Haematobia irritans parasitism of F1 yak × beef cattle (Bos grunniens × Bos taurus) hybrids.

The horn fly Haematobia irritans (Diptera: Muscidae) is a blood obligate ectoparasite of bovids that causes annual losses to the U.S. beef cattle industry of over US$1.75 billion. Climate warming, the anthropogenic dispersion of bovids and the cross-breeding of beef cattle with other bovid species may facilitate novel horn fly-host interactions. In particular, hybridizing yaks [Bos grunniens (Artiodactyla: Bovidae)] with beef cows (Bos taurus) for heterosis and carcass improvements may increase the exposure of yak × beef hybrids to horn flies. The present paper reports on the collection of digital images of commingled beef heifers (n = 12) and F1 yak × beef hybrid bovids (heifers, n = 7; steers, n = 5) near Laramie, Wyoming (∼ 2200 m a.s.l.) in 2018. The total numbers of horn flies on beef heifers and F1 yak × beef heifers [mean ± standard error (SE): 88 ± 13 and 70 ± 17, respectively] did not differ significantly; however, F1 yak × beef steers had greater total horn fly abundance (mean ± SE: 159 ± 39) than female bovids. The present report of this experiment is the first such report in the literature and suggests that F1 yak × beef bovids are as susceptible as cattle to horn fly parasitism. Therefore, similar monitoring and treatment practices should be adopted by veterinarians, entomologists and producers.

Transparency and sustainability in global commodity supply chains.

Over the last few decades rapid advances in processes to collect, monitor, disclose, and disseminate information have contributed towards the development of entirely new modes of sustainability governance for global commodity supply chains. However, there has been very little critical appraisal of the contribution made by different transparency initiatives to sustainability and the ways in which they can (and cannot) influence new governance arrangements. Here we seek to strengthen the theoretical underpinning of research and action on supply chain transparency by addressing four questions: (1) What is meant by supply chain transparency? (2) What is the relevance of supply chain transparency to supply chain sustainability governance? (3) What is the current status of supply chain transparency, and what are the strengths and weaknesses of existing initiatives? and (4) What propositions can be advanced for how transparency can have a positive transformative effect on the governance interventions that seek to strengthen sustainability outcomes? We use examples from agricultural supply chains and the zero-deforestation agenda as a focus of our analysis but draw insights that are relevant to the transparency and sustainability of supply chains in general. We propose a typology to distinguish among types of supply chain information that are needed to support improvements in sustainability governance, and illustrate a number of major shortfalls and systematic biases in existing information systems. We also propose a set of ten propositions that, taken together, serve to expose some of the potential pitfalls and undesirable outcomes that may result from (inevitably) limited or poorly designed transparency systems, whilst offering guidance on some of the ways in which greater transparency can make a more effective, lasting and positive contribution to sustainability.

Resonant generation of propagating second-harmonic spin waves in nano-waveguides.

Generation of second-harmonic waves is one of the universal nonlinear phenomena that have found numerous technical applications in many modern technologies, in particular, in photonics. This phenomenon also has great potential in the field of magnonics, which considers the use of spin waves in magnetic nanostructures to implement wave-based signal processing and computing. However, due to the strong frequency dependence of the phase velocity of spin waves, resonant phase-matched generation of second-harmonic spin waves has not yet been achieved in practice. Here, we show experimentally that such a process can be realized using a combination of different modes of nano-sized spin-wave waveguides based on low-damping magnetic insulators. We demonstrate that our approach enables efficient spatially-extended energy transfer between interacting waves, which can be controlled by the intensity of the initial wave and the static magnetic field.

Cross-Linked Fiber Network Embedded in Elastic Matrix.

The mechanical behavior of a three-dimensional cross-linked fiber network embedded in matrix is studied in this work. The network is composed from linear elastic fibers which store energy only in the axial deformation mode, while the matrix is also isotropic and linear elastic. Such systems are encountered in a broad range of applications, from tissue to consumer products. As the matrix modulus increases, the network is constrained to deform more affinely. This leads to internal forces acting between the network and the matrix, which produce strong stress concentration at the network cross-links. This interaction increases the apparent modulus of the network and decreases the apparent modulus of the matrix. A model is developed to predict the effective modulus of the composite and its predictions are compared with numerical data for a variety of networks.

Mortality, morbidity and evidence-based management amongst patients in regional New Zealand with severe left ventricular systolic dysfunction (1997-2011).

