Biomedical subjects

G Costa

Publications and source records attributed to G Costa.

At least 91 records · Page 5Linked to original sources

PubMed1999

[Social inequalities in the mortality due to cardiovascular diseases in Italy].

Social inequalities in cardiovascular disease mortality are described in this paper focusing on the results of the Studio Longitudinale Torinese (SLT), an investigation that links census data with the statistical data that are currently available. The overall results confirm that cardiovascular disease mortality is higher in less-advantaged socioeconomic groups, irrespectively of the social indicator used: education, social class, housing quality, job security. Stratified data shows less important inequalities among ischemic heart disease as compared to cerebrovascular mortality. The differences are even more complex when the age groups in the two genders are analyzed, revealing cohort effects. Overall, the results agree with the previous survey carried out by ISTAT on 1981 Italian mortality, which confirmed the variations in inequalities according to geographical areas, gender and age. Differences in access to the health system are likely to be related to the differences detected for geographical areas, while differences in personal history and attitude towards health-associated behavior should explain age and gender variations in inequalities. Equity must be included in the evaluation of preventive programs and health-care models. Epidemiological and social research should be encouraged to better understand the factors that influence inequalities in cardiovascular disease mortality and in the health status of the population at large.

Adolescent↗

PubMed1999

[Anterior approach and simultaneous tension-free repair of bilateral inguinal hernia under local anesthesia].

An analysis of prospectively collected data of 56 patients submitted to bilateral hernia repair is reported. Simultaneous repair was performed in 32 patients (Group S) while a sequential repair in 24 (Group D). Mean operating time was longer for the combination of two sequential repairs than for simultaneous repair (132 min +/- 8.9 vs 123 min +/- 11, p < 0.001). Mean hospital stay was similar in unilateral and bilateral repairs (18.0 hrs +/- 4 vs 21.2 hrs +/- 3.4, p = ns). Ther were no difference in complications between the two groups. Time taken to return to full activity was nearly double in the combination of two sequential repairs than in simultaneous repair (25 days, sd +/- 4 vs 16 days +/- 3, p < 0.001), while postoperative analgesia requirements were similar. The Authors conclude that bilateral simultaneous anterior tension free repair under local anesthesia is the treatment of choice in case of bilateral inguinal hernias.

Age Factors↗

PubMed1998

Hydroxyl radical production in the substantia nigra after 6-hydroxydopamine and hypoxia-reoxygenation.

To study the involvement of oxidative stress in 6-OHDA neurotoxicity, we investigated the production of the hydroxyl free radical (OH.) in the substantia nigra (SN) and the striatum (CS) several moments after intranigral injection of the neurotoxin, with or without an added episode of hypoxia (30 min, 95% N2, 5% O2). We utilized the hydroxylation of salicylate to 2,3 dihydroxybenzoic acid (2,3 DHBA) as indication of OH. production. When 2.3 DHBA levels were not modified, the levels of 2,5 DHBA were taken as an indication of cytochrome P450 (CYP 450) metabolism. 6-OHDA alone did not increase the production of 2,3 DHBA in the SN. 2,5 DHBA increased significantly after 120 min and was high up to 24 h. An episode of hypoxia (60 min after 6-OHDA injection) significantly worsened the decrease of dopamine (DA) in the striatum assessed 8 days after injection of 6-OHDA in the SN. Hypoxia performed 60 min and 24 h before or 24 h after 6-OHDA did not show any additional effect on striatal DA levels. Contrary to results obtained after 6-OHDA alone, 2,3 DHBA increased significantly 120 min after the injection, when the hypoxia-reoxygenation was added to the 6-OHDA treatment. Our data are showing a relationship between the increase in OH. production and a concomitant worsening of neuronal degeneration. As a whole, the results support the idea that neurons undergoing 6-OHDA neurotoxicity have their antioxidant defences affected and that oxidative stress is actually an important eliciting factor in 6-OHDA dependant neurodegeneration. However, OH. may not be the main radical species involved in this process. Additionally, 6-OHDA also appeared to provoke a long-term increase in CYP 450 activity.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures.

