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PubMed1992

Esmolol prevents and suppresses arrhythmias during halothane anaesthesia in dogs.

The antiarrhythmic effect of esmolol, a selective beta 1 adrenoreceptor blocker, was evaluated in the presence of epinephrine induced arrhythmias in dogs (n = 6). The arrhythmogenic dose of epinephrine (ADE) during 1.2 MAC halothane in dogs was increased from 3.23 +/- 0.25 (mean +/- SD) to 30.90 +/- 3.56 micrograms.kg-1.min-1 (P less than 0.001) by the prior administration of esmolol 0.5 microgram.kg-1 bolus followed by an infusion at the rate of 150 micrograms.kg-1.min-1. Higher esmolol infusion doses of 200 micrograms.kg-1.min-1 further increased ADE to 99.0 +/- 2.92 micrograms.kg-1.min-1 (P less than 0.001). After discontinuation of esmolol and during continued halothane anaesthesia, ventricular tachycardia was induced by increasing the infusion rate of the 100 micrograms.ml-1 solution of epinephrine. In all dogs ventricular tachycardia was restored to sinus rhythm by a bolus dose of esmolol (1 microgram.kg-1). We conclude that esmolol pretreatment increases the ADE during halothane anaesthesia in dogs. Our data suggest that esmolol may be useful as an antiarrhythmic agent in the management of epinephrine-related ventricular arrhythmias during anaesthesia in man.

Adrenergic beta-Antagonists↗

PubMed2004

Voluntary alcohol intake in two rat lines selectively bred for learned helpless and non-helpless behavior.

RATIONALE: A high comorbidity between depression and alcoholism has been reported in several studies, but the mechanisms underlying this relationship remain unknown. OBJECTIVES: We tested whether learned helplessness in rats as a model for depression is associated with enhanced alcohol intake and relapse behavior. METHODS: Congenital learned helplessness (cLH) and congenital non-learned helplessness (cNLH) rats were selectively bred for differences in an escape paradigm. Sucrose preference was tested at the first hour of the dark phase. In order to study an association with alcohol drinking behavior, rats underwent a free-choice procedure with access to water, and 5% and 20% alcohol solutions for 6 weeks. After acquisition of alcohol drinking behavior, the alcohol deprivation effect (ADE) was assessed. Sensitivity to the sedative-hypnotic effect of alcohol was measured by loss of the righting reflex. RESULTS: cLH rats showed significantly lower preference for sucrose solutions during the second half hour of the dark phase than cNLH rats. Alcohol intake of male cLH rats was not significantly different from that of male cNLH rats. In contrast, cLH female rats consumed higher amounts of alcohol than female cNLH rats. The ADE was more pronounced in female animals, although the magnitude of the ADE was similar in both cNLH and cLH female rats. The time to regain the righting reflex was significantly higher in both male and female cLH rats than in cNLH rats. CONCLUSIONS: In summary, these data suggest that an inborn depressive-like behavior in female rats is associated with enhanced alcohol intake.

Alcohol Drinking↗

PubMed2003

The effect of temperature on digestive and assimilation efficiency, gut passage time and appetite in an ambush foraging lizard, Cordylus melanotus melanotus.

In ectotherms, an increase in body temperature increases metabolic rate and may increase rates of digestive processes. We measured the thermal dependence of the apparent digestive and apparent assimilation efficiencies (ADE and AAE), gut passage time (GP) and appetite in Cordylus melanotus melanotus, a medium sized Crag Lizard, which is endemic to South Africa. Trials were conducted at 20, 22, 25, 30, 32 and 35 degrees C under controlled conditions. Trials lasted 14 days, during which, lizards were fed ca. 1 g mealworms per day. Glass beads were used as markers to determine GP at the beginning and end of trials. Faeces and urates were collected daily and oven dried at 50 degrees C. The energy content of egested matter was then measured using bomb calorimetry. ADE and AAE were not affected by temperature for either males or females. The mean+/-SE ADE and AAE were 94.4+/-0.3% and 87.2+/-0.6%, respectively. GP was not significantly different between males and females at any temperature, but decreased significantly with increasing temperature. Appetite was significantly different between the different temperatures measured. The decrease of gut passage time with increasing temperature was expected, since the digestive and assimilation efficiencies are similar over the range of temperatures tested. Lizards are thus assimilating a similar proportion of ingested energy, but at faster rates at higher temperatures. The results indicate that the digestive physiology of this species results in maximum energy gain per meal in environments where food is scarce.

