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Biomedical subjects

R Garay

Publications and source records attributed to R Garay.

At least 19 recordsLinked to original sources
PubMed2006

[The role of transesophageal echocardiopgraphy in detection of cardiogenic and aortic sources of embolism in stroke and transient ischaemic attacks].

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.

Adult↗
PubMed2004

Mechanisms of vasomotor rhinitis.

Nonallergic non-infectious perennial rhinitis (NANIPER) is a heterogeneous disorder comprising several pathophysiological entities. The etiology of some of these disorders (e.g. drug-induced rhinitis, nonallergic rhinitis with eosinophilia syndrome [NARES], occupational rhinitis, hormonal rhinitis, emotion-induced rhinitis, physical/chemical irritant-induced rhinitis) is well established. In contrast, the aetiology of idiopathic forms of rhinitis (also known as vasomotor rhinitis) is largely unknown. Mechanistic studies have suggested that non-IgE-mediated inflammatory and/or neurogenic processes may be involved. There is evidence that localized inflammation is the underlying cause of symptoms in drug-induced rhinitis and NARES, since eosinophilia is an important pathophysiological component in these conditions. In contrast, neurogenic reflex mechanisms initiated by environmental factors appear to be involved in idiopathic rhinitis. It has been suggested that there may be an imbalance of the sympathetic and parasympathetic nervous systems, with parasympathetic hyper-activity and sympathetic hypo-activity resulting in nasal congestion and rhinorrhoea. Indirect evidence suggests that C-fibres may also play an important role in the pathophysiology of idiopathic rhinitis.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1997

A randomized double-blind placebo controlled study of azelastine nasal spray in children with perennial rhinitis.

One hundred and twenty five children (median age 8.71 years) suffering from perennial allergic rhinitis were treated in a randomized, double-blind, parallel group study comparing azelastine nasal spray 0.14 mg/nostril twice daily (0.56 mg/day) and placebo nasal spray. Medication was given for a period of 6 weeks which followed a 2 week placebo washout period in all patients. Subjects were aged between 5 and 12 and were skin prick positive to either house dust mites and/or cat or dog dander. Concomitant anti allergic treatment was not permitted during the study. Severity of rhinitis symptoms was scored daily by the child or his/her parents on a diary card using a visual analogue scale (VAS) for each evaluated symptom: 0, absent-100, could not be worse. Mean weekly scores were calculated. Symptoms evaluated were: sneezing, nasal blockage, nasal itch and rhinorrhea. In addition, at each clinic visit the investigator evaluated symptoms using a verbal score of 0, no symptom-3, severe. Compared to the baseline, for each of the six study weeks, the reduction in the VAS scores for all four symptoms was statistically greater for the azelastine group compared to the placebo group. The investigator's assessment at clinic visits bore out these results. Both azelastine nasal spray and placebo were well tolerated, no serious adverse events were reported. During the treatment phase of the study a total of 36 adverse events were reported by 25 patients (azelastine 10, placebo 15). The most frequently occurring events were pharyngitis (azelastine 5, placebo 3), cough (azelastine 3, placebo 1) and bronchitis (azelastine 1, placebo 3). In conclusion, azelastine has been shown to be effective in the treatment of perennial rhinitis in children aged 5-12 years and to be superior to placebo in the relief of all symptoms assessed, namely sneezing, nasal blockage, nasal itch and rhinorrhea.

Child↗
PubMed1995

Detection of a circulating inhibitor of the Na(+)-K(+)-Cl(-) cotransport system in plasma and urine after high salt intake.

