Changes in windlass effect in response to different shoe and insole designs during walking.

Windlass effect occurs during the pre-swing phase of gait cycle in which the peak tensile strain and force of the plantar aponeurosis (PA) is reached. The increased dorsiflexion angle of the 1st metatarsophalangeal (MTP) joint is the main causing factor. The aim of this study was to investigate thoroughly in finding the appropriate shoe and insole combination that can effectively decrease the windlass effect. Foot kinematic analyses of 10 normal volunteers (aged 25.2±2.1 years, height of 167.4±9.1 cm, and weight of 66.2±18.1 kg) were performed during gait under the conditions of barefoot, standard shoe (SS) with flat insole (FI) or carbon fiber insole (CFI), and rocker sole shoe (RSS) with FI or CFI. The shoe cover consisting of transparent polymer was used for accurate measurement of kinematic data as specific areas on the cover can be cut away for direct placement of reflective markers onto the skin. Under barefoot condition, the mean of maximum dorsiflexion angle of the 1st MTP joint was measured to be 48.0±7.3°, and decreased significantly to 28.2±5.7° when wearing SS with FI, and 24.1±5.7° when wearing SS with CFI. This angle was further decreased to around 13° when wearing RSS with FI or CFI. Subjects wearing footwear alone can increase the minimum medial longitudinal angle and decrease the maximum plantarflexion angle of metatarsus related to the calcaneus as compared with barefoot condition, resulting in flatter medial foot arch. Results suggested that RSS is the effective footwear in reducing the windlass effect regardless the type of insole inserted. The findings in this study provided us with the evidences in finding the appropriate footwear for treating foot disorders such as plantar fasciitis by effectively reducing the windlass effect.

Mediation of vagal cardioinhibitory responses by glutamatergic receptors in the caudal medulla of turtles.

Our previous studies showed that electrical stimulation of the nuclei ambiguous (NA) or dorsomotor nuclei of the vagus (DMV) complex in the brain stem of spontaneously breathing pond turtles (Cyclemys fiavomarginata), anesthetized with chloralose (4 mg/100 g) and urethane (40 mg/100 g), produced a marked slowing or even cessation of the heart rate, and resulted in an immediate fall of blood pressure. Results of the present study further demonstrated that the cardioinhibitory responses could also be elicited by microinjection of monosodium glutamate (0.2-20 nl, 50 mM) into the NA/DMV complex in turtles. A two-barrel glass micropipette held in a manipulator was connected to a pneumatic pressure pump for microinjection. The glutamate-induced cardioinhibitory responses could be significantly reduced in a dose-dependent manner by pretreatment with AP-5 (a NMDA receptor antagonist, at 1-8 nmole) or CNQX (a non-NMDA receptor antagonist; at 0.1-0.8 nmole) 20 min before glutamate administration. Histochemical verification by injecting horseradish peroxidase into the cervical vagus nerves revealed that retrogradely labeled glutamatergic neurons in the NA/DMV complex were observed. These results suggest that glutamatergic receptors in the caudal medulla may mediate vagal cardioinhibitory responses in the turtle.

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke.

AIM: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. METHODS: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 °C for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 °C) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. RESULTS: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 levels during heatstroke. CONCLUSION: Our results suggest that systemic delivery of kynurenic acid may attenuate multiorgan dysfunction in rats after heatstroke.

Type 2 diabetes but not metabolic syndrome is associated with an increased risk of lower urinary tract symptoms and erectile dysfunction in men aged <45 years.

