Showing papers by "Research Triangle Park published in 1992"

Strand displacement amplification—an isothermal, in vitro DNA amplification technique

Abstract: Strand Displacement Amplification (SDA) is an isothermal, in vitro nucleic acid amplification technique based upon the ability of HincII to nick the unmodified strand of a hemiphosphorothioate form of its recognition site, and the ability of exonuclease deficient klenow (exo- klenow) to extend the 3'-end at the nick and displace the downstream DNA strand. Exponential amplification results from coupling sense and antisense reactions in which strands displaced from a sense reaction serve as target for an antisense reaction and vice versa. In the original design (G. T. Walker, M. C. Little, J. G. Nadeau and D. D. Shank (1992) Proc. Natl. Acad. Sci 89, 392-396), the target DNA sample is first cleaved with a restriction enzyme(s) in order to generate a double-stranded target fragment with defined 5'- and 3'-ends that can then undergo SDA. Although effective, target generation by restriction enzyme cleavage presents a number of practical limitations. We report a new target generation scheme that eliminates the requirement for restriction enzyme cleavage of the target sample prior to amplification. The method exploits the strand displacement activity of exo- klenow to generate target DNA copies with defined 5'- and 3'-ends. The new target generation process occurs at a single temperature (after initial heat denaturation of the double-stranded DNA). The target copies generated by this process are then amplified directly by SDA. The new protocol improves overall amplification efficiency. Amplification efficiency is also enhanced by improved reaction conditions that reduce nonspecific binding of SDA primers. Greater than 10(7)-fold amplification of a genomic sequence from Mycobacterium tuberculosis is achieved in 2 hours at 37 degrees C even in the presence of as much as 10 micrograms of human DNA per 50 microL reaction. The new target generation scheme can also be applied to techniques separate from SDA as a means of conveniently producing double-stranded fragments with 5'- and 3'-sequences modified as desired.

Acquired resistance in Arabidopsis.

Abstract: Acquired resistance is an important component of the complex disease resistance mechanism in plants, which can result from either pathogen infection or treatment with synthetic, resistance-inducing compounds In this study, Arabidopsis, a tractable genetic system, is shown to develop resistance to a bacterial and a fungal pathogen following 2,6-dichloroisonicotinic acid (INA) treatment Three proteins that accumulated to high levels in the apoplast in response to INA treatment were purified and characterized Expression of the genes corresponding to these proteins was induced by INA, pathogen infection, and salicylic acid, the latter being a putative endogenous signal for acquired resistance Arabidopsis should serve as a genetic model for studies of this type of immune response in plants

Isothermal in vitro amplification of DNA by a restriction enzyme/DNA polymerase system.

Abstract: An isothermal in vitro DNA amplification method was developed based upon the following sequence of reaction events. Restriction enzyme cleavage and subsequent heat denaturation of a DNA sample generates two single-stranded target DNA fragments (T1 and T2). Present in excess are two DNA amplification primers (P1 and P2). The 3' end of P1 binds to the 3' end of T1, forming a duplex with 5' overhangs. Likewise, P2 binds to T2. The 5' overhangs of P1 and P2 contain a recognition sequence (5'-GTTGAC-3') for the restriction enzyme HincII. An exonuclease-deficient form of the large fragment of Escherichia coli DNA polymerase I (exo- Klenow polymerase) [Derbyshire, V., Freemont, P. S., Sanderson, M. R., Beese, L., Friedman, J. M., Joyce, C. M. & Steitz, T. A. (1988) Science 240, 199-201] extends the 3' ends of the duplexes using dGTP, dCTP, TTP, and deoxyadenosine 5'-[alpha-thio]triphosphate, which produces hemiphosphorothioate recognition sites on P1.T1 and P2.T2. HincII nicks the unprotected primer strands of the hemiphosphorothioate recognition sites, leaving intact the modified complementary strands. The exo- Klenow polymerase extends the 3' end at the nick on P1.T1 and displaces the downstream strand that is functionally equivalent to T2. Likewise, extension at the nick on P2.T2 results in displacement of a downstream strand functionally equivalent to T1. Nicking and polymerization/displacement steps cycle continuously on P1.T1 and P2.T2 because extension at a nick regenerates a nickable HincII recognition site. Target amplification is exponential because strands displaced from P1.T1 serve as targets for P2 and strands displaced from P2.T2 serve as targets for P1. A 10(6)-fold amplification of a genomic sequence from Mycobacterium tuberculosis or Mycobacterium bovis was achieved in 4 h at 37 degrees C.

