Subcutaneous Vedolizumab Treatment in a Real-World Inflammatory Bowel Disease Cohort Switched From Intravenous Vedolizumab: Eighteen-Month Prospective Follow-up Study.

Background: Vedolizumab has since 2021 been available as a subcutaneous formulation. We aimed to assess 18-month drug persistence and possible predictive factors associated with discontinuation, safety, serum drug profile, drug dosing, and disease activity in a real-world cohort of patients with inflammatory bowel disease switched from intravenous to subcutaneous vedolizumab maintenance treatment. Methods: Eligible patients were switched to subcutaneous vedolizumab and followed for 18 months or until discontinuation of subcutaneous treatment. Data on preferred route of administration, adverse events, drug dosing, serum-vedolizumab, disease activity, fecal calprotectin, and C-reactive protein were collected. Persistence was described using Kaplan-Meier analysis. The impact of clinical and biochemical variables on persistence was analyzed with Cox proportional hazard models. Results: We included 108 patients, and the estimated 18-month drug persistence was 73.6% (95% CI [64.2-80.1]). Patients in clinical remission at switch were less likely to discontinue SC treatment (HR = 0.34, 95% CI [0.16-0.73], P = .006), and patients favoring intravenous treatment at switch were almost 3 times more likely to discontinue (HR = 2.78, 95% CI [1.31-5.90], P = .008). Four patients discontinued subcutaneous vedolizumab due to injection site reactions. At 18 months, 88% of patients administered subcutaneous vedolizumab with an interval of ≥ 14 days, and serum-vedolizumab was 39.1 mg/L. Disease activity was stable during follow-up. Conclusions: Three of the four patients remained on subcutaneous vedolizumab after 18 months, a large proportion received treatment at standard dosing intervals, and disease activity remained stable. This indicates that switching from intravenous to subcutaneous vedolizumab treatment is convenient and safe.

The cost of inflammatory bowel disease in high-income settings: a Lancet Gastroenterology & Hepatology Commission.

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.

Switching from intravenous to subcutaneous vedolizumab maintenance treatment in patients with inflammatory bowel disease followed by therapeutic drug monitoring.

OBJECTIVE: Vedolizumab (VDZ) for subcutaneous (SC) administration has recently become available. We aimed to assess feasibility, safety and clinical outcome when switching from intravenous (IV) to SC VDZ maintenance treatment in a real world cohort of patients with inflammatory bowel disease (IBD) followed by therapeutic drug monitoring (TDM). METHODS: Eligible IBD patients were switched from IV to SC treatment and assessed six months prior to switch, at baseline and six, twelve and twenty-six weeks after switch. Primary outcome was proportion of patients on SC treatment after 26 weeks. Secondary outcomes included adverse events (AEs), clinical disease activity, biochemical markers, treatment interval, serum-VDZ (s-VDZ), preferred route of administration and health-related quality of life. RESULTS: In total, 108 patients were switched. After 26 weeks, 100 patients (92.6%) were still on SC treatment and median s-VDZ was 47.6 mg/L (IQR 41.3 - 54.6). The most frequent AE was injection site reaction (ISR), reported by 20 patients (18.5%). There were no clinically significant changes in disease activity, biochemical markers and quality of life. The proportion of patients preferring SC administration increased from 28.0% before switch to 59.4% after 26 weeks (p < 0.001). CONCLUSIONS: Nine out of ten patients still received SC treatment after 26 weeks. No change in disease activity occurred, and levels of serum VDZ increased. Although almost one fifth of patients experienced ISRs, a higher proportion favored SC administration at 26 weeks. This study demonstrates that SC maintenance treatment is a safe and feasible alternative to IV treatment.