OBJECTIVE: To investigate the association of type 2 diabetes mellitus (T2DM) and metabolic syndrome with lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in Taiwanese men aged <45 years. PATIENTS, SUBJECTS AND METHODS: Voiding and erectile function in 226 men with T2DM, at one diabetes clinic, and 183 healthy men with normal fasting blood glucose levels, were compared. Participants were evaluated using the International Prostate Symptom Score (IPSS), the five-item version of the International Index of Erectile Function questionnaire (IIEF-5), and measurements of flow rate and postvoid residual urine volume. The association of metabolic syndrome with LUTS and ED was also evaluated. RESULTS: The mean (sd, range) age of the patients was 38.9 (6.1, 20-45) years and the mean duration of diabetes was 2.8 (3.1, 0.5-20) years. Compared with controls, men with T2DM had a significantly mean (sd) higher IPSS, of 6.1 (5.8) vs 4.1 (4.6) (P < 0.001), an increased of odds ratio (95% confidence interval) of having moderate to severe LUTS of 1.78 (1.12-2.84) (P = 0.01), greater voiding volume of 376 (177) vs 326 (102) mL (P = 0.04), a worse IIEF-5 score of 17.3 (6.4) vs 20.0 (3.8) (P < 0.001), an increased of odds ratio of having moderate to severe ED of 3.5 (2.1-5.8) (P < 0.001) but a similar maximum flow rate and postvoid residual. The IIEF-5 score was negatively correlated with the IPSS (P < 0.0001, coefficient = -0.23, 0.35-0.11) and glycosylated haemoglobin (P = 0.02, coefficient = -0.14, 0.26-0.01). In all, 156 (69%) patients met the criteria for metabolic syndrome. The mean age, duration of diabetes, glycosylated haemoglobin, IPSS, voided volume, maximum urinary flow rate and IIEF-5 score were similar between patients with and without metabolic syndrome. CONCLUSIONS: Men with T2DM and aged <45 years had more LUTS but a similar bladder emptying function than the controls. ED was highly prevalent and was associated with the severity of LUTS. Metabolic syndrome did not aggravate the severity of LUTS, emptying function or ED in the early stage of DM.

Diabetes-induced alternations in biomechanical properties of urinary bladder wall in rats.

OBJECTIVES: To determine whether diabetes mellitus and the associated changes in bladder function will trigger bladder wall tissue remodeling and concomitant alterations in the mechanical properties. We investigated the time course of changes in function and mechanical properties of diabetic and diuretic rat bladders using both in vivo and in vitro techniques METHODS: Cystometry was performed at 2, 4, and 8 weeks on female Sprague-Dawley rats that had received either a single injection of streptozotocin (65 mg/kg intraperitoneally) or 5% sucrose in drinking water for the duration of the experiments. At each point, the biaxial mechanical properties of 10 x 10-mm tissue specimens obtained from the posterior part of bladder wall were quantified. The changes in overall tissue compliance and mechanical anisotropy as a function of time were examined RESULTS: Both diabetic and diuretic conditions led to increases in bladder weight, bladder capacity, and in vivo compliance compared with the controls at all points tested. Under biaxial loading, all bladder wall tissues exhibited a nonlinear stress-strain relationship and mechanical anisotropy, with greater tissue compliance in the circumferential direction than in the longitudinal direction. Although the compliance of the bladder wall increased progressively and synchronously in both diabetic and diuretic bladders for < or = 4 weeks, only the diabetic bladders continued to increase the compliance for < or = 8 weeks (diabetic 0.64 +/- 0.04 vs diuretic 0.48 +/- 0.05, P = .03) CONCLUSIONS: The results of our study have shown that diuresis mainly contributes to the "early" changes of mechanical properties of the bladder, with diabetes inducing additional "late" changes of mechanical properties of the rat bladders after 4 weeks.

Modified transurethral incision of the bladder neck treating primary bladder neck obstruction in young men: a method to improve voiding function and to preserve antegrade ejaculation.

OBJECTIVES: To evaluate the voiding function, ejaculation status and sexual function after the novel modification of transurethral incision of the bladder neck (TIBN) treating young men with primary bladder neck obstruction (PBNO). METHODS: Using a videourodynamic study, PBNO was diagnosed in 33 young men 27-50 years of age who presented with chronic lower urinary tract symptoms and low urinary flow. TIBN was performed in all patients, with the modification of preserving a portion of the supramontanal tissue during the procedure. International Prostate Symptom Score (I-PSS), quality of life, uroflowmetry, postvoid residual urine, the status of ejaculation and sexual function using the 5-item version of the International Index of Erectile Function (IIEF-5) were assessed before, 3 and 24 months after treatment. RESULTS: Follow-up data were available in 32 (97%) and 26 (79%) patients at 3 and 24 months postoperatively, respectively. During the 2-year follow-up, mean I-PSS decreased from 20.7 to 5.9 (p < 0.01). Mean quality of life decreased from 4.2 to 2.3 (p < 0.01). Mean maximum flow increased from 10.7 to 19.2 ml/s (p < 0.01). Mean postvoiding residual urine decreased from 107 to 48 ml (p < 0.01). All patients had antegrade ejaculation postoperatively. Mean IIEF scores did not change significantly (22.6 +/- 2.6 vs. 20.7 +/- 4.3, p = 0.08). Successful overall outcome was achieved in 22 (84.6%) of 26 patients. CONCLUSIONS: Applying this modified TIBN to treat the sexually active young men with PBNO had the advantage of improving voiding function and preserving both antegrade ejaculation and sexual function.

