No evidence of HIV and SIV sequences in two separate lots of polio vaccines used in the first U.S. polio vaccine campaign.
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We obtained sealed vials of two different polio vaccine lots, expiration date 1955, which were used in the first U.S. polio vaccine campaign. These early lots were pulled from the market because they contained live infectious poliovirus which caused polio in some of the vaccines. Theoretically, these vaccines could have contained other infectious retroviruses, including HIV. No viral sequences were detected using RT-PCR analyses with primers capable of amplifying chimpanzee SIV and HIV-1-related viruses nor with primers for macaque SIV, sooty mangabey SIV, and HIV-2-related viruses. Poliovirus sequences were readily amplified by RT-PCR, suggesting that the technique used would have detected SIV or HIV sequences, if present. (+info)
Lysophosphatidylcholine and lyso-PAF display PAF-like activity derived from contaminating phospholipids.
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Lysophosphatidylcholine is an abundant component of plasma and oxidized LDL that displays several biological activities, some of which may occur through the platelet-activating factor (PAF) receptor. We find that commercial lysophosphatidylcholine, its alkyl homolog (lyso-PAF), and PAF all induce inflammation in a murine model of pleurisy. Hydrolysis of PAF to lyso-PAF by recombinant PAF acetylhydrolase abolished this eosinophilic infiltration, implying that lyso-PAF should not have displayed inflammatory activity. Saponification of lyso-PAF or PAF acetylhydrolase treatment of lyso-PAF or lysophosphatidylcholine abolished activity; neither lysolipid should contain susceptible sn-2 residues, suggesting contaminants account for the bioactivity. Lyso-PAF and to a lesser extent lysophosphatidylcholine stimulated Ca(2+) accumulation in 293 cells stably transfected with the human PAF receptor, and this was inhibited by specific PAF receptor antagonists. Again, treatment of lyso-PAF or lysophosphatidylcholine with recombinant PAF acetylhydrolase, a nonselective phospholipase A(2), or saponification of lyso-PAF destroyed the PAF-like activity, a result incompatible with lyso-PAF or lysophosphatidylcholine being the actual agonist. We conclude that neither lyso-PAF nor lysophosphatidylcholine is a PAF receptor agonist, nor are they inflammatory by themselves. We suggest that PAF or a PAF-like mimetic accounts for inflammatory effects of lysophosphatidylcholine and lyso-PAF. (+info)
Effects of ultrapure dialysis fluid on nutritional status and inflammatory parameters.
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BACKGROUND: Malnutrition and chronic systemic inflammatory response syndrome not only coexist in uraemia, but may also have a bi-directional cause-and-effect relationship. To evaluate the role of dialysate-related cytokine induction in inflammatory response and nutritional status, we conducted a prospective comparison of two dialysis fluids differing in their microbiological quality. METHODS: Forty-eight early haemodialysis patients were assigned to either treatment with conventional (potentially microbiologically contaminated) or on-line produced ultrapure dialysis fluid. Study parameters were bacterial growth, markers of systemic inflammation (C-reactive protein (CRP) and interleukin 6), and parameters of nutritional status (estimated dry weight, upper mid-arm muscle circumference, serum albumin concentration, insulin-like growth factor 1, leptin, and protein catabolic rate). Patients were followed for 12 months. RESULTS: There were no statistically significant differences in demographic and treatment characteristics, degree of bacterial contamination of the dialysate, markers of systemic inflammation, or parameters of nutritional status among the two treatment groups at recruitment. Changing from conventional to ultrapure dialysis fluid reduced significantly the levels of IL-6 (19+/-3 pg/ml to 13+/-3 pg/ml) and CRP (1.0+/- 0.4 mg/dl to 0.5+/-0.2 mg/dl), and resulted in significant increases in estimated dry body weight, mid-arm muscle circumference, serum albumin concentration, levels of the humoral factors, and in protein catabolic rate after 12 months. Continuous use of conventional dialysis fluid (median 40-60 c.f.u./ml) was not associated with significant alterations in markers of inflammation (IL-6 21+/-4 pg/ml vs 24+/-6 pg/ml, CRP 0.9+/-0.3 mg/dl vs 1.1+/-0.4 mg/dl) or of nutritional status at any time of the study. All differences in systemic inflammation and nutritional parameters observed during the study period (from recruitment to month 12) were significant between the two patient groups. CONCLUSIONS: Cytokine induction by microbiologically contaminated dialysis fluid has a negative impact on nutritional parameters of early haemodialysis patients. The microbiological quality of the dialysis fluid represents an independent determinant of the nutritional status in addition to known factors, such as dose of dialysis and biocompatibility of the dialyser membrane. Ultrapure dialysis fluid adds to the cost of the dialytic treatment, but may improve the nutritional status in long-term haemodialysis patients. (+info)
Effects of Stealth adulterant on immunoassay testing for drugs of abuse.
