Spectral Changes of EEG Following a 6-Week Low-Dose Oral Ketamine Treatment in Adults With Major Depressive Disorder and Chronic Suicidality.

BACKGROUND: Ketamine has considerable therapeutic potential in alleviating major depressive disorder and chronic suicidality. However, the clinical diagnosis of neuropsychiatric disorders requires more robust diagnostic criteria. Electroencephalography (EEG) has shown promise in classifying depressive and suicidal patients from healthy individuals. The present study aimed to identify changes in the spectral properties of EEG in patients with major depressive disorder and chronic suicidality after completing the 6-week Oral Ketamine Trial on Suicidality with follow-up occurring 4 weeks after final ketamine treatment and determine associations between EEG spectral output and clinical symptoms. METHODS: Participants (n = 25) had 4-minute eyes closed resting state EEG recorded at frontal, temporal, centro-parietal, and occipital regions. Spectral analysis was performed with Welch's power spectrum density method, and the power of 4 distinct frequency bands was analyzed: theta, alpha, low-beta, and high-beta. Correlation analyses between changes in clinical symptoms and spectral power were conducted using Spearman's ranked correlation. RESULTS: Between pre- and posttreatment, only centro-parietal alpha power decreased. Between posttreatment and follow-up, centro-parietal alpha increased again in addition to increases in temporal alpha, centro-parietal and temporal theta, and occipital low-beta and decreases in occipital theta and temporal low-beta. Additionally, the decrease of occipital theta positively correlated with clinical subscales for depression and stress. CONCLUSIONS: EEG spectral analysis revealed significant changes in theta, alpha, and low-beta frequency bands. Alpha band showed initial changes after treatment; however, this trended back toward baseline levels after the treatment cessation. In contrast, theta and low-beta showed significant power changes only after the treatment had ended.

Predictors of voter support for the legalization of recreational cannabis use and supply via a national referendum.

BACKGROUND: A national referendum to legalise recreational cannabis use and supply in New Zealand via the Cannabis Legalisation and Control Bill (CLCB) was recently narrowly defeated. Understanding the underlying factors for this result can inform the cannabis legalisation debate in other countries. AIMS: To investigate predictors of voter support for and opposition to the CLCB. METHOD: A representative population panel of 1,022 people completed an online survey of intended voting on the CLCB referendum, which included questions on demographics, drug use history, medicinal cannabis, perceptions of the health risk and moral views of cannabis use, political affiliation, religiosity, community size and reading of the CLCB. Regression models were developed to predict support for the CLCB, with additional predictor variables added over successive iterations. RESULTS: The most robust predictors of support for the CLCB were use of and policy support for medicinal cannabis use, voting for a left-wing political party, having a positive moral view of cannabis use, living in a small town and having read the CLCB. Predictors of opposing the CLCB were voting for right-wing parties, considering "frequent" cannabis use to be a high health risk, and lifetime use of other drugs. Age, ethnicity, education, employment status, religiosity and lifetime cannabis use were not significant predictors after controlling for other variables. CONCLUSIONS: Support for cannabis legalization was not based on broad demographics, but rather specific views concerning the medicinal benefit, morality of cannabis use, health risk of frequent cannabis use, political party affiliation, and knowledge of the proposed regulatory controls of the CLCB. The influence of moral views of cannabis use on voting behaviour suggest the need to debate the right to use cannabis. The importance of knowledge of the proposed regulatory controls of the CLCB on voting underlines the need to raise awareness of proposed regulatory controls during debate.

The prioritisation of invasive alien plant control projects using a multi-criteria decision model informed by stakeholder input and spatial data.

Invasions by alien plants are a significant threat to the biodiversity and functioning of ecosystems and the services they provide. The South African Working for Water program was established to address this problem. It needs to formulate objective and transparent priorities for clearing in the face of multiple and sometimes conflicting demands. This study used the analytic hierarchy process (a multi-criteria decision support technique) to develop and rank criteria for prioritising alien plant control operations in the Western Cape, South Africa. Stakeholder workshops were held to identify a goal and criteria and to conduct pair-wise comparisons to weight the criteria with respect to invasive alien plant control. The combination of stakeholder input (to develop decision models) with data-driven model solutions enabled us to include many alternatives (water catchments), that would otherwise not have been feasible. The most important criteria included the capacity to maintain gains made through control operations, the potential to enhance water resources and conserve biodiversity, and threats from priority invasive alien plant species. We selected spatial datasets and used them to generate weights that could be used to objectively compare alternatives with respect to agreed criteria. The analysis showed that there are many high priority catchments which are not receiving any funding and low priority catchments which are receiving substantial allocations. Clearly, there is a need for realigning priorities, including directing sufficient funds to the highest priority catchments to provide effective control. This approach provided a tractable, consensus-based solution that can be used to direct clearing operations.