Characterizing poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCP) copolymer micelles for doxorubicin (DOX) delivery: effects of crosslinked of amine groups.

New amine-groups containing tri-block copolymers and micelles that consisting of poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCL-b-COS-b-PEG, PCP), were synthesized, characterized, and evaluated for delivering doxorubicin (DOX) with or without crosslinked amine groups by genipin. The characteristics of the PCP copolymers of Fourier-transform infrared spectrometry (FT-IR) verify the amine and ester groups of the COS and the PCL of the copolymers, respectively. 1H nuclear magnetic resonance (1H NMR) spectra verify the structures of the PCP copolymers consisting two PCL and PEG polymers reacted onto the COS block. In addition, gel permeation chromatography (GPC) determines the number average molecular weight of the tri-block copolymers (Mn) of approximately 11340 Da/mole. The PCP copolymers can self-assemble to form polymeric micelles at the critical micelle concentration (CMC) of 1.0 microM as determined by the UV-VIS absorption spectra. The mean diameter of the PCP micelles is 90 nm, as determined using a dynamic light-scattering (DLS) analyzer. Moreover, the zeta potentials of PCP micelles change from neutral to cationic state when pH of suspension mediums varied from 7.4 to 3.0. For evaluating delivery characteristics of hydrophobic DOX, it was loaded into PCP micelles with or without crosslinked by genipin. The burst release and release period of DOX for the crosslinked micelles are significantly reduced (P < 0.003, n = 3, for pH = 7.4) and sustained (e.g., 8 days), respectively, than those non-crosslinked ones (e.g., 4 days). In conclusion, new tri-block amine groups containing PCP copolymers are synthesized that can self-assemble as PCP micelles. After post-crosslinked amine groups of DOX loaded the micelles, they can effectively reduce the burst release and sustain the release of DOX at different pH dissolution mediums. Further applications of PCP copolymers and micelles for drug delivery can be explored in future.

Preliminary investigations on a new disposable potentiometric biosensor for uric acid.

In this paper, uricase, catalase, and electron mediator were coimmobilized on the surface of the tin oxide (SnO2)/indium tin oxide (ITO) glass, to develop a disposable potentiometric uric acid biosensor. The SnO2/ITO glass was employed as a pH sensor, fabricated by sputtering SnO2 thin films on the ITO glass. 3-Glycidyloxypropyltrimethoxysilane (GPTS) was utilized to immobilize uricase, catalase and the electron mediator (ferrocenecarboxylic acid, FcA) on the sensing window. The experimental results reveal that the optimal weight ratio of uricase, FcA to catalase (CAT) is 4:1:2. The sensor responds linearly between 2 mg/dl and 7 mg/dl at pH 7.5, in 20 mM of test solution, with a correlation coefficient of 0.99213. Accordingly, no significant interference was observed when interfering substances, glucose, urea and ascorbic acid, were added to the uric acid solution. Moreover, the recorded voltage was relatively constant during the first 28 days of measurement. Consequently, a potentiometric uric acid biosensor was realized with the advantages of low cost and simple fabrication.

Different ratios of lactide and glycolide in PLGA affect the surface property and protein delivery characteristics of the PLGA microspheres with hydrophobic additives.