The aim of the study was to detect the presence of an endogenous Na(+)-K(+)-Cl- cotransport inhibitor factor in plasma and urine from salt-loaded subjects. Twenty-six essential hypertensive patients (13 men, 13 women) and 6 normotensive controls (2 men, 4 women) received a diet containing 260 mmol/day of NaCl tablets for 7 days. Human erythrocytes from healthy blood donors (using bumetanide-stimulated Li+ efflux) were used to test the inhibition of Na(+)-K(+)-Cl- cotransport by different plasma and urine concentrations collected the last day of the salt-loaded period. The addition of plasma and urine from salt-loaded subjects significantly inhibited erythrocyte Na(+)-K(+)-Cl- cotransport (P < .001). No differences were observed between hypertensive patients and normotensive controls. These results provide evidence of an Na(+)-K(+)-Cl- cotransport inhibitor factor in plasma and urine from salt-loaded humans, in concordance with previous reports in salt-loaded rats.

Adult↗
PubMed1995

Sodium-magnesium exchange in erythrocyte membranes from patients with affective disorders.

The Vmax of erythrocyte sodium-magnesium exchange was measured for the first time in 63 patients suffering from affective disorders and compared to that in 33 healthy subjects. Depressed patients had a significantly higher Vmax (215 +/- 13 vs. 151 +/- 14 mumol/l.cells/h; p < 0.005; mean +/- SEM). This tendency was conserved after division of the 63 patients into three clinical subgroups according to the DSM-III-R criteria. Thirty-four patients from this panel were divided into three subgroups according to the chemical class of the antidepressant drug used and were followed up during a 3-month period of drug treatment. Mood improvement over the 3-month period was associated with a slow increase in Vmax of Na/Mg exchange (delta increase approximately 25 mumol/l.cells/h), except in the subgroup of patients treated with non-tricyclic antidepressants (n = 8). These results are consistent with the previously reported link between high erythrocyte magnesium content and affective disorders. Indeed, enhanced Na/Mg exchange Vmax, which probably results from an increased number of transport units per cell, contributes to the normalization of red blood cell magnesium content correlated with mood improvement.

Adolescent↗
PubMed1994

[Edema-inducing properties of lacidipine, nitrendipine and nifedipine in the spontaneously hypertensive rat].

INTRODUCTION: Clinical studies suggest that lacidipine (LA) is better tolerated than other DHP, in terms of peripheral edema. We evaluated edema due to LA, nitrendipine (NT) and nifedipine (NF) in SHR. METHODS: Mean arterial pressure (MAP) was measured with an intra-femoral probe. Peripheral edema was determined (i) by the plasmatic distribution of 14C-albumin, (ii) by Evans blue extravasation. RESULTS: In bolus(ip), LA, NT and NF had non different effects on plasmatic *ALB, i.e. + 3.9 +/- 1.7 (delta % vs control at 60 min; mean +/- SEM, n = 18). Evans blue extravasation (hind paws muscle = EBM) was positively correlated to MAP reduction (EBM = 0.1 x delta MAP + 5.2; p < 0.025), without differences between the molecules. In chronical administration (9 days), at comparable MAP decreases (31 +/- 2 mmHg), there was less edema formation with LA (0.05 mg/kg/j) than with NT (0.5 mg/kg/j) or NF (1.4 mg/kg/j): the variations of *ALB were respectively (% vs control at 45 min after tracer injection; mean +/- SD): + 5% (n = 10) vs. 73% (n = 14; p < 0.01 vs LA) and + 34% (n = 10; p < 0.01 vs LA); no significant change of hematocrit or plasma volume was noted. CONCLUSION: Our results confirm, in SHR, that lacidipine induces a very moderate edema formation. This does not seem to be due to a renal effect, nor to an effect on peripheral resistances. It was only observed in chronical administration, which suggests that pharmacokinetic properties of lacidipine are involved.

Animals↗
PubMed1994

Erythrocyte ion transport as indicator of sensitivity to antihypertensive drugs.