Altered Gut Microbial Metabolism of Essential Nutrients in Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: To influence host and disease phenotype, compositional microbiome changes, which have been demonstrated in patients with primary sclerosing cholangitis (PSC), must be accompanied by functional changes. We therefore aimed to characterize the genetic potential of the gut microbiome in patients with PSC compared with healthy controls (HCs) and patients with inflammatory bowel disease (IBD). METHODS: Fecal DNA from 2 cohorts (1 Norwegian and 1 German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs, and 93 patients with IBD without PSC, were subjected to metagenomic shotgun sequencing, generating 17 billion paired-end sequences, which were processed using HUMAnN2 and MetaPhlAn2, and analyzed using generalized linear models and random effects meta-analyses. RESULTS: Patients with PSC had fewer microbial genes compared with HCs (P < .0001). Compared with HCs, patients with PSC showed enrichment and increased prevalence of Clostridium species and a depletion of, for example, Eubacterium spp and Ruminococcus obeum. Patients with PSC showed marked differences in the abundance of genes related to vitamin B6 synthesis and branched-chain amino acid synthesis (Qfdr < .05). Targeted metabolomics of plasma from an independent set of patients with PSC and controls found reduced concentrations of vitamin B6 and branched-chain amino acids in PSC (P < .0001), which strongly associated with reduced liver transplantation-free survival (log-rank P < .001). No taxonomic or functional differences were detected between patients with PSC with and without IBD. CONCLUSIONS: The gut microbiome in patients with PSC exhibits large functional differences compared with that in HCs, including microbial metabolism of essential nutrients. Alterations in related circulating metabolites associated with disease course, suggesting that microbial functions may be relevant for the disease process in PSC.

Erratum: Therapeutic Atmosphere in Psychotherapy Sessions. Int. J. Environ. Res. Public Health 2020, 17, 4105.

The authors wish to make the following correction to their paper [...].

Therapeutic Atmosphere in Psychotherapy Sessions.

There is uncertainty concerning what the active ingredients in psychotherapy are. The First Experimental Study of Transference interpretations (FEST) was a randomized controlled trial of the effects of transference work (TW) in psychodynamic psychotherapy. Women with low quality of object relations (QOR) showed a large positive effect of transference work, while men with high QOR showed a slight negative effect. The present study aimed to expand the knowledge from the FEST by investigating the therapeutic atmosphere with Structural Analysis of Social Behavior (SASB). Two-way ANOVAs were conducted to investigate differences between SASB cluster scores between subgroups. The therapeutic atmosphere was characterized by Protect-Trust, Affirm-Disclose and Control-Submit. Multilevel modeling was used to assess the relationship between a therapist variable and outcomes for men and women. Contrary to expectations, no significant differences in therapeutic atmosphere between subgroups (with or without TW in women with low QOR and men with high QOR) were observed using the process measure SASB.

Valor pronóstico del recuento de leucocitos y plaquetas, en tumores testiculares de células germinales / Leukocyte and platelet counts as prognostic values of testicular germ cell tumors

Introduction: The immune system plays an essential role in the organism's response to cancer. Several hematological markers can influence prognosis and survival of patients. The objective of this study is to determine their prognostic value in testicular germ cell tumors. Material and methods: Retrospective cohort study on 164 patients with germ cell tumors. Clinical, analytical, histological and evolutionary data were collected. The absolute neutrophil and absolute platelet counts, neutrophil-lymphocyte (NLR), platelet-lymphocyte and lymphocyte-monocyte ratios were estimated at diagnosis. The association that these markers can have with the classic prognostic factors, as well as their effect on prognosis and survival, have been analyzed. Results: 17.7% had NLR > 4 and 14.6% ANC > 8000/μL. These patients presented higher percentages of residual disease and stage II-III tumors. Patients with elevated absolute neutrophil showed also higher percentages of progression and exitus. 7.3% presented absolute platelet > 400,000/μL. These patients obtained higher rates of residual disease, nonseminomatous and stage III tumors. 28.4% showed platelet-lymphocyte values > 150. This data was associated to higher percentages of residual disease, progression, stage II and III tumors and seminomatous tumors. 83.3% had a lymphocyte-monocyte > 3. These patients presented: higher tumor markers in normal range, decreased residual disease rates and higher percentages of stage I and II tumors. The mean survival time was shorter in patients with NLR > 4 and absolute neutrophil > 8000/μL. The ROC curves showed significance in the prediction of progression and values of lymphocyte-monocyte >3, and prediction of survival and values NLR > 4. Conclusion: Our results indicate that the analyzed hematological markers are associated with poor prognoses at diagnosis. Therefore, their use in daily clinical practice can be a valuable tool in the diagnosis and prognosis of patients with testicular germ cell tumors

