Facing an unexpected reality - oscillating between health and suffering 4-6 years after bariatric surgery.

BACKGROUND: Obesity is a significant public health problem that is on the increase worldwide, and treatment with bariatric surgery is becoming more and more common. This type of surgery has proved to be good for weight reduction and for preventing complications, but few studies have investigated patients' long-term experiences of health and suffering. AIM: To explore people's experiences of health after bariatric surgery. What are their thoughts about their life, body and sexuality? METHODS: This study is based on semi-structured interviews with eight women and eight men, 4-6 years after bariatric surgery. The data were analysed using qualitative content analysis and resulted in 5 main themes and 14 subthemes. RESULTS: The new body enabled a healthy life due to better treatment in society, enhanced self-esteem, the pleasure of purchasing clothes and the courage to become more sexually active. At the same time, the body could be experienced as so unfamiliar that their life was dominated by despondency, a lack of freedom and a feeling of being lost, which made them wish to return to their old body. CONCLUSION AND IMPLICATIONS: The participants received extensive information before as well as follow-up conversations up to one year after surgery. Nevertheless, they all experienced that changing from life as an obese person to a radically reduced body often meant a confrontation with an unexpected reality that oscillated between health and suffering. This indicates that preparedness for the life changes that bariatric surgery may entail is inadequate and that moving towards health and suffering takes its own time. Therefore, more time should be allocated to talking about how life is and can become in the long term, which may facilitate a dialogical, person-centred approach to the setbacks and situations each person needs to manage in order to improve her/his health.

The physical and mental impact of surviving sepsis - a qualitative study of experiences and perceptions among a Swedish sample.

BACKGROUND: Sepsis is a critical illness with high morbidity and mortality rates. Each year, sepsis affects about 48.9 million people all over the world. This study aims to illuminate how sepsis survivors experience sepsis and the impact of sepsis, as well as the health-related quality of life thereafter. METHODS: An interview study with eight sepsis survivors was carried out in Sweden with an inductive qualitative method. The data were analyzed with content analysis. RESULTS: Four themes were identified during the analysis; The experience of health care and being a sepsis patient, New circumstances´ impact on life, Family and social interactions, and The psychological impact on life. The lack of information about how sepsis can impact the survivors' lives and what to expect can lead to prolonged agony. The long recovery time comes as an unexpected and unpleasant surprise to those affected. Initially, the sepsis survivors are almost euphoric that they have survived, which can later lead to chock and trauma when they realize that they could have died. This insight needs to be processed in order to reach reconciliation with life after sepsis. CONCLUSION: Sepsis has a huge impact on both physical and mental aspects of life. Many survivors suffer from persistent residual symptoms of varying degrees, to which they have to adapt. The sepsis survivors need individually adjusted information about the sepsis recovery trajectory, and what to expect during and after the hospital stay.

Similar alteration of motor unit recruitment strategies during the anticipation and experience of pain.

A motor unit consists of a motoneurone and the multiple muscle fibres that it innervates, and forms the final neural pathway that influences movement. Discharge of motor units is altered (decreased discharge rate and/or cessation of firing; and increased discharge rate and/or recruitment of new units) during matched-force contractions with pain. This is thought to be mediated by nociceptive (pain) input on motoneurones, as demonstrated in animal studies. It is also possible that motoneurone excitability is altered by pain related descending inputs, that these changes persist after noxious stimuli cease, and that direct nociceptive input is not necessary to induce pain related changes in movement. We aimed to determine whether anticipation of pain (descending pain related inputs without nociceptor discharge) alters motor unit discharge, and to observe motor unit discharge recovery after pain has ceased. Motor unit discharge was recorded with fine-wire electrodes in the quadriceps of 9 volunteers. Subjects matched isometric knee-extension force during anticipation of pain (anticipation: electrical shocks randomly applied over the infrapatellar fat-pad); pain (hypertonic saline injected into the fat-pad); and 3 intervening control conditions. Discharge rate of motor units decreased during pain (P<.001) and anticipation (P<.01) compared with control contractions. De-recruitment of 1 population of units and new recruitment of another population were observed during both anticipation and pain; some changes in motor unit recruitment persisted after pain ceased. This challenges the fundamental theory that pain-related changes in muscle activity result from direct nociceptor discharge, and provides a mechanism that may underlie long-term changes in movement/chronicity in some musculoskeletal conditions.

