Wound protectors for improved exposure in open hernia repair.

INTRODUCTION: Achieving adequate surgical exposure is fundamental to good surgical practice. Traditionally, in the repair of ventral and open inguinal hernias, this has been accomplished with the aid of self-retaining retractors or by extending the incision length. We propose that using disposable wound protectors, surgical exposure will be improved for a given incision length in the repair of ventral and open inguinal hernias, compared to traditional methods. METHOD: Through the use of an animal tissue model, we compared incisions of varying lengths and measured the dimensions of the exposure achieved with disposable wound protectors (Alexis™) and a Mollison self-retainer. We calculated the surface area and, therefore, exposure gained using the specified wound retraction devices and compared the results. RESULTS: The average superficial surface area of wound with a self-retainer compared to the small and extra-small disposable wound protector was 2.65 cm2 vs 2.27 cm2 (small) and 2.2 cm2 (extra-small) for 2 cm incision length, 3.6 cm2 vs 4.93 cm2 and 4.2 cm2 for 3 cm incision length, 5.19 cm2 vs 8.25 cm2 and 6.27 cm2 for 4 cm incision length, 6.17 cm2 vs 12.25 cm2 and 9.07 cm2 for 5 cm incision length, and 8.75 cm2 vs 16.73 cm2 and 10.78 cm2 for 6 cm incision length [p = 0.038 (small) and p = 0.049 (extra-small)]. Our results show a statistically significant increase in surface area of a wound for each incision length when a disposable wound protector was used for exposure, compared to a self-retainer. CONCLUSION: Our results demonstrate that the use of disposable wound protectors provides superior surgical exposure for a given incision length compared to traditional techniques in the repair of ventral and open inguinal hernia repairs.

Lipids, CHOs, proteins: can all macronutrients put a 'brake' on eating?

The gastrointestinal (GI) tract and specifically the most distal part of the small intestine, the ileum, has become a renewed focus of interest for mechanisms targeting appetite suppression. The 'ileal brake' is stimulated when energy-containing nutrients are delivered beyond the duodenum and jejunum and into the ileum, and is named for the feedback loop which slows or 'brakes' gastric emptying and duodeno-jejunal motility. More recently it has been hypothesized that the ileal brake also promotes secretion of satiety-enhancing GI peptides and suppresses hunger, placing a 'brake' on food intake. Postprandial delivery of macronutrients to the ileum, other than unavailable carbohydrates (CHO) which bypass absorption in the small intestine en route to fermentation in the large bowel, is an uncommon event and hence this brake mechanism is rarely activated following a meal. However the ability to place a 'brake' on food intake through delivery of protected nutrients to the ileum is both intriguing and challenging. This review summarizes the current clinical and experimental evidence for activation of the ileal brake by the three food macronutrients, with emphasis on eating behavior and satiety as well as GI function. While clinical studies have shown that exposure of the ileum to lipids, CHOs and proteins may activate GI components of the ileal brake, such as decreased gut motility, gastric emptying and secretion of GI peptides, there is less evidence as yet to support a causal relationship between activation of the GI brake by these macronutrients and the suppression of food intake. The predominance of evidence for an ileal brake on eating comes from lipid studies, where direct lipid infusion into the ileum suppresses both hunger and food intake. Outcomes from oral feeding studies are less conclusive with no evidence that 'protected' lipids have been successfully delivered into the ileum in order to trigger the brake. Whether CHO or protein may induce the ileal brake and suppress food intake has to date been little investigated, although both clearly have GI mediated effects. This review provides an overview of the mechanisms and mediators of activation of the ileal brake and assesses whether it may play an important role in appetite suppression.

Meningitis associated with strongyloidiasis in an area endemic for strongyloidiasis and human T-lymphotropic virus-1: a single-center experience in Japan between 1990 and 2010.

