reported the effect of antipsychotics or other treatment on anxiety when using a schizophrenia-specific scale. There are no specific guideline treatments for anxiety in schizophrenia. Among phenothiazines, cyamemazine is frequently prescribed in France, because of its potent anxiolytic activity and good neurological tolerance. Some authors have suggested a specific treatment with benzodiazepines. However, benzodiazepines should be used with caution, due to undesirable actions such as dependence, rebound and potentiation of certain lateral effects.

Vertical cutoff methods in serum protein electrophoresis for the measurement of monoclonal protein concentrations: Which is best?

BACKGROUND: Monoclonal protein (M-protein) concentrations are measured by serum protein electrophoresis (SPE). Two methods are used for demarcating the M-protein area in the electropherogram: perpendicular drop (PD) and tangent skimming (TS). The aim of this study was tocompare both methods and to establish which is the most accurate and precise. METHODS: We studied 24 sera containing M-protein (5-44 g/L). The systematic error (SE) was evaluated in a dilution series of 12 sera. Within-day, between-day, and interobserver variability were assessed. SPE was performed by capillary and agarose gel electrophoresis. M-protein concentrations were measured using both cutoff methods. RESULTS: The PD method shows a constant SE ranged 1.00-2.27 g/L, while constant SE for TS is ranged -0.30--0.57 g/L. None of the cutoff methods or electrophoretic methods showed a proportional SE, with the exception of the TS method in capillary electrophoresis for ß-migrating M-protein. The PD method was more precise than the TS method in all three estimates of imprecision. An increased CV for concentrations < 10 g/L in between-day imprecision was observed with the TS method. Interobserver imprecision was greater for M-protein concentrations < 17 g/L for both cutoff methods (14.85%, 26.42% respectively). CONCLUSIONS: Despite being less precise, the TS method provides a more accurate measurement of M-protein concentration.

[The role of transesophageal echocardiopgraphy in detection of cardiogenic and aortic sources of embolism in stroke and transient ischaemic attacks]. / Význam transezofageálnej echokardiografie v detekdii kardiogénnej a aortálnej embolizácie pri loziskovej ischémii mozgu a tranzitórnych ischemických atakoch.

OBJECTIVES: To prospectively investigate the prevalence of definite and potential sources of cardiogenic embolism and embolism from ascending aorta and aortic arch in patients with a cryptogenic stroke or transient ischaemic attack (TIA). MATERIAL/METHODS: The study group consisted of 218 consecutive patients (146 males, mean age 59.4 +/- 11.5, range 38-83 years) without significant stenoses of carotic and vertebral arteries. All patients underwent biplane/multiplane transesophageal echocardiography (TEE). 77.5% of patients suffered a stroke and 22.5% had a TIA. Sinus rhythm was in 74.8% of the patients, atrial fibrillation in 22.0% and pacemaker rhythm in 3.2%. RESULTS: 1. Definite source of embolism was identified in 21.6% of patients. The most frequent finding was a thrombus of the left atrial (LA) appendage - 12.4%. Less frequently found were mobile thrombus of aortic arch - 3.7%, thrombus of LA body - 2.3%, left ventricular thrombus - 2.3%, thrombus of valvular prosthesis - 1.4% and heart tumor - 0.5%. 2. The total prevalence of potential sources of embolism was 61.5%. Only potential source (without definite source) was demonstrated in 52.3% of patients. Very frequently were found patent foramen ovale - 58.3% and atherosclerosis of ascending aorta or aortic arch - 53.7%. Further sources were LA spontaneous echocontrast - 21.1%, reduced function of LA appendage - 18.3%, atrial septal aneurysm - 7.8%, atrial septal defect - 1.4%, cardiac foreign body - 0.5%. 3. TEE did not reveal any source of embolism in 26.1% of patients. CONCLUSIONS: 1. 21.6% of the patients suffering from stroke/TIA without hemodynamically significant stenoses of extracranial cerebral arteries had a definite cardiogenic or aortic source of embolism, 2. additional 52.3% of patients had only potential source of embolism (without definite source), 3. we consider TEE necessary in patients with stroke/TIA without a known etiology, despite complete neurological examination and transthoracic echocardography.

An Na+-stimulated Mg2+-transport system in human red blood cells.