Animals↗

PubMed1989

Isolation of methylcarbamoyl-adducts of adenine and cytosine following in vitro reaction of methyl isocyanate with calf thymus DNA.

Methylisocyanate (MIC) is the direct-acting acylating compound involved in the Bhopal, India disaster which occurred on December 3rd, 1984. The accidental release of MIC resulted in at least 2000 deaths, thousands of injuries and exposure of at least 200,000 people to varying amounts of MIC. We have studied how MIC reacts with 2'-deoxyribonucleosides at pH 7.0 and 37 degrees C for 1 h. MIC acylates exocyclic amino groups resulting in the following methylcarbamoyl (MC) adducts: N6-MC-Ade (0.5% yield) and N4-MC-dCyd (6%). No adducts were detected with dThd and dGuo. UV, NMR and mass spectrometry were employed to spectroscopically characterize these adducts. MIC was reacted with calf thymus DNA (pH 7.0, 37 degrees C, 1 h) and yielded N6-MC-Ade (0.3 nmol/mg DNA) and N4-MC-dCyd (2.0 nmol/mg DNA). The inability of others to observe genetic mutations by MIC in Salmonella and Drosophila is consistent with the exocyclic adducts at N4 of Cyt and N6 of Ade where normal hydrogen bonding can occur after rotation of the methylcarbamoyl group anti to the Watson-Crick side of the molecule assuming that MIC binds to DNA within the intact cell.

Adenine↗

PubMed1993

Optimized separation of purine bases and nucleosides in human cord plasma by capillary zone electrophoresis.

An optimized separation of the main purine compounds of human serum by capillary zone electrophoresis is presented. Separations were performed in an uncoated silica capillary (44 cm x 75 microns I.D., 37 cm to window) on a SpectraPhoresis 1000 system with UV detection. The separation of adenine (Ade), adenosine (Ado), guanine (Gua), guanosine (Guo), hypoxanthine (Hyp), inosine (Ino), xanthine (Xan) and uric acid (UA) was optimized with respect to pH, temperature, applied potential and hydrodynamic injection time. Optimum conditions were 20 mM borate buffer (pH 9.4), 37 degrees C, 20 kV and 9 s load and detection at 260 nm. Linearity extended from 1 to 125 microM. The sensitivity of the method was 0.5 microM, which is adequate for measuring Ade, Gua, Hyp and UA in plasma samples. Plasma samples from newborns were precipitated with an equal volume of perchloric acid (7%, v/v), the supernatant was adjusted to neutral pH with potassium carbonate and, before injection, the sample was alkalized with sodium hydroxide. The method presented here allows the determination of Ade, Guo, Hyp and UA. The levels of the determined purines were compared in samples from control newborns, preterm babies and newborns with asphyxia or acidic serum pH values.

Calibration↗

PubMed1984

Molecular cloning of the ADE1 gene of Saccharomyces cerevisiae and stability of the transformants.

Plasmid YEp ( ADE1 )1a, containing a 2.7-kb Sau3A fragment of Saccharomyces cerevisiae DNA inserted at the BamHI site of the yeast shuttle vector pBTI -1 (Morris et al., 1981), results in high frequency, unstable transformation of ade 1 yeast strains. A second plasmid, YRp ( ADE1 )2, containing adjacent 0.5-kb and 3.0-kb BamHI fragments in pBR322 gave three types of yeast transformants: (1) transformants carrying extrachromosomal copies of the plasmid which indicate the presence of a functional ars sequence, (2) transformants indistinguishable from ade 1 strains by hybridization analysis, and (3) a transformant carrying a multimeric form of YRp ( ADE1 )2. Cells transformed with either of the plasmids are free of the red pigment characteristic of ade 1 mutants and indicate potential for direct colour-based selection of yeast transformants using ADE1 plasmids.

