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Biomedical subjects

V Paul

Publications and source records attributed to V Paul.

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

Human cystathionine beta-synthase: gene organization and expression of different 5' alternative splicing.

The human cystathionine beta-synthase (CBS) gene spans in excess of 30 kb and consists of 19 exons, with three different 5' untranslated regions including three different exons 1 (exons 1 a, b, and c). Exon 1a and 1b are 390 bp apart from each other and are linked to exon 2 in cDNA << a >> and cDNA << b >>. Exon 1c, which linked to exon 5 in cDNA << c >>, is 7 kb apart from exon 1b. All splice sites conform to the GT/AG rule, including those from exon 1a or 1b to exon 2 and from exon 1c to exon 5. Upstream of exons 1a and 1b, we found two putative promoter sequences with high C + G nucleotide content, one CAAT box at -70 nucleotides (for exon 1b), no TATA box, several Spl binding regulatory consensus sequences, and some other regulatory sequences. Human adult and fetal Northern blots hybridized with total cDNA containing exon 1b, or specific probes from exons 1 (b and c) showed mRNAs of 2.5 kb, 2.7 kb, and 3.7 kb. These results suggest that the mRNAs containing the different exons 1 are under the control of different promoters.

Animals↗
PubMed1997

Effect of ammonia on motor function in adult rats.

Changes in motor function were assessed in male rats after injecting graded doses (100, 200, 400, and 800 mg/kg, IP) of ammonium chloride and ammonium acetate. The effects were correlated with the concentrations of ammonia and glucose in the brain and blood. Spontaneous motor activity and motor coordination were inhibited after injecting 100 and 200 mg/kg, whereas with 400 and 800 mg/kg the animals exhibited convulsive movements. A dose-dependent increase was found in the concentrations of ammonia and glucose in both blood and brain. These were restored, 25 min after treatment, to control levels in the blood and not in the brain. A correlation was found between the time courses of inhibitory motor events and a rise in brain ammonia levels. Convulsant action of ammonium salts was accompanied by a marked elevation of ammonia and glucose concentration in the brain. The findings suggest that detoxication of diffused ammonia is a rate-limiting process in the brain and that ammonia, at toxic concentrations, decreases glucose utilization in the brain, resulting in an inhibition of motor function. A very high concentration of ammonia in the brain, although inhibiting glucose utilization, produces clonic convulsions probably by activating directly the motor neurons.

Acetates↗
PubMed1995

A sex-related difference in the neurobehavioral and hepatic effects following chronic endosulfan treatment in rats.

The neurobehavioral and hepatic effects following chronic endosulfan administration were studied in adult male and female rats. The neurobehavioral effect was determined by testing spontaneous motor activity, motor coordination and learning and memory processes in rats of either sex, 30 days after treating the animal orally with endosulfan (3.0 and 6.0 mg/kg per day). Mortality occurring during the treatment and body weight gain at the termination of treatment were also recorded. Liver weight and liver and serum concentrations of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and acetylcholinesterase were measured in order to determine the hepatotoxic effect of endosulfan. Body weight gain, motor coordination and acetylcholinesterase activity were unaltered in either sex. Learning and memory processes were impaired in both groups indistinguishably. Liver weight and liver and serum transaminases concentrations were increased more markedly in female than in male animals. A 30% mortality occurred in female group that received 6 mg/Kg of endosulfan. Endosulfan stimulated spontaneous motor activity more markedly in male than in female animals. These findings suggest that a sex-related difference seems to occur in the stimulation of spontaneous motor activity, liver injury and mortality that result from repeated exposure to sublethal doses of endosulfan in rats.

Acetylcholinesterase↗
PubMed1995

Genomic organization of the human cystathionine beta-synthase gene: evidence for various cDNAs.

A CBS cDNA isolated from an adult liver cDNA library was cloned and sequenced. The 5' untranslated region (5'-UTR) contains a sequence which is only partially common (88nt) with that previously published (3). It is expressed as a 2.5kb species mostly in liver and pancreas and faintly in brain, heart, kidney and lung and as a 3.7 kb in pancreas and liver. The human cystathionine beta-synthase gene (CBS) was isolated from a cosmid genomic library and its structure was determined. The CBS gene is at least 23 kb long and is composed of 17 exons. The organization of the human gene is different from that of the rat especially in the 5'-UTR. In the rat gene the ATG is present in exon 1, conversely in the human gene first the ATG is present in exon 3 and second the 5'-UTR contains two different exons 1 (E1a and E1b) linked with exon 2.

Adult↗
PubMed1995

The concept of "direct mechanical ventricular assistance" in the treatment of left-ventricular failure. Part 2. Results of the new intrathoracic implantable multi-chamber pump system (IMPS) in an animal study.