OBJECTIVE: This work was carried out in order to investigate possible relationships between bone turnover rate, as evaluated by bone biomarkers and skeletal mass, as evaluated by bone mineral density (BMD). METHOD: Fifty-eight normal women and 30 female patients with osteoporotic fractures were enrolled. Three groups were defined: (1) fertile subjects (n = 24), mean age 33.7 +/- 8.1 years; (2) postmenopausal women (n = 32, including 11 patients with fractures) whose BMD values, in terms of T score, were less than -2.5 S.D. below the young adult mean obtained in our laboratory (mean age 61.7 +/- 7.9 years; and years since menopause (ysm), 12.6 +/- 8.3); (3) postmenopausal women (n = 32, including 19 patients with fractures) whose BMD values in terms of T score, were below -2.5 S.D. (mean age 62.9 +/- 8.6 years; and ysm 15.9 +/- 9.0). Groups II and III characterised, by inclusion criteria, by significant different mean BMD values, were similar as far as chronological and menopausal age were considered. Metabolic tests included a short urine collection to determine calcium, hydroxyproline, cross-linked N-telopeptides of type I collagen (NTx) and creatinine (Cr); half-way through this collection, a blood sample was taken for the measurement of total alkaline phosphatase activity (ALP) and tartrate-resistant acid phosphatase activity (TRAP). BMD at lumbar spine was evaluated. RESULTS: There were significant differences amongst the three groups in mean ALP (P < 0.001, by analysis of variance) TRAP (P < 0.006) and NTx/Cr (P < 0.001) values, but not as far as mean values of calcium/Cr or hydroxyproline/Cr ratios were concerned. Considering the group as a whole, there were significant inverse correlations between NTx/Cr, ALP, TRAP and BMD controlling for both age (r = -0.392, P < 0.001; r = -0.447, P < 0.001 and r = -0.327, P < 0.002, respectively) and ysm (r = -0.374, P < 0.001; r = -0.474, P < 0.001 and r = -0.333, P < 0.002). CONCLUSIONS: Our results indicate, that, even after controlling for both ageing and oestrogen status, there is an inverse relationship between bone mass (that at a given time represents the balance of all previous metabolic events) and a biochemical marker (which reflects bone turnover at the time of examination). These findings are in line with the belief that increased bone turnover should be regarded as a risk factor for osteoporosis. Furthermore, our results indicate that, unless there is no increase of hepatic isozyme, total ALP still maintains a possible role as a first analysis to evaluate bone turnover before requesting markers with greater specificity, sensitivity but also more expensive and whose analysis is sometimes time-consuming.

Adult↗

PubMed1998

The role of serum and gastric juice levels of carcinoembryonic antigen, CA19.9 and CA72.4 in patients with gastric cancer.

PURPOSE: The aim of the present study was to investigate carcinoembryonic antigen (CEA), CA19.9, and CA72.4 in the serum and gastric juice of patients with gastric cancer. METHODS: Serum and gastric juice tumor markers CEA, CA19.9, and CA72.4 were measured in 59 patients who had gastric adenocarcinomas and were undergoing curative gastrectomy. The same markers were measured in 47 patients with benign gastric disorders and in 40 healthy subjects. The correlation between the serum and gastric juice levels of tumor markers and several clinicopathological factors were evaluated by univariate analysis. The significance of the tumor markers as prognostic factors was assessed both by univariate and multivariate analysis. RESULTS: The positivity rates of serum CEA, CA19.9, and CA72.4 were 57.6%, 38.9%, and 18.6% respectively. The positivity rates of gastric juice CEA, CA19.9, and CA72.4 were 62.7%, 30.5%, and 23.7% respectively. The combination of serum and gastric juice markers gave a positivity of 81.3%. There was no correlation between serum and gastric juice level of each tumor marker. Positivity of gastric juice markers did not correlate with prognosis. A significant difference in prognosis was observed between patients positive and negative for serum CEA and CA19.9. Multivariate analysis also revealed that serum CEA and CA19.9 levels were independent prognostic factors. CONCLUSIONS: Levels of both serum and gastric juice tumor markers continue to have only limited diagnostic usefulness in gastric cancer patients. CEA and CA19.9 in the preoperative sera are good prognostic factors, whereas the presence of tumor markers in the gastric juice does not play any prognostic role.

