Search PubMed⌕ Search

Biomedical subjects

M Azizi

Publications and source records attributed to M Azizi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Obliteration of a posttraumatic spinal cord cyst with solid human embryonic spinal cord grafts: first clinical attempt.

Cystic lesions of the spinal cord (syringomyelia) may occur after spinal cord injury. Posttraumatic syringomyelia may result in a myelopathy causing symptoms of sensory and motor loss, as well as worsening spasticity, pain, hyperhidrosis, and autonomic dysreflexia. Shunting of the cyst cavity along with untethering of the scarred spinal cord is widely accepted as the treatment of choice. However, the long-term stabilization of the progressive myelopathy caused by a posttraumatic cyst is suboptimal because of arachnoidal rescarring, shunt tube blockage, and cyst reexpansion. A new neurosurgical strategy to overcome the complication of cyst reexpansion was designed. Experimental studies have shown the successful use of embryonic spinal cord grafts, including human grafts, to obliterate induced spinal cord cavities in rats. The authors report the first use of solid human embryonic spinal cord grafts to successfully obliterate 6 cm of a large cyst cavity in a patient becoming myelopathic from a posttraumatic cyst. The grafts are well visualized by MRI to the 7-month postoperative follow-up and cyst obliteration is seen in the region where the grafts were placed.

Fetal Tissue Transplantation↗
PubMed1997

Additive effects of losartan and enalapril on blood pressure and plasma active renin.

The combination of single oral doses of an angiotensin I-converting enzyme inhibitor (captopril) and a type 1 angiotensin II receptor antagonist (losartan) has additive effects on blood pressure fall and renin release in sodium-depleted normotensive subjects. We planned the present study to determine whether the magnitude of the hemodynamic and hormonal consequences of renin-angiotensin system blockade by such a combination is larger than that obtained by doubling the dose of the angiotensin-converting enzyme inhibitor given alone. In a single-dose, double-blind, randomized, three-way crossover study, 10 mg enalapril, 20 mg enalapril, and the combination of 50 mg losartan and 10 mg enalapril were administered orally to 12 sodium-depleted normotensive subjects. The area under the time curve from 0 to 24 hours (AUC0-24) of the mean blood pressure fall after losartan-enalapril combination intake (-220 +/- 91 mm Hg.h) was significantly greater than that of either 10 or 20 mg enalapril (-124 +/- 91 and -149 +/- 85 mm Hg.h, respectively, P < .05 vs both doses). The combination significantly increased by 2.3 +/- 1.2-fold the AUC0-24 of plasma active renin compared with either 10 or 20 mg enalapril given alone (P < .05) but had no additive effect on plasma aldosterone fall. The losartan-enalapril combination is more effective in decreasing blood pressure and increasing plasma active renin than doubling of the enalapril dose.

Adolescent↗
PubMed1997

High plasma level of N-acetyl-seryl-aspartyl-lysyl-proline: a new marker of chronic angiotensin-converting enzyme inhibition.

The acute administration of the angiotensin-converting enzyme (ACE) inhibitor captopril to healthy subjects transiently increases 5.5-fold the plasma levels of a natural stem-cell regulator, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). The aim of this study was to measure plasma Ac-SDKP levels during chronic treatment with all types of ACE inhibitors and to assess its relevance as a marker of ACE inhibition. Plasma levels of Ac-SDKP were blindly determined in age- and sex-matched hypertensive patients either treated (ACEI group, n=27) or not (non-ACEI group, n=23) with an ACE inhibitor for more than 1 month. Geometric mean [range] of plasma Ac-SDKP levels were significantly higher in the ACEI group (3.78 [1.48 to 14.5] pmol/mL) than in the non-ACEI group, with no overlap between the groups (0.75 [0.36 to 1.22] pmol/mL, P<.0001). The measurement of Ac-SDKP in plasma discriminated all the patients of the ACEI group, whereas the simultaneous determination of either in vitro (using hippuryl-histidine-leucine as substrate) or in vivo (angiotensin II/angiotensin I ratio) ACE activity failed to identify nine and five cases, respectively. We conclude that Ac-SDKP accumulates in plasma during chronic ACE inhibitor treatment. The long-term consequences of Ac-SDKP accumulation are unknown. The reliability of plasma Ac-SDKP measurement makes it the best marker of chronic ACE inhibition, which can help to verify patients' compliance to ACE inhibitor treatment.

