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Biomedical subjects

V Molina

Publications and source records attributed to V Molina.

At least 37 records · Page 2Linked to original sources

P300 amplitude as a possible correlate of frontal degeneration in schizophrenia.

The existence of neurodegeneration is a debated issue in schizophrenia research. The P300 component of event-related electrical potentials (ERP) has been related to the different degree of damage to gray and white matter. This study explores the possible relationship between P300 amplitude and/or latency and the existence of degenerative processes in schizophrenia, by assessing its correlation with volume of sulcal CSF and duration of illness, as transversal indicators of neurodegeneration. Nineteen patients (14 males, 5 females) and 13 controls (6 males, 7 females) were studied with MRI and electrophysiological records (P300). The possible influence of sex and age at the time of the exploration was statistically controlled in both groups. The results show a significant negative correlation between P300 amplitude and prefrontal CSF volume in the patient group. A lower though still significant correlation was also found between P300 amplitude and duration of illness, whereas no correlation was found in the control group. These results support the hypothesis that P300 amplitude may be interpreted as a marker of neurodegeneration in schizophrenia.

Adolescent↗

On the absorbance changes in the photocycle of the photoactive yellow protein: a quantum-chemical analysis.

Spectral changes in the photocycle of the photoactive yellow protein (PYP) are investigated by using ab initio multiconfigurational second-order perturbation theory at the available structures experimentally determined. Using the dark ground-state crystal structure [Genick, U. K., Soltis, S. M., Kuhn, P., Canestrelli, I. L. & Getzoff, E. D. (1998) Nature (London) 392, 206-209], the pipi* transition to the lowest excited state is related to the typical blue-light absorption observed at 446 nm. The different nature of the second excited state (npi*) is consistent with the alternative route detected at 395-nm excitation. The results suggest the low-temperature photoproduct PYP(HL) as the most plausible candidate for the assignment of the cryogenically trapped early intermediate (Genick et al.). We cannot establish, however, a successful correspondence between the theoretical spectrum for the nanosecond time-resolved x-ray structure [Perman, B., Srajer, V., Ren, Z., Teng, T., Pradervand, C., et al. (1998) Science 279, 1946-1950] and any of the spectroscopic photoproducts known up to date. It is fully confirmed that the colorless light-activated intermediate recorded by millisecond time-resolved crystallography [Genick, U. K., Borgstahl, G. E. O., Ng, K., Ren, Z., Pradervand, C., et al. (1997) Science 275, 1471-1475] is protonated, nicely matching the spectroscopic features of the photoproduct PYP(M). The overall contribution demonstrates that a combined analysis of high-level theoretical results and experimental data can be of great value to perform assignments of detected intermediates in a photocycle.

Bacterial Proteins↗

Auditory P300 event related potential and serotonin reuptake inhibitor treatment in obsessive-compulsive disorder patients.

Neuropsychological findings in obsessive-compulsive disorder (OCD) have been explained in terms of reduced cognitive shifting ability as a result of low levels of frontal inhibitory activity. This deficit could be reflected in an abnormal P300 component of the event-related potential. The improvement in cognitive processing due to pharmacological treatment would modify the P300 component, bringing it close to that of normal controls. Nineteen patients suffering from OCD and 19 normal controls were recorded. We used a computerized version of the auditory 'odd-ball paradigm' to obtain the P300 component at the Pz electrode. Patients were tested twice, drug-free and under treatment with clomipramine in 250-300 mg doses. We observed the P300 component to have lower amplitude and longer latency in drug-free OCD patients when compared with controls. P300 amplitude in OCD increased after treatment, although this was supported only by a statistical trend. There was no modification in P300 latency after treatment. It is possible that inhibitory activity improves with treatment and allows patients to answer with more confidence, which results in an increase in P300 amplitude. This study suggests that cognitive dysfunction in OCD fluctuates with changes in the clinical associated with treatment, probably in relationship to central serotoninergic transmission.