Introducción: El sistema inmune ejerce un papel clave en la respuesta del organismo frente al cáncer. Existen diversos marcadores hematológicos que pueden influir en el pronóstico y supervivencia de los pacientes. El objetivo de este estudio es determinar su valor pronóstico en tumores testiculares de células germinales. Material y métodos: Estudio de cohortes retrospectivo sobre 164 pacientes con tumores testiculares de células germinales. Se recogieron datos clínicos, analíticos, histológicos y evolutivos. Se estimaron, al diagnóstico, el recuento total de neutrófilos y plaquetas, la ratio neutrófilo-linfocito (RN/L), plaqueta-linfocito(RP/L) y linfocito-monocito (RL/M). Se analizó la relación que estos marcadores pueden tener sobre los factores pronósticos clásicos, así como sobre el pronóstico y supervivencia. Resultados: Un 17,7% tuvieron una RN/L > 4 y un 14,6% un RNT > 8000/μL. Estos enfermos, presentaron mayor porcentaje de enfermedad residual y tumores en estadios II y III. Los enfermos con recuento total de neutrófilos elevado también tuvieron mayor porcentaje de progresión y éxitus. Un 7,3%, tenían un recuento total de plaquetas > 400000/μL. Estos enfermos tuvieron un mayor porcentaje de tumores no seminomatosos, de enfermedad residual y tumores en estadio III. El 28,4% mostraron valores RP/L>150, asociándose este dato a mayor porcentaje de tumores seminomatosos, enfermedad residual, estadios II y III y progresión. El 83,3% tuvieron una RL/M > 3. Estos enfermos presentaron: mayor porcentaje de marcadores tumorales en rango normal, menor porcentaje de enfermedad residual y mayor porcentaje de pacientes en estadio I y II. El tiempo medio de supervivencia fue menor en pacientes con RN/L > 4 y con recuento total de neutrófilos > 8.000/μL. Las curvas ROC mostraron significación en la predicción de progresión y valores de RL/M > 3, y predicción de supervivencia y valores RN/L > 4. Conclusión: Nuestros resultados indican que los marcadores hematológicos analizados se asocian situaciones de mal pronóstico en el momento del diagnóstico. Por tanto, su utilización en la práctica clínica diaria puede ser considerada como una herramienta más en el diagnóstico y pronóstico de pacientes con tumores testiculares de células germinales de testículo

Leukocyte and platelet counts as prognostic values of testicular germ cell tumours. / Valor pronóstico del recuento de leucocitos y plaquetas, en tumores testiculares de células germinales.

INTRODUCTION: The immune system plays an essential role in the organism's response to cancer. Several haematological markers can influence prognosis and survival of patients. The objective of this study is to determine their prognostic value in testicular germ cell tumours. MATERIAL AND METHODS: Retrospective cohort study on 164 patients with germ cell tumours. Clinical, analytical, histological and evolutionary data were collected. The absolute neutrophil and absolute platelet counts, neutrophil-lymphocyte (NLR), platelet-lymphocyte and lymphocyte-monocyte ratios were estimated at diagnosis. The association that these markers can have with the classic prognostic factors, as well as their effect on prognosis and survival, have been analysed. RESULTS: 17.7% had NLR>4 and 14.6% ANC>8000/µL. These patients presented higher percentages of residual disease and stage II-III tumours. Patients with elevated absolute neutrophil showed also higher percentages of progression and exitus. 7.3% presented absolute platelet >400000/µL. These patients obtained higher rates of residual disease, nonseminomatous and stage III tumours. 28.4% showed platelet-lymphocyte values>150. This data was associated to higher percentages of residual disease, progression, stage II and III tumours and seminomatous tumours. 83.3% had an lymphocyte-monocyte >3. These patients presented: higher tumour markers in normal range, decreased residual disease rates and higher percentages of stage I and II tumours. The mean survival time was shorter in patients with NLR>4 and absolute neutrophil >8,000/µL. The ROC curves showed significance in the prediction of progression and values of lymphocyte-monocyte >3, and prediction of survival and values NLR>4. CONCLUSION: Our results indicate that the analysed haematological markers are associated with poor prognoses at diagnosis. Therefore, their use in daily clinical practice can be a valuable tool in the diagnosis and prognosis of patients with testicular germ cell tumours.