Adolescent↗
PubMed1997

Sandwich-type enzyme immunoassay for big endothelin-I in plasma: concentrations in healthy human subjects unaffected by sex or posture.

A sandwich-type enzyme immunoassay has been developed for measuring human big endothelin-1 (big ET-1) in human plasma and supernatant fluids from human cell cultures. Big ET-1 is the precursor of endothelin 1 (ET-1), the most potent vasoconstrictor known. A rabbit antibody raised against the big ET-1 COOH-terminus fragment was used as an immobilized antibody (anti-P16). The Fab' fragment of a monoclonal antibody (1B3) raised against the ET-1 loop fragment was used as the enzyme-labeled antibody, after being coupled to acetylcholinesterase. The lowest detectable value in the assay was 1.2 pg/mL (0.12 pg/well). The assay was highly specific for big ET-1, demonstrating no cross-reactivity with ET-1, <0.4% cross-reactivity with big endothelin-2 (big ET-2), and <0.1% with big endothelin-3 (big ET-3). We used this assay to evaluate the effect of two different postural positions (supine and standing) on plasma big ET-1 concentrations in 11 male and 11 female healthy subjects. Data analysis revealed that neither sex nor body position influenced plasma big ET-1 concentrations. This assay should thus permit the detection of possible variations in plasma concentrations of big ET-1 in certain pathologies and, in association with ET-1 assay, make possible in vitro study of endothelin-converting enzyme activity in cell models. Such studies could clarify the physiological and clinical roles of this family of peptides.

Adolescent↗
PubMed1996

[Natural history of renal artery stenosis].

The time delay necessary for the appearance of an atherosclerotic renal artery stenosis from the initial process of atherogenesis is not well known and is probably influenced by genetic factors and the classical risk factors (i.e. cholesterol, blood pressure levels...). The pathophysiology of fibromuscular dysplasic renal artery stenoses is even less known. Whatever the cause of a renal artery stenosis, blood pressure increases when the stenosis increases and becomes "significant" with a parallelism between the degree of the stenosis and the severity of hypertension. Renal artery stenoses can progress with time and lead to a complete occlusion of the involved renal artery. The progressive obstruction of the renal artery can lead to malignant hypertension and can also induce a gradual irreversible ischaemic renal damage leading to end-stage renal failure.

Arteriosclerosis↗
PubMed1996

Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline.

Angiotensin I-converting enzyme (ACE) has two homologous active NH2- and COOH-terminal domains and displays activity toward a broad range of substrates. The tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has been shown to be hydrolyzed in vitro by ACE and to be a preferential substrate for its NH2-terminal active site. This peptide is a regulatory factor of hematopoiesis which reversibly stem cells and normal early progenitors into S-phase. We found that a single oral dose of 50 mg of the ACE inhibitor, captopril, when administered to eight healthy subjects in a double-blind, crossover, placebo-controlled study, massively increased the plasma level of Ac-SDKP. ACE inhibition by captopril induced a 90-99% inhibition of in vitro [3H]Ac-SDKP hydrolysis and a long-lasting 5.5-fold (range: 4-8.5-fold) increase in the plasma levels of Ac-SDKP. These results demonstrate that Ac-SDKP is the first natural peptide hydrolyzed by the NH2-terminal domain of ACE not only in vitro but also in vivo, confirming that both catalytic sites of ACE are physiologically active. Our data suggest that ACE may also be implicated in the process of hematopoietic stem cell regulation, by permanently degrading this natural circulating inhibitor of cell entry into S-phase.

Administration, Oral↗
PubMed1996

Development of enzyme-linked immunoassays for human angiotensin I converting enzyme suitable for large-scale studies.

