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Biomedical subjects

M Morán

Publications and source records attributed to M Morán.

At least 19 recordsLinked to original sources

Disturbances of the sarcoplasmic reticulum and transverse tubular system in 24-h electrostimulated fast-twitch skeletal muscle.

Chronic low-frequency stimulation of rabbit tibialis anterior muscle over a 24-h period induces a conspicuous loss of isometric tension that is unrelated to muscle energy metabolism (J.A. Cadefau, J. Parra, R. Cusso, G. Heine, D. Pette, Responses of fatigable and fatigue-resistant fibres of rabbit muscle to low-frequency stimulation, Pflugers Arch. 424 (1993) 529-537). To assess the involvement of sarcoplasmic reticulum and transverse tubular system in this force impairment, we isolated microsomal fractions from stimulated and control (contralateral, unstimulated) muscles on discontinuous sucrose gradients (27-32-34-38-45%, wt/wt). All the fractions were characterized in terms of calcium content, Ca2+/Mg2+-ATPase activity, and radioligand binding of [3H]-PN 200-110 and [3H]ryanodine, specific to dihydropyridine-sensitive calcium channels and ryanodine receptors, respectively. Gradient fractions of muscles stimulated for 24 h underwent acute changes in the pattern of protein bands. First, light fractions from longitudinal sarcoplasmic reticulum, enriched in Ca2+-ATPase activity, R1 and R2, were greatly reduced (67% and 51%, respectively); this reduction was reflected in protein yield of crude microsomal fractions prior to gradient loading (25%). Second, heavy fractions from the sarcoplasmic reticulum were modified, and part (52%) of the R3 fraction was shifted to the R4 fraction, which appeared as a thick, clotted band. Quantification of [3H]-PN 200-110 and [3H]-ryanodine binding revealed co-migration of terminal cisternae and t-tubules from R3 to R4, indicating the presence of triads. This density change may be associated with calcium overload of the sarcoplasmic reticulum, since total calcium rose three- to fourfold in stimulated muscle homogenates. These changes correlate well with ultrastructural damage to longitudinal sarcoplasmic reticulum and swelling of t-tubules revealed by electron microscopy. The ultrastructural changes observed here reflect exercise-induced damage of membrane systems that might severely compromise muscle function. Since this process is reversible, we suggest that it may be part of a physiological response to fatigue.

Animals↗

Responses of rat myocardial antioxidant defences and heat shock protein HSP72 induced by 12 and 24-week treadmill training.

AIM: The purpose of this study was to determine the effects of both a short (12 weeks) and a long-term (24 weeks) endurance treadmill-training programme on the levels of oxidative stress markers, the activity of the enzymatic antioxidants, and the content of the 72 kDa heat shock protein (HSP72) in rat myocardium. METHODS: Thirty male Wistar rats were randomly assigned to exercise trained (n = 16) and sedentary (n = 14) groups. After 12 week of training, eight rats were killed while the remaining eight continued the training programme until 24 week. RESULTS: Seven sedentary controls were killed together with each trained group. Levels of thiobarbituric acid-reactive substances (TBARS), protein carbonyls, and total and oxidized glutathione (tGSH and GSSG) in myocardial homogenates were unchanged by training irrespective of the protocol duration. However, an increased content of the oxidative stress biomarkers was detected in hearts from both the 24-week trained rats and their sedentary controls when compared with their corresponding 12-week groups. The antioxidant enzymatic activities total and mitochondrial superoxide dismutase (tSOD and mtSOD, respectively), glutathione peroxidase (GPX) and glutathione reductase (GR), remained unchanged after the 12-week training period whereas a significant increase in tSOD and mtSOD activities (18%, P < 0.05) was observed in heart homogenates of 24-week trained animals as compared with their sedentary controls. HSP72 expression levels were not significantly modified after 12 week of training but a threefold increase was detected after 24 week (P < 0.05). CONCLUSION: These results demonstrate that a long-term endurance training (24 weeks) induced discrete increases in antioxidant enzyme activities in rat myocardium and elicited a marked enhancement in HSP72 expression levels. However, a shorter training programme (12 weeks), was not effective in increasing heart antioxidant defences.

Animals↗

Cobaltocenium-functionalized poly(propylene imine) dendrimers: redox and electromicrogravimetric studies and AFM imaging.

