Search PubMed⌕ Search

Biomedical subjects

G Costa

Publications and source records attributed to G Costa.

At least 55 records · Page 3Linked to original sources
PubMed2002

The presence of Lewis a epitopes in Arabidopsis thaliana glycoconjugates depends on an active alpha4-fucosyltransferase gene.

The presence of an alpha4-fucosyltransferase in plants was first deduced from the characterization of Lewis-a glycoepitopes in some N-glycans. The first plant gene encoding an alpha4-fucosyltransferase was recently cloned in Beta vulgaris. In the present paper we provide evidence for the presence of an alpha4-fucosyltransferase in A. thaliana by measurement of this glycosyltransferase activity from a purified microsomal preparation and by immunolocalization of Le(a) epitopes on glycans N-linked to glycoproteins located to the Golgi apparatus and on the cell surface. The corresponding gene AtFT4 (AY026941) was characterized. A unique copy of this gene was found in A. thaliana genome, and a single AtFT4 transcript was revealed in leaves, in roots, and at a lower extent in flowers. The coding sequence of AtFT4 gene is interrupted by two introns spanning 465 bp and 84 bp, respectively. The putative 393-amino-acid protein (44 kDa, pI: 6.59) contains an N-terminal hydrophobic region and one potential N-glycosylation site, but AtFT4 has poor homology (less than 30%) to the other alpha3/4-fucosyltransferases except for motif II. When expressed in COS 7 cells the protein is able to transfer Fuc from GDP-Fuc to a type 1 acceptor substrate, but this transferase activity is detected only in the culture medium of transfected cells

Amino Acid Sequence↗
PubMed2002

Brain function and effects of shift work: implications for clinical neuropharmacology.

Night or shift work is to a relevant extent unavoidable, suits a growing preference for flexibility and is predicted to spread. However, a significant percentage of shift workers report discomfort or health problems and they often (15-20% of cases) move to different occupations. Apart from social implications, the issue has medical and scientific relevance, with evidence suggesting that the circadian rhythm phases are neither equivalent nor interchangeable with respect to function and performance. Shift work may affect the gastrointestinal and cardiovascular functions, alter the hormonal and sleepiness cycles, favor sleep disturbances of medical relevance, interfere with behavior and social life and increase the risk of accidents (e.g. road accidents). The implications for clinical (neuro)pharmacology are relevant and, in several instances, critical. Shift work can interfere with mechanisms regulating drug kinetics in peripheral compartments and action at selective brain sites, either directly or through effects on the gastrointestinal/hormonal cycles. In this paper, the relevant literature is reviewed and original data on the effects of shift work are reported. Basic and clinical research should take into account the possible effects on drug action of an active life and working schedule in inappropriate phases of the circadian cycles and the risk of inadequate drug dosing or unexpected abnormal action in subjects under long-term or chronic treatment. A scientific approach, action by the scientific community involved in pharmacological research and monitoring by the regulating agencies are advisable. Regulation may help reduce the medical and social impact and improve quality of life.

Accident Proneness↗
PubMed2002

[Pancreatic anastomotic fistula after pancreaticoduodenectomy: incidence, significance and treatment].

The Authors reviewed the complications, and outcomes in a consecutives series of 97 patients undergoing pancreaticoduodenectomy. The clinical leak rate in this series was 21.8%. There was a difference in the pancreatic leak rate in those patients who underwent pancreatic ductal closure or end to end pancreaticojejunal invagination compared with end to side pancreaticojejunal anastomosis. The postoperative complication rate was 41.8% and the most common complications were pancreatic fistula. 9 deaths occurred in hospital or within 30 days from operation. Univariate and multivariate analysis revealed that operative technique, the pathological status of the pancreatic remnant, and mayor complications were the significant risk factors for the development of pancreatic anastomotic leak. In the 2000s pancreatic leak remains a potentially lethal problem. After pancreaticoduodenectomy, pancreatic remnant management by end to side pancreaticojejunostomy appeared safe in low-risk patients. Morbidity was greatest after pancreatic duct closure without anastomosis.

Aged↗
PubMed2001

Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia.

