Imported occupational lead poisoning: report of four cases.

BACKGROUND: In most industrialized countries, occupational lead poisoning has become increasingly rare, however this metal remains a serious health hazard in the rest of the world. REPORT OF CASES: We observedfour male patients (aged 35 / 54 years) who had suffered recurrent abdominal pain due to recent lead exposure (for 7 to 13 months) in two Chinese battery recycling plants. On their return to Italy, three of them presented normocytic, normochromic anaemia. The diagnosis was confirmed by high lead levels in the blood and urine, decreased erythrocyte delta-aminolevulinic acid dehydratase (ALA-D), raised erythrocyte zinc protoporphyrin (ZP), and elevated urinary excretion of b-aminolevulinic acid (ALA-U) and porphyrins. Chelation with EDTA resulted in increased urinary lead excretion, improvement of the clinical picture, decreased ZP, and progressive normalization of the other lead biomarkers (Pb-B, ALA-D, ALA-U, urinary porphyrins). CONCLUSIONS: Temporary work in developing countries may result in imported lead poisoning. Differential diagnosis of this unusual condition requires careful medical history collection and specific toxicological analysis. Preventive measures for workers going abroad are needed.

[Malignant mesothelioma: analysis of a hospital case series]. / Mesotelioma maligno: analisi di una casistica ospedaliera.

The 2000-2010 case record of our Institute includes 77 cases of malignant mesothelioma (MM) [67 pleural (40 males, 27 females; mean age 63.9 years), 9 peritoneal (7 males, 2 females; 67.9 years) and one testicular (38 year-old man)], often associated, with various degree of probability, to previous asbestos exposure (occupational or environmental). Twenty-four patients with pleural MM had undergone surgery (12 pleural decortication and 12 pneumonectomy), with median survival, respectively, of 14 +/- 4.33 (standard error) and 38 +/- 4.27 months, longer than that recorded without surgery (8 +/- 0.94 months). Four peritoneal cases underwent peritonectomy with hyperthermic intraoperative chemotherapy: one is still alive 20 months after diagnosis, the others died at 8, 18 and 36 months. The testicular case is still living 6 years after radical orchidectomy. In conclusion, due to past asbestos use, MM is often observed in the current clinical practice. Patients treated surgically present longer survivals.

[Multidisciplinary protocol for work resumption after occupational osteoarticular injury: case record]. / Protocollo interdisciplinare per il reinserimento lavorativo dopo infortunio osteoarticolare sul lavoro: casistica clinica.

The results obtained with a protocol aimed at work resumption after occupational osteoarticular injury and subsequent rehabilitation are presented: 159 patients (102 males and 57 females: mean age 43.7 years) were evaluated by the physiatrist and the occupational physician, providing indications based on their functional capabilities and task features. After 6 months, 105 out of 130 subjects available for telephonic follow-up (80.7%) had returned to work (8 after changing tasks, 7 part-time). The mean time for work resumption was 9.4 days for those who resumed working completely, 31.4 days for the others. After 12 months, the percentage of working patients (76 out of 93: 81.7%) was superimposable, indicating that the rehabilitation beneficial effect is maximal in the short-medium period. On the whole, the data prove the efficacy of the multidisciplinary rehabilitative approach.

[Return to work after occupational osteoarticular injury: presentation of a multidisciplinary protocol and preliminary data]. / Reinserimento lavorativo dopo infortunio osteoarticolare sul lavoro: presentazione di un protocollo interdisciplinare e dati preliminari.

A protocol for work resumption after occupational osteoarticular injury and subsequent rehabilitation is presented: 97 patients (68 males and 29 females; mean age 42 years) were evaluated by the physiatrist and the occupational physician, providing indications based on their functional capabilities and task features. Up to date, 38 underwent follow-up at 6 months: 30 had returned to work (3 after changing tasks, 4 part-time). The mean time for work resumption was 15 days for the 26 subjects who resumed working completely, 1 month for the 4 who resumed partially. These data are encouraging, and highlight the importance of a multidisciplinary rehabilitative approach to facilitate return to work after occupational injuries.

Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.

BACKGROUND: Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma. OBJECTIVES: It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea. METHODS: Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m(3) for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained. RESULTS: In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 +/- 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 microM. Conversely, the response to the maximal concentration of carbachol (3 microM) was increased (p < 0.01). CONCLUSION: Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma.