Prostaglandin D2 induces contractions through activation of TP receptors in peripheral lung tissue from the guinea pig.

Prostaglandin D(2) (PGD(2)), released through mast cell activation, is used as a non-invasive biomarker in patients with asthma. Since PGD(2) can elicit opposing effects on airway tone via activation of the PGD(2) receptors DP(1) and DP(2) as well as the thromboxane receptor TP, the aim of this study was to characterize the receptors that are activated by PGD(2) in the guinea pig lung parenchyma. PGD(2) and the thromboxane analog U46619 induced concentration-dependent contractions. U46619 was more potent and caused stronger effect than PGD(2). The specific TP receptor antagonist SQ-29548 and the combined TP and DP(2) receptor antagonist BAYu3405 concentration-dependently shifted the curves for both agonists to the right. The DP(1) receptor agonist BW245 induced a weak relaxation at high concentrations, whereas the DP(1) receptor antagonist BWA868C did not affect the PGD(2) induced contractions. The specific DP(2) receptor agonist 13,14-dihydro-15-keto-PGD(2) showed neither contractile nor relaxant effect in the parenchyma. Furthermore, studies in precision-cut lung slices specified that airways as well as pulmonary arteries and veins contracted to both PGD(2) and U46619. When the lung parenchyma from ovalbumin sensitized guinea pigs were exposed to ovalbumin, both thromboxane B(2) and PGD(2) were released. Ovalbumin also induced maximal contractions at similar level as PGD(2) in the parenchyma, which was partly reduced by SQ-29548. These data show that PGD(2) should be recognized as a TP receptor agonist in the peripheral lung inducing contraction on airways, arteries and veins. Therefore, a TP receptor antagonist can be useful in combination treatment of allergic responses in asthma.

Duration of methicillin-resistant Staphylococcus aureus colonization after diagnosis: a four-year experience from southern Sweden.

BACKGROUND: The duration of colonization with methicillin-resistant Staphylococcus aureus (MRSA) is not well known and there is debate as to whether a patient colonized with MRSA ever can be defined as 'MRSA-negative'. METHODS: Since 2003 all notified MRSA cases have been systematically followed in Skåne County, southern Sweden. Cultures are taken from the nares, throat, perineum and possible skin lesions. Contact tracing is conducted. The screening program continues as long as cultures are positive and then until 1 y of consecutive negative cultures for MRSA is completed. RESULTS: Of the 578 MRSA cases during 2003-2006, 535 were included in this retrospective study. The median duration of colonization with MRSA was 5.9 months. Having household contacts with MRSA, young age, spa-type t002 and colonization in 2 or more locations, were significantly associated with a longer duration of colonization. Having a clinical infection treated with antibiotics (compared to clinical infection with no antibiotic treatment or asymptomatic carriage) was significantly associated with a shorter carriage time. Eradication treatment was associated with a shorter carriage time. CONCLUSION: These results may have implications for the management of patients with MRSA carriage. The study indicates that MRSA carriage can be defined as 'negative' in a follow-up program and shows the importance of performing contact tracing among household members.

Parents' experiences of an abnormal ultrasound examination - vacillating between emotional confusion and sense of reality.

BACKGROUND: An ultrasound examination is an important confirmation of the pregnancy and is accepted without reflection to any prenatal diagnostic aspects. An abnormal finding often comes unexpectedly and is a shock for the parents. The aim was to generate a theoretical understanding of parents' experiences of the situation when their fetus is found to have an abnormality at a routine ultrasound examination. METHODS: Sixteen parents, mothers and fathers, whose fetus had been diagnosed with an abnormality during an ultrasound scan in the second or third trimester, were interviewed. The study employed a grounded theory approach. RESULTS: The core category vacillating between the emotional confusion and sense of reality is related to the main concern assessment of the diagnosis impact on the well-being of the fetus. Two other categories Entering uncertainty and Involved in an ongoing change and adaptation have each five sub-categories. CONCLUSIONS: Parents are aware of that ultrasound examination is a tool for identifying abnormalities prenatally. The information about the abnormality initially results in broken expectations and anxiety. Parents become involved in ongoing change and adaptation. They need information about the ultrasound findings and the treatment without prolonged delay and in a suitable environment. The examiner who performs the ultrasound examination must be aware of how anxiety can be intensified by environmental factors. All parents should to be offered a professional person to give them support as a part of the routine management of this situation.

