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Accidental Falls↗
Biomedical subjects
G Diana
Publications and source records attributed to G Diana.
Taurine administration during lactation modifies hippocampal CA1 neurotransmission and behavioural programming in adult male mice.
Taurine plays a role in neuronal development. In this study, we examined whether postnatal taurine administration influences the long-term consequences induced by mild neonatal stressors (10 min maternal deprivation plus sham injection, applied daily to neonatal mice up to 21 days). At 30 days of age stressed mice showed higher pain threshold both in the tail-flick--which measures mostly the spinal mechanisms of pain--and in the hot-plate test--which reflects mainly the supraspinal mechanisms of pain. The latter effect was prevented completely by neonatal taurine administration, while the tail-flick test was not affected, thus suggesting that spinal pain is not sensitive to taurine treatment. At 140 days of age, mice which were stressed during the neonatal period showed consistent decrease in immobility time in forced swimming test, and taurine did not influence this parameter. At the same age, the fear/anxiety axis, measured with elevated plus maze test, did not show any consistent changes. Electrophysiological experiments in brain slices obtained from adult mice showed that input-output curves in hippocampal CA1 were increased by taurine administration in lactation. Hence, neonatal administration of taurine might permanently modify the functioning of hippocampus, a brain area which is known to be crucial for learning and memory.
Analysis of Variance↗
Corticotropin-releasing factor triggers neurite outgrowth of a catecholaminergic immortalized neuron via cAMP and MAP kinase signalling pathways.
Corticotropin-releasing factor (CRF), a neuropeptide of 41 amino acids, acts as the major physiological regulator of the basal and stress-induced release of corticotropin (ACTH), beta-endorphin and other proopiomelanocortin-derived peptides from the anterior pituitary gland. In addition to its endocrine activity, CRF displays extrahypophysiotropic effects, mainly as a regulator of stress responses. We show here that CRF may additionally function as a differentiating factor in immortalized noradrenergic neuronal CATH.a cells that express CRF receptor type I and resemble locus coeruleus-derived neurons. CRF triggers morphological changes in CATH.a cells including the appearance of extended long, slender neurites with prominent growth cones. CRF-treated CATH.a cells exhibit a morphology similar to locus coeruleus neurons in primary culture. CRF-induced neurite outgrowth of CATH.a cells was blocked by addition of inhibitors for cAMP-dependent protein kinase or extracellular signal-regulated protein kinase (ERK), a subtype of the mitogen-activated protein kinases. The participation of ERK within the CRF signalling cascade was further confirmed by Western blot experiments, with antibodies directed against the phosphorylated form of ERK, and also with transcription-based assays. We conclude that CRF functions as a differentiating factor of CATH.a cells via the cAMP and the MAP kinase signalling pathways.
Animals↗
Prevention by L-alpha-phosphatidylcholine of antifungal activity in vitro of liposome-encapsulated imidazoles determined by using time-killing curves.
The antifungal activity of the imidazole derivatives miconazole and ketoconazole was reduced when they were entrapped in liposomal structures and significant differences were detected between small unilamellar vesicles (SUV) and multilamellar vesicles (MLV). To understand which component of liposomes interfered with the antifungal activity of miconazole and ketoconazole, we examined the influence of pure egg and soy L-alpha-phosphatidylcholine and cholesterol on activity against Candida albicans ATCC E10231 by time killing curves. Association of phospholipids-cholesterol-imidazole leads to an inhibitory effect on the antifungal activity comparable to that shown when miconazole or ketoconazole were entrapped in SUV liposomes or when miconazole and ketoconazole were incubated in the presence of L-alpha-phosphatidylcholine. The antifungal activity determined in the presence of cholesterol was comparable to that observed with the free drugs. Inhibition of the antifungal activity of miconazole and ketoconazole by phospholipids is dependent on the phospholipid concentration but is independent of the source of phospholipids (egg or soy). Cholesterol had no influence on the antifungal activity of the imidazoles, unlike the effect on other antifungal drugs, such as amphotericin B.
Antifungal Agents↗
Resveratrol, a natural stilbene in grapes and wine, enhances intraphagocytosis in human promonocytes: a co-factor in antiinflammatory and anticancer chemopreventive activity.