Cloning, Molecular↗

PubMedDate not supplied

Examination of the negative alcohol-deprivation effect in the golden hamster (Mesocricetus auratus).

When ethanol-consuming animals are denied access to their ethanol solution for a period of days, there is typically a temporary but substantial increase in their ethanol consumption when the solution is returned. Golden hamsters are unusual in that they actually decrease their consumption of a 7% ethanol solution (v/v) under these circumstances. There experiments were therefore undertaken to further investigate this unusual negative alcohol-deprivation effect (ADE) in hamsters. In Experiment 1, the negative ADE was observed across a wide range of ethanol concentrations; adult male hamsters were given access to food, water, and either a 7.5, 15, or 30% (v/v) ethanol solution, and when the ethanol solution was withdrawn for seven days and then returned, ethanol consumption decreased significantly for several days and then recovered. Experiment 2 demonstrated that similar negative deprivation effects occur with glucose (15% w/v) and saccharin (0.1%) solutions, suggesting that the nutritional and pharmacological properties of ethanol do not play an important role in the negative ADE of hamsters. In Experiment 3, when hamsters with continuous access to either an ethanol, glucose, or saccharin solution were switched to an alternate-days access schedule, their intake of solutions decreased substantially, supporting the conclusion that a common mechanism accounts for the golden hamster's negative deprivation responses to ethanol solutions and to other solutions, both nutritive and nonnutritive. Hypotheses relating to the mechanism underlying negative deprivation effects are presented and discussed.

Alcohol Drinking↗

PubMed2004

FrzA/sFRP-1, a secreted antagonist of the Wnt-Frizzled pathway, controls vascular cell proliferation in vitro and in vivo.

OBJECTIVE: FrzA, a member of the group of secreted frizzled related proteins (sFRP) that is expressed in the cardiovascular system, has been shown to antagonize the Wnt/frizzled signaling pathway. We have recently demonstrated its role in vascular cell growth control in vitro. In this study, we aimed to examine the mechanisms by which FrzA exerts its antiproliferative effect on vascular cells in vitro and its potential effect in vivo. METHODS AND RESULTS: On synchronized, growth-arrested endothelial cells (EC) and smooth muscle cells (SMC) treated with the recombinant purified FrzA protein, flow cytometry analysis showed that the recombinant FrzA protein delayed G1 phase and entry into S-phase. Western blot experiments demonstrated that the treatment of EC or SMC with FrzA was associated with a decrease in the level of the cyclins and cyclin-dependent kinases and an increase in cytosolic phospho-beta-catenin levels. The FrzA-induced cell cycle delay was resolved by 24 h. C57BL/6J mice underwent surgery to produce unilateral hindlimb ischemia and empty adenoviruses (AdE) or adenoviruses coding for FrzA (AdFrzA) were injected at the time of the surgery. In AdFrzA-treated mice in the 7 days following surgery, we showed a decrease in cell proliferation, capillary density, and blood flow recovery and a reduced expression of cyclin and cdk activity in the ischemic muscle compared to that in the AdE-treated ischemic muscle. To gain insight into the pathway activated by FrzA overexpression, we showed an increase in the level of cytosolic phospho-beta-catenin, a marker of beta-catenin degradation, in AdFrzA-treated ischemic muscle compared to that in control AdE-treated ischemic muscle. CONCLUSION: We provided the first evidence that an impairment of the Wnt-Frizzled pathway, via FrzA overexpression, controlled proliferation and neovascularization after muscle ischemia.

Adenoviridae↗

PubMed2006

Modelling the relationship between antibody-dependent enhancement and immunological distance with application to dengue.