Problems in families of male Vietnam veterans with posttraumatic stress disorder.

Abstract: Interviews were conducted with a nationally representative sample of 1,200 male Vietnam veterans and the spouses or co-resident partners of 376 of these veterans. The veteran interview contained questions to determine the presence of posttraumatic stress disorder (PTSD) and items tapping family and marital adjustment, parenting problems, and violence. The spouse or partner (S/P) interview assessed the S/P's view of these items, as well as her view of her own mental health, drug, and alcohol problems and behavioral problems of school-aged children living at home. Compared with families of male veterans without current PTSD, families of male veterans with current PTSD showed markedly elevated levels of severe and diffuse problems in marital and family adjustment, in parenting skills, and in violent behavior. Clinical implications of these findings are discussed.

Screening, predicting, and computer experiments

Abstract: Many scientific phenomena are now investigated by complex computer models or codes. Given the input values, the code produces one or more outputs via a complex mathematical model. Often the code is expensive to run, and it may be necessary to build a computationally cheaper predictor to enable, for example, optimization of the inputs. If there are many input factors, an initial step in building a predictor is identifying (screening) the active factors. We model the output of the computer code as the realization of a stochastic process. This model has a number of advantages. First, it provides a statistical basis, via the likelihood, for a stepwise algorithm to determine the important factors. Second, it is very flexible, allowing nonlinear and interaction effects to emerge without explicitly modeling such effects. Third, the same data are used for screening and building the predictor, so expensive runs are efficiently used. We illustrate the methodology with two examples, both having 20 input variables. I...

Drive mechanism for surgical instruments

Abstract: A surgical instrument for applying a ligating device to a surgical work site. The instrument is provided with a power subassembly which provides the power by which the ligating device is placed into proper position for being applied to the work site. In one embodiment, the instrument is a hemostatic clip applier and the power subassembly feeds the clips into position between the jaws of the applier which are then closed by squeezing the applier handles.

Antisense and antigene properties of peptide nucleic acids

Abstract: Peptide nucleic acids (PNAs) are polyamide oligomers that can strand invade duplex DNA, causing displacement of one DNA strand and formation of a D-loop. Binding of either a T10 PNA or a mixed sequence 15-mer PNA to the transcribed strand of a G-free transcription cassette caused 90 to 100 percent site-specific termination of pol II transcription elongation. When a T10 PNA was bound on the nontranscribed strand, site-specific inhibition never exceeded 50 percent. Binding of PNAs to RNA resulted in site-specific termination of both reverse transcription and in vitro translation, precisely at the position of the PNA.RNA heteroduplex. Nuclear microinjection of cells constitutively expressing SV40 large T antigen (T Ag) with either a 15-mer or 20-mer PNA targeted to the T Ag messenger RNA suppressed T Ag expression. This effect was specific in that there was no reduction in beta-galactosidase expression from a coinjected expression vector and no inhibition of T Ag expression after microinjection of a 10-mer PNA.

Ligating device cartridge with separable retainer

Abstract: A cartridge for storing and retaining a plurality of medical ligating devices such as hemostatic clips and surgical staples, the cartridge having a movable device retaining member situated in each device chamber. The retaining member is adapted to frictionally engage the legs of an open C-shaped device and is further adapted to be displaced away from engagement with the device when it is engaged in the jaws of a forceps-type applier. In one embodiment, the retaining member is adapted to fit between the legs of an open hemostatic clip and is further adapted to be displaced downwardly away from the clip when the clip is engaged by a clip applier. The disclosure further includes a method of storing hemostatic clips in a cartridge, the method incorporating retaining the clip within the cartridge by a separable member which is displaceable from engagement with a clip when the clip is engaged by a clip applier.

A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells

Abstract: HUMAN cytomegalovirus (HCMV) is a major pathogen in immunosuppressed individuals, including patients with acquired immune deficiency syndrome. The nucleoside analogue ganciclovir (9-(l,3-dihydroxy-2-propoxymethyl)-guanine) is one of the few drugs available to treat HCMV infections, but resistant virus is a growing problem in the clinic1 and there is a critical need for new drugs. The study of ganciclovir-resistant mutants has indicated that the selective action of ganciclovir depends largely on virus-controlled phosphorylation in HCMV-infected cells2–5. The enzyme(s) responsible have not been identified. Here we report that the HCMV gene UL97, whose predicted product shares regions of homology with protein kinases, guanylyl cyclase and bacterial phosphotransferases6–8, controls phosphorylation of ganciclovir in HCMV-infected cells. A four-amino-acid deletion of UL97 in a conserved region, which in cyclic AMP-dependent protein kinase participates in substrate recognition9, causes impaired ganciclovir phosphorylation. The implications of these results for antiviral drug development and drug resistance are discussed.