Adenocarcinoma↗

PubMed1998

Comparison of four minimally invasive methods of laparoscopic vagotomy in a porcine model.

BACKGROUND: An experimental study in a porcine model was undertaken to evaluate the currently available techniques of laparoscopic vagotomy. METHODS: Four groups of pigs were studied. Under general anesthesia, the animals were submitted to either bilateral vagotomy, bilateral highly selective vagotomy, posterior truncal vagotomy with anterior highly selective vagotomy, or Taylor's procedure. Gastric acid secretion and intestinal motility were evaluated before and after the surgical procedure. The feasibility of the four different techniques was assessed by means of a personal difficulty score. RESULTS: All four procedures produced significant acid secretory reduction. Multivariate analysis showed that the factor most affecting the outcome was the difficulty score. CONCLUSIONS: Taylor's procedure was the easiest and safest technique. It also produced the best functional results for secretion and motility.

Animals↗

PubMed1998

Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo.

Snake neurotoxins (NTX) have proven to be valuable tools for the characterisation of muscular nicotinic acetylcholine receptor structure and function. It is very likely that they could also be utilised to identify subtypes of neuronal nicotinic receptors controlling specific functions within the central nervous system. In this study we examined the effects of long alpha NTX (alpha-bungarotoxin, alpha-Bgt, and alpha-cobratoxin, alpha-Cbt) and short alpha NTX (alpha-erabutoxin a, alpha-Ebt) as well as the anticholinesterase toxin fasciculin-2 (FAS), on the nicotine-evoked release of dopamine (DA) in the striatum, using the in vivo push-pull technique. The short toxins alpha-Ebt and FAS blocked the extracellular increase of DA evoked by nicotine at 4.2 microM concentrations and alpha-Ebt was more potent, as reflected by the blockade at the lower dose of 0.42 microM. In contrast, the long toxins showed a different profile of action. Alpha-Cbt did not show any blockade of the nicotine-evoked release of DA at the doses studied while alpha-Bgt did block it only at the higher dose (4.2 microM) These results indicate that short neurotoxins show a stronger interaction with striatal nicotinic receptors subtypes controlling DA release when compared to the long ones. This interaction of short neurotoxin polypeptides and presynaptic receptors may permit the further elucidation of the particular nicotinic receptor populations responsible for the modulation of striatal DA release.

Animals↗

PubMed1998

Oral toxicity of bis(2-ethylhexyl) phthalate during pregnancy and suckling in the Long-Evans rat.

Bis(2-ethylhexyl) phthalate (DEHP) is a compound widely used in plastics technology to impart flexibility to rigid polymers. We sought to determine whether the oral exposure of female rats to DEHP during gestation and suckling produces alterations in the litter. Female rats were exposed to different concentrations of DEHP suspended in drinking water (32.5 and 325 microl/litre) from day 1 of pregnancy to day 21 after delivery. Pup body weight gain and kidney, liver and testes weight was measured at different times (21, 28, 35, 42 and 56 days) after birth. Plasma concentrations of DEHP and histopathological alterations in kidneys, liver and testes were also studied. In addition, the ability of female pups (1 month of age) to perform a learned avoidance test, the 'beam walking' test, was evaluated. Perinatal exposure to DEHP produced no statistically significant changes in the body weight gain of offspring. Conversely, it produced a significant decrease in kidney and testes relative weight (organ/body weight) with a significant increase in relative liver weight. Signs of histological damage in kidneys, liver, and particularly testes, were observed. Pups exposed perinatally to the highest concentration of DEHP elicited a significant increase in the time necessary to perform the beam walking test.