Molecular evolution of Theta-class glutathione transferase for enhanced activity with the anticancer drug 1,3-bis-(2-chloroethyl)-1-nitrosourea and other alkylating agents.

Glutathione transferase (GST) displaying enhanced activity with the cytostatic drug 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and structurally related alkylating agents was obtained by molecular evolution. Mutant libraries created by recursive recombination of cDNA coding for human and rodent Theta-class GSTs were heterologously expressed in Escherichia coli and screened with the surrogate substrate 4-nitrophenethyl bromide (NPB) for enhanced alkyltransferase activity. A mutant with a 70-fold increased catalytic efficiency with NPB, compared to human GST T1-1, was isolated. The efficiency in degrading BCNU had improved 170-fold, significantly more than with the model substrate NPB. The enhanced catalytic activity of the mutant GST was also 2-fold higher with BCNU than wild-type mouse GST T1-1, which is 80-fold more efficient than wild-type human GST T1-1. We propose that GSTs catalyzing inactivation of anticancer drugs may find clinical use in protecting sensitive normal tissues to toxic side-effects in treated patients, and as selectable markers in gene therapy.

Parents' worried state of mind when fetal ultrasound shows an unexpected finding: a comparative study.

OBJECTIVE: Most parents yearn for a second-trimester ultrasound examination and feel excitement about it, but some also worry about what the examination will show. According to prior research, using only generic instruments or specific questionnaires, anxiety decreases when the ultrasound findings are normal. The aim of this study was to compare parents' worry (Parents' Expectations, Experiences, and Reactions to Ultrasound [PEER-U] State of Mind Index) and sense of coherence before and after a routine second-trimester ultrasound examination when it showed normal or abnormal findings. METHODS: A 1-year cohort study was performed at a Swedish university hospital. A total of 2049 parents who had their second-trimester ultrasound examinations there filled in a questionnaire consisting of 2 parts before and after the examinations. RESULTS: Parents with normal ultrasound findings were less worried than parents with abnormal findings. The group with normal findings also showed less worry after the examination than before. A sex analysis showed similar patterns. CONCLUSIONS: Parents with abnormal ultrasound findings are more worried and anxious. The new instrument, the PEER-U State of Mind Index, not only measures parents' worry but can also expose what influences their ultrasound examination experience.

Specific mediator inhibition by the NO donors SNP and NCX 2057 in the peripheral lung: implications for allergen-induced bronchoconstriction.

BACKGROUND: The aim of this study was to examine potential therapeutic effect of the two NO donors NCX 2057 (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid) 4-(nitrooxy)butyl ester) and SNP (sodium nitroprusside) on the early allergic airway response in the peripheral lung. METHODS: The experiments were performed in guinea pig lung parenchyma (GPLP) derived from ovalbumin (OVA) sensitized guinea pigs. The effects of NCX 2057 and SNP were evaluated by contractile responses and mediator release during OVA challenge. The generation of nitrite and nitrate was assessed by chemiluminescence. Statistical analysis was evaluated by ANOVA. RESULTS: Cumulatively increasing concentrations of OVA (1-10,000 ng/ml) induced concentration-dependent contractions of the GPLP that were reduced by NCX 2057 (100 microM, p < 0.001) and SNP (100 microM, p < 0.05). Antigen-induced eicosanoid release was decreased by NCX 2057 (100 microM, p < 0.001) but not by SNP (100 microM), whereas the release of histamine was reduced by SNP (100 microM, p < 0.001) but not by NCX 2057 (100 microM). In addition, NCX 2057 (0.1-100 microM), but not SNP (0.1-100 microM), relaxed leukotriene D4 (10 nM) precontracted GPLP (p < 0.01). The guanylyl cyclase inhibitor ODQ had no effect on the NCX 2057 mediated relaxation. SNP released significantly less nitrite than NCX 2057. CONCLUSION: Although both SNP and NCX 2057 reduced the release of pro-inflammatory mediators, their profiles were distinctly different. Furthermore, NCX 2057 also induced smooth muscle dilation in the GPLP. The findings point to specific anti-inflammatory effects of different NO donors in the peripheral lung tissue.

Parental level of anxiety, sense of coherence and state of mind when choroid plexus cysts have been identified at a routine ultrasound examination in the second trimester of pregnancy: a case control study.