The initial rate of net Mg2+ efflux was measured in human red blood cells by atomic absorption. In fresh erythrocytes incubated in Na+,K+-Ringer's medium this rate was 7.3 +/- 2.8 mumol/l cells per h (mean +/- S.D. of 14 subjects) with an energy of activation of 13 200 cal/mol. Cells with total Mg2+ contents ([ Mg]i) ranging from 1.8 to 24 mmol/l cells were prepared by using a modified p-chloromercuribenzenesulphonate method. Mg2+ efflux was strongly stimulated by increases in [Mg]i and in external Na+ concentrations ([ Na]o). A kinetic analysis of Mg2+ efflux as a function of [Mg]i and [Na]o revealed the existence of two components: an Na+-stimulated Mg2+ efflux, which exhibited a Michaelian-like dependence of free internal Mg2+ content (apparent dissociation constant = 2.6 +/- 1.4 mmol/l cells; mean +/- S.D. of six subjects) and on external Na+ concentration (apparent dissociation constant = 20.5 +/- 1.9 mM; mean +/- S.D. of four subjects) and a variable maximal rate ranging from 35 to 370 mumol/l cells per h, and an Na+-independent Mg2+ efflux, which showed a linear dependence on internal Mg2+ content with a rate constant of (6.6 +/- 0.7) X 10(-3) h-1. Fluxes catalyzed by the Na+-stimulated Mg2+ carrier were partially dependent on the ATP content of the cells and completely inhibited by quinidine (IC50 = 50 microM) and by Mn2+ (IC50 = 0.5-1.0 mM).

Inhibition of the Na+/K+ cotransport system by cyclic AMP and intracellular Ca2+ in human red cells.

Human erythrocytes are able to incorporate cyclic AMP (cAMP) in amounts larger than those required to saturate cAMP-dependent protein kinase. In contrast to previous observations in avian red blood cells in which cAMP stimulates the Na+/K+ cotransport system, we demonstrate that cAMP inhibits this system in human erythrocytes. The cotransport inhibition is enhanced by addition of phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine to the incubation medium. The cAMP concentration giving half-maximal cotransport inhibition showed a wide variation among different individuals (from 0.1 to 5 mM external cAMP concentration). In contrast to cAMP, cyclic GMP showed little effect on the cotransport system. Ca2+ introduced into the cell interior was an inhibitor of the Na+/K+ cotransport system. These results suggest that in human cells in which endogeneous levels of cAMP and Ca2+ are modulated by hormones, the Na+/K+ cotransport system may be under hormonal regulation.

A kinetic analysis of Na-Li countertransport in human red blood cells.

We examined the kinetic properties of the interactions between inner and outer cation sites of the Na-Li countertransport system in human red blood cells. Li-stimulated Na efflux [V(Na)] was measured as a function of external Li [(Li)o] and internal Na [(Na)i] contents. At each (Li)o, a Hanes plot of (Na)i/V(Na) vs. (Na)i allowed us to calculate the apparent dissociation constant for internal Na (KiNa) and the maximal rate of Na efflux [Vmax(Na)]. In erythrocytes from 10 different subjects, the Vmax(Na)/KiNa ratios were independent of the external Li concentrations. In other experiments, Na-stimulated Li efflux [V(Li)] was measured as a function of external Na and internal Li contents. In three subjects studied, the Vmax(Li)/KiLi ratios were independent of the external Na concentrations. The data strongly suggest that the countertransport mechanism is consecutive ("ping-pong").

Endogenous sodium-potassium-chloride cotransport inhibitor in congestive heart failure.

