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Biomedical subjects

J Regnard

Publications and source records attributed to J Regnard.

At least 37 records · Page 2Linked to original sources

[Measurement of nasal transepithelial potential difference: a diagnostic test for cystic fibrosis].

Measurement of nasal transepithelial potential difference allows the exploration of transepithelial ionic transports in vivo. Cystic fibrosis is an interesting indication of this test. Indeed, this disease is characterized by a chloride and water secretion deficit across respiratory epithelium. We have measured nasal potential in 8 healthy volunteers. Measurements were repeated 3 times a day, during 3 days for each subject. The reproducibility of the data was analysed with factorial variance model. The mean nasal potential in the healthy volunteers group and in 10 patients with cystic fibrosis was compared. In the cystic fibrosis group, the nasal potential was measured 3 times with a 2 mn-interval between the measurements. No significant variation of the nasal potential values was found from day to day or in the same day from one measurement to another. Mean value was -19 +/- 3.5 mv in normal subjects and -42.6 +/- 5.1 mv in cystic fibrosis patients. We conclude that nasal potential measurement is an easy and reproducible test that might be a complementary tool routinely used along with the classical tests in the diagnosis of cystic fibrosis.

Adult↗

Characterization of human platelet receptors for atrial natriuretic peptide: evidence for clearance receptors.

Characterization of human platelet receptors for atrial natriuretic peptide (ANP) has been performed using two different methods. First, intracellular cGMP levels were measured after platelet stimulation with humanANP (hANP) and CNP, in order to detect the presence of ANP-A or ANP-B receptors. The intracellular cGMP content was not modified either after hANP or CNP platelet stimulation and thus indicated the lack of biological active receptors on these cells. Second, displacements of 125I-hANP were similar when induced by hANP or C4-23ANP (specific ligand of clearance receptor). Consequently, these results confirmed that human platelet membranes bore only clearance receptors for atrial natriuretic peptide.

Atrial Natriuretic Factor↗

Lack of evidence that cyclosporine treatment impairs calcium-phosphorus homeostasis and bone remodeling in normocalcemic long-term renal transplant recipients.

Since the effects of cyclosporine on mineral and bone metabolism are controversial, we studied calcium regulating hormones, calcium-phosphorus (Ca-P) metabolism, and bone remodeling, assessed by serum osteocalcin, in long-term renal transplant recipients (RT). Forty-seven normocalcemic patients with good renal function receiving cyclosporine (CT, n = 27) or not (NC, n = 20) were studied at baseline and after an oral Ca load. CT and NC had similar age, daily dose of steroids, GFR level, and duration of transplantation. Baseline evaluation included 24-hr urinary Ca, P, TRP, TmP/GFR, fasting serum intact PTH, 1,25-(OH)2D, 25OHD, osteocalcin, Ca, and P. Subjects of the two groups had excessive secretion of PTH, tubular P wasting, and high serum osteocalcin level, as is usual in RT. However, there was no difference between CT and NC regarding any baseline variable. Ten CT and ten NC, matched for duration of transplantation and serum PTH level, ingested 1g Ca to achieve an acute dynamic study of PTH secretion and Ca-P metabolism. In both CT and NC, this Ca load caused the same decreases in serum PTH (P < 0.001), NcAMP (P < 0.05), and urinary P (P < 0.001) and the same increases in serum and urinary Ca (P < 0.001), and in both TmP/GFR and TRP (P < 0.001). These results strongly suggest that cyclosporine treatment had no significant effect on calcium-regulating hormone secretion, P-Ca metabolism, and bone remodeling level. We therefore consider that cyclosporine is unlikely to have any prominent role in the abnormalities of bone endocrine and mineral metabolism that are common in long-term kidney recipients.

Administration, Oral↗

Increase in urinary calcium and oxalate after fructose infusion.

We have previously shown that an oral glucose load increased both calciuria and oxaluria while the ingestion of fructose induced a rise in calciuria and a decrease in oxaluria. This latter effect remains unclear and might be linked to the reduced intestinal oxalate absorption subsequent to digestive intolerance in some subjects. Such a hypothesis could be enlightened by the study of a parenteral fructose load. Therefore in 7 healthy subjects, we compared the effects of fructose infusion (F) (15 min iv infusion at 0.185 mmol/kg BW/min) to a control glucose infusion (G) on urinary calcium and oxalate. In this study, glycemia and insulinemia increased less after (F) than after (G) (respectively + 21% vs + 216%, p < 0.001 and + 230% vs + 402%, p < 0.05) and phosphatemia decreased less after (F) than after (G) (-7% vs -14%, p < 0.05). Urinary calcium and oxalate increased only after (F) (respectively + 64%, p < 0.01 and + 60%, p < 0.05). Urinary uric acid, another urolithiasis factor, increased after both (F) and (G) (respectively + 45%; p < 0.01 and + 42%; p < 0.01) but uricemia increased only after (F) (+ 25%; p < 0.01). Our results suggest an additional reason to avoid the use of fructose in parenteral nutrition, particularly in individuals with a known history of either calcium oxalate or urate urolithiasis.