Multiple ion transport defects have been characterized in red blood cell membranes from essential hypertensive patients. These seem to be biochemical markers of at least three different types of essential hypertension. A first type is characterized by low pump, low cotransport fluxes in erythrocytes. These hypertensive patients are apparently identical to the salt-sensitive, low-renin hypertensive patients, in whom low pump and cotransport seem to result from the presence of circulating endogenous ouabain-like and bumetanide-like factors. These hypertensive patients are sensitive to diuretic drugs and to vaso-relaxants with salidiuretic activity, as expected from a reduction in plasma volume and circulating levels of endogenous ion transport inhibitors. A second type of essential hypertension is characterized by increased red cell Na+:Li+ countertransport and [Na+, K+, Cl-] cotransport. These hypertensive patients tend to present normal or high plasma renin activity, disorders in lipid metabolism, and left ventricular hypertrophy. Hypertensive patients belonging to this group seem to be resistant to diuretic drugs but sensitive to vasorelaxants. A third type of essential hypertension is characterized by both high membrane sodium leak and high [Na+, K+, Cl-] cotransport in erythrocytes. Hypertensive patients in this group are resistant to diuretics, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, and centrally acting drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Molybdenum uptake through the anion exchanger in human erythrocytes.

Human red blood cells were incubated in the presence of Na2MoO4 and the initial rate of molybdenum uptake was measured by using inductively coupled plasma emission spectroscopy. About 99% of molybdenum uptake was inhibited by DIDS or by SITS. DIDS-sensitive molybdenum uptake was inhibited by external chloride, bicarbonate, sulphate and phosphate in the range of concentrations previously described for anion carrier fluxes. Trace elements, previously described to be translocated by the anion carrier, i.e. copper, zinc and cadmium, slightly inhibited molybdenum uptake. Molybdenum uptake was strongly stimulated by acidification, suggesting that the monovalent HMoO4- anion species, which is formed in acidic media (pK approximately 4.1), can be more rapidly translocated than the divalent anion complex MoO4(2-), which is the predominant form at physiological pH. In conclusion, the anion carrier can catalyse rapid molybdenum movements across red cells membranes. This supports previous reports of an enterohepatic circulation of molybdenum, with red blood cells acting as molybdenum carrier between the intestine and the liver.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

A circulating inhibitor of the RBC membrane calcium pump in chronic renal failure.

A humoral inhibitor of the membrane calcium pump was studied in plasma from 28 normal controls, 33 patients receiving long-term hemodialysis, and 26 with chronic renal failure (CRF; creatinine clearance range was 6 to 97 ml/min). Calcium pump activity was measured as the rate of Sr2+ efflux in normal erythrocytes (RBCs) loaded with Sr2+ (a substitute of Ca2+ in the calcium pump). Plasma, and plasma ultrafiltrates from hemodialysis patients strongly inhibited calcium pump activity compared with controls without plasma (36 +/- 18 vs. 25 +/- 12, %INHIBITION/CONTROL, P < 0.05). Inhibition markedly decreased with acute hemodialysis (16 +/- 12 vs. 5 +/- 14, %INHIBITION/NORMAL PLASMA, N = 15, P < 0.001). In CRF, degree of inhibition correlated with the serum creatinine concentration (r = 0.75, P < 0.001). A kinetic study showed that plasma decreased the maximal rate of the Ca2+ pumps (Vmax) without affecting the apparent affinity for internal cations (KSr). Moreover, the plasma inhibitory factor had a low molecular weight, and was dialyzable and heat stable. In conclusion, we found evidence for an RBC membrane calcium pump inhibitor in uremic plasma, which correlates with the degree of renal insufficiency. Possibly, it may increase calcium content in RBCs and other cells and could thus be related to uremic toxicity and/or hypertension.

Adult↗
PubMed1992

Ultrastructural study of the choroid plexus of spontaneously hypertensive rats.

We previously gave an account of an increased ion transport activity in choroid plexus from spontaneously hypertensive rats. We have since examined this organ in scanning and transmission electronic microscopy. In the choroid plexus from young spontaneously hypertensive rats, the epithelial cells showed the following: a partial loss of the brush border and infoldings of basolateral membranes, an increased number of Golgi apparatus, vesicles, and mitochondria, and an activated nucleus. In adult hypertensive rats, the mitochondria had increased in number and tended to fill the cytoplasma while the nuclei had returned to a resting level. These ultrastructural changes furthermore suggest an increased secretory activity in the choroid plexus in spontaneously hypertensive rats.

