Search PubMed⌕ Search

Biomedical subjects

M Roberto

Publications and source records attributed to M Roberto.

At least 19 recordsLinked to original sources
PubMed2006

Basis of the gabamimetic profile of ethanol.

This article summarizes the proceedings of a symposium held at the 2005 Research Society on Alcoholism meeting. The initial presentation by Dr. Wallner provided evidence that selected GABA(A) receptors containing the delta subunit display sensitivity to low intoxicating ethanol concentrations and this sensitivity is further increased by a mutation in the cerebellar alpha6 subunit, found in alcohol-hypersensitive rats. Dr. Mameli reported that ethanol affects gamma-aminobutyric acid (GABA) function by affecting neural circuits that influence GABA release. Dr. Parsons presented data from electrophysiological and microdialysis investigations that ethanol is capable of releasing GABA from presynaptic terminals. Dr. Morrow demonstrated that systemic ethanol increases neuroactive steroids in brain, the absence of which alters various functional responses to ethanol. Dr. Criswell presented evidence that the ability of ethanol to increase GABA was apparent in some, but not all, brain regions indicative of regional specificity. Further, Dr. Criswell demonstrated that neurosteroids alone and when synthesized locally by ethanol act postsynaptically to enhance the effect of GABA released by ethanol in a region specific manner. Collectively, this series of reports support the GABAmimetic profile of acutely administered ethanol being dependent on several specific mechanisms distinct from a direct effect on the major synaptic isoforms of GABA(A) receptors.

Alcoholism↗
PubMed2005

Epipregnanolone and a novel synthetic neuroactive steroid reduce alcohol self-administration in rats.

This study was designed to compare the effects of several neuroactive steroids with varying patterns of modulation of gamma-aminobutyric acid (GABA)(A) and NMDA receptors on operant self-administration of ethanol or water. Once stable responding for 10% (w/v) ethanol was achieved, separate test sessions were conducted in which male Wistar rats were allowed to self-administer ethanol or water following pre-treatment with vehicle or one of the following neuroactive steroids: (3beta,5beta)-3-hydroxypregnan-20-one (epipregnanolone; 5, 10, 20 mg/kg; n=12), (3alpha,5beta)-20-oxo-pregnane-3-carboxylic acid (PCA; 10, 20, 30 mg/kg n=10), (3alpha,5beta)-3-hydroxypregnan-20-one hemisuccinate (pregnanolone hemisuccinate; 5, 10, 20 mg/kg; n=12) and (3alpha,5alpha)-3-hydroxyandrostan-17-one hemisuccinate (androsterone hemisuccinate; 5, 10, 20 mg/kg; n=11). The effect of the 3beta-epimer of PCA, (3beta,5beta)-20-oxo-pregnane-3-carboxylic acid (10, 20, 30 mg/kg; n=9), on ethanol self-administration was also examined. The compounds were administered using a Latin-square design 45 min prior to the weekly test sessions. The effects of the 30 mg/kg dose of the steroidal hemisuccinates on ethanol intake were also examined 5 min after administration of these drugs. Both epipregnanolone and PCA attenuated ethanol self-administration. However, neither of the hemisuccinate compounds significantly altered this behavior. The steroidal hemisuccinates (30 mg/kg; n=7) were also tested 5 min before behavior testing and had no effect on ethanol intake 5 min after administration. The 3beta-epimer of PCA also failed to alter ethanol intake. None of the test compounds altered water intake. In electrophysiological studies, the effects of PCA and androsterone hemisuccinate on evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (GABA(A)-IPSCs) was examined in brain slices of the amygdala. PCA had a stimulatory effect at concentrations of 5 and 25 muM. Androsterone hemisuccinate had no agonist activity. The ability of epipregnanolone and PCA to alter ethanol intake appears to be related to different inhibitory actions of these compounds on either GABA(A) or NMDA receptors, respectively. Thus, dual modulation of these systems by selected neuroactive steroids may offer potential for modifying the reinforcing effects of alcohol.

Amygdala↗
PubMed2003

The transient depression of hippocampal CA1 LTP induced by chronic intermittent ethanol exposure is associated with an inhibition of the MAP kinase pathway.

