Polymorphisms of dopamine receptor genes and risk of visual hallucinations in Parkinson's patients.

BACKGROUND: Visual hallucinations (VHs) are frequent non-motor complication of Parkinson's disease (PD), associated to a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene (DR) variants and psychosis in Alzheimer's disease, addictions, schizophrenia, and bipolar disorder. However, there are only a few studies on DR variants and VHs in PD, which did not provide conclusive results. OBJECTIVES: The present study aimed to determine whether genetic differences of DR are associated with visual hallucinations (VHs) in a cohort of Parkinson's disease (PD) patients. METHODS: A case-control study of 84 PD subjects, 42 with and 42 without VHs,that were matched for age, gender, disease duration, and dopaminergic medication was conducted. Polymerase chain reaction for SNPs in both D1-like (DRD1A-48G [rs4532] and C62T [rs686], DRD5T798C [rs6283]) and D2-like DR (DRD2G2137A [rs1800497] and C957T [rs6277], DRD3G25A [rs6280] and G712C [rs1800828], DRD4C616G [rs747302] and nR VNTR 48bp) analyzed genomic DNA. RESULTS: Patients carrying allele T at DRD1C62T had an increased risk of VHs, expressed as OR (95 % CI, p value), of 10.7 (2.9-40, p = 0.0001). Moreover, patients with DRD1-48 GG and 62TT genotype displayed shorter time to VHs, whereas a longer time to VHs was found in subjects carrying the DRD4 CG alleles. CONCLUSIONS: PD patients with VHs display higher frequency of DR SNPs associated with increased D1-like activity and decreased D2-like activity. Our data are in line with associations reported in other neurodegenerative and psychiatric conditions. Results likely provide valuable information for personalizing pharmacological therapy in PD patients.

Use of herbal remedies by multiple sclerosis patients: a nation-wide survey in Italy.

Though recent progress in multiple sclerosis (MS) treatment is remarkable, numerous unmet needs remain to be addressed often inducing patients to look for complementary and alternative medicines (CAM), especially herbal remedies (HR). HR use, scarcely investigated in MS, may cause adverse reactions (AR) and interfere with conventional treatment. We performed a survey aimed at evaluating use and attitudes towards HR and factor associated to HR use. Other CAM use and attitudes have been investigated as well. Multiple-choice questionnaires were distributed to MS out patients attending 14 Italian referral Centers. Multivariable logistic regression was used to identify HR use determinants. Present/past HR use for either MS or other diseases was reported in 35.6 % of 2419 cases (95 % CI 36.0-40.0 %). CAM use was reported in 42.5 % of cases. Independent predictors of HR use were represented by higher education, geographic area, dissatisfaction with conventional treatment of diseases other than MS and benefit perception from CAM use. Both HR and CAM use were not always disclosed to the healthcare professional. In conclusion, HR and other CAM appear to be popular among MS patients. The involvement of the healthcare professionals appears to be scarce with potential risk of AR or interference with conventional treatments.

Breast density in NF1 women: a retrospective study.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in the NF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population. Mammograms from 98 NF1 women affected by NF1, and enrolled onto our monocentric BC screening program, were compared with those from 300 healthy subjects to verify differences in breast density. Mammograms were independently reviewed and scored by a radiologist and using a Computer-Aided Detection (CAD) software. The comparison of breast density between NF1 patients and controls was performed through Chi-squared test and with multivariable ordinal logistic models adjusted for age, body mass index (BMI), number of pregnancies, and menopausal status.breast density was influenced by BMI and menopausal status in both NF1 patients and healthy subjects. No difference in breast density was observed between NF1 patients and the healthy female population, even after considering the potential confounding factors.Although NF1 and a highly fibroglandular breast are known risk factors of BC, in this study, NF1 patients were shown to have comparable breast density to healthy subjects. The presence of pathogenic variants in the NF1 gene does not influence the breast density value.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

Placement of port-a-cath through the right internal jugular vein under ultrasound guidance.

