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S Strobel

Publications and source records attributed to S Strobel.

At least 19 recordsLinked to original sources
PubMed2005

Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes.

AIMS/HYPOTHESIS: Long-term trials in insulin-treated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA(1)c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed. METHODS: In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60+/-9 years, BMI 28.9+/-4.8 kg/m(2)) and 15 non-diabetic obese men (age 41+/-21 years, BMI 34.4+/-4.5 kg/m(2)) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 microg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. RESULTS: Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Delta-202+/-64 kcal, -23+/-8%, p<0.01) and obese (Delta-170+/-68 kcal, -16+/-6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. CONCLUSIONS/INTERPRETATION: The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.

Adult↗
PubMed2005

A distinct subset of chemokines dominates the mucosal chemokine response in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is characterised by intense mucosal recruitment of activated leukocytes. Chemokines determine inflammatory leukocyte recruitment and retention. AIM: To compare expression of the entire chemokine family within colonic mucosa from IBD patients and uninflamed controls. METHODS: A microarray of cDNAs, representing every member of this superfamily and their cognate receptors, was hybridised with probes derived from colonoscopic biopsies. RESULTS: A distinct subset of chemokines, consisting of CXCLs 1-3 and 8 and CCL20, was upregulated in active colonic IBD, compared with uninflamed areas or tissue from controls. Increased expression of their cognate receptors, CXCR1, CXCR2 and CCR6, was confirmed by quantitative PCR and immunohistochemistry. An identical chemokine response was induced in Caco-2 cells by stimulation with interleukin (IL)-1beta, but not tumour necrosis factor-alpha (TNF-alpha). By contrast, IL-1beta and TNF-alpha were synergistic in an HT29 cell line and primary keratinocytes. CONCLUSIONS: IL-1beta and TNF-alpha appear to be the pivotal mediators of a previously unidentified coordinated epithelial chemokine response that dominates the mucosal chemokine environment in inflamed IBD tissue.

Caco-2 Cells↗
PubMed2005

Adjunctive therapy with pramlintide lowers HbA1c without concomitant weight gain and increased risk of severe hypoglycemia in patients with type 1 diabetes approaching glycemic targets.

AIMS: In long-term clinical trials in patients with type 1 diabetes spanning a wide range of HbA1c, addition of pramlintide to existing insulin regimens led to reductions in HbA1c that were accompanied by weight loss and no increase in overall severe hypoglycemia event rates. Given that weight gain and increased hypoglycemia risk contribute to the difficulty of attaining HbA1c targets (<7 %), the question arose whether pramlintide could benefit patients approaching, but not reaching glycemic targets with insulin alone. To address this question, we conducted a pooled analysis from 3 long-term clinical trials, including all patients with an entry HbA1c between 7.0 % and 8.5 %. METHODS: Within the subset of patients with an entry HbA1c between 7.0 % and 8.5 % (approximately 28 % of all patients enrolled in the 3 studies), 196 were treated with placebo + insulin (baseline HbA1c 7.9+/-0.4 %, body weight 76.0+/-14.3 kg [mean+/-SD]) and 281 with pramlintide+insulin (baseline HbA1c 7.9+/-0.4 %, body weight 75.4+/-13.1 kg). Endpoints included placebo-corrected changes from baseline to week 26 in HbA1c, body weight, and the event rate of severe hypoglycemia. RESULTS: Adjunctive therapy with pramlintide resulted in significant reductions in HbA1c and body weight from baseline to week 26 (0.3 % and 1.8 kg, placebo-corrected treatment differences, respectively, both p<or=0.0009). These changes occurred without an increase in the overall risk of severe hypoglycemia (1.40 pramlintide vs. 1.86 placebo, events/patient-year of exposure). CONCLUSIONS: Addition of pramlintide to insulin therapy may help patients with type 1 diabetes who are approaching, but not yet reaching, glycemic targets with insulin alone to achieve further reductions in HbA1c without concomitant weight gain and increased risk of severe hypoglycemia.

Adult↗
PubMed2005

Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization.

