Biomedical subjects

A Cordier

Publications and source records attributed to A Cordier.

At least 37 records · Page 2Linked to original sources

PubMed1998

Hepatocellular effects of cyclosporine A and its derivative SDZ IMM 125 in vitro.

The novel immunosuppressive drug O-hydroxyethyl-D(Ser)8-cyclosporine (SDZ IMM 125) and cyclosporine A (CyA) were compared in different in vitro models with respect to hepatocellular side effects. SDZ IMM 125 was less lipophilic than CyA and also decreased liposomal membrane anisotropy less. Furthermore, SDZ IMM 125 increased Na+ and Ca++ permeability across the liposomal membranes significantly more than CyA. The uptake of CyA and SDZ IMM 125 into freshly isolated rat hepatocytes was neither saturable, Na+ dependent or temperature sensitive, nor could it be inhibited vice versa, indicating passive diffusion. The diffusion coefficient of CyA was about two times higher than that of SDZ IMM 125, reflecting its higher lipophilicity. In primary hepatocyte monolayers the cellular concentrations of CyA were about two times higher than that of SDZ IMM 125. As an indicator of cholestasis the saturable uptake of cholyltaurine into isolated cells was found to be apparently competitively inhibited to the same extent by both compounds. In isolated perfused rat livers SDZ IMM 125 caused a significantly greater decrease in bile flow than did CyA. Release of lactate dehydrogenase from hepatocyte primary cultures and from isolated perfused livers were determined as parameter of cell damage. In both systems the cytotoxicity of SDZ IMM 125 was significantly higher than that of CyA. The data suggest that SDZ IMM 125 causes greater cholestatic and cytotoxic effects than CyA at equimolar cellular exposure.

Animals↗

PubMed1998

Auditory evoked potentials for the assessment of noise induced hearing loss.

As it has been demonstrated in many animal experiments, noise can damage the cochlea and the central auditory pathways. It is very difficult in clinical studies to separate the relative contribution of both these sites. Auditory evoked potentials ABR, MLR and SVR study retrocochlear nervous conduction and collectively the results of these techniques proved an objective evaluation of the cochlear function. The Authors have studied a group of 130 sport shooters with high frequency hearing loss and found that in 38 ears a clear retrocochlear component could be recognised. Correlation with intensity, frequency and length of exposure to the traumatic noise demonstrates that explosive noise is an agent for NIHL. However athletes exposed to similar noises did not suffer from similar hearing loss, probably because of the well known individual noise susceptibility.

Adult↗

PubMed1998

Evaluation of a new procedure for the flow cytometric analysis of in vitro, chemically induced micronuclei in V79 cells.

Measurement of the frequency of micronuclei induced in cells by ionizing radiation or by chemical treatment is widely used to analyze cytogenetic damage. The microscopic scoring of micronuclei is a tedious and time-consuming procedure. Therefore, attempts have been made to automate micronuclei scoring by means of image analysis or flow cytometry. A new procedure for the flow cytometric analysis of chemically induced micronuclei in V79 Chinese hamster cells has been established in our laboratory. Debris was separated from micronuclei by means of a new gating procedure using area and width fluorescence of the stained suspension of micronuclei and nuclei. In order to test the sensitivity and specificity of this improved method of flow cytometric analysis, five well-known mutagenic compounds were tested. With the new technique, the frequency of micronuclei measured and analyzed corresponded well with results obtained by conventional microscopy. In addition, a large series of negative compounds, and weak, middle, and strong micronuclei inducers, were tested in order to establish criteria for discrimination between genotoxic and nongenotoxic compounds by flow cytometry. This new procedure for flow cytometric detection of micronuclei represents a quick, reliable, and relatively simple method for in vitro micronucleus testing.

Animals↗

PubMed1997

Decrease in kidney calbindin-D 28kDa as a possible mechanism mediating cyclosporine A- and FK-506-induced calciuria and tubular mineralization.