The first four generations of cobaltocenium-functionalized, diaminobutane-based poly(propylene imine) dendrimers DAB-dend-Cb,(PFb)x (x = 4, 8, 16, and 32; Cb=[Co(eta5-C5H4CONH)(eta5-C5H5)] (1-4) have been synthesized and characterized. The redox activity of the cobaltocenium centers in 1-4 has been characterized by using cyclic voltammetry and the electrochemical quartz-crystal microbalance (EQCM). All of the dendrimers exhibit reversible redox chemistry associated with the cobaltocenium/cobaltocene redox couple. Upon reduction. the dendrimers exhibit a tendency to electrodeposit onto the electrode surface, which is more pronounced for the higher generations. Pt and glassy carbon electrodes could be modified with films derived from 1-4,exhibiting a well-defined and persistent electrochemical response. EQCM measurements show that the dendrimers adsorb, at open circuit, onto platinum surfaces at monolayer or submonolayer coverage. Cathodic potential scanning past -0.75 V at which the cobaltocenium sites are reduced, gave rise to the electrodeposition of multilayer equivalents of the dendrimers. The additional material gradually desorbs upon re-oxidation so that only a monolayer equivalent remains on the electrode surface. Changes in film morphology as a function of dendrimer generation and surface coverage were studied by using admittance measurements of the quartz-crystal resonator on the basis of its electrical equivalent circuit, especially in terms of its resistance parameter. In general, we find that films of the lower dendrimer generation 1 behave rigidly, whereas those of the higher generation 4 exhibit viscoelastic behavior with an intermediate behavior being exhibited by 2 and 3. Using tapping-mode atomic force microscopy (AFM). we have been able to obtain molecularly resolved images of dendrimer 4 adsorbed on a Pt(111) electrode.

Journal Article↗

[Care of patients with the sleep apnea syndrome in the Czech Republic].

In the Czech Republic, for ten million inhabitants there are eight sleep laboratories (two neurological, one otorhinolaryngological and five pneumological), equipped with twelve units monitoring four or eight parameters. The first OSAS laboratory was established in 1991. In 1994, health insurance began providing patients with CPAP and doctors began publicising sleep syndromes. Since 1994, 3,860 patients were examined. Patients were referred: by general practitioners (34%), by otorhinolaryngologists (16%), by pneumologists (15%) or by neurologists (12%) and 24% came voluntarily. The ratio was eight men to one woman. Nearly all came because partners requested it. Of the 3,860 examined, 740 (around 19%) began using CPAP. The criteria for using CPAP are following: an oxygen saturation in the blood below 90% for more than 20% of the sleeping period. In very serious cases BiPAP was used (27 patients--0.7%). 185 patients (4.8%) underwent surgery on soft palate.

Czech Republic↗

Short-term effects of marathon running in master runners: no evidence of myocardial injury.

The purpose of this investigation was to analyze the short-term effects of marathon running on serum levels of cardiac markers in a group of master runners (> 60 yrs). Ten marathoners (9 male and 1 female; 63+/-4 yrs) were enrolled in the study. All of them completed the Madrid Marathon (1998). Venous blood was drawn from each subject three times during the study (48 h before the race, immediately after the race, and 24 h post-competition) for the determination of the several biochemical markers, such as total creatine kinase catalytic activity (total CK), mass concentration of creatine kinase isoenzyme MB (CK-MB mass), and cardiac troponin I (Tnl-c). The most important finding was that in each sample (pre- or post-race) serum Tnl-c was below the commonly accepted level of 0.1 ng x m(-1) indicative of myocardial injury. Although further research is needed using more complete methodology, our results suggest that marathon running does not have an acute deleterious effect on the hearts of the elderly.

Aged↗

Rat liver lysosomal and mitochondrial activities are modified by anabolic-androgenic steroids.

PURPOSE: The aim of this study was to examine the separate and combined effects of an 8-wk treatment with high doses of 17alpha-alkylated anabolic-androgenic steroids (AAS) and exercise training on selected lysosomal and mitochondrial enzyme activities in rat liver. METHODS: Sedentary and treadmill-trained (25 m x min(-1), 45 min x d(-1), 5 d x wk(-1)) male rats were treated with fluoxymesterone, methylandrostanolone, or stanozolol (2 mg x kg body weight(-1), 5 d x wk(-1)) for 8 wk. RESULTS: Acid phosphatase, arylsulfatase, beta-glucuronidase, and beta-galactosidase activities were increased in liver homogenates of sedentary and trained AAS-treated rats. The mitochondrial respiratory chain activities rotenone-sensitive NADH-cytochrome c reductase (NCCR), succinate cytochrome c reductase (SCCR), and cytochrome oxidase (COX) showed a significant decrease in steroid-administered rats, whereas citrate synthase (CS), a matrix enzyme, exhibited no changes in activity, pointing to a selective effect of AAS on mitochondrial membrane complexes. In vitro studies in mitochondrial fractions isolated from the liver of control rats showed that COX and CS activities were insensitive to the AAS, whereas NCCR and SCCR activities were partly inhibited. On the other hand, the mean values of serum parameters related to hepatic function were within normal ranges in all the experimental groups of animals. CONCLUSIONS: The present data show that 8-wk ingestion of three different anabolic-androgenic steroids, either with or without concurrent exercise training, affects lysosomal hydrolases and mitochondrial respiratory chain electron transport in rat liver without modifying classical serum indicators of hepatic function.