Aging↗
PubMed1991

Action of azelastine on intracellular Ca2+ in cultured airway smooth muscle.

Azelastine, a novel antiasthmatic/antiallergic agent, was tested for Ca2+ antagonistic properties in cultured rabbit airway smooth muscle, vascular smooth muscle and cardiocytes. In airway smooth muscle cells, the basal cytosolic free calcium content was 195 +/- 72 nM (mean +/- S.D., n = 18). These basal values were decreased by azelastine with an IC50 value of 1.1 +/- 0.3 x 10(-4) M. Endothelin-1 (10(-7) M) induced a rapid increase in free cytosolic calcium up to 806 +/- 314 nM, which returned to normal levels in 3-5 min. This was fully blocked by azelastine in a concentration-dependent manner, with an IC50 value of 6.7 +/- 2.9 x 10(-5) M. Moreover, azelastine fully blocked histamine-induced calcium mobilization (IC50 = 7 x 10(-5) M). In cultured vascular smooth muscle cells and cardiocytes, azelastine was unable to decrease the basal cytosolic free calcium content or inhibit agonist-induced calcium mobilization. Therefore, at therapeutic levels, a specific, mild inhibition of calcium mobilization in airway smooth muscle may be one component of the antiasthmatic action of azelastine.

Animals↗
PubMed1991

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.

Animals↗
PubMed1991

Cadmium uptake through the anion exchanger in human red blood cells.

1. The initial rate of Cd2+ uptake in human red cells was measured by atomic absorption spectrophotometry. 2. About 96% of Cd2+ uptake was inhibited by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) with IC50 (concentration giving 50% of maximal inhibition) of 0.3 microM and by furosemide with IC50 of 500 microM and was resistant to ouabain and amiloride. This indicates the implication of the [Cl(-)-HCO3-] anion exchanger in Cd2+ uptake. 3. DIDS-sensitive Cd2+ uptake required the presence of external HCO3-. HCO3- ions had a biphasic effect on Cd2+ uptake. Low bicarbonate concentrations were stimulatory, suggesting formation of translocating bicarbonate-cadmium complexes. Higher bicarbonate concentrations were inhibitory, suggesting further bicarbonate complexation with formation of non-translocating species. Depending on the presence or absence of external Cl-, a maximal Cd2+ uptake of 1.7 or 0.37 mmol (l cells)-1 h-1 was observed at bicarbonate concentrations of 15.6 or 11 mM respectively. 4. In the presence of bicarbonate, external Cl- ions strongly stimulated Cd2+ uptake, with linear increase between 70 and 125 mM. This suggests that one translocating species may have chloride as ligand. 5. DIDS-sensitive Cd2+ uptake was modestly inhibited by physiological concentrations of external phosphate and was resistant to external K+, Mg2+ and Ca2+. 6. In conclusion, the anion exchanger is the major transport mechanism for red cell cadmium uptake. Translocating species appear to be monovalent anion complexes of cadmium with HCO3- such as [Cd(OH)(HCO3)2]- and [Cd(OH)(HCO3)Cl]-.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1990

Typology of Na+ transport abnormalities in erythrocytes from essential hypertensive patients. A first step towards the diagnosis and specific treatment of different forms of primary hypertension.

Over the last 5 years, several authors have measured apparent affinities and maximal translocation rates of the different erythrocyte Na+ transport systems in essential hypertensive patients. These kinetic studies have clearly shown that no unique red cell Na+ transport defect characterizes the whole population of essential hypertensive patients. Conversely, several complex patterns of erythrocyte Na+ transport abnormalities may be present in different subsets of essential hypertensive patients. These kinetic studies are now providing a more profound biochemical insight into the molecular heterogeneity of primary hypertension. In particular, they may permit the diagnosis and specific treatment of different forms of primary hypertension in the next decade.