Meningitis caused by enteric flora is a known complication of strongyloidiasis, and human T-lymphotropic virus-1 (HTLV-1) predisposes individuals to severe strongyloidiasis. We reviewed the clinical features of bacterial meningitis associated with strongyloidiasis seen at a single center in subtropical Japan, in an area endemic for both strongyloidiasis and HTLV-1. We found 33 episodes in 21 patients between 1990 and 2010. The results were remarkable for the high incidence of meningitis due to Gram-positive cocci (27.3 %), especially Streptococcus bovis, and culture-negative cases (42.4 %). Given the high incidence of Gram-positive meningitis, a modified approach to corticosteroid use would be advisable in areas where strongyloidiasis is endemic, due to the potentially adverse consequences of glucocorticoid therapy.

The emulsified lipid Fabuless (Olibra) does not decrease food intake but suppresses appetite when consumed with yoghurt but not alone or with solid foods: a food effect study.

The lipid emulsion Fabuless (Olibra) has been shown in some studies to decrease short/medium term energy intake (EI) and prevent weight regain. The purported mechanism is the ileal brake. Whether Fabuless is efficacious under a range of dietary conditions is unknown since studies have administered the emulsion within a fermented, semi-liquid dairy yoghurt, and outcomes have been inconsistent. To determine whether Fabuless suppresses post-ingestive satiety and short-term food intake under a range of dietary conditions and forms we administered the emulsion co-presented with 185 mL water, stirred into a semi-liquid dairy yoghurt, and co-presented with a solid food breakfast muffin. This was a cross-over study in 18 lean men randomised to 6 treatments: (i) lipid emulsion, LE (15 g Fabuless, containing 4.2g lipid, 0.2 MJ)+water, (ii) lipid control, LC (15 g non-emulsified lipid/water, containing 4.2g lipid, 0.2 MJ)+water, (iii) lipid emulsion+yoghurt, LE+Y (1.2 MJ), (iv) lipid control+yoghurt, LC+Y (1.2 MJ), (v) lipid emulsion+muffin, LE+M (1.2 MJ), (vi) lipid control+muffin, LC+M (1.2 MJ), each given as a test breakfast at 8.30 am. Participants rated postprandial appetite sensations using visual analogue scales (VAS), and ad libitum energy intake was measured at a lunch meal 3.5h later. The lipid emulsion increased fullness compared with an energy-matched lipid control but only when administered within the semi-liquid fermented yoghurt (P<0.05). There were no effects on satiety ratings when co-presented with water or with the solid food muffin. Energy and macronutrient intake were not significantly decreased by any of the emulsion treatments. We conclude that effects are small, the format in which lipid emulsions are consumed influences postprandial satiety, and there is no evidence that this emulsion alters eating behaviour at the subsequent meal.

Fatty acid chain length, postprandial satiety and food intake in lean men.

High-fat diets are associated with obesity, and the weak satiety response elicited in response to dietary lipids is likely to play a role. Preliminary evidence from studies of medium (MCT) and long chain triglycerides (LCT) supports greater appetite suppression on high-MCT diets, possibly a consequence of direct portal access, more rapid oxidation and muted lipaemia. No data is as yet available on high-SCT diets which also have direct hepatic access. In this study SCT- (dairy fats), MCT- (coconut oil) and LCT-enriched (beef tallow) test breakfasts (3.3 MJ) containing 52 g lipid (58 en% fat) were investigated in a randomized, cross-over study in 18 lean men. All participants were required to complete the 3 study days in randomised order. Participants rated appetite sensations using visual analogue scales (VAS), and energy intake (EI) was measured by covert weighing of an ad libitum lunch meal 3.5 h postprandially. Blood samples were collected by venous cannulation. There were no detectable differences between breakfasts in perceived pleasantness, visual appearance, smell, taste, aftertaste and palatability (P>0.05). There was no significant effect of fatty acid chain length on ratings of hunger, fullness, satisfaction or current thoughts of food, nor did energy (mean, sem: SCT: 4406, 366 kJ; MCT: 4422, 306 kJ; LCT: 4490, 324 kJ; P>0.05) or macronutrient intake at lunch differ between diets. The maximum difference in EI between diets was less than 2%. Postprandial lipaemia also did not differ significantly. We conclude that there was no evidence that fatty acid chain length has an effect on measures of appetite and food intake when assessed following a single high-fat test meal in lean participants.

