Functionally different pads on the same foot allow control of attachment: stick insects have load-sensitive "heel" pads for friction and shear-sensitive "toe" pads for adhesion.

Stick insects (Carausius morosus) have two distinct types of attachment pad per leg, tarsal "heel" pads (euplantulae) and a pre-tarsal "toe" pad (arolium). Here we show that these two pad types are specialised for fundamentally different functions. When standing upright, stick insects rested on their proximal euplantulae, while arolia were the only pads in surface contact when hanging upside down. Single-pad force measurements showed that the adhesion of euplantulae was extremely small, but friction forces strongly increased with normal load and coefficients of friction were [Formula: see text] 1. The pre-tarsal arolium, in contrast, generated adhesion that strongly increased with pulling forces, allowing adhesion to be activated and deactivated by shear forces, which can be produced actively, or passively as a result of the insects' sprawled posture. The shear-sensitivity of the arolium was present even when corrected for contact area, and was independent of normal preloads covering nearly an order of magnitude. Attachment of both heel and toe pads is thus activated partly by the forces that arise passively in the situations in which they are used by the insects, ensuring safe attachment. Our results suggest that stick insect euplantulae are specialised "friction pads" that produce traction when pressed against the substrate, while arolia are "true" adhesive pads that stick to the substrate when activated by pulling forces.

Discrimination of Type 2 diabetic patients from healthy controls by using metabonomics method based on their serum fatty acid profiles

Metabonomics, the study of metabolites and their roles in various disease states, is a novel methodology arising from the post-genomics era. This methodology has been applied in many fields, including work in cardiovascular research and drug toxicology. In this study, metabonomics method was employed to the diagnosis of Type 2 diabetes mellitus (DM2) based on serum lipid metabolites. The results suggested that serum fatty acid profiles determined by capillary gas chromatography combined with pattern recognition analysis of the data might provide an effective approach to the discrimination of Type 2 diabetic patients from healthy controls. And the applications of pattern recognition methods have improved the sensitivity and specificity greatly. (C) 2004 Elsevier B.V. All rights reserved.

Study of urinary 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in diabetic nephropathy patients

Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Urinary 8-hydroxydeoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. This article studied oxidative DNA damage in patients with diabetic nephropathy and in healthy control subjects by urinary 8-OHdG evaluations. Contents of 8-OHdG in urine were analyzed by capillary electrophoresis with end-column amperometric detection (CE-AD) after a single-step solid-phase extraction (SPE). Levels of urinary 8-OHdG in diabetic nephropathy patients with macroalbuminuria was significant higher than in control subjects (5.72 +/- 6.89 mumol/mol creatinine versus 2.33 +/- 2.83 mumol/mol creatinine, P = 0.018). A significant difference of 24 h urinary 8-OHdG excretions exists between the patients with macroalbuminuria and the patients with nonnoalbuminuria (19.2 +/- 16.8 mug/24 h versus 8.1 +/- 1.7 mug/24 h, P = 0.015). There was a positive correlation between urinary excretion of 8-OHdG and glycosylated hemoglobin (HbA(1)c) (r = 0.287, P = 0.022). A weak correlation exists between the levels of 8-OHdG and triglyceride (r = 0.230, P = 0.074). However, the urinary 8-OHdG contents are not correlated with blood pressure and total cholesterol. The increased excretion of urinary 8-OHdG is seen as indicating an increased systemic level of oxidative DNA damage in diabetic nephropathy patients. (C) 2004 Elsevier B.V. All rights reserved.