Systematic approximations to the optimized effective potential: Application to orbital-density-functional theory

Abstract: The integral equation originally derived by Sharp and Horton for the optimized effective potential (OEP) is exactly transformed into an equivalent form from which it is manifestly clear that the OEP, ${\mathit{V}}_{\mathit{x}\mathrm{\ensuremath{\sigma}}}^{0}$(r), is an implicit functional of only {${\mathit{n}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$}, the orbital densities of the occupied states {${\mathrm{\ensuremath{\psi}}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$}, and the corresponding single-particle exchange potentials {${\mathit{v}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$}. Furthermore, the transformed OEP has exactly the same form as one recently developed by the authors [Phys. Rev. A 45, 101 (1992)] from a more heuristic approach, the only difference being that in the present work a term proportional to the gradient of ${\mathit{n}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$ is added to each ${\mathit{v}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$ whose average value when taken over the i\ensuremath{\sigma} state is zero. This result leads to the natural development of an iterative approximation for ${\mathit{V}}_{\mathit{x}\mathrm{\ensuremath{\sigma}}}^{0}$, with the zeroth approximation being given by our previous result. The application of this technique to the calculation of the total energy and highest-energy single-particle eigenvalue for selected atoms is presented. In addition, we note that our results are applicable to the calculation of the OEP for any assumed exchange-correlation functional ${\mathit{E}}_{\mathrm{xc}}$[{${\mathrm{\ensuremath{\psi}}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$}], where ${\mathit{v}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$ is taken as the appropriate functional derivative of ${\mathit{E}}_{\mathrm{xc}}$. In the case that ${\mathit{E}}_{\mathrm{xc}}$ is a functional of {${\mathit{n}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$} only, as in the case of the local-density approximation with self-interaction correction, the resulting ${\mathit{V}}_{\mathrm{xc}\mathrm{\ensuremath{\sigma}}}^{0}$ is a functional of the {${\mathit{n}}_{\mathit{i}\mathrm{\ensuremath{\sigma}}}$} only.

Clomipramine hydrochloride in childhood and adolescent obsessive-compulsive disorder--a multicenter trial.

Abstract: Children and adolescents with obsessive compulsive disorder were studied in an 8-week, multicenter, double-blind, parallel groups trial of clomipramine hydrochloride (CMI) versus placebo. Efficacy assessments included the child version of the Yale-Brown Obsessive Compulsive Scale and the National Institute of Mental Health Global rating scale. At the end of 8 weeks, CMI-treated patients showed a mean reduction in Yale-Brown Obsessive Compulsive Scale score of 37% compared to 8% in the placebo group. Side effects were typical of tricyclic antidepressants. In a 1-year open label treatment, CMI continued to be effective and well tolerated.

The anti-hepatitis B virus activities, cytotoxicities, and anabolic profiles of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.

Abstract: The anti-hepatitis B (anti-HBV) activities of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (2'-deoxy-3'-thia-5-fluorocytosine [FTC]) were studied by using an HBV-transfected cell line (HepG2 derivative 2.2.15, subclone P5A). The (-) isomer was found to be a potent inhibitor of viral replication, with an apparent 50% inhibitory concentration of 10 nM, while the (+) isomer was found to be considerably less active. Both isomers showed minimal toxicity to HepG2 cells (50% inhibitory concentration, > 200 microM) and showed minimal toxicity in the human bone marrow progenitor cell assay. In accord with the cellular antiviral activity data, the 5'-triphosphate of (-)-FTC inhibited viral DNA synthesis in an endogenous HBV DNA polymerase assay, while the 5'-triphosphate of the (+) isomer was inactive. Unphosphorylated (-)-FTC did not inhibit product formation in the endogenous assay, suggesting that the antiviral activity of the compound is dependent on anabolism to the 5'-triphosphate. Both (-)- and (+)-FTC were anabolized to the corresponding 5'-triphosphates in chronically HBV-infected HepG2 cells. The rate of accumulation and the steady-state concentration of the 5'-triphosphate of (-)-FTC were greater. Also, (-)-FTC was not a substrate for cytidine deaminase and, therefore, is not subject to deamination and conversion to an inactive uridine analog. The (+) isomer is, however, a good substrate for cytidine deaminase.