[Objective assessment of risk factors of work-stress: first experience of application of the method OSFA(Objective Stress Factors Analysis)]. / La valutazione obiettiva dei fattori di rischio stress lavoro-correlati: prime esperienze applicative del metodo OSFA (Objective Stress Factors Analysis).

The OSFA (Objective Stress Factors Analysis) method is an approach to stress evaluation based on objective risk factors recording, according to the Italian law (legislative decree 81/08) as well as to national and international guidelines. The method evaluates the work conditions recognized as hazardous for the workers' psychophysical health. It comprises two main phases: phase A (company data analysis) and phase B (analysis of work-related stress conditions). Particularly, phase B is centred on the work conditions peculiar to the different organizational units, and it is conducted by means of structured interviews to experienced employees who know the specific company reality. The interviews, based on a 72 items questionnaire, take into consideration four main work aspects: organization, social environment, safety, and management. The final version of the instrument has been tested on 13 medium-small companies of Lumbardy (Italy), operating in various fields, with a number of employees ranging from 5 to 107 (median = 37). These first OSFA method experimentations allowed to verify its adequacy in relation to the exhaustiveness of the examined areas, the intelligibility of the items, and their capacity to discriminate the stress risk factors peculiar to the various productive activities. The preliminary results indicate that the described approach is easy to apply, and favourably accepted by employers and workers for its objectivity. Additionally, the OSFA method allows to plan preventive and ameliorative interventions, according to both the legislative decree 81/08 and the European agreement of October 8, 2004. Finally, the information obtained can represent the basis for a further stress risk evaluation through subjective evaluation methods.

Two cases of asbestosis and one case of rounded atelectasis due to non-occupational asbestos exposure.

Asbestos is a well-known cause of several neoplastic (malignant mesothelioma, lung cancer) and non-neoplastic (asbestosis, pleuropathies) occupational diseases. Lower-level exposure in the general environment may induce pleural plaques and thickenings, and is associated with an increased mesothelioma risk. We present two patients (a 68-year-old man and a 72-year-old woman) who developed asbestosis (in association with pleural plaques and calcifications), and a 78-year-old man who developed rounded atelectasis (with pleural plaques and benign effusion), after living for several decades in the proximity of large Italian asbestos-cement plant. None of them had been exposed to asbestos occupationally. Besides living in a contaminated area, the woman used to clean the work clothes of her brother, who was employed in the local asbestos factory. The three cases indicate that non-neoplastic, long-latency asbestos-related diseases which are usually observed as a consequence of occupational exposures, may rarely develop in subjects living in contaminated geographical sites and buildings. These unusual environmental diseases raise the diagnostic problem of differentiating them from other, more common respiratory illnesses, and impose the duties of patient notification, assessment and follow-up, to assess the possibility of progression of disease and increased neoplastic risk.

Role of carbon monoxide in electrically induced non-adrenergic, non-cholinergic relaxations in the guinea-pig isolated whole trachea.

BACKGROUND AND PURPOSE: Nitric oxide (NO) and vasoactive intestinal peptide (VIP) are considered transmitters of non-adrenergic, non-cholinergic (NANC) relaxations in guinea-pig trachea, whereas the role of carbon monoxide (CO) is unknown. This study was designed to assess the participation of CO, and to investigate the localization of haem oxygenase-2 (HO-2), the CO-producing enzyme, in tracheal neurons. EXPERIMENTAL APPROACH: NANC responses to electrical field stimulation (EFS) at 3 and 10 Hz were evaluated in epithelium-free whole tracheal segments as intraluminal pressure changes. Drugs used were: L-nitroarginine methyl ester (L-NAME, 100 microM) to inhibit NO synthase (NOS), alpha-chymotrypsin (2 U ml(-1)) to inactivate VIP, zinc protoporphyrin-IX (ZnPP-IX, 10 microM) to inhibit HO-2, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM), a soluble guanylyl cyclase inhibitor. For immunohistochemistry, tissues were exposed to antibodies to PGP 9.5, a general neuronal marker, HO-2 and NOS, and processed with an indirect immunofluorescence method. KEY RESULTS: alpha-Chymotrypsin did not affect NANC relaxations. ODQ inhibited NANC responses by about 60%, a value similar to that obtained by combining L-NAME and ZnPP-IX. The combination of ODQ, L-NAME and ZnPP-IX reduced the responses by 90%. Subpopulations of HO-2 positive neurons containing NOS were detected in tracheal sections. CONCLUSIONS AND IMPLICATIONS: In the guinea-pig trachea, NANC inhibitory responses at 3 and 10 Hz use NO and CO as main transmitters. Their participation is revealed following inhibition of NOS, HO-2 and soluble guanylyl cyclase. The involvement of CO as a relaxing transmitter paves the way for novel therapeutic approaches in the treatment of airway obstruction.