OBJECTIVES: This study sought to evaluate the relation, if any, between fluid overload in congestive heart failure (CHF) and a newly discovered endogenous natriuretic factor acting like loop diuretic drugs: cotransport inhibitory factor (CIF). BACKGROUND: The humoral mechanisms regulating volume overload in CHF are not fully understood. Therefore, we investigated whether there is a role for CIF in this pathologic condition. METHODS: Plasma and urinary CIF levels were investigated in 23 patients with chronic CHF and compared with changes in plasma atrial natriuretic peptide (ANP). Twelve patients without CHF served as control subjects. RESULTS: CHF was associated with a highly significant threefold increase in both plasma CIF levels (mean +/- SD 7.10 +/- 3.01 vs. 2.28 +/- 0.92 U/ml, p < 0.0001) and urinary CIF excretion (7,849 +/- 3,600 vs. 2,351 +/- 1,297 U/day, p < 0.0001) with respect to patients without CHF. CIF increased as a function of impairment in left ventricular ejection fraction (r = -0.703, p < 0.0001) and the severity of clinical status. Plasma ANP was also increased in patients with CHF, although to a lesser extent (68%, p = 0.0501) than plasma CIF, and was also significantly correlated with left ventricular ejection fraction (r = -0.552, p = 0.0004). CONCLUSIONS: Plasma and urinary CIF activities were strongly and very significantly increased in chronic CHF. In addition to ANP, this long-term natriuretic agent may be of potential importance in reducing fluid overload in CHF.

Kinetic aspects of red blood cell sodium transport systems in essential hypertension.

A kinetic study of the interaction of internal sodium with four different erythrocyte sodium transport pathways (ouabain-sensitive Na+-K+ pump, bumetanide-sensitive Na+-K+ cotransport system, Na+-Li+ countertransport, and Na+leak) has facilitated the distinction of the following subgroups of patients with essential hypertension: 1) Leak (+), exhibiting increased passive sodium permeability; 2) Co (-), showing low apparent affinity of the Na+-K+ cotransport system for internal sodium; 3) Counter (+), characterized by increased maximal rates of Na+-Li+ countertransport; and 4) Pump (-), characterized by an abnormally low apparent affinity of the Na+-K+ pump for internal sodium. We present here a new and simple sodium-loading method that allows a simultaneous kinetic study of the above abnormalities. The use of this kinetic assay may improve estimation of the frequencies, clinical features, and other properties of each subgroup of hypertensive patients in different populations.

Sodium transport kinetics in erythrocytes from spontaneously hypertensive rats.

Rat erythrocytes with five different amounts of Na+ content have been prepared by using a new, nondetrimental Na+-loading method (net NaHPO4-influx through the anion carrier). This method allowed the determination of 1) maximal translocation rates and apparent dissociation constants for internal Na+ of the Na+-K+ pump, outward Na+-K+ cotransport, and Na+-Li+ countertransport and 2) rate constants of Na+ leak in erythrocytes from spontaneously hypertensive rats of the Okamoto strain and Wistar-Kyoto normotensive controls aged 2 to 26 weeks. Two major abnormalities were found in erythrocytes from spontaneously hypertensive rats: 1) a decreased cotransport affinity for internal Na+, which was constantly observed from 2 to 26 weeks of age (mean intracellular Na+ content for half-maximal stimulation of outward Na+-K+ cotransport = 33.1 +/- 7.0 [SD] mmol/L cells in spontaneously hypertensive rats vs 16.7 +/- 4.7 mmol/L cells in Wistar-Kyoto rats; p less than 0.001), and 2) a decreased maximal pump rate in adult (15- to 26-week-old) spontaneously hypertensive as compared with that for age-matched Wistar-Kyoto rats (9-37 vs 34-70 mmol/L cells/hr). Therefore, the low cotransport affinity for internal Na+ appears to be a stable, possibly genetic defect of spontaneously hypertensive rats. Conversely, the decreased maximal pump rate may be a secondary event, possibly reflecting the appearance of endogenous pump inhibitors in the plasma of adult spontaneously hypertensive rats.

Abnormal erythrocyte cation transport in primary hypertension. Clinical and experimental studies.