OBJECTIVE: To develop and validate a simple immunological assay for human angiotensin converting enzyme (ACE) based on monoclonal antibodies. METHODS: Microtitre plates were coated with mouse monoclonal antibody (MoAb) to human ACE (9B9) and incubated with diluted samples of human plasma. In the sandwich enzyme-linked immunosorbent assay (ELISA), the plasma ACE, bound to MoAb 9B9, was revealed using polyclonal anti-ACE antibodies and alkaline phosphatase conjugated to goat anti-rabbit immunoglobulin G. In the plate precipitation assay the ACE activity, quantitatively precipitated from human plasma by MoAb 9B9, was measured by enzymatic fluorimetric assay with p-benzyloxycarboxyl-glycyl-L-histidyl-L-leucine or p-benzyloxycarboxyl-L-phenylalanyl-L-histidyl-L-leucine as substrate, directly in the wells. RESULTS: These assays are specific for the amino-terminal domain of ACE and recognize differences in the conformations of native and recombinant ACE. The sensitivity of the sandwich ELISA was 200 pg/ml assay medium; it quantifies the ACE in 10 microliters human plasma or less. Intra- and inter-assay variability coefficients were 6.2 and 13.6%, respectively. Both variants of the assay determined the plasma ACE concentration in the presence of ACE inhibitors or EDTA. The ACE concentrations were determined by sandwich ELISA in a population of 138 middle-aged healthy Caucasian subjects. They were strongly correlated with the ACE gene insertion/deletion (I/D) polymorphism, which accounted for 20% of the variance of plasma ACE concentration in this population and 16-24% of the variance in plasma ACE activity as measured with three different enzymatic assays. CONCLUSION: The ACE concentration (but not inhibition) can be determined by this ELISA which is suitable for large-scale studies of plasma ACE levels.

Animals↗
PubMed1996

Immunohistochemical studies of proinflammatory cytokines and their receptors in hair follicles of normal human skin.

Immunoreactivity to interleukin-1 alpha, interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and their receptors, as well as the endogenous interleukin-1 receptor antagonist, was investigated in hair follicles in paraffin-embedded normal human skin. Interleukin-1 beta- and tumour necrosis factor-alpha-like immunoreactivities were found in the inner root sheath layer of hair follicles, at the suprapapillary level. Interleukin-1 receptor-like immunoreactivity was also found in this layer, while there was a variable immunoreactivity to the interleukin-1 receptor antagonist. In the outer root sheath there was a weak to moderate staining for the four cytokines, in addition to intense staining for their receptors and a weak staining for the antagonist. The fibrous root sheath had a moderate immunoreactivity for interleukin-1 alpha and interleukin-6. The distribution patterns suggest that these cytokines, particularly interleukin-1 beta and tumour necrosis factor-alpha, may have a protective role in hair formation, while all the investigated proinflammatory cytokines may have a role in the differentiation process.

