SEARCH · PubMed Health

Results for “ADE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

PubMed2001

Using a clinical data repository to estimate the frequency and costs of adverse drug events.

As a result of increased attention to medical errors, many institutions are contemplating increased use of information technology and clinical decision support. We conducted a retrospective analysis to estimate the frequency and cost of adverse drug events (ADEs) for inpatients at the University of Virginia. Applying published criteria for the detection of potential adverse events, we used a clinical data warehouse to identify patients and cases with potential ADEs. Again using published criteria, we then estimated the actual number of adverse drug events and preventable adverse drug events, as well as their attributable costs and excess length of stay. Our results showed a higher estimate (10.4-11.5 events per 100 admissions) for ADEs than seen in the ADE Prevention Study, highlighting the importance of considering the generalizability of published ADE studies to other settings. Our analysis demonstrates that retrospective analysis can be an efficient and powerful technique to evaluate rules and criteria used to detect ADEs and to assess their impact.

Adverse Drug Reaction Reporting Systems↗

PubMed2002

Central nervous system mechanisms in alcohol relapse.

BACKGROUND: Alcohol relapse is a major problem in the treatment of alcohol abuse and alcoholism. Understanding the long-term neuronal alterations that promote relapse of alcohol drinking is critical for the development of pharmacotherapies to treat alcoholism and alcohol abuse. The major objectives of this workshop were to present recent findings, by using rodent models, on behavioral and neurobiological factors that may underlie alcohol relapse and the results of clinical and pharmacological treatment strategies for preventing relapse. METHODS: Prolonged ethanol drinking and repeated periods of alcohol deprivation were studied in nonselected rats and in rats selectively bred for high alcohol preference (P rat). The expression of a robust alcohol deprivation effect (ADE) was used as a model for alcohol relapse in rodents. Operant techniques were used to examine responding for ethanol after deprivation in both rats and C57BL/6J mice. Environmental cues and stress were used to assess their effects on reinstatement of alcohol responding. Microdialysis and [14C]-2-deoxyglucose techniques were used to examine neuronal alterations associated with alcohol relapse. RESULTS: Prolonged free-choice ethanol drinking followed by deprivation produced an ADE in both stock and P rats. These rats demonstrated loss of control on reinstatement after chronic drinking and after prolonged deprivation. Acamprosate and naltrexone effectively reduced the ADE in stock rats. Stress reinstated operant responding for alcohol, and rats trained to associate a cue with ethanol presentation increased responding on the ethanol-associated lever in the absence of ethanol. After repeated deprivations, P rats shifted their preference toward drinking higher concentrations of ethanol, which increased the magnitude and duration of the ADE. Stock rats also shifted their preference toward solutions with higher ethanol concentrations and demonstrated a loss of control after prolonged ethanol drinking and deprivation. Long-lasting alterations in neuronal activity, serotonin-3 receptor function, and dopamine neurotransmission within the mesolimbic system were evident after chronic drinking that followed a prolonged deprivation period. CONCLUSIONS: The ADE is a useful model for studying alcohol relapse in both rats and mice. The potential validity of this model is supported by the findings that acamprosate and naltrexone are effective in preventing the ADE in rodents, and both compounds have gained recognition for their therapeutic effects in clinical populations. Genetics, stress, and environmental cues are all important factors that influence alcohol relapse. Long-term alterations in neuronal activity within the mesolimbic system, which possibly involve dopamine and serotonin, may underlie alcohol relapse.

Acamprosate↗

PubMed2002

Effect of pretreatment with adenosine, diazoxide or ischemic preconditioning on ischemia- reperfusion injury in the limbs of rats.