Inhibition of bromophenols against PTP1B and anti-hyperglycemic effect of Rhodomela confervoides extract in diabetic rats

Protein tyrosine phosphatase 1B (PTP1B) plays an important role as a negative regulator in insulin signaling pathways. PTP1B is an effective target for the treatment of type 2 diabetes mellitus. Four bromophenol derivatives from red algae Rhodomela confervoides, 2,2',3,3'-tetrabromo-4,4',5,5'-tetra-hydroxydiphenyl methane (1), 3-bormo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl) pyrocatechol (2), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (3) and 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxy-methyldiphenylmethane (4) showed significant inhibitory activity against PTP1B (IC50 were 2.4, 1.7, 1.5 and 0.84 mu mol/L, respectively) as potential therapeutical agents for the treatment of type 2 diabetes mellitus. The anti-hyperglycemic effects of the ethanol extracts from R. confervoides on streptozotocin-induced diabetes (STZ-diabetes) in male Wistar rats fed with high fat diet were investigated. The STZ-diabetic rats treated with medium-dose and high-dose alga extracts showed remarkable reductions in fasting blood glucose (FBG) as compared with the STZ-diabetic control. The results indicate that the in vivo anti-hyperglycemic activity of the R. confervoides extracts can be partially attributed to the inhibitory actions against PTP1B of the bromophenol derivatives and that may be of clinical importance in improving the management of type 2 diabetes mellitus.

Do diabetic veterans use the Internet? Self-reported usage, skills, and interest in using My HealtheVet Web portal.

OBJECTIVE: The Veterans Health Administration has developed My HealtheVet (MHV), a Web-based portal that links veterans to their care in the veteran affairs (VA) system. The objective of this study was to measure diabetic veterans' access to and use of the Internet, and their interest in using MHV to help manage their diabetes. MATERIALS AND METHODS: Cross-sectional mailed survey of 201 patients with type 2 diabetes and hemoglobin A(1c) > 8.0% receiving primary care at any of five primary care clinic sites affiliated with a VA tertiary care facility. Main measures included Internet usage, access, and attitudes; computer skills; interest in using the Internet; awareness of and attitudes toward MHV; demographics; and socioeconomic status. RESULTS: A majority of respondents reported having access to the Internet at home. Nearly half of all respondents had searched online for information about diabetes, including some who did not have home Internet access. More than a third obtained "some" or "a lot" of their health-related information online. Forty-one percent reported being "very interested" in using MHV to help track their home blood glucose readings, a third of whom did not have home Internet access. Factors associated with being "very interested" were as follows: having access to the Internet at home (p < 0.001), "a lot/some" trust in the Internet as a source of health information (p = 0.002), lower age (p = 0.03), and some college (p = 0.04). Neither race (p = 0.44) nor income (p = 0.25) was significantly associated with interest in MHV. CONCLUSIONS: This study found that a diverse sample of older VA patients with sub-optimally controlled diabetes had a level of familiarity with and access to the Internet comparable to an age-matched national sample. In addition, there was a high degree of interest in using the Internet to help manage their diabetes.

Bioburden after Staphylococcus aureus inoculation in type 1 diabetic rats undergoing internal fixation.

SUMMARY: Fracture stabilization in the diabetic patient is associated with higher complication rates, particularly infection and impaired wound healing, which can lead to major tissue damage, osteomyelitis, and higher amputation rates. With an increasing prevalence of diabetes and an aging population, the risks of infection of internal fixation devices are expected to grow. Although numerous retrospective clinical studies have identified a relationship between diabetes and infection, currently there are few animal models that have been used to investigate postoperative surgical-site infections associated with internal fixator implantation and diabetes. The authors therefore refined the protocol for inducing hyperglycemia and compared the bacterial burden in controls to pharmacologically induced type 1 diabetic rats after undergoing internal fracture plate fixation and Staphylococcus aureus surgical-site inoculation. Using an initial series of streptozotocin doses, followed by optional additional doses to reach a target blood glucose range of 300 to 600 mg/dl, the authors reliably induced diabetes in 100 percent of the rats (n = 16), in which a narrow hyperglycemic range was maintained 14 days after onset of diabetes (mean ± SEM, 466 ± 16 mg/dl; coefficient of variation, 0.15). With respect to their primary endpoint, the authors quantified a significantly higher infectious burden in inoculated diabetic animals (median, 3.2 × 10 colony-forming units/mg dry tissue) compared with inoculated nondiabetic animals (7.2 × 10 colony-forming units/mg dry tissue). These data support the authors' hypothesis that uncontrolled diabetes adversely affects the immune system's ability to clear Staphylococcus aureus associated with internal hardware.