Adult↗
PubMed1995

Additive effects of combined angiotensin-converting enzyme inhibition and angiotensin II antagonism on blood pressure and renin release in sodium-depleted normotensives.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors do not decrease plasma angiotensin (Ang) II levels 24 hours after drug intake to the same extent as at peak. This intermittent partial "escape" is explained either by a renin-mediated reactive rise in plasma Ang I or by non-ACE-dependent Ang II generation. We therefore tested the hypothesis that a combination of ACE inhibition and Ang II blockade may have additive biological and hemodynamic effects. METHODS AND RESULTS: In a single-dose, double-blind, randomized, four-way, crossover study, an Ang II antagonist (losartan 50 mg), an ACE inhibitor (captopril 50 mg), their combination, and matched placebos were orally administered to 12 normotensive male volunteers maintained in mild sodium depletion. When captopril 50 mg and losartan 50 mg were given alone, the magnitude of their effects on blood pressure, plasma active renin, Ang I, and aldosterone was similar, whereas the kinetics of their effects were different, reflecting differences in drug pharmacokinetics. The losartan-captopril combination completely suppressed the rise in plasma Ang II induced by losartan 2 hours after drug intake (3.3 +/- 3.6 pg/mL versus 20.3 +/- 19.1 pg/mL, respectively, P < .05). Six hours after drug intake, the losartan-captopril combination induced a significantly greater decrease in mean blood pressure than that produced by either losartan or captopril alone (73 +/- 7 mm Hg versus 79 +/- 8 mm Hg versus 81 +/- 7 mm Hg, respectively, P < .05). The maximum placebo-subtracted falls in mean blood pressure for the losartan-captopril combination, captopril 50 mg, and losartan 50 mg were 14 +/- 5 mm Hg, 10 +/- 3 mm Hg, and 9 +/- 6 mm Hg, respectively (F2.22 = 3.45, P < .05). The duration of the mean blood pressure fall was not prolonged by the combination. After combined losartan-captopril administration, the area under the plasma active renin versus time curve (0 to 24 hours) was significantly increased when compared with either losartan or captopril alone (6404 +/- 2961 pg.h.mL-1 versus 3105 +/- 1461 pg.h.mL-1 versus 2092 +/- 867 pg.h.mL-1, respectively, P < .05). The combination had no additive effects on plasma aldosterone decrease when compared with either losartan or captopril alone (58 +/- 17% versus 51 +/- 20% versus 53 +/- 21%, respectively, NS). CONCLUSIONS: The combined administration of a standard single oral dose of an ACE inhibitor and an Ang II antagonist to mildly sodium-depleted normal subjects (1) had a major additive effect on plasma renin rise, (2) induced an additional mean blood pressure reduction, and (3) had no additive effect on plasma aldosterone fall.

Adolescent↗
PubMed1995

Angiotensin-converting enzyme gene polymorphism has no influence on the circulating renin-angiotensin-aldosterone system or blood pressure in normotensive subjects.

BACKGROUND: Angiotensin-converting enzyme (ACE) is involved in the metabolism of two major vasoactive peptides, converting angiotensin (Ang) I into Ang II and inactivating bradykinin. An insertion/deletion (I/D) polymorphism is present in the 16th intron of the ACE gene and is strongly associated with plasma and cellular ACE levels. Contrasting with the lack of relation between ACE gene polymorphism and blood pressure level, a large case-control study has shown that the deletion marker allele of the ACE gene was associated with an increased risk of myocardial infarction. The pathophysiological link between ACE gene polymorphism and cardiovascular events remains hypothetical. One hypothesis is that this polymorphism influences Ang II and bradykinin concentrations in the peripheral and/or local circulations through its effects on ACE levels in plasma and endothelial cells. The aim of this study was to investigate the effect of the ACE gene I/D polymorphism on blood pressure, plasma active renin, and aldosterone regulation in normal subjects. METHODS AND RESULTS: Twenty-four normotensive male volunteers homozygous for the ACE I/D polymorphism (12 DD and 12 II) received a renin inhibitor infusion (remikiren 0.1 mg.kg-1.h-1 for 130 minutes) to suppress endogenous Ang I and Ang II production. Forty minutes after initiating the remikiren infusion, an exogenous Ang I infusion was begun and increased gradually every 15 minutes from 1 to 10 ng.kg-1.min-1. Median (range) plasma ACE levels (mU/mL) were 39 (32 to 57) and 24 (12 to 30) in the DD and II groups, respectively. Remikiren suppressed plasma Ang I and Ang II, increased plasma active renin (from 23 +/- 12 to 154 +/- 161 pg/mL), decreased plasma aldosterone (from 106 +/- 42 to 82 +/- 33 pg/mL), and slightly decreased diastolic blood pressure (from -2.4 +/- 2.7 mm Hg). The blood pressure and hormonal responses to Ang I infusion after renin inhibition and the slope of the rise in plasma Ang II with increasing Ang I dose were identical in both groups, as was the plasma Ang I/Ang II ratio before (DD, 2.09 +/- 1.04; II, 2.59 +/- 0.76) and after (DD, 0.15 +/- 0.13; II, 0.09 +/- 0.03) combined renin inhibitor and Ang I infusion. CONCLUSIONS: Despite its association with a major difference in plasma ACE levels, the ACE I/D polymorphism did not influence the Ang II and plasma aldosterone production, plasma active renin decrease, or diastolic blood pressure increase induced by exogenous Ang I infusion, suggesting that ACE has no limiting influence on systemic Ang II generation and effects under these experimental conditions.