PURPOSE: This study was undertaken to demonstrate the effectiveness of ultrasound (US)-guided placement of porta-cath (PC) through the right internal jugular vein (RIJV) by evaluating the onset of early and late complications. MATERIALS AND METHODS: From 30 June 2008 to 30 June 2011, we placed 695 port-a-caths in 694 patients with a mean age of 58 years. Exclusion criteria were active infection, bleeding disorders and life expectancy <6 months. The procedures were performed in the angiography suite under local anaesthesia. After US-guided puncture of the RIJV, the subcutaneous pocket was prepared, followed by tunnelling of the vein and closure of the surgical wound. In order to evaluate pneumothorax (PNX), all patients underwent chest X-ray a few hours after the end of the procedure unless there were clinical indications. We evaluated the technical success of the procedure and the rate of complications. RESULTS: Technical success was achieved in all cases. The device was kept in place for an average of 168 days. There was one case of PNX (0.14%) as shown on chest X-ray and five cases of late complications (0.70%): one case of intracatheter thrombosis (0.14%), two cases of disconnection between the reservoir and catheter (0.28%) and two cases of PC infection (0.28%). CONCLUSIONS: This procedure incurs very small number of complications compared with other positioning techniques using accesses such as the subclavian vein. Complications recorded in our study are comparable, in type and incidence, to those found by other authors, with the most frequent being device infection.

Selling androgenic anabolic steroids by the pound: identification and analysis of popular websites on the Internet.

Internet websites offering androgenic anabolic steroids (AAS) were identified and available products were examined. Keywords for the website search were: "anabolic steroids," "anabolic steroids buy," "anabolic steroid purchase." The first 10 websites offering AAS in the first 10 pages of results were considered. At least two AAS-containing products per website were selected. Thirty AAS-selling websites were identified, mainly located in the United States (46.7%) and Europe (30%). Most websites sold other anabolic/ergogenic products (clenbuterol, 76.7%; GH/IGF, 60.0%; thyroid hormones, 46.7%; erythropoietin, 30.0%; insulin, 20.0%) or products for AAS-related adverse effects (mainly: estrogen antagonists, 63.3%; products for erectile dysfunction, 56.7%; 5α-reductase inhibitors, 33.3%; anti-acne products, 33.3%). AAS were sold as medicines (69.6%) or as dietary supplements (30.4%). AAS in medicines were mainly: nandronole (20.4%), methandrostenolone (18.4%), and testosterone (12.2%). Dietary supplements contained mainly DHEA and included several fake compounds. Manufacturers were declared for 97.9% of medicines and 66.7% of dietary supplements; however, several manufacturers were not found on the Internet. Described benefits were usually few adverse effects and no estrogenicity. Toxicity was seldom reported and presented as mild. Recommended doses were two-fourfold higher than current medical recommendations. In conclusion, misleading information and deceiving practices were common findings on AAS-selling websites, indicating their deleterious potential for public health.

The role of human papilloma virus test in men: First exhaustive review of literature. / Evaluación del virus del papiloma humano en varones: primera revisión exhaustiva de la literatura.

Human papilloma virus (HPV) infection is the most common sexually transmitted infection worldwide. There is a high detection rate in sexually active young people but the risk, in males, persists over years. Currently, the American Center for Disease Control and Prevention does not recommend the evaluation of men for HPV and, the extant bibliography, backs up this stance for several reasons. Objective of the paper was to evaluate the usefulness of HPV detection methods for men; A comprehensive and exhaustive review of the literature was performed. Many are methods for HPV detection used in cervical cancer screening as well as in the study and management of patients with cytological alterations of the lower genital tract. Need for HPV detection methods in men are numerous: screening for both partner/gender; anogenital warts; recurrent respiratory papillomatosis; HPV-related cancer in men; fertility. No HPV test for men has been approved by the FDA, nor has any test been approved for detection of the virus in areas other than the cervix. Many are methods for HPV detection that have shown their usefulness in some of the pathologies associated with male HPV but, despite this, none of them has been approved for man.

Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation.