The aim of the study was to compare parents' experience of a routine ultrasound examination in the second trimester, when a choroid plexus cyst/cysts (CPC) were found (Study group; n = 22), with matched controls where no fetal deviations were identified (Control group, n = 66). All the parents had participated in a larger cohort study. The instruments used for measuring anxiety were STAI-state/trait, sense of coherence (SOC) and Parents' Expectations, Experiences, Reactions to an Ultrasound examination during pregnancy (PEER-U, State of Mind Index). Regarding the SOC and STAI-state/trait no significant differences were found between the cases and controls or within the respective group before and after the ultrasound examination. The cases had an increase in anxiety (more anxious) as measured by the instrument PEER-U after the examination, while the controls showed a significant better level of State of Mind Index (less anxious) after the examination, compared to before. Therefore PEER-U can be a more reliable instrument when studying state of mind (anxiety) in connection with ultrasound examinations, and as it is specific for this situation it does not appear to be time dependent.

Information for better or for worse: interviews with parents when their foetus was found to have choroid plexus cysts at a routine second trimester ultrasound.

The aim of the study was to gain a theoretical understanding of parents' experiences and handling of the situation, when their foetus was diagnosed as having choroid plexus cysts, at a routine second trimester ultrasound examination. Nine couples and one mother were interviewed using one open question. Analysis method was Grounded Theory. The main concern was anxiety and the core category became need for knowledge. The other categories were frightening and confusing, judging risk and making a choice and comforting. The parents felt information during the ultrasound examination was insufficient. The time delay between the diagnosis and the doctor's appointment was also often criticized. Most of the parents in this study wanted to know what can be diagnosed by ultrasound, even if there is a small risk that the child will have a malformation or chromosome abnormality. However, when the diagnosis is made, they need adequate information, otherwise unnecessary anxiety arises. By giving sufficient information without days of delay, anxiety can hopefully be minimized. Some written information was also requested. It is of utmost importance that the staff use the same terminology and the correct name of the soft marker to the parents.

Lipid metabolites as regulators of airway smooth muscle function.

Compelling evidence identifies airway smooth muscle (ASM) not only as a target but also a cellular source for a diverse range of mediators underlying the processes of airway narrowing and airway hyperresponsiveness in diseases such as asthma. These include the growing family of plasma membrane phospholipid-derived polyunsaturated fatty acids broadly characterised by the prostaglandins, leukotrienes, lipoxins, isoprostanes and lysophospholipids. In this review, we describe the enzymatic and non-enzymatic biosynthetic pathways of these lipid mediators and how these are influenced by drug treatment, oxidative stress and airways disease. Additionally, we outline their cognate receptors, many of which are expressed by ASM. We describe potential deleterious and protective roles for these lipid mediators in airway inflammatory and remodelling processes by describing their effects on diverse functions of ASM in asthma that have the potential to contribute to asthma pathogenesis and symptoms. These functions include contractile tone development, cytokine and extracellular matrix production, and cellular proliferation and migration.

Care during pregnancy and childbirth in Sweden: perspectives of lesbian women.

OBJECTIVE: to explore the views and experiences of care of lesbian women during pregnancy and childbirth. DESIGN, SETTING AND PARTICIPANTS: a qualitative study of 18 lesbian women in southern Sweden. FINDINGS: valid text units were formed through categorisation into four main categories: recognition of sexual orientation; openness; relationships within the homosexual family; and different encounters and attitudes within the health-care system. The interviewed women were positive about their care during pregnancy and childbirth. However, as in studies regarding women's experiences of care in general, lesbian women raised concerns about postnatal care, parent education and the structure of the patient records with no place for the female partner. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: confirmation of parenthood was important, especially for the co-parent. The participants in this study felt that when they were open about their sexuality, this was met with an openness that they felt was confirming about their homsexuality. It is important for health-care providers not to make assumptions about women's sexuality.

Multivariate-activity mining for molecular quasi-species in a glutathione transferase mutant library.