[Silicoasbestosis: report of three cases]. / Silicoasbestosi: presentazione di tre casi clinici.

Silicoasbestosis is a rare pneumoconiosis due to the combined sclerosing effect of crystalline silica and asbestos fibres. We present here three cases (males, age: 66-75 years), recently reported to the judicial and workers' compensation authorities. The exposures occurred in the building and siderurgic industries, several years before retirement. The radiological pictures were characterized by diffuse nodular opacities, interstitial alterations, emphysema, pleuric plaques and thickenings. The patients described show that, still nowadays, silicoasbestosis may be observed in the clinical setting. Accurate occupational and environmental anamnesis are helpful for the correct diagnosis which, in turn, is important for prognosis and treatment, and in relation to medicolegal issues.

[Exposure to ammonium persulphate by inhalation: effect on the NANC inhibitory neurotransmitters in the guinea pig trachea]. / Esposizione inalatoria a persolfato d'ammonio: effetto sulle componenti del sistema NANC inibitorio della trachea di cavia.

To evaluate the effect of ammonium persulphate (AP) inhalation on NANC inhibitory (i-NANC) neurotransmitters of guinea pig airways, we exposed eight guinea pigs to AP (1 mg/m3), by aerosol inhalation for 30 minutes daily for three weeks. Control animals inhaled saline aerosol. After the last exposure, the isolated trachea was mounted in an organ bath and electrically stimulated in the presence of hyoscine, piperoxane and propranolol. The i-NANC responses were evaluated as decreases in intraluminal pressure and expressed as area under the curve (AUC, Pa x seconds). The isolated tracheae were treated with a-chymotrypsin, L-NAME, zinc protoporphyrin IX and ODQ, that inhibit the production or action of the single neurotransmitters, like peptides, NO and CO. In the exposed individuals, the NANC relaxations were below 50%, as compared to controls (P < 0.01). NO and CO were the neurotransmitters responsible for all the i-NANC responses, in similar proportions either in exposed individuals or in controls. In conclusion, ammonium persulphate exposure impairs the i-NANC control of airway tone without specifically affecting any neurotransmitter.

[Rhabdomyolysis in a worker exposed to paraffinic mineral oils. Unusual association with bronchiolitis obliterans and organizing pneumonia (BOOP)]. / Rabdomiolisi in operaio esposto ad olii minerali paraffinici. Insolita associazione con bronchiolite obliterante e polmonite organizzativa (BOOP).

We describe a 29-year-old worker; exposed to metal dust, sawdust and paraffinic mineral oils in a factory producing accessories for leather articles and clothing, who came to observation with fever (39 degrees C), chest pain and marked increase of muscular enzymes. Chest computed tomography showed two areas of lung consolidation, that subsequently appeared enlarged with central escavation. Lung biopsy lead to the diagnosis of BOOP. The case has been reported to the judicial and workers' compensation authorities as probable occupational toxic myopathy. Indeed, exposure to paraffinic mineral oils is a known, though unusual, cause of rhabdomyolysis. The association with BOOP has never been previously described.

[Exercise electrocardiography in the sanitary surveillance of workers with physical strain]. / Elettrocardiografia da sforzo nella sorveglianza sanitaria di lavoratori con impegnativo dispendio energetico.