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Stealth is an adulterant advertised as being undetectable by adulteration tests. It has been described as peroxidase and peroxide, which, when added to urine samples, are intended to prevent a positive drug test. Characterization of the effect of Stealth on urine samples and immunoassay results was undertaken to assist in detection of this adulterant. Stealth was added to a number of urine matrices, and various parameters were evaluated including pH, specific gravity, color, creatinine, chloride, urea, blood, glucose, and nitrite. Samples were spiked with THC acid metabolite, benzoylecgonine, morphine, secobarbital, PCP, amphetamine, and lysergic acid diethylamide (LSD) then tested by Roche OnLine and Microgenics CEDIA immunoassay reagents. Results of these analyses showed Stealth did not cause the urine sample to exceed any of the monitored parameters including those routinely used in drug-testing laboratories that would indicate adulteration of a sample. It did, however, cause samples positive for the marijuana metabolite (11-nor-delta9-tetrahydrocannibinol-9-carboxylic acid), LSD, and opiate (morphine) at 125-150% of cutoff to screen negative by immunoassay. Adulterating an authentic positive sample provided by a marijuana user caused that sample to screen negative using these immunoassay reagents as well. (+info)
TT virus contaminates first-generation recombinant factor VIII concentrates.
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Recombinant factor VIII and factor IX concentrates, human-plasma-derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein-free) concentrates were negative for the virus. In 59% of patients treated with either first- or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin. (+info)
Reduction of endotoxin levels in influenza virus vaccines by barium sulfate adsorption-elution.
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The level of endotoxin in influenza virus vaccine lots was reduced 10- to 20-fold after barium sulfate adsorption-elution. The amount of viral antigen lost was negligible. (+info)
Ethanol inhibition of glycine-activated responses in neurons of ventral tegmental area of neonatal rats.
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The brain is particularly sensitive to alcohol during the period of its rapid growth. To better understand the mechanism(s) involved, we studied ethanol effects on glycine-activated responses of ventral tegmental area (VTA) neurons isolated from the newborn rat, using whole cell and gramicidin perforated patch-clamp techniques. Previously we reported that 0.1-40 mM ethanol enhances glycine-induced responses of 35% of VTA neurons. We now direct our attention to the inhibitory effects of ethanol observed in 45% (312 of 694) of neonatal VTA neurons. Under current-clamp conditions, 1 mM ethanol had no effect on the membrane potential of these cells, but it decreased glycine-induced membrane depolarization and the frequency of spontaneous action potentials. Under voltage-clamp conditions, 0.1-10 mM ethanol did not elicit a current but depressed the glycine-induced currents. The ethanol-induced inhibition of glycine current was independent of membrane potential (between -60 and +60 mV). Likewise, ethanol did not alter the reversal potential of the glycine-activated currents. Ethanol-mediated inhibition of glycine current depended on the glycine concentration. While ethanol strongly depressed currents activated by 30 microM glycine, it had no appreciable effect on maximal currents activated by 1 mM glycine. In the presence of ethanol (1 mM), the EC(50) for glycine increased from 32 +/- 5 to 60 +/- 3 microM. Thus ethanol may decrease the agonist affinity of glycine receptors. A kinetic analysis indicated that ethanol shortens the time constant of glycine current deactivation but has no effect on activation. In conclusion, by altering VTA neuronal function, ethanol-induced changes in glycine receptors may contribute to neurobehavioral manifestations of the fetal alcohol syndrome. (+info)
L-tryptophan contaminant 'peak E' induces the release of IL-5 and IL-10 by peripheral blood mononuclear cells from patients with functional somatic syndromes.
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In 1989, the development of eosinophilia myalgia syndrome (EMS) was observed in some patients after the intake of l-tryptophan containing several contaminants, including 1,1'-ethylidenebis[l-tryptophan] ('peak E'). Since l-tryptophan has been taken particularly by individuals suffering from functional somatic syndromes (FSS), such as fibromyalgia syndrome (FMS), we put forward the hypothesis that EMS may have developed preferentially in patients with FSS as an allergic reaction towards the contaminant peak E. We therefore studied the immunological reactivity towards l-tryptophan and peak E in these individuals (n = 12) and compared these data with those obtained in 12 healthy controls and 12 patients with other chronic disorders. Peripheral blood mononuclear cells (PBMC) were cultured for 7 days with pure l-tryptophan and peak E. Supernatant fluids were collected at day 7. The type 2 cytokines IL-4, IL-5 and IL-10, and the type 1 cytokines IL-2 and IFN-gamma, were determined by a double sandwich ELISA. PBMC from seven of the 12 FSS patients, but only three of the 24 controls, produced cytokines after incubation with peak E (P < 0.05). Interestingly, six of the seven FSS patients reacting with peak E produced IL-5 and/or IL-10. In contrast, PBMC from only one patient with other chronic disorders and one healthy control secreted type 2 cytokines in response to peak E. The observed heightened type 2 reactivity towards the more immunogenic contaminant 1,1'-ethylidenebis[l-tryptophan] in FSS patients may therefore be taken as an additional argument for our concept that EMS may have developed as a kind of drug-induced allergic disease. (+info)