Textural and Rheological Properties of Oat Beta-Glucan Gels with Varying Molecular Weight Composition.

The impact of oat ß-glucan concentration and molecular weight (MW) on gel properties was investigated. Mixed MW gels/viscous solutions at 3, 4, and 5% ß-glucan with high molecular weight (HMW):low molecular weight (LMW) ratios of 0:100, 25:75, 50:50, 75:25, and 100:0 were evaluated. The 100:0 and 50:50 gels had the lowest tan δ values. The 50:50 gels had the highest storage moduli (G'), whereas 100:0 solutions did not gel. Peak melting temperature (TP) was highest for 0:100 gels and decreased with the addition of HMW ß-glucan. Hardness, at 40% compression, increased with concentration, and 25:75 and 50:50 gels were hardest at each concentration. Ordered microstructure, apparent in 0:100 gels, diminished with HMW ß-glucan addition. Glucose addition resulted in lower tan δ values and firmer, harder gels compared to gels without glucose. Thus, the textural properties and melting profiles of ß-glucan gels can be manipulated by adjusting the ratios of molecular weight fractions or addition of sugar for different applications.

Ovarian 11ß-hydroxysteroid dehydrogenase (11ßHSD) activity is suppressed in women with anovulatory polycystic ovary syndrome (PCOS): apparent role for ovarian androgens.

CONTEXT: Altered hepatic cortisol-cortisone metabolism by type 1 11ß-hydroxysteroid dehydrogenase (11ßHSD1) has previously been linked with polycystic ovary (PCO) syndrome (PCOS). OBJECTIVES: Our objectives were to establish whether ovarian 11ßHSD activities are also altered in PCOS and to determine whether any changes in ovarian cortisol metabolism might reflect exposure to elevated concentrations of insulin or androgens. DESIGN: Cortisol and cortisone concentrations were measured in follicular fluid aspirated from size-matched follicles dissected from normal, ovulatory, and anovulatory PCOs. Human granulosa-lutein cells, recovered during oocyte retrieval for assisted conception, were maintained in primary culture for 4 days, after which 11ßHSD1 activities were measured as the net oxidation of [(3)H]cortisol (100 nmol/L) in the absence and presence of insulin (100 nmol/L) with or without metformin (1 µmol/L) or a range of androgens/oxy-androgen metabolites (0.01-10 µmol/L). RESULTS: Intrafollicular cortisol to cortisone ratios were elevated in anovulatory PCOs (2.1 ± 0.4, P < .05, n = 13) but did not differ between follicles from ovulatory PCOs (1.6 ± 0.1, n = 24) and normal ovaries (1.2 ± 0.1, n = 14). 11ßHSD1 activities were lower in granulosa-lutein cells recovered from patients with PCOS compared with all other causes of infertility (median = 5.8 vs 14.9 pmol cortisone/4 h, respectively; P < .05). Cortisol oxidation was unaffected by insulin with or without metformin, dehydroepiandrosterone, and androstenedione, but was inhibited in a concentration-dependent manner by testosterone, 11ß-hydroxyandrostenedione, and 7α- and 7ß-hydroxy-dehydroepiandrosterone (P < .01). CONCLUSIONS: There is decreased inactivation of cortisol in follicles from anovulatory PCOS. This may reflect inhibition of 11ßHSD1 by androgens and their 7/11-oxy-metabolites, local concentrations of which are increased in PCOS, and may contribute to the block to folliculogenesis seen in PCOS.

Physicochemical properties of oat ß-glucan influence its ability to reduce serum LDL cholesterol in humans: a randomized clinical trial.