OBJECTIVE: To study the effect of ischemic preconditioning (PC) and pharmacological preconditioning with adenosine or diazoxide on ischemia-reperfusion (IR) injury in the limbs of rats. METHODS: According to different treatment received before ischemic-reperfusion injury, 66 SD rats were divided into 6 groups including a normal control and a ischemia-reperfusion control group, IP10 group in which the rats received 10-min ischemia followed by 10-min interval for reperfusion for 3 times before IR, IP5 group in which the rats were subjected to 5-min ischemia with 5-min reperfusion intervals for 3 times before IR, adenosine (Ade) pretreatment group and diazoxide (Dia) pretreatment group. Except the normal control group, which consisted of 6 rats, each group contained 12 rats, and IR injury was induced by blocking the blood flow in bilateral limbs for 4 h, followed by reperfusion for 2 or 24 h when twitch and spastic contractility of the tibialis anterior muscle and serum creatine phosphokinase (CPK) were measured. RESULTS: In IP5 and Ade pretreatment group, the twitch tension of the tibialis anterior muscle of the rats was significantly enhanced after 2 and 24 h of reperfusion, achieving the level of the normal control. The twitch tension was also enhanced in rats of IP10 group at 24 h, but at 2 h, though with less effectiveness than that in IP5 and Ade group. Dia pretreatment reduced twitch and tetanic contraction forces of the tibialis anterior muscle after 2 h of reperfusion, but obviously improved twitch tension at 24 h. Improvement in the tetanic tension, however, was seen in none of the groups. Serum CPK of IP5, IP10 and Ade groups after 2 and 24 h while Dia at only 24 h of reperfusion was obviously lower than that of IR group. CONCLUSIONS: Ischemic and Ade preconditioning can protect the limbs of rats from ischemia-reperfusion injury, and Dia has delayed protective effect. IP5 is superior than IP10 and Ade PC can produce similar effect to that of ischemic PC.

Adenosine↗

PubMed1992

[Adverse drug reactions: Naranjo's and Venulet's algorithms].

Prospective evaluation of adverse drug experiences (ADE) in patients admitted in the Respiratory Section of a General Hospital. 32 ADE's were collected (14.6%). Mean age and stay-length were longer in ADE group but with no statistical significance. Theophyllines, beta-mimetics and antibiotics were the more frequent responsibilities of ADE's. ADE's class more frequently reported was epigastralgia-nausea in 40.6%, followed by dermic disorders in 18.75%. No deaths were attributed to ADE's ans only 9 required an specific treatment. Using Naranjo's and Venulet's algorithms we have found them as non-comparable tests.

Adolescent↗

PubMed1990

A pharmaceutical manufacturer's perspective on reporting adverse drug experiences.

The important cooperative roles that pharmacists and manufacturers can play in submitting and evaluating adverse drug experience (ADE) reports are described. Hoffmann-La Roche receives approximately 100,000 drug-related reports and inquiries annually. These reports must be evaluated, and ADEs must be distinguished from anecdotal reports, queries, lack-of-effectiveness reports, or product complaints. An ADE report should include information about (1) the patient, including history and demographics; (2) the drug, including dosage and concomitant medications; and (3) the onset, resolution, and outcome of the event, which may be a reaction, an abnormal laboratory value, or a finding that the drug did not work as expected. Complete and accurate reports are more valuable, but reports of all potential ADEs should be submitted. The evaluation process that occurs at Hoffmann-La Roche when an ADE report is received is described. Possible outcomes include reports submitted to FDA, site visits (if clusters of reactions are reported), and introduction of new product labeling with stronger warnings. Pharmacists and other healthcare professionals should report ADEs to manufactures as well as to FDA.

Drug Industry↗

PubMed1995

[Something more about adverse reactions to medications].

OBJECTIVE: To describe adverse drug effects (ADE) and their frequency in primary care patients. DESIGN: Descriptive and longitudinal study during 1 year (1990). SETTING: Urban Health Center. Primary Care. Madrid (Spain). PATIENTS AND OTHER PARTICIPANTS: 15,483 persons, nine general practitioner and one pharmacist. INTERVENTIONS: Doctors were invited to register any adverse drug effects they had notice in their patients. Doctors registered information and gave notice to the pharmacist about medicines, dosage and period of administration, clinical manifestations, and improving or not if drug was withdrawal. MEASUREMENTS AND MAIN RESULTS: 326 adverse drugs effects were notified, 30.9 ADE per thousand attended patients. 117 principles actives were involved, and 415 clinical manifestations were registered. The more affected patients were women (2/1). The age groups with higher ADE relative frequencies were children under one year and older people. CONCLUSIONS: The absolute frequency of medicines involved in ADE are different to relative frequencies when ADE per thousand prescription units are used. Some of the ADE notified were not referred before in the bibliography, so primary care is a good place to research on pharmacosurveillance.