An assist device was developed which is able to support the pumping function of the heart by direct application of pressure to the left ventricle. The goal of this animal study in pigs was to determine whether it is possible to maintain sufficient blood circulation with the aid of the new system when the heart is fibrillating or its capacity has been greatly reduced. Following sternotomy complete invasive monitoring was installed. The intrathoracic implantable mechanical multi-chamber pump system (IMPS) was placed around the left ventricle. By means of the beta-blocker carazolol, systolic left-ventricular pressure (LVPsys), cardiac output, heart rate, and left-ventricular dp/dtmax (LVdp/dtmax) were gradually lowered and the pump system was tested intermittently. Then the heart was fibrillated and the system was tested again. When cardiac output, LVdp/dtmax, and systolic blood pressure were reduced by approximately 50% IMPS was able to increase LVPsys by 83% (IMPS) on: 96 +/- 9 mmHg vs. IMPS off: 63 +/- 6 mmHg), and the blood pressure in the carotid artery by 86% (IMPS on: 95/40 +/-15 mmHg vs. IMPS off: 69/38 +/- 9 mmHg). The mean cardiac output was 64% (IMPS on: 4.3 L/min vs. IMPS off: 3.9L/min); in most cases a great variability could be observed depending on the preload, the heart rate, and the mode of pressure application. When the heart was fibrillating, IMPS was able to maintain adequate circulatory conditions with LVPsys = 88%, blood pressure in the carotid artery = 85%, and LVdp/dtmax = 57% of the control values measured before fibrillation and beta-blockade. The system presented here is able to support the impaired left ventricle and to replace its pumping function. The advantages of the system are its efficiency and the lack of contact of the circulating blood with foreign surfaces. Whether the system is suited for bridging and recovery support shall be clarified in further studies.

Adrenergic beta-Antagonists↗
PubMed1995

The concept of "direct mechanical ventricular assistance" in the treatment of left-ventricular failure. Part 1: Idea, development and construction of an implantable multi-chamber pump system partially surrounding the heart.

In this paper we present a therapeutic concept for the treatment of heart failure due to muscular inability to pump properly. The basic principle of this concept triggered numerous studies, then with the aim of cardiopulmonary resuscitation, back in the 1970s. In general, it dealt with mechanical systems which led to an increase in stroke volume, systolic blood pressure, and cardiac output through the application of pressure directly to the left ventricle. After a critical appraisal of the relevant literature from technical, physical, and medical viewpoints, and our own preliminary studies on animal hearts within the framework of mock circulation experiments, we have conceived a new functional principle for direct mechanical ventricular assistance based on squeezing the left ventricle only. We have begun development of the system which has the advantages of ease of use, high biocompatibility due to lack of contact between blood and system components, the prevention of infection through complete intrathoracic implantation (long-range goal), and the fact that the patient's own heart can be supported by the system without being removed from the circulatory system (support of the residual myocardial function). Technical as well as medical prerequisites are indicated, and the materials selection and construction principles of the control, pressure generation, pressure transduction, and ventricular compression unit are described. It has proved possible to construct a prototype system to be used in animal experiments, which, through pneumatic inflation of a chamber system partially surrounding the left ventricle, should be able to augment or take over the pumping function of the left ventricle.

Animals↗
PubMed1995

Cyclodiene insecticides-induced changes in the central depressive effect of chlorpromazine in rats.

Spontaneous motor activity (SMA), conditioned avoidance response (CAR), muscle coordination (MC) and pentobarbital sleep were tested in rats treated orally for 90 days with tolerated doses of the cyclodiene insecticides, aldrin (1 mg/kg) and endosulfan (2 mg/kg). The same tests were repeated in similarly treated animals after injecting chlorpromazine (4 mg/kg, i.p.). Both the insecticides shortened pentobarbital sleeping time indicating their microsomal enzyme inducing property. Aldrin suppressed SMA, CAR and MC, whereas endosulfan stimulated SMA, inhibited CAR and unaltered MC. However, their concurrent action with CPZ did not result in change in the central depressive effects of the latter, but its potency during the course of its action was altered. Its potency 15 min after injection was greater and 60-180 min later was lesser in these animals than that observed in control animals. This finding was interpreted to suggest that aldrin and endosulfan has quickened the biotransformation of CPZ and thereby shortened its duration of action. A temporary promotion of its potency was accounted to its active metabolites, since prior to inactivation, CPZ is known to be metabolized by the microsomal enzymes to active compounds.

Aldrin↗
PubMed1994

The neurobehavioural toxicity of endosulfan in rats: a serotonergic involvement in learning impairment.