The prevalence of lifetime and partial post-traumatic stress disorder in vietnam theater veterans

Abstract: A complete understanding of the consequences of service in a war zone includes examining the lifetime and current prevalence of post-traumatic stress disorder (PTSD), and of partial PTSD. Cases of partial PTSD are persons who have clinically significant symptoms of PTSD, but who do not meet the full diagnostic criteria. The National Vietnam Veterans Readjustment Study (NVVRS) estimated the lifetime prevalence of PTSD to be 30.9% among male theater veterans, 26.% among females; lifetime prevalence of partial PTSD was an additional 22.5% and 21.2%, respectively; current prevalence of partial PTSD was 11.1% in males and 7.8% in females. NVVRS findings indicate that of the 1.7 million veterans who ever experienced significant symptoms of PTSD after the Vietnam war, approximately 830,000 (49%) still experience clinically significant distress and disability from symptoms of PTSD. The contribution of partial PTSD represents an estimated additional 350,000 veterans.

Amino acid ester prodrugs of acyclovir

Abstract: Summary Eighteen amino acid esters of the antiherpetic drug, acyclovir, were synthesized as potential prodrugs for oral administration. The esters were examined for in vitro antiviral activity against herpes simplex virus Type 1 (HSV-1). They were found to have less potency than the parent compound. Their efficiencies as pro­ drugs were evaluated in rats by measuring the urinary recovery of acyclovir. Ten prodrugs produced greater amounts of the parent drug in the urine. The L-amino acid esters were better prodrugsthan the correspond­ ing D- or D,L-isomers, suggesting the involvement of a stereoselectivetransporter. The L-valyl ester, 256U87, was the best prodrug. Sixty three per cent of its administered dose was excreted as acyclovir in the urine, a considerable improvement over acyclovir itself, for which this value was 19%. Since 256U87 was stable in aqueoussolutions, its conversion to acyclovir in vivo was probably enzyme catalyzed. This L-valyl ester prodrug of acyclovir is now undergoing clinical evaluation.

Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein

Abstract: The E7 gene of human papillomavirus type 16 encodes a multifunctional nuclear phosphoprotein that is functionally and structurally similar to the adenovirus (Ad) E1A proteins and the T antigens of other papovaviruses. E7 can cooperate with an activated ras oncogene to transform primary rodent cells, trans activate the Ad E2 promoter, and abrogate transforming growth factor beta-mediated repression of c-myc. Recent studies suggest that these functions may in part be a consequence of the ability of E7 to associate with the product of the retinoblastoma tumor suppressor gene (pRB). In this study, a series of site-specific mutations of the human papillomavirus type 16 E7 gene product were constructed and assessed for their effects on intracellular protein stability, ras cooperativity, transcriptional trans activation, pRB association, and phosphorylation. The results of these studies indicate that the transforming and trans-activating domains extensively overlap within a region of the protein analogous to conserved region 2 of Ad E1A, suggesting that pRB binding is necessary for both activities. Deletion of sequences in conserved region 1 abrogates cellular transformation but has only a marginal effect on trans activation. These data suggest that E7 trans activation and cellular transformation are interrelated but separable functions.

Comparison of the biotransformation of 1,3-butadiene and its metabolite, butadiene monoepoxide, by hepatic and pulmonary tissues from humans, rats and mice.