Adult↗

Influence of different antidepressant drugs on the effect of chronic variable stress on restraint-induced dopamine release in frontal cortex.

The aim of this study was to evaluate the influence of an early chronic variable stress procedure (CVS) associated or not with repeated administration of various antidepressants on cortical restraint-induced dopamine (DA) release in vivo. Animals were subjected to the CVS schedule and one day after submitted to persistent administration with vehicle, desipramine (DMI, 10 mg/kg, i.p.), fluoxetine (FLU, 10 mg/kg, i.p.) or phenelzine (PHE; 10 mg/kg, i.p.) and later on exposed to a 60-min restraint period. In addition, we also explored the effect of acute administration of these antidepressants on cortical DA overflow in response to restraint in CVS treated rats. A higher increase in cortical DA release in response to restraint was observed in CVS animals as compared with those without previous CVS. Persistent, but not acute, administration with DMI, FLU and PHE blocked the sensitized output induced by restraint following CVS exposure.

Animals↗

Early exposure to chronic variable stress facilitates the occurrence of anhedonia and enhanced emotional reactions to novel stressors: reversal by naltrexone pretreatment.

The present research studied the influence of an early chronic variable stress (CVS) paradigm - an animal model of depression - on behavioral responses to subsequent environmental challenges suggested to model anhedonia and emotional reactions such as anxiety and fear. In order to explore a potential involvement of an endogenous opiate mechanism - presumably activated during CVS exposure - in the development of such behavioral reactions, in all experiments rats were administered naltrexone (NAL, 2 mg/kg, i.p.) or vehicle (VH) prior to each daily stressor of the CVS procedure. Animals were exposed to CVS and 1 week later tested for sucrose preference (1%) in a free choice paradigm after the presentation or not of a 90-min restraint period. Only CVS treated animals that were later exposed to restraint showed a reduction of sucrose preference, this reduction was absent when CVS rats were pretreated previously with NAL. Moreover, CVS rats were one week later tested on the elevated plus maze (EPM) and in their conditioned and unconditioned freezing response to a single shock session. Early chronic stress resulted in an anxiogenic behavior in the EPM and in an enhanced conditioned and unconditioned freezing which were all abolished by NAL pretreatment. These behavioral findings suggest that the potential activation of an endogenous opiate mechanism during CVS participates in the development of anhedonia and exaggerated emotional reactions in response to subsequent stressful experiences.

Animals↗

Antiplatelet and antithrombotic effect of D-003.

D-003 is a mixture of higher primary aliphatic saturated acids purified from sugar cane wax whose main component is octacosanoic acid followed by triacontanoic, dotriacontanoic, and tetratriacontanoic acids. The aim of this study was to evaluate the effects of D-003 on: ex vivo platelet aggregation, arterial thrombosis and bleeding time in rats. In addition, time course of antiplatelet effects of D-003 was also investigated on ex vivo platelet aggregation in guinea-pigs. D-003 (25-200 mg kg(-1)) orally administered at single or repeated doses (3 days) inhibited platelet aggregation induced by collagen (2.2 microg ml(-1)) and ADP (2 micromol l(-1)) in rats, and collagen (0.25 microg ml(-1)) induced aggregation in guinea-pigs in a dose-dependent manner. Single doses of D-003 (5-500 mg kg(-1)) administered orally 2 h before induction of arterial thrombosis significantly inhibited the reduction of rectal temperature. D-003 administered at a single dose (50-200 mg kg(-1)) 2 h before the experiment significantly increased the bleeding time in a dose-dependent manner. The time-course effects of D-003 on platelet aggregation, arterial thrombus formation, and bleeding time showed no effect 0.5 h after dosing, and maximal effects exhibited 1-2 h after treatment, whereas no significant effects were found 4 h after treatment.

Adenosine Diphosphate↗

Effect of D-002 on gastric mucus composition in ethanol-induced ulcer.