When antibodies raised in response to a particular pathogen bind with immunologically similar pathogens it may facilitate infection through a phenomenon known as antibody-dependent enhancement (ADE). This process occurs between the four serotypes of dengue virus and, furthermore, secondary infection is a major risk factor in dengue hemorrhagic fever (DHF). Theory has suggested that ADE may be responsible for the large immunological distance between dengue serotypes. We investigate this hypothesis using an epidemic model for dengue in which immunological distance and the strength of immune cross-reaction are expressed separately. Cross-enhancement is considered in three alternative forms acting on susceptibility, transmission and mortality. Previous models have shown that transmission and mortality enhancement can lead to periodicity or chaos. We confirm this result for reasonable levels of susceptibility and transmission enhancement but not for mortality enhancement. We also show that when the two strains have identical basic reproductive numbers no form of enhancement leads to competitive exclusion. When the two strains have different basic reproductive numbers susceptibility or transmission enhancement allow strains with greater immunological similarity to stably coexist but mortality enhancement forces strains to be more distinct. All three forms of enhancement can be associated with DHF and we conclude that mortality enhancement must be dominant if ADE really is responsible for the immunological distance between dengue serotypes.

Antibody-Dependent Enhancement↗

PubMed2006

Diagramming patients' views of root causes of adverse drug events in ambulatory care: an online tool for planning education and research.

OBJECTIVE: Diagram patients' views of the causes of adverse drug events (ADEs) in ambulatory care, examine characteristics of causes reported by patients, and identify those that have been studied in the medical and social science literatures. METHODS: Twenty-two primary care patients were interviewed using a root cause analysis approach. Diagrams derived from interviews were consolidated and displayed online as a composite interactive causal diagram. Patient-reported causes were compared to evidence in the social science and medical literatures. RESULTS: Patients ascribed 164 causes to ADEs occurring through eight major pathways, including medication nonadherence, prescriber-patient miscommunication, patient medication error, failure to read medication label/insert, polypharmacy, patient characteristics, pharmacist-patient miscommunication, and self medication. Most frequently reported causes were intrapsychic and interpersonal in nature. Most patient-reported causes have been studied, however, several practical and motivational antecedents lack research. CONCLUSION: Conducting root cause analysis with patients reveals multiple logically linked aspects of medication safety in community settings that merit further research and consideration in patient and prescriber education. PRACTICE IMPLICATIONS: This causal diagram provides a broadly accessible planning tool for reducing ambulatory ADEs by showing a comprehensive picture of potential causes, identifying causal factors supported by evidence, and disclosing likely consequences of change efforts. Also, patient-centered medication safety strategies should address psychological and practical barriers patients face in their everyday lives.

Adolescent↗

PubMed2003

Vaccine efficacy of a cell lysate with recombinant baculovirus-expressed feline infectious peritonitis (FIP) virus nucleocapsid protein against progression of FIP.

The Type II feline infectious peritonitis virus (FIPV) infection of feline macrophages is enhanced by a monoclonal antibody (MAb) to the S protein of FIPV. This antibody-dependent enhancement (ADE) activity increased with the MAb that showed a neutralizing activity with feline kidney cells, suggesting that there was a distinct correlation between ADE activity and the neutralizing activity. The close association between enhancing and neutralizing epitopes is an obstacle to developing a vaccine containing only neutralizing epitopes without enhancing epitopes. In this study, we immunized cats with cell lysate with recombinant baculovirus-expressed N protein of the Type I FIPV strain KU-2 with an adjuvant and investigated its preventive effect on the progression of FIP. Cats immunized with this vaccine produced antibodies against FIPV virion-derived N protein but did not produce virus-neutralizing antibodies. A delayed type hypersensitivity skin response to N protein was observed in these vaccinated cats, showing that cell mediated immunity against the FIPV antigen was induced. When these vaccinated cats were challenged with a high dose of heterologous FIPV, the survival rate was 75% (6/8), while the survival rate in the control group immunized with SF-9 cell-derived antigen was 12.5% (1/8). This study showed that immunization with the cell lysate with baculovirus-expressed N protein was effective in preventing the progression of FIP without inducing ADE of FIPV infection in cats.