Abstract: 1,3-Butadiene (BD), a widely used monomer in the production of synthetic rubber and other resins, is one of the 189 hazardous air pollutants identified in the 1990 Clean Air Act Amendments. BD induces tumors at multiple organ sites in B6C3F1 mice and Sprague-Dawley rats; mice are much more susceptible to the carcinogenic action of BD than are rats. Previous in vivo studies have indicated higher circulating blood levels of butadiene monoepoxide (BMO), a potential carcinogenic metabolite of BD, in mice compared to rats, suggesting that species differences in the metabolism of BD may be responsible for the observed differences in carcinogenic susceptibility. The metabolic fate of BD in humans is unknown. The objective of these studies was to quantitate in vitro species differences in the oxidation of BD and BMO by cytochrome P450-dependent monooxygenases and the inactivation of BMO by epoxide hydrolases and glutathione S-transferases using microsomal and cytosolic preparations of livers and lungs obtained from Sprague-Dawley rats, B6C3F1 mice and humans. Maximum rates for BD oxidation (Vmax) were highest for mouse liver microsomes (2.6 nmol/mg protein/min) compared to humans (1.2) and rats (0.6). The Vmax for BD oxidation by mouse lung microsomes was similar to that of mouse liver but greater than 10-fold higher than the Vmax for the reaction in human or rat lung microsomes. Correlation analysis revealed that P450 2E1 is the major P450 enzyme responsible for oxidation of BD to BMO. Only mouse liver microsomes displayed quantifiable rates for metabolism of BMO to butadiene diepoxide (Vmax = 0.2 nmol/mg protein/min), a known rodent carcinogen. Human liver microsomes displayed the highest rate of BMO hydrolysis by epoxide hydrolases. The Vmax in human liver microsomes ranged from 9 to 58 nmol/mg protein/min and was at least 2-fold higher than the Vmax observed in mouse and rat liver microsomes. The Vmax for glutathione S-transferase-catalyzed conjugation of BMO with glutathione was highest for mouse liver cytosol (500 nmol/mg protein/min) compared to human (45) or rat (241) liver cytosol. In general, the KMs for the detoxication reactions were 1000-fold higher than the KMs for the oxidation reaction. Because of the low solubility of the BD and the relatively high KM for oxidation, it is likely that the Vmax/KM ratio will be important for BD and BMO metabolism in vivo. In vivo clearance constants were calculated from in vitro data for BD oxidation and BMO oxidation, hydrolysis and GSH conjugation.(ABSTRACT TRUNCATED AT 400 WORDS)

The prevalence of post-traumatic stress disorder in the Vietnam generation : a multimethod, multisource assessment of psychiatric disorder

Abstract: Findings from the Congressionally mandated National Vietnam Veterans Readjustment Study indicate that nearly one-half million Vietnam veterans—15.2% of the men and 8.5% of the women who served in Vietnam—suffer from post-traumatic stress disorder (PTSD) fifteen or more years after their military service. Current PTSD prevalence rates for Vietnam veterans are significantly and substantially higher than the rates for their comparable Vietnam generation peers, which range from 0.3% to 2.5%. Additionally, the current prevalence rate among male Vietnam veterans was found to differ significantly among race/ethnicity subgroups: 27.9% among Hispanic men, 20.6% among black men, 13.7% among white/other men. Multivariate analyses indicated that although background factors are significantly related to the current prevalence of PTSD, the current prevalence is much higher among Vietnam veterans than among era veteran and civilian counterpart comparison groups even after background differences are taken into account. These analyses also demonstrated the important role of exposure to combat and other types of war zone stress in the current prevalence of the disorder.

Emerging Strategies for Enhancing Crop Resistance to Microbial Pathogens

Abstract: There are marked differences in the pattern of host gene expression in incompatible plant: microbial pathogen interactions compared with compatible interactions, associated with the elaboration of inducible defenses Constitutive expression of genes encoding a chitinase or a ribosome-inactivating protein in transgenic plants confers partial protection against fungal attack, and a large repertoire of such antimicrobial genes has been identified for further manipulation In addition, strategies are emerging for the manipulation of multigenic defenses such as lignin deposition and synthesis of phytoalexin antibiotics by overexpression of genes encoding rate determining steps, modification of transcription factors or other regulatory genes, and engineering production of novel phytoalexins by interspecies transfer of biosynthetic genes The imminent cloning of disease resistance genes, futher molecular dissection of stress signal perception and transduction mechanisms, and identification of genes that affect symptom development will provide attractive new opportunities for enhancing crop protection Combinatorial integration of these novel strategies into ongoing breeding programs should make an important contribution to effective, durable field resistance

High-affinity binding of [125I]RTI-55 to dopamine and serotonin transporters in rat brain