Peripheral blood lymphocytes (PBL) were obtained from HIV-1-infected patients at different stages of disease. The absolute number of IgM-, IgG-, and IgA-producing lymphocytes per 10(6) PBL was increased 2.8-, 3.4-, and 1.9-fold, respectively, compared with normal controls. 2-17% of IgG-secreting patient cells reacted with the gp160 envelope glycoprotein of HIV-1 (a 737-fold increase over background), while 1-9% reacted with p24 (140-fold over background). In addition to this HIV-specific B cell activation, the number of lymphocytes reactive with nonviral antigens such as DNA, myosin, actin, trinitrophenylated keyhole limpet hemocyanin, and ovalbumin was increased by a mean of 17.9-fold. Evidence suggests that the latter changes reflect an HIV-induced polyclonal B cell activation unrelated to the production of anti-HIV antibodies. For example, the proportion of IgG anti-gp160- and anti-p24-secreting lymphocytes declined in patients with advanced disease, whereas the number of B cells producing antibodies to non-HIV antigens rose. Moreover, CD4 cell count and T4/T8 ratio showed a significant inverse correlation with the degree of polyclonal activation but not with anti-HIV responsiveness. These observations demonstrate that both quantitative and qualitative changes in B cell activation accompany (and may be predictive of) disease progression in HIV-infected individuals.

A natural pharma standard supplement formulation to control treatment-related toxicity and oxidative stress in genitourinary cancer: a preliminary study.

OBJECTIVE: Oncological treatments are associated with toxicities that may decrease compliance to treatment in most genitourinary cancer patients. Supplementation with pharmaceutical-standardized supplement may be a supplementary method to control the side effects after chemo- and radiotherapy and the increased oxidative stress associated to treatments. This registry study evaluated a natural combination of supplements containing curcumin, cordyceps, and astaxanthin (Oncotris™) used as supplementary management in genitourinary cancer patients who had undergone oncological therapy. PATIENTS AND METHODS: Patients with genitourinary cancers (prostate or bladder malignancies) who had undergone and completed cancer treatments (radiotherapy, chemotherapy or intravesical immunotherapy with increased oxidative stress and residual symptoms) were recruited in this registry, supplement study. Registry subjects (n = 61) freely decided to follow either a standard management (SM) (control group = 35) or SM plus oral daily supplementation (supplement group = 26). Evaluation of severity of treatment-related residual side effects, blood count test, prostate-specific antigen (PSA) test and plasma free radicals (oxidative stress) were performed at inclusion and at the end of the observational period (6 weeks). RESULTS: Two patients dropped out during the registry. Therefore, the analysis included 59 participants: 26 individuals in the supplementation group and 33 in the control group. In the supplement group, the intensity of signs and symptoms (treatment-related) and residual side effects significantly decreased at 6 weeks: minimal changes were observed in controls. Supplementation with Oncotris™ was associated with a significant improvement in blood cell count and with a decreased level of plasmatic PSA and oxidative stress. CONCLUSIONS: Naturally-derived supplements, specifically Oncotris™ (patent pending), could support the body to overcome the treatment-related toxicities - and the relative oxidative stress in cancer patients.

Colonization by multidrug-resistant organisms in long-term care facilities in Italy: a point-prevalence study.

OBJECTIVES: To determine prevalence and risk factors for colonization by multidrug-resistant organisms (MDROs) in long-term care facility (LTCF) residents in Italy. Genotypes of MDRO isolates were investigated. METHODS: A point-prevalence study was conducted at 12 LTCFs located in four Italian cities (2 February to 14 March 2015). Rectal swabs, faeces and nasal/auxiliary swabs were cultured for extended-spectrum ß-lactamase (ESBL)- and/or carbapenemase-producing Enterobacteriaceae, Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA) respectively. Antimicrobial susceptibility testing, detection of ESBL and/or carbapenemase genes and molecular typing of MDROs were performed. Risk factors for colonization were determined by univariate and multivariate analysis. RESULTS: A total of 489 LTCF residents aged ≥65 years were enrolled. The prevalence of colonization by ESBL-producing Enterobacteriaceae, MRSA and C. difficile was 57.3% (279/487), 17.2% (84/487) and 5.1% (21/409) respectively. Carriage rate of carbapenemase-producing Enterobacteriaceae was 1% (5/487). Being bedridden was a common independent risk factor for colonization by all MDROs, although risk factors specific for each MDRO were identified. ESBL-producing Escherichia coli carriage was associated with the sequence type (ST) 131-H30 subclone, but other minor STs predominated in individual LTCF or in LTCFs located in the same city, suggesting a role for intrafacility or local transmission. Similarly, MRSA from LTCF residents belonged to the same spa types/ST clones (t008/ST8 and t032/ST22) commonly found in Italian acute-care hospitals, but infrequent spa types were recovered in individual LTCFs. The prevalent C. difficile PCR ribotypes were 356/607 and 018, both common in Italian acute-care hospitals. CONCLUSIONS: MDRO colonization is common among residents in Italian LTCFs.