Adolescent↗

PubMed1995

Safety of levosimendan and other calcium sensitizers.

Levosimendan belongs to a new group of heart failure drugs, the calcium sensitizers. Because these compounds are not yet available for clinical use, the adverse drug events (ADEs) during levosimendan treatment cannot be predicted in detail. To evaluate the tolerability of levosimendan in human subjects, ADEs, safety laboratory values before and after treatment, and ambulatory ECG findings have been collected from several phase I and phase II clinical studies. By June 1994, approximately 200 subjects had received levosimendan. The most common ADE seen in healthy volunteers is headache, reported by some 40% of subjects in oral dosing but only 10% in i.v. dosing. The incidence of headache does not correlate well with the total daily dose of the drug. However, the controlled release formulations tested appear to cause vasodilatory symptoms more frequently than i.v. or rapid release oral formulations. The other typical vasodilatory ADEs seen in healthy volunteers are nausea, palpitation, and dizziness. Symptomatic hypotension is rarely encountered. It appears that heart failure patients tolerate the vasodilatory actions of the drug better than healthy volunteers. Only individual cases of headache, vertigo, and flushing have been reported, and injection site irritation has been the most commonly reported ADE (with an incidence <5%). However, because the longest administration of the i.v. infusion has been only 24 h, the duration of exposure to the drug is too short to allow any definitive conclusions to be drawn. All patients who have received levosimendan have been monitored with an ambulatory ECG. Even though some increase in heart rate is seen with high doses of the drug, there are thus far no signs of an increased incidence of ventricular tachyarrhythmias, nor have there been any noteworthy changes in the clinical laboratory safety tests. The experience with levosimendan is limited thus far and long-term data are lacking. It can be concluded, however, that at least in i.v. dosing the drug is devoid of ADEs with significant medical seriousness.

Cardiotonic Agents↗

PubMed2001

Dose discrepancies between the Physicians' Desk Reference and the medical literature, and their possible role in the high incidence of dose-related adverse drug events.

BACKGROUND: Adverse drug events (ADEs) are a major cause of morbidity and mortality, and even minor ADEs may adversely affect patients' compliance with treatment. Because most ADEs are dose-related phenomena, adjusting drug dosages to account for individual patients' needs and tolerances is fundamental to good therapeutics. OBJECTIVE: To determine whether the Physicians' Desk Reference (PDR), the leading source of drug information for physicians, provides the full range of effective drug doses, especially the lowest, least ADE-prone doses of medications, for physicians to consider in treating patients. METHODS: Review of dosage guidelines and dose-response information in the PDR. Comparison with dose-response data obtained from articles listed in MEDLINE from 1966 to 2000. RESULTS: For many types of medications, physicians are frequently advised to use the lowest effective doses of drugs, especially initially. Yet, effective low doses determined in prerelease studies or in postrelease work are often omitted from the PDR, even when they have been recommended by expert panels. CONCLUSIONS: Optimal therapeutics depends on the availability of comprehensive information. However, the PDR contains only the limited dose information from package inserts. Because the PDR was originally developed as a promotional device, there is no mechanism by which all clinically relevant dose-response data or important postrelease discoveries are regularly and rapidly incorporated into it. Thus, a gap exists in the availability of current and comprehensive dose information for physicians. This article provides information on lower, effective doses for 48 major medications, with an extensive reference list-a compilation of low-dose information not previously published, to our knowledge, in the medical literature. Physicians must have a readily accessible source of current and complete dose-response information to individualize drug therapy and minimize the risks of ADEs.

Adverse Drug Reaction Reporting Systems↗

PubMed2003

Pharmacists on rounding teams reduce preventable adverse drug events in hospital general medicine units.