Several abnormalities concerning sodium (Na+) transport in erythrocytes of essential hypertensive patients have been recently observed. An abnormal extrusion of an erythrocyte Na+ load was described in our laboratory. This defect appeared to be specific for essential hypertension since it was absent in the secondary forms of the disease. The present investigation was performed on 194 Caucasian subjects with essential hypertension or born of hypertensive parents, 86 normotensive controls, and 14 families (78 subjects) studied over two to three generations. The distribution pattern of the erythrocyte defect is compatible with the expression of a single gene transmitted according to an autosomic and dominant mode. To confirm the genetic association between the red blood cell abnormality and primary hypertension, genetically hypertensive rats were investigated in parallel to our clinical studies. A reduction in the net Na+ extrusion from red blood cells was found in two varieties of genetic hypertension (SHR and H-prone-Na+-sensitive Sabra rats). The abnormality could be detected before the development of a significant hypertension. When these various rat sub-strains were acutely or chronically loaded with Na+ (either intraperitoneally or orally), a significant increase in erythrocyte Na+ content was observed only in those substrains having a genetic propensity to develop hypertension. This finding, which appears to be a consequence of the reduction in net Na+ efflux, is of interest for several reasons. It confirms the existence of a close association between a genetic predisposition to develop high blood pressure and cell Na+ retention in the presence of an excess Na+ intake. It draws attention to the possible role of intracellular Na+ in the pathogenesis of primary hypertension. Of more practical importance, the abnormal Na+ handling in erythrocytes may be a genetic marker of primary hypertension.

Interaction of internal Na+ and external K+ with the erythrocyte Na+, K+ cotransport system in essential hypertension.

External K+ inhibits the maximal rate of outward Na+, K+ cotransport in human red cells with no effect on the apparent affinity for internal Na+. The K+ concentration giving half-maximal inhibition (KIK) varied from 16 to 30 mM in 24 normotensive control subjects. Six of the 38 hypertensive patients showed a KIK above the upper limit of this normal range. Only three hypertensive patients showed a KIK below normal range. The internal Na+ content giving half-maximal stimulation of outward Na+, K+ cotransport (KSNa) was measured in the hypertensive patients (a normal range of KSNa = 9 to 16 mmol/liter cells was previously established in 50 normotensive control subjects). Eighteen hypertensive patients showed an abnormally high KSNa, as previously described in hypertensive patients whose Na+, K+ cotransport system had a low affinity for internal Na+ (Co -). Comparison of KSNa with KIK showed that all six hypertensive patients with high KIK and all three hypertensive patients with low KIK were Co - hypertensive.

Salidiuretic action by genistein in the isolated, perfused rat kidney.

The urinary isoflavonoid genistein inhibits membrane Na-K-Cl cotransporters at similar concentrations as furosemide, but the significance of this action is unknown. Genistein was therefore investigated in rats for its potential salidiuretic actions. In the isolated, perfused rat kidney, genistein induced a maximal salidiuretic action similar to that of furosemide but was 3 to 5 times less potent than furosemide in terms of active doses (natriuresis EC50, 237+/-92 versus 56+/-20 micromol/L for genistein and furosemide, respectively). Genistein and furosemide had no additive salidiuretic actions. Genistein had no significant effect on glomerular filtration rate but was able to significantly reduce renal vascular resistance with respect to vehicle isolated perfused kidney. Indomethacin (10 micromol/L), a blocker of prostaglandin biosynthesis, reduced salidiuresis and renal vasorelaxation by genistein. Subcutaneous genistein (15 mg/kg) induced a statistically significant increase in diuresis and natriuresis with respect to vehicle during the first 6 hours of administration in rats. In conclusion, genistein compares well with furosemide in vitro for its salidiuretic profile and potency in the isolated perfused rat kidney and is also natriuretic by the subcutaneous route in the rat. Further studies are required to investigate potential natriuretic and perhaps hypotensive actions of dietary genistein.

Flow-dependent stimulation of sodium and cholesterol uptake and cell growth in cultured vascular smooth muscle.

A10 vascular smooth muscle cells were placed in a flow chamber and exposed to the circulation of foetal calf serum at different rates and pressures. Under unidirectional laminar flow, physiological flow rates and pressures had almost no effect on internal sodium content. Indeed, pressure values greater than 150 mmHg were required to observe modest increases in sodium content. Conversely, a short exposure to turbulent flow (3 min) induced a strong increase in cell sodium content. At flow rates found in large human arteries, the onset of such ionic change required pressure levels of 50-85 mmHg. The restoration of laminar flow allowed the elimination of the excess cell sodium content, with a half-life of 3-4 h. Opening of calcium channels by the turbulent flow was suggested by the following observations: (1) nitrendipine fully prevented sodium uptake, with an inhibitory concentration of 50% of approximately 2 x 10(-7) mol/l; and (2) exposure to turbulent flow increased cytosolic free calcium content by approximately 80%. In addition to sodium uptake, turbulent flow stimulated cell uptake of exogenous cholesterol. Although the restoration of laminar flow allowed the rapid elimination of approximately two-thirds of the excess in cell cholesterol (with a half-life of 30-60 min), one-third of the excess cholesterol remained in the cells for more than 24 h. Finally, cell replication was faster in cells exposed to turbulent flow than in control cells subjected to laminar flow. The results show that turbulent flow provokes membrane ion transport changes in vascular smooth muscle cells, which are associated with enhanced cholesterol uptake and cell hyperplasia. Therefore, the departure from unidirectional laminar flow may be a pathogenic factor in primary hypertension and/or atherosclerosis.

