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Biomedical subjects

F Mora

Publications and source records attributed to F Mora.

At least 19 recordsLinked to original sources
PubMed2006

Environmental enrichment reduces the function of D1 dopamine receptors in the prefrontal cortex of the rat.

Environmental enrichment produces changes in spontaneous and psychostimulant-induced motor activity. Dopamine in the prefrontal cortex (PFC), through the activation of D1 receptors, has been suggested to play a role in modulating motor activity. The present study investigated the effects of environmental enrichment on spontaneous motor activity, prefrontal acetylcholine release following local D1 receptor stimulation and D1 receptor expression in the PFC. Male wistar rats (3 months of age) were housed in enriched or isolated conditions during 90 days. Animals were then implanted with guide cannulae to perform microdialysis experiments in the PFC. Spontaneous motor activity and acetylcholine extracellular concentrations were monitored simultaneously. Also spontaneous motor activity was measured in an open field. On completion of the experiments, the density of D1 receptors in the PFC was studied by immunocytochemistry. Rats housed in an enriched environment showed significantly lower spontaneous motor activity in the open field compared to isolated animals. Perfusion of the D1 agonist SKF38393 (50 microM; 40 min) in the PFC produced long lasting increases of spontaneous motor activity and of local dialysate concentrations of acetylcholine in both groups of rats. However, increases of both motor activity and acetylcholine concentrations were significantly lower in enriched compared to isolated animals. Moreover, the density of D1 receptors in the PFC was significantly reduced in animals housed in an enriched environment. These results are the first evidence suggesting that environmental enrichment during adult life changes the function of D1 dopamine receptors in the PFC.

Acetylcholine↗
PubMed2006

Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced hyperactivity, acetylcholine release and dopamine metabolism in the nucleus accumbens.

The aim of the present study was to investigate the effects of stimulation of D2 receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the effects of prefrontal D2 stimulation under PCP treatment on dialysate concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus accumbens were also investigated. Sprague-Dawley male rats were implanted with guide cannulae to perform bilateral injections into the medial PFC of the D2 agonist quinpirole (1.5 and 5 microg/side). Horizontal and vertical spontaneous motor activity and the motor activity induced by systemic injections of the PCP (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole (1.5 and 5 microg/side) significantly decreased horizontal and vertical spontaneous motor activity in a dose-related manner. These effects were blocked by the D2 antagonist raclopride (5 microg/side). Microinjections of quinpirole (1.5 and 5 microg/side) into the PFC also significantly attenuated the hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate concentrations of acetylcholine, and dopamine metabolites in the nucleus accumbens. These increases were also reduced by injections of quinpirole (5 microg/side) into the PFC. These results suggest that the stimulation of prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and PCP-induced motor activity and also in the neurochemical changes produced by PCP in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy.

The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficient lower oesophageal sphincter (LOS) relaxation and a higher percentage of simultaneous waves (P < 0.01). Patients with CVAN (n = 22) showed a higher prevalence of pathological simultaneous contractions (>10%), and the prevalence of simultaneous waves related to the degree of autonomic neuropathy was: 9% of patients without CVAN, 7% of those suspected to have it and 50% of patients with CVAN (P < 0.001). Factors associated with the presence of pathological simultaneous waves (>10%) were the presence of CVAN and duration of diabetes (P < 0.05, logistic regression analysis). Increase in simultaneous waves and impaired relaxation of LOS are more frequent in diabetic patients with CVAN.

Adult↗
PubMed2005

Changes in dopamine and acetylcholine in striatum of the awake rat after chronic treatment with a dopamine uptake blocker.

The effects of chronic treatment with a dopamine uptake blocker on dopamine and acetylcholine extracellular concentrations in striatum of the awake rat was studied. Male Wistar rats received daily injections (i.p.) of the dopamine uptake blocker nomifensine (10 mg/kg) during 22 days. Control group was injected with vehicle (saline). Microdialysis experiments were performed on days 1, 8, 15 and 22 of treatment. Nomifensine injections increased extracellular concentration of dopamine in striatum in all days of treatment without differences among days. In contrast, acetylcholine levels showed no changes in days 1 and 8 but increased in days 15 and 22 of treatment. These results shows that chronic treatment with a dopamine uptake inhibitor, nomifensine, has no effects on dopamine release but it increases acetylcholine release in striatum of the awake rat. These results would help to further understand the effects of chronic dopamine uptake inhibition.