Incorporating stakeholder preferences in the selection of technologies for using invasive alien plants as a bio-energy feedstock: applying the analytical hierarchy process.

Invasive alien plants (IAPs) impose significant social costs on the population of the Agulhas Plain region in South Africa due to their adverse impacts on ecosystem goods and services (decreased water supply and increased fire risk). While the cost of clearing IAPs is considerable, this paper assesses opportunities to reduce some of the social and environmental burdens (e.g. disruptions of ecosystems which have negative impacts on livelihoods) by using IAP biomass to produce bio-energy. However, such an initiative could increase financial dependency on these plants and is thus considered to be a major risk factor which could create adverse incentives to illegally grow these plants. A participatory decision-making process with active stakeholder participation is a key element in managing such an initiative. We used a multi-stakeholder engagement process and the analytical hierarchy process to define and weigh suitable criteria for the assessment of different "IAP biomass to bio-energy" technology scenarios on the Agulhas Plain. Feasible scenarios were constructed by means of an expert panel which were then ranked according to stakeholder preference. The six criteria were: minimising impacts on natural resources; job creation; certainty of benefits to local people in the study area; development of skills for life; technology performance and cost efficiency. This ranking was largely determined by the preference for resource efficiency in terms of minimising impacts on natural ecosystems and the localisation of benefits. The smaller, modular technologies were consequently preferred since these realise direct local benefits while developing local skills and capacity in their manufacture, sales and maintenance. The rankings as obtained in this study are context-bound, which implies that the findings only have limited application to areas with similar biophysical and socio-economic characteristics. However, the method itself is fully generalisable, and the same prioritisation process can be followed in any study area to ensure that a participatory decision-making process fulfils local energy needs and contributes to sustainable development.

Chloride concentration affects Kv channel voltage-gating kinetics: Importance of experimental anion concentrations.

Chloride concentration has been shown to have a dramatic impact on protein folding and subsequent tertiary conformation [K.D. Collins, Ions from the Hofmeister series and osmolytes: effects on proteins in solution and in the crystallization process, Methods 34 (2004) 300-311; I. Jelesarov, E. Durr, R.M. Thomas, H.R. Bosshard, Salt effects on hydrophobic interaction and charge screening in the folding of a negatively charged peptide to a coiled coil (leucine zipper), Biochemistry 37 (1998) 7539-7550]. As it is known that Kv channel gating is linked to the stability of the cytoplasmic T1 multimerization domain conformation [D.L. Minor, Y.F. Lin, B.C. Mobley, A. Avelar, Y.N. Jan, L.Y. Jan, J.M. Berger, The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel, Cell 102 (2000) 657-670; B.A. Yi, D.L. Minor Jr., Y.F. Lin, Y.N. Jan, L.Y. Jan, Controlling potassium channel activities: interplay between the membrane and intracellular factors, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 11016-11023] and that intracellular chloride concentration has been linked to Kv channel kinetics [L.K. Bekar, W. Walz, Intracellular chloride modulates A-type potassium currents in astrocytes, Glia 39 (2002) 207-216; W.B. Thoreson, S.L. Stella, Anion modulation of calcium current voltage dependence and amplitude in salamander rods, Biochim. Biophys. Acta 1464 (2000) 142-150], the objective of the present study was to address how chloride concentration changes affect Kv channel kinetics more closely in an isolated expression system. Initially, no significant chloride concentration-dependent effects on channel steady-state gating kinetics were observed. Only after disruption of the cytoskeleton with cytochalasin-D did we see significant chloride concentration-dependent shifts in gating kinetics. This suggests that the shift in gating kinetics is mediated through effects of intracellular chloride concentration on cytoplasmic domain tertiary conformation as cytoskeletal interaction appears to mask the effect. Furthermore, as cytoskeletal disruption only impacts channel gating kinetics at low physiological intracellular chloride concentrations, these studies highlight the importance of paying close attention to anion concentrations used under experimental conditions.