This study was designed to determine the effect of D-002, a natural product isolated and purified from beeswax (Apis mellifera), on gastric mucus composition on ethanol-induced ulcer in rats. The morphology of the lesions was analysed histologically, and morphometric analysis of gastric-gland content in total glycoprotein and sulphated macromolecules were done. Oral pretreatment with D-002 at 5 and 25 mgkg(-1)1 before oral administration of ethanol at 60%, produced a significant increase in the amount of gastric mucus and total protein. The histomorphometric evaluation of the gastric damage at the same doses showed a significant increase in neutral glycoproteins and sulfated macromolecules. It is concluded that enhancement of the quantity and quality of the mucus could partly explain the gastroprotective effect of D-002.

Animals↗

Protective effect of policosanol on atherosclerotic lesions in rabbits with exogenous hypercholesterolemia.

Policosanol is a mixture of higher aliphatic alcohols purified from sugar cane wax, with cholesterol-lowering effects demonstrable in experimental models and in patients with type II hypercholesterolemia. The protective effects of policosanol on atherosclerotic lesions experimentally induced by lipofundin in rabbits and rats and spontaneously developed in stumptail monkeys have been described. The present study was conducted to determine whether policosanol administered orally to rabbits with exogenous hypercholesterolemia also protects against the development of atherosclerotic lesions. Male New Zealand rabbits weighing 1.5 to 2 kg were randomly divided into three experimental groups which received 25 or 200 mg/kg policosanol (N = 7) orally for 60 days with acacia gum as vehicle or acacia gum alone (control group, N = 9). All animals received a cholesterol-rich diet (0.5%) during the entire period. Control animals developed marked hypercholesterolemia, macroscopic lesions and arterial intimal thickening. Intima thickness was significantly less (32.5 +/- 7 and 25.4 +/- 4 microm) in hypercholesterolemic rabbits treated with policosanol than in controls (57.6 +/- 9 microm). In most policosanol-treated animals, atherosclerotic lesions were not present, and in others, thickness of fatty streaks had less foam cell layers than in controls. We conclude that policosanol has a protective effect on the atherosclerotic lesions occurring in this experimental model.

Administration, Oral↗

Comparative study of D-002 versus sulfasalazine on acetic acid-induced colitis in rats.

D-002 is a natural mixture of higher aliphatic primary alcohols purified from beeswax and has experimentally proven mild antiinflammatory and effective antiulcer effects. It reduces leukotrienes in the exudate of carrageenan-induced pleurisy and has a protective effect on the preulcerative phase of carrageenan-induced colonic ulceration in the guinea pig. This study was conducted to compare the effect of D-002 and sulfasalazine on acetic acid-induced colitis in rats administered at 1, 5.25 and 100 mg kg-1, 24 h before colitis induction. Significant reductions in wet weight, macroscopic injury, polymorphonuclear infiltration and wall thickness were observed in the colonic mucosa of D-002 and sulfasalazine-treated animals compared with controls, except at the dose of 1 mg kg-1. It was concluded that the effects of D-002 and sulfasalazine were comparable in this experimental model.

Acetic Acid↗

Genetic diversity among isolates of Trichinella spiralis from the Province of Buenos Aires, Argentina.

Random Amplified Polymorphic DNAs, (RAPDs) are used to study the occurrence of Trichinella britovi and T5 among domestic animals in the Province of Buenos Aires, Argentina and to assess the genetic diversity among isolates of T. spiralisfrom this area in a number of infected hosts. All the local isolates proved to be T. spiralis. Six of the eight primers used indicate that the Buenos Aires isolates are distinct from each other as they produce a considerable number of polymorphic bands. Our overall estimates are relatively higher than other intraspecific distances previously estimated within species of this genus and among T. spiralis isolates. Such high degrees of variability observed among local isolates and between isolates from Buenos Aires and Spain should be taken into account when defining isolates within this species, and considering differences in the epidemiology of T. spiralis.

Animals↗

Chronic stress sensitizes frontal cortex dopamine release in response to a subsequent novel stressor: reversal by naloxone.