Using electrophysiological and biochemical approaches, we investigated the effects of chronic, intermittent ethanol (CIE) treatment on activation of the mitogen activated protein kinase (MAPK), also known as extracellular signal regulated protein kinase 1 and 2. In hippocampal slices taken from control rats, brief high-frequency stimulation to Schaffer collateral fibers induced a large post-tetanic potentiation (PTP) in the CA1 region that decayed to stable long-term potentiation (LTP) of field extracellular postsynaptic potentials. Western blot analyses showed that phosphorylation of MAPK was increased during PTP and returned to baseline levels during LTP. In slices from the rats removed immediately from CIE treatment, PTP and MAPK activation during the PTP was significantly less than that observed in control slices and LTP was absent. In slices from rats subjected to 1 day withdrawal from CIE treatment, both the reduction in MAPK phosphorylation during PTP and the impairment of PTP and LTP were still evident. Recovery of PTP and partial recovery of LTP was observed in slices obtained from 5-day withdrawn rats. However, MAPK activation during PTP was still attenuated significantly. Interestingly, MAPK activation was enhanced significantly during LTP in 5-day withdrawn rats as well as the sensitivity to MAPK inhibitor PD 098059. In addition to these changes in HFS-induced MAPK activation, we also observed a significant reduction in the basal phosphorylation of MAPK in slices removed from rats immediately after CIE treatment. These results implicate the MAPK signal transduction pathway as a potential cellular target of ethanol. Alterations in MAPKs could play an important role in the alcohol-induced changes in synaptic plasticity associated with the effects of alcohol abuse on learning and memory processes.

Alcoholism↗
PubMed2002

Long-term potentiation in the rat hippocampus is reversibly depressed by chronic intermittent ethanol exposure.

Alcohol exposure induces multiple neuroadaptive changes in the CNS that can have serious long-term consequences on CNS function including cognitive effects and attenuation of learning and memory. The cellular mechanisms underlying the CNS effects of alcohol have yet to be fully elucidated and are likely to depend on the pattern and dose of alcohol exposure. Using electrophysiological recordings from hippocampal slices obtained from control and chronic alcohol-treated rats, we have investigated the effects of a binge pattern of alcohol abuse on synaptic plasticity in the CNS. The alcohol-treated animals were exposed to ethanol vapor for 12-14 days using an intermittent exposure paradigm (14 h ethanol exposure/10 h ethanol withdrawal daily; blood alcohol levels approximately 180 mg/dl), a paradigm that models human binge alcohol use. Induction of long-term potentiation (LTP) in the CA1 region of the hippocampus by tetanic stimulation of Schaffer collaterals was completely blocked in slices from the chronic alcohol-treated animals. LTP remained blocked 1 day after withdrawal of animals from alcohol, indicating that the neuroadaptive changes produced by alcohol were not readily reversible. Partial recovery was observed after withdrawal from alcohol for 5 days. Other measures of synaptic plasticity including posttetanic potentiation and paired-pulse facilitation were also altered by the intermittent alcohol treatment paradigm. The results suggest that alterations in synaptic plasticity induced by chronic intermittent ethanol consumption play an important role in the effects of binge alcohol use on learning and memory function.

Alcoholism↗
PubMed2001

Pituitary adenylate cyclase-activating polypeptide hormone (PACAP) at very low dosages improves memory in the rat.

To ascertain whether very low dosages of pituitary adenylate cyclase-activating polypeptide (PACAP) influence learning in mammals, immediately after the acquisition trial of a passive avoidance response (PAR) paradigm, PACAP-38 was administered intracerebroventricularly at increasing dosages (0, 0.02, 0.2, 2, 20, and 200 ng in 10 microl saline) to different groups of rats. The mnemonic effects were measured by means of retention testing 48 and 96 h later. At intermediate PACAP-38 concentrations there was a significant mnemonic improvement of the PAR. The maximal effect was observed after the 0.2-ng PACAP-38 administration (longer step-through latencies). There was a lesser effect at the subsequent higher concentration, 2 ng. Higher dosages had no effects. It is concluded that PACAP-38 acts as an enhancer of mammalian mnemonic processes even at very low dosages. The positive effect follows an inverted U-shaped dose-response curve. The results may be of interest for the therapy of some neuropathological conditions.

Animals↗
PubMed2001

Caulerpenyne, a toxin from the seaweed Caulerpa taxifolia, depresses afterhyperpolarization in invertebrate neurons.

