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Biomedical subjects

B Costa

Publications and source records attributed to B Costa.

At least 37 records · Page 2Linked to original sources
PubMed2001

2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.

A new class of N,N-diethyl-(2-arylpyrazolo[1,5-a]pyrimidin-3-yl)acetamides (3f-y), as azaisosters of Alpidem, was prepared following a novel synthetic method and their affinities for both the peripheral (PBR) and the central (CBR) benzodiazepine receptors were evaluated. Binding assays were carried out using both [3H]PK 11195 and [3H]Ro 5-4864 as radioligands for PBR, whereas [3H]Ro 15-1788 was used for CBR, in rat kidney and rat cortex, respectively. The tested compounds exhibited a broad range of binding affinities from as low as 0.76 nM to inactivity and most of them proved to be high selective ligands for PBR. The preliminary SAR studies suggested some of the structural features required for high affinity and selectivity; particularly the substituents on the pyrimidine moiety seemed to play an important role in PBR versus CBR selectivity. A subset of the highest affinity compounds was also tested for their ability to stimulate steroid biosynthesis in C6 glioma rat cells and some of these were found to increase pregnenolone formation with potency similar to Ro 5-4864 and PK 11195.

Acetamides↗
PubMed2001

Description of a clinical technique for tooth extraction in the cleft lip and palate area.

Cleft lip and palate are relatively common congenital malformations, which may require specialist paedodontic treatment. In this article, the case of a 9-year-old boy with bilateral complete cleft lip and palate is presented. He attended the Hospital for Rehabilitation of Craniofacial Anomalies (HRAC) for routine examination, during which the presence of pre-canine supernumeraries bilaterally in the cleft area was seen. The extraction of these dental elements was justified by extensive carious lesions and because they represented a potential problem during secondary palatoplasty. The precautions needed in tooth extraction in patients with cleft lip and palate are described, together with illustrations of the clinical procedure.

Child↗
PubMed2001

The incidence, natural history and associated outcomes of influenza-like illness and clinical influenza in Italy.

OBJECTIVES: This study investigated the epidemiology, natural history and resource use associated with influenza in the general population setting in Italy. METHODS: For a 3-month winter epidemic period, 202 GPs reported daily the number of visits performed for influenza-like illness (ILI), clinical influenza and any other cause. In addition, the first 10 cases of clinical influenza requiring a doctor's visit in each month of the 3-month period and for a total of 30 cases per GP were recorded carefully and followed-up, for evaluation of clinical evolution, associated outcomes and resource use. RESULTS: Almost 200 000 visits were performed by 202 GPs, ILI and clinical influenza accounting for 13.8 and 8.3% of all-cause visits, respectively. A total of 6057 cases of clinical influenza were also recorded and evaluated for associated outcomes and resource use. Twenty percent of the patients were at risk because they were elderly (>65 years) or presented with concomitant chronic conditions. Almost all the patients received at least one prescription for symptomatic drugs and 36% received a prescription for antibiotics. Thirty-five percent of patients had at least one complication from influenza, primarily upper and lower respiratory tract bacterial infections. At-risk patients had a significantly higher complication rate (odds ratio = 2.89) and required more instrumental exams and hospitalizations compared with the general population, accounting for most of the direct costs associated with clinical influenza. Patients with clinical influenza had an average of 5 days absence from work or school. CONCLUSIONS: Influenza is associated with significant morbidity in the general and at-risk population, a high degree of resource use in the at-risk population and substantial reduction or loss of productivity in the active working Italian population.

Absenteeism↗
PubMed2001

Relation between blood pressure variability and carotid artery damage in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis (ELSA).