No effect of an oleoylethanolamide-related phospholipid on satiety and energy intake: a randomised controlled trial of phosphatidylethanolamine.

BACKGROUND: Phosphatidylethanolamine (PE) is a phospholipid which is biosynthesized into long chain N-acylethanolamines (NAEs) including oleoylethanolamide (OEA), a known inhibitor of food intake. The aim of this study was to investigate whether PE-containing lipids can also inhibit intake. This was a 4 treatment intervention where 18 male participants were given a high-fat test breakfast (2.5 MJ, 53 en% fat) containing (i) high-phospholipid, high-PE lipid (ii) high-phospholipid, medium-PE lipid (iii) no-phospholipid, no-PE control lipid or (iv) water control, in a randomised cross-over. Visual analogue scales (VAS) were used to assess post-ingestive hunger and satiety, and energy intake (EI) was measured at an ad libitum lunch meal after 3.5 hours. RESULTS: When compared with the water control, the 3 lipid treatments resulted in lower levels of hunger and thoughts of food, greater fullness and satisfaction (all, treatment*time interaction, P<0.001), and a lower EI (P<0.05). However, there was no difference in any of the VAS measures when the 2 PE lipid treatments were compared with no-PE control lipid, nor when medium-PE was compared with high-PE. Unexpectedly participants ate significantly more energy at the lunch meal when the 2 PE lipid treatments (medium-PE:5406 kJ, 334 sem; high-PE:5288 kJ, 244 sem) were compared with the no-PE control lipid (5072 kJ, 262 sem, P<0.05), although there was no dose effect between the medium- and high-PE treatments. CONCLUSION: Despite the close relationship of PE with OEA, there was no evidence from this acute study that dietary phospholipids containing PE can favourably modify eating behaviour.

Nitrogen transformation in a denitrification layer irrigated with dairy factory effluent.

Adoption of land-based effluent treatment systems can be constrained by the costs and availability of land. Sufficient land area is needed to ensure nitrate leaching from applied effluent is minimised. One approach to decrease required land area is to enhance N removal by denitrification. Layers of organic matter (100 mm thick) were installed below topsoil of a site irrigated with dairy factory effluent. These "denitrification" layers were tested to determine whether they could decrease nitrate leaching by increasing denitrification. Four plots (10x10 m2 each) were constructed with a denitrification layer installed at 300 mm below the surface, and N losses were measured in leachate using suction cups every 3 weeks for 19 months. N in leachate was compared with 4 control plots. Denitrifying enzyme activity, nitrate concentrations, and carbon availability were measured in samples collected from the denitrification layers. These measurements demonstrated that denitrification occurred in the layer; however, denitrification rates were not sufficiently high to significantly decrease nitrate leaching. Total N leaching was 296 kg N ha(-1) from control plots and 238 kg N ha(-1) from plots with denitrification layers; a total of 798 kg N ha(-1) was applied in effluent. More than 50% of the leached N to 40 cm was as organic N, presumably due to bypass flow. Other studies have demonstrated that thicker denitrification layers (more than 300 mm) can reduce nitrate leaching from small-scale septic tank drainage fields but this study suggests that it is probably not practical to use denitrification layers at larger scales.

Urinary excretion of equol by postmenopausal women consuming soymilk fermented by probiotic bifidobacteria.