Polyphasic identification of Bacillus and Brevibacillus strains from clinical, dairy and industrial specimens and proposal of Brevibacillus invocatus sp. nov..

Thirty-three clinical, dairy and industrial isolates of aerobic endospore-forming bacteria which were unreactive in routine identification tests were characterized genotypically by using amplified rDNA restriction analysis (ARDRA), 16S rDNA sequencing and DNA-DNA reassociation, and phenotypically by using fatty acid methyl ester (FAME) analysis, SDS-PAGE of whole-cell proteins, API Biotype 100 assimilation tests and 16 other routine phenotypic tests. Three isolates were identified as strains of Bacillus badius, 12 as Brevibacillus agri, including 3 strains associated with an outbreak of waterborne illness, 4 as Brevibacillus centrosporus and 2 as Brevibacillus parabrevis; 12 strains contaminating an antibiotic production plant were recognized as members of a new species, for which the name Brevibacillus invocatus is proposed, with the type strain LMG 18962T (= B2156T = CIP 106911T = NCIMB 13772T).

Aerobic endospore-forming bacteria from geothermal environments in northern Victoria Land, Antarctica, and Candlemas Island, South Sandwich archipelago, with the proposal of Bacillus fumarioli sp. nov.

Aerobic endospore-forming bacteria were isolated from soils taken from active fumaroles on Mount Rittmann and Mount Melbourne in northern Victoria Land, Antarctica, and from active and inactive fumaroles on Candlemas Island, South Sandwich archipelago. The Mt Rittmann and Mt Melbourne soils yielded a dominant, moderately thermophilic and acidophilic, aerobic endospore-former growing at pH 5.5 and 50 degrees C, and further strains of the same organism were isolated from a cold, dead fumarole at Clinker Gulch, Candlemas Island. Amplified rDNA restriction analysis, SDS-PAGE and routine phenotypic tests show that the Candlemas Island isolates are not distinguishable from the Mt Rittmann strains, although the two sites are 5600 km apart, and 16S rDNA sequence comparisons and DNA relatedness data support the proposal of a new species, Bacillus fumarioli, the type strain of which is LMG 17489T.

Cloning a chloride conductance mediator from the apical membrane of porcine ileal enterocytes.

Attempts to attribute ileal brush-border chloride conductance to specific proteins were pursued by screening a porcine intestinal cDNA library. A 0.94-kb clone was identified on expression screening with a monoclonal antibody that inhibited enterocyte brush-border chloride conductance. Further screening approaches led to the isolation of a 3.1-kb full-length sequence called pCLCA1, consistent with the identification of a 2.9-kb transcript through Northern analysis. This sequence had significant homology to the CLCA gene family of calcium-regulated chloride channels, especially to hCLCA1. However, a strong A-kinase consensus phosphorylation site in a predicted cytoplasmic loop of the protein was a notable difference from the hCLCA1 gene product. Several porcine exocrine epithelial tissues, including ileum, trachea, and the major salivary glands express pCLCA1 mRNA. In situ hybridization studies localized the expression of pCLCA1 mRNA to the crypt and villus epithelia of porcine ileum, whereas tracheal expression was observed in both surface epithelium and submucosal glands. In situ expression of pCLCA1 in mouse 3T3 cells induces an ionomycin-dependent chloride conductance activity in these cells.

Isoform-specific exon skipping in a variant form of ClC-2.

A new form of the widely expressed, volume-regulated chloride channel, ClC-2, has been cloned from a pig ileal cDNA library. This ClC-2 homologue, called ClC-2i, has interesting variability within its cDNA sequence, including the deletion of bases that correspond to positions 1326 through 1401 in rat ClC-2 cDNA sequence. This 75 bp deletion corresponds to the complete loss of exon 13 plus the first four bases of exon 14, and involves an atypical intron-exon splice site. Tissue-specific mRNA expression patterns in the pig show variable degrees of exon 13 skipping in ClC-2i. Exon 13 skipping was also observed in rat ClC-2i, albeit at a higher frequency than in the pig in tissues that were examined. A relatively purine-rich 76 bp insertion in the pig genomic sequence of ClC-2i, close to the 3' end of intron 12, may be responsible for the relatively high frequency of exon 13 skipping during the processing of this mRNA.