BACKGROUND: Baseline data from the European Lacidipine Study on Atherosclerosis (ELSA) have shown that carotid intima-media thickness (IMT) is not related to diastolic blood pressure (BP), but that it is related to clinic systolic (S) or pulse pressure (PP) and more so to their 24 h average values. The aim of the present study was to determine whether IMT independently relates to additional information obtained through ambulatory BP, in particular to SBP or PP variability. METHODS AND RESULTS: In 1663 hypertensive patients, after a wash-out period from antihypertensive treatment (mean age 56.2 +/- 7.65 years), IMT was assessed from 12 different carotid sites. Ambulatory BP measurements were performed every 15 min (day) and every 20 min (night). IMT values were positively related to 24 h, day and night average SBP and PP. There was some relationship of IMT with day-night or clinic-day SBP and PP differences. The most important finding, however, was that IMT values were related with 24 h SBP or PP standard deviation (P < 0.001), a measure of overall SBP or PP variability. The relationship was seen also by multiple regression analysis, the standard deviation for SBP or PP only following age and 24 h average SBP or PP in accounting for IMT values. CONCLUSIONS: This is the first demonstration from a large database that not only average 24 h PP and SBP values, but also 24 h BP fluctuations, are associated with, and possibly determinants of, the alterations of large artery structure in hypertension.

Aged↗
PubMed2000

[Undiagnosed diabetes and impaired glucose metabolism on high risk Spanish population. The IGT study].

BACKGROUND: To estimate the prevalence of undiagnosed diabetes and impaired glucose metabolism on high risk Spanish population, contrasting phenotypic features according to both sets of criteria, World Health Organization (WHO) and American Diabetes Association (ADA). SUBJECTS AND METHODS: Cross-sectional, multicentre (10 health-care centres, 230,000 inhabitants), selective risk-factor study. WHO diagnoses (normal, impaired glucose tolerance [IGT] and diabetes) were based on the 2 h plasma glucose (2hPG) following a 75 g oral glucose tolerance test (OGTT) and ADA diagnoses according the fasting plasma glucose (FPG) (normal, impaired FPG and diabetes). Prevalence, diagnostic overlap index and 22 clinical and biological parameters were compared. RESULTS: The study included 580 subjects (330 women), mean age 58.1 years and body mass index 31.2 kg/m2, 292 (50.3%) with only one risk factor and 288 (49.7%) with two or more risk factors. WHO diagnoses were: 291 (50.2%) normal glucose tolerance (95% CI: 46.2-54.2%), 157 (27.1%) IGT (23.5-30.7%) and 132 (22.7%) diabetes (19.3-26.1%). ADA diagnoses were: 355 (61.2%) normal FPG (57.2-65.2%), 146 (25.2%) IFG (21.7-28.7%) and 79 (13.6%) diabetes (10.9-16.3%). The prevalence of diabetes decreased 9.1% (from -11.4 to -6.8%). The diagnostic overlap was 33.5% for diabetes and 19.3% for impaired glucose homeostasis (IGT-FPG). Omitting the OGTT half the diabetic subjects with 2hPG > or = 200 mg/dl (11.1 mM) but FPG < 126 mg/dl (7 mM) would remain undiagnosed. By changing screening criteria (FPG instead of 2hPG) the risk related to traditional factors such as age or a first-degree relative with diabetes would reduce. CONCLUSIONS: Applying ADA criteria, the high prevalence of undiagnosed glucose abnormalities would decrease. These results suggest that it is strongly advisable the continued use of the 2hPG for diabetes screening on high risk Spanish population.

Blood Glucose↗
PubMed2000

Changes in rat brain energetic metabolism after exposure to anandamide or Delta(9)-tetrahydrocannabinol.

The objective of this study was to investigate whether single and repeated administration of the cannabinoids anandamide or Delta(9)-tetrahydrocannabinol affected brain energetic metabolism. Single administration of either anandamide (20 mg/kg) or Delta(9)-tetrahydrocannabinol (10 mg/kg) in rats induced a behaviour typical with cannabinoids. An increase in both brain mitochondria oxidative phosphorylation and cerebral lipoperoxidation was shown ex vivo. The cannabinoid CB(1) receptor-specific antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716A; 3 mg/kg), reversed the anandamide-induced metabolic effects. Prolonged exposure to anandamide (20 mg/kg, 16 days) induced behavioural tolerance and the disappearance of the increased mitochondria oxygen uptake and lipoperoxidation. Repeated Delta(9)-tetrahydrocannabinol injection (10 mg/kg, twice daily, 4.5 days) reduced brain metabolism and uncoupled respiration from oxidative phosphorylation. The present findings showed that both anandamide and Delta(9)-tetrahydrocannabinol enhanced the energetic brain metabolism, probably via the cannabinoid CB(1) receptor; the anandamide-tolerant brain of rats showed tolerance to the drug for metabolic effects, while the brain of Delta(9)-tetrahydrocannabinol-tolerant rats showed metabolic signs of neuronal damage, i.e. low energy production.