To evaluate the opportunity of exercise electrocardiography (ECG) in the sanitary surveillance of workers with physical strain, we estimated the energy consumption of the duties of 22 electrical workers (males; age: 35-56 years). They subsequently underwent Treadmill exercise ECG, determining for each worker the maximal METs (multiples of basal metabolism) and the critical potency (P(CRIT)). In one subject, myocardial ischemia arose 9 minutes after the beginning of the test. The others interrupted the test after 7-13 minutes for tiring; 5 of them showed ventricular extra systoles, paired or isolated. Twelve subjects presented arterial hypertension, at rest and/or during exercise. Ergonomic analysis revealed that the occupational duties were between 1.5 and 8.0 METs. The energy consumption of the job on the whole was 4-6 METs (medium intensity). The maximal METs reached by the examined subjects were between 8.8 and 15.6; however, only 11 workers went reassuringly over the 4 METs required by duty analysis at P(CRIT). One subject was declared unfit for the job, and a judgement of partial idoneity was expressed for 3 workers. Preventive and therapeutic indications were given to 12 subjects. Aerobic training was suggested to 10 workers. The study indicates that an ergonomic evaluation is advisable for the most energy consuming occupational duties. In such cases, the sanitary surveillance should include a cardiologic assessment with exercise ECG, reproducing the physical strain of the specific job.

[Analysis of a case series of workers with mobbing syndrome]. / Analisi di una casistica di lavoratori con patologia da mobbing.

Mobbing represents nowadays a major challenge for Occupational Medicine. We examined, during the last seven years, 253 patients who asked medical assistance for psychopathological problems by them ascribed to mobbing in the working environment. All patients underwent occupational health visit, psychological counselling (including personality tests administration), and psychiatric evaluation. A clinical picture probably due to mobbing was diagnosed in 37 workers: 2 cases of Post-Traumatic Stress Disorder (PTSD), 33 of Adjustment Disorder (AD), and 2 of anxiety disorder. Regarding mobbing typology, we found 19 cases of vertical mobbing (by an employer/manager to employees), 14 cases of strategic mobbing, 3 cases of horizontal mobbing (among colleagues), and one non intentional mobbing. In conclusion, a pure mobbing syndrome was diagnosed in a lower proportion than that reported by other investigators. The described interdisciplinary approach appears useful for the diagnostic assessment of suspect mobbing cases, that in turn is crucial for prognosis and treatment, as well as in relation to medico-legal issues and work-related compensation claims.

[Management of occupational stress among patients with cardiac diseases]. / Gestione dello stress occupazionale in pazienti cardiopatici.

The object of our study was the evaluation of psycophysic condition, stress perception and coping in a sample of subject in cardiac rehabilitation. Our study recruited 48 worker patients (44 male, M = 50.5 +/- 8.8; 4 female, M = 50.8 +/- 8.7). They were submitted to: 1) cardiac evaluation and rehabilitation in DH regimen; 2) psychological assessment; 3) work's characteristic evaluation. The evaluation were made at the moment of recruitment and six month later 42 subjects went back to work after 81.8 +/- 49 days; 2 subjects had a worsening of their clinic conditions not consistent with an occupational resumption; 4 subjects didn't go back to work. In the 42 worker subjects we have find a significant decrease of anxiety (p < 0.019) and depression levels (p < 0.004); a significant improvement of Quality of Life perception in its physical (p < 0.000) and psychic aspects (p < 0.021) and an improvement about the ability to reorganize the work to better ménage stress (p < 0.012).

[Neurally-mediated syncope and occupational accidents: prevention strategies and case report]. / Sincope neuromediata e infortuni sul lavoro: strategie preventive e considerazioni su un caso clinico.

A bus driver came to our observation after an occupational traffic accident due to a syncopal event. The positive result of the tilt testing demonstrated the neurally-mediated nature of the syncope. The accident involved approximately 40 people (all the bus passengers), fortunately without severe injuries or deaths. The described episode indicates the need for a procedural algorithm, commonly approved, applicable in the field of prevention, for those occupational categories with severe accident risk. Indeed, the possibility exists to identify at least a part of the subjects predisposed to neurally-mediated syncope. Fundamental steps for such screening are history taking (looking for previous events, familiarity), the physical examination (useful, for example, to exclude orthostatic hypotension or carotid sinus syncope), and, in particular, the tilt testing, a diagnostic investigation recommended for all the workers who have had a previous syncope and are at high occupational accident risk. Moreover, the reported case recalls the need to strengthen the collaboration between the cardiologist and the occupational health physician.

[Accidents with risk of blood-borne infections in obstetricians: analysis of a hospital case records]. / Infortuni a rischio di malattie a trasmissione ematica nel personale ostetrico: analisi di una casistica ospedaliera.