Adolescent↗
PubMed1995

Short-term effects of octreotide on blood pressure and plasma catecholamines and neuropeptide Y levels in patients with phaeochromocytoma: a placebo-controlled trial.

OBJECTIVE: The observation that phaeochromocytoma possess specific somatostatin binding sites led us to test the hypothesis that octreotide may have antisecretory potential in patients with phaeochromocytoma. We therefore compared the effects of octreotide and placebo on blood pressure and plasma catecholamines and neuropeptide Y. PATIENTS: Ten consecutive patients referred to a tertiary care centre for the diagnosis and treatment of a phaeochromocytoma. DESIGN AND MEASUREMENTS: We performed a crossover comparison of either three 100 micrograms subcutaneous injections of octreotide over one day or 3 injections of octreotide vehicle over another. Blood pressure was measured over 24 hours on each test day using an automatic ambulatory recorder. Blood samples were collected before (at 0800 and 0900 h) and after (at 1000, 1100, 1200, 1300 and 1500 h) placebo or octreotide injection. Plasma catecholamines were assayed by high-performance liquid chromatography and neuropeptide Y was determined using a two-site amplified enzyme immunoassay. All patients then underwent surgery and tumoral somatostatin binding site density was determined by quantitative autoradiography. RESULTS: Compared to placebo, octreotide did not alter mean 24-hour ambulatory blood pressure or plasma neuropeptide Y, or plasma or urinary catecholamine, levels. Although a moderate reduction in plasma noradrenaline was found in the two patients with the highest tumoral somatostatin binding site densities, overall octreotide-induced variations in plasma noradrenaline did not correlate with somatostatin binding site density. Blood glucose increased from 5.4 +/- 0.3 on placebo to 7.8 +/- 0.5 mmol/l on octreotide (P < 0.01). CONCLUSION: In the present controlled conditions, short-term administration of octreotide had no antisecretory effect in patients with phaeochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1995

Comparison of biological activities of two low molecular weight heparins in 10 healthy volunteers.

1. Low molecular weight heparins (LMWHs) are produced by different depolymerization processes and may therefore differ with respect to their pharmacokinetic properties. 2. We designed a single dose, randomized cross-over study in 10 healthy volunteers to compare the 24 h pharmacokinetics of two LMWHs, reviparin and enoxaparin, which have been previously shown to be clinically equivalent in terms of post-operative deep vein thrombosis prevention, despite significant differences in their in vivo biological activity. The two LMWHs were subcutaneously administered at the same dosages that are used in clinical studies: 4250 anti-Xa iu for reviparin and 40 mg for enoxaparin which have similar in vitro anti-Xa activities. 3. The overall 24 h profiles of the plasma anti-Xa and anti-thrombin activities were similar for reviparin and enoxaparin. The Amax and the AUC(0, 24h) of plasma anti-Xa activity after reviparin administration were both slightly but significantly lower than those observed after enoxaparin administration (difference between treatments of 0.03 95% CI[0.01-0.05] iu ml-1 h and 0.56 95% CI[0.22-0.90] iu ml-1 for Amax and AUC(0, 24h) respectively). After adjustment for in vitro anti-Xa activity, the statistical difference between the two LMWHs persisted for the AUC(0, 24h) but not for the Amax of plasma anti-Xa activity. The tmax and the MRT values for plasma anti-Xa activity did not significantly differ between the two drugs. The t1/2 for reviparin did not significantly differ from that of enoxaparin (2.7 +/- 0.7 h vs 3.5 +/- 0.9 h respectively, NS). The Amax of the plasma anti-thrombin activity after reviparin administration was also slightly but significantly lower than that observed after enoxaparin administration, (difference between treatments of 0.018 95% CI[0.01-0.025] iu ml-1) whereas the AUC(0, 24h) of anti-thrombin activity vs time was not. A slight but significant increase of the activated partial thromboplastin time of a similar magnitude was observed after both reviparin and enoxaparin injections. 4. The calculated surface under the thrombin generation curve vs time (or thrombin potential) at peak was significantly higher after reviparin than after enoxaparin (367 +/- 53 UA vs 305 +/- 48 UA respectively, P < 0.05). Four hours after injection, thrombin potential was significantly correlated to plasma anti-Xa activity after reviparin but not after enoxaparin injection (r = 0.65, n = 10, P = 0.05 and r = -0.38, n = 10, P = 0.25 respectively). 5. After a single-dose injection in healthy subjects, two LMWHs with comparable in vitro activities differed slightly kinetically. Such minor differences are probably of little importance in the prevention of post-operative deep vein thrombosis, since these two LMWHs were previously shown to be comparable in this setting.