Animals↗
PubMed2000

Precipitated and spontaneous withdrawal in rats tolerant to anandamide.

RATIONALE: There is evidence that cannabinoids cause tolerance and physical dependence in humans and animals. OBJECTIVES: The aim of this work was to study whether the endogenous ligand for the cannabinoid receptor, arachidonylethanolamide (anandamide), induced behavioral tolerance and physical dependence in rats. METHODS: Rats were injected with anandamide (20 mg/kg i.p.) daily for 2 weeks. To assess tolerance, on days 1, 8 and 15 of treatment rats were observed and behavior was tested. Two common methods were employed to assess physical dependence: interruption of anandamide dosing and vehicle substitution or administration of the cannabinoid CB1 receptor antagonist SR141716A (3 mg/kg i.p.). RESULTS: Full or partial tolerance developed to the classical behavioral effects elicited by the cannabinoids: hypothermia, catalepsy, hypomotility, decrease in stereotypic activity (rearing and grooming) and hindlimb splaying. No tolerance to anandamide was observed for reduced defecation. An abstinence syndrome appeared after abrupt cessation of cannabinoid intake and after withdrawal precipitated by SR141716A; the withdrawal signs were scratching, licking and biting, eating of feces, ptosis, arched back, wet dog shakes, head shakes, myoclonic spasms, writhing, forepaw fluttering, teeth chattering and piloerection. CONCLUSIONS: These findings indicate that the endogenous cannabinoid ligand, administered exogenously, induces both tolerance and physical dependence in rats.

Animals↗
PubMed2000

C-nucleoside analogues of furanfurin as ligands to A1 adenosine receptors.

Furanfurin (2-beta-D-ribofuranosylfuran-4-carboxamide) derivatives and analogues were synthesized and their affinity for adenosine receptors was determined. The agonistic behavior of furanfurin against A1 receptors is preserved only when the furan ring is substituted with isosteric pentatomic ring systems such as oxazole, thiazole or thiophene, and the carboxamide group is unsubstituted. Replacement of the hydrogen atoms of the carboxamide group with alkyl, cycloalkyl or arylalkyl groups generates compounds endowed with moderate antagonistic activity.

Adenylyl Cyclase Inhibitors↗
PubMed2000

Loss of cannabinoid-stimulated guanosine 5'-O-(3-[(35)S]Thiotriphosphate) binding without receptor down-regulation in brain regions of anandamide-tolerant rats.

The endogenous cannabinoid anandamide has been reported to produce well-defined behavioral tolerance, but studies on the possible mechanisms underlying this process are few and often contradictory. The present study was designed to survey the cellular events involved in anandamide tolerance, in terms of the effects on receptor number, coupling with G proteins, and activation of the cyclic AMP (cAMP) cascade. Chronic treatment of rats with anandamide (20 mg/kg i.p. for 15 days) resulted in behavioral tolerance without any change in cannabinoid receptor binding in the brain regions studied (striatum, cortex, hippocampus, and cerebellum), suggesting that receptor down-regulation was not involved in the development of anandamide behavioral tolerance. In contrast, prolonged exposure to anandamide significantly reduced agonist-stimulated guanosine 5'-O:-(3-[(35)S]thiotriphosphate) binding in the same areas, with losses of >50%, suggesting that receptor desensitization may be part of the molecular mechanism underlying this tolerance. Finally, concerning the cAMP cascade-the most well-known intracellular signaling pathways activated by CB(1) receptors-in the brain regions from rats tolerant to anandamide, we found no alteration in cAMP levels or in protein kinase A activity. We propose that anandamide, unlike Delta(9)-tetrahydrocannabinol and other cannabinoids, does not alter the receptor system at multiple levels but that desensitization of the CB(1) receptor might account for behavioral tolerance to the drug.

Animals↗
PubMed2000

Prevalence of intranasal ectopic teeth in children with complete unilateral and bilateral cleft lip and palate.