BACKGROUND: Food allergies are an important cause of life-threatening hypersensitivity reactions. Oral tolerance can be considered the default immune response to dietary antigens, with immune deviation resulting in allergic sensitization. However, primary sensitization to food allergens may not solely be through the gastrointestinal mucosa, as strong T-helper type 2 (Th2)-biased immunity can result from exposure to protein allergens on barrier-disrupted skin. OBJECTIVE: The purpose of this study was to examine whether exposure to allergens through the skin may interfere with the normal development of oral tolerance and promote allergic sensitization to food proteins. METHODS: Female BALB/c mice were exposed epicutaneously to peanut protein and induction of systemic oral tolerance through high dose feeds of peanut protein was subsequently assessed. Other mice were rendered tolerant prior to epicutaneous peanut exposure. Sensitivity to peanut was determined by assessing delayed-type hypersensitivity, proliferative, cytokine and antibody responses. RESULTS: Epicutaneous exposure to peanut protein induced potent Th2-type immunity with high levels of IL-4 and serum IgE. Primary skin exposure prevented the subsequent induction of oral tolerance to peanut in an antigen-specific manner. Upon oral challenge, mice became further sensitized and developed strong peanut-specific IL-4 and IgE responses. Furthermore, animals with existing tolerance to peanut were partly sensitized following epicutaneous exposure. CONCLUSION: Epicutaneous exposure to peanut protein can prevent induction of oral tolerance, and may even modify existing tolerance to peanut. Epidermal exposure to protein allergens selectively drives Th2-type responses, and as such may promote sensitization to food proteins upon gastrointestinal exposure.

Administration, Cutaneous↗
PubMed2005

Patterns of food allergen-specific cytokine production by T lymphocytes of children with multiple allergies.

BACKGROUND: The contribution of different T cell subsets to the overall measured cytokine response to food allergens is largely unexplored. METHOD: The patterns of cytokine production of peripheral blood-derived T cells after allergen stimulation were studied in 22 children with multiple food allergies and in 20 non-allergic children as controls, using flow cytometry. RESULTS: Proportions of T cells of food-sensitized children spontaneously secreting IFN-gamma and IL-10 (without antigen stimulation) were lower than non-atopic children and adult controls (P<or=0.001). The proportions of IL-4-producing cells in vitro were significantly increased (P<or=0.04) and IFN-gamma-producing cells were significantly reduced (P<or=0.05) in sensitized children after incubation with and without dendritic cell presentation of peanut extract, beta-lactoglobulin and ovalbumin. The reverse pattern was found in non-sensitized children and adult controls. IL-4 secretion in allergic children to sensitizing allergens was mainly restricted to the CD4(+) CD45 RO(+) population while in non-atopic controls both CD4(+) and CD8(+) CD45 RO(+) cells produced mostly IFN-gamma. Food-specific IgE values did not correspond with cytokine responses but IL-4 production and IFN-gamma reduction relative to normal children were closely associated with total IgE levels. CONCLUSION: Food-allergic children's IL-4 cytokine response to their relevant allergens is predominantly from a memory population of CD4(+) CD45 RO(+) cells, whereas IL-4 and IFN-gamma secretion of non-allergic controls was predominantly from mixed CD4(+) and CD8(+) CD45 RO(+) populations.

Allergens↗
PubMed2004

Oral administration of bovine whey proteins to mice elicits opposing immunoregulatory responses and is adjuvant dependent.

Most studies investigating the induction of oral tolerance (OT) use purified proteins such as ovalbumin (OVA), bovine serum albumin (BSA) and beta-lactoglobulin (beta-LG). Little information is available regarding the induction of OT to a protein mixture, e.g. cow's milk. In this study we compared the regulatory mechanisms induced after the oral administration of a whey protein concentrate (WP) derived from cow's milk following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum. OVA was used as a control antigen. Animals were given a single feed of these proteins at an equivalent dose of 1 mg/g body weight before they were immunized seven days later with the antigen in Freund's adjuvant or alum. Delayed type hypersensitivity (DTH) responses were suppressed by both a feed of WP and OVA after immunization with CFA. However, only OVA feeding suppressed antigen specific IgG responses. In an attempt to investigate whether WP would tolerize the more susceptible IgE responses, alum immunization replaced CFA as the adjuvant used for systemic immunizations. WP, after a single feed, significantly primed for DTH and IgE responses indicating oral sensitization to WP. In contrast, OVA suppressed DTH, IgE and IgG responses. Antigen specific proliferation of mononuclear cells was suppressed in mice fed OVA, but primed in those fed with WP. In addition cells taken from sensitized mice fed WP up-regulated levels of specific interleukin (IL) -4, -10 and -12 in vitro whereas these cytokines were suppressed in cultures from tolerant WP fed mice. Global suppression was obtained in cultures from tolerant OVA fed mice. TGF-beta was not detected in draining PLN cell cultures of either tolerant or sensitized mice. These data suggest that a whey protein mixture induces divergent responses following immunization with either CFA or alum despite being fed at an identical dose. We suggest that that the choice of the adjuvant may determine the immunoregulatory outcome and this is also reflected by the systemic cytokine profile.