BACKGROUND: Consumption of 3 g oat ß-glucan/d is considered sufficient to lower serum LDL cholesterol, but some studies have shown no effect. LDL cholesterol lowering by oat ß-glucan may depend on viscosity, which is controlled by the molecular weight (MW) and amount of oat ß-glucan solubilized in the intestine (C). OBJECTIVES: Our 2 primary objectives were to determine whether consumption of 3 g high-MW oat ß-glucan/d would reduce LDL cholesterol and whether LDL cholesterol lowering was related to the log(MW × C) of oat ß-glucan. DESIGN: In a double-blind, parallel-design, multicenter clinical trial, subjects with LDL cholesterol ≥3.0 and ≤5.0 mmol/L (n = 786 screened, n = 400 ineligible, n = 19 refused, n = 367 enrolled, and n = 345 completed) were randomly assigned to receive cereal containing wheat fiber (n = 87) or 3 g high-MW (2,210,000 g/mol, n = 86), 4 g medium-MW (850,000 g/mol, n = 67), 3 g medium-MW (530,000 g/mol, n = 64), or 4 g low-MW (210,000 g/mol, n = 63) oat ß-glucan/d (divided doses, twice daily) for 4 wk. RESULTS: LDL cholesterol was significantly less with 3 g high-MW, 4 g medium-MW, and 3 g medium-MW oat ß-glucan cereals than with the wheat-fiber cereal by 0.21 (5.5%; 95% CI: -0.11, -0.30; P = 0.002), 0.26 (6.5%; 95% CI: -0.14, -0.37; P = 0.0007), and 0.19 (4.7%; 95% CI: -0.08, -0.30; P = 0.01) mmol/L, respectively. However, the effect of 4 g low-MW oat ß-glucan/d (0.10 mmol/L) was not significant (2.3%; 95% CI: 0.02, -0.20). By analysis of covariance, log(MW × C) was a significant determinant of LDL cholesterol (P = 0.003). Treatment effects were not significantly influenced by age, sex, study center, or baseline LDL cholesterol. CONCLUSIONS: The physicochemical properties of oat ß-glucan should be considered when assessing the cholesterol-lowering ability of oat-containing products; an extruded breakfast cereal containing 3 g oat ß-glucan/d with a high-MW (2,210,000 g/mol) or a medium-MW (530,000 g/mol) lowered LDL cholesterol similarly by ≈0.2 mmol/L (5%), but efficacy was reduced by 50% when MW was reduced to 210,000 g/mol. This trial was registered at www.clinicaltrials.gov as NCT00981981.

Processing affects the physicochemical properties of beta-glucan in oat bran cereal.

The tendency of mixed linkage oat beta-glucan to form viscous solutions is generally assumed to be related to its ability to lower serum cholesterol levels in humans. However, the association has not been clearly demonstrated. To conduct a clinical trial showing the relationship between LDL-cholesterol levels and viscosity, a series of extruded oat bran cereals were prepared in which the beta-glucan had a range of molecular weights and modified solubility. An extraction protocol using physiological enzymes at 37 degrees C was used to estimate the effect that the cereals would have on gut viscosity. By reducing the molecular weight from 1,930,000 to 251,000 g/mol, the apparent viscosity in the physiological extract dropped from 2900 to 131 mPa.s (at 30 s(-1)). Microscopic examination showed that as the extrusion conditions were made more severe, to cause depolymerization, the integrity of the cell walls was lost and beta-glucan dispersed throughout the cereal. Differences in the hardness and density of the extruded cereals were also evident as the molecular weight was reduced.

Physicochemical properties of beta-glucan in differently processed oat foods influence glycemic response.

To assess the effect of food processing on the capacity of oat beta-glucan to attenuate postprandial glycemia, isocaloric crisp bread, granola, porridge, and pasta containing 4 g of beta-glucan as well as control products with low beta-glucan content were prepared. The physicochemical properties (viscosity, peak molecular weight (M(p)), and concentration (C)) of beta-glucan in in-vitro-digestion extracts were evaluated, and fasting and postprandial blood glucose concentrations were measured in human subjects. Porridge and granola had the highest efficacy in attenuating the peak blood glucose response (PBGR) because of their high M(p) and viscosity. beta-Glucan depolymerization in bread and pasta reduced beta-glucan bioactivity. Pastas, known to have low glycemic responses, showed the lowest PBGR. The analyses of these products with previously reported data indicated that 73% of the bioactivity in reducing PBGR can be explained by M(p) x C. Characterizing the physicochemical properties of beta-glucan in bioactive foods aids functional food development.

Effect of blood sampling schedule on the ability to discriminate between postprandial glycemic responses.