OBJECTIVE: To study the effects of consuming isoflavone aglycone-enriched soymilk fermented by bifidobacteria on urinary excretion of equol with respect to fermentation, daidzein dose, supplementation duration and background diet. DESIGN: Double-blind crossover pilot study comprising three 14-day supplementation periods separated by a washout. SETTING: Victoria University, Melbourne, Australia. SUBJECTS: Sixteen postmenopausal women. INTERVENTION: SUBJECTS randomized into two groups consuming either fermented (FS) or non-fermented soymilk (NFS), ingested three daily dosages of daidzein via soymilk and collected pooled urine specimens. Daidzein and equol were quantified using high-performance liquid chromatography. RESULTS: After 14-days supplementation six women (38%) excreted equol (>1 micromol equol/day), including four from the FS group, two of whom were classified as non-producers at day 4. Bifidobacteria ingestion, composition of daidzein and its glucosides, and carbohydrate intake appeared to influence equol formation among equol producers. CONCLUSIONS: Pilot-study group mean urinary equol excretion results provided insufficient evidence (P>0.05) that FS consumption instigates equol production in women predetermined as non-producers.

Analysis of the binding of monoclonal and polyclonal antibodies to the glycoproteins of antigenic variants of human respiratory syncytial virus by surface plasmon resonance.

The surface glycoproteins of human respiratory syncytial virus (hRSV), F and G, are the major protective antigens of the virus. Both are antigenically variable, although to different degrees, but the role of antigenic variation in the pathogenesis of hRSV disease has not been fully evaluated. Assessment of immunity to different virus strains is difficult with conventional antibody assays where differing properties of the virus antigens, other than antigenicity, may influence the outcome of the assay. Here, we have developed BIAcore surface plasmon resonance based assays for antibodies to the glycoproteins of hRSV which allow valid comparison of antibody titres against multiple hRSV strains. Glycoproteins from a number of lineages of hRSV sub-group A were captured from lysates of infected cells onto the dextran coated surface of a BIAcore sensor chip via primary monoclonal antibodies (MAbs) to conserved epitopes. For the G glycoprotein, primary MAbs were conjugated directly to the dextran of the sensor chip via free amide groups. For the F glycoprotein, direct conjugation was found to inactivate the MAb and primary MAb was immobilised on the chip via rabbit anti-mouse Fc antibody fragments in an indirect system. Using monoclonal antibodies as secondary MAbs, the glycoproteins in both systems were shown to exhibit a sub-set of conserved and variable epitopes, with some epitopes of both sorts being unavailable, presumably blocked by the primary antibody. Polyclonal anti-hRSV sera raised against viruses of different genotype bound equally to both F and G glycoproteins from homologous and heterologous viruses suggesting that mice immunised systemically with lysates of cells infected with recent isolates of virus do not respond well to genotype specific epitopes.

Land application of domestic effluent onto four soil types: plant uptake and nutrient leaching.

Land application has become a widely applied method for treating wastewater. However, it is not always clear which soil-plant systems should be used, or why. The objectives of our study were to determine if four contrasting soils, from which the pasture is regularly cut and removed, varied in their ability to assimilate nutrients from secondary-treated domestic effluent under high hydraulic loadings, in comparison with unirrigated, fertilized pasture. Grassed intact soil cores (500 mm in diameter by 700 mm in depth) were irrigated (50 mm wk(-1)) with secondary-treated domestic effluent for two years. Soils included a well-drained Allophanic Soil (Typic Hapludand), a poorly drained Gley Soil (Typic Endoaquept), a well-drained Pumice Soil formed from rhyolitic tephra (Typic Udivitrand), and a well-drained Recent Soil formed in a sand dune (Typic Udipsamment). Effluent-irrigated soils received between 746 and 815 kg N ha(-1) and 283 and 331 kg P ha(-1) over two years of irrigation, and unirrigated treatments received 200 kg N ha(-1) and 100 kg P ha(-1) of dissolved inorganic fertilizer over the same period. Applying effluent significantly increased plant uptake of N and P from all soil types. For the effluent-irrigated soils plant N uptake ranged from 186 to 437 kg N ha(-1) yr(-1), while plant P uptake ranged from 40 to 88 kg P ha(-1) yr(-1) for the effluent-irrigated soils. Applying effluent significantly increased N leaching losses from Gley and Recent Soils, and after two years ranged from 17 to 184 kg N ha(-1) depending on soil type. Effluent irrigation only increased P leaching from the Gley Soil. All P leaching losses were less than 49 kg P ha(-1) after two years. The N and P leached from effluent treatments were mainly in organic form (69-87% organic N and 35-65% unreactive P). Greater N and P leaching losses from the irrigated Gley Soil were attributed to preferential flow that reduced contact between the effluent and the soil matrix. Increased N leaching from the Recent Soil was the result of increased leaching of native soil organic N due to the higher hydraulic loading from the effluent irrigation.