Several studies have indicated that multiple sclerosis (MS) is associated and linked to the major histocompatibility complex (MHC)/human leukocyte antigen (HLA) region of chromosome 6p21.3, but the exact location and nature of the primarily associated locus within the HLA complex is still controversial and largely presumptive. By linkage disequilibrium mapping, we have systematically investigated this chromosome region in the founder population of Sardinia to determine the relative associations of the various loci with MS. An overall 11.4 Mb region, which encompasses the whole HLA complex, was scanned with 19 microsatellite markers and with single nucleotide polymorphisms within 12 functional candidate genes and assessed for MS association using the extended transmission disequilibrium test (ETDT). A peak of association represented by the three adjacent DRB1, -DQA1 and -DQB1 loci was detected in the class II region. Two additional less significant areas of association were detected, respectively, in the centromeric side of the class II region at the DPB1 locus and, telomeric of the classically defined class I loci, at the D6S1683 microsatellite. Conditional ETDT analysis indicated that these regions of association could be independent of each other. Within the main peak of association, DRB1 and DQB1 contribute to the disease association independently of each other whereas DQA1 had no detectable primary genetic effects. We evaluated the haplotype distribution at the region showing the strongest association and found five DQB1-DRB1 haplotypes positively associated with MS in Sardinia. These consistently included all the haplotypes previously found associated with MS in the various human populations, thus supporting a primary effect of the products of these loci in MS. Overall these results are consistent with a multilocus model of the MHC encoded susceptibility to MS.

Adolescent↗
PubMed2001

Halo structure of (14)Be.

The two-neutron halo nucleus (14)Be has been investigated in a kinematically complete measurement of the fragments ((12)Be and neutrons) produced in dissociation at 35 MeV/nucleon on C and Pb targets. Two-neutron removal cross sections, neutron angular distributions, and invariant mass spectra were measured, and the contributions from electromagnetic dissociation (EMD) were deduced. Comparison with three-body model calculations suggests that the halo wave function contains a large nu(2s(1/2))(2) admixture. The EMD invariant mass spectrum exhibited enhanced strength near threshold consistent with a nonresonant soft-dipole excitation.

Journal Article↗
PubMed2001

Nicotine prevents striatal dopamine loss produced by 6-hydroxydopamine lesion in the substantia nigra.

While the work of several groups has shown the neuroprotective effects of nicotine in vitro, evidences for the same effects in vivo are controversial, mainly regarding neuroprotection in experimental models of Parkinson's disease. In this context, we investigated the capability of various systemic administration schedules of nicotine to prevent the loss of striatal dopamine levels produced by partial or extensive 6-hydroxydopamine (6-OHDA) lesion of rat substantia nigra (SN). Eight days after 6- and 10-microg injections of 6-OHDA in the SN there was a significant decrease of dopamine concentrations in the corpus striatum (CS) and a concomitant increase in dopamine turnover. While 10 microg 6-OHDA produced an almost complete depletion of dopamine in the SN, 6 microg decreased dopamine levels by 50%. Subcutaneous nicotine (1 mg/kg) administered 4 h before and 20, 44 and 68 h after 6 microg 6-OHDA, prevented significantly the striatal dopamine loss. Administered only 18 or 4 h before or only 20, 44 and 68 h after, nicotine failed to counteract the loss of dopamine or the increase in dopamine turnover observed in the CS. Nicotine also failed to prevent significantly the decrease of striatal dopamine levels produced by the 10-microg 6-OHDA intranigral dose. Chlorisondamine, a long-lasting nicotinic acetylcholine receptor antagonist, reverted significantly the nicotinic protective effects on dopamine concentrations. These results are showing that putative neuroprotective effects of nicotine in vivo depend on an acute intermittent administration schedule and on the extent of the brain lesion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Total mesorectal excision and low rectal anastomosis for the treatment of rectal cancer and prevention of pelvic recurrences.