The massive invasion of the Mediterranean Sea by the tropical seaweed Caulerpa taxifolia (Vahl) C. Agardh has stimulated several investigations in order to test the environmental risk from an ecotoxicological point of view. The studies carried out on various experimental models have shown that caulerpenyne, the major metabolite synthesized by the seaweed, affects several cellular and molecular targets. In addition, neurological disorders have been reported in patients who accidentally ate C. taxifolia, but no evidence about the potential effects of the seaweed and of its metabolites on nerve cells were up to now available. Herein we describe that caulerpenyne modifies the electrical properties of touch mechanosensory cells of the leech Hirudo medicinalis. The physiological firing of these cells causes an afterhyperpolarization that is mainly due to the activity of the Na+/K+-ATPase and to a lesser extent to a calcium-dependent potassium current. Caulerpenyne depressed this afterhyperpolarization; the effect was dose-dependent and partially reversible. Experiments have been carried out in order to understand the mechanism through which caulerpenyne reduced the afterhyperpolarization. The action of the biotoxin has been tested in the presence of pharmacological blockers of calcium-dependent potassium channels such as cadmium and apamin. In these experimental conditions, caulerpenyne still reduced the residual afterhyperpolarization, suggesting a direct effect of the toxin on the Na+/K+-ATPase. In order to test this hypothesis, we have performed experiments where the Na+/K+-ATPase was activated by the intracellular injection of sodium and where also its basal activity was modified as well. From the data collected we suggest that caulerpenyne inhibits both the basal and the sodium-induced activity of the Na+/K+-ATPase in leech touch neurons.

Animals↗
PubMed2001

Long-lasting hippocampal potentiation and contextual memory consolidation.

In order to ascertain whether there are hippocampal electrophysiological modifications specifically related to memory, exploratory activity and emotional stress, extracellular electrical activity was recorded in hippocampal slices prepared from the brains of male adult rats. Several groups of animals were employed: (i) rats which had freely explored the experimental apparatus (8 min exposure); (ii) rats which had been subjected, in the same apparatus, to a fear conditioning paradigm training entailing the administration of aversive electrical footshocks (8 min exposure); (iii) rats to which the same number of aversive shocks had been administered in the same apparatus, but temporally compressed so as to make difficult the association between painful stimuli and the apparatus (30 s exposure); (iv) naïve rats never placed in the apparatus. Half of the rats from each treatment group were used for retrieval testing and the other half for hippocampal excitability testing. The conditioned freezing response was exhibited for no less than 4 weeks. Hippocampal excitability was measured by means of input-output curves (IOC) and paired-pulse facilitation curves (PPF). Retrieval testing or brain slices preparation were performed at increasing delays after the training sessions: immediately afterwards or after 1, 7 or 28 days. Only the rats subjected to the fear conditioning training exhibited freezing when placed again in the apparatus (retrieval testing). It was found that IOCs, with respect to naïve rats, increased in the conditioned animals up to the 7-day delay. In free exploration animals the IOCs increased only immediately after the training session. In all other rats no modification of the curves was observed. IOC increases do not appear to imply presynaptic transmitter release modifications, because they were not accompanied by PPF modifications. In conclusion, a clear-cut correlation was found between the increase in excitability of the Schaffer collateral-CA1 dendrite synapses and freezing response consolidation.

Animals↗
PubMed2000

Neurotoxic effects of caulerpenyne.

1. In this paper the authors tested the effect of caulerpenyne (CYN), a sesquiterpene synthesized by the green alga Caulerpa taxifolia onto the central nervous system of the leech Hirudo medicinalis. Investigations have been performed with three different approaches: neuroethological, electrophysiological and neurochemical techniques. 2. CYN application mimics the effect of a nociceptive stimulation (brushing), eliciting a clear-cut potentiation of the animal swim response to the test stimulus (non associative learning process such as sensitization). This effect is similar to that one induced by the endogenous neurotransmitter serotonin (5HT). 3. CYN strongly reduces the after-hyperpolarization (AHP) recorded from T sensory neurons. This effect overlaps that one produced by 5HT, but it is not affected by the serotonergic antagonist methysergide. 4. The decrease of AHP amplitude due to CYN application is observed also in presence of apamin, a blocking agent of Ca++-dependent K+ channels, suggesting that CYN is acting through the inhibition of the Na+/K+ electrogenic pump. 5. The depression of the AHP driven by CYN is not prevented by application of MDL 12330A, an adenylate cyclase inhibitor. On the other hand MDL 12330A counteracts the reduction of AHP due to 5HT application. 6. Incubation of the leech central nervous system with CYN induces the phosphorylation of proteins of 29, 50, 66 and 100 kDa. This pattern of phosphorylation is similar to that one elicited by 5HT treatment. 7. The data demonstrate that CYN exerts remarkable effects on leech neurons by acting onto specific molecular targets such as the Na+/K+ ATPase. This effect may influence important neural integrative functions and may explain the sensitizing action produced by the toxin on swim induction. Finally, caulerpenyne does not act through the pathways involved in the 5HT action, and its effect is not mediated by the second messenger cyclic AMP. The mechanism of action of CYN are still under investigations.