Adult↗
PubMed1994

[Therapeutic approach in arterial hypertension with renal artery stenosis].

Screening for renal artery stenoses in hypertensive patients aims at detecting lesions whose treatment (renal revascularization) will normalize or reduce blood pressure and correct or prevent reduced glomerular filtration. Consequently, screening tests such as renal artery duplex Doppler scanning, renal scintigraphy or digital-subtraction angiography are used in patients in whom hypertension is severe, drug-resistant or associated with renal failure. Surgical repair or transluminal angioplasty is not warranted for all stenoses, however, particularly in atheromatous stenoses where these procedures have a 1% mortality, a 10% morbidity and a 30% failure rate to improve blood pressure despite adequate anatomical outcome. Predictors of favourable blood pressure outcome following revascularization are aetiological (fibrous dysplasia rather than atheroma), historical (young age, short duration of hypertension), physiological (renal ischaemia confirmed by scintigraphy, lateralizing renal vein renin ratio) and anatomical (truncal rather than ostial or branch stenoses). Outcome of surgery and transluminal angioplasty has only been documented in retrospective, uncontrolled reports in which blood pressure improvement is overestimated via the placebo effect, habituation to blood pressure readings and optimization of drug treatment, the latter being frequently required despite adequate revascularization. The first prospective randomized trials evaluating angioplasty in atheromatous stenoses are underway and should provide objective information concerning the risk/benefit ratio of this procedure.

Dilatation↗
PubMed1994

Blood pressure effects of acute intravenous renin or oral angiotensin converting enzyme inhibition in essential hypertension.

OBJECTIVE: To assess the participation of the renin-angiotensin system in the blood pressure regulation of essential hypertensive patients through acute specific renin inhibition. DESIGN AND METHODS: Fifty-three consecutive untreated hypertensive patients (mean +/- SD age 55 +/- 10 years, 42 male) were investigated on their usual sodium diet in a 3-h protocol. The first 11 patients did not receive any drug, the following 20 patients ingested a single oral dose of captopril (1 mg/kg) and the last 22 patients received a renin inhibitor infusion (remikiren; 1 mg/kg over 60 min). RESULTS: The maximum diastolic blood pressure fall was comparable in the two treated groups. Diastolic blood pressure changes analysed as area under the curve were similar for both drugs (overall F1,40 = 1.26, P = 0.27). Even though the baseline renin levels were within the narrow range 5-80 pg/ml, the diastolic blood pressure fall analysed as area under the curve from time 32 min to time 60 min was significantly correlated with the baseline active renin level in both groups (remikiren r = 0.44, P < 0.05; captopril r = 0.47, P < 0.05). The plasma active renin levels were significantly increased at 30, 90 and 120 min in both groups, and the maximum active renin levels were significantly correlated with the baseline active renin level (remikiren r = 0.62, P < 0.01; captopril r = 0.66, P < 0.01). The plasma prorenin levels did not change. CONCLUSIONS: This study suggests that acute renin inhibition and acute angiotensin converting enzyme inhibition similarly decrease the blood pressure and increase the plasma active renin levels. Acute blockade of the renin-angiotensin system at its initial step by a renin inhibitor can therefore be used to investigate the renin dependence of the blood pressure in essential hypertension.

Administration, Oral↗