Trans-resveratrol, a natural stilbene present in wine and grapes, has been studied mainly for its antiinflammatory and anticancer activities. In this study the activity of resveratrol on proliferative immunological parameters (differentiation, apoptosis, phagocytosis and intracellular killing) was studied using a U937 human promonocytic cell line in comparison with another polyphenol, quercetin. After incubation of the pathogen, Candida albicans, intracellular killing by macrophage-like cells was decreased by quercetin and resveratrol 10 microM but was enhanced by resveratrol 1 microM after 20 h of treatment. Phagocytosis rate, expressed as phagocytosis frequency, (i.e., percentage number of phagocytosing cells/total cells) at 20 h was highest with resveratrol 10 microM and was higher with quercetin 10 microM than with resveratrol 1 microM. The phagocytosis index exhibited the same trend. While both polyphenols demonstrated cytostatic activity on U937 growth, a prointraphagocytic effect for resveratrol 10 microM-treated cells at 10 min, resveratrol 1 microM-treated cells at 20 h and resveratrol 10 microM-treated cells at 48 h was observed. Morphological examination with optic microscopy demonstrated both apoptotic and differentiating cells, even after 10 min treatment. Resveratrol-induced apoptosis (following 4 h treatment) was confirmed by flow cytometry at concentrations as low as 1 microM and 100 nM in the assay for detection of membrane phosphatidylserine. Resveratrol- or quercetin-treated, but unstimulated cells, did not produce tumor necrosis factor-alpha protein. As phosphatidylserine externalization triggers specific recognition by monocytes and macrophages, removal of intact apoptotic cells is important a) in cell population selection and differentiation for antiblastic therapy, and b) in preventing the release of toxic inflammatory substances such as reactive oxygen substances and proteolytic enzymes by dying cells. This observation suggests that wine polyphenols, at the same concentrations as those found in plasma after moderate wine consumption, are important cofactors in antiinfective, antiinflammatory and anticancer nonspecific immune reactions.
Anti-Inflammatory Agents, Non-Steroidal↗
[The prognosis of surgery on the elderly. Proposal for a parametric evaluation].
BACKGROUND AND AIMS: To data there are no preoperative systems of evaluating surgical risk specifically in geriatric patients. Given that it was thought useful to formulate a score-based prognostic system for these patients based on surgical risk, the authors collected a wide range of preoperative data with the aim of identifying the easily determined variables. METHODS: While data from other hospital centres are in the process of being collected, the authors report the data for 122 over 65-year-old patients who underwent elective surgery up until 30-1-1996 out of a total of 329 hospitalized patients. In addition to a wide series of objective, laboratory and instrumental data, the study also took into account the pathology requiring to surgery, any associated morbid conditions, psychic and social conditions, the type of surgery and local and/or general postoperative complications. RESULTS: Hernia of the abdominal wall were found to be the most frequent cause of surgery (41 cases), followed by 27 neoplasias of various organs and biliary lithiasis (20 cases). Cardiovascular diseases were the most common associated pathologies (85 patients). A total of 13 major and 80 medium operations were performed, including 16 cholecystectomies. Among the general complications, an altered acid-base balance was found in 7 patients. Two deaths were recorded within 30 days of surgery. When the data collection is complete, the results will be analysed statistically in order to obtain a numerical calculation of the coefficients of risk correlated to the individual variables. CONCLUSIONS: This will enable the criteria of operability to be broadened, thereby allowing surgery to be performed in those patients who are currently excluded merely on the basis of the personal judgement of the surgeon and anesthetist.
Aged↗
Ultrastructural synaptic correlates of spatial learning in rat hippocampus.
Memory formation is believed to alter neural circuitry at the synaptic level. Although the hippocampus is known to play an important role in spatial learning, no experimental data exist on the synaptic correlates of this process at the ultrastructural level. Here, we have employed quantitative electron microscopy in order to compare the density, size and spatial arrangement of synapses in the dentate gyrus, and in area CA1, of spatially trained (water maze, invisible platform) versus control (visible platform) rats. No training-associated changes of hippocampal volume were found using a stereological estimaion (disector) of the volume density of dentate granule, or CA1 pyramidal cells. Nor were changes found in either density, or sizes of synapses (spinous or dendritic), in CA1 or dentate gyrus. However, analysis of synaptic spatial distribution showed a training-associated increase in the frequency of shorter distances (i.e. clustering) between synaptic active zones in CA1, but not dentate, thus indicating alterations in local neural circuitry. This finding indicates subtle changes in synaptic organization in area CA1 of the hippocampus following a learning experience, suggesting that spatial memory formation in mammalian hippocampus may involve topographical changes in local circuitry without synapse formation de novo.