BACKGROUND: Previous studies found that medication errors result from lack of sufficient information during the prescribing step. Therefore, it is proposed that having a pharmacist available when patients are evaluated during the rounding process may reduce the likelihood of preventable adverse drug events (ADEs). The objectives of this study were to evaluate the impact of having a pharmacist participate with a physician rounding team on preventable ADEs in general medicine units and to document pharmacist interventions made during the rounding process. METHODS: A single-blind, standard care-controlled study design was used to compare patients receiving care from a rounding team including a pharmacist with patients receiving standard care (no pharmacist on rounding team). Patients admitted to and discharged from the same general medicine unit were included in the study. The main outcome measure of this study was preventable ADEs. Patient records were randomly selected and evaluated by a blinded process involving independent senior pharmacist specialists and a senior staff physician. Interventions made by the pharmacists in the treatment group were documented. RESULTS: The rate of preventable ADEs was reduced by 78%, from 26.5 per 1000 hospital days to 5.7 per 1000 hospital days. There were 150 documented interventions recommended during the rounding process, 147 of which were accepted by the team. The most common interventions were (1) dosing-related changes and (2) recommendations to add a drug to therapy. CONCLUSION: Pharmacist participation with the medical rounding team on a general medicine unit contributes to a significant reduction in preventable ADEs.

Drug Utilization Review↗

PubMed2005

Patient-reported medication symptoms in primary care.

BACKGROUND: Little is known about the prevalence and character of medication-related symptoms in primary care and their relationship to adverse drug events (ADEs) or about factors that affect patient-physician communication regarding medication symptoms. METHODS: The study included 661 patients who received prescriptions from physicians at 4 adult primary care practices. We interviewed patients 2 weeks and 3 months after the index visit, reviewed patients' medical records, and surveyed physicians whose patients identified medication-related symptoms. Physician reviewers determined whether medication symptoms constituted true ADEs. We used multivariable regression to examine factors associated with patients' decision to discuss symptoms with a physician and with physicians' decision to alter therapy. RESULTS: A total of 179 patients identified 286 medication-related symptoms but discussed only 196 (69%) with their physicians. Physicians changed therapy in response to 76% of reported symptoms. Patients' failure to discuss 90 medication symptoms resulted in 19 (21%) ameliorable and 2 (2%) preventable ADEs. Physicians' failure to change therapy in 48 cases resulted in 31 (65%) ameliorable ADEs. In multivariable analyses, patients who took more medications (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.04-1.08; P<.001) and had multiple medication allergies (OR = 1.07; 95% CI = 1.03-1.11; P = .001) were more likely to discuss symptoms. Male physicians (OR = 1.20, 95% CI = 1.09-1.26; P = .002) and physicians at 2 practices were more likely to change therapy (OR = 1.24; 95% CI = 1.17-1.28; P<.001; and OR = 1.17; 95% CI = 1.08-1.24; P = .002). CONCLUSION: Primary care physicians may be able to reduce the duration and/or the severity of many ADEs by eliciting and addressing patients' medication symptoms.

Adult↗

PubMed1999

Pharmacist participation on physician rounds and adverse drug events in the intensive care unit.

CONTEXT: Pharmacist review of medication orders in the intensive care unit (ICU) has been shown to prevent errors, and pharmacist consultation has reduced drug costs. However, whether pharmacist participation in the ICU at the time of drug prescribing reduces adverse events has not been studied. OBJECTIVE: To measure the effect of pharmacist participation on medical rounds in the ICU on the rate of preventable adverse drug events (ADEs) caused by ordering errors. DESIGN: Before-after comparison between phase 1 (baseline) and phase 2 (after intervention implemented) and phase 2 comparison with a control unit that did not receive the intervention. SETTING: A medical ICU (study unit) and a coronary care unit (control unit) in a large urban teaching hospital. PATIENTS: Seventy-five patients randomly selected from each of 3 groups: all admissions to the study unit from February 1, 1993, through July 31, 1993 (baseline) and all admissions to the study unit (postintervention) and control unit from October 1, 1994, through July 7, 1995. In addition, 50 patients were selected at random from the control unit during the baseline period. INTERVENTION: A senior pharmacist made rounds with the ICU team and remained in the ICU for consultation in the morning, and was available on call throughout the day. MAIN OUTCOME MEASURES: Preventable ADEs due to ordering (prescribing) errors and the number, type, and acceptance of interventions made by the pharmacist. Preventable ADEs were identified by review of medical records of the randomly selected patients during both preintervention and postintervention phases. Pharmacists recorded all recommendations, which were then analyzed by type and acceptance. RESULTS: The rate of preventable ordering ADEs decreased by 66% from 10.4 per 1000 patient-days (95% confidence interval [CI], 7-14) before the intervention to 3.5 (95% CI, 1-5; P<.001) after the intervention. In the control unit, the rate was essentially unchanged during the same time periods: 10.9 (95% CI, 6-16) and 12.4 (95% CI, 8-17) per 1000 patient-days. The pharmacist made 366 recommendations related to drug ordering, of which 362 (99%) were accepted by physicians. CONCLUSIONS: The presence of a pharmacist on rounds as a full member of the patient care team in a medical ICU was associated with a substantially lower rate of ADEs caused by prescribing errors. Nearly all the changes were readily accepted by physicians.