The use of the immunosuppressant cyclosporine A (CsA) is limited by its adverse renal effects. Most recently, we reported that the drug markedly decreases the levels of the calcium-binding protein calbindin-D 28kDa in kidneys of male Wistar rats. In the present study, the potential relationship between drug-induced nephrotoxicity and the decrease in kidney calbindin-D 28kDa was investigated. Four groups of male Wistar rats were treated for 10 or 31 days with either the immunosuppressant CsA (50 mg/kg/day), FK-506 (5 mg/kg/day), rapamycin (5 mg/kg/day) or with the nonimmunosuppressive cyclosporine derivative 3'keto-[Bmt1]-[Val2]-CsA (SDZ PSC-833) (50 mg/kg/day), and the effects on calcium homeostasis, kidney histology and renal calbindin-D 28kDa were examined. Similar effects were found with CsA and FK-506; both drugs strongly reduced kidney calbindin-D 28kDa protein levels, increased urine calcium excretion, caused intratubular calcification, and induced basophilic tubules. In contrast, rapamycin and SDZ PSC-833 caused no decrease in renal calbindin-D 28kDa levels, no noticeable alterations in calcium metabolism, and no renal calcification. The results provide evidence for a link between decreased renal calbindin, increased calcium urine excretion, and intratubular kidney calcification. The present data show no correlation between the decrease in renal calbindin and the induction of basophilic tubules; however, it needs to be investigated if these apparently independent kidney effects may have a common origin upstream of calbindin expression.

Animals↗

PubMed1997

Enhancement of SDZ ICT 322-induced cataracts and skin changes in rats following vitamin E- and selenium-deficient diet.

The indole-3-carboxylic acid scopoine ester. SDZ ICT 322, is a selective hydroxytryptamine (5-HT3) antagonist, which after chronic treatment causes posterior subcapsular cataracts and skin changes such as hair loss, hyperaemia, desquamation and hyperkeratosis in rats. The detailed mechanisms underlying these changes are not yet known. In order to evaluate a possible oxidative stress-induced pathomechanism of SDZ ICT 322, the antioxidative defence capacity in rats was modulated by feeding a special vitamin E- and selenium-deficient (VE/SeD) diet. For this purpose 32 male Wistar rats, age 4 weeks, were pretreated for 8 weeks with either a VE/SeD diet or a normal standard diet. Each dietary group was divided into 8 control and 8 SDZ ICT 322-treated animals. SDZ ICT 322 was administered in feed to rats at an adjusted daily dose level of 125 mg/kg for 14 weeks. Plasma levels of SDZ ICT 322 as well as of the N-desmethyl metabolite were similar in rats fed the different diets in weeks 3, 6 and 14. In SDZ ICT 322 treated VE/SeD rats cataracts were observed by week 7, whereas in rats fed normal diet cataracts were first seen in week 14. In the normal dietary group no corneal opacity was found after SDZ ICT 322-treatment; however, a corneal opacity was seen in the deficiency group in parallel with one of the cataract animals in week 7. The incidence and severity of clinical skin signs were greater and their onset was earlier in the deficiency dietary group: onset occurred after 6 weeks compared to 9 weeks on the normal diet. Thiobarbituric acid reactive substances, an indicator mainly of oxidized lipids, were statistically significantly increased in the urine of rats administered SDZ ICT 322 and the VE/SeD diet. Uric acid, which is an endogenous antioxidant was statistically significantly decreased in the urine and plasma of SDZ ICT 322 VE/SeD treated rats. The clinical eye and skin changes occurring early after VE/SeD feeding, the unchanged drug plasma exposure and unchanged drug metabolite formation in combination with the general pro-oxidative activity of the drug suggest an oxidative stress-mediated pathomechanism of SDZ ICT 322 at high dose levels in rats.

Animals↗

PubMed1997

Cyclosporine A-induced contraction of isolated rat aortic smooth muscle cells.