Adult↗

Acute oral calcium load decreases parathyroid secretion and suppresses tubular phosphate loss in long-term renal transplant recipients.

Persistent hyperparathyroidism and impaired tubular reabsorption of phosphate (P) are common after kidney transplantation. In order to assess the suppressibility of these abnormalities, we studied the effects of a single oral calcium (Ca) load (1 g) in 7 healthy subjects (HS) and in 14 normocalcemic long-term renal transplant recipients with good renal function (RT). In HS and RT, serum and urinary Ca were similar at baseline, and increased (p < 0.001) to the same extent after Ca ingestion. Serum parathyroid hormone (PTH) and nephrogenic cAMP (NcAMP) levels were higher at baseline in RT than HS (mean +/- SEM; respectively, PTH 7.8 +/- 0.8 vs. 3.5 +/- 0.6 pmol/l, p < 0.001, and NcAMP 24.8 +/- 2.3 vs. 13.9 +/- 2.3 nmol/l GFR, p < 0.01). After Ca, PTH (p < 0.001) and NcAMP (p < 0.01) decreased markedly in both RT and HS. Maximal changes in PTH and NcAMP were larger in RT than HS (PTH - 3.3 +/- 0.4 vs. -2.1 +/- 0.03 pmol/l, p < 0.01, and NcAMP -18.2 +/- 3.3 vs. -8.1 +/- 2.6 nmol/l GFR, p < 0.05). Although PTH levels remained significantly higher in RT than HS from baseline to the end of the study (p < 0.001), PTH decreased to the normal range in RT after Ca load. Moreover, NcAMP reached similar values in RT and HS after Ca (16.0 +/- 3.3 vs. 13.2 +/- 2.8 nmol/l GFR at the end of the survey, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of pretreatment with inhaled methoxamine on bronchial responses to histamine in asthmatic subjects.

The underlying mechanisms of bronchial obstruction in asthma are complex. Both bronchospasm and bronchial oedema are thought to play pivotal roles in asthma, but their respective importance in a given asthmatic individual is unknown. To address this question, we assessed the effects of pretreatment with inhaled methoxamine, a potent alpha 1-adrenoceptor agonist, on bronchial response to inhaled histamine in 10 asthmatic subjects. The study was conducted according to a double-blind, cross-over, randomized and placebo-controlled design. In each subject, dose-response curves for the effects on forced expiratory volume in one second (FEV1) of serially doubling doses of inhaled histamine were obtained on three different days, 15 min after pretreatment with either methoxamine (10 mg) or duplicated placebo. Histamine, first dose 100 micrograms (543 nmol), was delivered by a breath-activated dosimeter every 5 min. FEV1 was measured in triplicate after each dose and the largest value was retained. There was no difference in baseline and prechallenge FEV1 after placebo and methoxamine. Mean coefficient of variation of decrease in FEV1 induced by histamine on the two placebo days was 6.7 +/- 2%. On average, the bronchial responses to histamine were not modified by pretreatment with methoxamine as compared to placebo (delta FEV1 = 0.83 +/- 0.14 l on methoxamine versus 0.85 +/- 0.11 l and 0.86 +/- 0.13 l on the two placebo days).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

The effect of intravenous phenylephrine on airway calibre in asthma.

Tracheobronchial vasoconstriction and subsequent reduction of airway wall thickness due to the alpha 1-agonist methoxamine, might be responsible for prevention of exercise-induced asthma, and reduction of bronchial hyperresponsiveness to methacholine increase in exercise performance in patients with impaired left ventricular function. Since bronchial wall oedema plays an important role in asthma, we have now investigated the bronchial response to the intravenously administered alpha 1-agonist, phenylephrine, in asthma of various severity. Increasing noncumulative intravenous phenylephrine doses (100 to 600 micrograms) were injected in 18 asthmatic subjects (three groups: mild asthma, mild asthma with recent acute attack, severe obstructive asthma) and in 11 control subjects. Changes in specific airways resistance (sRaw) on phenylephrine were linearly related to the dose administered in 16 out of 18 asthmatic subjects, and in only 3 out of 11 control subjects. In the asthmatic subjects, sRaw increased in 10 patients whose asthma was mild, or bronchial obstruction mild to moderate, and decreased in the remaining 8 asthmatic subjects with more severe disease or with a higher degree of bronchial obstruction. Changes in forced expiratory volume in one second (FEV1) were consistent with those of sRaw. In the five asthmatic subjects who underwent the protocol twice, results were reproducible. There was no difference in the responses of heart rate between the three groups of asthmatic subjects. It is likely that phenylephrine acts both via airway smooth muscle contraction, an effect which might predominate in mild asthma, and via mucosal vasoconstriction, which might overcome the effect on smooth muscle in more severe asthma with bronchial wall oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Increase in calciuria and oxaluria after a single chocolate bar load.