BACKGROUND: Health care workers (HCW) are at high risk of accidental contact with biological fluids. In spite of extensive recom mendations concerning HCW accidents continue to be frequent and seem to be related to specific factors. OBJECTIVES: To evaluate the factors influencing risk of blood-borne infections in a particular category of HCW--obstetricians, and obtain information useful for prevention guidelines. METHODS: Data were obtained from the exposure registers of nursing and of the Emergency Ward staff where HCWfirst report after accidental contact with biological fluids. RESULTS: Accidents with risk of blood-borne diseases were more frequent in obstetricians with lower job seniority. They usually occurred between 8 a.m. and 4p. m., in the patient's room. The hands and face (particularly the eyes) were the body parts more often involved In almost half of the accidents, the worker was not wearing any personal protective device. Although some contacts were with infected blood, no seroconversion occurred. CONCLUSIONS: Obstetricians are at high risk of contact with biologicalfluids. Prevention requires a global strategy including the availability of protective and safety devices, as well as worker education, especially concerning the use of such devices, the application of the universal rules of prevention and the improvement of risk awareness. An adequate post-exposure management of accidents in also required

[Accident risk perception in high-voltage electrical maintenance workers]. / Percezione del rischio infortunistico in manutentori di linee elettriche ad alta tensione.

Promoting safety at work represents a fundamental task for achieving improvement in the quality of working life and preventing accidental injuries at work. Nevertheless, over the last few decades injuries at work have continued to constitute a significant problem. The aim of this study was to examine accident risk perception in a sample of 45 subjects employed in the electricity sector and to relate their risk perception to personality characteristics, cognitive functioning, and personal and professional history. The instruments used were: "Cognitive Behavioral Assessment 2.0", the "Workplace safety questionnaire" (an Italian questionnaire on safety at work), and a battery of neuropsychological tests. Findings show that electricity (current variability) was perceived as the most serious risk factor, while the most frequent perceived risk factors for accidents were accidental falls, cuts and bruises. The subjects of our sample showed a good awareness of risk perception, and good mood response and augmented psychophysiological activation during accidental injuries.

[Occupational risks among public safety and security forces]. / Rischi professionali nelle Forze dell'Ordine.

The present paper tries to identify the occupational risk factors (physical, chemical, biological, psychological), variable depending on jobs and tasks, to which the heterogeneous public safety/security workers are exposed. The fight against criminality and public order maintenance imply (sometimes fatal) traumatic risks, and expose to psychophysical and sensorial tiring, unfavourable macro- and microclimatic conditions, the risk of baropathy (air navigation, underwater activities), noise (generated by firearms and several other sources), vibrations and shakings (automatic weapons, transport vehicles), the risk of electric injury, ionizing (X and gamma rays) and non-inonizing (ultraviolet rays, microwaves and radiofrequencies, electromagnetic fields) radiations. Chemical hazards include carbon monoxide and other combustion products (fires, urban traffic), substances released in chemical accidents, tear gases, lead (firing grounds, metal works, environmental pollution), solvents, lubrificants and cutting oils (mechanic repair and maintenance), laboratory materials and reagents, irritant and/or sensitizing agents contained in gloves. The main biological risks are tetanus, blood-borne diseases (viral hepatitis, AIDS), aerogenous diseases (e.g., tuberculosis, Legionnaire's disease, epidemic cerebrospinal meningitis), dog- or horse-transmitted zoonosis. Finally, emotional, psychosomatic and behavioural stress-related disorders (e.g., burn-out syndrome, post-traumatic stress disorder) are typically frequent. The presence of numerous and diversified hazards among public safety/security forces imposes the adoption of occupational medicine measures, including risk assessment, health education, technical and environmental prevention, personal protective devices, sanitary surveillance and biological monitoring, clinical interventions (diagnosis, therapy and rehabilitation of occupational accidents and illnesses), prompt medico-legal evaluation of occupational-related compensation claims.

[Noise-induced hypoacusia in maintenance workers of high voltage electric lines]. / Ipoacusia da rumore in manutentori di linee elettriche ad alta tensione.

Noise-induced hypoacusia continues to represent an important issue in Occupational Medicine in relation to epidemiology, diagnostics, medicolegal issues and occupation related compensation claims. We present the clinical and audiometric findings of 45 maintenance workers of high tension electric lines, undergoing medical surveillance. Noise-induced hearing loss was diagnosed in 49% of cases ("pure" in 27% and mixed--with the concurrence of other causes--in 22% of cases). These unexpected data indicate that electric lines maintenance should be considered a high risk occupation for noise-induced damage, and confirm the need of enforcing current protective laws.