The present study examined the influence of an early chronic variable stress procedure with or without concurrent naloxone administration at different doses (1, 2 or 3 mg/kg, i.p.) on stress (restraint)-induced dopamine release in the frontal cortex in vivo. A higher increase in cortical dopamine release in response to a subsequent restraint event was observed in chronically stressed rats as compared with those without chronic stress exposure. Naloxone pretreatment normalized this sensitized response only at the higher dose (3 mg/kg, i.p.). The present results indicate that cortical dopamine response to a novel and uncontrollable stressor sensitizes after exposure to a chronic variable stress procedure and that an endogenous opiate mechanism, presumably activated during chronic stress, may be involved in the development of such a sensitization process.

Animals↗

Effect of policosanol on cerebral ischemia in Mongolian gerbils.

Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg) administered immediately after unilateral carotid ligation and at 12- or 24-h intervals for 48 h significantly inhibited mortality and clinical symptoms when compared with controls, whereas lower doses (100 mg/kg) were not effective. Control animals showed swelling (tissue vacuolization) and necrosis of neurons in all areas of the brain studied (frontal cortex, hippocampus, striatum and olfactory tubercle), showing a similar injury profile. In the group treated with 200 mg/kg policosanol swelling and necrosis were significantly reduced when compared with the control group. In another experimental model, comparison between groups showed that the brain water content of control gerbils (N = 15) was significantly higher after 15 min of clamping and 4 h of recirculation than in sham-operated animals (N = 13), whereas policosanol (200 mg/kg) (N = 19) significantly reduced the edema compared with the control group, with a cerebral water content identical to that of the sham-operated animals. cAMP levels in the brain of control-ligated Mongolian gerbils (N = 8) were significantly lower than those of sham-operated animals (N = 10). The policosanol-treated group (N = 10) showed significantly higher cAMP levels (2.68 pmol/g of tissue) than the positive control (1.91 pmol/g of tissue) and similar to those of non-ligated gerbils (2.97 pmol/g of tissue). In conclusion, our results show an anti-ischemic effect of policosanol administered after induction of cerebral ischemia, in two different experimental models in Mongolian gerbils, suggesting a possible therapeutic effect in cerebral vascular disorders.

Animals↗

Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients.

This randomized, double-blind study was undertaken to compare the effects of policosanol and pravastatin administered at 10 mg/day on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk. After 6 weeks on a lipid-lowering diet, patients with low-density lipoprotein (LDL) cholesterol levels > 3.4 mmol/l were randomized to receive, under double-blind conditions, policosanol or pravastatin 10 mg tablets that were taken with the evening meal for 8 weeks. Policosanol significantly (p < 0.00001) lowered LDL-cholesterol (19.3%), total cholesterol (13.9%) and the ratios of LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol (28.3%) and total cholesterol/HDL-cholesterol (24.4%). Pravastatin significantly (p < 0.00001) lowered LDL-cholesterol (15.6%), total cholesterol (11.8%) and the ratios (p < 0.0001) of LDL-cholesterol/HDL-cholesterol (18.9%) and total cholesterol/HDL-cholesterol (15.7%). Policosanol, but not pravastatin, significantly increased (p < 0.001) levels of HDL-cholesterol (18.4%) and reduced (p < 0.01) triglycerides (14.1%). Policosanol was more effective (p < 0.05) than pravastatin in inhibiting platelet aggregation induced by all agonists and it significantly reduced (p < 0.0001) platelet aggregation induced by arachidonic acid at 1.5 and 3 mmol/l by 42.2% and 69.5%, respectively, platelet aggregation induced by collagen 0.5 microgram/ml (p < 0.05) (16.6%) and that induced by adenosine diphosphate 1 mumol/l (p < 0.01) (20.3%). Pravastatin significantly reduced (p < 0.001) (27%) only platelet aggregation induced by arachidonic acid 3 mmol/l. Both drugs significantly decreased (p < 0.00001) endothelemia levels but final values were significantly lower (p < 0.001) in the policosanol than in the pravastatin group. Both treatments were safe and well tolerated. Pravastatin significantly (p < 0.01) increased serum levels of alanine amine transferase but individual values remained within normal. Two patients on pravastatin discontinued the study because of adverse experiences (myocardial infarction and jaundice, respectively). In conclusion, the effects of policosanol (10 mg/day) on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk are more favorable than those induced by the same doses of pravastatin.

