Finite Element Analysis of Male Urethral Sphincter Loss Synergy / 医用生物力学

Objective To investigate the influence of internal and external sphincter loss synergy on stress distributions and urine flow rates of lower urinary tract organs and tissues. Methods Based on collodion slice, the geometric model of the lower urinary tract was reconstructed, and finite element model of the lower urinary tract with muscle active force was established. Through fluid structure coupling simulation, the changes of tissue stress and urine flow rate were simulated under four conditions: normal contraction of internal and external sphincter, total loss of muscle active force and single loss of muscle active force for internal and external sphincters at the end of urination. Results The urethral stress changes in normal contraction of internal and external sphincter muscles were the same as the clinically measured urethral pressure changes. Compared with normal contraction, when the internal sphincter lost its muscle active force alone, stress of the internal sphincter and the urethra of the prostate was reduced by 33.6% and 13.8%, and flow rate of urine in this position was also reduced. When the external sphincter lost its muscle active force alone, the urethral stress of the external sphincter and external urethra was reduced by 59.5% and 24.03%, respectively. When the internal and external sphincter lost muscle active force, stress of the internal sphincter, the prostate, the external sphincter and the external urethra were reduced by 38.77%, 18.6%, 63.58%, 29.74%, respectively, and flow velocity in the corresponding position was also reduced. Conclusions Internal and external sphincter loss synergy resulted in the difference of tissue stress and urine flow rate. The results can provide the theoretical basis for surgical treatment of urinary incontinence caused by sphincter.

A Continuum Constitutive Model of skeletal Muscle at Variable Strain Rate / 医用生物力学

Objective Aiming at the problem that mechanical properties for the continuum of muscle tissues cannot be considered in active and passive behaviors of different structurally coupled muscles, a method of passive and active coupling in the same constitutive equation was proposed to construct ahyperelastic active and passive constitutive model of skeletal muscle continuum. Methods In order to calibrate parameters of the passive constitutive model, the uniaxial tensile experiment method and conditions were given, and through theoretical derivation, the specific method of using experimental data to solve the passive model parameters was introduced. In order to verify effectiveness of the active model, the model was verified with an example. Results The curves predicted by the model were in good agreement with the experimental output stress-stretch ratio curves. At the same strain, the maximum error of passive stress and total stress were only 20 kPa and 40 kPa. Conclusions The continuum hyperelastic constitutive model can better simulate active and passive behavior of skeletal muscles, which is beneficial for modeling and simulation of human muscles in further study.

Application of benchmark dose (BMD) in estimating biological exposure limit (BEL) to cadmium / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To estimate the biological exposure limit (BEL) using benchmark dose (BMD) based on two sets of data from occupational epidemiology.</p><p><b>METHODS</b>Cadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium (UCd) was used as an exposure biomarker and urinary beta2-microgloburin (B2M), N-acetyl-13-D-glucosaminidase (NAG) and albumin (ALB) as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S.A) was used to calculate BMD.</p><p><b>RESULTS</b>The cut-off point (abnormal values) was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers (urinary B2M, NAG; and ALB) and exposure biomarker (UCd). BEL value was 5 microg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 microg/g creatinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected.</p><p><b>CONCLUSION</b>BMD can be used in estimating the biological exposure limit (BEL). UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.</p>

Capacitative Ca²⁺ entry is involved in ACh-induced distal colon smooth muscle contraction in rats / 生理学报

Contraction of smooth muscle cells is triggered by an increase in cytosolic Ca(2+) upon agonist stimulation. Ca(2+) influx across the plasma membrane constitutes a major component of the agonist-induced response in smooth muscle cells. Traditionally, voltage-operated Ca(2+) channel (VOCC) is considered as the channel mediating the Ca(2+) entry. However, this view has been challenged by recent discoveries, which demonstrated that other types of ion channels, such as store-operated and/or receptor-operated Ca(2+) channels (SOCC and/or ROCC), also participate in Ca(2+) response induced by agonists in smooth muscle cells. SOCC is defined as the channel activated in response to the depletion of the internal Ca(2+) stores, an event secondary to G protein coupled receptor or receptor tyrosine kinase stimulation. The Ca(2+) flow mediated by SOCC is termed as capacitative Ca(2+) entry (CCE). Previous study from other group has demonstrated that VOCC played a predominant role in ACh-induced contraction of distal colon smooth muscle in guinea pig. However, whether SOCC participates in the agonist-induced contractile response in this particular tissue is unknown. The present study was performed to investigate the role of CCE in ACh-induced mechanical activity of distal colon smooth muscle in rats. The contractile function of the smooth muscle was assessed by measuring isometric force of isolated rat distal colon rings. We showed that both high extracellular K(+) (40 mmol/L) and ACh (5 mumol/L) evoked striking contraction of the smooth muscle. The contractile responses were almost abolished by removal of extracellular Ca(2+) with ethylene glycol-bis(2-aminoethylether)-N,N,N',N' tetraacetic acid (EGTA), suggesting a critical contribution of extracellular source of Ca(2+) to the contraction. Verapamil (5 mumol/L), an L-type VOCC blocker, significantly attenuated, but didn't completely eliminate the high K(+)- and ACh-induced contraction (74% and 41% for high K(+) and ACh, respectively), indicating that additional channels might be involved in the contractile mechanism. Furthermore, ACh only induced transient contractions in the absence of extracellular Ca(2+). Readmission of Ca(2+) into the extracellular compartment resulted in a significant and sustained increase in the tension of the smooth muscle. This response was not affected by verapamil (5 mumol/L) and Cd(2+) (5 mumol/L), both of which efficiently block VOCC at the doses. However, La(3+), a known inhibitor of SOCC, significantly suppressed the Ca(2+) readdition-induced contraction in a dose-dependent manner. On the basis of these results, we conclude that contraction of smooth muscle in the distal colon is regulated by multiple Ca(2+) channels. In addition to VOCC-mediated Ca(2+) influx, SOCC-mediated CCE participates in agonist-induced contractile response of distal colon smooth muscle in rats.