Chocolate, a foodstuff rich in sucrose, fat and oxalate, is considered unsuitable in cases of obesity, diabetes mellitus, urolithiasis and postprandial hypoglycemia. However the pathophysiological effects of chocolate are poorly documented. Therefore we investigated the effects of ingestion of 100 g dark chocolate bar (45 g cocoa and 55 g sucrose) on carbohydrate, calcium and oxalate metabolisms in 10 healthy subjects. Results were compared to those of 55 g sucrose intake (control group) performed on another day. Chocolate caused i) a lesser but longer increase in plasma glucose, insulin, and C-peptide than sucrose (respectively +23% of baseline vs +60%, p < 0.001; +436% of baseline vs +755%, p < 0.01 and +200% of baseline vs +331%, p < 0.01), ii) a striking increase in triglyceridemia, calciuria and oxaluria (respectively +96%, p < 0.01; +147%, p < 0.01 and +213%, p < 0.001). Thus, chocolate (cocoa+sucrose) causes a lesser pancreatic stimulation than sucrose. However, the increases in both calciuria and oxaluria (induced respectively by sucrose and cocoa) following chocolate ingestion might contribute to urinary conditions favoring the development of calcium oxalate calculi.

Adult↗

Effect of furosemide on prostaglandin synthesis by human nasal and bronchial epithelial cells in culture.

Inhaled furosemide protects asthmatic subjects against bronchial obstruction caused by indirect provocants. We have attempted to correlate the protective effect of furosemide with its ability to alter prostaglandin (PG) synthesis by the airway epithelium. Human epithelial cells from nasal polyps and bronchi were cultured in DME-Ham's F12 medium with 10% fetal calf serum. Confluent cells (days 6 through 8) were incubated for 30 min in fresh medium, and the PGs in the supernatant were measured by radioimmunoassay. Spontaneous output (ng.ml-1.mg-1 cell protein) was as follows (mean +/- SEM): PGE2 = 7.74 +/- 2.10 (n = 12), PGF2 alpha = 1.66 +/- 0.12 (n = 15), 6-keto-PGF1 alpha = 4.32 +/- 1.37 (n = 11), PGD2 = 0.73 +/- 0.16 (n = 11) for bronchial cells and PGE2 = 7.24 +/- 0.80 (n = 32), PGF2 alpha = 1.38 +/- 0.12 (n = 17), 6-keto-PGF1 alpha = 6.79 +/- 2.50 (n = 15), PGD2 = 0.42 +/- 0.07 (n = 17) for nasal cells. Incubation with arachidonic acid (25 micrograms/ml) for 30 min significantly increased the amounts of the four PGs. Incubation with furosemide (10(-4) M) for 30 min caused a marked reduction in both basal and arachidonic acid-stimulated production of PGE2 and PGF2 alpha but did not reduce production of 6-keto-PGF1 alpha and PGD2. Incubation with bumetanide (10(-4) M) for 30 min did not modify the PGE2 synthesis by nasal epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Hemodynamic responses to 30-min cycling exercise at 70% VO2 max both in ambiant air and during chest-immersion.

The aim of this study was to examine the influence of water immersion to the chest on cardio-vascular adaptation to exercise. Upright or sitting immersion causes an increase in central blood volume, but it remains controversial whether central blood volume remains elevated during dynamic exercise in water and facilitates cardiac adaptation, depending particularly on the intensity of exercise which can be matched for O2 consumption (metabolic range) or for mechanical intensity (work load). We have compared hemodynamic variables measured during two cycling exercises at the same mechanical intensity, performed both in ambiant air and during immersion up to the chest.

Adult↗

Atrial natriuretic factor receptors on human platelets.