Real world data on effectiveness, safety and therapeutic drug monitoring of vedolizumab in patients with inflammatory bowel disease. A single center cohort.

BACKGROUND AND AIMS: The efficacy of vedolizumab (VDZ) has been demonstrated in clinical trials. The aim of this report is to evaluate the long-term effectiveness and safety of VDZ in a real-world cohort and to explore possible associations between concentration measurements of VDZ and treatment effectiveness. METHODS: This is a prospective clinical follow-up including all adult patients with ulcerative colitis (UC) and Crohn's disease (CD) treated with VDZ from October 2014 until September 2017 at a single center in Norway. The patients were followed for at least 14 weeks or until termination of treatment. Clinical and biochemical activity were obtained at every infusion throughout follow-up. Plasma measurements of VDZ (p-VDZ) were performed before every infusion during maintenance therapy. RESULTS: In total, 71 patients received VDZ. Improvement of CRP and hemoglobin was observed in CD but not in UC, whereas Partial Mayo Score improved in UC while no change in Harvey Bradshaw Index was revealed in CD. Furthermore, CRP at baseline was negatively correlated with p-VDZ at week 14 in CD but not in UC patients. CONCLUSION: Improvement of biochemical markers of inflammation was observed in CD while clinical activity scores improved in UC patients. For CD, baseline CRP was correlated with lower concentrations of p-VDZ at week 14.

Switching from originator to biosimilar infliximab - real world data of a prospective 18 months follow-up of a single-centre IBD population.

BACKGROUND AND AIMS: Long-term data regarding switching from originator infliximab to biosimilar CT-P13 are sparse. Concerns about increased immunogenicity after switching have been raised. We aimed to study the effectiveness, safety and immunogenicity after switching from originator infliximab to CT-P13 in a real-world IBD population with 18 months prospective follow-up. METHODS: All adult IBD patients treated with originator infliximab at the Department of Gastroenterology, Oslo University Hospital, were switched to CT-P13 and followed prospectively for 18 months. The primary endpoints were (i) the proportion of patients remaining on CT-P13 18 months after switching and (ii) immunogenicity during 18 months after switching. The secondary endpoints included (i) adverse events, (ii) changes in disease activity, C-reactive protein, anaemia, faecal calprotectin, infliximab dose and interval and p-infliximab. RESULTS: In total, 143 IBD patients were switched, 99 with Crohn's disease and 44 with ulcerative colitis. Altogether, 130 (91%) remained on CT-P13 throughout 18 months. Two patients developed ADAs at moderate level and discontinued CT-P13. Another 10 patients discontinued CT-P13 (two due to loss of response without ADAs, four due to adverse events, and four in remission and a personal wish to stop). There was no overall change in disease activity scores or in the other studied variables except for p-infliximab, which increased significantly. CONCLUSIONS: The present study provides valuable evidence for the safety and effectiveness of switching from originator to biosimilar infliximab over a prolonged period of 18 months and demonstrates that switching was well tolerated and did not affect the long term clinical outcome.

Combining Anti-TNF-α and Vedolizumab in the Treatment of Inflammatory Bowel Disease: A Case Series.