OBJECTIVE: The blood glucose responses elicited by foods are often determined using blood samples taken at 15-min intervals. Our objective was to see whether taking blood samples at 10-min intervals affected the results. METHODS: Overnight-fasted healthy subjects (n=11) were studied on nine different occasions with seven different test meals. Blood samples were obtained at fasting and at 10, 15, 20, 30, 40, 45, 50, 60, 90, and 120 min after starting to eat. Peak rise, incremental area under the curve, and relative glycemic response were calculated using the 10- and 15-min sampling schedules. RESULTS: With 10-min intervals, peak rise was 4% greater than with 15-min intervals (P<0.001), but sampling interval did not significantly affect mean incremental area under the curve or relative glycemic response. The 10-min blood sampling schedule had a slightly greater ability to discriminate between foods and between subjects for peak rise and relative glycemic response. CONCLUSIONS: We conclude that the blood sampling schedule used may influence the accuracy and precision of measurements of glycemic response; however, the difference between taking blood samples at 10-min and 15-min intervals is quite small.

Who are sexual offenders? A survey of pre-trial psychiatric reports.

Sexual offending is a serious and growing problem in our society. The aim of the study was to investigate the main characteristics of people charged with sexual offences who presented before the criminal courts. The survey was conducted retrospectively between August 2001 and August 2006 on pre-trial court reports stored in a computer database shared by forensic psychiatrists using The Grange consulting rooms in West Yorkshire. A data collection form was used to gather the characteristics of sexual offenders. The data collected was analysed using descriptive statistics. Our survey revealed the following results. Out of 78 cases evaluated, the commonest sexual offence was against children (68.8%). Thirty-two per cent of those with paedophilic behaviour had a history of childhood sexual abuse. Rape was alleged as the main sexual offence in 27.27% cases. Substance abuse (30.76%) and sexual motivation (42.30%) were the predominant motives for offending behaviour. Low rates of sexual fantasy and sadistic behaviour (8.97%) in our sample could be due to the non-disclosure by sexual offenders. Mental disorder was observed in 7.69% cases. Significant personality factors were observed in 14.10% of the sample. A sexual offending treatment programme was recommended in 57.69% cases. A very high risk of re-offending was recorded in 32.25% cases. Of the total sample, 93.50% were deemed fit to plead.

Thyroid function during coronary surgery with and without cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass (CPB) is associated with thyroid hormone changes consistent with euthyroid sick syndrome. Similar changes have been observed after general surgical operations. Thyroid hormone changes and their association with global oxygen consumption were studied in low-risk patients undergoing coronary artery bypass grafting (CABG) with and without CPB. METHODS: Fifty-two patients undergoing primary CABG by the same surgeon were randomised into either on-pump (ONCAB, n=26) or off-pump (OPCAB, n=26) groups. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) levels were measured at sequential time-points using chemiluminescence assays. Global oxygen consumption was measured at sequential time-points using a continuous cardiac output Swan-Ganz catheter. RESULTS: In both groups TSH and fT4 remained within normal range throughout the study. There was a similar and progressive decline in fT3 levels with no significant difference between the groups over time (p=0.42). Mean fT3 levels at 24h were below the normal range and significantly lower than baseline values (ONCAB, 3.3+/-0.69 pmol/L vs 5.1+/-0.41 pmol/L, p<0.001; OPCAB, 3.3+/-0.51 pmol/L vs 5.0+/-0.46 pmol/L, p<0.001). There was a significant inverse relationship between fT3 levels and global oxygen consumption. CONCLUSIONS: Off-pump surgery is associated with thyroid hormone changes similar to conventional surgical revascularisation. The data suggest that further studies into T3 administration during OPCAB may be warranted.

Cushing's syndrome in women with polycystic ovaries and hyperandrogenism.