Isolation of Bacillus thuringiensis from Northern Victoria Land, Antarctica.

Sixty-two samples of Antarctic soils, mosses, penguin guano, algae and lichens were examined for the presence of aerobic endospore-forming bacteria; 36 samples (58%) yielded such organisms, and two samples from Edmonson Point (74 degrees 21'S 165 degrees 08'E) and one sample from Apostrophe Island (73 degrees 32'S 167 degrees 24'E), northern Victoria Land, yielded strains of Bacillus thuringiensis. Further isolations from two of the samples, appreciable variation in biotypes among the strains, failure of the strains to grow on routine B. thuringiensis media, and the fact that one of the sampling sites is very rarely visited by humans, suggest that the organisms were living in these soils rather than being chance contaminants. A representative strain, from Apostrophe Island, was identified as serovar pirenaica (H57).

Proposal of Virgibacillus proomii sp. nov. and emended description of Virgibacillus pantothenticus (Proom and Knight 1950) Heyndrickx et al. 1998.

A polyphasic study of strains originally received as Bacillus (now Virgibacillus) pantothenticus, along with strains representing species belonging to Bacillus, Halobacillus and Paenibacillus, was undertaken using amplified rDNA restriction analysis (ARDRA), fatty acid methyl ester (FAME) analysis, SDS-PAGE of whole-cell proteins and routine diagnostic characters comprising 61 biochemical tests in the API system and 15 observations of vegetative cell and sporangial morphology. It revealed the presence within Virgibacillus of an as yet undescribed new species, for which the name Virgibacillus proomii is proposed; V. proomii can be distinguished from V. pantothenticus and members of Bacillus sensu stricto, and from members of Paenibacillus and other aerobic endospore-forming bacteria, by routine phenotypic tests. The type strain of Virgibacillus proomii is LMG 12370T.

Sequence and structure specific antibodies from phage display libraries.

A large combinatorial phage display library was panned against five nucleic acid antigens, calf thymus DNA, poly[d(GC)], poly[d(AT)], poly(dA) x poly(dT) and poly(rA) x poly(dT). After the third and fourth rounds of panning, many positive clones were selected against poly[d(GC)], poly(dA) x poly(dT) and poly(rA) x poly(dT). The specificity of these antibodies was tested by both direct and competitive solid phase radioimmune assays. All the clones derived from panning with poly[d(GC)] were non-specific and bound to all nucleic acids. The poly(rA) x poly(dT) derived clones were specific for single-stranded nucleic acids, with some sequence preferences, and the poly(dA) x poly(dT) derived clones showed considerable specificity for this antigen. The sequences of these phage-derived antibodies showed no similarities with DNA-binding antibodies from other sources. Even after six rounds of panning no positive clones were detected which bound to poly[d(AT)] and after seven rounds only two were derived from panning with calf thymus DNA. Therefore, sequence- and structure specific antibodies can be recovered from phage display libraries but not all sequences may be represented in the repertoire.

Monoclonal antibody against conductive chloride transport in pig ileal apical membrane vesicles.

Conductive chloride transport in the small intestine is an important factor controlling fluid movement from the blood to the lumen of the gut. Several proteins with potential conductive chloride ion channel activity are expressed in the enterocyte cell population. However, it is not clear whether one or more than one protein species is normally responsible for mediating conductive chloride transport. We have raised monoclonal antibodies that inhibit conductive chloride transport in apical membrane vesicles prepared from porcine ileal enterocytes. These monoclonal antibodies have been used to identify a unique protein involved with this conductive chloride transport. Here, we report that anti-chloride conductance monoclonal antibodies did not detect any antigen in Western blots of enterocyte apical membrane protein. Dot blotting and immunoprecipitation experiments indicated that the antigen recognized by these monoclonal antibodies was not the cystic fibrosis transmembrane conductance regulator. The antigen was localized to both villus and crypt regions of ileum on immunohistochemistry. A 90-kDa protein species was immunoprecipitated from a primary enterocyte cell line by these monoclonal antibodies. This 90-kDa protein may be a chloride ion channel or may play some regulatory role in conductive chloride transport in enterocyte apical membrane vesicles.

Time course of recovery during cardiac rehabilitation.