Administration, Oral↗
PubMed2003

Helicobacter pylori eradication and gastric ulcer healing--comparison of three pantoprazole-based triple therapies.

AIM: To study the efficacy of three pantoprazole-based triple therapy regimens for the eradication of Helicobacter pylori infection and gastric ulcer healing. METHODS: In an open, multi-centre, randomized study, 519 H. pylori-positive patients with active gastric ulcer were randomized to receive pantoprazole (40 mg) (P) and two of three antibiotics: clarithromycin (500 mg) (C), metronidazole (500 mg) (M) or amoxicillin (1000 mg) (A). Triple therapy (PAC, PCM, PAM) was administered twice daily for 7 days, followed by pantoprazole until the ulcer had healed. Antrum and corpus biopsies were taken to determine the pattern of gastritis, to assess the H. pylori status and to determine the strain susceptibility to antibiotics, and from the ulcer margins and base to exclude malignancy. Scores based on the Sydney system were used to categorize the gastritis phenotypically. RESULTS: The H. pylori eradication rates for the per protocol (intention-to-treat) analysis were 89% (67%) for PAC, 83% (68%) for PCM and 76% (60%) for PAM, with a significant difference between PAC and PAM. Healing rates after 4 weeks were 91% for PAM, 90% for PCM and 88% for PAC (per protocol analysis). The eradication rates were lower in patients in whom strains resistant to any antibiotic used in the triple therapies were detected. Successful eradication [odds ratio, 5.2 (3.3; 8.3)] and the ulcer size (< 15 mm) were significant predictors for healing after 4 weeks. The regimens showed a comparable safety profile and compliance. CONCLUSIONS: Pantoprazole-based triple therapies are effective in the eradication of H. pylori infection in gastric ulcer patients, as reported in previous similar sized studies in duodenal ulcer patients. Successful eradication and an ulcer size of < 15 mm are the best predictors of gastric ulcer healing after 4 weeks.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Prenatal diagnosis of congenital rubella infection in the second trimester of pregnancy.

OBJECTIVES: This case report describes the clinical presentation, diagnosis and management of a case of acute rubella infection in the second trimester. The complex issues of prenatal diagnosis of a congenital rubella infection are discussed. METHODS: A 30-year-old woman presented with a fine macular rash at 15 weeks' gestation. Laboratory testing included maternal rubella-specific IgG and IgM detection (booking blood and acute-phase sample) together with measurement of IgG avidity. Prenatal diagnosis at 19 weeks (amniocentesis) and 23 weeks (amniocentesis and fetal blood) was done using a reverse-transcriptase polymerase chain reaction to detect rubella-specific RNA. The fetal blood sample was also tested for rubella-specific IgM. RESULTS: Maternal serological results confirmed an acute rubella infection at 15 weeks' gestation. Rubella-specific RNA and IgM were detected in the fetal blood taken at 23 weeks' gestation. However, no rubella RNA was detected in either of the amniotic fluid samples collected at 19 and 23 weeks. CONCLUSION: In second-trimester rubella where risk of fetal damage is low, prenatal diagnosis can identify the rubella-infected fetus, allowing the parents to make a more informed decision about their options. The optimal sample for prenatal diagnosis is fetal blood as no rubella-specific RNA was detected in the amniotic fluid.

Adult↗
PubMed2003

Effect of pramlintide on A1C and body weight in insulin-treated African Americans and Hispanics with type 2 diabetes: a pooled post hoc analysis.

An unresolved problem in the management of type 2 diabetes is that improvement of glycemic control with insulin, insulin secretagogues, and insulin sensitizers is often accompanied by undesired weight gain. This problem is of particular concern in ethnic groups with a high propensity for diabetes and obesity, such as African Americans and Hispanics. Two 1-year, randomized, double-blind, placebo-controlled clinical trials in insulin-treated patients with type 2 diabetes have shown that adjunctive therapy with pramlintide, an analog of the human beta-cell hormone amylin, reduces A(1C) with concomitant weight loss, rather than weight gain. To assess the effect of pramlintide in various ethnic groups with type 2 diabetes using insulin, we conducted a pooled post hoc analysis of the 2 trials, which included all Caucasian (n = 315), African American (n = 47), and Hispanic (n = 48) patients (age 57 years, A(1C) 9.1%, body mass index [BMI] 33 kg/m(2), mean values) who completed 52 weeks of treatment with either pramlintide (120 microg twice daily or 150 microg 3 times a day) or placebo. Primary endpoints included changes from baseline to week 52 in A(1C) and body weight. Collectively, pramlintide-treated patients achieved significant reductions from baseline in both A(1C) and body weight (placebo-corrected treatment effects at week 52: -0.5% and -2.6 kg, respectively, both P <.0001). The simultaneous reduction in A(1C) and body weight at week 52 was evident across all 3 ethnic groups and appeared to be most pronounced in African Americans (-0.7%, -4.1 kg), followed by Caucasians (-0.5%, -2.4 kg) and Hispanics (-0.3%, -2.3 kg). The glycemic improvement with pramlintide was not associated with an increased incidence of hypoglycemia over the entire study period (43% pramlintide v 40% placebo). Nausea, the most common adverse event associated with pramlintide treatment, was mostly mild and confined to the first 4 weeks of therapy (25% pramlintide v 16% placebo) with comparable patterns in the 3 ethnic groups. Thus, pending further experience, the combined improvement in glycemic and weight control with pramlintide treatment appears to be generalizable to a broad population of mixed ethnicity.

