A comparative study between tear protein electrophoresis and accessory salivary gland biopsy in Sjögren's syndrome.
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Biomedical subjects
Publications and source records attributed to F Carré.
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A group of 18 well-trained white-water kayakers performed maximal upper body exercise in the laboratory and during a field test. Laboratory direct peak oxygen uptake (VO2) values were compared, firstly by a VO2 backward extrapolation estimation and secondly by an estimation calculated from VO2 measured during the first 20 s of exercise recovery. Direct peak VO2 correlated with VO2 backward extrapolation (r = 0.89), but the results of this study showed that the backward extrapolation method tended to overestimate significantly peak VO2 by [0.57 (SD 0.31) l.min-1 in the laboratory, and 0.66 (SD 0.33) l.min-1 in the field, P < 0.001]. The VO2 measured during the first 20 s of recovery, whether the exercise was performed in the laboratory or in the field, correlated well with the laboratory direct peak VO2 (r = 0.92 and r = 0.91, respectively). The use of the regression equation obtained from field data (VO2F20s), that is peak VO2 = 0.23 + 1.08 VO2F20s, gave an estimated peak VO2, the mean difference of which compared with direct peak VO2 was 0.22 (SD 0.13) l.min-1. In conclusion, we propose the use of a regression equation to estimate peak VO2 from a single sample of the gas expired during the first 20 s of recovery after maximal exercise involving the upper part of the body.
Reduced heart rate variability (HRV) has a strong predictive value in terms of sudden death, as compared to other prognostic criteria, but it has never been previously studied in experimental models of cardiac hypertrophy and failure. However, it has been quantified in rats using Holter monitoring and the peak and trough method of analysis. In normal rats, as in humans, short and long oscillations, sensitive, respectively, to atropine and propranolol were detected. Both correlate with heart rate. Cardiothyrotoxicosis was characterized by tachycardia and, independently, by a pronounced alteration in long oscillations. HRV was normal in compensatory cardiac hypertrophy due to aortic stenosis, but in this model the normal correlation existing between HRV and heart rate had disappeared. It is suggested that the main determinants of the above modifications of HRV are the changes in the new myocardial phenotype observed in terms of beta-adrenoceptor and muscarinic densities.
The analysis of heart rate variability (HRV) provides information on neural control of the heart. We investigated HRV in normal rats and in models of experimental cardiac hypertrophy using the Holter monitoring and peak/trough method. In normal rats, two heart rate oscillations with different wavelengths, high frequency (HF) and low frequency (LF) oscillations, were detected. The HF oscillations were insensitive to propranolol and suppressed by atropine. The LF oscillations were sensitive to both antagonists. Thyrotoxicosis resulted in cardiac hypertrophy (+20%) and tachycardia. The HF oscillations were unchanged, whereas LF oscillations were hampered at low heart rate in this group. Aortic stenosis resulted in cardiac hypertrophy (+53%), but heart rate oscillations were unchanged. The (number x amplitude) product for both types of oscillations correlated with heart rate in controls but not in the thyrotoxicosis or aortic stenosis models. Alterations of HRV in cardiac hypertrophy occur in rats as in humans. They may reflect the changes in the molecular components of the adrenergic/muscarinic system, which defines the new myocardial phenotype.
Muscle relaxation times can now be measured accurately with magnetic resonance imaging (MRI), distinguishing working muscles from non-working muscles. A correlation between T2 increase and work intensity has been shown in healthy volunteers. The small amount of data on T1 relaxation times is contradictory. In addition, all the published studies have concerned short-duration exercise in subjects of unknown training level. The goals of this study were (i) to determine T1 and T2 variations in thigh muscles after long dynamic exercise, (ii) to analyse the effects of training and (iii) to determine the relationship between power output and relaxation times after exercise. Sedentary men, soccer players and tri-athletes performed submaximal dynamic exercise at a constant heart rate for 15 min. MRI was performed before and 5 min after the end of exercise. The results showed (i) that T1 increased in parallel to T2 in anterior thigh muscles and (ii) that multiple correspondence analysis and hierarchical ascending classification can discriminate three subjects classes according to power output, training level and relaxation times, which fitted well with our three groups of subjects.