Detection of human respiratory syncytial virus genotype specific antibody responses in infants.

Infection and reinfection of infants with human respiratory syncytial virus (HRSV) occur despite the presence of serum anti-viral glycoprotein antibodies similar to those, which afford protection in animal models of infection. Antigenic variation of the viral glycoproteins between different genotypes of the virus which co-circulate in the population may contribute to the ability of the virus to escape from antibody-mediated protection. In this study, we have investigated whether human infants infected with HRSV produced antibody responses recognising the antigenic differences between different contemporary genotypes of virus. Acute and convalescent sera from 26 infants were analysed for antibody responses to the glycoproteins of the virus isolated from their respiratory tract and to representative viruses of homologous and heterologous genotypes. All infants developed antibodies with similar reactivity for viruses of all contemporary isolates and genotypes when measured in an immunofluorescence assay against unfixed virus infected cells. However, when antibody responses to the individual glycoproteins were measured in a surace plasmon resonance (SPR) assay, although all infants developed genotype cross-reactive antibodies to the F glycoprotein, anti-G antibodies were detectable in only half of the infants and in all cases these were genotype specific. Possession of no or only genotype specific antibodies to the G glycoprotein may contribute to the susceptibility of infants to reinfection. In both assays, reactivity of anti-glycoprotein antibodies with the sub-group A archetypal strain, A2, was markedly lower than with any contemporary virus tested indicating that this strain alone is unsuitable for accurate assessment of infant antibody responses. .

The effect of the dietary supplement, Chitosan, on body weight: a randomised controlled trial in 250 overweight and obese adults.

CONTEXT: Chitosan, a deacetylated chitin, is a widely available dietary supplement purported to decrease body weight and serum lipids through gastrointestinal fat binding. Although evaluated in a number of trials, its efficacy remains in dispute. OBJECTIVE: To evaluate the efficacy of chitosan for weight loss in overweight and obese adults. DESIGN AND SETTING: A 24-week randomised, double-blind, placebo-controlled trial, conducted at the University of Auckland between November 2001 and December 2002. PARTICIPANTS: A total of 250 participants (82% women; mean (s.d.) body mass index, 35.5 (5.1) kg/m(2); mean age, 48 (12) y) INTERVENTIONS: Participants were randomly assigned to receive 3 g chitosan/day (n=125) or placebo (n=125). All participants received standardised dietary and lifestyle advice for weight loss. Adherence was monitored by capsule counts. MAIN OUTCOME MEASURES: The primary outcome measure was change in body weight. Secondary outcomes included changes in body mass index, waist circumference, body fat percentage, blood pressure, serum lipids, plasma glucose, fat-soluble vitamins, faecal fat, and health-related quality of life. RESULTS: In an intention-to-treat analysis with the last observation carried forward, the chitosan group lost more body weight than the placebo group (mean (s.e.), -0.4 (0.2) kg (0.4% loss) vs +0.2 (0.2) kg (0.2% gain), P=0.03) during the 24-week intervention, but effects were small. Similar small changes occurred in circulating total and LDL cholesterol, and glucose (P<0.01). There were no significant differences between groups for any of the other measured outcomes. CONCLUSION: In this 24-week trial, chitosan treatment did not result in a clinically significant loss of body weight compared with placebo.

