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Biomedical subjects

L Mancuso

Publications and source records attributed to L Mancuso.

At least 19 recordsLinked to original sources
PubMed2006

Restricted diffusion of a freely diffusible second messenger: mechanisms underlying compartmentalized cAMP signalling.

It is becoming increasingly evident that the freely diffusible second messenger cAMP can transduce specific responses by localized signalling. The machinery that underpins compartmentalized cAMP signalling is only now becoming appreciated. Adenylate cyclases, the enzymes that synthesize cAMP, are localized at discrete parts of the plasma membrane, and phosphodiesterases, the enzymes that degrade cAMP, can be targeted to selected subcellular compartments. A-kinase-anchoring proteins then serve to anchor PKA (protein kinase A) close to specific targets, resulting in selective activation. The specific activation of such individual subsets of PKA requires that cAMP is made available in discrete compartments. In this presentation, the molecular and structural mechanisms responsible for compartmentalized PKA signalling and restricted diffusion of cAMP will be discussed.

Animals↗
PubMed2002

Changes in GABA(A) receptor gene expression induced by withdrawal of, but not by long-term exposure to, zaleplon or zolpidem.

The effects of long-term treatment with and subsequent withdrawal of the two hypnotic drugs zaleplon and zolpidem on the abundance of gamma-aminobutyric acid type A (GABA(A)) receptor subunit mRNAs in cultured rat cerebellar granule cells were investigated. Incubation of neurons with either drug at a concentration of 10 microM for 5 days did not significantly affect the amounts of mRNAs encoding the alpha(1), alpha(4), beta(1), beta(2), beta(3), gamma(2)L, or gamma(2)S subunits. As expected, similar treatment with the nonselective benzodiazepine diazepam resulted in a decrease in the abundance of alpha(1), beta(2), gamma(2)L, and gamma(2)S subunit mRNAs as well as an increase in that of the beta(1) subunit mRNA. Withdrawal of zaleplon or zolpidem, like that of diazepam, induced a marked increase in the amount of the alpha(4) subunit mRNA. In addition, discontinuation of treatment with either hypnotic drug resulted in a decrease in the amounts of alpha(1), beta(2), gamma(2)L, and gamma(2)S subunit mRNAs as well as an increase in that of the beta(1) subunit mRNA. These effects of zaleplon and zolpidem on GABA(A) receptor gene expression are consistent with the reduced tolerance liability of these drugs, compared with that of diazepam, as well as with their ability to induce both physical dependence and withdrawal syndrome.

Acetamides↗
PubMed2002

Changes in GABAA receptor gamma 2 subunit gene expression induced by long-term administration of oral contraceptives in rats.

The effects of oral contraceptives (OCs) on neurosteroid concentrations were evaluated in female rats and women. In rats, ethynylestradiol and levonorgestrel (0.030 and 0.125 mg, respectively, subcutaneously) administered daily for 6 weeks reduced the concentrations of pregnenolone (-41%) progesterone (-74%) and allopregnanolone (-79%) in the cerebral cortex; the plasma concentrations of these steroids were also reduced but by smaller extents. OC administration for 3 months also reduced the serum concentrations of pregnenolone, progesterone and allopregnanolone in women. Chronic administration of OCs in rats increased the abundance of gamma-aminobutyric acid type A (GABA(A)) receptor gamma 2L and gamma 2S subunit mRNAs and the relative protein in the cerebral cortex, while the amounts of various alpha and beta subunit mRNAs were unaffected. Ovariectomy did not modify the effect of OCs administration on the concentrations of neurosteroids in the rat cerebral cortex (but not in the plasma) as well as on the GABA(A) receptor gene expression, suggesting a direct effect of OCs in brain. Finally, rats treated with OCs exhibited an anxiety-like behavior in the elevated plus-maze test. These results indicate that long-term treatment with OCs induced a persistent reduction in the concentrations of pregnenolone, progesterone and its GABA(A) receptor-active metabolite, allopregnanolone, both in rats and women. In rats this effect was associated with a plastic adaptation of GABA(A) receptor gene expression in the rat cerebral cortex.

Adult↗
PubMed2002

Comparison of two brief neuropsychological batteries in people with multiple sclerosis.

BACKGROUND: We compared two brief neuropsychological batteries devised to assess people with multiple sclerosis (MS) and used them to assess the relationship between cognitive impairment and dinical characteristics. METHODS: We administered either the Brief Repeatable Battery of Neuropsychological Tests (BRBNT) or the Screening Examination for Cognitive Impairment (SEFCI) to 213 consecutive MS outpatients and 213 individually matched controls. RESULTS: Administration times were longer for BRBNT than SEFCI, for MS and controls (p=0.001). People with MS had lower scores in all individual tests than controls (p<0.001, BRBNT and SEFCI). By the criterion of poor performance on one or more tests, the sensitivity of BRBNT was 41.9% and that of SEFCI 31.5%. The corresponding figures by poor performance on two or more tests were 16.2% for BRBNT and 18.5% for SEFCI. The Buschke Selective Reminding and Paced Auditory Serial Addition were the tests best discriminating between people with MS and controls for BRBNT, and the Symbol Digit Modalities test for SEFCI. The only clinical variable independently associated with impaired performance on these batteries was EDSS. CONCLUSIONS: Both cognitive batteries were well accepted and easy to administer. Administration time for SEFCI was significantly shorter than for BRBNT; however, alternative forms for serial evaluation are available only for BRBNT. The BRBNT was slightly more sensitive in detecting impairment by the criterion of poor perfomance on one or more tests. EDSS score was the only clinical variable independently associated with cognitive impairment

Adolescent↗
PubMed2001

Increase in expression of the GABA(A) receptor alpha(4) subunit gene induced by withdrawal of, but not by long-term treatment with, benzodiazepine full or partial agonists.