Boston↗

PubMed1998

Quantitative analysis of 1,3-butadiene-induced DNA adducts in vivo and in vitro using liquid chromatography electrospray ionization tandem mass spectrometry.

1,3-Butadiene (BD) is a high volume industrial chemical which is known as a multi-site rodent carcinogen and is classified as a probable human carcinogen. Covalent interactions of the reactive epoxy metabolites of BD with DNA lead to the formation of DNA adducts which may cause mutations and tumor formation. In the present work, liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was employed for analyses of BD-induced DNA adducts in vitro and in vivo. Selected reaction monitoring (SRM) using the fragmentation of the [M + H]+ ions of the adducts to the corresponding protonated nucleobases under collision-induced dissociation was performed. Quantitation was based on isotope dilution with 13C- and 15N-labeled internal standards. The methods were applied in vitro [calf thymus DNA and TK6 cell cultures treated with epoxy metabolites of BD, 3,4-epoxy-1-butene (EB) and diepoxybutane (DEB)] and in vivo [DNA isolated from tissues of BD-exposed laboratory animals]. Two regioisomers of N-7-EB-guanine adducts, N-7-(2-hydroxy-3-buten-1-yl)guanine (N-7-EB-Gua I) and N-7-(1-hydroxy-3-buten-2-yl)guanine (N-7-EB-Gua II) and two N-3-EB-adenine isomers, N-3-(2-hydroxy-3-buten-1-yl)adenine and N-3-(1-hydroxy-3-buten-2-yl)adenine (N-3-EB-Ade I and II), were found in EB-exposed samples. N-7-(2',3',4'-trihydroxybut-1'-yl)guanine (N-7-THB-Gua), N6-(2',3',4'-trihydroxybut-1'-yl)adenine (N6-THB-Ade), and N-3-(2',3',4'-trihydroxybut-1'-yl)adenine (N-3-THB-Ade) were detected in DEB-treated DNA. DNA isolated from liver and lung of rats and mice exposed to 1250 ppm BD for 2 weeks contained both regioisomers of N-7-EB-Gua and N-3-EB-Ade, as well as N-7-THB-Gua and N6-THB-Ade. The methods developed in this work provide the means to study accumulation, repair and dose-response relationships of BD-DNA adducts in vivo. Although less sensitive than gas chromatography/electron capture negative ionization high-resolution mass spectrometry (GC/ECNI-HRMS), LC/ESI(+)-MS/MS in the SRM mode is extremely useful for analysis of BD-DNA adducts, which are not amenable to GC and derivatization owing to the presence of several adjacent polar functional groups. Using LC/ESI-MS/MS and isotope dilution, multiple structurally diverse BD-DNA adducts can be analyzed simultaneously in the same sample with minimal sample preparation.

Animals↗

PubMed2006

Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes.