The high incidence of arrhythmias in human left ventricular hypertrophy has been well established but the mechanisms of arrhythmias are not well defined. In attempt to clarify these mechanisms, we tried to determine if a relationship might exist in the hypertrophied or senescent hearts between the incidence of arrhythmias and alterations in the gene expression of the main membrane proteins involved in the regulation of calcium movements. Holter monitoring was used in young and senescent rats where hypertrophy had been induced by aortic stenosis and hyperthyroidism (young rats) or by DOCA-salt treatment (senescent rats). Different types of spontaneous arrhythmias were detected. In the aortic stenosis group, the heart rate and the number of supraventricular premature beats were increased significantly, whereas the number of ventricular premature beats was increased in some animals but not in all. In senescent rats, the numbers of ventricular and supraventricular premature beats and the incidence of atrioventricular block were very high. At the cellular level, the density of calcium channels from the sarcolemma and of the alpha 1 subunit of the Na+/K(+)-ATPase were unchanged in the hypertrophied and senescent hearts but most of the proteins involved in the regulation of calcium movements (calcium release channel and Ca(2+)-ATPase from the sarcoplasmic reticulum, Na+/Ca2+ exchange, and beta adrenergic and muscarinic receptors from the sarcolemma) have a decreased density or activity. These changes might account for the slowing of the maximum shortening velocity and the impaired contractility of the hypertrophied and senescent hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: The aim of this study was to determine the expression of genes coding for the beta 1 adrenergic receptor and the alpha subunit of Gs in the adult rat normal and hypertrophied left ventricle, and in the left ventricle of the hypophysectomised rat after T4 intoxication. METHODS: Total RNA was extracted from normal, control, or hypertrophied left ventricles 5 weeks after aortic stenosis, and from left ventricles of control or T4 injected hypophysectomised animals. The expression of beta 1 adrenergic receptor and G alpha s mRNAs was quantitated by northern blot analysis and hybridisation with specific 32P-dCTP labelled DNA probes. RESULTS: beta 1 Adrenergic receptor mRNA was decreased (by 33%) in compensated left ventricular hypertrophy without modification of the relative level of G alpha s mRNA. The relative level of beta 1 adrenergic receptor mRNA correlated negatively with the degree of left ventricular hypertrophy, suggesting that the expression of the beta 1 adrenergic receptor gene is not activated by pressure overload. In the left ventricle of the hypophysectomised rat, a rapid increase in beta 1 adrenergic receptor mRNA (by 180% 3 h after hormone injection) was observed in response to T4, with no change in the relative content of G alpha s mRNA. These results provide evidence that beta 1 adrenergic receptor mRNA and G alpha s mRNA accumulate to different levels of abundance in the adult left ventricle, as indicated by their ratios (0.053 and 0.043 in sham operated and hypertrophied left ventricles respectively). This suggests that distinct mechanisms are involved in the control of the accumulation of these two mRNAs in cardiac tissue. CONCLUSIONS: The reduction in beta 1 adrenergic receptor density in the hypertrophied rat left ventricle is associated with a parallel reduction in the level of beta 1 adrenergic receptor mRNA. The beta 1 adrenergic receptor gene may belong to a group of genes which are not activated by pressure overload, but are responsive to thyroid hormone.
This review paper deals with recent data concerning the physiopathology of chronic heart failure. Broadly speaking, the cause of chronic heart failure is arterial hypertension and/or coronary disease. Myocardial hypertrophy is only one example of biological adjustment to the environment, and chronic heart failure, an adaptation disease, indicates its limits. Diastolic dysfunction includes 3 elements. Relaxation is slowed down by a decrease in density of Ca(2+)-ATPase in the sarcoplasmic reticulum and by a fall in Na+/Ca2+ exchange activity. The decline of tissue compliance is mainly explained by probably hormonal changes in collagen. Changes in isomyosins account for abnormalities of atrial contraction. At the beginning of mechanical overload, the fall in systolic function enables the heart to produce a normal tension. The determinant element is slowing down of intracellular calcium movements. Enlarged hearts generate arrhythmias. The origin is probably the presence of unstable calcium homeostasis.