Background: Anti-tumor necrosis factor α (anti-TNF-α) is important in the treatment of inflammatory bowel disease, but some patients experience only a partial response. In these patients, a combination of anti-TNF-α and vedolizumab (VDZ) may act as a bridge until the full VDZ effect occurs. At present, clinical data on combination treatment with anti-TNF-α and VDZ are not available. The aim of this case series was to evaluate the safety and clinical response of combination therapy with anti-TNF-α and VDZ in clinical practice. Methods: All patients started on combination treatment with anti-TNF-α and VDZ from November 2015 to July 2016 were prospectively followed for at least 12 months. Results: Six patients with ulcerative colitis and four patients with Crohn's disease received combination treatment. These patients were followed for a median of 1712-20 months. No more adverse events than expected with anti-TNF-α alone were observed during combination treatment. At the end of follow-up, all patients were in clinical remission, and 8 patients could discontinue anti-TNF-α treatment and receive VDZ monotherapy. Two of the patients with Crohn's disease required combination treatment throughout follow-up to obtain sustained remission. Conclusion: Our findings suggest that combination treatment with anti TNF-α and VDZ is safe and might represent a long-term treatment option in selected patients.

Guanylate Cyclase C Activation Shapes the Intestinal Microbiota in Patients with Familial Diarrhea and Increased Susceptibility for Crohn's Disease.

BACKGROUND: With 25% prevalence of Crohn's disease, Familial GUCY2C diarrhea syndrome (FGDS) is a monogenic disorder potentially suited to study initiating factors in inflammatory bowel disease (IBD). We aimed to characterize the impact of an activating GUCY2C mutation on the gut microbiota in patients with FGDS controlling for Crohn's disease status and to determine whether changes share features with those observed in unrelated patients with IBD. METHODS: Bacterial DNA from fecal samples collected from patients with FGDS (N = 20), healthy relatives (N = 11), unrelated healthy individuals (N = 263), and IBD controls (N = 46) was subjected to sequencing of the V3-V4 region of the 16S rRNA gene to determine gut microbiota composition. Food frequency questionnaires were obtained from patients with FGDS and their relatives. RESULTS: Compared with healthy controls, FGDS displayed prominent changes in many microbial lineages including increase in Enterobacteriaceae, loss of Bifidobacterium and Faecalibacterium prausnitzii but an unchanged intraindividual (alpha) diversity. The depletion of F. prausnitzii is in line with what is typically observed in Crohn's disease. There was no significant difference in the dietary profile between the patients and related controls. The gut microbiota in related and unrelated healthy controls was also similar, suggesting that diet and familial factors do not explain the gut microbiota alterations in FGDS. CONCLUSIONS: The findings support that the activating mutation in GUCY2C creates an intestinal environment with a major influence on the microbiota, which could contribute to the increased susceptibility to IBD in patients with FGDS.

The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls.

OBJECTIVE: Gut microbiota could influence gut, as well as hepatic and biliary immune responses. We therefore thoroughly characterised the gut microbiota in primary sclerosing cholangitis (PSC) compared with healthy controls (HC) and patients with ulcerative colitis without liver disease. DESIGN: We prospectively collected 543 stool samples. After a stringent exclusion process, bacterial DNA was submitted for 16S rRNA gene sequencing. PSC and HC were randomised to an exploration panel or a validation panel, and only significant results (p<0.05, QFDR<0.20) in both panels were reported, followed by a combined comparison of all samples against UC. RESULTS: Patients with PSC (N=85) had markedly reduced bacterial diversity compared with HC (N=263, p<0.0001), and a different global microbial composition compared with both HC (p<0.001) and UC (N=36, p<0.01). The microbiota of patients with PSC with and without IBD was similar. Twelve genera separated PSC and HC, out of which 11 were reduced in PSC. However, the Veillonella genus showed a marked increase in PSC compared with both HC (p<0.0001) and UC (p<0.02). Using receiver operating characteristic analysis, Veillonella abundance yielded an area under the curve (AUC) of 0.64 to discriminate PSC from HC, while a combination of PSC-associated genera yielded an AUC of 0.78. CONCLUSIONS: Patients with PSC exhibited a gut microbial signature distinct from both HC and UC without liver disease, but similar in PSC with and without IBD. The Veillonella genus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC.