Animals↗

PubMed1990

Direct injection of blood samples into a high-performance liquid chromatographic adenine analyser to measure adenine, adenosine, and the adenine nucleotides with fluorescence detection.

Adenine (Ade), adenosine (Ado) and its nucleotides such as AMP, cAMP, ADP and ATP in blood or plasma were determined by a high-performance liquid chromatographic (HPLC) adenine analyser with fluorescence detection. In order to inject samples directly into the HPLC system without pretreatment except dilution, the analyser consisted of two systems each, having three columns (pre-, mini- and analytical). A precolumn with an inlet filter of pore size 40 microns was common to both systems and packed with Butyl-Toyopearl 650-M to remove hydrophobic compounds and blood cell membranes. In the system for analysis of the nucleotides, a mini-column of Hitachi anion-exchange gel 3013-N was used for adsorbing AMP, cAMP, ADP and ATP. The adsorbed nucleotides were separated by the Hitachi gel 3013-N analytical column. In the other system for analysis of Ado and Ade, they were adsorbed on a Develosil ODS-5 mini-column and separated by an Asahipak GS-320H size-exclusion analytical column. The adenine compounds in each eluate were derivatized on-line in a 15-m reaction coil at 115 degrees C with bromoacetaldehyde as the fluorescent reagent in each mobile phase for the analytical column, and detected by spectrofluorimetry. ATP, ADP and AMP were accurately determined by the direct injection of hamster, rat and human whole blood. Authentic Ade and Ado were well separated and Ado in human plasma was determined, but it was difficult to determine it in rat plasma owing to interference from an unknown compound.

Adenine↗

PubMed2003

Measurement and analysis of non-Fickian dispersion in heterogeneous porous media.

Contaminant breakthrough behavior in a variety of heterogeneous porous media was measured in laboratory experiments, and evaluated in terms of both the classical advection-dispersion equation (ADE) and the continuous time random walk (CTRW) framework. Heterogeneity can give rise to non-Fickian transport patterns, which are distinguished by "anomalous" early arrival and late time tails in breakthrough curves. Experiments were conducted in two mid-scale laboratory flow cells packed with clean, sieved sand of specified grain sizes. Three sets of experiments were performed, using a "homogeneous" packing, a randomly heterogeneous packing using sand of two grain sizes, and an exponentially correlated structure using sand of three grain sizes. Concentrations of sodium chloride tracer were monitored at the inflow reservoir and measured at the outflow reservoir. Breakthrough curves were then analyzed by comparison to fitted solutions from the ADE and CTRW formulations. In all three systems, including the "homogeneous" one, subtle yet measurable differences between Fickian and non-Fickian transport were observed. Quantitative analysis demonstrated that the CTRW theory characterized the full shape of the breakthrough curves far more effectively than the ADE.

Chemical Phenomena↗

PubMed2000

Lymph node metastasis in maxillary sinus carcinoma.

PURPOSE: To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma. METHODS AND MATERIALS: We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months. RESULTS: The median survival for all patients was 22 months (range: 2.4-356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3-4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the ipsilateral level 1-2 nodal regions (11/13). Patients with nodal relapse had a significantly higher risk of distant metastasis on both univariate (p = 0.02) and multivariate analysis (hazard ratio = 4.5, p = 0.006). The 5-year actuarial risk of distant relapse was 29% for patients with neck control versus 81% for patients with neck failure. There was also a trend for decreased survival with nodal relapse. The 5-year actuarial survival was 37% for patients with neck control and 0% for patients with neck relapse. CONCLUSION: The overall incidence of lymph node involvement at diagnosis in patients with maxillary sinus carcinoma was 9%. Following treatment, the 5-year risk of nodal relapse was 12%. SCC histology was associated with a high incidence of initial nodal involvement and nodal relapse. None of the patients presenting with SCC histology and N0 necks had nodal relapse after elective neck irradiation. Patients who had nodal relapse had a higher risk of distant metastasis and poorer survival. Therefore, our present policy is to consider elective neck irradiation in patients with T3-4 SCC of the maxillary sinus.