Measurement of antibody against contemporary virus lineages of human respiratory syncytial virus sub-group A in infants and their mothers.

BACKGROUND: Human respiratory syncytial virus (hRSV) infects the majority of infants in their first year of life. Maternal antibodies offer some protection although a small proportion of infected infants develop bronchiolitis and require admission to hospital. A number of lineages of the virus co-circulate in the population and the prevalent virus lineage changes from epidemic to epidemic. The effect of antigenic variation between virus lineages upon the protection offered by maternal antibodies has not been assessed. OBJECTIVES: To explore the possibility that infants may develop bronchiolitis because of a virus lineage-specific deficiency in their maternal antibodies. STUDY DESIGN: Virus isolates from infants admitted to hospital in Newcastle upon Tyne with hRSV infection during two consecutive winter epidemics were classified into lineages by genotypic analysis. Antibodies to the surface glycoproteins of contemporary sub-group A lineages and to the A2 virus strain were assayed in the acute sera of infected infants, in a group of uninfected infants and in the mothers of both groups. RESULTS: Four lineages of sub-group A hRSV were found circulating during the study period. Antibody titres measured against all virus lineages in the acute serum of infants with hRSV bronchiolitis were similar. In the uninfected infants and in the mothers of both infected and uninfected groups antibody titres to all four contemporary virus lineages were also similar. However, in these groups antibodies to the A2 virus strain were four-fold lower than those to contemporary isolates. CONCLUSIONS: Infants admitted to hospital with hRSV bronchiolitis exhibited no apparent selective deficiency in maternal antibodies to the viral glycoproteins of the infecting virus strain or lineage.

Working patterns of trainee anaesthetists in the UK: results of a national postal survey.

The 'New Deal' restrictions on junior doctors' hours have major implications for the staffing of anaesthetic departments and the provision of adequate training. The results of a national postal survey demonstrate a decline in traditional on-call arrangements, especially in hard-pressed work sectors such as intensive care. A substantial number of anaesthetic departments have still completely to satisfy the hours restrictions in many work sectors. Many departments experience recruitment difficulties and express concern about both service and training issues.

N-nitrosoanilines: a new class of caspase-3 inhibitors.

Caspases are a family of cysteine proteases activated during apoptosis. In cultured human endothelial cells, physiological levels of NO prevent apoptosis and interfere with the activation of the caspase cascade. Previous studies have demonstrated that NO inhibits the activity of caspase-3 by S-nitrosylation of the enzyme. In this study, the inhibitory effect of a new class of NO donors. N-nitrosoaniline derivatives, were examined against caspase-3. Initially eight small molecule inhibitors bearing N-nitroso moieties were assayed. It was found that the presence of an electron-donating group on the phenyl ring led to better inhibitory potency, a trend consistent with the results from the previous papain studies. Based on the analysis of the enzyme and substrates' structures, two peptidyl N-nitrosoaniline inhibitors [Ac-DVAD-NNO (1) and Ac-DV-AMO (2)] were designed and synthesized. Both compounds exhibited enhanced inhibitory potency against caspase-3.

Estimation of glomerular filtration rate in cancer patients.