Administration, Oral↗

PubMed1998

Ambulatory blood pressure in air traffic controllers.

Conflicting reports exist as to whether air traffic controllers (ATC) have an increase in blood pressure (BP) and prevalence of hypertension because of the stressful nature of their job. We have addressed the issue in male ATC working at the Linate airport of Milan. A total of 80 ATC participated, and the 24 h blood pressure monitoring was obtained during two working shifts separated by one night of rest. Blood pressure was measured conventionally and by 24 h ambulatory monitoring; data were compared with those of an age matched male sample three times as large, selected from the data of the Studio delle Pressioni Ambulatoriali delle Loro Associazioni (PAMELA), ie, a large sample representative of the population of the nearby town of Monza. Treated hypertensive subjects were excluded from both groups. Conventional diastolic BP and heart rate were similar in ATC and controls, whereas conventional systolic BP was significantly greater in the former than in the latter group. No difference, however, was seen between ATC and controls as far as ambulatory BP and heart rate were concerned; namely, 24 h, day, and night average systolic BP, and diastolic BP and heart rate were similar in the two groups. Thus daily life BP is not increased in ATC. This may result from the fact that, being a highly selected group with suitable training, these subjects adequately cope with the stress inherent to the job.

Adult↗

PubMed1998

DRB1-DQA1-DQB1 loci and multiple sclerosis predisposition in the Sardinian population.

Multiple sclerosis (MS) is a common neurological disease caused by genetic and environmental factors. Previous genetic analyses have suggested that theMHC/HLA region on chromosome 6p21 contains an MS-predisposing component. Which of the many genes present in this region is primarily responsible for disease susceptibility is still an open issue. In this study, we evaluated, in a large cohort of MS families from the Mediterranean island of Sardinia, the role of allelic variation at the HLA-DRB1, DQA1 and DQB1 candidate loci in MS predisposition. Using the transmission disequilibrium test (TDT), we found significant evidence of association with MS in both the Sardinian-specific DRB1*0405(DR4)- DQA1*0501-DQB1*0301 haplotype and the DRB1* 0301(DR3)-DQA1*0501-DQB1*0201 haplotype. Detailed comparative analysis of the DRB1-DQA1- DQB1 haplotypes present in this data set did not identify an individual locus that could explain MS susceptibility. The predisposing effect is haplotype specific, in that it is confined to specific combinations of alleles at the DRB1, DQA1 and DQB1 loci. Cross-ethnic comparison between the two HLA haplotypes associated with MS in Sardinians and the DRB1*1501 (DR2)-DQA1*0102-DQB1* 0602 haplotype, associated with MS in other Caucasian populations, failed to identify any shared epitopes in the DR and DQ molecules that segregated with disease susceptibility. These results suggest that another MHC gene(s), in linkage disequilibrium with specific HLA-DRB1, DQA1, DQB1 haploypes, might be primarily responsible for genetic susceptibility to MS. Alternatively, the presence of complex interactions between different HLA haplotypes, other non-HLA predisposing genes and environmental factors may explain different associations in different populations.

Adolescent↗

PubMed1998

Antivasospastic and brain-protective effects of a hydroxyl radical scavenger (AVS) after experimental subarachnoid hemorrhage.