PURPOSE: Exercise-based rehabilitation programs improve effort tolerance in patients with cardiovascular disease. Little is known regarding the time course of recovery of objective and subjective indices of exercise tolerance. METHODS: Twenty-six patients were studied at 0, 4, 8, and 12 weeks following early entry into rehabilitation following acute myocardial infarction (AMI), coronary artery bypass graft surgery (CABGS), or valve surgery. Exercise tolerance was assessed objectively by percent predicted cycle power output (%PO), and subjectively by a self-efficacy questionnaire for ambulatory (ASE) and muscular (MSE) items and by a disease-specific, health-related, quality-of-life questionnaire (HRQL). RESULTS: With the exception of percent predicted cycle power output, all exercise tolerance measures improved throughout the rehabilitation program. Extrapolation of recovery curves suggest that recovery to 85% predicted can be achieved in 10, 11, 18, and 21 weeks for a disease-specific, health-related, quality-of-life questionnaire, self-efficacy questionnaire for ambulatory items, muscular items, and power output, respectively. CONCLUSIONS: The data demonstrate that evaluation of both objective and subjective indices of exercise tolerance may be important in documenting outcomes of participation in structured rehabilitation programs. The time course of recovery of objective and subjective indices of exercise tolerance may not be highly correlated.

The binding of analogues of coralyne and related heterocyclics to DNA triplexes.

Coralyne has been shown previously to bind well to both T.A.T- and C.G.C(+)-containing triplexes. Derivatives of coralyne were prepared and their binding to poly(dT).poly(dA).poly(dT) and poly[d(TC)].poly[d(GA)].poly[d(C+T)] was assessed from thermal denaturation profiles. A tetraethoxy derivative showed only weak binding to both types of triplex. Analogues with extended 8-alkyl chains showed good binding to poly(dT).poly(dA).poly(dT), but the preference for triplex poly[d(TC)].poly[(GA)].poly[d(C+T)] was decreased compared with the duplex. Sanguinarine, a related alkaloid, bound well to poly(dT).poly(dA).poly(dT) but only weakly to the protonated triplex. It is hypothesized that the position of the protonated nitrogen ring is important for binding to poly[d(TC)].poly[d(GA)].poly[d(C+T)]. A series of other chromophores was studied and only those with a positive charge bound to triplexes. All of these bound well to poly(dT),poly(dA).poly(dT) but only weakly if at all to the duplex poly(dA).poly(dT). In contrast, most of them did not bind well to the triplex poly[d(TC)].poly[d(GA)].poly[d(C+T)] and those that did still showed a preference for duplex poly[d(TC)].poly[d(GA)]. In general, preference for triplex poly(dT).poly(dA).poly(dT) compared with the duplex is a common feature of intercalating drugs. On the other hand, specificity for protonated triplexes may be very difficult to achieve.

Variable expression of leukocyte cytosolic broad-specificity beta-glucosidase activity.

The cytosolic beta-glucosidase activity that is found in a variety of mammalian tissues has no clearly defined function. In vitro assay conditions under which the broad-specificity beta-glucosidase hydrolyzes glucocerebroside at a significant rate have not been described. Nonetheless, it has been suggested that this enzyme might play an accessory role with lysosomal glucocerebrosidase in catalyzing the hydrolysis of glucosylceramide. However, this hypothesis would require that activity of both enzymes be low in severe cases of Gaucher disease in which there are pathological accumulations of glucosylceramide in one or more of the affected organs, i.e. spleen, liver and bone marrow. Information is lacking regarding the normal range of cytosolic beta-glucosidase activity in humans. p-Nitrophenyl-beta-D-mannoside was found to be a potent inhibitor (Ki = 0.068 mM) of cytosolic beta-glucosidase. In parallel studies, the activity of glucocerebrosidase was found to be minimally affected by p-nitrophenyl-beta-D-mannoside at concentrations as high as 2.5 mM. This information was used to design an assay system that would allow us to estimate glucocerebrosidase and cytosolic beta-glucosidase activities in extracts of human leukocytes. Average cytosolic beta-glucosidase activity with 4-heptyl-umbelliferyl-beta-D-glucoside as a substrate was 8.8 nmol/h/mg protein in leukocytes from 356 subjects (range, 0.2-28). Average leukocyte glucocerebrosidase specific activity was 16 nmol/h/mg protein (range 5.3-45.7). No correlation was observed between cytosolic beta-glucosidase and glucocerebrosidase activity for control and Gaucher heterozygote populations (r = 0.19 and 0.25, respectively). The wide range of leukocyte cytosolic beta-glucosidase activity in individuals tested in this study indicates that a substantial proportion of the population may lack sufficient cytosolic beta-glucosidase activity to assist a defective lysosomal glucocerebrosidase in hydrolyzing glucosylceramide.