The erythrocyte Na,K,Cl cotransporter and its circulating inhibitor in Dahl salt-sensitive rats.

BACKGROUND: Abnormal Na,K,Cl cotransport is thought to be a pathogenic factor in Dahl salt-sensitive rat models, but the only direct evidence for this is an increased cotransport activity found in erythrocytes from salt-loaded Dahl salt-sensitive rats. OBJECTIVE: To re-examine erythrocyte cotransport fluxes and a circulating cotransport inhibitory factor (CIF) in inbred Dahl rats maintained on a low (0.2%) salt diet. Cotransport fluxes were investigated both under basal conditions and after stimulation by cell shrinking. METHODS: Blood was drawn from 12 male Dahl salt-sensitive and 12 Dahl salt-resistant rats of the inbred John Rapp strain. Erythrocyte Na,K,Cl cotransport activity was equated to the bumetanide-sensitive fluxes of sodium, rubidium or lithium. Plasma CIF activity was tested in human erythrocytes. RESULTS: In Dahl salt-sensitive rats: (1) plasma CIF activity (5.7+/-0.4 units/ml) was modestly higher than in Dahl salt-resistant rats (2.97+/-0.12 units/ml, P < 0.0001), but much lower than that previously found in salt-loaded Dahl salt-sensitive rats (16.1 units/ml), and (2) erythrocytes exhibited a similar bumetanide-sensitive sodium efflux (rate constant 0.056+/-0.008 h(-1)) as in Dahl salt-resistant rats (0.047+/-0.007 h(-1)). Following hypertonic shock, the bumetanide-sensitive rubidium influx reacted more to cell shrinkage in Dahl salt-sensitive than in Dahl salt-resistant erythrocytes (cell volume decrease required to stimulate bumetanide-sensitive rubidium influx by 4000 micromol/l cells per h=-4.04+/-0.36 versus -5.89+/-0.44 fl, respectively; P< 0.01). CONCLUSIONS: When fed a low-salt diet, Dahl salt-sensitive rats present slightly increased plasma CIF levels and normal erythrocyte cotransport fluxes under basal conditions, but an increased response to a hypertonic shock. Therefore, if there is any primary cotransport abnormality in Dahl salt-sensitive rats, it appears to be restricted to the renal Na,K,Cl cotransporter BSC1 isoform. Alternatively, any such change may be the consequence of abnormal regulation by osmolarity-dependent mechanisms.

Kinetic study of the Ca2+ pump in erythrocytes from essential hypertensive patients.

Ca2+ pump kinetics were investigated in erythrocytes from 22 essential hypertensive patients and 20 normotensive controls (under initial-rate and steady-state conditions, using Sr2+ as a Ca2+ analogue). The mean value of the apparent dissociation constant for total internal Ca2+ (KCa) was slightly but significantly increased in the hypertensive population (73 +/- 7 versus 55 +/- 3 mumol/l cells, mean +/- s.e.m., P = 0.042 Mann-Whitney U-test). The statistical analysis showed that this was due to six essential hypertensives who exhibited a dissociation constant for Ca2+ that was higher than the upper 95% normal confidence limit (KCa = 116 +/- 7 mumol/l cells), and abnormally high maximal pump rates (7.7 +/- 0.6 versus 5.0 +/- 0.2 mmol/l cells per h in normotensives, P less than 0.001). In addition, the apparent dissociation constant for Ca2+ was inversely correlated with plasma renin activity, although the correlation was only borderline (P = 0.076). In the remaining 16 hypertensive patients, all kinetic parameters of the Ca2+ pump were within the normal range. Finally, a simultaneous study of Na+ transport kinetics suggested that erythrocyte Ca2+ and Na+ transport abnormalities were independent phenomena. Our results do not support the concept that primary hypertension (as a whole entity) is associated with a ubiquitous defect in the plasma membrane Ca2+ pump. However, in some essential hypertensive patients (about 25%) the erythrocyte Ca2+ pump exhibited an apparent decreased affinity for internal Ca2+. A similar defect in vascular smooth muscle may induce a delayed Ca2+ extrusion after the opening of Ca2+ channels, a disturbance likely to be translated into increased vascular reactivity.