BACKGROUND: Heart failure and its management represents a significant health burden, the extent of which is poorly understood in regional New Zealand. AIMS: To investigate mortality, quality of life, hospitalisation, and evidence-based medical and device management of severe left ventricular (LV) systolic dysfunction in a regional New Zealand setting. METHODS: A retrospective case series was undertaken of 1126 patients with a LV ejection fraction <36% on transthoracic echocardiograms performed between 1 October 1997 and 31 March 2011 in Nelson Marlborough District Health Board. All-cause mortality and hospitalisation data were analysed for all participants. Substudies were undertaken regarding pharmacotherapy, demographics, implantable cardioverter-defibrillator implantation rates and quality of life based on the EQ-5D questionnaire and New York Heart Association class. RESULTS: Five-year cumulative survival was 44.5%. The mean annual medical admission rate was 204/100 000; 54.84% of which were readmissions in the same year. Prescription rates for angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, beta-blockers and spironolactone were 68.3%, 74.2% and 24.9%, respectively, with only 17.6%, 19.0% and 16.4% on maximum recommended doses. implantable cardioverter-defibrillator devices were inserted in 11.5% of eligible patients. Quality of life was impaired in patients <70 years relative to the age-approximated New Zealand index population. Mean EQ-5D visual analogue score was 72.6 ± 0.032 and self-reported New York Heart Association class 2.09 ± 0.107 CONCLUSION: Patients with severe LV systolic dysfunction in this regional New Zealand community experience similar mortality and first hospitalisation rates to those seen elsewhere in patients with clinical heart failure, but a greater number of readmissions. Medical and device therapy utilisation was suboptimal, and quality of life impaired, together supporting the need for a dedicated heart failure service.

A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis.

BACKGROUND: Alemtuzumab (CD52-specific humanized monoclonal antibody) was found to be an effective therapy for treatment-naive patients with relapsing-remitting multiple sclerosis. OBJECTIVE: Evaluate alemtuzumab's effects in patients with treatment-refractory relapsing-remitting multiple sclerosis. METHODS: Forty-five relapsing-remitting multiple sclerosis patients who experienced ≥2 relapses during 2 years prior to the study entry whilst receiving interferon therapy were administered 24 mg i.v. alemtuzumab/day for 5 days at baseline and 3 days 12 months later. Patients received premedication with 1 g i.v. methylprednisolone on days 1-3 at both times. RESULTS: After 2-year follow-up, the annualized relapse rate was reduced by 94% compared to pre-treatment levels, from 1.6 (2 years prior to treatment) to 0.17 for the 2 years following (P<0.0001). Moreover, 86% of patients showed stable or improved scores on the Expanded Disability Status Scale, and only 1 experienced an increase in disability lasting ≥6 months. The majority (70-88%) showed stable or improved leg, arm and cognitive function as measured by the Multiple Sclerosis Functional Composite. Serious adverse events observed in single patients were transient neutropenia and pneumonia, pulmonary emboli and deep vein thrombosis. Five patients developed clinical thyroid disorders but no opportunistic infections or cases of immune thrombocytopenic purpura were observed. CONCLUSIONS: Alemtuzumab effectively reduced relapse rates and improved clinical scores in patients with active relapsing-remitting multiple sclerosis not controlled by interferon therapy.

Effect of supplemental trace minerals on standard and novel measures of bull fertility.