OBJECT: The radical scavenger (+/-)-N,N'-propylenedinicotinamide (AVS) was shown recently to ameliorate delayed neurological deficits resulting from ischemia in patients who have had an aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to evaluate the effect of AVS administration after experimental SAH on 1) behavioral deficits; 2) angiographically confirmed basilar artery (BA) spasm; and 3) blood-brain barrier (BBB) permeability changes. METHODS: These parameters were measured by 1) using a battery of well-characterized chronic assessment tasks over a 5-day observation period; 2) assessing in vivo the mean vessel diameter 2 days after SAH; and 3) evaluating the extravasation of protein-bound Evans Blue dye by using a spectrophotofluorimetric technique 2 days after SAH. Groups of eight to 10 rats received injections of 400 microl of autologous blood into the cisterna magna. Within 5 minutes after the surgical procedures were completed the rats were treated with an intravenously administered continuous infusion of saline (Group III) or AVS (1 mg/kg/minutes, Group IV). Results were compared with those in sham-operated animals treated with intravenously administered saline (Group I) or AVS (Group II). The AVS-treated rats had significantly improved balance beam scores on Days 1 to 2 (p < 0.05), shorter beam traverse times on Day 1 (p < 0.05), and better beam walking performance on Days 1 to 4 (p < 0.01), but no significant effect was seen in terms of SAH-related changes in body weight. Treatment with AVS also attenuated the SAH-induced BA spasm (p < 0.05) and decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices, and in the subcortical and cerebellar gray matter and brainstem (p < 0.01). CONCLUSIONS: These results demonstrate useful antivasospastic and brain-protective actions of AVS after induction of experimental SAH and provide support for observations of beneficial effects of AVS made in the clinical setting.

Animals↗

PubMed1998

[Canalith repositioning maneuver: proposal of a new therapy for benign paroxysmal positional vertigo of the posterior semicircular canal].

A new therapy is proposed for the treatment of Benign Paroxysmal Positional Vertigo (B.P.P.V.) of the Posterior Semicircular Canal (P.S.C.): the Canalith Repositioning Maneuver (C.R.M.). The need for a new maneuver to treat B.P.P.V. of the P.S.C. arises from the difficulties encountered in daily practice, under particular conditions (i.e. elderly, obese, traumatized patients and in the presence of rachis pain, etc.), to perform the most common rehabilitative techniques such as the Semont Maneuver and Epley's Canalith Repositioning Procedure (C.R.P.). The results achieved using this new technique on a group of 47 consecutive out-patients are presented and compared to those achieved using the Semont Maneuver in an analogous group of 23 patients. C.R.M. and the Semont Maneuver were performed once per treatment session and all patients were checked every 3 days until the symptoms of B.P.P.V. disappeared. Thereafter they were invited to return for check-up if signs of vertigo returned (follow-up 6-25 months). The two techniques proved equally effective: 87.5% of the cases were resolved with C.R.M., 82.6% with the Semont Maneuver. However, the C.R.M. provided other advantages as it resolved the problem immediately (i.e. in a single session) in 81% of the cases vs. 68.4% for the Semont Maneuver. In view of the Canalith theory, the action mechanism envisaged for all three maneuvers--C.R.M., the Semont Maneuver and the Epley C.R.P.--can be explained assuming that the canalith passes from the ampullar to the non ampullar branch of the (P.S.C.) passing finally through the Common Duct and into the Utricle. C.R.M. is a specific treatment for the B.P.P.V. of the P.S.C. and is simple to perform, well tolerated and quite effective. It is indicated in all cases of B.P.P.V. of the P.S.C. both as initial treatment and as alternative to other treatment methods which have proved ineffective or difficult to perform. Indeed, in therapy it is best to be quite skilled in more than one technique, availing oneself of a full range possibilities; in this way the cure can be tailored to the patient in each individual case and not vice versa.

Adolescent↗

PubMed1998

[Learning curve for "tension-free" reparation of inguinal hernia].

A prospective randomized study of 106 patients with unilateral primary inguinal hernia who underwent "tension-free" mesh repair was carried out. Fifty-nine procedures (group A) were performed by a single experienced surgeon and 47 (group B) procedures were performed by a team of residents each with an experience level of less than ten cases. In group A the length of operation was statistically shorter; local anesthesia was more frequently used in group A, while intra-operative sedation and general anesthesia were more frequently used in group B. A subgroup of twenty patients (group C) operated on by residents with a personal experience of at least 5 tension free repairs was selected. No statistically significant difference in operation time and in anesthesia used were found between group A and group C. No significant difference was found between group A and group B in morbidity rate, mean postoperative stay, median time to return to work, and recurrence rate. Because easy, efficacy, and minimally invasive, the tension-free mesh repair remains the gold standard in the treatment of inguinal hernia.