Thyroid hormone and thyrotropin regulate intracellular free calcium concentrations in human polymorphonuclear leukocytes: in vivo and in vitro studies.

Intracellular free calcium concentrations (Ca++i) were studied in polymorphonuclear leukocytes (PMNs) from 13 athyreotic patients who had been previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice, when hypothyroid (visit 1) and after restoration of euthyroidism by L-T4 TSH-suppressive therapy (visit 2). PMNs from patients at visit 1 had significantly lower resting (Ca++)i levels compared to both visit 2 and controls. Values at visit 2 did not differ from those of the controls. Stimulus-induced (Ca++)i rise was also significantly blunted at visit 1 and normalized at visit 2, possibly through a differential contribution of distinct intracellular Ca++ stores, as suggested by the response pattern to the chemotactic agent, N-formyl-Met-Leu-Phe (fMLP), to the selective SERCA pump inhibitor, thapsigargine, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP). In vitro treatment of PMNs from healthy subjects with high TSH concentrations impaired intracellular Ca++ store function. Both resting (Ca++)i levels and fMLP-induced (Ca++)i rise increased in the presence either of low-concentration TSH or of T4, but effects of TSH and T4 were not additive. T3, rT3, and TRIAC had no effect. In conclusion, this study provides evidence for a direct relationship between thyroid status and (Ca++)i homeostasis in human PMNs, mainly related to direct actions of TSH and T4 on these cells.

Anti-inflammatory effects exerted by Killox®, an innovative formulation of food supplement with curcumin, in urology.

OBJECTIVE: In this Open Controlled Trial we administered an innovative formulation of food supplement with curcumin (Killox®) to test its efficacy, safety and compatibility with other drugs, in the therapy of post-surgery complications of transurethral resection of prostate (TURP) and transurethral resection of bladder (TURB), and in the prevention of late complications. Furthermore, Killox® effects were verified in subjects with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Killox® was administered to 40 TURP patients for 20 days, to 10 TURB patients for 10 days and to 30 BPH patients for 60 days. The study was an open controlled trial, approved by the internal Review Board, with a completely independent set of retrospective observations. RESULTS: In the subjects who underwent surgery the treatment warded off postoperative and late complications, whereas among controls, without anti-inflammatory therapy after surgery until one week later, 21 (52.5%) out of 40 TURP subjects and 4 (40%) out of 10 TURB subjects were still found with symptoms of inflammation and urinary burning, and they had to be treated with nonsteroidal anti-inflammatory drugs (NSAIDs) for seven days. Moreover among controls 2 in TURP group presented an urethral stricture, and no one in TURB group. Killox® patients did not report any adverse effect and the therapy was well tolerated, instead among 21 control subjects, who were treated with NSAIDs, 7 reported nausea and epigastric pain. Also in BPH patients the product was effective in a satisfying manner, shortening the duration of irritation symptoms. Noteworthy, Killox® administration did not modify the efficacy of the other treatments. The effect of Killox® was found statistically significant vs controls. CONCLUSIONS: The therapeutic activity and safety of Killox® in urology allow physicians to administer a new efficient product in substitution of NSAIDs.

Surgical treatment of Peyronie's disease with small intestinal submucosa graft patch.