Animals↗
Reduced hippocampal CA1 Ca(2+)-induced long-term potentiation is associated with age-dependent impairment of spatial learning.
Expression of Ca(2+)-induced CA1 long-term potentiation (LTP) was analysed in hippocampal slices obtained from (1) 3-month-old and (2) 18-20-month-old Sprague-Dawley rats selected for their performances in the Morris water maze task. In all slices, a transient (10 min) increase of extracellular Ca2+ concentration (4 mM) caused a long-lasting enhancement of potentials evoked by electrical stimulation of radiatum fibers. However, a significant difference was found in the degree of potentiation among groups. In particular, increases of the CA1 response amplitudes were significantly lower in old rats impaired in spatial learning than in young at 30 (P < 0.05), 60, 90 and 120 min (P < 0.01) after restoring the normal Ca2+ concentration. On the contrary, no differences were observed between young animals and the old ones with good performances in spatial learning. The data suggest that amplitude of CA1 Ca(2+)-induced LTP in old rats is related to spatial learning abilities.
Aging↗
The structure of coxsackievirus B3 at 3.5 A resolution.
BACKGROUND: Group B coxsackieviruses (CVBs) are etiologic agents of a number of human diseases that range in severity from asymptomatic to lethal infections. They are small, single-stranded RNA icosahedral viruses that belong to the enterovirus genus of the picornavirus family. Structural studies were initiated in light of the information available on the cellular receptors for this virus and to assist in the design of antiviral capsid-binding compounds for the CVBs. RESULTS: The structure of coxsackievirus B3 (CVB3) has been solved to a resolution of 3.5 A. The beta-sandwich structure of the viral capsid proteins VP1, VP2 and VP3 is conserved between CVB3 and other picornaviruses. Structural differences between CVB3 and other enteroviruses and rhinoviruses are located primarily on the viral surface. The hydrophobic pocket of the VP1 beta-sandwich is occupied by a pocket factor, modeled as a C16 fatty acid. An additional study has shown that the pocket factor can be displaced by an antiviral compound. Myristate was observed covalently linked to the N terminus of VP4. Density consistent with the presence of ions was observed on the icosahedral threefold and fivefold axes. CONCLUSIONS: The canyon and twofold depression, major surface depressions, are predicted to be the primary and secondary receptor-binding sites on CVB3, respectively. Neutralizing immunogenic sites are predicted to lie on the extreme surfaces of the capsid at sites that lack amino acid sequence conservation among the CVBs. The ions located on the icosahedral threefold and fivefold axes together with the pocket factor may contribute to the pH stability of the coxsackieviruses.
Amino Acid Sequence↗
Anticholinergic antiparkinsonian therapy in outpatients treated with neuroleptic drugs: a prescription survey.
Extrapyramidal adverse effects (EPAs) due to neuroleptic treatment are routinely treated with anti-cholinergic antiparkinsonian drugs (APDs). We studied the use of these drugs in the general population exposed to neuroleptic drugs to improve our knowledge of the epidemiology of EPAs. We selected all the neuroleptic and antiparkinsonian drug prescriptions delivered in the province of Rome (ca. 3,750,000 inhabitants) from 1986 to 1989. During the study period, 10.6% of neuroleptic-treated subjects were concurrently prescribed anticholinergic antiparkinsonian drugs. The influence of different factors on APD prescriptions was evaluated through a logistic regression model. The highest probability of receiving APDs was associated with trifluperidol treatment (odds ratio = 5.0, using chlorpromazine as baseline); among the commonly prescribed neuroleptics, sulpiride, levosulpiride and tiapride chlorydrate had the lowest probability of coprescription with APDs (odds ratios less than 0.1). The probability of being prescribed anticholinergic antiparkinsonian drugs decreased with age and increased with the amount of neuroleptics prescribed. This study surveys a very large sample using a population-based approach, whereas the same topics have previously only been studied in limited inpatient populations.