Adult↗

PubMed1998

[Primary neuroendocrine carcinoma of the skin: clinical case].

A case of Merkel cell carcinoma of the skin is described. It is a rare primary skin tumor originating within the dermis with an aggressive biologic behavior. Clinical presentation of these tumors are not sufficiently distinctive to allow the preoperative diagnosis. Wide surgical excision with postoperative irradiation to the local site and regional lymphatics is recommended as the therapy of choice. Indications for chemotherapy are discussed and the guidelines for an appropriated follow-up are reported.

Aged↗

PubMed1998

Local delivery of cytokines by retrovirally transduced antigen-specific TCR+ hybridoma cells in experimental autoimmune encephalomyelitis.

Autoimmune diseases in humans represent an immune attack on self tissue. Current therapies for almost all autoimmune diseases utilize potent and nonspecific immunosuppressive regimens. These therapies are complicated by their side effects and also place the patient at increased risk for opportunistic infections and malignancies. Our current understanding of immune mechanisms underlying autoimmune diseases remains limited. Ongoing studies include identifying genes that predispose an individual to developing autoimmunity, identification of autoantigens that trigger or perpetuate autoimmunity, and studies of immune cell interactions that lead to immune response. Although it may be many years before a full understanding of autoimmunity is obtained, treatment in animal models of autoimmune disease and some human clinical trials have begun to study alternative treatment approaches to therapy of autoimmune disease. Future therapies for autoimmune diseases should target the inappropriate autoimmune response. This article will describe the use of gene therapy in the treatment of autoimmune disease. We believe that autoimmunity can be ameliorated by delivering trans-acting immunoregulatory molecules by retrovirally transduced autoantigen specific T cells that home to lesions of autoimmunity. Until recently, there has not been a practical alternative to systemic delivery of immunoregulatory molecules, however systemic delivery suffers from toxic side effects and dangerous global immunosuppression. In order to study immune regulation using retroviral transduction for local delivery of immunoregulatory products, we used myelin basic protein (MBP) reactive T cell hybridomas in the murine model of multiple sclerosis (MS), experimental allergic encephalomyelitis (EAE). In this report, we show that MBP reactive T cell hybridomas transduced to express IL-4 or TNF, ameliorated or exacerbated disease, respectively. Additionally, the effects of these cells were dependent on T cell receptor (TCR) expression, indicating that the effects were due to homing of the T cells and the local delivery of cytokines. We believe that gene therapy, allowing local delivery of immunoregulatory proteins by autoantigen specific T cells, represents an interesting potential therapy for autoimmune disease.

Adoptive Transfer↗

PubMed1998

Guidelines for the medical surveillance of shift workers.

Occupational health physicians should evaluate workers' fitness for shift and night work before their assignment, at regular intervals, and in cases of health problems connected with night work. The evaluation should be accompanied by a careful job analysis to ensure that shift schedules are arranged according to ergonomic criteria. This arrangement can reduce health problems and make coping with irregular workhours possible, even for people suffering from contraindicative illnesses. Both health disorders representing absolute or relative contraindication and actual work conditions should be taken into account. Health checks should be aimed at detecting early signs of intolerance, such as sleeping and digestive trouble, drug consumption, accidents, and reproductive function. Their periodicity should be set in relation to specific work conditions, individual characteristics, and social factors known to influence tolerance to shift work. Shift workers should receive clear information on the possible negative effect of shift work, and also counseling for coping with shift and night work.

Counseling↗

PubMed1998

Socio-economic inequalities in mortality. Methodological problems illustrated with three examples from Europe.