Fifteen normotensive athletes specializing in dynamic sports took part in a randomized double-blind and cross-over study: captopril (50 mg/24 h) vs placebo. Each treatment lasted one month. Maximal exercise tests on cycle ergometer were performed at the end of each period. No significant differences were observed in the maximal values of oxygen uptake, power, heart rate or blood lactate value. The anaerobic threshold, defined as the exercise intensity which corresponded to a 4 mmol.l-1 blood lactate level was unchanged. With captopril, the end-of-exercise systolic and diastolic BP were slightly altered (NS). Lower limb muscle strength, as explored with a Cybex isokinetic system, was not modified by captopril intake. The results indicate that maximal aerobic performance and isokinetic strength of the lower limbs are not altered by captopril chronic administration (50 mg/day) in normotensive trained subjects.
OBJECTIVE: The aim was to define experimental models of spontaneous arrhythmias in various models of cardiac hypertrophy in rats. METHODS: Cardiac hypertrophy was induced by several methods and 24 h Holter monitoring was recorded in conscious rats to quantify spontaneous arrhythmias in hypertrophied hearts. Male Wistar rats were studied. A group of young controls 1-2 months old (n = 16) was compared to four groups of animals with cardiac hypertrophy: (1) thyrotoxic rats which received a daily intraperitoneal injection of L-thyroxine for 7 d (n = 6); (2) rats subjected to abdominal suprarenal aortic stenosis (n = 11); (3) senescent rats 22-24 month old (n = 6); and (4) S-DOCA-salt (senescent animals rendered hypertensive by uninephrectomy and DOCA-salt treatment, n = 8). RESULTS: (1) Thyroxine resulted in 20% cardiac hypertrophy, with normal arterial tension, sinus tachycardia, a shorter P wave length and PR interval, and frequent (5/6) atrioventricular block. No premature beats were seen. (2) In aortic stenosis, atria and left ventricle were hypertrophied by 53% and systolic carotid pressure increased by 63%. The incidence of supraventricular premature beats was increased [frequency = 0.70 (SEM 0.3) per 24 h in control v 99(61) in aortic stenosis, p < 0.05]. Ventricular premature beats remained as rare as in control. (3) In senescent and S-DOCA-salt rats all types of spontaneous arrhythmias, but specially supraventricular arrhythmias and atrioventricular block, were frequent. Cardiac hypertrophy produced by DOCA-salt treatment in senescent rats had no effect on the incidence and nature of arrhythmias, but resulted in an increased QTc interval. CONCLUSIONS: Senescent rats and rats with aortic stenosis represent valid models of spontaneous arrhythmias occurring in the absence of ischaemia or toxic insult. Spontaneous arrhythmias in rats are mainly of supraventricular origin. Hyperthyroidism in rats is a model of atrioventricular block probably related to tachycardia. Holter monitoring in rats may have several potential pathophysiological and pharmacological applications.
We now have a biological explanation for most of the physiological characteristics of the hypertrophied chronically overloaded heart: (i) the slowing of the active relaxation is, at least in part, explained by a diminished density in the Ca2+ ATPase of SR, a majority of the modifications in passive myocardial compliance are due to an enhanced collagen density and the diminution of the atrial contribution to ventricular filling is certainly a consequence of an isomyosin change in this particular tissue. (ii) The systolic dysfunction reflects, in fact, one of the most essential parts of the adaptational process, the slowing of Vmax. In human, this diminution is a consequence of a rather complex change in the expression of various genes coding for proteins responsible for myoplasmic calcium transient. (iii) Arrhythmogenecity, a well-known detrimental property of the hypertrophied heart, reflects the fragility of calcium homeostasis in this type of cell, and this fragility is likely to be a direct consequence of the rearrangement of the membrane proteins.
Using an excimer laser working in the far ultraviolet and cutting fresh corneas of human cadaver eyes, we were able to demonstrate that there is an ideal fluence (joule/cm2/pulse) that allows a maximum tissue ablation depth per shot. Above the threshold of 1 J/cm2/pulse the depth of tissue ablated does not increase and both thermal and mechanical damage appears at the cut edges.