Adenocarcinoma↗

PubMed2003

Suppression by baclofen of alcohol deprivation effect in Sardinian alcohol-preferring (sP) rats.

Alcohol deprivation effect (ADE), i.e. the transient increase in alcohol intake that takes place in laboratory animals after a period of alcohol deprivation, has been proposed to model alcohol relapses in alcoholics. The present study investigated the effect of the GABA(B) receptor agonist, baclofen, on the development of ADE in selectively bred Sardinian alcohol-preferring (sP) rats. Acute administration of non-sedative doses of baclofen (0, 1, 1.7 and 3 mg/kg, i.p.) resulted in the complete suppression of the extra-amount of alcohol consumed during the first hour of re-access to alcohol after 7 days of deprivation. These results implicate the GABA(B) receptor in the neural substrate mediating ADE and suggest that baclofen may possess anti-relapse properties.

Alcoholism↗

PubMed2003

Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats.

Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption.

Alcohol Drinking↗

PubMed1999

The effect of experimental conditions on the levels of oxidatively modified bases in DNA as measured by gas chromatography-mass spectrometry: how many modified bases are involved? Prepurification or not?

Recently, an artifactual formation of a number of modified DNA bases has been alleged during derivatization of DNA hydrolysates to be analyzed by gas chromatography-mass spectrometry (GC-MS). These modified bases were 8-hydroxyguanine (8-OH-Gua), 5-hydroxycytosine (5-OH-Cyt), 8-hydroxyadenine (8-OH-Ade), 5-hydroxymethyluracil (5-OHMeUra), and 5-formyluracil, which represent only a small percentage of more than 20 modified DNA bases that can be analyzed by GC-MS. However, relevant papers reporting the levels of these modified bases in DNA of various sources have not been cited, and differences in experimental procedures have not been discussed. We investigated the levels of modified bases in calf thymus DNA by GC-MS using derivatization at three different temperatures. The results obtained with GC/isotope-dilution MS showed that the levels of 5-OH-Cyt, 8-OH-Ade, 5-OH-Ura, and 5-OHMeUra were not affected by increasing the derivatization temperature from 23 degrees C to 120 degrees C. The level of 8-OH-Gua was found to be higher at 120 degrees C. However, this level was much lower than those reported previously. Formamidopyrimidines were readily analyzed in contrast to some recent claims. The addition of trifluoroacetic acid (TFA) adversely affected the levels of pyrimidine-derived lesions, suggesting that TFA is not suitable for simultaneous measurement of both pyrimidine- and purine-derived lesions. The data obtained were also compared with those previously published. Our data and this comparison indicate that no artifactual formation of 5-OH-Cyt, 8-OH-Ade, and 5-OHMeUra occurred under our experimental conditions in contrast to recent claims, and no prepurification of DNA hydrolysates by a tedious procedure is necessary for accurate quantification of these compounds. The artifactual formation of 8-OH-Gua can be eliminated by derivatization at room temperature for at least 2 h, without the use of TFA. The results in this article and their comparison with published data indicate that different results may be obtained in different laboratories using different experimental conditions. The data obtained in various laboratories should be compared by discussing all relevant published data and scientific facts, including differences between experimental conditions used in different laboratories.

Adenine↗

PubMed2003

Suppression of antiviral responses by antibody-dependent enhancement of macrophage infection.

Antibody-dependent enhancement (ADE) of macrophage and monocyte infection has been demonstrated in vitro for some of the most deadly RNA viruses known. Recent evidence suggests that ADE-mediated ligation of Fc receptors might suppress host-cell antiviral gene expression by promoting early interleukin-10 (IL-10) secretion, resulting in the expression of suppressor-of-cytokine-signalling (SOCS) proteins and a Th2 bias. These findings provide potential new insights into how ADE might enhance viral infections and exacerbate disease.

Antibody-Dependent Enhancement↗