Animals↗
PubMed1990

Evidence for a DIOA-sensitive [K+,Cl-]-cotransport system in cultured vascular smooth muscle cells.

The existence of a [K+,Cl-]-cotransport system in vascular smooth muscle cells was investigated in the A10 cell line by studying the effect of DIOA (dihydroindenyl-oxy-alkanoic acid, a potent inhibitor) on K+, Rb+ and Cl- fluxes. Hypotonic medium (150 mOsm) increased initial rates of ouabain and bumetanide-resistant (OBR) Rb+ uptake by 100%, bumetanide and DIDS-resistant Cl- uptake by 200%, and OBR net K+ efflux by 130%. DIOA inhibited 40 to 100% of the Rb+ influx and net K+ efflux stimulation with an IC50 of 4 X 10(-5) mol/L. DIOA-sensitive Rb+ influx was a sigmoidal function of the decrease in osmolarity, with a threshold at about 230 mOsm. Our results suggest that vascular smooth muscle cells have a DIOA-sensitive [K+,Cl-]-cotransport system. Dissipation of the outwardly directed Cl- gradient with an apparent [Cl- to K+] stoichiometry much higher than one may provide the energy to ensure net KCl (and osmotic water) extrusion and cell volume regulation in these cells.

Animals↗
PubMed1990

Stimulatory action of endothelin-1 on membrane Na+ transport in vascular smooth muscle cells in culture.

Endothelin-1 was able to induce an immediate and transient increase in cytosolic free Ca2+ concentrations in the A10 cell line of vascular smooth muscle. This was associated with a strong stimulation of the Na+:H+ exchange, the Na+, K+ pump and the [Na+,K+,Cl-]-cotransport system. Pump stimulation appeared to be secondary to sodium entry through Na+:H+ exchange because it was absent in Na+ loaded cells and in the presence of ethyl-isopropyl-amiloride. Cotransport stimulation was blocked by indomethacin, suggesting the involvement of a cyclooxygenase product. In conclusion, the monovalent ionic perturbations associated to the vasoconstrictor and mitogenic actions of endothelin-1 are counterbalanced by activation of the Na+,K+ pump and the [Na+,K+,Cl-]-cotransport system.

Animals↗
PubMed1990

Chloride (or bicarbonate)-dependent copper uptake through the anion exchanger in human red blood cells.

The initial rate of Cu2+ uptake in human red blood cells was measured by atomic absorption. About 80% of Cu2+ uptake was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) concentrations greater than 5-10 microM. DIDS-sensitive Cu2+ uptake required the presence of external HCO3- or external Cl-. Cl- strongly stimulated Cu2+ uptake following a Michaelis-like function, with apparent dissociation constant (KCl) of 72 +/- 9.4 (SD) mM (n = 6 experiments). HCO3- stimulated DIDS-sensitive Cu2+ uptake following a Michaelis-like function, with apparent dissociation constant (Kbic) of 10 +/- 1.9 (SD) mM (n = 4 experiments). Maximal rates (of Cl(-)- or HCO3(-)-stimulated Cu2+ uptake) were nonadditive. DIDS-sensitive Cu2+ uptake was not modified by physiological concentrations of phosphate or sulfate. Conversely, it was strongly inhibited by physiological concentrations of L-histidine and cysteine (at a Cu2+ concentration of 100 microM, these physiological ligands exhibited KHis and KCys of 50 and 80 microM, respectively). By using a copper-selective electrode, we found that at pH 7-7.4 copper is associated with OH-, particularly in the form of Cu(OH)2 complexes. In conclusion, the anion exchanger is the major transport mechanism for red blood cell Cu2+ uptake. The translocating species can be the monovalent anion complexes of copper with OH-, Cl-, and/or HCO3-.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