OBJECTIVE: To determine associations of methotrexate (MTX) efficacy and toxicity with single-nucleotide polymorphisms (SNPs) in genes coding for folate pathway enzymes in patients with early rheumatoid arthritis (RA). METHODS: Patients (n=205) with active RA received MTX at an initial dosage of 7.5 mg/week, which was increased to 15 mg/week and combined with folic acid (1 mg/day) after 4 weeks. If the Disease Activity Score in 44 joints (DAS44) was >2.4 at 3 months, MTX was increased to 25 mg/week. MTX efficacy was evaluated at 3 and 6 months and compared for genotypes in 3 analyses: patients with and without good response (DAS44 1.2), and patients with and without moderate improvement (DeltaDAS44>0.6). The association between MTX-related adverse drug events (ADEs) and genotype was evaluated by comparing genotypes between patients with and without ADEs, specifically pneumonitis, gastrointestinal ADEs, skin and mucosal ADEs, and elevated liver enzyme levels. The following SNPs were analyzed: methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, dihydrofolate reductase (DHFR) -473G>A, DHFR 35289G>A, and reduced folate carrier 80G>A. In case of significant differences, odds ratios (ORs) were calculated. RESULTS: At 6 months, MTHFR 1298AA was associated with good improvement relative to 1298C (OR 2.3, 95% confidence interval [95% CI] 1.18-4.41), which increased with increased copies of the MTHFR 677CC haplotype. In contrast, MTHFR 1298C allele carriers developed more ADEs (OR 2.5, 95% CI 1.32-4.72). CONCLUSION: Patients with MTHFR 1298AA and MTHFR 677CC showed greater clinical improvement with MTX, whereas only the MTHFR 1298C allele was associated with toxicity. In the future, MTHFR genotypes may help determine which patients will benefit most from MTX treatment.

Antirheumatic Agents↗

PubMed1991

Expression of a human cDNA encoding a protein containing GAR synthetase, AIR synthetase, and GAR transformylase corrects the defects in mutant Chinese hamster ovary cells lacking these activities.

The isolation of a human cDNA encoding the multifunctional protein containing GAR synthetase, AIR synthetase, and GAR transformylase by functional complementation of purine auxotrophy in yeast has been reported. Chinese hamster ovary (CHO) cell mutant purine auxotrophs deficient in GAR synthetase (Ade-C) or AIR synthetase plus GAR transformylase (Ade-G) activities were transfected with this human GART cDNA subcloned into a mammalian expression vector. This restored 49-140% of the activities of GAR synthetase, AIR synthetase, and GAR transformylase in transfected cells when compared to wild-type CHO K1 parental cells. Study of one stably expressing transfectant, AdeC2, revealed that the human GART cDNA was incorporated into the CHO genome. The enzyme activities appear to be associated with an expressed protein of 110 kDa, very similar to that of purified human GART trifunctional enzyme. The Ade-C mutant shows reduced amounts of GART mRNA compared to CHO K1 and a protein of apparently reduced size, results consistent with the purine requirement and enzyme deficiency observed in the mutant. These experiments provide definitive evidence that the human GART cDNA encodes and can direct the production of active human GART trifunctional protein in mammalian cells. They also provide important evidence that the Ade-C and Ade-G mutants of CHO cells are defective in this gene.

Acyltransferases↗

PubMed1975

Possibilities of the conjugation process in mycobacteria.

Results obtained when studying conjugation in mycobacteria by means of different methods are summarized. The method of conjugation on surface of a solid complete medium was tested with different auxotrophic mutants of different strains of Mycobacterium smegmatis. It was not possible to obtain positive results even by means of the above method. This was probably due to unsuitability of the chosen strains of Mycobacterium smegmatis. Preparation of the donor strain by transfer of the F factor from Escherichia coli F'ORF 1 ade+ lac+ pro+ to Mycobacterium phlei PA ade Stmr by means of sexduction is described. Frequency of the phenotype PA ade+ Stmr increased in the average by two and a half orders of magnitude with respect to the control, however, a further transfer from cultures of the cells ade+ Stmr to cells ade could not be demonstrated. Experiments aimed at transferring the R factor from strains Escherichia coli K-12 to Mycobacterium phlei were unsuccessful.

Conjugation, Genetic↗

PubMed2004

Xanthine dehydrogenase and aldehyde oxidase impact plant hormone homeostasis and affect fruit size in 'Hass' avocado.