Aged↗

Anti-inflammatory activity of D-002: an active product isolated from beeswax.

D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results.

Administration, Oral↗

Effect of policosanol on platelet aggregation in type II hypercholesterolemic patients.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects proved in experimental models and healthy volunteers. This study reports the results of a 4-week, randomized, double-blind, placebo-controlled trial investigating the effects of policosanol on platelet aggregation in type II hypercholesterolemic patients. Patients started or continued on a step-one cholesterol-lowering therapy for 4 weeks and those with total cholesterol > 5.0 mmol/L despite dietary conditions were randomized to receive under double-blind conditions placebo or policosanol (10 mg/day) for 30 days. Both groups were similar at randomization. Effects of policosanol on platelet aggregation induced by arachidonic acid (3.2 mM), collagen (0.5-1 microgram/ml) and ADP (0.5-1 uM) were determined at baseline and after 30 days of treatment. Policosanol significantly reduced platelet aggregation induced by arachidonic acid and collagen, meanwhile it only inhibited significantly the platelet aggregation induced by the lowest doses of ADP (0.5 uM). No adverse events occurred during the trial. Only one patient (placebo) discontinued from the study because of arthralgia.

Adenosine Diphosphate↗

Technetium-99m-HMPAO in Tourette's syndrome on neuroleptic therapy and after withdrawal.

UNLABELLED: Both decreased and increased perfusion and metabolism have been described with PET and SPECT in different areas of the brain in patients with Gilles de la Tourette's syndrome. The aim of this study was to define the regional cerebral perfusion pattern in drug-free patients and the changes in perfusion with the usual neuroleptic treatment. METHODS: A group of 13 normal control subjects and 15 unmedicated Gilles de la Tourette's syndrome patients were studied with 99mTc-HMPAO brain SPECT. Thirteen of the initial group of patients were retested on neuroleptic treatment. A semiquantitative analysis of the images was performed. RESULTS: Decreased perfusion in orbital and anterior medial regions of both frontal lobes as well as in both temporal lobes was observed in the nontreated group compared with control subjects. With treatment, a perfusion increase in these frontal regions and in the left medial temporal cortex was observed. CONCLUSION: Neuroleptic treatment could decrease the hyperactivity of the dopaminergic system leading to improvement of the clinical symptoms and reperfusion of some previously hypoperfused regions.

Adolescent↗

The Wisconsin Card Sorting Test and the assessment of frontal function: a validation study with event-related potentials.

The Wisconsin Card Sorting Test (WCST) is generally regarded as the prototype of abstract reasoning task and has been routinely used to assess frontal lobe function in a variety of clinical and research contexts. However, there are growing concerns that the WCST fails to discriminate frontal patients from those with lesions in other brain regions or from normals. Event-related potentials (ERP) from frontal, fronto-temporal, temporal, parietal and occipital areas were recorded during the performance of a computerized version of the WCST in order to explore frontal versus non-frontal ERP indexes during WCST activation. The task protocol was contrived to focus on the differences between early and late trials of each WCST series. Cognitive processes underlying these two task conditions have been described as extradimensional and intradimensional shifts in attention, respectively. Differences between early and late WCST trials appeared as soon as 120 msec poststimulus and were associated with a negative field potential centred at the fronto-temporal region of the left hemisphere. Significantly larger amplitudes of the posterior P3b wave for late as compared with early WCST trials also lent support to claims of a strong involvement of working memory mechanisms during WCST performance. Results are discussed in terms of the implications for the utility of ERP measures in clinical neuropsychology.

Adult↗