Acetylcholine↗
PubMed2004

Energy gradients for the homeostatic control of brain ECF composition and for VT signal migration: introduction of the tide hypothesis.

The present paper enlightens a new point of view on brain homeostasis and communication, namely how the brain takes advantage of different chemical-physical phenomena such as pressure waves, and temperature and concentration gradients to allow the renewal of the extra-cellular fluid (i.e., the homeostasis of the brain internal milieu) as well as some forms of intercellular communications (Volume Transmission) at an energy cost much lower than the classical synaptic transmission (the prototype of Wiring Transmission). In particular, the possible functional meaning of the intracranial pressure waves is discussed in the frame of the so called "tide hypothesis" which maintains that the pressure waves, created by the cardiac pump, modulate the cerebro-spinal fluid flow from and towards the subarachnoid space as well as towards and from the Virchow-Robin spaces. These fluid push-pull movements favor both the migration of signals and the extra-cellular fluid renewal, especially in the cerebral cortex.

Animals↗
PubMed2004

Glutamate-dopamine in vivo interaction in the prefrontal cortex modulates the release of dopamine and acetylcholine in the nucleus accumbens of the awake rat.

In the context of the in vivo neurochemical literature this article reviews some recent microdialysis studies in our laboratory of glutamate-dopamine interaction in the prefrontal cortex (PFC) and its possible role in modulating dopamine and acetylcholine release in the nucleus accumbens. A functional glutamate-dopamine interaction in PFC has been reported by microdialysis studies showing that both stimulation and blockade of prefrontal glutamate receptors produce changes of basal and/or stimulated release of dopamine in this area of the brain. These studies suggest that dopamine function in PFC is modulated locally by prefrontal glutamatergic inputs and that glutamate and dopamine can act simultaneously to regulate GABA release in PFC. In particular, dopamine can enhance the increases of extracellular GABA produced by the stimulation of prefrontal glutamate receptors. We report also that the stimulation of prefrontal D2 and mGluI receptors and their interaction changes the release of dopamine and acetylcholine in the nucleus accumbens.

Acetylcholine↗
PubMed2004

Studies on homocysteine plasma levels in Alzheimer's patients. Relevance for neurodegeneration.

Homocysteine (HC) may work inter alia as a Volume Transmission signal since HC is present in the brain and cerebrospinal fluid and binds to NMDA receptors. Furthermore, in cell cultures increased HC formation increases its export. In the present study we have shown that after intravenous injection in intact animals HC penetrates the blood-brain barrier. Hence, it works as a blood-born humoral signal. Furthermore, we have studied HC plasma levels in a group of Alzheimer's (AD) patients and compared with a group of age-matched patients. It has been confirmed that a positive correlation exists between age and HC plasma levels in the control group, but not in the AD patients. These results may depend on the fact that in AD patients high HC plasma levels (possibly associated with high glycine levels and/or excessive glutamate release) have favored neurodegeneration and, once this pathological process has been triggered off, the plasma HC levels become independent of the "physiological" aging-induced increase of HC plasma levels.

Aged↗
PubMed2004

Restoration of immune-mediated sensorineural hearing loss with sodium enoxaparin: a case report.

The aim of the study was to assess the efficacy of sodium enoxaparin in the treatment of autoimmune sensorineural hearing loss. A small number of patients with unilateral sensorineural hearing loss were selected and divided randomly into two numerically equal groups (groups A and B) if they fulfilled the inclusion criteria, i.e. being between 20 and 65 years of age, had been affected by systemic lupus erythematosus, had presented with a hearing loss of at least 30 dB of audibility threshold involving the medium frequencies (2000-4000 Hz), and had provided informed consent. Group A received sodium enoxaparin while group B (control) received placebo. In group A, all patients except one showed an improvement in hearing after sodium enoxaparin treatment. In group B, no patients showed an improvement in auditory function. In conclusion, our results underline the important role of sodium enoxaparin in the therapeutic management of this disease. The low number of patients suggests that further studies are required to confirm this initial data but this study suggests that sodium enoxaparin provides encouraging results in the treatment of autoimmune sensorineural hearing loss.

Adult↗
PubMed2004

Rheopheresis for sudden hearing loss (SHL).