The contribution of xanthine dehydrogenase (XDH, EC 1.1.1.204) to fruit size was investigated using the normal and small-fruit variants of Persea americana Mill. cv. 'Hass'. Inhibition of XDH by treatment of normal fruit, in the linear phase of growth (phase II), with allopurinol (Allo) arrested fruit growth. Adenine (Ade), a less effective inhibitor of this enzyme, also arrested fruit growth when applied in phase II and slowed fruit growth when applied in phase III. A time-course study on the activity of XDH in mesocarp tissue from normal and small fruit showed that maximum activity occurred late in phase II and that the peak in activity was absent in mesocarp of the small fruit. Feeding Ade to growing fruit in phase III caused a transient decline in fruit growth (measured as change in fruit length). Thereafter, growth resumed although fruit size was irreversibly affected. Treatment of fruit with Ade and Ade-containing cytokinins altered activity of another molybdenum enzyme, aldehyde oxidase (EC 1.2.3.1). Cytokinin oxidase was induced by cytokinin and auxin. Purine catabolism via hypoxanthine/xanthine was operative in normal fruit and in mesocarp from the small-fruit variant and as expected, Allo treatment caused accumulation of xanthine and adenine. In the absence of an increase in XDH during growth of the small-fruit phenotype, low levels of Ade were interpreted as resulting from respiration-enhanced adenylate depletion. Stress and/or pathogen induction of the alternative oxidase pathway is proposed as a possible cause.

Adenine↗

PubMed1990

Complement-mediated antibody-dependent enhancement of HIV-1 infection requires CD4 and complement receptors.

In this study it is demonstrated that complement-mediated antibody-dependent enhancement (C'-ADE) of HIV-1 infection in vitro is blocked by murine monoclonal antibodies to CD4 and complement receptor type 2 (CR2) while HIV-1 infection in the absence of C'-ADE is blocked by anti-CD4 but not anti-CR2 monoclonal antibodies. The anti-CR2 murine monoclonal antibody, OKB7, blocked C'-ADE of HIV-1 infection at concentrations greater than 1 microgram/ml. The anti-CD4 monoclonal antibody, OKT4a, but not OKT4f blocked C'-ADE at concentrations greater than 0.06 microgram/ml. HIV-1 infections were quantitated by cytopathic effect, indirect immunofluorescence, and reverse transcriptase release. It appears from these in vitro studies that C'-ADE of HIV-1 infection requires both CD4 and complement receptors while HIV-1 infection in the absence of antibody and complement requires only CD4.

Antibodies, Monoclonal↗

PubMed2006

Effects of multiple alcohol deprivations on operant ethanol self-administration by high-alcohol-drinking replicate rat lines.

Previously, we reported that the expression of an alcohol deprivation effect (ADE) under 24-h free-choice alcohol-drinking access in high-alcohol-drinking (HAD) replicate lines of rats is dependent upon repeated cycles of alcohol access and forced abstinence. In the present study, operant techniques (including progressive ratio measures) were used to examine the effects of initial deprivation length and number of deprivation cycles on the magnitude and duration of the ADE in HAD rats to test the hypothesis that repeated deprivations increase the reinforcing effects of ethanol. Adult male HAD-1 and HAD-2 rats were trained in two-lever operant chambers to concurrently self-administer 15% ethanol (v/v) on a fixed-ratio (FR)-5 schedule and water on an FR-1 schedule of reinforcement in daily 1-h sessions. Following 10 weeks of daily 1-h sessions, the HAD-1 and HAD-2 rats were randomly assigned to one of four groups (n=6-8/group/line): nondeprived, or deprived of alcohol for 2, 5, or 8 weeks. Following this initial period, the deprived groups were given 15% ethanol again in the operant chambers for a 2-week period, following which they were deprived again for 2 weeks (all three deprived groups). Following the fifth deprivation, the rats underwent a progressive ratio test to determine the breakpoints for the nondeprived and deprived groups. The expression of an ADE under operant conditions in HAD rats was dependent upon exposure to repeated cycles of ethanol access and abstinence. Additionally, repeated deprivations increased both the magnitude and the duration of the ADE as indicated by increased responding on the ethanol lever for more sessions. Breakpoint values for the deprived groups were 1.5-fold and twofold higher than the value for the nondeprived group for the HAD-1 and HAD-2 rats, respectively. The results suggest that repeated alcohol deprivations increased the expression of an ADE and the reinforcing effects of ethanol in both HAD replicate lines of rats, and these effects were more pronounced in the HAD-2 line than the HAD-1 line.

Alcohol Drinking↗