Two studies were conducted to evaluate the effects of trace mineral supplementation on traditional and novel measures of bull fertility. In Experiment 1, 37 mature bulls received one of three dietary supplements daily for 71 d: 1) Supplement without Cu, Zn, and Mn (CON); 2) Supplement with Cu, Zn, and Mn sulfate (SULF); and 3) Supplement with basic Cu chloride, and Zn and Mn hydroxychloride (CHLR). In Experiment 2, 128 Angus or Angus-Hereford bull calves were maintained on a growing diet for 75 d (year 1) or 119 d (year 2) in Calan gate equipped pens without mineral supplementation. Bulls (n = 32 head/treatment) received one of four trace mineral supplements daily for 84 d: 1) Zn with no Cu (ZN), 2) Cu with no Zn (CU), 3) Cu and Zn (ZNCU), or 4) no Cu or Zn (CON). Bull fertility measures included a breeding soundness evaluation (BSE) and novel fertility measures conducted using flow cytometry. In mature bulls, final liver Zn concentration was positively correlated (P = 0.02) with sperm concentration (r = 0.31) and tended (P = 0.06) to be negatively correlated with acrosome damage (r = -0.39). Peripubertal bulls receiving ZNCU had greater ADG than bulls in the CU group (P = 0.05). Each BSE and novel fertility component improved from Day 0-84 in peripubertal bulls and were not affected (P > 0.10) by mineral supplementation. Bulls that received no supplement (CON) had greater (P < 0.01) percentage of sperm with distal midpiece reflex (6.9 vs 4.0% for CON and TM supplement, respectively) and Dag or Dag-like defect (2.6 vs 1.4% for CON and TM supplement, respectively) in their ejaculates. Sperm viability after 30 min of incubation were not affected by trace mineral supplementation, but after 3 h incubation, sperm viability tended to differ (P = 0.06) between treatments and tended to be less for CON bulls (48.5%) compared to ZNCU bulls (55.1%). Among contrast comparisons, trace mineral supplemented bulls had greater (P < 0.05) percentage of viable sperm at 3 h post collection and reactive oxygen resistant sperm than CON bulls. Addition of Zn to trace mineral containing Cu (ZNCU) improved (P < 0.05) percentage of sperm in the ejaculate with high mitochondrial energy potential and viable sperm with intact acrosome membrane. In summary, it appears the homeostasis mechanisms for bull trace mineral maintenance are extremely efficient and mineral supplementation of mature and peripubertal bulls did not have major improvements in any laboratory or chute-side measures of bull fertility, however bulls exposed to breeding or in environments with diet antagonists might respond differently.

Pre-synchronization of ovulation timing and delayed fixed-time artificial insemination increases pregnancy rates when sex-sorted semen is used for insemination of heifers.

This study was conducted to determine effects of pre-synchronization of ovulation timing among heifers and delayed fixed-time artificial insemination (TAI) with sex-sorted semen on proportion of heifers pregnant after TAI (PR/AI). Heifers were assigned to one of eight treatments: 1 and 2), 7-d CO-Synch + CIDR treatment regimen with administration of gonadotropin-releasing hormone and a CIDR insert on Day 0, prostaglandin F2α (PGF) at CIDR removal on Day 7, and TAI occurring 54 h later with conventionally processed (CTRL54-CNV) or sex-sorted semen (CTRL54-SEX); 3 and 4), same as CTRL54 but TAI delayed to 72 h with conventionally processed (CTRL72-CNV) or sex-sorted semen (CTRL72-SEX); 5 and 6), same as CTRL54 but additional administration of PGF on Day -7 and TAI with conventionally processed (PRE54-CNV) or sex-sorted semen (PRE54-SEX); 7 and 8), same as PRE54 treatments but TAI delayed to 72 h with conventionally processed (PRE72-CNV) or sex-sorted semen (PRE72-SEX). Proportion of heifers pregnant after TAI was greater (P ≤  0.02) with conventionally processed semen compared with sex-sorted semen, yet PR/AI did not differ (P =  0.14) between heifers in PRE72-CNV and PRE72-SEX groups. There were greater PR/AI in the PRE72-SEX (P =  0.03) than CTRL54-SEX group (46.1 % and 36.9 %) and there was no difference (P =  0.31) in PR/AI between CTRL54-CNV and PRE72-SEX groups (50.4 % and 46.1 %). In conclusion, pre-synchronization of ovulation timing among heifers combined with delayed TAI resulted in increased PR/AI with sex-sorted semen compared with the 7-d CO-Synch+CIDR treatment regimen.

Sex preselection in mammals? Separation of sperm bearing Y and "O" chromosomes in the vole Microtus oregoni.

The two sex determining sperm populations of the vole Microtus oregoni were separated according to DNA content by use of flow sorting instrumentation. Although the sperm were not viable, they should be useful for addressing the question of haploid expression of genes linked to sex chromosomes and for efficiently searching for biochemical markers that differentiate the two populations.

Design and testing of Electrostatic Aerosol in Vitro Exposure System (EAVES): an alternative exposure system for particles.