Mortality and Causes of Death in Ulcerative Colitis: Results from 20 Years of Follow-up in the IBSEN Study.

BACKGROUND: The best way to obtain knowledge about the natural history, including mortality, of ulcerative colitis (UC) is to conduct a longitudinal, population-based, prospective study. The aims of this study were to calculate the mortality rates and causes of death in patients with UC. METHODS: A prospective, population-based, longitudinal cohort study was conducted in South-Eastern Norway. A total of 519 patients (51.4% men) with UC were included over a 4-year period. A gastroenterologist from a university hospital reviewed the clinical information of all of the patients. Mortality data were retrieved from the Cause of Death Registry and from Statistics Norway. RESULTS: No statistically significant increases in total mortality or cause-specific mortality between the patients with UC and the controls were found. CONCLUSIONS: The present 20-year population-based cohort study revealed a good prognosis regarding the mortality, which partially might be explained by the patients' coverage by a generally well-functioning health care system.

Complementary and alternative medicine in patients with inflammatory bowel disease: the results of a population-based inception cohort study (IBSEN).

BACKGROUND AND AIMS: The use of complementary and alternative medicine (CAM) has been increasing in recent decades. Our aim was to determine the proportion of CAM use among patients with inflammatory bowel disease (IBD) in a longitudinal, population-based cohort and to identify predictive factors for CAM use. METHODS: The Inflammatory Bowel South-Eastern Norway (IBSEN) study is a population-based IBD cohort that has been followed prospectively for 10 years. The ten-year follow-up was conducted from 2000 to 2004 and included a questionnaire regarding CAM, a structured interview, a review of hospital records, a clinical examination, laboratory tests, and an ileocolonoscopy. RESULTS: Of the 620 patients evaluated at the ten-year follow-up, 517 (84%) completed the CAM questionnaire, 353 had ulcerative colitis (UC), 164 had Crohn's disease (CD), and 50% were male. Thirty percent reported the use of CAM at some point since their IBD diagnosis, and 7.5% reported current CAM use. More CD patients than UC patients reported CAM use (38% vs. 27%, respectively; p=0.01). Younger age, female gender, and higher education level predicted CAM use in UC, whereas younger age was the only predictor of CAM use in CD. Thirty-six percent of the CAM users were mostly satisfied or very satisfied with the treatment. CONCLUSION: One third of the patients in this population-based cohort had used CAM at some point during a ten-year disease course, but only 7.5% reported current CAM use. CAM use was more common in the CD than in the UC patients. Only socio-demographic factors, such as age, gender and education, predicted CAM use.

Health-related quality of life in patients with ulcerative colitis after a 10-year disease course: results from the IBSEN study.

BACKGROUND: Ulcerative colitis (UC) negatively affects health-related quality of life (HRQoL), but population-based and long-term data on this topic are scarce. Our aim was to determine the HRQoL in UC patients after a 10-year disease duration. METHODS: UC patients from a population-based inception cohort met at a prescheduled 10-year follow-up visit. In addition to a clinical examination, interview, and blood samples, the patients completed the Short Form 36 (SF-36) and the Norwegian Inflammatory Bowel Disease Questionnaire (N-IBDQ). The SF-36 scores were compared to scores from a general population sample using one-sample t-tests. Standardized scores were calculated and interpreted according to Cohen's effect size index. The associations between relevant clinical and demographic factors and HRQoL were examined through linear regression analyses. RESULTS: A total of 196 patients completed the HRQoL questionnaires (response rate: 80%), of whom 54% were women; the mean age of all patients was 48 years (range: 22-86). The SF-36 scores were comparable to those of the general population except for lower scores in the General Health dimension. The SF-36 scores were significantly lower in the presence of current symptoms, in patients who had used corticosteroids, and in patients who reported not working. Overall N-IBDQ scores were equivalent to scores of patients in remission. Female gender, work status (not working), current symptoms, and smoking were associated with significantly lower N-IBDQ scores. CONCLUSIONS: SF-36 scores were not reduced compared to the general population sample. The presence of current symptoms, the use of corticosteroids, work status (not working), female gender, and smoking had a negative impact on HRQoL.