BACKGROUND: Studies from most European countries have been able to demonstrate that lower socioeconomic groups have higher risks of disease, disability and premature death. Uncertain is, however, whether these studies have also been able to estimate the precise magnitude of these inequalities, their patterns and their trends over time. The purpose of this paper is to illustrate the extent to which results of descriptive studies can be biased due to problems with the data that are commonly available to European countries. METHODS: Three illustrations are presented from a project on socio-economic inequalities in premature morbidity and mortality in Europe. These illustrations concern three problems often encountered in data on social class differences in mortality among middle aged men: the numerator/denominator bias in cross-sectional studies (illustrated for France), the exclusion of economically inactive men (illustrated for 4 countries), and the use of approximate social class schemes (illustrated for Sweden). RESULTS: In each illustration, inequalities in mortality among middle aged men could be demonstrated, but data problems appeared to bias estimates of the precise magnitude of inequalities in mortality, their patterns by social class and cause of death, and their trends over time. The bias was substantial in most cases. Usually, it was difficult to predict in which ways and to what extent inequality estimates would have been biased. CONCLUSIONS: When the aim of a study is to determine the precise magnitude, patterns or time trends of health inequalities, the results should be evaluated carefully against a number of potential data problems. Investments are needed, e.g. in data sources and in the measurement of socio-economic status, to secure that future studies can describe socio-economic inequalities in health in Europe in more detail and with more reliability.

Bias↗

PubMed1997

Histamine receptors in isolated bovine oviductal arteries.

The present in vitro study was designed to evaluate the effect of histamine on isolated rings of bovine oviductal artery and to characterize the histamine receptors involved in the histamine-induced response. Endothelial dependence of the response was also investigated. Cumulative addition of histamine and 2-pyridylethylamine (histamine H receptor agonist) induced a concentration-dependent relaxation in intact arterial segments precontracted with noradrenaline. The histamine H1 receptor antagonist mepyramine showed non-competitive antagonism in the histamine-induced concentration-response curve. However, when the response to histamine was evaluated in the presence of mepyramine and histamine H1 and H3 receptors were blocked, Schild analysis yielded a line with a slope of 1.10 and a pA2 value of 8.91, indicating simple competitive antagonism of mepyramine at histamine H1 receptor sites. The histamine H2 receptor agonist, dimaprit, caused marked dilatation only at high doses. Cimetidine, propranolol and mepyramine failed to inhibit this relaxant effect. In precontracted oviductal arteries, cimetidine did not modify the histamine-induced concentration-response curves. Combined treatment with histamine H1 and H2 receptor antagonists did not induce an additional displacement with respect to the isolated effect of mepyramine thus excluding activation of histamine H2 receptors. Histamine and (R)-alpha-methylhistamine, a selective histamine H3 receptor agonist, produced a moderate contractile effect on the resting tone of preparations. Pretreatment with the selective histamine H1 receptor antagonist decreased the (R)-alpha-methylhistamine response but increased the maximal relaxant effect and abolished the contractile effect of histamine, suggesting the presence of a limited population of contractile histamine H3 receptors. Removal of the endothelium or pretreatment with methylene blue produced a significant inhibition of the relaxant response to histamine. Remaining dilatation was practically abolished by mepyramine and also by indomethacin. The L-arginine analogue, N(omega)-nitro-L-arginine methyl ester (L-NAME) inhibited the effect of histamine and basal production of nitric oxide. L-Arginine, which on its own induced significant endothelium-dependent vasodilatation, reversed the effect of L-NAME on histamine relaxation. Indomethacin only caused a slight modification of the sensitivity of the vessels to histamine, suggesting that prostacyclin or other cyclo-oxygenase products did not make a significant contribution to the model. The absence of the endothelium did not modify the contractile effect of histamine. The results suggest that the relaxant response of isolated oviductal arteries to histamine is dependent on the functional integrity of the endothelium and is mainly mediated by histamine H1 receptors. These receptors may mask a minority presence of histamine H3 contractile receptors located on smooth muscle. The main relaxing factor released from the endothelium by mediation of histamine is nitric oxide, which may also exert an effect on vascular tone.

Animals↗