Anabolic Agents↗

Short-term effects of marathon running: no evidence of cardiac dysfunction.

PURPOSE: The purpose of this study was to analyze the short-term effects of a marathon race (Madrid Marathon) on both markers of cardiac damage and echocardiographic parameters in a group of 22 runners (17 male and 5 female; 34 +/- 5 yr; VO2max: 55.7 +/- 9.1 mL x kg(-1) x min(-1) with a wide range of fitness levels. METHODS: Venous blood samples were collected from each subject 48 h before the race, at race finish, and 6, 24, and 48 h postexercise for the determination of myoglobin, total creatine kinase catalytic activity (total CK), mass concentration of creatine kinase isoenzyme MB (CK-MB mass), and cardiac isoforms of troponin T and I (TnT-c and TnI-c, respectively). In addition, echocardiographic parameters (M-mode two-dimensional and Doppler analysis) indicative of both left ventricular (LV) systolic and diastolic function were obtained three times from each runner: 2-5 d before the race, at race finish, and 24-36 h after exercise. RESULTS: Except in one subject, levels of TnT-c and TnI-c were within normal limits (<0.1 ng x mL(-1)) in all the samples collected before or after the race. Overall LV systolic function was not altered by marathon running. Finally, LV diastolic function was transiently altered after the race since the ratio between peak early and late transmitral filling velocities (E/A) was significantly reduced at race finish (P < 0.01) and returned to resting levels after 24-36 h. CONCLUSIONS: Our findings suggest that marathon running does not adversely affect the hearts of healthy individuals independently from their training status.

Adult↗

Chronic and acute exercise do not alter Ca2+ regulatory systems and ectonucleotidase activities in rat heart.

The purpose of this investigation was to examine the effects of chronic and acute exercise on the main components involved in excitation-contraction coupling and relaxation in rat heart. Sixty male Wistar rats were divided into a sedentary (S) and three 12-wk treadmill-trained groups (T-1, moderate intensity; T-2, high intensity; T-3, interval running). After 12-wk, 15 rats from the S group and 15 rats from the T-2 group were subjected to a single treadmill-exercise session until exhaustion before being killed at 0, 24, or 48 h (acute exercise). The remaining animals were killed 48 h after the last standard exercise session (chronic exercise). The efficacy of the training programs was confirmed by an increase in treadmill endurance time and in skeletal muscle citrate synthase activity. None of the exercise programs modified heart weight or cardiac oxidative capacity. [(3)H]PN200-110 and [(3)H]ryanodine binding to cardiac homogenates indicated that the density of L-type and sarcoplasmic reticulum (SR) Ca(2+) channels was the same in S and trained rats. The SR Ca(2+)-ATPase activity was also unmodified. Finally, the activities of the ectoenzymes Mg(2+)-ATPase and 5'-nucleotidase, which are involved in degradation of extracellular nucleotides, were not affected by either of the running programs. After the acute exercise session, no changes were detected in either of the tested parameters in heart homogenates of S and T-2 animals. We conclude that neither treadmill-exercise training for 12 wk nor exhaustive exercise alters the density of Ca(2+) channels involved in excitation-contraction coupling or the SR Ca(2+)-ATPase and the ectonucleotidase activities in rat heart.

5'-Nucleotidase↗

[Use of EEG in electroconvulsive therapy].

BACKGROUND: From the point of view of time we can divide the use of EEG in the electroconvulsive therapy into 1) screening before starting the treatment, 2) the EEG correlates of the ECT: recording of the paroxysm, immediate postparoxysmal recording, interparoxysmal recording during a series of ECT, and persistent changes after finishing the series of ECT. METHODS AND RESULTS: EEG screening has shown that the patients with abnormal EEG do not respond well to ECT. In the recording of the paroxysm EEG correlates with therapeutic effect of ECT are looked for--particularly the length of the paroxysm on the EEG, intensity and pattern of the paroxysmal activity, and the suppression of the EEG curve in the terminal part of the paroxysm. The suppression models are in the focus of interest also in the immediate postparoxysmal recording. In the interparoxysmal recordings during a series of ECT the associations of the generalised slowing in the range of the theta and delta activity with the therapeutic effect were looked for, particularly in the past. Persistent changes after finishing the ECT are usually examined especially to look if ECT does not cause persistent abnormalities of the EEG recording which would be an evidence for brain damage or for epileptic kindling. The results in this direction have been negative so far.