OBJECTIVE: The objective of this study was to determine the prevalence of ectopic eruption of intranasal teeth. DESIGN: This was a retrospective study, where records of children with repaired cleft lip and palate were analyzed. SETTING: The study was conducted at a large craniofacial center, the Hospital for Rehabilitation of Craniofacial Anomalies, USP, Bauru, São Paulo, Brazil. SUBJECTS: The sample consisted of 815 records from patients with bilateral cleft lip and palate (BCLP) and 1,495 records from patients with unilateral cleft lip and palate (UCLP). The age of the subjects was 5 to 10 years old and the groups included both males and females. RESULTS: The results showed that 0.61% of the children with BCLP and 0.40% of those with UCLP had an intranasal tooth. The prevalence of an intranasal tooth for the whole group was 0.48%, and it appeared to be more common in females.

Brazil↗
PubMed2000

Evaluation of primary dentition in cleft lip and palate children with and without natal/neonatal teeth.

OBJECTIVE: Natal/neonatal teeth are very common in children with complete unilateral and bilateral cleft lip and palate. The extraction of these teeth is the usual treatment in the Hospital for Rehabilitation of Craniofacial Anomalies. The objective of this study was to verify whether these teeth could be of the normal complement or whether they were supernumerary. DESIGN: The primary dentition of children with cleft lip and palate with and without natal/neonatal teeth was compared at the Hospital for Rehabilitation of Craniofacial Anomalies. SUBJECTS: The sample consisted of 55 children with complete unilateral and bilateral cleft lip and palate with natal/neonatal teeth and 54 without. RESULTS: No positive association between these groups and missing lateral incisor or supernumerary or complete dentition was found. CONCLUSION: The extraction of the natal/neonatal teeth did not alter the final complement of primary teeth, and these teeth could be the lateral incisor or supernumerary.

Anodontia↗
PubMed2000

Dental anesthetic procedures for cleft lip and palate patients.

Many dentists refuse to offer dental assistance to cleft lip and palate patients because they lack understanding about this malformation and do not want to make a professional mistake with the anesthesia. The aim of this work is to guide clinical practitioners, who want to work with these patients about the anatomical features of the cleft lip and palate area and the implications in the anesthetic procedures.

Anesthesia, Dental↗
PubMed1999

Cross-tolerance and convergent dependence between morphine and cannabimimetic agent WIN 55,212-2 in the guinea-pig ileum myenteric plexus.

The cross-tolerance and convergent dependence between morphine and the cannabimimetic agent R(+)-[2,3-dihydro-5-methyl-3[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-+ ++benzoxazin-yl]-(1-naphthalenyl) methanone mesylate (WIN 55,212-2) were assessed in vitro on guinea-pig ileum. To induce tolerance and dependence the myenteric plexus-longitudinal muscle was incubated at 37 degrees C for 5 h with a fixed concentration representing the IC50 for each compound. Myenteric plexus-longitudinal muscle exposed to WIN 55,212-2 (5 x 10(-8) M) was less sensitive to its inhibitory effect on electrically evoked contractions than naive myenteric plexus-longitudinal muscle. The exposure to cannabinoid induced a parallel rightward shift in the lower part of the concentration-response curve of WIN 55,212-2 and a marked reduction in the maximal inhibitory effect of the drug. Myenteric plexus-longitudinal muscle tolerant to WIN 55,212-2 was subsensitive to the inhibitory effect of morphine on the twitch response. The cross-tolerance between WIN 55,212-2 and morphine was bidirectional. In fact, after 5 h the morphine (10(-7) M)-incubated myenteric plexus-longitudinal muscle was less sensitive to the inhibitory effect of WIN 55,212-2. The tissue tolerant to morphine or WIN 55,212-2 was tested for the presence of physical dependence. Naloxone (10(-5) M) produced a typical withdrawal contracture in morphine-tolerant myenteric plexus-longitudinal muscle which could be reduced by a 15-min pretreatment with WIN 55,212-2 (5 X 10(-8) M). In contrast, SR141716 (10(-6) M) [N-(piperidino)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyr azole-carboxamide], a concentration which fully antagonized the inhibitory effect of WIN 55,212-2 (10(-7) M) in control preparations, did not produce significant contracture in WIN 55,212-2-tolerant myenteric plexus-longitudinal muscle. The mechanisms underlying the cross-tolerance and convergent dependence remain to be ascertained.