Blood pressure and erythrocyte Na+ transport systems in a French urban male population.

This paper reports an investigation of blood pressure (taken as a continuous variable) as a function of: erythrocyte Na+ content; Na+,K+ pump; Na+,K+ cotransport and Na+,Li+ countertransport fluxes, and passive cation permeabilities in fresh erythrocytes from 129 French males who were living in an urban area and were not under treatment for any medical condition (after allowing for the effects of age, body mass index, alcohol and tobacco consumption). In contrast with previous findings in a North American population, we were unable to confirm that blood pressure was correlated with erythrocyte Na+ content and Na+,K+-AT-Pase activity. Conversely, the only transport parameter correlated (negatively) with blood pressure was outward Na+,K+ cotransport [r = -0.20, P less than 0.05 and r = -0.19, P less than 0.05, for systolic (SAP) and diastolic arterial pressure (DAP), respectively; n = 114]. When allowing for age, body mass index and alcohol consumption, the correlation coefficient between the Na+,K+ cotransport system and blood pressure increased from -0.20 to -0.28 (P less than 0.01) for SAP and from -0.19 to -0.28 (P less than 0.01) for DAP (n = 105). We conclude that the correlations between blood pressure and erythrocyte Na+ transport function could differ between North American and French (or Mediterranean) populations. In any case, a decreased pump or outward Na+,K+ cotransport activity may lead hypertensive subjects to a similar increase in cell Na+ (and Ca2+) content in the vascular wall.

Renal and vascular actions of equol in the rat.

BACKGROUND: The urinary isoflavonoid equol inhibits membrane Na-K-Cl cotransporters at similar concentrations to those at which furosemide inhibits them, but the significance of this action is not known. OBJECTIVE: To investigate the potential salidiuretic and vascular actions of equol in the rat. METHODS: Renal functioning was assessed in vitro in the isolated perfused kidney and in vivo in conscious rats. The vascular contractility of isolated aorta was assessed. RESULTS: In the isolated perfused kidney equol was concentrated 50- to 70-fold in the urinary fluid, it was 3-4 times less potent than furosemide at increasing diuresis, natriuresis and kaliuresis (the difference was due to its higher protein-binding affinity), and it induced a modest but significant increase in glomerular filtration rate. In vivo, orally administered equol was a modest natriuretic agent, about 8-fold less potent than orally administered furosemide (in molar terms). In isolated aortic rings precontracted by administration of phenylephrine, administration of equol relaxed the contracted aorta at 10-fold lower concentrations (concentration for half-maximal activity 58.9 +/- 16 micromol/l, n = 3) than did furosemide (concentration for half-maximal activity 633 +/- 145 micromol/l, n = 3). CONCLUSIONS: Equol is a modest natriuretic and vasorelaxant agent in the rat. Further studies are required in order to investigate the potential natriuretic and perhaps hypotensive actions of dietary equol precursors (daidzein).

Erythrocyte cation transport systems and plasma lipids in a general male population.

The relationships between five erythrocyte cation transport systems (Na(+)-K+ pump, Na(+)-K+ cotransport, Na(+)-Li+ countertransport and Na+ and K+ passive permeabilities) and plasma lipids (total plasma cholesterol, high-density lipoprotein cholesterol and triglycerides) were investigated in 129 male adult subjects with no known history of hypertension. Na+ and K+ erythrocyte contents were also considered for their possible relationships with plasma lipids. Na(+)-K+ cotransport and passive Na+ permeability were both significantly correlated with plasma triglycerides. Conversely, no significant correlation was found between erythrocyte cation transport systems or erythrocyte cation contents and total cholesterol. These findings suggest that plasma lipids can modulate erythrocyte ion transport activity in the general population.