Inhibition of ileal brush-border chloride conductance by specific antibody.

Antibody raised in mice was used in attempting to identify proteins responsible for the conductive chloride transport that can be measured in porcine ileal brush border membrane vesicles. Ileal brush-border membrane vesicle protein from pig was separated into five different molecular mass fractions by preparative SDS polyacrylamide disc gel electrophoresis. Separated protein fractions were used to immunize mice. Antibody was screened for reactivity with antigen by Western blotting, and for effects on conductive chloride transport in ileal brush border membrane vesicles. Immunization with brush-border protein from fraction I proteins (> 110 kDa) produced polyclonal antisera which specifically inhibited the conductive component of chloride uptake by ileal brush border vesicle preparations. Western blotting of the antigen showed the presence of several protein species of molecular mass > 100 kDa that were recognized by immune serum. Spleen cells from a mouse producing antiserum that inhibited conductive chloride transport were fused with a myeloma cell line. The resulting hybridoma colonies produced antibody that reacted with at least seven distinct protein bands by Western blot assay and inhibited chloride conductance in brush-border membrane vesicles.

Effect of covalent modification on the binding of cholera toxin B subunit to ileal brush border surfaces.

A competitive binding assay has been developed to determine how modifications to the B subunit of cholera toxin affect the binding affinity of the subunit for an ileal brush border membrane surface. The Ricinus communis120 agglutinin (RCA120) specifically binds to terminal beta-D-galactosyl residues such as those found in oligosaccharide side chains of glycoproteins and ganglioside GM1. Conditions were designed to produce binding competition between the B subunit of cholera toxin and the RCA120 agglutinin. Displacement of RCA120 from brush border surfaces was proportional to the concentration of B subunit added. This assay was used to study the effect of modification of B subunit on competitive binding affinity for the ileal brush border surface. The B subunit of cholera toxin was modified by coupling an average of five sulfhydryl groups to each B subunit molecule and by reaction of the SH-modified B subunit with liposomes containing a surface maleimide group attached to phosphatidylethanolamine. SH-modified B subunit was approximately 200-fold more effective than native B subunit in displacing lectin from brush border surfaces in the competitive binding assay. The enhanced binding activity was retained on covalent attachment of the modified B subunit to the liposome surface. We conclude that the B subunit of cholera toxin may be a useful targeting agent for directing liposomes to cell surfaces that contain a ganglioside GM1 ligand.

Liposomes targeted to deliver antisecretory agents to jejunal mucosa.

The B subunit of cholera toxin has been covalently attached to the surface of liposomes made from a mixture of phosphatidylethanolamine, phosphatidylcholine and cholesterol. Adenylate cyclase inhibitors and chloride conductance inhibitors were encapsulated within the liposomes. These "targeted" liposomes were used to study the combined effects of this novel delivery system, and a limited number of possible antisecretory agents, on net fluid flux into the pig jejunum. A state of net secretory fluid flux was induced in isolated jejunal loops in weanling pigs by adding theophylline or cholera toxin to the lumen of the isolated loops. There was no reduction in net fluid secretion when liposome suspensions without encapsulated secretory inhibitors were added to fluid in the lumen of loops treated with theophylline. There was also no reduction in net fluid secretion when miconazole, alpha-phenylcinnamate or 5 nitro-2-(3-phenethylamino)benzoate were encapsulated within targeted liposomes added to isolated jejunal loops. The net fluid flux induced by exposure of jejunal loops to theophylline was significantly reduced by adding targeted liposomes containing 2'-deoxy-3'-AMP. The reduction involved a reversal of net secretory fluid flux to an absorptive value. The net fluid secretory response to treatment of loops with cholera toxin was also inhibited by treating loops with targeted liposomes containing 2'-deoxy-3'-AMP. However, the reversal of secretion was less complete for secretion induced by cholera toxin than for secretion induced by theophylline. The reduced antisecretory efficacy versus cholera toxin was not improved by encapsulating higher concentrations of 2'-deoxy-3'-AMP.(ABSTRACT TRUNCATED AT 250 WORDS)