The mechanisms by which the immunosuppressive drug cyclosporine A (CsA) induces hypertension and nephrotoxicity are still not fully understood. Although smooth muscle cell (SMC) contraction is probably the mechanism of vasoconstriction, the direct contractive effect of CsA on SMCs has not yet been demonstrated. Thus, it was the purpose of this study to evaluate the direct effects of CsA in cultured SMCs through interactive image analysis. In aortic SMCs, CsA at the concentrations of 0.01, 0.1 and 1 microM, caused a concentration-dependent decrease of the planar cross-sectional area (PCSA) after 30 min and 60 min of treatment. The PCSA decreases were statistically significantly different from control at all concentrations. No cytotoxicity was observed under these conditions. Ten minutes preincubation of SMCs with a monoclonal antibody against endothelin-1 (ET-1) significantly prevented the CsA effects at 1 microM. When the same antibody was heat inactivated or an unspecific antibody (anti-desmin immunoglobulin G) was applied, the CsA-induced contractions were not affected. These data suggest that CsA can cause a direct contractive effect on vascular SMCs. This effect is partly mediated by ET-1.

Animals↗

PubMed1997

Osmotic drugs in the treatment of cochlear disorders: a clinical and experimental study.

On the grounds of positive results obtained with Meniere's patients, agents such as glycerol and mannitol have been included in the therapeutical protocol of other cochlear disorders presenting with hearing loss either of sudden onset, but not observed at an early stage, or accompanied by tinnitus and aural pressure. Intravenous infusions of either 10% glycerol or 18% mannitol were given to selected patients 3 to 6 times with a time interval of 1 to 3 days. Hearing loss, tinnitus and aural pressure were evaluated as improved, unchanged or worsened. In 33% of the glycerol group and 23.8% of the mannitol group we observed hearing threshold improvement, while aural fullness improved in 45% of the glycerol and 56.2% of the mannitol groups, and tinnitus was only relieved in 13.1% of the glycerol and 5.8% of the mannitol group. A parallel experimental study was carried out on guinea-pigs in order to shed light on the effects of mannitol and glycerol on the inner ear. Cochlear blood flow was measured with a laser Doppler flowmeter at the level of the basal turn of the cochlear lateral wall, both in normal and hydropic guinea-pigs, before and after osmotic intraperitoneal infusion. Basal values in the normal cochlea were much higher than in the hydropic one, and both mannitol and glycerol markedly influenced the local blood flow in the normal cochlea, giving few or no changes in the hydropic one.

Animals↗

PubMed1997

Electrocochleographic findings: Menière's disease versus sudden sensorineural hearing loss.

Electrocochleography was conducted in 185 patients with Menière's disease and 117 with sudden deafness. Electrophysiological findings from the two groups were compared in order to identify pathogenic similarities between the two conditions. Parameters investigated were the summating potential (SP)/action potential (AP) ratio, audiometric profiles and audiometric changes after medical therapy. A high SP/AP ratio was found in the patients with sudden deafness, thus supporting a possible hydropic aetiology in this group. In conclusion, electrocochleography can be considered a useful technique as it permits identification of an hydropic condition in certain cases of sudden deafness.

Audiometry↗

PubMed1997

Cyclosporine A-induced oxidative stress in rat hepatocytes.

In man the immunosuppressive drug Cyclosporine A (CsA) has been used successfully in organ transplantation and in the treatment of autoimmune disorders. The drug, however, causes side effects which occur mainly in the kidney but also in the liver. The mechanisms leading to the hepatic side effects are not yet fully understood. Because reactive oxygen production is a common mechanism of drug toxicity, the goal of this study was to evaluate whether CsA induces oxidative stress in rat liver cells. In primary rat hepatocyte 20-h cultures, CsA caused a concentration-dependent increase of free reactive oxygen species, thiobarbituric acid reactive substances, loss of protein thiols and decrease of molar ratios of glutathione and glutathione disulfide in the range of 0 to 50 microM CsA. The weakening or enforcement of the cellular glutathione state by the glutathione synthesis inhibitor buthionine sulfoximine or the glutathione disulfide -reducing agent dithiothreitol either increased or inhibited the CsA cytotoxicity, as determined by lactate dehydrogenase release. CsA also decreased the level of endogenous antioxidant ascorbic acid and increased its oxidation product dehydroascorbic acid. Supplementation of the cell cultures with ascorbic acid significantly reduced the CsA toxicity. The antioxidant DL-alpha-tocopherol-polyethylene-glycol-1000-succinate partly decreased CsA-mediated reactive oxygen species formation, totally decreased thiobarbituric acid reactive substances formation, prevented the loss of protein-bound sulfhydryl groups and in addition totally inhibited the CsA cytotoxicity. The present data provide good evidence that oxidative stress is part of the mechanism by which CsA causes toxicity in rat liver cells.