Adolescent↗
Estimate of parkinsonism prevalence through drug prescription histories in the Province of Rome, Italy.
INTRODUCTION: The objective of the study was to estimate the prevalence of parkinsonism in the Province of Rome using antiparkinsonian prescription histories from 1986 to 1991. METHODS: A subject was defined as a case of parkinsonism if he/she had received "specific" and "consistent" antiparkinsonian therapy in the study period. RESULTS: In November 1990, 6,572 patients were defined as prevalent cases of parkinsonism. The crude prevalence ratio, for the total population of the Province of Rome, is 173.5 per 100,000 inhabitants (165.9 per 100,000 in men and 180.5 per 100,000 in women). The method was validated by record-linkage with clinical records of all patients visited during 1990 at the Department of Neurological Sciences of the University of Rome "La Sapienza". The sensitivity of the prevalence study was 83.6%. CONCLUSIONS: The use of a computerized data base of all prescription data, routinely collected for administrative purposes, enabled us to obtain a prevalence estimate based on a very large population, with low costs and in a relatively short time.
Adolescent↗
Selective reduction of hippocampal dentate frequency-potentiation in striatally lesioned rats with impaired place learning.
The induction of hippocampal frequency-potentiation (i.e. post-tetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in rat hippocampal slices obtained from animals showing impaired place learning in the Morris water maze as a consequence of bilateral striatal injection of quinolinic acid. Vehicle-injected animals, showing normal performances in the Morris water maze, behaved as controls. After the application of an electrical tetanus (1 s, 100 Hz, 50 microA) in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from lesioned and sham-operated rats. After the application of an electrical tetanus (1 s, 100 Hz 50 microA) in the stratum moleculare, a significant difference was found in the percent of dentate PTP induction in hippocampal slices obtained from lesioned and sham-operated rats. Specifically, dentate PTP induction was significantly (P < 0.01) higher in slices obtained from sham-operated rats with a good performance in the Morris water maze than in slices obtained from striatally lesioned rats, which had shown poor performance in the Morris water maze. On the contrary, no significant differences were found in the percent of dentate LTP in hippocampal slices obtained from rats of the two groups. The data demonstrate that the impairment of the place learning in striatally lesioned rats is associated with a selective reduction of hippocampal dentate frequency-potentiation.
Animals↗
Age and strain differences in rat place learning and hippocampal dentate gyrus frequency-potentiation.
Induction of post-tetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in hippocampal slices obtained from (i) young (6 months old) rats of different strains (Sprague-Dawley, SD; spontaneously hypertensive rats, SHR; and Wistar-Kyoto, WKY), and (ii) from aged (20-24 months old) SD and Fischer 344 (F 344) rats, each group showing a different performance in the Morris maze test. After the application of an electrical tetanus (1 s, 100 Hz, 50 microA) in the stratum moleculare, a significant difference was found in the percent of induction of the dentate PTP in hippocampal slices obtained from rats of different strains and ages. In particular, the induction of the dentate PTP was significantly (P < 0.01) higher in slices obtained from young SD or spontaneously SHR rats, having the better performance in the Morris maze than in slices obtained from old SD or F 344 rats or young WKY rats which had poorer performances in the Morris maze. On the contrary, no significant differences were found in the percent of induction of the LTP in the dentate area of hippocampal slices obtained from rats of different strains and ages. Moreover, after the application of an electrical tetanus (1 s, 100 Hz, 50 microA) in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from rats of different strains and ages.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Different capability of N-methyl-D-aspartate antagonists to affect locomotor/exploratory activity of mice in a computerized on-line open field test.
The effects of the competitive N-methyl-D-aspartate (NMDA) antagonists CGS 19755 and CPP, and of the noncompetitive NMDA antagonists PCP, MK 801, and dextromethorphan (DM) have been studied on the locomotor/exploratory activity of mice in a computerized on-line open field test. CGS 19755 (12.5-25 mg/kg, IP) induced a dose-dependent decrease in the locomotor/exploratory activity of mice; CPP (25-50 mg/kg, IP) did not present such an effect. PCP (1.25-10 mg/kg, IP) induced a dose-dependent increase/decrease in the locomotor/exploratory activity of mice, and DM (25-50 mg/kg, IP) and MK 801 (0.125-0.250 mg/kg, IP) increased it. The data show that NMDA antagonists affect locomotor/exploratory activity of mice in different ways, inducing both potentiating and inhibitory effects.