Electroencephalography↗

Bis-naphthalimides 3: synthesis and antitumor activity of N,N'-bis[2-(1,8-naphthalimido)-ethyl] alkanediamines.

The bis-naphthalimides are a new class of antitumor agent. Previously, we have described initial synthetic series which established that two naphthalimide chromophores joined by polyamine linkers can produce agents with antitumor activity. We now extend these studies to describe the synthesis of a N,N'-bis[1,8-naphthalimido)-ethyl]alkanediamine series and examine the alkyl linker and chromophore substitution requirements for optimal antitumor activity. As a result, a bis-naphthal-imidoethyl derivative with no chromophore substitution and a NH-(CH2)3-NH bridge was identified. This agent (LU 79553) had both potent cellular cytotoxicity (IC50 = 0.014 microM) and was curative against MX-1 tumors grown in athymic mice. It has now been selected for clinical development.

Amines↗

[EEG correlates of therapeutic effects of electroconvulsive therapy].

In a group of 52 patients electroconvulsive treatment by means of a Thymatron apparatus was provided under simultaneous EEG control. In addition to parameters of the EEG curve (type of curve according to intensity of the paroxysmal process, duration of electroconvulsion on EEG, type of termination of paroxysm of EEG) also other variables were investigated in relation to the therapeutic effect. The following were identified as significant predictors for marked clinical improvement: type of EEG curve with more marked paroxysmal activity, shorter cumulative duration of electroconvulsions on EEG before first clinical improvement of the patient and a higher CGI entering score. Other variables proved unimportant, e.g. the patient's age, total number of electroconvulsions, total cumulative duration of electroconvulsions on EEG and type of termination of electroconvulsions on EEG.

Adult↗

[Experience with the Thymatron DG apparatus in determining the duration of electroconvulsions].

Electroconvulsive therapy was administered, using a Thymatron apparatus DG in a group of 29 female patients with a total number of 150 convulsions. The apparatus makes it possible to take an EEG reading and to evaluate it automatically. Moreover, the paroxysm were evaluated clinically and visually from EEG tracings. The authors proved a significant disagreement as regards evaluation of the length of electroconvulsions assessed by the three methods of evaluation (clinical, automatic EEG analyzer and visual EEG evaluation). They identified moreover in the group, using the automatic EEG analyzer, 11.7% abortive convulsions, by visual EEG evaluation 10.3%, while according to clinical evaluation the rate was as high as 59.2%. Conversely on clinical evaluation no convulsion appeared to be protracted, while according to EEG this was the case in 9.6% (automatic analyzer) and in 10.3% (visual evaluation). On qualitative discrimination of abortive and protracted convulsions and convulsions with a satisfactory duration the automatic and visual EEG evaluation did not differ significantly, and the function of the automatic analyzer seems satisfactory for this basic evaluation of electroconvulsions.

Electroconvulsive Therapy↗

Synthesis, structure and antitumor activity of new benz[d,e]isoquinoline-1,3-diones.

New benz[d,e]isoquinoline-1,3-diones related to mitonafide (CAS 54824-17-8) and amonafide (CAS 69408-81-7) with double substitution on the chromophore and branched side chains have been synthesized and their biological activity determined. Molecular modeling studies of 3a based on X-ray crystallographic data of mitonafide have shown that the aromatic system intercalates between GC steps of DNA. The in vitro cytotoxic test data using CX-1 and LX-1 cells showed higher cytotoxic activities in disubstituted derivatives compared to both lead compounds. Some of the compounds have been selected for in vivo test using L1210 tumor cells and CX-1 cells. Two of them (3b and 3j) have shown promising activity as good candidates for clinical development.

Adenine↗

Synthesis of new derivatives of flavone-8-acetic acid.

The synthesis of new flavone-8-acetic acid derivatives is described. It is studied the influence of a dialkylaminomethyl group in the 3-position on the activity. None of the new compounds showed cytostatic activity.

Antineoplastic Agents↗

[Sleep apnea syndrome--serious complications in a female patient treated with psychopharmaceutic agents].

The authors present the case-history of a patient treated in the past on account of depressive syndrome who suffered repeatedly from somnolence or even unconsciousness with dyspnoea which called for hospitalization in an anaesthesiological and resuscitation department. The repeatedly expressed suspicion of attempted suicide by drugs was always ruled out by toxicological examination. Based on the clinical picture a preliminary diagnosis of the sleep apnoea syndrome was established confirmed later by polysomnographic examination. The evoking factors of the mentioned serious complications were probably respiratory infections and psychiatric medication, in particular hypnotics--flunitrazepam and triazolam.

Female↗