Black or African American↗
PubMed2003

Addition of pramlintide to insulin therapy lowers HbA1c in conjunction with weight loss in patients with type 2 diabetes approaching glycaemic targets.

AIM: Two long-term, randomized, double-blind, placebo-controlled clinical trials in insulin-using patients with type 2 diabetes, spanning a wide range of baseline glycaemic control, have shown that the addition of pramlintide, an analogue of the beta-cell hormone amylin, to pre-existing insulin regimens results in reductions in HbA1c that are accompanied by weight loss. METHODS: To assess whether this profile of pramlintide is observed in patients approaching, but not yet reaching, glycaemic targets, we conducted a pooled post hoc analysis of the two trials, including all patients with an entry HbA1c between 7.0 and 8.5%. Within this subset of patients, 80 were treated with placebo + insulin [baseline HbA1c 8.0 +/- 0.3%, weight 87.3 +/- 19.3 kg (mean +/- s.d.)] and 86 with pramlintide (120 micro g bid) + insulin [HbA1c 8.0 +/- 0.4%, weight 92.5 +/- 20.4 kg (mean +/- s.d.)]. Endpoints included changes from baseline to Week 26 in HbA1c, body weight, and the event rate of severe hypoglycaemia. RESULTS: Adjunctive therapy with pramlintide resulted in significant reductions in both HbA1c and body weight from baseline to Week 26 (-0.43% and -2.0 kg differences from placebo, respectively, both p < 0.001). These changes were achieved without a concomitant increase in the overall rate of severe hypoglycaemic events (0.13 pramlintide vs. 0.19 placebo, events/patient year of exposure). CONCLUSIONS: The data from this post hoc analysis indicate that the addition of pramlintide to insulin therapy may help patients with type 2 diabetes who are approaching, but not yet reaching, glycaemic targets to achieve further reductions in HbA1c without concomitant weight gain and increased risk of severe hypoglycaemia.

Aged↗
PubMed2003

Non-responders to hepatitis B vaccination: a review.

Hepatitis B virus (HBV) infection is a major public health issue throughout the world and vaccination of those at risk is the main method of containment. Of healthy vaccinees, 5-10% fail to mount an adequate antibody response. The antibody levels of an unknown further fraction of vaccinees fall considerably over time rendering them at a potential risk of infection. The scope of this article is to review the factors that might influence the immune response to HBV vaccination, to review the methods used to overcome the problem of poor response and to discuss what possible guidelines are available or needed in treating these vaccinees.

Hepatitis B↗
PubMed2002

Food allergy in children.

Food allergies are increasing in prevalence and as a disease burden throughout the world, however they seem to increasingly affect countries with a formerly low prevalence. Consideration and diagnosis of food allergies are important as it has ramifications that affect a child's diet, care at school and home and is recognised to be associated with anxiety of parents, family and care takers. Food allergies vary significantly between countries, however nut allergies appear to be widely associated with serious reactions and death. The value of specific food immunoglobulin E (IgE) and skin prick tests (SPT) has been extensively analysed in children in recent years and can provide very useful information in an appropriately selected population. Diagnosis may require formal challenges to confirm a genuine allergic reaction condition rather than an intolerance reaction due to other mechanisms. The medical care of a food allergic child requires concurrent dietary advice and management, risk avoidance and emergency management plans. Reintroduction of foods occurs when the risk profile is appropriate based mainly on the predictive information obtained by SPTs and specific IgE levels. Fortunately allergies to egg and milk resolve by 3-5 years in about 80% of children. There have been some recent advances in immunotherapeutic approaches to food allergy although this has not translated to success in human treatment to date.