Animals↗
PubMed1999

Radiation dose for pedicle screw insertion. Fluoroscopic method versus computer-assisted surgery.

STUDY DESIGN: Comparison of the radiation dose between the traditional fluoroscopic approach and computed tomography (CT)-based computer-assisted surgery for pedicle screw placement was determined. OBJECTIVES: To evaluate the radiation dose delivered by fluoroscopy-controlled pedicle screw placement versus insertion guided by computer. To define the CT computer-assisted protocol, involving lower radiation exposure for the patient, that still provides acceptable image quality. SUMMARY OF BACKGROUND DATA: There are no published data describing the dose delivered in CT-based image-guided surgery, and there are few studies in which the organ dose and the effective dose delivered during pedicle screw insertion that is performed traditionally with fluoroscopic control are described. METHODS: Dose measurements were performed on two types (REMAB and RANDO) of anthropomorphic phantoms. Thermoluminescent dosimeters were used to measure the organ dose. Both phantoms were exposed to the fluoroscopic x-ray beam. The representative intraoperative scenario was determined by observation of 20 consecutive surgical interventions featuring pedicle screw implantation. For the CT dose measurement only, the REMAB phantom was used with two types of CT scanners. Three scanning protocols were evaluated: sequential, spiral optimized, and sequential optimized. Optimization of the scanning protocol included changes of anode current. The CT images were subsequently processed to achieve three-dimensional reconstruction of the lumbar spine for the computer-assisted intervention. RESULTS: Organ and effective doses were higher in any of the CT examinations than in the fluoroscopic procedure. There was a slight difference between doses registered during optimized spiral scanning and doses in the calculated optimized sequential CT protocol. Optimized sequential scanning was associated with an effective dose 40% lower than that in nonoptimized sequential scanning. The small anatomic structures of the spine could be easily recognized on each of the three-dimensional reconstructions, and all of them were suitable for use in computer-assisted surgery. CONCLUSIONS: Percutaneous pedicle screw insertion in the lumbar region of the spine, performed using fluoroscopic control, requires a lower radiation dose than do CT scans necessary for computer-assisted surgery. The CT radiation dose can be significantly decreased by optimization of the scanner settings for computer-assisted surgery. The advantages of computer-assisted surgery justify CT scans, when based on correctly chosen indications.

Adult↗
PubMed1998

Monitoring clinical quality in Medicaid managed care.

With the recent exponential growth in managed-care plan enrollment by Medicaid beneficiaries, a variety of quality monitoring systems have emerged. This paper argues that existing quality monitoring systems, originally designed for use by employers in the private sector, are a useful starting point for quality monitoring in the Medicaid program, but that substantial enhancements are needed to provide adequate quality assurance for Medicaid beneficiaries. This paper describes the development of a range of indicators for monitoring the clinical aspect of the quality of care for Medicaid beneficiaries and offers a framework for adapting existing monitoring systems to the needs of the Medicaid population. This work is part of a larger collaborative effort by the Connecticut Department of Public Health and the Department of Epidemiology and Public Health of Yale University School of Medicine to develop a blueprint for state government's role in quality assessment and performance management for managed care.

Adult↗
PubMed1997

A topographical analysis of the post-natal bone growth in the cochlea of the dog.

The distribution of post-natal bone deposition was examined in the cochlea of 10-, 25-, 50- and 90-day-old dogs that had been intraperitoneally injected with tetracycline (20 mg/kg) five days before sacrifice. The temporal bones were embedded in methylmethacrylate and sectioned in a single mid-modiolar section 30 microns thick. The post-natal bone deposition occurs both on the periosteal surfaces and on the vascular canals of the endochondral layer until the age of 90 days. Scattered bone deposition is also shown on the endosteal layer of the three turns and on the spiral lamina until the age of 25 and 10 days respectively. The percentage extension of the osteogenetic fronts shows a higher value at the periosteal layer than at the endochondral or endosteal layers.

Age Factors↗
PubMed1995

False hydatic aneurysm of the thoracic aorta.

