Comparison of [3H]choline and D-[3H]aspartate efflux from guinea pig and human neocortex

The outflow of [3H]choline ([3H]Ch) evoked by electrical field stimulation and the efflux of D-[3H]Asp induced by 35 mM KCl and 1-10 microM ouabain were studied in human and guinea pig cortical slices, kept under identical experimental conditions. [3H]Ch outflow was significantly lower whereas D-[3H]Asp efflux was significantly higher in humans than in guinea pigs. This suggests a different proportion of the two neuronal systems in these two species. Blockade of muscarinic autoreceptors with atropine increased, whereas stimulation of alpha 2 receptors with norepinephrine (NE) reduced, the evoked [3H]Ch outflow to the same extent in human and guinea pig cortical slices. Conversely, NE did not affect ouabain-induced D-[3H]Asp efflux, suggesting that an alpha 2-mediated control is not operative in the glutamatergic cortical structures. Desmethylimipramine, 2-5 microM, was able to increase [3H]Ch outflow through atropine-like mechanisms only in the human. This drug at 20-50 microM inhibited [3H]Ch and D-[3H]Asp efflux in both species, through mechanisms unrelated to its monoamine reuptake blocking properties. Thus, similarities and differences can be detected between humans and guinea pigs with regard to (a) the relative potency of the cholinergic and acidic amino acidergic signals and (b) the modulation of neurotransmitter outflow by drugs acting on auto- and the heteroreceptors

Increased urinary NO2-/NO3- and cyclic guanosine monophosphate levels in patients with Bartter's syndrome: relationship to vascular reactivity.

Nitric oxide (NO) is a potent endogenous vasodilator and plays a pivotal role in the control of vascular tone by the formation of cyclic guanosine monophosphate (GMP). Patients affected by Bartter's syndrome have lower than normal vascular reactivity with normohypotension and decreased peripheral resistances in spite of biochemical and hormonal abnormalities typical of hypertension, and it is possible that increased production of NO may be involved in maintaining this reduced vascular response and vasodilatation. We have examined this possibility by studying NO2-/NO3- and cyclic GMP urinary excretions to assess NO production in vivo in seven patients affected by Bartter's syndrome compared with seven healthy controls. A group of five patients with hypokalemia other than Bartter syndrome (pseudo-Bartters) was also included in the study to evaluate the effect of hypokalemia on NO production. NO2-/NO3- urinary excretion (0.45 +/- 0.14 v 0.25 +/- 0.04 micromol/micromol urinary creatinine [controls], P < 0.005, v 0.28 +/- 0.05 [pseudo-Bartters], P < 0.01) and cyclic GMP urinary excretion (0.057 +/- 0.028 v 0.022 +/- 0.01 micromol/micromol of urinary creatinine [controls], P < 0.009, v 0.024 +/- 0.004 [pseudo-Bartters], P < 0.02) were increased in patients with Bartter's syndrome in comparison with controls and pseudo-Bartters, and a linear correlation between these two parameters was also present (P < 0.001). We conclude that in Bartter's syndrome the increased NO2-/NO3- and cyclic GMP urinary excretions point to an increased NO synthesis, which could account for the reduced vascular response of the disease, therefore adding its role in determining the vascular hyporeactivity of Bartter's syndrome

Is hydrochlorothiazide-induced hypocalciuria due to inhibition of prostaglandin E2 synthesis?

1. Since prostaglandin E2 could play a role in idiopathic hypercalciuria, and considering the well-established hypocalciuric action of hydrochlorothiazide, we have evaluated the effect of 15 days' treatment with hydrochlorothiazide in 10 hypercalciuric male stoneformers on urinary Ca2+ and prostaglandin E2, as well as on plasma bicyclo-prostaglandin E2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone. 2. In addition to lowering urinary Ca2+ (P less than 0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E2 (P less than 0.001), plasma bicyclo-prostaglandin E2 (P less than 0.001) and 1,25-dihydroxyvitamin D (P less than 0.01), and an increase in plasma parathyroid hormone (P less than 0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca2+ and prostaglandin E2 was present before (P less than 0.00005), but not after, hydrochlorothiazide. Plasma bicyclo-prostaglandin E2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before (P less than 0.005) and after (P less than 0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug (P less than 0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated (P less than 0.05). 4. It is suggested that a block of prostaglandin E2 synthesis plays a role in the effect of hydrochlorothiazide on Ca2+ metabolism, most probably through an inhibition of 1 alpha-hydroxylase activity

Is hydrochlorothiazide-induced hypocalciuria due to inhibition of prostaglandin E2 synthesis?

1. Since prostaglandin E2 could play a role in idiopathic hypercalciuria, and considering the well-established hypocalciuric action of hydrochlorothiazide, we have evaluated the effect of 15 days' treatment with hydrochlorothiazide in 10 hypercalciuric male stoneformers on urinary Ca2+ and prostaglandin E2, as well as on plasma bicyclo-prostaglandin E2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone. 2. In addition to lowering urinary Ca2+ (P less than 0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E2 (P less than 0.001), plasma bicyclo-prostaglandin E2 (P less than 0.001) and 1,25-dihydroxyvitamin D (P less than 0.01), and an increase in plasma parathyroid hormone (P less than 0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca2+ and prostaglandin E2 was present before (P less than 0.00005), but not after, hydrochlorothiazide. Plasma bicyclo-prostaglandin E2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before (P less than 0.005) and after (P less than 0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug (P less than 0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated (P less than 0.05). 4. It is suggested that a block of prostaglandin E2 synthesis plays a role in the effect of hydrochlorothiazide on Ca2+ metabolism, most probably through an inhibition of 1 alpha-hydroxylase activity

Is the red cell morphology really useful to detect the source of hematuria?