Rheopheresis has met an increasing interest and application in different disease conditions affecting microcirculation. Its last applications are for the management of Macular and Cochlear disorders. The sudden hearing loss syndrome is a condition that affects 20 out of 100,000 persons per year, reduces the patient's social interaction and quality of life. It is associated with vascular and coagulation risk factors and it is considered as a result of local hypoperfusion secondary both to inflammatory and dysimmune conditions determining inadequate NO release and endothelial dysfunction. Rheopheresis treatment is a new approach which brings to satisfactory clinical results. Cascade filtration, heparin induced lipid precipitation and conventional plasma exchange are equally effective, and only 2 sessions are required for producing long lasting benefits. Our experience is with 60 patients, 90% of which getting from partial to complete recovery after treatment as measured by pure tone audiometry.

Blood Circulation↗
PubMed2003

OSAS in children.

BACKGROUND: Major risk factors for obstructive sleep apnea syndrome (OSAS) in children include adenotonsillar hypertrophy, neuromuscular disease and syndromes such as Down's or Pierre-Robin's syndrome; there is currently no consensus concerning diagnosis and therapy. METHODS: The study analyses 40 children, aged 2 through 14 years, with macroscopic tonsillar hypertrophy (without recurrent tonsillitis but with OSAS) underwent adenotonsillectomy. Parents were invited to indicate the intensity of their children's symptomatology using a subjective evaluation scale, each patient underwent cephalometric analysis and polysomnography (PSG) before and after surgery. RESULTS: The subjective scale of symptoms passed from 3.01 before treatment to 0.42 after treatment, rhinomanometry, passed from 3.456 to 0.896 p after 1 month the surgical operation (P<0.05). The polysomnography showed a resolution of the number of obstructive events in 37 patients and a reduction in 3 patients and RDI index fell from a mean of 26.9-2.6 after therapy. The average of oxygen saturation changed from 79% before treatment to 95% after therapy. CONCLUSIONS: Adenotonsillectomy plays a major role in the treatment of OSAS.

Adenoidectomy↗
PubMed2003

Dental and periodontal lesions in patients with gastro-oesophageal reflux disease.

OBJECTIVE: Dental erosion has been considered an extraesophageal manifestation of gastro-oesophageal reflux disease, but few reports have studied the relationship between this disease and other periodontal or dental lesions. The aim of this study was to investigate the prevalence of dental and periodontal lesions in patients with gastro-oesophageal reflux disease. PATIENTS AND METHODS: A total of 253 subjects were prospectively studied between April 1998 and May 2000. Two study groups were established: 181 patients with gastro-oesophageal reflux disease and 72 healthy volunteers. Clinical assessment, including body mass index and consumption of tobacco and alcohol, was performed in all subjects, as well as a dental and periodontal examination performed by a dentist physician, blind as to the diagnosis of subjects. Parameters evaluated were: (a) presence and number of dental erosion, location and severity, according to the Eccles and Jenkins index [Prosthet Dent 1979;42:649-53], modified by Hattab [Int J Prosthes 2000;13:101-71; (b) assessment of dental condition by means of the CAO index; and (c) periodontal status analysed by the plaque index, the haemorrhage index, and gingival recessions. RESULTS: Clinical parameters were similar in both groups (p > 0.05). Age was statistically associated with the CAO index, presence of dental erosion, and gingival recession (p < 0.001, Student's t-test). Compared with the control group, the percentage of dental erosion was significantly higher in the gastro-oesophageal reflux disease group (12.5 vs. 47.5%, p < 0.001, chi2-test), as was the number and severity of dental erosions (p < 0.001, Student's t-test). Location of dental erosion was significantly different between groups. Age was not statistically related to either the amount or severity of dental erosion. CAO and periodontal indices were similarly distributed between groups. CONCLUSIONS: Dental erosion may even be considered as an extraesophageal manifestation of gastro-oesophageal reflux disease. The fact that the prevalence of caries and periodontal lesions is similar in patients with gastro-oesophageal reflux disease and in healthy volunteers suggests a lack of relationship with gastro-oesophageal reflux disease.

Adolescent↗
PubMed2003

Effects of activation of NMDA and AMPA glutamate receptors on the extracellular concentrations of dopamine, acetylcholine, and GABA in striatum of the awake rat: a microdialysis study.