Oral administration of the insecticide endosulfan (2 mg/kg per day) for 90 days in immature male rats resulted in an inhibition of pole-climbing escape response to electric shock (unconditioned) and avoidance response to buzzer (conditioned). These responses reflect respectively their learning and memory processes. The escape response but not the avoidance response was reinstated significantly by the 5-hydroxytryptamine (5-HT) depletor, p-chlorophenylalanine (PCPA, 100 mg/kg per day for 3 days). Endosulfan increased 5-HT concentrations in the cerebrum and midbrain regions. Protein content and acetylcholinesterase activity were unaltered in the brain. The spontaneous motor activity of these animals was stimulated. Their muscle coordination on rota-rod apparatus was unaffected. These findings were interpreted as an indication that a motivation deficit and not motor impairment was responsible for the inhibitory action of endosulfan on pole-climbing escape and avoidance responses. Thus, endosulfan was suggested to produce learning and memory deficit. A serotonergic involvement was significant in endosulfan-induced learning impairment and it appeared to be negligible in its memory disrupting action.

Acetylcholinesterase↗
PubMed1994

Postoperative hemodynamic improvement with paced linkage of the donor and recipient hearts following heterotopic cardiac transplantation.

It has been shown that following heterotopic heart transplantation the recipient left ventricle ejects more effectively when it contracts out of phase with the donor left ventricle. However, this is rarely the situation, as the two hearts beat independently of one another and the denervated donor heart tends to beat faster than the recipient. In this study the hemodynamic effects of connecting the two hearts by an external temporary dual-chamber pacemaker were evaluated. The donor right ventricle was sensed and the recipient right atrium paced after a timed delay. The delay was adjusted so that recipient systole coincided with donor diastole. Eleven patients were studied in the first postoperative day. Pacing resulted in an improvement in cardiac output from 5.0 to 5.6 l/min (p = 0.003) and a reduction in pulmonary capillary wedge pressure from 16 to 12 mmHg (p = 0.0035). This was associated with a 35% reduction in inotrope requirements. It is concluded that sequential pacing of the two hearts is a useful adjunct to inotropic support in the postoperative period.

Cardiac Output↗
PubMed1994

A rate responsive pacemaker that physiologically reduces pacing rates at rest.

Current rate responsive pacemakers incorporate sensors such as minute ventilation (MV) for adapting to changing patient conditions during exercise and periods of exertion. However, for sleep and/or rest periods, the only pacemakers currently on the market that slow the pacing rate utilize an internal timer to determine a decrease in pacing rate. It would be advantageous if the pacing rate could be automatically lowered during periods of sleep or rest. This study utilized a rate responsive sensor, MV, to track the patient's sleeping and resting periods and to decrease the pacing rate at such times. A total of eight patients implanted with Sentri 1210 single chamber MV sensor pacemakers were studied. A sleep rate (SR) of 45 beats/min was selected. A sleep rate response function, which indicated the relationship between changes in MV and corresponding heart rate, was initially set at a value of 16 and continually and automatically updated in a 3-month study. Adaptation was based on the premise that 3 hours per day should be spent at the SR. The average decrease in pacing rates from onset to 3 month for the eight patients was 12.4% +/- 5.3%. Correspondingly, the histograms of the lowest datalog histogram (40-59 beats/min) increased from 0% to 15.4% +/- 0.9% of paced beats. Correlation between the patients' 24-hour diary and Holter recordings showed that the pacing rates during sleep were consistently lower than when the patients were awake and active. This was also the case with a patient whose nocturnal and daily routine was intentionally altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Septal short atrioventricular delay pacing: additional hemodynamic improvements in heart failure.

Controversy exists as to whether short AV delay pacing is beneficial in left ventricular dysfunction with the studies performed coming to disparate conclusions. The right ventricular apical pacing previously studied results in asynchronous contraction and relaxation sequences and may limit the potential benefits of short AV delay pacing. In this study the hemodynamic effects of septal (resulting in a more physiological activation sequence) and apical right ventricular activation were compared in 15 patients with heart failure. VDD pacing with AV delays of 50, 100, and 150 msec was evaluated. Apical VDD pacing did not increase the cardiac output significantly, 4.1 +/- 0.75 to 4.45 +/- 0.74 L/min, whereas septal VDD pacing increased the cardiac output to 4.86 +/- 0.79 L/min (P = 0.037). Apical pacing increased the cardiac output in 10 patients and septal pacing in 11 patients. We conclude that selected patients with ventricular dysfunction benefit from short AV delay pacing. Septal ventricular activation confers significant hemodynamic improvements over apical activation.

Atrioventricular Node↗
PubMed1994

Hemodynamic and metabolic effects of paced linkage following heterotopic cardiac transplantation.