HYPOTHESIS: Total mesorectal excision lowers the rate of pelvic recurrence and positively affects the survival after surgical treatment of rectal cancer. DESIGN: Case series. SETTING: Tertiary care university hospital. PATIENTS: Fifty-three consecutive patients were admitted with curative intent to surgery at the First Department of Surgery of the University of Rome "La Sapienza," Rome, Italy, with diagnoses of rectal carcinoma. The mean follow-up was 68.9 months; follow-up was complete for all patients who entered the trial. INTERVENTIONS: Low anterior resection and total mesorectal excision were performed in all cases, regardless of the location of the rectal cancer. A straight mechanical colorectal anastomosis was performed on a rectal stump, never exceeding 5 cm. No kind of adjuvant therapy was given. Mesorectum and open rectum were studied by serial transverse section at 5-mm intervals. A search for depth of penetration and distal intramural extension of the tumor was made. Lymph nodes were detected by clearing method, and nodal metastases (NM) and nonnodal metastases (NNM) were recorded as situated proximally, distally, or at the level of the tumor. RESULTS: There was no postoperative mortality. Clinical and radiologic leaks occurred in 2 and 4 patients, respectively. Mean disease-free survival was 65.9 months. Pelvic recurrence occurred in 5 patients (9%). Overall 5-year survival rate was 75%. Involvement of mesorectum by NM and NNM was detected in 27 and 24 cases, respectively. Both NM and NNM were found to be distal in 33% and 40% of cases, respectively. CONCLUSIONS: Microscopic spread to the distal mesorectum may exceed the intramural spread of rectal cancer. Failure to perform total mesorectal excision leaves a potentially residual disease in the distal mesorectum, thus predisposing the patient to pelvic recurrence.

Adenocarcinoma↗
PubMed2001

Nitrergic relaxation in urethral smooth muscle: involvement of potassium channels and alternative redox forms of NO.

We examined the contribution of K+ channels to the relaxation responses induced by different redox forms of nitric oxide (NO., NO- and NO+) in comparison with those evoked by electrical field stimulation (EFS) of nitrergic nerves in the sheep urethra. K+ channel blockers with different selectivity profile were used. Sodium nitroprusside (SNP) and different S-nitrosothiols were used as NO+ donors, Angeli's salt as an NO- donor and nitroglycerin (GTN) was chosen as a representative compound known to require metabolic activation in the target tissue. Pure NO gas was used to prepare NO. solutions. Relaxation evoked by EFS of nitrergic nerves or by exogenous NO was not inhibited by any of the K+ channel blockers, but was enhanced by 4-aminopyridine [inhibitor of voltage-dependent K+ (KV) channels]. This suggests that, whereas K+ channel activation and hyperpolarization of the postsynaptic membrane do not contribute to relaxation, prejunctional modulation of the nitrergic neurotransmission by Kv channels may be relevant. Relaxation induced by NO+ or NO- donors was not affected by K+ channel blockade with the following exceptions: glybenclamide, a blocker of ATP-sensitive K+ channels (KATP), enhanced responses to SNP and Angeli's salt, 4-aminopyridine inhibited relaxation evoked by Angeli's salt and GTN, and charybdotoxin, a blocker of large-conductance, Ca2+-activated K+ channels (BKCa) inhibited those induced by the S-nitrosothiol S-nitrosoglutathione. These results do not suggest the existence of a general mechanism of action on K+ channels for compounds releasing either NO+ or NO- in the sheep urethra. None of the K+ channel blockers affected relaxation induced by the membrane-permeable analogue of cGMP, 8-bromo-cGMP. However, the fact that the addition of the phosphodiesterase inhibitor zaprinast (0.1 mM) enhanced the relaxation to Angeli's salt, while preventing the inhibition induced by 4-aminopyridine, suggests that involvement of guanylate cyclase activation in the action of NO donors on K+ channels can not be excluded. Accordingly, the guanylate cyclase inhibitors 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ, 10 microM) and 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS 2028, 10 microM) almost abolished relaxations to EFS and Angeli's salt. In contrast, ODQ only moderately inhibited relaxations to NO.. In addition, the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide (carboxy-PTIO) effectively inhibited responses to NO. whilst not affecting those to EFS or NO-, suggesting a close similarity between the nitrergic transmitter and nitroxyl ion. We conclude that nitrergic relaxation induced either by the endogenous transmitter or by exogenous NO donors in the ovine urethra is not mediated by postsynaptic alterations in the K+ conductance; only a prejunctional modulation through Kv channels seems to be significant. In addition, the production and/or release of alternative redox forms of NO, such as NO-, may be involved in neurotransmission processes in the urethra.