Animals↗
Selective reduction of hippocampal dentate frequency potentiation in aged rats with impaired place learning.
Induction of posttetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in hippocampal slices obtained from a) young 6-month-old Sprague-Dawley (SD) rats, all of them performing well in the Morris Maze, and b) aged SD 20-month-old and Fischer 344 24-month-old rats showing different degrees of ability in the same test. After the application of an electrical tetanus 1 s, 100 Hz, 50 microA in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from rats of different strains and ages. After the application of an electrical tetanus 1 s, 100 Hz, 50 microA in the stratum moleculare, a significant difference was found in the percent of dentate PTP induction in hippocampal slices obtained from rats of different ages. Specifically, dentate PTP induction was significantly (p < 0.01) higher in slices obtained from young SD rats, and from old SD rats with a better performance in the Morris maze, escape latency less than 10 s and 150 cm, than in slices obtained from old SD or Fischer 344 rats that had shown poor performance in the Morris Maze. On the contrary, no significant differences were found in the percent of dentate LTP in hippocampal slices obtained from rats of different strains and ages. The data demonstrate that the induction of hippocampal dentate high-frequency PTP is selectively reduced in old rats with impaired Morris Maze performance.
Aging↗
Behavioral and electrophysiological correlates of the quinolinic acid rat model of Huntington's disease in rats.
The influence of bilateral intrastriatal injection of quinolinic acid (QA, 300 nmol) was studied in male Wistar rats. Behavioral and electrophysiological experiments were conducted in 15 lesioned plus 15 vehicle-injected (control) animals. With respect to control animals, QA-lesioned rats showed marked, statistically significant alterations from both the behavioral (greater motor activation in response to d-amphetamine, place-learning deficit in the Morris water maze), and the electroencephalographic (reduced voltage amplitude and EEG power at the level of frontal cortex) points of view. In addition, a significant loss in body weight and a marked striatal gliosis (GFAP staining) were observed in lesioned rats. Conversely, QA-lesioned rats did not show modifications in posttetanic potentiation (P.T.P.) or long-term potentiation (L.T.P.) in CA1 hippocampal area. The present results confirm that QA lesions of rat striatum may be regarded as a suitable model of Huntington's disease (HD).
Animals↗
Effect of iron overload on the response to recombinant interferon-alfa treatment in transfusion-dependent patients with thalassemia major and chronic hepatitis C.
The purpose of this study was to determine whether interferon-alfa (IFN-alpha) therapy benefits patients with transfusion-dependent thalassemia and chronic active hepatitis C, and whether their iron burden modifies the response to this therapy. We conducted a controlled trial of recombinant IFN-alpha (3 million units per square meter of body surface area, three times a week for 15 months) in 65 patients with thalassaemia major and chronic active hepatitis C; 14 of them were untreated control subjects. In 21 of the 51 treated patients, alanine aminotransferase values returned to normal within 6 months, and hepatitis C virus ribonucleic acid was no longer detected in serum; no changes were detected among control subjects. The response to IFN-alpha therapy was inversely related (p < 0.002) to the liver iron burden as assessed by atomic absorption, the histologic semiquantitative method, or both methods. During 3 years of follow-up, two responder patients had relapses. We conclude that IFN-alpha represents a useful therapeutic option for children with transfusion-dependent thalassemia and chronic active hepatitis C with a mild to moderate iron burden.
Adolescent↗
The use of an algorithmic method for small molecule superimpositions in the design of antiviral agents.
The inability to reliably predict relative orientations of drug molecules within our series of antipicornavirus agents has severely limited the usefulness of available structure-activity data in the drug design process. A reported method of overlapping molecules has been evaluated to see if it could provide a solution to this problem. Although it initially succeeded remarkably well with a series of molecules whose bound X-ray structures were known, this success was shown to be only a function of the bound conformation of these molecules. Thus, this method did not provide a general solution to the problem at hand.
Algorithms↗