The frequent need to obtain an estimate of renal function in cancer patients, not least for targeting carboplatin dose, has led to a number of approaches to estimate glomerular filtration rate (GFR). This study aimed to develop a simple and reliable method to estimate GFR using readily-available patient characteristics. Data from 62 patients with estimates of 51Cr-EDTA clearance were analysed to determine the most appropriate formula relating this method of measuring GFR to patient characteristics. The population pharmacokinetics of 51Cr-EDTA were analysed using NONMEM to evaluate the influence of each covariate. The formulae derived were then validated using a further 38 patients and compared with those obtained using existing formulae. 51Cr-EDTA clearance (GFR) was positively related to Dubois surface area, negatively related to age, and inversely related to serum creatinine (SCr). Females had lower 51Cr-EDTA clearance than males. The enzymatic method of SCr assay gave more reliable results than the Jaffe colorimetric method. A measure of creatine kinase significantly improved the estimation of GFR. The new formula produced estimates of GFR which were less biased (Mean Prediction Error = -3%) and more precise (Mean Absolute Prediction Error = 12%) than Cockcroft and Gault (-8% and 16%) or Jelliffe (-15% and 19%) estimates. The formulae developed here can be used to provide reliable estimates of GFR, particularly in regard to targeted dosing of carboplatin.

Mutability and propensity in causal selection.

We examined differences in causal ratings of 1 factor depending on the mutability (defined as the ease with which a factor can be imagined to be different) and causal propensity (defined as the likelihood that the event would occur in the presence of a factor) of another factor that conjoined to produce the event. In 3 studies, causal ratings of the target factor depended on the interaction of mutability and propensity of the other factor. When the other factor was high in mutability, ratings of the target decreased as the propensity of the contributing factor increased, but when the other was low in mutability, ratings of the target increased as the propensity of the contributing factor increased. Mediation analysis indicated that mutability and propensity affected causal ratings by determining the comparison against which the event was considered. Comparison judgments also mediated beliefs about which factor should have adjusted to the other.

para-Substituted N-nitroso-N-oxybenzenamine ammonium salts: a new class of redox-sensitive nitric oxide releasing compounds.

N-Nitroso-N-oxybenzenamine ammonium salts with -OMe, -Me, -H, -F, -Cl, -CF3, and -SO2Me substituents at the para position of the phenyl ring constitute a new class of-redox sensitive nitric oxide (NO) releasing compounds. These compounds yield nitric oxide and the corresponding nitrosobenzene derivatives by a spontaneous dissociation mechanism after undergoing a one electron oxidation. Oxidation of these compounds can be achieved through chemical, electrochemical and enzymatic methods. It was observed electrochemically that the amount of NO generated was dependent on the substituent effect and the applied oxidation potential. Electron-withdrawing substituents increase the oxidation potential of the compound. A linear correlation was observed when the peak potentials for the oxidation were graphed versus the Hammett substituent constant. Density functional theory calculations were also performed on this series of compounds. The theoretical oxidation energies of the corresponding anions show a strong linear correlation with the experimental potentials. Furthermore, enzymatic oxidation using horseradish peroxidase showed a similar substituent effect. These results indicate that substitution at the para position of the phenyl ring has a profound effect on the stability, oxidation potential and enzymatic kinetic properties of the compounds. Thus para-substituted N-nitroso-N-oxybenzenamine salts comprise a new class of redox-sensitive nitric oxide releasing agents.

Inhibition of protein tyrosine phosphatases by low-molecular-weight S-nitrosothiols and S-nitrosylated human serum albumin.

The homogeneous recombinant mammalian protein tyrosine phosphatase 1B (PTP1B) and Yersinia protein tyrosine phosphatase (PTPase) are inactivated by a series of low-molecular-weight S-nitrosothiols. These compounds exhibited different inhibitory activities in a time- and concentration-dependent manner with second-order rate constants (k(inact)/K(I)) ranging from 37 to 113 M(-1) min(-1) against mammalian PTP1B and from 66 to 613 M(-1) min(-1) against Yersinia PTPase. Furthermore, the inactivation of Yersinia PTPase by S-nitrosylated protein:S-nitroso human serum albumin was investigated. Both single-S-nitrosylated and poly-S-nitrosylated human serum albumin show good inhibitory ability to Yersinia PTPase. The second-order rate constants are 472 and 1188 M(-1) min(-1), respectively. This result indicates a possibility that S-nitrosylated albumin in vivo may function as an inhibitor for a variety of cysteine-dependent enzymes.