Analgesics, Opioid↗
PubMed1999

Benzodiazepine receptor ligands. III. Synthesis and biological evaluation of 2- and/or 3-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides.

A new series of 2- and/or 3-substituted pyrazolo [5,1-c][benzotriazine 5-oxides and their 8-chloro derivatives were synthesized, and their benzodiazepine receptor (BZR) affinities were evaluated in vitro in comparison to lead compound 3-ethoxycarbonyl-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide (29) [1,2]. None of the new compounds showed significant affinity for BZR. On the basis of a pharmacophore/receptor model suggested for lead compound 29, some hypotheses to explain the inactivity of new derivatives are discussed.

Animals↗
PubMed1999

Benzodiazepine receptor ligands. 4. Synthesis and pharmacological evaluation of 3-heteroaryl-8-chloropyrazolo[5,1-c][1,2,4] benzotriazine 5-oxides.

The synthesis of new 3-heteroaryl-8-chloropyrazolo[5,1-c][1,2, 4]benzotriazine 5-oxides and their binding activities at the central benzodiazepine receptor (BZR) are reported. The derivatives substituted at the 3-position with electron-rich five-membered rings, such as pyrrole 11, 2-thiophene 13c, or 3-thiophene 13d, showed good affinity values for BZR. In in vivo tests the 3-(thien-3-yl)-8-chloropyrazolo[5,1-c][1,2,4] benzotriazine 5-oxide (13d) showed selective anticonvulsant activity.

Animals↗
PubMed1999

Characterization of a cloned xenopus laevis serotonin 5-HT1A receptor expressed in the NIH-3T3 cell line.

In a previous work we isolated a Xenopus 5-HT1A receptor gene and now report the characterization of this receptor. The HindIII-XbaI fragment of this gene was cloned into the pcDNA I NEO vector and stably transfected into eukaryotic cells (NIH-3T3). To determine the specific 5-HT1A receptor binding, [3H]8-OH-DPAT was used as radioligand. The selective 5-HT1A receptor agonist bound only a single class of saturable high-affinity binding sites with pharmacological characteristics similar to those of the mammalian 5-HT1A receptor. The effects of X5-HT1A receptor activation on cell growth were also investigated in stably transfected NIH-3T3 cells. The 5-HT1A agonist 8-OH-DPAT was found to increase DNA synthesis and accelerated cell growth.

3T3 Cells↗
PubMed1999

Impact of the American Diabetes Association diagnosis criteria on high-risk Spanish population. IGT Research Group. Impaired glucose tolerance.

To research into the impact of the new American Diabetes Association (ADA) diagnostic criteria on high risk Spanish population, two cross-sectional studies involving seven primary health care centers in Catalonia (Spain) were revised. Individuals aged > 40 years with any major risk factor for diabetes were screened according to the World Health Organization (WHO) rules using a 75 g oral glucose tolerance test to measure fasting plasma glucose (FPG) and 2 h plasma glucose. The changes on diabetes prevalence and on epidemiological characteristics were evaluated applying the ADA criteria on the basis of FPG alone. A total of 970 individuals, 453 males (46.7%), mean age 59 years and mean body mass index (BMI) 30.6 kg/m2 were screened. Among the 459 diabetic subjects according to either the WHO or the ADA criteria, 314 (68.4%) were classified as having diabetes with respect to both sets of criteria (WHO and ADA). The overlap between impaired glucose tolerance (WHO) and impaired fasting glucose (ADA) diagnoses was 20.7%. Using the ADA criteria results in a decrease of the prevalence of diabetes by 1.5% (95% confidence interval (CI) = -2.2 to -0.8%). No changes in the diabetic phenotype (age, sex and BMI) were found. Impaired fasting glucose prevalence was 18.4% (95% CI = 16-21%). Overall concordance in terms of crude and weighted kappa-value was only acceptable (kappa = 0.51 and kappa = 0.61, respectively). To apply the new ADA diagnostic criteria on high risk Spanish population evidenced a decrease on diabetes prevalence. Nevertheless, the change of criteria undervalued the risk of postprandial hyperglycaemia related to impaired glucose tolerance.

Adult↗