The objective of the study was to report our results using a porcine small intestinal submucosa graft (Surgisis ES, Cook Medical) for tunica albuginea substitution after plaque incision. We retrospectively evaluated patients surgically treated at our institution for Peyronie's disease (PD) by means of plaque incision and porcine small intestinal submucosa grafting (Surgisis) between 2009 and 2013. At the same time a literature review was conducted, searching for similar reports and results. Forty-four patients were identified who had been diagnosed with PD between 2009 and the beginning of 2013, and had been treated with corporoplasty, plaque incision and grafting with Surgisis for a severe curvature of the penis. Curvature of the penis was dorsal in 40 patients (90%) and laterally on the right in 4 patients (10%). Mean duration of surgery was 165 min (range 90-200). Mean size of the graft was 6.5 cm(2) and the mean follow-up was 19.2 months (range 11-48). In patients with severe curvature of the penis due to PD and the need for corporoplasty with plaque incision and graft placement, Surgisis represents a good option with a low risk of complications, below the rate described with previously investigated graft tissues.

Calcium-channel blockers and gastrointestinal motility: basic and clinical aspects.

Several calcium-channel blockers currently in use for the treatment of cardiovascular disorders have recently been tested for their effects on gastrointestinal motility. The rationale for this approach centers on the concept that calcium-channel blockers are at least as potent in inhibiting intestinal smooth muscle as in relaxing vascular smooth muscle. This review will give an outline of the most recent findings on the role of calcium and calcium channels in smooth muscle and neuronal function in the digestive system. It will also consider the mechanisms by which calcium-channel blockers may affect gastrointestinal motility and assess potential clinical applications in gastroenterology. The main goal for researchers in this field will be the development of gut-selective agents, with no cardiovascular side effects.

Adrenergic mechanisms in the control of gastrointestinal motility: from basic science to clinical applications.

Over the years, a vast literature has accumulated on the adrenergic mechanisms controlling gut motility, blood flow, and mucosal transport. The present review is intended as a survey of key information on the relevance of adrenergic mechanisms modulating gut motility and will provide an outline of our knowledge on the distribution and functional role of adrenoceptor subtypes mediating motor responses. alpha1-Adrenoceptors are located postsynaptically on smooth muscle cells and, to a lesser extent, on intrinsic neurons; alpha2-adrenoceptors may be present both pre- and postsynaptically, with presynaptic auto- and hetero-receptors playing an important role in the modulation of neurotransmitter release; beta-adrenoceptors are found mainly on smooth muscle cells. From a clinical standpoint, adrenoceptor agonists/antagonists have been investigated as potential motility inhibiting (antidiarrheal/antispasmodic) or prokinetic agents, although at present their field of application is limited to select patient groups.

Diazepam-binding inhibitor-derived peptides induce intracellular calcium changes and modulate human neutrophil function.

We studied the effects of two diazepam-binding inhibitor (DBI)-derived peptides, triakontatetraneuropeptide (DBI 17-50, TTN) and eiksoneuropeptide (DBI 51-70, ENP), on cytosolic free Ca2+ concentrations ([Ca2+]i), chemotaxis, superoxide anion (O2-) generation, and phagocytosis in human neutrophils. Both TTN and ENP induced a rapid and transient rise of [Ca2+]i. The effect of TTN depended on the presence of extracellular Ca2+, whereas the effect of ENP also persisted after extracellular Ca2+ chelation. TTN induced neutrophil chemotaxis, stimulated O2- generation, and enhanced phagocytosis. ENP did not affect cell migration and oxidative metabolism but enhanced phagocytosis. Both peptides modulated N-formyl-methionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced O2- generation. Because neutrophils express benzodiazepine receptors of the peripheral type (pBRs) and DBI-derived peptides may interact with such receptors, we investigated the possible role of pBRs in TTN- or ENP-induced effects. The synthetic pBR ligand RO 5-4864 increased [Ca2+]i through extracellular Ca2+ influx and this effect was prevented by the pBR antagonist PK-11195. RO 5-4864, however, was ineffective on neutrophil migration and O2- generation and only slightly affected phagocytosis. Moreover, PK-11195 delayed the [Ca2+]i rise induced by TTN but did not significantly affect its extent, and had no effect on the [Ca2+]i rise induced by ENP. We conclude that DBI-derived peptides induce [Ca2+]i changes and modulate neutrophil function mainly through pBR-independent pathways. In view of the wide cell and tissue distribution of DBI in the brain and in peripheral organs, modulation of neutrophil function by DBI-derived peptides may be relevant for both the neuroimmune network and the development and regulation of the inflammatory processes.