Viscoelastic solutions formed by worm-like micelles of amine oxide surfactant.

Formation and properties of viscoelastic wormlike aqueous micellar solutions of the zwitterionic surfactant p-dodecyloxybenzyldimethylamine oxide (pDoAO) were studied. Semi-dilute aqueous solutions of pDoAO show a sharp increase in viscosity, which exceeds 160 cST for concentrations >50 mM, leading to viscoelastic solutions. Viscoelasticity relates to the surfactant charge type. In fact this viscoelastic system reverses to fluid when acid is added (pH<2), which changes the system to cationic. Under acidic conditions the system resembles solutions of the similar cationic surfactant p-dodecyloxybenzyltrimethylammonium bromide, (pDoTABr) in terms of viscosity. Properties of aqueous solutions of pDoAO were investigated by dynamic light scattering (DLS), rheology and small angle neutron scattering (SANS). Data support the idea that small micelles grow in length (wormlike or threadlike micelles) as surfactant concentration increases and viscoelastic solutions form as micelles become entangled. The micellar diameter as calculated by different techniques is about 5 nm.

Activation and stabilization of alpha-chymotrypsin by cationic additives.

alpha-Chymotrypsin activity was tested with N-glutaryl-l-phenylalanine p-nitroanilide (GPNA) in aqueous media in the presence of synthetic surfactants, which differ in the flexibility of their bulky head groups. Superactivity can be ascribed to the presence of the tributylammonium residue on the surfactant head group, as in p-octyloxybenzyltributylammonium bromide (pOOTBABr), while in the presence of a more rigid moiety, i.e. a cyclic one, no activation was found. A nonmicellizable quaternary ammonium salt, the tetrabutylammonium bromide (TBABr), which has a head group structure very similar to pOOTBABr, not only induces a remarkable superactivation, at a concentration 80-fold higher than pOOTBABr, but also allows the enzyme to retain a high residual activity for long periods of time. The presence of a lipophilic chain, which by interacting with apolar residues on the enzyme surface, probably penetrates into hydrophobic pockets of the protein and causes a rapid inactivation. In 0.4 m TBABr, a 20-fold increase both in kcat and Km values, with respect to buffer alone, was found. The increase of Km could be attributed either to a true decrease in affinity between enzyme and substrate or alternatively to the presence of TBA+ ions near the catalytic region. They could interact with protein residues around the active site and bind to negatively charged GPNA molecules, lowering the local substrate concentration. Spectroscopic experiments (CD and fluorescence) show minor changes of protein conformation in 0.4 m TBABr, while at 1 m a strong modification of both spectra was observed.

Effects of beta-alanine treatment on the taurine and DNA content of the rat heart and retina.

Experimental evidence has suggested that the high endogenous levels of taurine found in the rat heart and retina are maintained to a large extent by transport processes out of the blood, rather than by endogenous biosynthesis. When these high levels are depleted, dysfunction ensues. In vitro studies have shown that beta-alanine is a good antagonist of these transport processes. The current studies were done to evaluate the feasibility of depleting heart and retinal taurine levels in vivo through treatment of adult rats either orally or with injections of beta-alanine. None of the treatments had significant effects on retinal taurine content; ventricular taurine was reduced in some situations, but the effects were not maintained, nor as large as with another transport antagonist. No functional changes were observed. Oral treatment with beta-alanine had fewer obvious side effects than injections, but all treated rats had body weights less than age-matched controls.