BACKGROUND AND PURPOSE: Heterotopic cardiac transplantation is a valuable surgical technique that maximizes the use of donor organs. However, recipient heart function may decline steadily postoperatively with resulting clinical deterioration. Paced linkage has the potential of reducing afterload and enhancing coronary flow of both hearts, thereby improving recipient- and donor-heart function. This may have long-term as well as short-term benefits. METHODS AND RESULTS: The study was performed on 11 heterotopic transplant recipients. The two hearts were linked with a pacemaker (paced linkage) to produce recipient heart systole during different periods of donor-heart diastole. The recipient ventricular contraction was timed to occur during early, mid, and late diastole of the donor heart. Hemodynamic baseline measurements were compared with the optimal counterpulsated data. Paced linkage produced significant improvements in total cardiac output, 5.0 +/- 0.9 compared with baseline 4.5 +/- 0.8 L/min (P = .021); recipient coronary sinus flow, 278 +/- 145 versus 186 +/- 108 mL/min (P = .022); and aortic systolic pressure, 135 +/- 27 versus 123 +/- 27 mm Hg (P = .005). There was an overall improvement in systolic ventricular performance in the recipient heart when pace linked, as evidenced by a significant increase in left ventricular systolic pressure of 118 +/- 36 compared with the baseline value of 108 +/- 33 mm Hg (P = .016), an increase in ejection period from 174 +/- 30 versus 203 +/- 48 (P = .046), and a decrease in the pre-ejection period of 147 +/- 37 when paced versus 181 +/- 39 milliseconds (P = .013). The metabolic studies showed a significant decrease in hypoxanthine release from a baseline level of 0.4 mumol/L to a paced value of -0.06 mumol/L (P = .002); these very low values would suggest that there is no evidence of ischemia. Hemodynamic changes in the donor heart included a significant reduction in the left ventricular end-diastolic pressure from 6.8 +/- 4.4 versus baseline of 10.5 +/- 5.8 mm Hg (P = .029) and in maximum -dP/dT from 3.2 +/- 1.7 versus baseline of 2.1 +/- 1.1. CONCLUSIONS: Paced linkage after heterotopic cardiac transplant produces significant functional improvements in both hearts. Permanent pacemaker implantation may sustain these acute benefits and prevent the premature deterioration of the recipient heart.

Adult↗
PubMed1994

A technique for quantitative measurement of clonic convulsions in rats.

A capacitance sensor which detects vibrations caused by the movements of animals can be used for measuring automatically the clonic convulsions induced by chemical convulsants. This knowledge has been utilized to devise an instrument which has satisfactorily measured the clonic convulsions induced by picrotoxin in rats.

Animals↗
PubMed1993

Effects of procainamide on the signal-averaged electrocardiogram in relation to the results of programmed ventricular stimulation in patients with sustained monomorphic ventricular tachycardia.

OBJECTIVES: The aim of this study was to assess the ability of the signal-averaged electrocardiogram (ECG) to predict the efficacy of procainamide. BACKGROUND: The main role of the signal-averaged ECG has been the identification of postinfarction patients at risk of sudden death. Prediction of the efficacy of antiarrhythmic drugs represents another potential clinical application of this technique. METHODS: The study examined the effects of procainamide on the time domain and spectral temporal analysis of the signal-averaged ECG in relation to the results of programmed ventricular stimulation studies in 31 patients with inducible sustained monomorphic ventricular tachycardia. RESULTS: Procainamide significantly prolonged the total and the initial QRS complex and low amplitude signal durations (mean +/- SD 135 +/- 30 vs. 161 +/- 46 ms, p < 0.0001; 87 +/- 16 vs. 98 +/- 20 ms, p < 0.0001, and 48 +/- 23 vs. 63 +/- 36 ms, p < 0.001, respectively) whereas the root-mean-square voltage of the total QRS complex and of the last 40 ms of the QRS complex was significantly reduced (mean +/- SD 112 +/- 36 vs. 87 +/- 36 microV, p < 0.0001; 21 +/- 19 vs. 13 +/- 12 microV, p < 0.002, respectively). The results of spectral temporal mapping of the signal-averaged ECG were similar before and after procainamide administration. Procainamide prevented the inducibility of sustained ventricular tachycardia or prolonged the cycle length of ventricular tachycardia by > or = 100 ms in 16 patients (52%) (responders). The fractional prolongation of the total QRS duration was significantly greater in responders (26 +/- 15%) than in nonresponders (10 +/- 10%) (p < 0.002) and, when this prolongation was > or = 15%, identified responders with a sensitivity of 94%, a specificity of 87% and an overall predictive accuracy of 90%. CONCLUSIONS: The effects of procainamide on inducibility of ventricular tachycardia during programmed ventricular stimulation can be predicted by the degree of drug-induced prolongation of the signal-averaged QRS complex.

Aged↗