Abstract: RTI-55 (3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester), one of the most potent inhibitors of dopamine uptake reported to date, was radioiodinated and tested as a probe for the cocaine receptor in Sprague-Dawley rat brain. Saturation and kinetic studies in the striatum revealed that [125I]RTI-55 bound to both a high- and low-affinity site. The Kd for the high-affinity site was 0.2 nM, while the Kd for the low-affinity site was 5.8 nM. The corresponding number of binding sites in the striatum was 37 and 415 pmol/g protein. The pharmacological profile of specific [125I]RTI-55 binding in the striatum was consistent with that of the dopamine transporter. Additionally, [125I]RTI-55 was found to bind with high affinity to the cerebral cortex. Scatchard analysis revealed a single high-affinity component of 0.2 nM with a density of 2.5 pmol/g protein. The pharmacological profile demonstrated by [125I]RTI-55 in the cerebral cortex matched that of the serotonin transporter. Autoradiographic analysis of sagittal brain sections with [125I]RTI-55 binding was consistent with these findings. Specific binding of [125I]RTI-55 was blocked by dopamine uptake inhibitors in areas rich in dopaminergic nerve terminals. Conversely, serotonin uptake inhibitors blocked the binding of [125I]RTI-55 in brain areas rich in serotonergic neurons. These results demonstrate that [125I]RTI-55 may be a very useful ligand for the dopamine and serotonin transporters.

Method for transmitting broadcast information in a digital control channel

Abstract: The present invention provides a method for transmitting information on a communications channel, e.g. , a digital control channel between a base station and a mobile station in a cellular system. The method includes the steps of grouping the information into a plurality of information elements, providing at least one change flag to indicate whether the value of at least one of the information elements has changed and transmitting the change flag and the information element over the communications channel.

Method and apparatus for communication control in a radiotelephone system

Abstract: In a radiotelephone system, the control channel of each cell can be configured to broadcast absolute information about its cell and relative information about other cells including the characteristic of the cell. Further, the location of other control channels may also be included among the information broadcast over a control channel of a particular cell. This information is then used to lock a mobile unit to a preferred cell.

Cellular verification and validation system

Abstract: A system for the validation and verification of base stations and mobile stations within a cellular radio communications network. The system includes a fixed key and a changeable key which are applied as inputs to an authentication algorithm. The algorithm generates key-dependent responses, at least one of which is independent of the changeable key. The responses generated by a particular mobile station are compared to the responses generated by the network and the presence of fraudulent users may be detected.

Characterization and quantitation of urinary metabolites of [1,2,3-13C]acrylamide in rats and mice using 13C nuclear magnetic resonance spectroscopy.

Abstract: Acrylamide, widely used for the production of polymers and as a grouting agent, causes neurotoxic effects in humans and neurotoxic, genotoxic, reproductive, and carcinogenic effects in laboratory animals In this study, 13C NMR spectroscopy was used to detect metabolites of acrylamide directly in the urine of rats and mice following administration of [1,2,3-13C]acrylamide (50 mg/kg po) Two-dimensional NMR experiments were used to correlate carbon signals for each metabolite in the urine samples and to determine the number of hydrogens attached to each carbon Metabolite structures were identified from the NMR data together with calculated values of shift for biochemically feasible metabolites and by comparison with standards The metabolites assigned in rat and mouse urine are N-acetyl-S-(3-amino-3-oxopropyl)cysteine, N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)cysteine, N-acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)cysteine, glycidamide, and 2,3-dihydroxypropionamide These metabolites arise from direct conjugation of acrylamide with glutathione or from oxidation to the epoxide, glycidamide, and further metabolism Acrylamide was also detected in the urine Quantitation was carried out by integrating the metabolite carbon signals with respect to that of dioxane added at a known concentration The major metabolite for both the rat (70% of total metabolites excreted) and the mouse (40%) was formed from direct conjugation of acrylamide with glutathione The remaining metabolites for the rat (30%) and mouse (60%) are derived from glycidamide The species differences in extent of metabolism through glycidamide may have important consequences for the toxic and carcinogenic effects of acrylamide

A critical review of the toxicology of glutaraldehyde.

Abstract: Glutaraldehyde, a low molecular weight aldehyde, has been investigated for toxicity in humans and animals. Examination of this dialdehyde was indicated from previous studies with other aldehydes in which carcinogenicity of formaldehyde and toxicity of acetaldehyde and malonaldehyde have been disclosed. Information gaps concerning the actions of glutaraldehyde have been identified in this review and recommendations are suggested for additional short- and long-term studies. In particular, information regarding irritation of the respiratory tract, potential neurotoxicity, and developmental effects would assist in a complete hazard evaluation of glutaraldehyde. Further study related to disposition, metabolism, and reactions of glutaraldehyde may elucidate the mechanism of action.