The Application of an Exogenous Linear and Radial Electrical Field to an In Vitro Chronic Diabetic Ulcer Model for Evaluation as a Potential Treatment

Chronic diabetic ulcers affect approximately 15% of patients with diabetes worldwide. Currently, applied electric fields are being investigated as a reliable and cost-effective treatment. This in vitro study aimed to determine the effects of a constant and spatially variable electric field on three factors: endothelial cell migration, proliferation, and angiogenic gene expression. Results for a constant electric field of 0.01 V demonstrated that migration at short time points increased 20-fold and proliferation at long time points increased by a factor of 1.40. Results for a spatially variable electric field did not increase directional migration, but increased proliferation by a factor of 1.39 and by a factor of 1.55 after application of 1.00 V and 0.01 V, respectively. Both constant and spatially variable applied fields increased angiogenic gene expression. Future research that explores a narrower range of intensity levels may more clearly identify the optimal design specifications of a spatially variable electric field.

Examining the effect of exit separation on aircraft evacuation performance using evacuation modelling techniques: "Is the 60 foot rule relevant?"

This paper examines the influence of exit separation, exit availability and seating configuration on aircraft evacuation efficiency and evacuation time. The purpose of this analysis is to explore how these parameters influence the 60 foot exit separation requirement found in aircraft certification rules. The analysis makes use of the airEXODUS evacuation model and is based on a typical wide-body aircraft cabin section involving two pairs of Type-A exits located at either end of the section with a maximum permissible loading of 220 passengers located between the exits. The analysis reveals that there is a complex relationship between exit separation and evacuation efficiency. Indeed, other factors such as exit flow rate and exit availability are shown to exert a strong influence on critical exit separations. A main finding of this work is that for the cabin section examined under certification conditions, exit separations up to 170 feet will result in approximately constant total evacuation times and average personal evacuation times. This practical exit separation threshold is decreased to 114 feet if another combination of exits is selected. While other factors must also be considered when determining maximum allowable exit separations, these results suggest it is not possible to mandate a maximum exit separation without taking into consideration exit type, exit availability and aircraft configuration. This has implications when determining maximum allowable exit separations for wide and narrow body aircraft. It is also relevant when considering the maximum allowable separation between different exit types on a given aircraft configuration.

Effects of the novel (Pro(3))GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin

AIMS/HYPOTHESIS: This study examined the biological effects of the GIP receptor antagonist, (Pro3)GIP and the GLP-1 receptor antagonist, exendin(9-39)amide.

METHODS: Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic ( ob/ ob) mice.

RESULTS: In GIP receptor-transfected fibroblasts, (Pro(3))GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5% and 73.5+/-3.2% at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7% at 10(-6) mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86%; p<0.001) from clonal BRIN-BD11 cells, but had no effect on GLP-1-stimulated insulin release. In contrast, exendin(9-39)amide inhibited both GIP and GLP-1-stimulated insulin release (57% and 44%, respectively; p<0.001). Administration of (Pro(3))GIP, exendin(9-39)amide or a combination of both peptides (25 nmol/kg body weight, i.p.) to fasted (ob/ob) mice decreased the plasma insulin responses by 42%, 54% and 49%, respectively (p<0.01 to p<0.001). The hyperinsulinaemia of non-fasted (ob/ob) mice was decreased by 19%, 27% and 18% (p<0.05 to p<0.01) by injection of (Pro3)GIP, exendin(9-39)amide or combined peptides but accompanying changes of plasma glucose were small.

CONCLUSIONS/INTERPRETATION: These data show that (Pro(3))GIP is a specific GIP receptor antagonist. Furthermore, feeding studies in one commonly used animal model of obesity and diabetes, (ob/ob) mice, suggest that GIP is the major physiological component of the enteroinsular axis, contributing approximately 80% to incretin-induced insulin release.

Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug

AIMS/HYPOTHESIS: To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. METHODS: Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. RESULTS: Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p<or =0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p<or =0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal capillary basement membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p<or =0.0001). CONCLUSION/INTERPRETATION: This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.