In this article we report the successful treatment of a lower descending thoracic aorta hydatidosis that mimicked a posterior saccular aneurysm; surgical excision was performed and the aorta was repaired with a prosthetic Dacron patch. At a 26-month follow-up, the patient is alive and conducting a normal life. Discussion about the management of this rare case also is given.

Adult↗
PubMed1995

Aortic arch surgery: pros and cons of selective cerebral perfusion. A multivariable analysis for cerebral injury during hypothermic circulatory arrest.

Thirty-five consecutive patients with aortic arch aneurysm who required surgical reconstruction were operated on with the aid of extracorporeal circulation between February 1985 and December 1993. Nineteen patients (54.3%) were treated with hypothermic circulatory arrest (HCA) (Group A) and 16 (45.7%) (Group B) with HCA and selective cerebral perfusion (SCP) through the carotid arteries. Preoperative characteristics didn't show any significant differences between the two groups: mean age was 58.7 +/- 12 vs 62.1 +/- 7, p = ns, male sex 73.6% vs 75%, p = ns; atherosclerotic aneurysms were 57.8% vs 43.7%, p = ns; Type A dissections 42.2% vs 56.3%, p = ns and emergency operation were 68.4% vs 43.7%, p = ns in Groups A and B respectively. For SCP, blood was infused initially at a rate of 200-300 ml/min, maintaining the 30-40% of cerebral blood flow in normothermia, successively, with the aid of transcranial Doppler sonography (TDS) SCP-flow was improved to 500-1000 ml/min. The MHz pulsed TDS was used to measure the middle cerebral artery flow velocity in deep hypothermia before the arrest, in order to adjust the SCP flow during the HCA. In all patients we used open aortic anastomosis; in two cases an extraanatomical ascending-descending aorta was required, and in other two the "elephant trunk" technique was used in case of combined aortic arch and descending aneurysms. The HCA times were similar in the two groups 47.5 +/- 22 vs 47.7 +/- 78, p = ns. Early deaths occurred in 5 patients of the Group A (26.3%) and in 3 patients of the group B (18.7%), p = ns.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

[Impulsive noise: PTS and anatomic correlations].

The EEH (Equal Energy Hypothesis) postulates that permanent hearing loss (PTS) produced by exposure to noise is a function of sound energy of the exposure. The validity of EEH for continuous noise exposure was confirmed by large scale demographic studies and experiments in controlled laboratory setting. However, for impulse noise, EEH may not be as valid. This study was designed to test the applicability of EEH in impulse noise exposure in chinchillas. 9 groups of chinchillas were exposed to impulse noise. The intensity of the impulses (113, 125 and 137 dB SPL) and the rate (900, 3,600 and 14,400 impulses/hour) of the 9 exposure conditions were counterbalanced so that the 9 groups received the same total energy. PTS was obtained at 0.5, 2. and 8.0 kHz, by recording the evoked potentials from a chronic electrode implanted in the inferior colliculus. The cochleas were dissected and evaluated using conventional histological surface preparations and examined through scanning electron microscopy (SEM) employing a JEOL 35 microscopy. In our experimental conditions only the 113 dB SPL exposures were consistent with EEH (PTS less than 20 dB). The 125 dB SPL peak level is a critical value in that the validity of EEH also depends on exposure duration. As duration increases, so does PTS. At a 137 dB SPL peak level, EEH is not applicable. The amount of PTS is higher than 50 dB. It slightly increases when the impulse rate per hour becomes higher. In all cases examined PTS is less at 0.5 kHz than at 2.0 or 8 kHz. In these animals excellent informations concerning the sensory cell losses and cells damage was obtained with SEM.

Animals↗
PubMed1993

Bone tissue kinetics in the surgically disarticulated dog incus.

The incus of the right ear from 4 growing mongrel dogs was surgically disarticulated and left in the middle ear space. The external auditory canal was then filled with teflon paste and sutured. After 6 weeks (D-6 group) and 13 weeks (D-13 group) the animals were sacrificed. The right experimental incus and the left control one were embedded in methyl methacrylate and sectioned in single 50-microns-thick sections according to the principal axis of the two processes. On the microradiographs of each section we evaluated the thickness of the body and of both processes and the percentage area of the primary channels of the secondary osteons and that of the appositional bone tissue. The thickness of the body and of the two processes was more pronounced in all the experimental incuses, in which 6% (in D-6) and 8% (in D-13) of the total area were occupied by new appositional woven bone. In the body of the D-13 group, 9% of the pre-existing bone was substituted by secondary osteons. The results indicate that the incus react to the variations of mechanical stimuli.

Animals↗