This study investigated whether the surface quantities of the additives and protein delivery characteristics for protein-loaded PLGA 85 (85:15), PLGA75 (75:25) and PLGA 50 (50:50) microspheres with hydrophobic additives, phosphatidylcholine (PC) as a model, are affected by the different ratios of lactide and glycolide in PLGA polymers. By applying phospholipids analysis, surface PC quantities of the microspheres are 2.1 +/- 1.2, 1.2 +/- 0.3 and 1.0 +/- 0.7 Pg (n = 3) per mg of PLGA 85, PLGA 75 and PLGA 50 microspheres with PC addition, respectively, that are affected by the ratio of lactide and glycolide in PLGA. The addition of PC causes the decreased encapsulation efficiency (E.E.) of albumin of the microspheres and the decreased percentages of E.E. are negative correspondent to ratio of lactide and glycolide in PLGA (e.g. -13.5, -20.2 and -24.5% for PLGA 85, PLGA 75 and PLGA 50, respectively) compared with those without addition. The cumulative releases of albumin were influenced by the ratio of lactide and glycolide in PLGA for both PC addition and non-addition microspheres. Moreover, the additions of PC reduce the initial burst and cumulative releases of albumin of the microspheres compared with those of non-added ones. Further investigation suggests that resistant water uptake of PC added microspheres may play a role on affecting those reduced protein release behaviours. In conclusion, the different ratios of lactide and glycolide in PLGA affect the surface quantities of PC, E.E. and cumulative release profiles of albumin for the PLGA microspheres with PC addition. The results of the study may help the better practical applications for protein delivery of the microspheres with hydrophobic additives.

Videourodynamics identifies the causes of young men with lower urinary tract symptoms and low uroflow.

OBJECTIVES: Using videourodynamics (VUDS) we prospectively investigated the etiologies of lower urinary tract symptoms (LUTS) and low uroflow in young men and correlated the results with clinical symptoms and noninvasive exams. METHODS: From 1999 to 2001, 90 men 18-50 years old with LUTS and low uroflow were enrolled. Patients with active urinary tract infection, congenital urogenital diseases, neurological diseases, diabetes mellitus or urinary tract malignancy were excluded. Evaluation included International Prostate Symptom Score (I-PSS), renosonography, transrectal ultrasonography of prostate and VUDS. The clinical parameters were compared in the different diagnostic groups of patients classified by VUDS. RESULTS: Mean patient age was 37.5+/-7.8 years and mean symptom duration was 28.3+/-21.3 months. Mean total I-PSS was 19.8, voiding 11.1 and storage 8.7. VUDS showed dysfunctional voiding in 39 (43%), primary bladder neck obstruction in 37 (41%), impaired detrusor contractility in 9 (10%) and benign prostatic obstruction in 5 (6%). Patients with impaired detrusor contractility had higher symptoms scores and poorer quality of life than those in the other diagnostic groups. Mean age and size of prostate in patients with benign prostatic obstruction were greater than those in the remaining groups. The remaining clinical symptoms or noninvasive tests could not predict a specific urodynamic diagnosis. CONCLUSIONS: VUDS is recommended to make an accurate diagnosis in young men with LUTS and low uroflow because few clinical symptoms or noninvasive tests were helpful in this regard.

Shear stress-induced aggregation of oxidized platelets.

Although shear stress-induced platelet aggregation (SIPA) has been noted, the shear stress-induced aggregation of oxidized platelets (SIOPA) has not been investigated. To investigate SIOPA, small quantity of hemoglobin (Hb) solution was first added to plasma to induce oxidation stress of platelets and then the plasma was sheared by a cone/plate viscometer at shear stress of 66 dyn/cm2. In addition, to investigate the change in expression of the membrane receptors of glycoprotein Ib (GpIb) for oxidized platelets, mean fluorescence intensity (MFI) for those platelets was detected by flow cytometric technique. The results showed that the level of the oxidation stress of platelets, as presented in malondialdehyde (MDA) values, was well correlated with the quantities of added Hb. Moreover, the aggregation of SIOPA corresponded with the levels of oxidation stress of platelets. Platelets pretreated with aspirin could only partially reduce the aggregation of SIOPA. Similarly, aspirin pretreatment could partially reduce the lowering of MFI value that indicated downexpression of GpIb receptors. Furthermore, the aggregations of SIOPA corresponded with the lowered percentage of those MFI values for studied cases. We thereby suggested that the aggregation of SIOPA is related to both the level of oxidation stress and the downexpression of GpIb receptors for oxidized platelets.