Animals↗
PubMed2001

Subjective effects of AMPT-induced dopamine depletion in schizophrenia: correlation between dysphoric responses and striatal D(2) binding ratios on SPECT imaging.

Approximately one third of schizophrenic patients treated with neuroleptic drugs experience unpleasant subjective responses, that are collectively known as neuroleptic dysphoria. Experimental research in animals indicates that drug induced dopaminergic blockade in mesolimbic circuits, especially the nucleus accumbens, leads to impaired pleasure responsivity and dysphoria. The present study tested this putative mechanism in drug-free schizophrenic patients (n = 12), through inducing dysphoric responses with alphamethyl paratyrosine (AMPT) and simultaneously quantifying their baseline striatal dopmine (D(2)) function with (123)IBZM-SPECT imaging. Results showed a wide variability in the occurrence and severity of dysphoric responses, clearly distinguishing a dysphoric group from non-dysphoric responders. Severity of dysphoric responses, measured by standardized rating scales, correlated inversely with changes in D(2) receptor binding ratios (r = +0.82, p <.01). These results support the notion that striatal dopaminergic activity is not uniformly elevated in all schizophrenic patients, and the sub-group of individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic blocking drugs.

Adult↗
PubMed2001

The influence of somatostatin on bacterial translocation.

BACKGROUND: Bacterial translocation is defined as the passage of bacteria from the gastrointestinal tract to extraintestinal sites mostly as a consequence of the loss of the gut barrier function. Somatostatin and octreotide, exerting many inhibitory effects on the gastrointestinal tract, have been evidenced to promote bacterial translocation. METHODS DESIGN: experimental research. SETTING: University teaching Hospital. INTERVENTIONS: Sixteen pigs forming the study group received 25 mg/kg of octreotide twice a day for ten days. A control group (n=16) received an equal volume of saline solution for the same period. All animals were sacrificed and tissue cultures were obtained from mesenteric lymph nodes (MLN), liver and spleen. Portal venous and central venous blood samples were also withdrawn for culture. RESULTS: In the octreotide group, cultures were positive for bacteria in 43.7% (7/16) of animals. Viable bacteria were recovered from MLN, liver and spleen. Portal and systemic blood cultures showed no growth of bacteria. The mean value of bacterial detection in MLN, liver and spleen was 196+/-13 CFU/g, 190+/-26 CFU/g, and 173+/-0 CFU/g, respectively. P value was not statistically significant. Bacterial translocation did not occur in the animals of the control group. Fisher s exact test revealed a statistically significant difference (p<0.007) between the two groups regarding bacterial translocation to MLN. CONCLUSIONS: The administration of octreotide is followed by a conspicuous increase in bacterial translocation in pigs. Further clinical studies are needed to demonstrate similar effects on humans.

Animals↗
PubMed2001

Clinical significance of normobasemia in early post-operative outcome of hepatic resections.

BACKGROUND: Major hepatic resections are usually followed by acid-base unbalance. Adjustment of the acid-base disorders is considered central when dealing with these critical patients and normobasemia is thought to be a favourable prognostic factor when occurring in the immediate postoperative outcome after major surgery. The present study was undertaken to investigate the influence of acid base balance on the early outcome after hepatic resection. METHODS: A series of fifty-seven cirrhotic patients was submitted to liver resection for hepatocellular carcinoma. Forty-eight patients experienced an uneventful early postoperative outcome (CTR group). Nine died in the postoperative course (HD group). In all patients pulmonary, renal and hepatic functions were monitored pre- and postoperatively. The pH values were detected daily preoperatively and in the course of the first three days after hepatic resection. In the same days acid base balance and arterial ketone body ratio were assessed on arterial blood samples. Data were collected in a data base and statistical analysis was performed. RESULTS: A significantly higher metabolic alkalosis was found to characterize the first and second postoperative days (POD1 and POD2) in the CTR group (pH 7.43+/-0.007 vs pH 7.33+/-0.001; pH 7.45+/-0.006 vs pH 7.35+/-0.009; p<0.05). Lower values of pH and an associated impaired energetic status of the liver were found to characterise the postoperative course of the poor prognosis patients. At POD1 AKBR decreased in both groups but while recovering at POD2 in patients of CTR group maintained significantly lower values in HD group (AKBR 1+/-0.3 vs 0.5+/-0.2; p<0.01). A lower energetic status of the liver is associated with an inadequate tricarboxylic acid cycle and is responsible for an impaired production of HCO3-. CONCLUSIONS: Apparent normobasemia is then expressive of liver failure leading to poor postoperative outcome.