Neural and endogenous catecholamines in the bone marrow. Circadian association of norepinephrine with hematopoiesis?

Members of our research team have recently reported that adrenergic agents may affect hematopoiesis via alpha1-adrenoceptors present on bone marrow B cell precursors. In this paper we demonstrate that murine bone marrow contains a substantial amount of catecholamines. Norepinephrine (NE) and dopamine (DA) exhibited a daily rhythmicity, with peak values observed during the night. The rhythm was disrupted by chemical sympathectomy, whereas epinephrine (E) showed no rhythmicity or sensitivity to 6-hydroxydopamine. High and low values of NE and DA were associated with high and low values of their metabolites, which indicated a rhythmic catecholamine release. NE, but not DA or E, was positively associated with the proportion of cells in the G2/M and S phases of the cell cycle. Moreover, NE and DA were found in both short-term and long-term bone marrow cultures as well as in human or murine B lymphoid cell lines. These findings indicate that endogenous catecholamines in the bone marrow have both neural and cellular origins. The neural input shows a daily rhythm and may be implicated in the regulation of hematopoiesis.

Endogenous catecholamine synthesis, metabolism storage, and uptake in human peripheral blood mononuclear cells.

Evidence has been obtained that peripheral blood mononuclear cells contain dopamine, norepinephrine, epinephrine, and their metabolites. Pharmacologic inhibition of tyrosine hydroxylase or monoamine oxidase profoundly affected intracellular catecholamines (CTs) and their metabolites, indicating that these cells are able to synthesize and breakdown CTs. The sensitivity of intracellular CTs to reserpine and the presence of CTs in the extracellular medium suggest that CTs are stored and released. Moreover, the increase of extracellular CTs in the presence of monoamine uptake blockers point to the presence of functional uptake mechanisms. Altogether, these results indicate the existence of a CT lifecycle in human mononuclear cells and warrant further studies to investigate the role of adrenergic autoregulatory mechanisms in modulation of the immune response and in the pathogenesis of diseases involving the immune system.

Inhibitory effects of SR 58611A on canine colonic motility: evidence for a role of beta 3-adrenoceptors.

1. In order to clarify whether atypical or beta 3-adrenoceptors can modulate canine colonic motility in vivo, we studied the effects of SR 58611A (a selective agonist for atypical beta-adrenoceptors) alone and after pretreatment with beta-adrenoceptor antagonists on colonic motility in the conscious dog. The gastrocolonic response (postprandial increase in motility) was monitored by means of electrodes and strain-gauge force transducers chronically implanted along the distal colon. In some experiments, heart rate was also measured. The possible role of beta 3-adrenoceptors in mediating the effects of SR 58611A was also tested in vitro in circular muscle strips taken from the canine distal colon. 2. Intravenous infusion of SR 58611A, ritodrine or isoprenaline at doses inducing the same degree of tachycardia inhibited the gastrocolonic response to a different extent, with SR 58611A and ritodrine being more effective than isoprenaline. 3. In a dose-response study, SR 58611A was more potent in inhibiting colonic motility than in inducing tachycardia: the ED35 values for inhibition of colonic motility and induction of tachycardia were 23 and 156 micrograms kg-1, i.v., respectively. 4. The inhibitory effect of SR 58611A 100 micrograms kg-1, i.v., on the gastrocolonic response was reversed by alprenolol (non-selective beta-adrenoceptor antagonist), but resistant to CGP 20712A (beta 1-adrenoceptor antagonist) or ICI 118551 (beta 2-adrenoceptor antagonist). 5. In vitro, SR 58611A concentration-dependently relaxed circular muscle strips, an effect that was competitively antagonized by alprenolol with a pA2 value of 7.1, but resistant to CGP 20712A (100 nM), ICI 118551 (100 nM) or tetrodotoxin (1 microM). 6. The present study provides strong functional evidence for a role of atypical or beta 3-adrenoceptors in the modulation of canine colonic motility both in vivo and in vitro by an inhibitory effect most likely at the smooth muscle level.