BACKGROUND: A 41-year-old woman presented to an endocrinology-gynecology clinic having been diagnosed 7 years earlier with polycystic ovarian syndrome on account of hirsutism, subfertility, greasy skin, acne and multiple ovarian cysts. Ovulation induction had led to a successful pregnancy. Subfertility recurred, however, and persisted alongside a new diagnosis of hypertension and progressive weight gain. Upon examination, the patient was hypertensive with facial plethora, rounded facies and violaceous abdominal striae. INVESTIGATIONS: Low-dose dexamethasone test, bedtime salivary and 24-h urinary free cortisol estimations, CT scan of the abdomen, and serum hormone and gonadotropin analyses. DIAGNOSIS: Cushing's syndrome due to a right adrenocortical adenoma. MANAGEMENT: The patient underwent laparoscopic right adrenalectomy, which led to resolution of all symptoms, signs and biochemical abnormalities.

Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome.

OBJECTIVE: Enhancement of negative feedback control of the HPA axis in patients with chronic fatigue syndrome (CFS) has been reported using the low dose dexamethasone suppression test. We have developed the use of prednisolone (5mg) as a more physiologically appropriate alternative to dexamethasone in the investigation of mild degrees of glucocorticoid resistance or supersensitivity. The objective of the study was to use this test to look for alterations in negative feedback control of the HPA axis in CFS patients. METHODS: Fifteen patients with CFS were recruited after fulfilling strict criteria including the absence of comorbid psychiatric diagnosis. They collected urine between 0900 and 1800h and saliva at 0900h pre-prednisolone. At midnight, they took prednisolone (5mg) orally and then collected urine and saliva at the same intervals the following day. RESULTS: Salivary cortisol was lower in CFS subjects pre-prednisolone than controls. Urinary cortisol metabolites were lower in CFS subjects pre-prednisolone, but did not reach significance. Both measures were significantly lower in CFS subjects post-dose. Mean percentage suppression of both salivary cortisol and urinary cortisol metabolites was significantly higher in CFS compared to controls. CONCLUSION: There is enhanced sensitivity of the HPA axis to negative feedback in CFS as demonstrated using the prednisolone suppression test. This provides further evidence of alterations in the control of the HPA axis in patients with established CFS.

In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development.

In humans, sexual differentiation of the external genitalia is established at 7-12 weeks post conception (wpc). During this period, maintaining the appropriate intrauterine hormone environment is critical. In contrast to other species, this regulation extends to the human fetal adrenal cortex, as evidenced by the virilization that is associated with various forms of congenital adrenal hyperplasia. The mechanism underlying these clinical findings has remained elusive. Here we show that the human fetal adrenal cortex synthesized cortisol much earlier than previously documented, an effect associated with transient expression of the orphan nuclear receptor nerve growth factor IB-like (NGFI-B) and its regulatory target, the steroidogenic enzyme type 2 3beta-hydroxysteroid dehydrogenase (HSD3B2). This cortisol biosynthesis was maximal at 8-9 wpc under the regulation of ACTH. Negative feedback was apparent at the anterior pituitary corticotrophs. ACTH also stimulated the adrenal gland to secrete androstenedione and testosterone. In concert, these data promote a distinctive mechanism for normal human development whereby cortisol production, determined by transient NGFI-B and HSD3B2 expression, provides feedback at the anterior pituitary to modulate androgen biosynthesis and safeguard normal female sexual differentiation.

Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome.

OBJECTIVE: The aim of this study was to obtain comprehensive information on basal hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome (CFS) patients who were not affected by medication or comorbid psychiatric disorder likely to influence the HPA axis. METHOD: Steroid analysis of urine collections from 0600 to 2100 h at 3-h intervals in CFS patients and in controls. RESULTS: Urinary free cortisol and cortisone concentrations showed a significant normal diurnal rhythm, but levels were lower across the cycle in CFS. In contrast, while urinary cortisol metabolites also showed a normal diurnal rhythm, levels were not significantly different between the CFS and controls at any time. Derived metabolite ratios were similar in both groups. CONCLUSION: This study provides further evidence for reduced basal HPA axis function in patients with CFS, based on lower free cortisol and cortisone levels, but this is not corroborated by cortisol metabolite data. The difference between these measures cannot be explained by an altered timing of the diurnal rhythm.

Assessment of subtle changes in glucocorticoid negative feedback using prednisolone: comparison of salivary free cortisol and urinary cortisol metabolites as endpoints.