Animals↗

PubMed1997

Role of transient-evoked otoacoustic emissions for hearing preservation in acoustic neuroma surgery.

OBJECTIVE: This study aimed to assess whether transient-evoked otoacoustic emissions (TEOAEs), which are known to be expressions of an intact cochlear function, could be useful for the rationale of hearing preservation in acoustic neuroma (AN) surgery. STUDY DESIGN: The TEOAEs were measured before, during, and after surgery in a consecutive series of patients affected by cerebellopontine angle tumors. SETTING: The study was performed at the Department of Otolaryngology, University "La Sapienza" of Rome. PATIENTS: Five patients with AN and one with a meningioma totally involving the Cochlear (VIII) nerve. INTERVENTION: Retrosigmoid approach on the ground of the limited AN size (within 20 mm) and the 30/70 rule, as proposed by the American Academy of Otolaryngology-Head and Neck Surgery nomogram. Two patients also were selected despite a poor hearing level and the absence of TEOAEs. MAIN OUTCOME MEASURES: Preoperative and postoperative pure tone audiometry compared with TEOAEs. Intraoperative TEOAEs were compared with electrocochleographic findings. RESULTS: The TEOAEs were found to be present also in patients with AN with poor pure-tone average (PTA) threshold (i.e., > 75 dB). Intraoperatively, TEOAEs recording showed to be markedly affected by the environmental noise as well as by specific intraoperative maneuvers, such as drilling of the internal auditory canal or tumor removal or both. In the three patients in whom hearing successfully was preserved. TEOAEs were present in the first postoperative days, despite a temporary deterioration of the PTA threshold. CONCLUSIONS: The intraoperative use of TEOAEs showed to be scarcely reliable, whereas their presence in the preoperative assessment of patients with AN could lead to an extended number of patients to be selected for hearing-preservation surgery. Finally, an early postoperative identification of TEOAEs may be considered a favorable prognostic sign for foreseeing a delayed pure-tone hearing threshold recovery.

Acoustic Stimulation↗

PubMed1996

RNase P from a photosynthetic organelle contains an RNA homologous to the cyanobacterial counterpart.

RNase P is a ribonucleoprotein enzyme in all organisms and organelles investigated so far, with the exception of chloroplasts where no enzyme-associated RNA has been detected to date. As an approach to answer the question whether an RNA component is present in RNase P from photosynthetic organelles, we have used a phylogenetically oriented strategy and searched for RNase P RNA in a postulated intermediate in plastid evolution, the cyanelle of Cyanophora paradoxa. We have detected a 351 nucleotide long RNA similar to cyanobacterial RNase P RNAs, with a proposed secondary structure that closely resembles a bacterial consensus. The RNA is encoded on the cyanelle genome and copurifies with enzyme activity. The RNA is not catalytically active by itself, but the activity of the cyanelle RNase P holoenzyme is destroyed by nuclease treatment, indicating an essential role of the RNA. Hence cyanelle RNase P, combining properties of bacterial and eukaryotic enzymes, occupies an intermediate position in RNA enzyme evolution. The first description of an RNA component in RNase P from a photosynthetic organelle might thus be an important step towards an understanding of plastid RNase P structure and function.

Base Sequence↗

PubMed1996

Cyclosporine A decreases the protein level of the calcium-binding protein calbindin-D 28kDa in rat kidney.