Child↗
PubMed2002

The human amylin analog, pramlintide, reduces postprandial hyperglucagonemia in patients with type 2 diabetes mellitus.

AIMS: Amylin is a second beta-cell hormone that is normally co-secreted with insulin in response to meals; it complements the effects of insulin in postprandial glucose control, in part by suppressing glucagon secretion. In patients with type 2 diabetes, mealtime administration of the human amylin analog pramlintide markedly improves postprandial glucose excursions. The aim of this study was to examine whether pramlintide reduces the postprandial hyperglucagonemia that is often seen in this patient population. METHODS: Utilizing a single-blind, placebo-controlled crossover design, 24 patients with type 2 diabetes, 12 insulin-treated and 12 non-insulin-treated, underwent a standardized mixed meal test on 2 occasions during which they received, in randomized order, a five-hour intravenous infusion of placebo or pramlintide (100 microg/h). RESULTS: During the placebo infusion, plasma glucose and plasma glucagon concentrations increased substantially after the meal. During the pramlintide infusion, postprandial plasma glucose and plasma glucagon responses were significantly (p < 0.05, all) reduced following ingestion of the same meal, both in the insulin-treated and non-insulin-treated subgroups. CONCLUSION: Supplementation of mealtime amylin with pramlintide reduces postprandial hyperglucagonemia in patients with type 2 diabetes, a mechanism that likely contributes to pramlintide's postprandial glucose-lowering effect.

Adult↗
PubMed2001

Immunity induced after a feed of antigen during early life: oral tolerance v. sensitisation.

There is good clinical and experimental evidence that oral tolerance exists in man and that the timing of antigen (food) administration is an important factor in the development of food allergic sensitisation and disease. Induction of tolerance is often seen as a T-helper 2-skewed response, which on one side may prevent harmful mucosal immune reactions, but on the other side may contribute to adverse responses in the susceptible individual. The primary mechanisms by which tolerance may be mediated include T-cell deletion, anergy, suppression 'ignorance' and apoptosis. Cell-mediated delayed hypersensitivity reactions (T-helper 1), which are implicated as a pathogenetic principle in the development of autoimmune and gastrointestinal inflammation are particularly well suppressed. Regulatory events during the induction of tolerance (or sensitisation) are not well characterised and remain at times controversial. The balance between tolerance (suppression) and sensitisation (priming) is dependent on several factors, such as: (a) genetic background; (b) nature of antigen and dose of antigen; (c) frequency of administration; (d) age (maturity v. immaturity) at first antigen exposure; (e) immunological status of the host (e.g. virus infection); dietary exposure of the mother; (g) antigen transmission via breast milk, and others. Overall, there is evidence in rodents that multiple low-dose feeds are more likely to induce regulatory cytokines (e.g. transforming growth factor-beta, interleukins 10 and 4) in part secreted by CD4+CD25+ T-regulatory cells. Despite the powerful suppressive effect of oral antigen exposure observed in experimental models, its application in clinical trials of autoimmune diseases has not yet yielded the expected beneficial results.

Administration, Oral↗
PubMed2000

Identification and molecular analysis of superoxide dismutase isoforms in Helicobacter pylori.

Three electromorphs of iron superoxide dismutase (FeSOD) were identified among 29 Helicobacter pylori isolates by native gel electrophoresis and activity staining. The electromorphs designated isoforms A, B, and C are characterized by slow, intermediate and fast electrophoretic migration, respectively, which was not observed under denaturing conditions. The isoforms were not associated with virulence determinants and with the outcome of disease. Sequence analysis of the sodB gene in strains producing different FeSOD isoforms and comparison of deduced protein sequences revealed that differences in the electric migration behavior are associated with exchange of charged amino acids, suggesting that faster migration is caused by a more negative total charge of the proteins. Electrophoretic migration of native FeSOD was not influenced by changes in the iron cofactor concentration, oxidative stress, and different media, indicating that FeSOD isoforms represent stable strain-specific markers.

Amino Acid Sequence↗
PubMed2000

Immunomodulatory effects of breast milk oligosaccharides.

Breast milk oligosaccharides are excreted in urine in amounts that suggest that they may exist in the circulation at levels compatible with a physiological function. Some oligosaccharides have structural similarity to cellular adhesion molecules and may influence adhesion of cells in breast fed infants. In this study, breast milk oligosaccharides were purified and incubated in assays of cell adhesion. They were found to inhibit neutrophil adhesion to stimulated vascular endothelial cells in a dose dependent fashion. In contrast they enhanced platelet-neutrophil complex formation. These results indicate that breast milk oligosaccharides may play a physiological role in modulating cellular adhesion in vivo.

Absorption↗