The interaction of antidepressant drugs with central and peripheral (enteric) 5-HT3 and 5-HT4 receptors.

1. A combined study of receptor binding in central neuronal cell membranes and functional responses in isolated segments of guinea-pig small intestine allowed characterization of the interaction of four antidepressant drugs with central and peripheral 5-HT3 and 5-HT4 receptors. 2. Clomipramine, paroxetine and fluoxetine inhibited [3H]-DAU 6215 binding to 5-HT3 recognition sites in NG 108-15 cells with IC50 values in the range 1.3-4 microM. Litoxetine had an IC50 of 0.3 microM. The specific binding of [3H]-GR 113808 to 5-HT4 recognition sites in pig striatal membranes was inhibited by all four antidepressants with negligible potency (IC50 values > or = 20 microM). 3. In whole ileal segments, concentration-response curves to 5-HT were biphasic, with the high- and low-potency phases involving 5-HT4 and 5-HT3 receptors, respectively. Curves to 2-methyl-5-hydroxytryptamine (2-methyl-5-HT: a 5-HT3 receptor agonist) and 5-methoxytryptamine (5-MeOT: a 5-HT4 receptor agonist) were monophasic. All antidepressants were used at concentrations lacking anticholinoceptor properties, as demonstrated in both electrically stimulated longitudinal muscle-myenteric plexus preparations (LMMPs) and in unstimulated LMMPs following addition of acetylcholine (100 nM). 4. Fluoxetine (0.1-1 microM) and litoxetine (0.3-3 microM) antagonized both the high- and low-potency phases of the 5-HT curve. Schild analysis for the low-potency phase yielded pA2 estimates of 6.6 +/- 0.3 (Schild slope of 1.1) and of 6.6 +/- 0.1 (Schild slope of 1.1), respectively. At higher concentrations (3 microM), fluoxetine markedly inhibited the 5-HT response maximum. Clomipramine (10-300 nM) inhibited, by a mechanism independent of concentration, both phases of the 5-HT curve with a reduction of the maximum response. Paroxetine (1 microM) was ineffective on the high-potency phase, but caused a rightward shift of the low-potency phase (pKB: 6.1 +/- 0.01). 5. Responses to 2-methyl-5-HT were inhibited by 1 microM fluoxetine (pKB: 5.4 +/- 0.02). Like clomipramine(30 and 100 nM), litoxetine (1 and 3 microM) produced rightward displacements of 2-methyl-5-HT-induced contractions, which were virtually independent of antidepressant concentration (pKB values: 6.0 +/- 0.02 and 5.5 +/- 0.01, respectively). At higher concentrations, fluoxetine (3 microM) and clomipramine (300 nM)markedly reduced the 2-methyl-5-HT response maximum. Paroxetine (1 micro M) was ineffective.6. Responses to 5-MeOT were shifted to the right by fluoxetine (0.1-1 micro M) and litoxetine (1 and 3 microM)in a concentration-dependent manner. At higher concentrations, fluoxetine (3 microM) markedly reduced the 5-MeOT response maximum, an effect also observed with 100 and 300 nM clomipramine. Paroxetine(1 microM) was ineffective.7. In unstimulated LMMPs, the excitatory effects evoked by 5-HT, 2-methyl-5-HT and 5-MeOT and the antagonism produced by 300 nM clomipramine were comparable to those obtained in whole ileal segments. This suggests that 5-HT contained in the mucosa of whole preparations does not interfere with agonist-induced contractile responses and with the inhibitory effect of antidepressant drugs.8. In conclusion, our results show that clomipramine, fluoxetine, paroxetine and litoxetine possess low to moderate potency/affinity at both central and peripheral (enteric) 5-HT3 receptors. In contrast, all four antidepressants are virtually ineffective at central 5-HT4 receptors. Inhibition of 5-HT4 receptor mediated ileal contractions by fluoxetine, litoxetine and clomipramine may result from allostericant agonism or, more likely, from post-receptor blockade of second messenger generation. The interaction of antidepressants with central and peripheral 5-HT3 and 5-HT4 receptors may be relevant for both potential therapeutic action and adverse effects at gastrointestinal level.