Rabbits were injected intravenously with a single dose of sodium salicylate (350 mg kg-1) in order to study the following in vivo: (i) the distribution of the drug in the various eye tissues and fluids, particularly the cornea and aqueous humour, and (ii) transfer of the drug from corneal grafts obtained from donors receiving sodium salicylate to the eye tissues of the recipient. In additional experiments, the in vitro effects of sodium salicylate on the growth and protein synthesis of corneal cells grown in tissue culture were also studied. In vivo experiments showed that the periods during which we observed the highest concentration of salicylate in the serum and in the eye tissues were within 30 min and 2 hr respectively following the injection. These experiments also showed that salicylate was transferred from the treated donor via corneal graft to the recipient's eye tissues where it could still be detected 48 hr after the operation. In vitro experiments showed that a 50% inhibition of cell growth was obtained at a concentration of about 1000 micrograms salicylate ml-1 while protein synthesis was decreased by 50% at a concentration of about 200 micrograms ml-1. A consideration of our data from the in vivo and in vitro experiments together suggests that ingestion by the donor of high concentrations of salicylate may have the potentiality of subjecting the corneal endothelial cells to cytotoxic concentrations of the drug thus jeopardizing the success rate of corneal graft operations.
The distribution of sodium pentobarbital in the eye after lethal and anesthetic doses and the possibility of the drug's transfer via corneal grafting were studied in rabbits. The drug was found in all the ocular tissues and humours following the intravenous injection of a single lethal (60 mg/kg) or anesthetic (30 mg/kg) dose, and it was still present 24 hours after the anesthetic injection. In both instances the largest quantity was found in the cornea. After grafting of corneal tissue containing pentobarbital the drug dispersed into the recipients' corneas and other ocular tissues. In-vitro studies showed that 250 micrograms of the drug per millilitre of incubation medium reduced the rate of growth of the corneal fibroblasts to 50%, and 300 micrograms/mL reduced their protein synthesis to 66%. Calculations showed that these concentrations could be reached in the cornea or the aqueous humour in vivo following either the lethal or the anesthetic injection of the drug.
We compared the bovine melanotic and amelanotic retinal pigment epithelial (RPE) cells cultivated in vitro using a number of parameters. Both cell types could be readily harvested from the eye by dissection or by enzyme treatment of the RPE. Both types of cells grew equally well in the primary culture, and in serial subcultures for over 600 days, and also after being stored frozen for over two months. The two types of cells were similar in their growth patterns, morphology, chromosome characteristics and phagocytic activity but they differed in their tyrosinase activity. Although in long-term cultures cells showed chromosome loss, a high proportion of the cells retained their normal diploid chromosome number (2n = 60) with apparently normal karyotype.
The phagocytic activity of the pigmented epithelium of the bovine retina was studied with an organ culture model. Latex particles coated with immunoglobulin, or bovine rod outer segments, both labelled with radioactive iodine, were the objects to be phagocytosed. Various agents were tested with this model for their effects on phagocytosis by the retinal pigment epithelium. Iodoacetate significantly inhibited phagocytosis, as did penicillin, though to a lesser extent. Concanavalin A and gentamicin enhanced phagocytosis. Dimethyl sulfoxide had no effect. The results with lymphokines were not conclusive.
We wished to devise a simple in vitro test for identifying the presence of antigen sensitive lymphocytes in corneal tissue having an immunological inflammatory reaction. A number of rabbits were immunized by subcutaneous injections of human serum albumin (HSA). A final injection of the same antigen was given in the centre of the cornea to produce an immunological corneal inflammation. Other rabbits were immunized by an antigen unrelated to HSA. A non-immunological corneal inflammation was produced in another group of animals by applying sodium hydroxide. Five days after the immunogenic and non-immunogenic corneal insults, when the limbus showed vascularization, the eyes of the different groups of animals were enucleated. From each eye, small corneal discs containing a portion of the limbus were cut with a trephine. The discs (explants) were then incubated for 20-24 hours at 37 degrees C in the presence or absence of HSA or in the presence of an antigen unrelated to HSA. At the end of incubation, the extent of leucocyte migration from each explant was measured. Only in the presence of the specific antigen did leucocytes from explants of the immunized animals show marked inhibition of migration.
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