A library of recombinant glutathione transferases (GSTs) generated by shuffling of DNA encoding human GST M1-1 and GST M2-2 was screened with eight alternative substrates, and the activities were subjected to multivariate analysis. Assays were made in lysates of bacteria in which the GST variants had been expressed. The primary data showed clustering of the activities in eight-dimensional substrate-activity space. For an incisive analysis, the rows of the data matrix, corresponding to the different enzyme variants, were individually scaled to unit length, thus accounting for different expression levels of the enzymes. The columns representing the activities with alternative substrates were subsequently individually normalized to unit variance and a zero mean. By this standardization, the data were adjusted to comparable orders of magnitude. Three molecular quasi-species were recognized by multivariate K-means and principal component analyses. Two of them encompassed the parental GST M1-1 and GST M2-2. A third one diverged functionally by displaying enhanced activities with some substrates and suppressed activities with signature substrates for GST M1-1 and GST M2-2. A fourth cluster contained mutants with impaired functions and was not regarded as a quasi-species. Sequence analysis of representatives of the mutant clusters demonstrated that the majority of the variants in the diverging novel quasi-species were structurally similar to the M1-like GSTs, but distinguished themselves from GST M1-1 by a Ser to Thr substitution in the active site. The data show that multivariate analysis of functional profiles can identify small structural changes influencing the evolution of enzymes with novel substrate-activity profiles.

Functionally diverging molecular quasi-species evolve by crossing two enzymes.

Molecular evolution is frequently portrayed by structural relationships, but delineation of separate functional species is more elusive. We have generated enzyme variants by stochastic recombinations of DNA encoding two homologous detoxication enzymes, human glutathione transferases M1-1 and M2-2, and explored their catalytic versatilities. Sampled mutants were screened for activities with eight alternative substrates, and the activity fingerprints were subjected to principal component analysis. This phenotype characterization clearly identified at least three distributions of substrate selectivity, where one was orthogonal to those of the parent-like distributions. This approach to evolutionary data mining serves to identify emerging molecular quasi-species and indicates potential trajectories available for further protein evolution.

Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant.

The crystal structures of wild-type human theta class glutathione-S-transferase (GST) T1-1 and its W234R mutant, where Trp234 was replaced by Arg, were solved both in the presence and absence of S-hexyl-glutathione. The W234R mutant was of interest due to its previously observed enhanced catalytic activity compared to the wild-type enzyme. GST T1-1 from rat and mouse naturally contain Arg in position 234, with correspondingly high catalytic efficiency. The overall structure of GST T1-1 is similar to that of GST T2-2, as expected from their 53% sequence identity at the protein level. Wild-type GST T1-1 has the side-chain of Trp234 occupying a significant portion of the active site. This bulky residue prevents efficient binding of both glutathione and hydrophobic substrates through steric hindrance. The wild-type GST T1-1 crystal structure, obtained from co-crystallization experiments with glutathione and its derivatives, showed no electron density for the glutathione ligand. However, the structure of GST T1-1 mutant W234R showed clear electron density for S-hexyl-glutathione after co-crystallization. In contrast to Trp234 in the wild-type structure, the side-chain of Arg234 in the mutant does not occupy any part of the substrate-binding site. Instead, Arg234 is pointing in a different direction and, in addition, interacts with the carboxylate group of glutathione. These findings explain our earlier observation that the W234R mutant has a markedly improved catalytic activity with most substrates tested to date compared to the wild-type enzyme. GST T1-1 catalyzes detoxication reactions as well as reactions that result in toxic products, and our findings therefore suggest that humans have gained an evolutionary advantage by a partially disabled active site.

Inhibition of nitric-oxide synthase enhances antigen-induced contractions and increases release of cysteinyl-leukotrienes in guinea pig lung parenchyma: nitric oxide as a protective factor.

Nitric oxide (NO) in exhaled air is a biomarker of airway inflammation. However, the role of NO in the peripheral lung is not known. The aim of this study was to determine the role of endogenous NO in antigen-induced contractions of ovalbumin (OVA)-sensitized guinea pig lung parenchyma (GPLP). The contraction in this in vitro model of the peripheral lung closely resembles the corresponding response in human airways. Cumulatively increasing concentrations (10-10,000 microg/l) of OVA induced concentration-dependent contractions of the GPLP that were enhanced by the NO synthase (NOS) inhibitors N(omega)-nitro-L-arginine (L-NOARG; 100 microM), N(omega)-monomethyl-L-arginine (100 microM), N(omega)-nitro-L-arginine methyl ester (100 microM), and N-(3-(aminomethyl)benzyl)acetamidine (1400W; 1 microM). The enhancement induced by L-NOARG was reversed by coadministration with the 5-lipoxygenase inhibitor (R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid (BAY x1005; 3 microM), whereas coadministration of L-NOARG with the cyclooxygenase inhibitor indomethacin (10 microM) did not change the effect of L-NOARG alone. L-NOARG (100 microM) did not affect the cumulative concentration-response relations for either leukotriene (LT) D4 (0.1-100 nM) or histamine (1-30 microM). The NO donor NONOate (0.001-100 microM) was ineffective in GPLP but potently relaxed precontracted guinea pig pulmonary artery. Furthermore, L-NOARG enhanced the release of LTE4 and decreased the release of prostaglandin E2 induced by OVA. In conclusion, endogenous NO exerts an inhibitory effect on antigen-induced contractions in the peripheral lung. The action of NO apparently involves inhibition of the release of mediators rather than direct relaxation of airway smooth muscle. The findings support the belief that endogenous NO has a protective anti-inflammatory effect in the airways.