Conventional in vitro exposure methods for cultured human lung cells rely on prior suspension of particles in a liquid medium; these have limitations for exposure intensity and may modify the particle composition. Here electrostatic precipitation was used as an effective method for such in vitro exposures. An obsolete electrostatic aerosol sampler was modified to provide a viable environment within the deposition field for human lung cells grown on membranous support. Particle deposition and particle-induced toxicological effects for a variety of particles including standardized polystyrene latex spheres (PSL) and diesel exhaust emission particle mixtures are reported. The Electrostatic Aerosol in Vitro Exposure System (EAVES) efficiently deposited particles from an air stream directly onto cells. Cells exposed to the electric field of the EAVES in clean air or in the presence of charged PSL spheres exhibited minimal cytotoxicity, and their release of inflammatory cytokines was indistinguishable from that of the controls. For the responses tested here, there are no significant adverse effects caused neither by the electric field alone nor by the mildly charged particles. Exposure to diesel exhaust emissions using the EAVES system induced a threefold increase in cytokines and cytotoxicity as compared to the control. Taken together, these data show that the EAVES can be used to expose human lung cells directly to particles without prior collection in media, thereby providing an efficient and effective alternative to the more conventional particle in vitro exposure methods.

The role of polymorphisms at beta tubulin isotype 1 codons 167 and 200 in benzimidazole resistance in cyathostomins.

Cyathostomins are recognised as the primary parasitic pathogens of horses. Despite the use of benzimidazole (BZ) anthelmintics in horses for more than 40 years and widespread drug resistance in the field, the mechanisms of resistance to this drug class in cyathostomins are not fully understood. The results presented here constitute a detailed comparison of beta tubulin gene mutations and mRNA transcript levels in populations of BZ-susceptible (BZ-S) and -resistant (BZ-R) cyathostomins. Full-length cDNA sequences were generated from individual parasites of four (n=24) and two (n=19) cyathostomin species for isotypes 1 and 2, respectively. Levels of intra- and inter-specific nucleotide sequence variation were comparable with previous findings and single amino acid substitutions were observed at several locations. On comparison of BZ-S and BZ-R parasites, differences were consistently observed at only two sites, codons 167 and 200 of the beta tubulin isotype 1 gene. Four populations of parasites were genotyped at these two loci by pyrosequencing; one that was fenbendazole (FBZ)-sensitive (FBZ-rS), two that were FBZ-resistant (FBZ-R1 and -R2) and one that was oxibendazole-resistant (OBZ-R), as previously assessed by faecal egg count reduction tests. This analysis revealed statistically significant differences between FBZ-rS and FBZ-R populations at both loci and this was highly significant for codon 167. For the OBZ-R population, the only significant difference compared with the FBZ-rS population was observed at codon 200. These observations suggest that mutations at codons 167 and 200 are important in BZ resistance and raise the possibility that selection at different loci may occur in FBZ- and OBZ-resistant parasites. Multiple parasites (n=158) were genotyped for both codons 167 and 200, the majority of which showed homozygous 'resistant' mutations at one locus only and none showed homozygous 'resistant' genotypes at both loci. No significant differences in mRNA levels of beta tubulin isotypes 1 and 2 were observed between the FBZ-rS and FBZ-R1 populations.

Evaluation of a decision support system to predict preoperative investigations.

BACKGROUND: We have developed the 'Optimising Surgical Care and Assessment Record' (OSCAR), a clinical decision support system, to help nurses in predicting necessary preoperative investigations before surgery. OSCAR applies the hospital's protocols, which are based on the National Institute for Health and Clinical Excellence guidelines, to the patient's medical history and surgical details before recommending required investigations. METHODS: We selected case notes of 50 patients randomly from the OSCAR system that were recorded between October 2006 and January 2007. To form a reference standard, these case histories were anonymized and then sent to 10 consultant anaesthetists across the country. They were asked to study the case history and choose which tests they would carry out and which they would not. Then we have evaluated OSCAR's ability to predict the necessary investigations and the nurses' judgement, in comparison with the reference standard. RESULTS: OSCAR's ability to identify which investigations should be carried out, that is, its sensitivity, was 91.5% and its ability to identify which investigations not to carry out, that is, its specificity, was 82.7%. OSCAR was consistent in predicting investigations for differing severities of surgery, for ASA grade and gender. We were unable to demonstrate any overall difference between OSCAR and the nurse's ability to predict preoperative investigations. When combining the nurse's predictions with OSCAR's recommendations, an even greater sensitivity of 98.2% could be achieved. CONCLUSIONS: OSCAR's prediction algorithm cannot replace the nurse's judgement, but it can be used as a supplementary decision aid to promote consistency and improve accuracy.

Rat supraspinatus tendon expresses cartilage markers with overuse.

The goals of this study were to investigate the response of the rat supraspinatus tendon to overuse at the molecular level using transcriptional profiling, and to identify potential markers of tendinopathy. Adult rats were subjected to an overuse protocol that consists of downhill running (10% grade) at 17 m/min for 1 h/day, 5 days/week, for a total of either 1, 2, or 4 weeks. Another group of rats served as nonrunning time 0 controls. Transcriptional profiling was performed on the supraspinatus and patellar tendons using an Affymetrix rat genome array. A gene was considered to be differentially expressed if the p value from an ANOVA test was less than 0.01 and the difference between runners and controls was at least twofold at any time point. The supraspinatus tendon had increased expression of well-known cartilage genes such as col2a1, aggrecan, and sox9. These genes were not regulated in the patellar tendon, an internal comparator. Few genes associated with inflammation, or angiogenesis, were differentially expressed, and no significant change in the regulation of matrix metalloproteinases was detected. The results of this study suggest that by expressing more cartilage genes, the tendon is converting toward a fibrocartilage phenotype as a result of the repetitive loading and repeated compression of the tendon as it passes through the acromial arch.

Influence of post-insemination nutrition on embryonic development in beef heifers.

Previous studies have demonstrated that a decrease in nutrition immediately following AI reduces pregnancy success in beef heifers. The objective of this experiment was to determine if nutrient restriction following AI impacted early embryonic development among non-super ovulated heifers. Beef heifers in eight replications (Rep; Rep 1; n = 14, Rep 2; n = 15, Rep 3; n = 15, Rep 4; n = 14, Rep 5; n = 15, Rep 6; n = 15, Rep 7; n = 25, Rep 8; n = 25) across two locations (UMN, SDSU) were developed in a dry-lot and fed 125% NRC requirements from weaning to timed-AI (d 0). Heifers were timed-AI to a single sire in all replications. Immediately following AI, heifers were assigned, based on age, weight, and estrous response to one of two post-AI nutritional treatments. Half the heifers in each replication continued on the pre-insemination diet, serving as the control treatment (CON) and the remaining heifers were restricted to a sub-maintenance diet (RES). At UMN, heifers in the RES treatment were fed the same diet, but intake was limited to 80% NEm, while at SDSU, DMI remained the same, but diet composition was altered with the addition of straw to reduce NEm to 50% of requirements. On d 6, single embryos were collected nonsurgically and recovered embryos (CON; n = 46, RES; n = 42) were evaluated to determine quality (grade 1-9) and stage (1-4). Embryos were then stained and evaluated to determine the number of dead cells and total blastomeres. In Reps 1 through 6, concentrations of IGF-1 were assessed on d 0 and 6 and progesterone concentrations on d 4 and 6. Data were analyzed using the Mixed procedures of SAS. There were no treatment by Rep or treatment by location interactions for any embryo parameter evaluated, thus all data were pooled. Embryo stage and quality were improved (P < 0.01) in the CON (4.4 ± 0.16, 2.2 ± 0.19, respectively) compared to RES treatment (3.7 ± 0.16, 2.9 ± 0.19, respectively). Embryos in the CON treatment had greater total blastomeres (66.9 ± 5.05; P < 0.01) and tended to have a greater percentage of live cells (P < 0.10; 80.9 ± 4.19%) compared to RES (47.9 ± 5.41; 69.7 ± 4.39%, respectively). Progesterone and IGF-1 concentrations did not differ between treatments. In summary, nutrient restriction for 6 days immediately following AI resulted in poorer quality embryos that were delayed in stage of development, suggesting that immediate changes in nutritional status after insemination can alter early embryonic development.

Large-scale purification of human islets utilizing discontinuous albumin gradient on IBM 2991 cell separator.

A new method is described for the large-scale purification of human pancreatic islets with a discontinuous gradient of bovine serum albumin formed on an IBM 2991 cell separator. Fifteen human pancreases were processed, and after density-gradient centrifugation, a mean of 2643 islets/ml pancreatic digest were recovered with a mean purity of 63% and contained in 430 microliter mean vol. Viability of gradient-isolated islets was compared with that of non-density-gradient islets (handpicked) and showed no difference in function. This technique allows isolation of intact, viable human islets of Langerhans of sufficient purity for potential human transplantation.

Successful reversal of diabetes in nude rats by transplantation of isolated adult human islets of Langerhans.

A method is described in which the viability of isolated adult human islets of Langerhans can be assessed in vivo. The Rowett nude rat, made diabetic with streptozocin (STZ), has been used as the islet recipient in these studies. Although these animals are athymic and are able to accept xenogeneic grafts for prolonged periods, they are very susceptible to dehydration and infection once made diabetic. Therefore, a considerably shortened diabetes induction period was used. The basis of the study was to prepare pure adult human pancreatic islets that were cultured for 48 h. Nude rats were given 80 mg/kg i.v. STZ during islet isolation and were transplanted with 800-1000 islets under the renal capsule at 48 h. To monitor islet function, animals were bled regularly for random blood glucose measurements and were given a glucose tolerance test at day 20. The kidney containing the graft was removed on day 21 to allow histological assessment of the graft and to confirm that glucose control was due to the transplanted islets and was not secondary to reversion of the animal's own islets. Seven rats were transplanted, and five were deemed to have received viable human islets. Two rats that received islets from the same donor did not reverse their diabetes and were found by histology to have vacuolated islet structures with scant insulin-staining tissue under the kidney capsule. This method allows a definitive judgment of the ability of isolated adult human islets to reverse diabetes.

Using topical negative pressure therapy to resolve wound failure following perineal resection.

Elective resection of the rectum and perineum in a patient with recurrent squamous cell carcinoma of the anus resulted in significant wound failure. Full healing was achieved with topical negative pressure, with no recurrence of the cancer.

Understanding the patient's lived experience of neovascular age-related macular degeneration: a qualitative study.

PURPOSE: In industrialised populations age-related macular degeneration (ARMD) is the leading cause of visual disability of the elderly. Successful new treatment with anti-endothelial growth factors for neovascular-classified ARMD has led to a divergence in treatment and experiences of people ARMD. This study aimed to understand the participant's experience of neovascular ARMD, including ongoing treatment with anti-vascular endothelial growth factor. METHODS: Twenty-five participants from one clinical site were qualitatively interviewed to elicit their experiences of treatment for neovascular ARMD. RESULTS: Two major themes were identified. A life negotiated by neovascular ARMD captures the participants' experience of living with the condition and treatment regime for neovascular ARMD. The second major theme: Uncertainty displayed their appraisal of life, treatment and their perceived future. CONCLUSIONS: Anxieties concerning the injections, new limitations to lifestyles, and an uncertain future all emerged from the data analysis. However, thankfulness for the treatment, the importance of familiar patterns in treatments and recovery and a guarded optimism also emerged. Knowledge of the experiences, anxieties and concerns of this patient population can be used to inform clinical practice and lead to patient-centred care.

Cloning of the rat and human prostaglandin F2 alpha receptors and the expression of the rat prostaglandin F2 alpha receptor.

We have cloned the FP receptor from rat corpus luteum and human uterus cDNA libraries, respectively. The coding DNA sequence in the rat cDNA is 1101 bp and is similar to the mouse cDNA coding for a receptor protein of 366 amino acids. The human sequence shows a 5 bp deficiency in the 3' region, truncating the coding sequence to 359 amino acids. Northern blot analysis indicates highest expression in the ovary. Cell lines have been established giving stable expression of the FP receptor. Activation of the cloned FP receptor gave an increase in intracellular calcium, indicating signaling via phospholipase C-mediated phosphoinositide turnover. Using [3H]PGF2 alpha, binding of PGs showed the rank order of fluprostenol > PhXA70 > PGF2 alpha > or = PhXA85 > PGD2 > PGE2.

Differential effects of beta-adrenergic agonists on insulin secretion from pancreatic islets isolated from rat and man.

The selective beta 2-adrenergic agonist clenbuterol was ineffective as a stimulus for insulin secretion when isolated rat pancreatic islets were incubated with glucose at concentrations between 4 and 20 mM. Inclusion of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine led to potentiation of glucose-induced insulin secretion, but did not facilitate stimulation by clenbuterol. Furthermore, maintenance of isolated rat islets for up to 3 days in tissue culture also failed to result in the appearance of a secretory response to beta-agonists. By contrast, clenbuterol induced a dose-dependent increase in insulin release from isolated human islets incubated with 20 mM glucose. Clenbuterol did not increase the basal rate of insulin secretion (4 mM glucose) in human islets. Under perifusion conditions, the secretory response of human islets to clenbuterol was rapid, of similar magnitude to that seen under static incubation conditions and could be sustained for at least 30 min. The increase in insulin secretion induced by clenbuterol was inhibited by propranolol, indicating that the response was mediated by activation of beta-receptors. In support of this, a similar enhancement of glucose-induced insulin secretion was elicited by a different beta 2-agonist, salbutamol, in human islets. The results indicate that the B cells of isolated rat islets are unresponsive to beta-agonists, whereas those of human islets are equipped with functional beta-receptors which can directly influence the rate of insulin secretion.