Specific binding sites for ANF have been identified on human platelets. To determine maximal binding (Bmax) and dissociation constant (Kd), we adapted the only original method by developing a specific sequence of platelet preparation. From venous blood collected on citrated anticoagulant, platelets were prepared by successive centrifugations at 20 degrees C (blood centrifugated at 1500 rpm for 10 min., supernatant centrifugated at 3000 rpm for 1 min., supernatant centrifugated at 2800 rpm for 10 min, the inner platelet-rich layer resuspended in citrated solution) and aliquoted (200 microliters at 5.10(5) platelets/microliters). Competition experiments [incubation of platelets with fixed concentration (20-25 pM) of labeledhuman ANF (125Ih ANF) and increasing concentrations (10(-12) to 10(-6) pM) of unlabeled hANF] led to the drawing of a mean displacement curve (n = 8), usable as reference, and to verification of the specificity of binding assay (cross-reactivity with ratANF, no cross-reactivity with arginine-vasopressine). From saturation experiments [incubation of platelets with increasing concentrations (3.5 to 63.7 pM) of labeled hANF and with (10(-8) M) or without unlabeled hANF], we determined (n = 11): Bmax (m +/- SEM) = 4.5 +/- 0.7 pM or 5.4 +/- 0.8 sites per cell and Kd (m +/- SEM) = 10.84 +/- 1.70 pM.

Atrial Natriuretic Factor↗

[Mechanisms of bronchial hyperreactivity. Bronchial edema, mechanical and vascular factors].

Hindrance to gas flow in the bronchi is affected not only by airway smooth muscle tone but also by airway circulation. Congestion and oedema increase airway wall thickness and act in series with airway smooth muscle contraction to reduce airway calibre, an effect which is more marked in small and intermediate bronchi. Many mediators, neuromediators, paracrine mediators produced by resident (epithelium) or migrant (inflammatory cells) cells share bronchomotor and vascular effects. In addition, contraction of airway smooth muscle and vascular phenomena are mechanically coupled. Contraction of airway smooth muscle facilitates vascular congestion and oedema because the diameter of the muscle ring is more reduced than the external diameter of the airways. In addition, a negative intrathoracic pressure, e.g. in asthma, increases the mechanical loading of both ventricles, thereby facilitating pulmonary and bronchial oedema. The effects of this mechanical coupling are enhanced by airway inflammation that facilitates both vascular congestion and leakage. Stimuli such as exercise and hyperventilation cause airway vasodilatation which, in turn, facilitates and, possibly, triggers the post-exercise asthma attack. Conversely, congestion and vasodilatation may have a protective effect through an increase in the clearance of bronchoconstrictor substances, or in reducing the amplitude of airway cooling and water loss in exercise-induced asthma. The relative role in bronchial hyperresponsiveness of airway smooth muscle contraction and vascular phenomena probably depends upon individual factors such as, for instance, both intensity and nature of inflammation of the airway walls.

Airway Obstruction↗

Locally deposited but not inhaled frusemide reduces nasal potential difference in healthy subjects.

Previous publications suggest that prolonged inhalation of frusemide (F) does not cause a fall in the nasal transepithelial potential difference (PD) whereas locally deposited F does. In an attempt to reconcile these observations, we have measured the effect of inhalation through the nose and local deposition of F, amiloride (A), bumetanide (B) and salbutamol (S) on nasal PD in 7 healthy male volunteers in a randomised, double blind study. Solutions of drugs ranging from 10(-6) M to 10(-3) M (3 x 10(-8) M to 3 x 10(-5) M for B) in phosphate buffered saline 0.5 ml (PBS) were sequentially deposited in both nostrils, and nasal PD was measured 5 min after each dose. In 10 further volunteers, 10(-2) M solutions of A, F and S (3 x 10(-4) M for B) 5 ml were nebulised through the nose for 15 min, when nasal PD was measured. Resting PD was similar in the left and right nostrils averaging -17.1 mV (lumen negative). Placebo, inhaled of deposited B and S, and inhaled F did not change nasal PD. Topically deposited F significantly lowered PDmax in a dose-dependent manner [10(-4) M, -12% from baseline; 10(-3) M, -24%] as did the more potent A [10(-5) M, -19%; 10(-4) M, -31%; 10(-3) M, -47%]. Nebulised A (10(-2) M) had the same effect on nasal PD as deposited A (10(-4) M). The effects of locally deposited F and A (10(-3) M) on nasal PD were additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Carbohydrate metabolism and urinary excretion of calcium and oxalate after ingestion of polyol sweeteners.