The effects of activation of the AMPA and NMDA ionotropic glutamate receptors on the extracellular concentration of dopamine, acetylcholine, (ACh) and GABA in striatum of the awake rat was investigated. Also the levels of DOPAC, HVA, and choline (Ch) were included in this study. Seven to eight days after stereotaxical implantation of a guide-cannulae assembly, microdialysis experiments were performed. The dopamine and ACh content of samples were measured by HPLC coupled to electrochemical detection. GABA was measured using fluorometric detection. Perfusion of AMPA (1, 20, 100 microM) produced a dose-related increase of dopamine and a dose-related decrease of DOPAC and HVA. AMPA 100 microM decreased extracellular concentrations of ACh and increased the extracellular concentration of Ch and GABA. Perfusion of NMDA 500 microM increased the concentration of dopamine and decreased DOPAC and HVA. Also, NMDA 100 microM decreased DOPAC. NMDA 500 microM decreased the extracellular concentrations of ACh and increased the concentrations of Ch and GABA. Perfusion of the AMPA/kainate-antagonist DNQX (100 microM) blocked the effects of AMPA (100 microM) on dopamine, DOPAC, HVA, ACh, and GABA concentrations. Perfusion of the NMDA-antagonist CPP (100 microM) blocked the effects of NMDA 500 microM on dopamine, DOPAC, HVA, ACh, Ch, and GABA concentrations. These results suggest an interaction between glutamate-dopamine-ACh-GABA in striatum of the awake rat.

Acetylcholine↗
PubMed2003

Changes in dialysate concentrations of glutamate and GABA in the brain: an index of volume transmission mediated actions?

Brain microdialysis has become a frequently used method to study the extracellular concentrations of neurotransmitters in specific areas of the brain. For years, and this is still the case today, dialysate concentrations and hence extracellular concentrations of neurotransmitters have been interpreted as a direct index of the neuronal release of these specific neurotransmitter systems. Although this seems to be the case for neurotransmitters such as dopamine, serotonin and acetylcholine, the extracellular concentrations of glutamate and GABA do not provide a reliable index of their synaptic exocytotic release. However, many microdialysis studies show changes in extracellular concentrations of glutamate and GABA under specific pharmacological and behavioural stimuli that could be interpreted as a consequence of the activation of specific neurochemical circuits. Despite this, we still do not know the origin and physiological significance of these changes of glutamate and GABA in the extracellular space. Here we propose that the changes in dialysate concentrations of these two neurotransmitters found under specific treatments could be an expression of the activity of the neurone-astrocyte unit in specific circuits of the brain. It is further proposed that dialysate changes of glutamate and GABA could be used as an index of volume transmission mediated actions of these two neurotransmitters in the brain. This hypothesis is based firstly on the assumption that the activity of neurones is functionally linked to the activity of astrocytes, which can release glutamate and GABA to the extracellular space; secondly, on the existence of extrasynaptic glutamate and GABA receptors with functional properties different from those of GABA receptors located at the synapse; and thirdly, on the experimental evidence reporting specific electrophysiological and neurochemical effects of glutamate and GABA when their levels are increased in the extracellular space. According to this concept, glutamate and GABA, once released into the extracellular compartment, could diffuse and have long-lasting effects modulating glutamatergic and/or GABAergic neurone-astrocytic networks and their interactions with other neurotransmitter neurone networks in the same areas of the brain.

Animals↗
PubMed2003

Growth hormone and aging.

In elderly people, vascular alterations and degenerative alterations of the Central Nervous System (CNS) are two of the most common reasons for illness and death. Lipid pattern modifications and menopause in women are some of the causes for the appearance of these alterations. Vascular endothelium is in part responsible for vascular homeostasis, through the production of several vasoactive factors. Growth hormone (GH) exerts effects on the CNS and on the vascular endothelium, since GH deficient subjects exhibit endothelium-dependent alterations, which recover under substitutive GH treatment. Growth hormone has important actions on lipid metabolism that also play a role on vascular and endothelial function. Moreover, cardiac function improves when GH is associated to angiotensin II receptor blockers. Elderly people exhibit a physiological GH deficiency that could affect their vascular and cerebral functions. A study was carried out using old Wistar rats to clarify the effects of GH on the vessels under chronic "in vivo" conditions. The response to various vasoactive substances in aortic rings has been evaluated. An increase in the aortic media thickness was seen in old rats, which showed also a reduction in the vasodilator response to isoprenaline as compared to young animals. GH treatment partially restored the vasodilator response and reduced media thickness. Neuronal population was reduced in the hypocampus of old rats as compared to young ones and GH treatment was able to significantly enhance the number. Neurotransmitters were measured in several cerebral areas to establish differences between young and old GH-treated or untreated animals. Glutamine, Arginine and Aspartate were reduced in old animals whereas Citruline was increased. GH treatment restored in all cases the levels corresponding to young rats.