BACKGROUND: Prednisolone is better than dexamethasone to probe subtle changes in HPA axis sensitivity but cortisol assay as an endpoint risks cross-reaction with prednisolone. We compared capillary gas chromatography, which distinguishes urinary cortisol and prednisolone metabolites, and salivary cortisol immunoassay. METHODS: Twenty adult volunteers (10 m) collected urine for consecutive 3 h periods and saliva at 3 h intervals from 2100 for 24 h, took prednisolone (5 mg) at midnight and continued collecting until 2100. RESULTS: Suppression of urine cortisol metabolites began at 0600 and ceased after 1800. The lowest CV was obtained for the period 0900-1800: mean suppression was 56 +/- 7% for males and 55 +/- 9% for females. Suppression of salivary cortisol was only consistently seen at 0900: mean suppression was 41 +/- 5% in males and 47 +/- 9% in females. Chromatography revealed significant cross reactivity of prednisolone in saliva at 0300 and 0600, but not by 0900. Suppression of salivary cortisol and urinary cortisol metabolites was not correlated for either gender. CONCLUSION: Both urinary cortisol metabolite and salivary cortisol assay following administration of 5 mg prednisolone have potential for investigation of changed HPA axis negative feedback, based on a convenient pre- and post-dose urinary collection between 0900 and 1800 and salivary sampling at 0900.

Variants in the human insulin gene that affect pre-mRNA splicing: is -23HphI a functional single nucleotide polymorphism at IDDM2?

Predisposition to type 1 diabetes and juvenile obesity is influenced by the susceptibility locus IDDM2 that includes the insulin gene (INS). Although the risk conferred by IDDM2 has been attributed to a minisatellite upstream of INS, intragenic variants have not been ruled out. We examined whether INS polymorphisms affect pre-mRNA splicing and proinsulin secretion using minigene reporter assays. We show that IVS1-6A/T (-23HphI+/-) is a key INS variant that influences alternative splicing of intron 1 through differential recognition of its 3' splice site. The A allele resulted in an increased production of mature transcripts with a long 5' leader in several cell lines, and the extended mRNAs generated more proinsulin in culture supernatants than natural transcripts. The longer mRNAs were significantly overrepresented among beta-cell-expressed sequenced tags containing the A allele as compared with those with T alleles. In addition, we show that a rare insertion/deletion polymorphism IVS1+5insTTGC (IVS-69), which is exclusively present in Africans, activated a downstream cryptic 5' splice site, extending the 5' leader by 30 bp. These results indicate that -23HphI and IVS-69 are the most important INS variants affecting pre-mRNA splicing and suggest that -23HphI+/- is a common functional single nucleotide polymorphism at IDDM2.

Midazolam in the reduction of surgical stress: a randomized clinical trial.

OBJECTIVE: The objective of this study was to assess the role of midazolam in reducing surgical stress as measured using subjective and objective variables. STUDY DESIGN: The study was a double-blind randomized controlled trial. Thirty-eight male patients undergoing surgical removal of third molars under general anesthesia were recruited for this study, each patient was given premedication (midazolam or placebo) and subjective variables (HAD scale) were obtained and objective variables (salivary cortisol samples and vital signs) were collected pre-, peri-, and postoperatively. The salivary samples were analyzed by direct immunofluorimetric assay using the "DELFIA" system. RESULTS: There were no significant differences in anxiety between the treatment group and the control group before the administration of the premedication. Following the administration of premedication, the majority of the control group showed high cortisol levels on the day of surgery, compared with relatively low cortisol levels in the majority of the treatment group. A few patients in the control group gave a placebo effect (sedative effect) and a number of the treatment group were unresponsive to the drug. There was a slight drop in the blood pressure and respiration rate with a slight increase in the heart rate in the treatment group; however these results were not statistically significant. The HAD scores were not statistically different between the 2 groups. CONCLUSION: Midazolam has proved to be very successful in reducing anxiety and stress pre-, peri-, and postoperatively with no significant effect on the vital signs of a healthy patient. Salivary cortisol technique is an easy, noninvasive method to assess anxiety and stress level in patients undergoing surgery.

Circulating cortisone levels are associated with biochemical markers of bone formation and lumbar spine BMD: the Hertfordshire Cohort Study.