Despite the widespread use of cyclosporine A (CsA), its mechanism of action and side effects are not yet completely understood. There exists a large body of evidence suggesting that disturbance of calcium homeostasis is a critical step in the cascade of cellular and molecular events induced by the drug. As recently shown in our laboratory by two-dimensional protein gel electrophoresis (2-DE) analysis of kidney homogenates, CsA induced numerous changes in several kidney proteins. One kidney protein in particular was shown to be strongly down-regulated by the drug. In this work we report the identification of the strongly decreased kidney protein as calbindin-D 28kDa, a vitamin D-dependent calcium-binding protein associated with calcium handling by cells. The assignment of the down-regulated protein spot is based on its internal amino acid sequence analysis and its specific reaction with a monoclonal antibody raised against calbindin-D 28kDa. In kidney homogenates of male Wistar rats treated with 50 mg/kg/d CsA for up to 28 days, calbindin levels were measured by ELISA and were shown to be continuously decreased with prolonged CsA treatment. To our knowledge, this is the first report describing the effect of CsA on kidney calbindin-D 28kDa protein levels. Further studies are needed to elucidate whether the CsA-mediated down-regulation of the calcium-binding protein calbindin-D 28kDa may be a critical factor for the renal adverse effects induced by this drug.

Amino Acid Sequence↗

PubMed1996

Induction of the adipose differentiation-related protein in liver of etomoxir-treated rats.

The effects of etomoxir, an irreversible carnitine palmitoyltransferase I inhibitor, on the liver protein pattern and on liver morphology were examined by two-dimensional gel electrophoresis in female Sprague-Dawley rats treated with 125 mg/kg/day etomoxir for 28 days. In livers of treated animals a protein spot was found which was not present in controls. The spot was identified by internal amino acid sequence analysis as the adipose differentiation-related protein (ADRP). The expression of ADRP in liver is a novel finding as the protein has been described previously as adipocyte-specific. Additionally we found histopathologic evidence of lipid accumulation in the livers of etomoxir rats. The data show that for each treated rat there was a good correlation between ADRP levels and degree of lipid droplet formation. This observation may suggest a potential relationship between drug-induced expression of ADRP in liver and lipid accumulation.

Amino Acid Sequence↗

PubMed1996

Lingual thyroid: value of integrated imaging.

Lingual thyroid is an uncommon cause of oropharyngeal mass, due to a congenital anomaly of thyroidal development and migration: It is defined precisely as the presence of thyroid tissue in the midline of the tongue base between circumvallatae papillae and the epiglottis. We report a case of lingual thyroid in which the integration of clinical data, sonography, color-duplex Doppler, MRI and scintigraphy was determinant in demonstrating the disease. A 22-year-old woman presented with a sensation of foreign body in the throat, dysphonia, dyspnoea and dysphagia; we performed sonography (7.5 MHz linear probe), color Doppler (7 MHz Doppler frequency, PRF 3500 Hz) and MRI (1.5 T, spin-echo T1- and T2-weighted images with administration of Gd-DTPA); a scan with 123I demonstrated a relevant uptake at the base of the tongue, but no uptake at the typical thyroid location. The gland was removed and partially transplanted in the strap muscles of the neck.

Adult↗

PubMed1996

Crystalloid cardioplegia route of delivery and cardiac troponin I release.

BACKGROUND: Cardiac troponin I (CTn I) has been shown to be a marker of myocardial injury. Incomplete distribution of cardioplegic solution may be responsible for injury in jeopardized myocardial areas. The aim of this study was to compare CTn I release with respect to the route of delivery of crystalloid cardioplegia, either antegrade only or initially antegrade followed by retrograde cardioplegia for the remainder of the operation, in patients undergoing elective coronary artery bypass grafting. METHODS: Sixty patients were randomly assigned to one of two cardioplegia groups. Cardiac troponin I concentrations were measured in serial venous blood samples drawn just before cardiopulmonary bypass and after aortic unclamping at 6, 9, 12, and 24 hours and daily thereafter for 5 days. Analysis of variance with repeated measures was performed to test the effect of route of delivery, coronary disease, collateral circulation, risk of cardioplegia maldistribution, and number of grafts on release of CTn I. RESULTS: Compared with the antegrade route, the combined route offered no advantage in an unselected group of patients undergoing an elective first cardiac operation and having preserved left ventricular function. The CTn I concentration did not differ between groups for any of the samples considered. In patients with major left main coronary artery stenosis, CTn I release was significantly higher at hour 9 in the antegrade group than in the group with combined delivery. CONCLUSIONS: A combined route of delivery of crystalloid cardioplegia is beneficial in patients with major stenosis of the left main coronary artery. Cardiac troponin I sensitivity is relevant in this study. Release of CTn I should be useful in determining the best form of myocardial protection for each patient.