Aged↗
PubMed2003

Population pharmacokinetics of high dose ibuprofen in cystic fibrosis.

AIMS: To evaluate ibuprofen population pharmacokinetics in a large series of data collected in children with cystic fibrosis (CF) treated with high doses of ibuprofen (59 patients; 2-18 years), and to identify the main causes responsible for the considerable interindividual variability in ibuprofen serum levels. METHODS: Blood samples were collected during routine clinical care; serum ibuprofen concentrations were determined by HPLC. Fitting of the concentration/time data to a one compartment kinetic population model was performed by a non-linear mixed effect regression method. RESULTS: Body weight, dose, and ibuprofen dosage form (lysinate salt or the free acid form), for elimination clearance (CL/F); and body weight, dose, and fasting status for the apparent distribution volume (Vd/F) proved to be the covariates with influence in the model. The four factors identified helped to explain part of the interindividual variability observed, but the remaining unexplained variability made therapeutic drug monitoring absolutely essential.

Administration, Oral↗
PubMed2003

High frequency surgery in the treatment of turbinate hypertrophy: 11 years' experience.

For over a century, surgical management of lower turbinate hypertrophy has given rise to much discussion. Aim of the present investigation was to establish, by means of the analysis of a large patient population, the efficacy and reproducibility of high frequency surgery in the treatment of this condition. A total of 1689 non-allergic patients with nasal obstruction, presenting hypertrophy of the lower turbinates, were submitted, under local anaesthesia, to turbinates decongestion using a high frequency instrumental unit with a bipolar terminal electrode. Efficacy of the procedure was evaluated on the basis of objective examination, results of questionnaires, active anterior rhinomanometry and mucociliar transport time. Results revealed a reduction of hypertrophy, an improvement in symptoms, a reduction in nasal resistances and an improvement of mucociliar transport time. The large patient population, low post-operative complication rate and the good patient compliance, due also to the fact that no haemostatic procedure is necessary, would suggest that this method is particularly valid, effective and safe for the treatment of hypertrophy of the lower turbinates.

Adolescent↗
PubMed2002

A preventive measure for otitis media in children with upper respiratory tract infections.

Recurrent upper respiratory tract infections (URTI) are very common in patients of all ages. Rhinitis, bronchitis, chronic sinusitis and otitis appear to be the prevalent forms of recurrent respiratory infections in the paediatric population. The aim of treatment is so the solution of the respiratory pathology and the also the prevention of their complications. Antibacterial therapy is still the classical treatment approach in patients both with respiratory tract infections and with otitis media, despite the fact that antibacterials have several well known drawbacks, especially when used to treat recurrent infections. Eighty-four paediatric patients of both sexes (range: 4-14 years) with otitis were enrolled in the study. Patients were included if they had a >2 years' history of recurrent or chronic respiratory infections, and/or had experienced at least three episodes requiring medical consultations and/or treatment during the winter prior to the study. The young patients were randomised to receive Immucytal (group A) or placebo (group B) treatment according to the following protocol: (1) starting therapy (1 month): one tablet daily in the morning 4 days per week for 3 consecutive weeks; (2) maintenance period (5 months): one tablet daily in the morning 4 days per week for 1 week every month. Placebo and Immucytal tablets were identical in shape and size, in order to maintain double-blind conditions. Patients of group A with recurrent URTI had a significantly decreased incidence of ENT infections, fever and shorter duration of illness, decreased requirement for ancillary medications and fewer work-days lost. The reduction in the incidence of infectious episodes became significant vs. placebo. A significantly improved outcome vs. placebo was also observed on the incidence of fever, frequency and duration of infectious episodes, ancillary therapies. Immucytal treatment was associated with significant changes in both immunological and auditory function parameters. Serum concentrations of immunoglobulins were significantly increased in Immucytal. For both evaluations, a significant difference between treatment groups was found (P>0.001). Preventive strategies, such as ribosomal immunotherapy, may represent a valid alternative approach.

Administration, Oral↗