Polyols are widely used instead of glucose and sucrose in sweets and dietary products because they are barely cariogenic, and their energy value is lower. In addition, it has been shown that calciuria and oxaluria increase after an oral glucose (Glu) load. We, therefore, investigated the effects of a single polyol ingestion on carbohydrate, calcium, phosphate, and oxalate metabolism in 10 healthy subjects. On 5 experimental days, subjects ingested 20 g Glu, Lycasin (Lyc), Maltisorb (Mal), sorbitol (Sor), or xylitol (Xyl). Glu, Lyc, and Mal intake caused an increase in glycemia [respectively, +34% (P < 0.001), +15% (P < 0.001), and +15% (P < 0.001)], insulinemia [respectively, +358% (P < 0.001), +88% (P < 0.05), and +94% (P < 0.01)], and C-peptide level [respectively, +170% (P < 0.001), +15% (P < 0.01), and +15% (P < 0.001)]. Conversely, no change occurred in glycemia, insulinemia, or C-peptide levels after ingestion of Sor or Xyl. Urinary calcium increased after Glu (+64%; P < 0.01) and Xyl (+74%; P < 0.01) intake, and urinary phosphate increased after Xyl (+27%; P < 0.05), but decreased after a Glu load (-68%; P < 0.01). Only Xyl increased urinary excretion of oxalate (+53%; P < 0.05). Our results suggest that ingestion of polyols causes a much lesser pancreatic stimulation than Glu intake. Also, Lyc, Mal, and Sor sweeteners have no effect on urinary excretion of calcium and oxalate, whereas calciuria and oxaluria increase after Xyl ingestion.

Adult↗

Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function.

BACKGROUND: Bronchial hyperresponsiveness to cholinergic stimuli such as the inhalation of methacholine is common in patients with impaired left ventricular function. Such hyperresponsiveness is best explained by cholinergic vasodilation of blood vessels in the small airways, with extravasation of plasma due to high left ventricular filling pressure. Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction. METHODS: We studied 19 patients with a mean left ventricular ejection fraction of 22 +/- 4 percent and moderate exertional dyspnea. In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance). In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption. Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double-blind, crossover design. RESULTS: In group 1, the mean (+/- SD) duration of exercise increased from 293 +/- 136 seconds after the inhalation of placebo to 612 +/- 257 seconds after the inhalation of methoxamine (P = 0.001). In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03). CONCLUSIONS: The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction. However, the improvement in the duration of exercise at a constant workload (endurance) was much more than the improvement in maximal exercise capacity assessed with a progressive workload. These data suggest that exercise-induced vasodilation of airway vessels may contribute to exertional dyspnea in such patients. Whether or not inhaled methoxamine can provide long-term benefit in patients with heart failure will require further study.

Administration, Inhalation↗

Cold and the airways.

Physiological and pathological respiratory responses are triggered by various conditions of exposure to cold climates. Beside airway smooth muscle, both the pulmonary and the tracheobronchial vasculatures are major effectors of respiratory responses to cold. General exposure to cold causes pulmonary vasoconstriction known as "Raynaud's phenomenon of the lung" in subjects with primary Raynaud syndrome and favors acute pulmonary oedema in subjects with congestive heart failure. In healthy subjects acute hyperventilation of very cold air has led to acute respiratory failure closely similar to hypoxic pulmonary oedema. In outdoor exercising people years long repetition of hyperventilation of subfreezing air causes "eskimo lung" made of obstructive lung disease and increased wall thickness of pulmonary arteries. At a lesser degree hyperventilation of dry air cools the central airways and triggers subclinical bronchial obstruction in healthy subjects. In asthmatic subjects hyperventilation of dry air causes asthma attacks. Results of recent animal and human experiments point to a key role of mucosal vessels in thermal balance of the airways. Simultaneously, there is increasing evidence that hyperventilation-induced asthma is triggered by a thermal stimulus.

Acute Disease↗

Effect of airway blood flow on airflow.

Resistance to gas flow of an airway is a function of both airway smooth muscle tone and thickness of the airway wall internal to the outer ring of airway smooth muscle. Schematically, the increase in airway resistance caused by shortening of airway smooth muscle may be potentiated by a concomitant increase in airway wall thickness caused by vasodilation of the bronchial vessels and/or microvascular leakage. Conversely, bronchial vasoconstriction may limit to some extent the increase in resistance to gas flow caused by airway smooth muscle shortening and/or congestion and edema of the airway wall. Many endogenous paracrine mediators, putatively involved in asthma and bronchial hyperresponsiveness, have both bronchomotor and vascular effects. The overall effects on resistance to airflow of endogenous or exogenous agents depend not only upon pre-existing airway smooth muscle tone and pre-existing condition of bronchial vessels but also upon two factors that facilitate microvascular leakage, namely, inflammation of the airway wall and outflow pressure of the bronchial circulation, which is close to left atrial pressure.

Airway Obstruction↗