Aged↗

PubMed1995

Effects of cyclosporine A on the rat liver and kidney protein pattern, and the influence of vitamin E and C coadministration.

The effects of cyclosporine A (CsA), a potent immunosuppressive drug, were examined in rat liver and kidney samples using two-dimensional electrophoretic protein analysis. Of a total of 370 liver and 336 kidney spots analyzed, 8% (29 spots) and 6% (19 spots), respectively, showed a significant drug-induced change (p < 0.01), which was predominantly reflected in increased protein abundance (62% and 74% of the changes, respectively). Of the 48 proteins changed in either organ, 14 were most probably common to both tissues and one of these was significantly increased in both the liver and the kidney. Most of the other 13 showed similar trends (either increases or decreases) in both organs. However, the most striking drug effect seen in this study concerned an unidentified protein present only in the kidney, which completely disappeared upon CsA treatment. It was also investigated whether the drug-induced changes could be prevented by the coadministration of the radical scavengers vitamin E and C with CsA. Spots changed by the administration of the drug were classified according to three different categories, based on their response profiles in rats treated with CsA in combination with the vitamins: (i) spots which were changed by CsA as well as by CsA in combination with the vitamins (12 liver and 4 kidney spots), (ii) spots which were changed by CsA and showed an additional increase of this change by CsA plus the vitamins (no liver and 4 kidney spots), and (iii) spots which were changed by CsA but not by CsA in combination with the vitamins (8 liver and 6 kidney spots). These results showed that in both organs the vitamins were able to prevent around 30% of the effects caused by CsA, and that two-dimensional gel electrophoresis is an excellent tool to demonstrate such drug interactions at the molecular level.

Animals↗

PubMed1995

Use of cardiac troponin I as a marker of perioperative myocardial ischemia.

Troponin I is a contractile protein comprising three isoforms, two related to the skeletal muscle and one to the cardiac fibers. Cardiac troponin I (CTn I) is specific, without any cross-reactivity with the other two. Several studies have demonstrated its release after acute myocardial infarction. In contrast, CTn I never has been found in a healthy population, marathon runners, people with skeletal disease, or patients undergoing non-cardiac operations. Thus, CTn I is a more specific marker of cardiac damage than common serum enzymes. It is also more sensitive, allowing diagnosis of perioperative microinfarction and detection of acute myocardial infarction much earlier after the onset of ischemia (4 hours). Using a rapid one-step assay, we measured the release of CTn I in two groups of patients after operation: 20 with calcified aortic stenosis and normal coronary arteries (aortic valve replacement group and control group) and 20 undergoing coronary artery bypass grafting. In the overall population CTn I peaked at hour 6 and practically disappeared after day 5. Mean values were higher in the coronary artery bypass grafting group. In the aortic valve replacement group, a positive correlation was found between aortic cross-clamping time and CTn I, which is a reliable marker of cardiac ischemia during heart operations and can be used to evaluate cardioprotective procedures.

Aged↗

PubMed1994

[Cerebral protection by retrograde perfusion in the treatment of acute aortic dissection].

Four consecutive patients underwent resection and graft replacement of ascending aorta or aortic arch for acute dissection. Retrograde cerebral perfusion (RCP) was used during circulatory arrest. RCP at 15 degrees C was administered through the superior vena cava. Duration of cerebral ischaemia and cardiopulmonary bypass averaged 33 and 156 minutes respectively. Retrograde perfusion flow was regulated from 100 to 800 ml/minute to maintain an internal jugular vein pressure of about 25 cm H2O. All patients survived. Three patients awoke neurologically intact. Minor neurological disturbance was found in 1 patient, he was discharged from hospital at day 11 without any detectable neurological deficit. This technique was attractive because it provided a dry operative field unencumbered by perfusion cannulas or clamps, facilitated construction of a more secure distal anastomosis, and avoided the risk of further injury resulting from the aortic cross clamp. It seems that RCP allows longer circulatory arrest time.

Acute Disease↗