Acid-Base Equilibrium↗
PubMed2001

The 24-hour society between myth and reality.

The 24-hour society appears to be an ineluctable process towards a social organisation where time constraints are no more "restricting" the human life. But, what kind of 24-hour society do we need? At what costs? Are they acceptable/sustainable? Shift work, night work, irregular and flexible working hours, together with new technologies, are the milestone of this epochal passage, of which shift workers are builders and victims at the same time. The borders between working and social times are no more fixed and rigidly determined: not only the link between work place and working hours is broken, but also the value of working time changes according to the different economic/productive/social effects it can make. What are the advantages and disadvantages for the individual, the companies, and the society? What is the cost/benefit ratio in terms of physical health; psychological well-being, family and social life? The research on irregular working hours and health shows us what can be the negative consequences of non-human-centered working times organisations. Coping properly with this process means avoiding a passive acceptance of it with consequent maladjustments at both individual and social level, but adopting effective preventive and compensative strategies aimed at building a more sustainable society, at acceptable costs and with the highest possible benefits.

Adaptation, Psychological↗
PubMed2001

Flexible work hours, health and well-being in the European Union: preliminary data from a SALTSA project.

Demand for flexible work hours (FWH) is increasing in Europe aimed at increasing the number of production hours on one hand, and, on the other, reducing individual working hours and/or increasing autonomy and control on them. In view of the lack of knowledge of the effects of FWH on health and safety, we started a pilot project, funded by the Joint Programme for Working Life Research in Europe (SALTSA), aimed at: a) comparing the most relevant national legislation and how the EU Directive 93/104 "concerning certain aspects of working time" has been implemented in the member States; b) reporting prevalence and trend of FWH in Europe according to the three EU Surveys on Working Conditions carried out in the last decade; c) collecting practical examples of innovative FWH; d) evaluating their impact on health and safety in relation to work sectors, job demands, social life, aging and gender. Consequent actions are going to include information and consultancy for pertinent authorities and social parties involved, as well as training programmes for Union officials and similar groups concerning the organisation of FWH according to ergonomic principles.

Choice Behavior↗
PubMed2001

The effect of a change in sleep-wakefulness timing, bright light and physical exercise interventions on 24-hour patterns of performance, mood and body temperature.

Experiments consisting of baseline, bright light and physical exercise studies were carried out to compare the effect of a 9-hour delay in sleep-wakefulness timing, and the effects of bright light and physical exercise interventions on 24-hour patterns of performance, mood and body temperature were examined. Each study comprised a 24-hour constant routine at the beginning followed by 3 night shifts and 24-hour constant routine at the end. Performance on tasks differing in cognitive load, mood and body temperature was measured during each constant routine and the interventions were applied during the night shifts. The 24-hour pattern of alertness and performance on the tasks with low cognitive load in post-treatment conditions followed the change in sleep-wakefulness timing while more cognitively loaded tasks tended to show a reverse trend when compared to pre-treatment conditions. There was a phase delay around 4 hours in circadian rhythms of body temperature in post-treatment conditions.

Adult↗
PubMed2001

Health conditions of bus drivers in a 6 year follow up study.