Morphological analysis of urinary red blood cells by phase-contrast microscopy to identify the source of bleeding was, and still is, widely used also as a starting point for workup. To evaluate the reliability of this approach, we studied 129 outpatients presenting with persistent isolated microhematuria; 31 subjects also had mild proteinuria (1 g/day), while 21 had pathological albumin levels. All patients were followed for a period of 6 years. During this time, 6 patients underwent renal biopsy for the onset of macrohematuria episodes and proteinuria of 2-3 g/day. Glomerular bleeding was identified in only 14.7% of the patients, despite the persistent microhematuria and the presence of proteinuria or microalbuminuria. The renal origin of the urinary erythrocytes correlated with histological findings in only 2 of 6 patients with dysmorphic erythrocytes who developed proteinuria (exceeding 1 g/day), and none with isomorphic erythrocytes showed urological abnormalities. These results challenge the validity and reliability of morphological analysis to identify the source of bleeding along the urinary tract

Validation of an easy questionnaire on the assessment of salt habit: the MINISAL-SIIA Study Program

BACKGROUND/OBJECTIVES: The aim of the present study was to validate a short questionnaire on habitual dietary salt intake, to quickly and easily identify individuals whose salt consumption exceeds recommended levels. SUBJECTS/METHODS: A total of 1131 hypertensive subjects participating in the MINISAL-SIIA study were included in the analysis. Anthropometric indexes, blood pressure, and 24-h urinary sodium excretion (NaU) were measured. A fixed-sequence questionnaire on dietary salt intake was administered. RESULTS: NaU was significantly associated with scores, with a linear association across categories (p for trend \u200985\u2009mmol/day) and "very high NaU" (NaU\u2009>\u2009170\u2009mmol/day) was 86 and 35%, respectively. The score of the questionnaire had a significant ability to detect both "high NaU"-with a specificity of 95% at the score of 10 points-and "very high NaU"-with a specificity of 99.6% at score of 13 points. CONCLUSIONS: The main results of the study indicates that a higher score of this short questionnaire is distinctive of habitual high salt consumption in hypertensive patients

Validation of an easy questionnaire on the assessment of salt habit: the MINISAL-SIIA Study Program

Background/objectives: The aim of the present study was to validate a short questionnaire on habitual dietary salt intake, to quickly and easily identify individuals whose salt consumption exceeds recommended levels. Subjects/methods: A total of 1131 hypertensive subjects participating in the MINISAL-SIIA study were included in the analysis. Anthropometric indexes, blood pressure, and 24-h urinary sodium excretion (NaU) were measured. A fixed-sequence questionnaire on dietary salt intake was administered. Results: NaU was significantly associated with scores, with a linear association across categories (p for trend &lt;0.0001). In addition, participants who achieved a total score above the median value (eight points) had significantly higher NaU than those whose score was below median (p &lt; 0.0001). In the total sample, the prevalence of \u201chigh NaU\u201d (NaU &gt; 85 mmol/day) and \u201cvery high NaU\u201d (NaU &gt; 170 mmol/day) was 86 and 35%, respectively. The score of the questionnaire had a significant ability to detect both \u201chigh NaU\u201d\u2014with a specificity of 95% at the score of 10 points\u2014and \u201cvery high NaU\u201d\u2014with a specificity of 99.6% at score of 13 points. Conclusions: The main results of the study indicates that a higher score of this short questionnaire is distinctive of habitual high salt consumption in hypertensive patients

Excess dietary sodium and inadequate potassium intake by hypertensive patients in Italy

NTRODUCTION: The aim of the study was to assess the age-specific, sex-specific, and region-specific average sodium and potassium intake and its association with anthropometric characteristics in a sample of the Italian adult hypertensive population. METHODS: A total of 1232 hypertensive patients were recruited consecutively by 47 centers recognized by the Italian Society of Hypertension. The enrolled participants were on stable antihypertensive treatment. Anthropometric indices, blood pressure, 24-h urinary sodium, and potassium excretion were measured and used as proxy for the average daily sodium and potassium intake. RESULTS: The average sodium intake was 172mmol (or 10.1g of salt/day) among men and 138 (or 8.1) among women, with no difference among geographical areas. Over 90% of men and 81% of women had a consumption higher than the recommended standard dietary intake of 5g/day. The average potassium intake was 63 and 56mmol, respectively in men and women, again without geographical differences, nearly 92% of men and 95% of women having an intake lower than the recommended intake (100mmol/day or 3.9g/day). There was a significant trend to a gradual decrease in sodium intake with age in both sexes (P<0.001). There was also a direct association between BMI and sodium intake in both sexes, this association being independent of age (P<0.001). CONCLUSION: In this national sample of the Italian hypertensive population, dietary sodium intake was largely higher and potassium intake much lower than the recommended intakes, and this was true for all geographical areas. Overweight and obese hypertensive patients had particularly high sodium intakes

Second asymptomatic carotid surgery trial (ACST-2) : a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86-1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91-1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable