Predicting Pharmacist Dispensing Practices and Comfort Related to Pre-exposure Prophylaxis for HIV Prevention (PrEP).

To identify factors associated with pharmacist dispensing practice and comfort counseling patients about pre-exposure prophylaxis for HIV prevention (PrEP). Cross-sectional 2016 census of Indiana managing pharmacists measured PrEP awareness, comfort dispensing and counseling patients. Modified Poisson models with robust error variance estimated relative risks and confidence intervals. 15.8% of 284 pharmacists had dispensed PrEP and 11.6% had consulted about it. Dispensing and comfort counseling were associated with confidence in knowledge about PrEP medication adherence and adverse effects of PrEP medication; awareness about PrEP before the survey, number of full time pharmacists in their pharmacy, and increases in new HIV cases from 2015 to 2016 in communities served. Comfort counseling about PrEP was associated with the belief that pharmacists can be an important resource for HIV and HCV treatment.

Gadolinium DTPA Enhancement Characteristics of the Rat Sciatic Nerve after Crush Injury at 4.7T.

BACKGROUND AND PURPOSE: Traumatic peripheral nerve injury is common and results in loss of function and/or neuropathic pain. MR neurography is a well-established technique for evaluating peripheral nerve anatomy and pathology. However, the Gd-DTPA enhancement characteristics of acutely injured peripheral nerves have not been fully examined. This study was performed to determine whether acutely crushed rat sciatic nerves demonstrate Gd-DTPA enhancement and, if so, to evaluate whether enhancement is affected by crush severity. MATERIALS AND METHODS: In 26 rats, the sciatic nerve was crushed with either surgical forceps (6- to 20-N compressive force) or a microvascular/microaneurysm clip (0.1-0.6 N). Animals were longitudinally imaged at 4.7T for up to 30 days after injury. T1WI, T2WI, and T1WI with Gd-DTPA were performed. RESULTS: Forceps crush injury caused robust enhancement between days 3 and 21, while clip crush injury resulted in minimal-to-no enhancement. Enhancement after forceps injury peaked at 7 days and was seen a few millimeters proximal to, in the region of, and several centimeters distal to the site of crush injury. Enhancement after forceps injury was statistically significant compared with clip injury between days 3 and 7 (P < .04). CONCLUSIONS: Gd-DTPA enhancement of peripheral nerves may only occur above a certain crush-severity threshold. This phenomenon may explain the intermittent observation of Gd-DTPA enhancement of peripheral nerves after traumatic injury. The observation of enhancement may be useful in judging the severity of injury after nerve trauma.

Ranking freshwater fish farms for the risk of pathogen introduction and spread.

A semi-quantitative model is presented to rank freshwater rainbow trout farms within a country or region with regards to the risk of becoming infected and spreading a specified pathogen. The model was developed to support a risk-based surveillance scheme for notifiable salmonid pathogens. Routes of pathogen introduction and spread were identified through a process of expert consultation in a series of workshops. The routes were combined into themes (e.g. exposure via water, mechanical transmission). Themes were weighted based on expert opinion. Risk factors for each route were scored and combined into a theme score which was adjusted by the weight. The number of sources and consignments were used to assess introduction via live fish movements onto the farm. Biosecurity measures were scored to assess introduction on fomites. Upstream farms, wild fish and processing plants were included in assessing the likelihood of introduction by water. The scores for each theme were combined to give separate risk scores for introduction and spread. A matrix was used to combine these to give an overall risk score. A case study for viral haemorrhagic septicaemia is presented. Nine farms that represent a range of farming practices of rainbow trout farms in England and Wales are used as worked examples of the model. The model is suited to risk rank freshwater salmonid farms which are declared free of the pathogen(s) under consideration. The score allocated to a farm does not equate to a quantitative probability estimate of the farm to become infected or spread infection. Nevertheless, the method provides a transparent approach to ranking farms with regards to pathogen transmission risks. The output of the model at a regional or national level allows the allocation of surveillance effort to be risk based. It also provides fish farms with information on how they can reduce their risk score by improving biosecurity. The framework of the model can be applied to different production systems which may have other routes of disease spread. Further work is recommended to validate the allocated scores. Expert opinion was obtained through workshops, where the outputs from groups were single point estimates for relative weights of risks. More formal expert opinion elicitation methods could be used to capture variation in the experts' estimates and uncertainty and would provide data on which to simulate the model stochastically. The model can be downloaded (in Microsoft(®)-Excel format) from the Internet at: http://www.cefas.defra.gov.uk/6701.aspx.

Zinc modulation of glycine receptors.

Glycine receptors are widely expressed in the mammalian central nervous system, and previous studies have demonstrated that glycine receptors are modulated by endogenous zinc. Zinc is concentrated in synaptic vesicles in several brain regions but is particularly abundant in the hippocampus and olfactory bulb. In the present study, we used patch-clamp electrophysiology of rat hippocampal and olfactory bulb neurons in primary culture to examine the effects of zinc on glycine receptors. Although glycine has been reported to reach millimolar concentrations during synaptic transmission, most previous studies on the effects of zinc on glycine receptors have used relatively low concentrations of glycine. High concentrations of glycine cause receptor desensitization. Our current results extend our previous demonstration that the modulatory actions of zinc are largely prevented when co-applied with desensitizing concentrations of glycine (300 µM), suggesting that the effects of zinc are dependent on the state of the receptor. In contrast, pre-application of 300 µM zinc, prior to glycine (300 µM) application, causes a slowly developing inhibition with a slow rate of recovery, suggesting that the timing of zinc and glycine release also influences the effects of zinc. Furthermore, previous evidence suggests that synaptically released zinc can gain intracellular access, and we provide the first demonstration that low concentrations of intracellular zinc can potentiate glycine receptors. These results support the notion that zinc has complex effects on glycine receptors and multiple factors may interact to influence the efficacy of glycinergic transmission.

The semantics of sexual behavior and their implications for HIV/AIDS research and sexual health: US and UK gay men's definitions of having "had sex".

Understanding the definition and meaning of the word "sex" has implications for sexual medicine, HIV/AIDS research, and clinical practices. Previous studies have reported variations in the definition of having "had sex" and the necessity of using behaviorally specific terminology when taking sexual histories and assessing sexual risk. The purpose of the current study is to assess gay men's definitions of what constitutes having "had sex." Two international convenience samples are compared: a UK sample of 180 self-identified gay men ranging from 18 to 56 years of age (M=36 years; SD=8.29) and a US sample of 190 self-identified gay men ranging 18-74 years of age (M=33.9 years; SD=12.49). Both groups were asked to indicate whether each of a list of sexual behaviors was considered having "had sex." Almost all participants (~95%) believed that penile-anal intercourse constituted having "had sex." US and UK gay men differed in defining the following as having "had sex": giving oral-genital stimulation (US 71.6%, UK 84.9%, P=0.002); giving (G) and receiving (R) manual-anal stimulation (G: US 53.4%, UK 70.9%, P=0.001; R: US 53.7%, UK 71.2%, P=0.001); giving and receiving oral-anal stimulation (G: US 61.2%, UK 78.4%, P<0.001; R: US 59.3%, UK 78.1, P<0.001); and giving and receiving sex-toy stimulation (G: US 55%, UK 77.1%, P<0.001; R: US 56.1%, UK 77.7%, P<0.001). It is important to note that regardless of country there was not overall consensus on which behaviors constituted having "had sex." These findings reinforce the need for behavioral specificity in documenting sexual histories and assessing sexual risk. Further, researchers and clinicians should exercise caution by not assuming that their own definitions of the term "sex" is shared by their gay male participants or patients.

High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage.

The mechanisms underlying the massive gastrointestinal tract CD4 T-cell depletion in human immunodeficiency virus (HIV) infection are not well understood nor is it clear whether similar depletion is manifest at other mucosal surfaces. Studies of T-cell and virus dynamics in different anatomical sites have begun to illuminate the pathogenesis of HIV-associated disease. Here, we studied depletion and HIV infection frequencies of CD4 T cells from the gastrointestinal tract, bronchoalveolar lavage (BAL), and blood with the frequencies and functional profiles of HIV-specific T cells in these anatomically distinct sites in HIV-infected individuals. The major findings to emerge were as follows: (i) depletion of gastrointestinal CD4 T cells is associated with high frequencies of infected CD4 T cells; (ii) HIV-specific T cells are present at low frequencies in the gastrointestinal tract compared to blood; (iii) BAL CD4 T cells are not massively depleted during the chronic phase; (iv) infection frequencies of BAL CD4 T cells are similar to those in blood; (v) significantly higher frequencies and increased functionality of HIV-specific T cells were observed in BAL compared to blood. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might circumvent global depletion of mucosal CD4 T cells.

The need for effective disease control in international aquaculture.

Globally, aquaculture is steadily expanding both in terms of total production and the range of species farmed. At an overall annual growth rate of about 10%, it is by far the fastest growing sector of food animal production in the world and is providing an increasing proportion of the total production of fish and shellfish for human consumption. However, diseases continue to cause significant economic losses in international aquaculture production and to have a detrimental effect on valuable export trade for some countries. Financial losses have been drastic in some cases and the national economies of some developing countries have been adversely affected. Even just at the local level, disease can have a serious impact on the livelihoods and food security of many individual small farmers and their families, particularly in poorer countries. Despite all the problems caused, diseases continue to be spread internationally even where import health safeguards are in place. Recent examples of such spread are presented and some reasons for the appearance of a disease in a country for the first time are given. It is an unfortunate fact that despite many years of damaging economic and social impact of disease in different sectors of aquaculture, and large sums being spent on research around the world, there are relatively few effective and officially approved products available to control or prevent them. Despite the potential market, there are as yet no commercial vaccines available to prevent the damaging effects of many of the most serious diseases. Without such vaccines, it is likely that the serious impact of diseases in international aquaculture will continue for many years to come.

Evidence for increased T cell turnover and decreased thymic output in HIV infection.

The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation, including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected individuals undergoing temporary interruption of therapy. We found an inverse association between increased T cell proliferation with rapid viral recrudescence and a decrease in TREC levels. However, during early HIV infection, we found that CD45RO-CD27high (naive) CD4+ T cell proliferation did not increase, despite a loss of TREC within naive CD4+ T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. This suggests that the loss of TREC during HIV infection can arise from a combination of increased T cell proliferation and decreased thymic output, and that both mechanisms can contribute to the perturbations in T cell homeostasis that underlie the pathogenesis of AIDS.

Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet.

Intracellular Ca(2+) store loading has been shown to alter proliferation and apoptosis of several cell types. In addition, HMG-CoA reductase inhibitors (i.e. atorvastatin) are effective in treating diabetic dyslipidemic patients. Thus, we hypothesized that chronic atorvastatin treatment would prevent increased Ca(2+) uptake into intracellular Ca(2+) stores in vascular smooth muscle cells from diabetic dyslipidemic pigs. Male Yucatan pigs were divided into four groups for 20 weeks-- (1) low fat fed (control); (2) hyperlipidemic (F); (3) alloxan-induced diabetic dyslipidemic (DF); and (4) diabetic dyslipidemic pigs treated with atorvastatin (DFA). The F, DF, and DFA groups were fed a high fat/cholesterol diet. Cells were isolated from the coronary artery and the myoplasmic Ca(2+) (Ca(m)) response measured using single cell fura-2 imaging. The Ca(m) response to caffeine (5 mM to release Ca(2+) from the sarcoplasmic reticulum, SR) and ionomycin (10 microM; to release the total Ca(2+) store) was determined in either the presence of low Na (19Na; inhibits Na(+)-Ca(2+) exchange), thapsigargin (TSG; inhibits the SR Ca(2+) pump), and a 19Na+TSG solution. Low Na induced the uptake of Ca(2+) into both SR and non-SR Ca(2+) stores in the DF group, but not the DFA group. Furthermore, after depletion of the SR Ca(2+) store with TSG, 19Na evoked Ca(2+) uptake into non-SR Ca(2+) stores in all three groups except in the DFA group. In summary, this study demonstrates that atorvastatin prevents the enhanced uptake of Ca(2+) by SR and non-SR Ca(2+) stores in diabetic dyslipidemic pigs.

Traceability of aquatic animals.

Effective methods of traceability are urgently required for use in research as well as in different types of aquaculture operations and to control trade in aquatic animals and products. In regard to the marking of fish, many different tagging methods have been described and the method to be used depends on the purpose and need for tagging. In contrast, for molluscs and crustaceans, only a few methods of marking such animals have been described, due to the practical difficulties. The authors first describe the different methods for tracing fish and fishery products, by means of external tags, such as Floy tags, Carlin tags and passive integrated transponder tags; chemical marking using inorganic substances such as silver nitrate or potassium nitrate, pigments, oxytetracycline, etc.; and several different types of electronic devices in which basic information such as the strain of fish, farm of origin or weight can be stored. Genetic traceability using deoxyribonucleic acid profiling is developing quite rapidly for cultured brood stocks and wild populations. This technique may be used with very high degrees of confidence to assign to or exclude animals or products from their claimed origin, paternity or strain, and may be used as evidence in court proceedings. The second section of this paper describes the traceability of live molluscs for restocking and for human consumption. In these applications, genetic markers have been demonstrated to be suitable. Mechanical tagging on a small scale for research purposes has also been used. Otherwise, the only means of tracing live molluscs are the movement documents and the labelling on boxes that certifies the origin of the commodity. The third section describes the methods available for tracing live and dead crustaceans. A large variety of physical tagging methods for decapod crustaceans is described, such as the injection of biological stains (fast green, Niagara sky blue, trypan red and blue) and external tags such as coloured streamer tags, wire tags and a variety of anchor tags. Furthermore, a number of different internal coding methods, such as the coded micro-wire tags and injected elastomer tags are discussed in detail. As is the case for fish, genetic molecular techniques are also applied in population studies of crustaceans; some of the molecular genetic methods are described. Prawns for human consumption are most frequently packed whole or as tails after the necessary sorting, washing and freezing and the only way of performing a traceback is through documents relating to movement, invoices, health certificates and labelling of the boxes. The minimum requirements for labelling would be the content of the packages, i.e. species, quantity, identification of the manufacturer (name and address), packing place, importer/exporter or vendor of the product, in addition to the loading bill number.

Functional nucleotide receptor expression and sarcoplasmic reticulum morphology in dedifferentiated porcine coronary smooth muscle cells.

The phenotypic dedifferentiation of vascular smooth muscle cells (SMCs) is an early event associated with cell culturing and vascular injury. The purpose of this study was to evaluate the SMC phenotype underlying the functional responsiveness of SMCs to nucleotides in organ culture. Porcine coronary arteries were either used fresh, cold stored (5 degrees C) 4 days, or organ cultured (37 degrees C) 4 days. Fura-2 digital imaging of single SMCs was used to measure the myoplasmic calcium (Ca(m)) response to 10 microM of the following nucleotide receptor agonists: UTP, UDP, ATP, ADP, and 2-MeSATP. In contrast to the nucleotides UDP, ATP, ADP, and 2-MeSATP, the Ca(m) response increased 10-fold and the number of cells that responded to UTP increased 5-fold in SMCs from organ culture compared to SMCs from fresh or cold-stored arteries. Simultaneous imaging of Ca(m), DNA content, and SR distribution in SMCs from organ culture indicated that the UTP-induced Ca(m) increase occurred exclusively in SMCs that had a dedifferentiated cell phenotype. Three-dimensional image reconstruction of the nucleus and sarcoplasmic reticulum (SR) revealed a novel transnuclear SR distribution that intertwined with the nucleus in fresh SMCs, while in SMCs from organ culture the SR was predominantly perinuclear and cytoplasmic. This study demonstrates that the functional up-regulation of UTP-sensitive receptors and the disappearance of the transnuclear SR distribution are novel features of dedifferentiated coronary SMCs.

Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is followed by profound immunodeficiency. Thymic function is necessary for de novo generation of T cells after HSCT. Circulating CD45RA(+) naive T-cell levels are predictive of antigen-specific T-cell responses in the absence of graft-versus-host disease (GVHD). These T cells may not represent recent thymic emigrants, since naive T cells may maintain this phenotype if not antigen-activated. To accurately measure thymic output after HSCT and determine the factors that influence thymic function, T-cell receptor excision circles (TRECs) were examined in CD4(+) and CD8(+) cells from a cross-section of patients following HSCT. TREC levels rose weeks after HSCT and could be detected in patients 6 years after HSCT. TREC levels correlated with the frequency of phenotypically naive T cells, indicating that such cells were not expanded progeny of naive T cells present in the donor graft. Chronic GVHD was the most important factor that predicted low TREC levels even years after HSCT. Patients with a history of resolved GVHD had decreased numbers of TREC, compared with those with no GVHD. Because few adults had no history of GVHD, it was not possible to determine whether age alone inversely correlated with TREC levels. Recipients of cord blood grafts had no evidence of decreased TREC induced by immunosuppressive prophylaxis drugs. Compared with unrelated donor grafts, recipients of matched sibling grafts had higher TREC levels. Collectively, these data suggest that thymopoiesis is inhibited by GVHD. Larger studies will be needed to determine the independent contributions of age and preparative regimen to post-transplant thymopoietic capacity.

Enhanced endothelin(A) receptor-mediated calcium mobilization and contraction in organ cultured porcine coronary arteries.

Arterial injury models for coronary artery disease have demonstrated an enhanced expression and function of either the endothelin(A) or endothelin(B) (ET(A) or ET(B)) receptor subtype. We hypothesized that organ culture would enhance the physiological function of ET receptors in the porcine right coronary artery. Arteries were either cold stored (4 degrees C) or organ cultured (37 degrees C) for 4 days. After 4 days, the artery was either 1) sectioned into rings to measure the ET-1-induced isometric tension response (3 x 10(-10)-3 x 10(-7) M), or 2) enzymatically dispersed and the isolated smooth muscle cells imaged using fura-2 to measure the myoplasmic calcium (Ca(m)) response to 3 x 10(-8) M ET-1 ( approximately EC(50)). Isometric tension and Ca(m) to ET-1 were measured in the absence and presence of bosentan (nonselective ET(A) or ET(B) receptor antagonist), BQ788 (ET(B)-selective antagonist), and BQ123 (ET(A)-selective antagonist). Compared with cold storage, organ culture induced a 2-fold increase in tension development (3 x 10(-7) M ET-1) and Ca(m) (3 x 10(-8) M ET-1), which was inhibited with bosentan, thus confirming the enhanced responses to ET-1 were due to ET receptor activation. BQ123 also inhibited the enhanced contraction and Ca(m) responses to ET-1. In contrast, BQ788 failed to inhibit tension development and Ca(m) responses to ET-1 in organ culture and cold storage. Sarafotoxin 6C (ET(B) agonist) failed to elicit an increased Ca(m) response in organ culture compared with cold storage. Our results indicate the increased tension development and Ca(m) responses to ET-1 in organ culture are attributable to ET(A) receptors, and not ET(B) receptors.

Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution.

BACKGROUND: The potential benefits of haematopoietic stem-cell transplantation are tempered by the depletion of T-cells accompanying this procedure. We used a new technique which quantifies the excisional DNA products of T-cell-receptor (TCR) gene rearrangement to measure thymic output directly in patients with multiple myeloma, and thus assessed the contribution of the thymus to immune recovery after transplantation. METHODS: We studied 40 patients, 34-66 years of age, who had been randomly assigned myeloablative chemotherapy and autologous peripheral-blood haematopoietic stem-cell transplantation with unmanipulated grafts or grafts enriched for CD34 stem cells. CD4 and CD8 T-cell counts were measured, thymic output was estimated serially until 2 years after transplantation, and percentages of naive T-cells were measured. FINDINGS: The production of substantial numbers of new naive T cells by the thymus could be detected by 100 days post-transplant; there was a significant inverse relation between age and recovery of new T cells. In the CD34-unselected group, numbers of TCR-rearrangement excision circles returned to baseline after 2 years, whereas in the CD34-selected group, numbers at 2 years were significantly higher than both baseline numbers (p=0.004), and 2-year numbers in the unselected group (p=0.046). Increased thymic output correlated with, and was predictive of, increased naive T-cell numbers and broader T-cell-receptor repertoires. INTERPRETATION: Our results provide evidence that the adult thymus contributes more substantially to immune reconstitution after haematopoietic stem-cell transplantation than was previously thought, and therefore could be a target for therapeutic intervention.

Probing the extracellular release site of the plasma membrane calcium pump.

The plasma membrane Ca(2+) pump is known to mediate Ca(2+)/H(+) exchange. Extracellular protons activated (45)Ca(2+) efflux from human red blood cells with a half-maximal inhibition constant of 2 nM when the intracellular pH was fixed. An increase in pH from 7.2 to 8.2 decreased the IC(50) for extracellular Ca(2+) from approximately 33 to approximately 6 mM. Changing the membrane potential by >54 mV had no effect on the IC(50) for extracellular Ca(2+). This argues against Ca(2+) release through a high-field access channel. Extracellular Ni(2+) inhibited Ca(2+) efflux with an IC(50) of 11 mM. Extracellular Cd(2+) inhibited with an IC(50) of 1. 5 mM, >10 times better than Ca(2+). The Cd(2+) IC(50) also decreased when the pH was raised from 7.1 to 8.2, consistent with Ca(2+), Cd(2+), and H(+) competing for the same site. The higher affinity for inhibition by Ni(2+) and Cd(2+) is consistent with a histidine or cysteine as part of the release site. The cysteine reagent 2-(trimethylammonium)ethyl methanethiosulfonate did not inhibit Ca(2+) efflux. Our results are consistent with the notion that the release site contains a histidine.

Prolonged activation of the mitogen-activated protein kinase pathway is required for macrophage-like differentiation of a human myeloid leukemic cell line.

The role of the mitogen-activated protein kinase (MAPK) signal transduction pathway in the proliferation of mammalian cells has been well established. However, there are relatively few reports concerning cell differentiation being mediated by MAPK. The effect of phorbol 12-myristate 13-acetate (PMA) on cell differentiation and signal transduction in a human myeloid leukemia cell line, TF-1a, was investigated. When TF-1a cells were treated with 10(-6), 10(-7), 10(-8), and 10(-9) M PMA for 24 h, they underwent 98, 93, 91, and 51% macrophage-like differentiation, respectively. PMA treatment rapidly (10 min) induced phosphorylation of MAPK kinase (MEK and p44/42 MAPK), which persisted for at least 24 h. p44/42 MAPK immunoprecipitates from lysates of PMA-treated cells had increased ability to phosphorylate the transcription factor Elk-1. This is important because phosphorylated Elk-1 can be considered an "end-product" of the MAPK pathway. In contrast, treatment of TF-1a cells with granulocyte/macrophage-colony stimulating factor induced only transient activation of MEK and p44/42 MAPK (10-20 min) and an increase (approximately 50%) in cell proliferation, without any change in cellular differentiation. These results suggest that macrophage-like differentiation may be dependent on prolonged activation of the MAPK pathway. Additional support for this conclusion was obtained from experiments showing that treatment of TF-1a cells with antisense oligonucleotides for MEK1 coding sequences prior to adding PMA inhibited macrophage-like differentiation. Furthermore, transient transfection with an inactive, dominant-negative MEK mutant also inhibited PMA-induced differentiation, whereas transient transfection with a plasmid coding for constitutively activated MEK led to macrophage-like differentiation in the absence of PMA.

Interactions between GABA and glycine at inhibitory amino acid receptors on rat olfactory bulb neurons.

Whole cell voltage-clamp electrophysiology was used to examine interactions between GABA and glycine at inhibitory amino acid receptors on rat olfactory bulb neurons in primary culture. Membrane currents evoked by GABA and glycine were selectively inhibited by low concentrations of bicuculline and strychnine, respectively, suggesting that they activate pharmacologically distinct receptors. However, GABA- and glycine-mediated currents showed cross-inhibition when the two amino acids were applied sequentially. Application of one amino acid inhibited the response to immediate subsequent application of the other. In the majority of neurons, GABA inhibited subsequent glycine-evoked currents and glycine inhibited subsequent GABA-evoked currents. In a small proportion of neurons, however, GABA inhibited glycine-evoked currents but glycine had little effect on GABA-evoked currents. The reverse was true in other neurons, suggesting that alterations in chloride gradients alone did not account for the cross-inhibition. Furthermore, no cross-inhibition was observed between GABA- and glycine-evoked currents in some neurons. The amplitude of the current evoked by the coapplication of saturating concentrations of GABA and glycine in these neurons was nearly the sum of the currents evoked by GABA and glycine alone. In contrast, the currents were not additive in neurons demonstrating cross-inhibition. These results suggest that olfactory bulb neurons heterogeneously express a population of inhibitory amino acid receptors that can bind either GABA or glycine. Interactions between GABA and glycine at inhibitory amino acid receptors may provide a mechanism to modulate inhibitory synaptic transmission.

Successful aquatic animal disease emergency programmes.

The authors provide examples of emergency programmes which have been successful in eradicating or controlling certain diseases of aquatic animals. The paper is divided into four parts. The first part describes the initial isolation of viral haemorrhagic septicaemia (VHS) virus in North America in the autumn of 1988 from feral adult chinook (Oncorhynchus tshawytscha) and coho salmon (O. kisutch) returning for spawning. The fish disease control policies at both State and Federal levels in the United States of America required quarantine and emergency eradication measures upon the finding of certain exotic fish pathogens, including VHS virus. The procedures for emergency plans, destruction of stocks and disinfection of facilities are described, as well as challenge experiments with the North American strains of VHS virus and the detection of the virus in marine fish species (cod [Gadus macrocephalus] and herring [Clupea harengus pallasi]) in the Pacific Ocean. The second part of the paper outlines the aquatic animal legislation in Great Britain and within the European Union, in regard to contingency plans, initial investigations, action on the suspicion of notifiable disease and action on confirmation of infection. The legal description is followed by an account of an outbreak of viral haemorrhagic septicaemia in turbot (Scophthalmus maximus) in Great Britain, including the stamping-out process at the affected farm and investigations conducted to screen other farms in the vicinity for possible infection. The third part provides a historical review of the build-up of infectious salmon anaemia (ISA) in Norway and the attempts to control the disease using legal measures in the absence of detailed knowledge of the aetiology, epizootiology, pathogenesis, etc. of the disease. The measures taken show that the spread of ISA can be controlled using restrictions on the movement of fish, disinfection procedures, etc. However, acceptance and understanding of the chosen strategy by the fish farmers is a pre-requisite to reach that goal. Finally, the paper summarises future needs for national and international legislation, including the development of standard approaches for control, the creation of appropriate infrastructures and a better understanding of the epidemiology of aquatic animal diseases.