The bus drivers of a public bus company, working in a fast rotating 4 shift system from 05.00 to 24.30, were examined in 1993 (230 persons) and 1999 (266 persons). The comparison between the two years showed no significant differences for all the parameters evaluated by the Standard Shiftwork Index and medical examination. In both surveys work organisation was considered "efficient-fairly good" by most workers, who were mostly satisfied with their job. Work load was rated significantly higher for "afternoon" and "morning" shifts, during which most accidents at work and "in itinere" occurred. Night sleep was reduced by 3 hours on "early" shift and about 2 hours on "morning" shifts. The most prevalent health troubles dealt with low back pain, gastritis, headache and haemorrhoids. Neuroticism was the trait more correlated with poorer health conditions, whereas shiftwork exposure appeared as a significant predictor of risk of critical Effort/Reward Imbalance and minor psychological disorders. Both extrinsic and intrinsic efforts significantly increased with age, but not reward. The comparison of the same cohort of 108 persons examined both in 1993 and in 1999 showed a significant increase of low back pain, gastrointestinal troubles, haemorrhoids and lipids disorders.

Adult↗
PubMed2000

Spontaneous photo-relaxation of urethral smooth muscle from sheep, pig and rat and its relationship with nitrergic neurotransmission.

1. In the present work we have characterized the relaxant response induced by light stimulation (LS) in the lower urinary tract from sheep, pig and rat, establishing its relationship with nitrergic neurotransmission. 2. Urethral, but not detrusor, preparations showed pronounced photo-relaxation (PR) which declined progressively following repetitive LS. Sheep urethral PR was again restored either spontaneously or (to a greater extent) by exogenous nitric oxide (NO) addition and by electrical field stimulation (EFS) of intrinsic nitrergic nerves. 3. Greater NO generation was detected from sheep urethral than from detrusor homogenates following illumination. 4. Sheep urethral PR was inhibited by oxyhaemoglobin, but not by methaemoglobin, carboxy-PTIO, extracellular superoxide anion generators or superoxide dismutase. Guanylyl cyclase but not adenylyl cyclase activation mediates urethral relaxation to LS. 5. Urethral PR was more resistant to inhibition by L-thiocitrulline than EFS-induced responses, although this agent prevented PR restoration by high-frequency EFS. 6. Urethral PR was TTX insensitive and partially modified in high-K+ solutions. Cold storage for 24 h greatly impaired urethral PR, although it was restored by high-frequency EFS. 7. Repetitive exposure to LS, EFS or exogenous NO induced changes in the shape of the EFS-induced nitrergic relaxation, possibly by pre-synaptic mechanisms. 8. In conclusion, we suggest the presence of an endogenous, photo-labile, nitro-compound store in the urethra, which seems to be replenished by neural nitric oxide synthase activity, indicating a close functional relationship with the nitrergic neurotransmitter.

Adenine↗
PubMed2000

Effects of the radical scavenger AVS on behavioral and BBB changes after experimental subarachnoid hemorrhage.

Free radicals are important contributors to the global brain dysfunction that follows subarachnoid hemorrhage (SAH). We evaluated the effects of hydroxyl radical scavenger AVS [(+/-)-N,N'-propylenedinicotinamide; Nicaraven] after experimental SAH on rodent behavioral deficits (employing a battery of well-characterized assessment tasks over a 2-day observation period) and blood-brain barrier (BBB) permeability changes two days after SAH (quantifying the microvascular alterations according to the extravasation of protein-bound Evans Blue using a spectrophotofluorimetric technique) in dose-response and time-window experiments. Groups of 10 rats were injected with 400 microl of autologous blood into the cisterna magna, and followed by intravenous continuous infusion of saline or 0.1, 03 or 1 mg/kg/min of AVS beginning within 5 minutes or 6 or 12 hours after SAH. The results were compared with sham-operated saline-treated and with SAH saline-treated animals. AVS significantly ameliorated performances on Beam Balance (p < 0.01) and decreased BBB permeability changes in frontal, temporal, parietal, occipital and cerebellar cortices and subcortical and cerebellar nuclei and brainstem (p < 0.01), but did not significantly affect changes in Beam Walking. This study demonstrates the neuroprotective effects of AVS when administered after experimental SAH in rats. These effects were dose-dependent and, moreover, were evident within the therapeutic window of 6-12 hours after SAH. These results reinforce the concept of a participation of reactive oxygen intermediates in the cerebral dysfunction following SAH.

Animals↗