The effects of long-term exposure to, and subsequent withdrawal of, diazepam or imidazenil (full and partial agonists of the benzodiazepine receptor, respectively) on the abundance of GABA(A) receptor subunit mRNAs and peptides were investigated in rat cerebellar granule cells in culture. Exposure of cells to 10 microM diazepam for 5 days significantly reduced the amounts of alpha(1) and gamma(2) subunit mRNAs, and had no effect on the amount of alpha(4) mRNA. These effects were accompanied by a decrease in the levels of alpha(1) and gamma(2) protein and by a reduction in the efficacy of diazepam with regard to potentiation of GABA-evoked Cl- current. Similar long-term treatment with 10 microM imidazenil significantly reduced the abundance of only the gamma(2)S subunit mRNA and had no effect on GABA(A) receptor function. Withdrawal of diazepam or imidazenil induced a marked increase in the amount of alpha(4) mRNA; withdrawal of imidazenil also reduced the amounts of alpha(1) and gamma(2) mRNAs. In addition, withdrawal of diazepam or imidazenil was associated with a reduced ability of diazepam to potentiate GABA action. These data give new insights into the different molecular events related to GABA(A) receptor gene expression and function produced by chronic treatment and withdrawal of benzodiazepines with full or partial agonist properties.

Animals↗
PubMed1996

Ascites, pleural, and pericardial effusions in acute pancreatitis. A prospective study of incidence, natural history, and prognostic role.

Ascites and pleural and pericardial effusions can be observed during acute pancreatitis. The aims of this study were to evaluate their incidence, natural history, and prognostic role in patients with acute pancreatitis. One hundred patients consecutively admitted with a diagnosis of acute pancreatitis were prospectively submitted to abdominal, pleural, and cardiac ultrasonography at admission and during follow-up. Ascites was found in 18 patients, pleural effusion in 20, and pericardial effusion in 17. Twenty-four patients of this series had severe pancreatitis; three of them died. All effusions disappeared spontaneously in patients who survived pancreatitis up to two months after dismissal. At multivariate analysis ascites and pleural effusion were demonstrated to be accurate independent predictors of severity. The respective odds ratios were 5.9 [95% confidence interval (CI), 1.5-23.0%) and 8.6 (95% CI, 2.3-32.5%). Furthermore the presence of pleural effusion, ascites, and pericardial effusion were associated with an increased incidence of pseudocyst during follow-up. Ascites and pleural and pericardial effusions are frequent during acute pancreatitis. Pleural effusion and ascites are accurate predictors of severity in these patients.

Acute Disease↗
PubMed1991

Constrictive pericarditis versus restrictive cardiomyopathy: the role of Doppler echocardiography in differential diagnosis.

Doppler ultrasound recordings of velocities of flow across the mitral and tricuspid valves and in the hepatic veins, and their variation with respiration, were recorded in seven patients with constrictive pericarditis and in six patients with restrictive cardiomyopathy. Deceleration of mitral and tricuspid flow was also evaluated during apnea. Color flow Doppler was performed in order to evaluate mitral and tricuspid regurgitation. Eight healthy adults served as controls. The patients with constrictive pericarditis showed higher peak diastolic velocities of mitral flow, as well as marked increase of velocity of flow at the onset of expiration and decrease at the onset of inspiration. Reciprocal respiratory variation of the velocities were also observed across the tricuspid valve. The patients with restrictive cardiomyopathy showed moderate or severe mitral and tricuspid regurgitation. They also showed shorter deceleration of flow across the mitral and tricuspid valves during apnea. The pattern of flow in the hepatic veins showed reversal during systole with accentuated reversion during inspiration. These results suggest that patient with constrictive pericarditis and restrictive cardiomyopathy can be differentiated by comparing Doppler echocardiographic data, along with changes induced by respiration.

Adult↗
PubMed1988

Echocardiographic recognition of mediastinal masses.

The aim of our study was to assess the ability of echocardiography to recognize mediastinal masses. We studied 50 patients: 25 with acute lymphoblastic leukemia, nine with lymphomas, four with pleural effusion and previously known neoplastic diseases, ten with nonlymphomatous mediastinal masses, and two with compression of the superior vena cava. In 33 of 50 patients, computed tomography (CT) showed mediastinal masses, and in one, an aneurysm of the thoracic descending aorta. All patients had previously had chest x-ray and two-dimensional echocardiographic (2-DE) examinations in order to recognize the presence of masses. Two-DE was found to have similar specificity (94.1 percent) but higher sensitivity (90.9 percent vs 60.6 percent) if related to radiographic examination. The positive predictive value was 96.7 vs 95.2 percent and the negative predictive value was 84.2 percent vs 55.1 percent. In particular, 2-DE was more useful than chest x-ray examination when a concomitant pleural or pericardial effusion was present. Moreover, abnormalities of cardiac function due to compression or infiltration and the follow-up of patients were better evaluated.

Adolescent↗
PubMed1987

Echocardiographic detection of right-sided cardiac thrombi in pulmonary embolism.

Echocardiography has proved useful in detecting right-sided heart thrombi in cases of pulmonary embolization. We found echocardiographic evidence of right-sided cardiac thrombi in six of seven patients affected by pulmonary embolism referred to our hospital within the past five months. In one patient with clinical evidence of pulmonary and paradoxic embolization, echocardiography revealed, besides thrombi within the inferior cava and right atrium, a transient, wide, systolic movement of the valvula foraminis ovalis toward the left atrium, suggesting an interatrial communication that was confirmed by contrast echocardiography. Five patients had a good outcome, with disappearance of the thrombi following IV heparin therapy, and one patient died.

Adult↗