OBJECTIVE: Cortisone is an endogenous corticosteroid that has negligible intrinsic glucocorticoid activity but can be converted to the active corticosteroid cortisol by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). 11beta-HSD1 is expressed in osteoblasts and may play a role in determining susceptibility to glucocorticoid-induced osteoporosis. In intact osteoblasts enzyme activity, and thus cortisol generation, is dependent on substrate concentration with an almost linear increase in activity across the physiological range. We have therefore attempted to measure the impact of 11beta-HSD1 activity on bone in vivo by examining the association of circulating cortisone with bone markers, bone mineral density (BMD) and bone loss in a cohort of women and men. DESIGN AND SUBJECTS: Baseline cross-sectional association study involving 135 women and 171 men aged 61-73 years from the Hertfordshire Cohort Study and a 4 year follow-up study examining changes in BMD. MEASUREMENTS: Serum cortisone, cortisol and osteocalcin, and urinary type I collagen cross-linked N-telopeptide (NTX) were measured at baseline. BMD at spine and hip was measured at baseline and 4 years later. RESULTS: In men serum cortisone levels were negatively correlated with serum osteocalcin (r = -0.20, P = 0.01); a similar relationship was seen in women (r = -0.16, P = 0.06). No correlation was seen between serum cortisone and urinary NTX (r = 0.03, P = 0.74 for women; r = -0.03, P = 0.72 for men). A negative correlation was observed between serum cortisone and spine BMD in women (r = -0.18, P = 0.04); a similar relationship was also seen in men (r =-0.14, P = 0.07). However, cortisone did not correlate with BMD at the femoral neck or total hip or changes in BMD at any site over time. In analyses adjusted for adiposity, osteoarthritis grade and a range of life-style variables, these relationships did not change substantially. All these relationships were independent of cortisol concentrations. CONCLUSIONS: The most plausible explanation for the association of circulating cortisone levels with osteocalcin is the presence of 11beta-HSD1 activity within osteoblasts. The measurement of serum cortisone may independently give insights into the action of glucocorticoids on bone.

Is there a gender difference in the associations of birthweight and adult hypothalamic-pituitary-adrenal axis activity?

OBJECTIVE: Increased hypothalamic-pituitary-adrenal (HPA) axis activity in men of low birthweight may be an important link between early life and the adult metabolic syndrome. In animal models females are more sensitive than males to HPA axis programming, but whether gender influences susceptibility in humans is unknown. DESIGN: Birth cohort study. METHODS: We studied 106 women aged 67-78 years, from Hertfordshire, UK, in whom birthweight was recorded. Negative feedback sensitivity was assessed by an overnight low-dose (0.25 mg) dexa-methasone suppression test, and adrenal sensitivity by a low-dose (1 microg) ACTH(1 - 24) stimulation test. Cortisol and its metabolites were analysed in a 24 h urine collection. Data were compared with previously published identical measurements in 205 men aged 66-77 years from the same cohort. RESULTS: In women, plasma cortisol levels after dexamethasone were lower (P < 0.0001) and peak cortisol following ACTH(1 - 24) were higher (P < 0.0001) than in men, suggesting a more responsive HPA axis. As in men, women with lower birthweight had enhanced plasma cortisol responses to ACTH(1 - 24) (P = 0.05 for trend) but no difference in plasma cortisol after dexamethasone or in urinary cortisol metabolite excretion. The strength of the association in women was not different from that in men; a 1 lb decrease in birthweight was associated with an incremental rise in cortisol of 12.6 nmol/l (95% confidence interval (CI) 1.4, 23.8) in men, P = 0.03, and 14.8 nmol/l (95% CI -0.4, 29.9) in women, P = 0.05 (P = 0.82 for birthweight x gender interaction). In a combined analysis of men and women adjusted for gender (n = 302), a 1 lb decrease in birthweight was associated with a 13.4 nmol/l (95% CI 4.5, 22.4) greater incremental rise in plasma cortisol, P = 0.003. CONCLUSIONS: Associations between lower birthweight and increased HPA axis activity are similar in men and women, supporting the hypothesis that HPA axis activation is an important mechanism underlying programming of adult disease.