Residue 234 in glutathione transferase T1-1 plays a pivotal role in the catalytic activity and the selectivity against alternative substrates.

GST (glutathione transferase) T1-1 plays an important role in the biotransformation of halogenated alkanes, which are used in large quantities as solvents and occur as environmental pollutants. Many reactions that are catalysed by GST T1-1 qualify as detoxification processes, but some reactions with dihalogenated alkanes lead to reactive products more toxic than the substrates. Murine GST T1-1 is particularly active with dichloromethane, which may explain the high carcinogenicity of dichloromethane in the mouse. Human GST T1-1 activity is considerably lower with halogenated hydrocarbons and some related substrates. Human GST T1-1 is polymorphic with a frequent null phenotype, suggesting that it is advantageous, under some circumstances, to lack the functional enzyme, which catalyses GSH conjugations that may cause bioactivation. The present study shows that amino acid residue 234 is a determinant of the differences in catalytic efficiency between the human and the rodent enzymes. The replacement of Trp234 in human GST T1-1 by arginine, found in the rodent enzyme, enhanced the alkyltransferase activity by an order of magnitude with a series of homologous iodoalkanes and some typical GST substrates. The specific activity of the alternative mutant Trp234-->Lys was lower than for the parental human GST T1-1 with many substrates, showing that a positive charge is not sufficient for increased activity. The enhanced activity of Trp234-->Arg with alkylating agents was dependent on the substrate tested, whereas no increase of the peroxidase activity with cumene hydroperoxide was noted. Residue 234 therefore is also involved in the control of the substrate selectivity of GST T1-1.

Directed enzyme evolution guided by multidimensional analysis of substrate-activity space.

The directed evolution of protein function frequently involves identification of mutants with improved properties from a population of variants obtained by mutagenesis. The selection of clones to parent the subsequent generation is crucial to the continued creation of superior progeny. In the present study, multivariate analysis guided the evolution of human glutathione transferase (GST) T1-1 to 65-fold enhanced alkyltransferase activity. Six alternative substrates monitored the substrate-activity space that characterized a mutant library of enzymes, obtained by recombination of DNA and heterologous expression in Escherichia coli. A subset of mutants was identified by their proximity in the targeted region of six-dimensional factor space. DNA from these mutants was recombined to create a new generation of GST variants from which an improved enzyme was isolated. The multidimensional cluster analysis is applicable to quantitative properties in any population of molecules undergoing evolution and can guide the tailoring of proteins, nucleic acids and other chemical structures to novel and improved functions.

High-resolution capillary zone and gel electrophoresis of structurally similar amphipathic glutathione conjugates based on interaction with beta-cyclodextrins.

The tripeptide glutathione is a prominent intracellular constituent that provides protection against genotoxic and carcinogenic electrophiles and is also a component of several biological signal substances. Glutathione conjugates, free glutathione, and glutathione disulfide contain charged amino acid residues, which contribute to solubility in aqueous media. However, the amphipathic nature of glutathione conjugates and the small differences that may distinguish the S substituents, pose analytical problems in their resolution. The present study demonstrates how homologous S-alkyl and S-benzyl conjugates of high structural similarity can be efficiently resolved by capillary electrophoresis. Inclusion of beta-cyclodextrins in the buffer or in a polyacrylamide gel affords baseline separation of the analytes. The separation methods described are applicable to enzyme assays in vitro and to the identification and quantification of glutathione conjugates of importance in toxicology and physiology. The contribution of beta-cyclodextrin to the separation is primarily based on interactions between its hydrophobic cavity and the S-alkyl and S-benzyl groups of the analytes.