Application of benchmark dose (BMD) in a bone-effect study on a general population environmentally exposed to cadmium / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To estimate the benchmark dose for osteoporosis caused by cadmium exposure in a Chinese general population with an epidemiological study.</p><p><b>METHODS</b>The inhabitants living in both cadmium polluted and non-polluted areas served as the exposure group and the control group. Urinary cadmium (UCd) and Blood cadmium (BCd) were used as exposure biomarkers while the Z score was used as effect biomarker for the osteoporosis.</p><p><b>RESULTS</b>The UCd and BCd in the habitants of the polluted areas were significantly higher than those in the habitants of the control area on average (P < 0.05) and the UCd and BCd in the habitants of the highly polluted areas were significantly higher than those in the habitants of the moderately polluted area on average (P < 0.05). The bone mineral density was significantly decreased in the groups of the highest UCd and BCd level compared with the 5 microg/g Cr group with the significant difference (P < 0.05). The morbidity of the osteoporosis would increase significantly with the increase of the cadmium exposure (P < 0.05) with the linear correlation (P < 0.05). BMDs were calculated using BMDS Version l.3.2 software and BMDLs were also determined. The BMDL of UCd for cadmium-induced osteoporosis was higher than those representing cadmium-induced renal dysfunction.</p><p><b>CONCLUSION</b>High level of cadmium exposure can induce osteoporosis, which occurs later than renal damage related to cadmium exposure. The BMD is a practical method.</p>

Application of Benchmark dose (BMD) in estimating biological exposure limit (BEL) / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>Based on two sets of data from occupational epidemiology, Benchmark dose (BMD) was applied to estimate biological exposure limit (BEL).</p><p><b>METHODS</b>Cadmium exposed workers were selected from a cadmium smelting and a zinc products factory and control group was selected from doctors or nurses and staff from shops living in the same area; Urinary cadmium (UCd) was used as exposure biomarker and urinary beta(2) microglobulin (UBM), NAG (UNAG) and albumin (UALB) were as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S) was used to calculate BMD.</p><p><b>RESULTS</b>Calculated abnormal prevalence was based on the upper limit of 95% of effect biomarkers in control group; There are significant dose response relationship between the prevalence of effect biomarkers (UBM, UNAG and UALB) and exposure biomarker (UCd); BEL was 5 microg/g creatinine for UBM as effect biomarker, It consists with the recommendation of WHO; BEL was 3 microg/g creatinine for UNAG as effect biomarker; BEL can be estimated by using the method of BMD; the more sensitive biomarker would used, the more occupational people would protected.</p><p><b>CONCLUSION</b>The application of BMD in estimating biological exposure limit (BEL) is proper. UNAG is suggested as most sensitive biomarker to be used to estimate BEL for cadmium exposure.</p>

Store-operated Ca2+ channels in rat colonic smooth muscle cells / 中国应用生理学杂志

<p><b>AIM</b>To study whether store-operated Ca2+ channel (SOC) is present in rat colonic smooth muscle cells.</p><p><b>METHODS</b>Intracellular Ca2+ ([Ca2+]i) changes induced by thapsigargin- or caffeine-activated SOC channel were measured in enzymatically dissociated rat colonic smooth muscle cells with the fluorescent indicator Fura-2/AM.</p><p><b>RESULTS</b>In the absence of external Ca2+ , the sarco-endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (1 micromol/L) and ryanodine receptor (RyR) activator caffeine both transiently elevated [Ca2+]i from (68.32 +/- 3.43) nmol/L to (240.85 +/- 12.65 ) nmol/L, (481.25 +/- 34.77) nmol/L. A subsequent reintroduction of Ca2+ into the extracellular solution resulted in [Ca2+]i further elevated to (457.55 +/- 19.80) nmol/L, (1005.93 +/- 54.62) nmol/L; (643.88 +/- 34.65) nmol/L, (920.16 +/- 43.25) nmol/L, respectively. And the elevated response was blocked by lanthanum (1 mmol/L), but was insensitive to L-type voltage calcium channels blocker verapamil and membrane depolarization.</p><p><b>CONCLUSION</b>SOC activated by store depletion are present in rat colonic smooth muscle cells. And we further prove the existence of such Ca2+ channels in excitable cells.</p>

Bombesin-mediated non-cholinergic late slow excitatory postsynaptic potentials in guinea pig inferior mesenteric ganglion in vitro / 生理学报

The effect of bombesin (BOM) on non-cholinergic excitatory synaptic transmission of the guinea pig inferior mesenteric ganglion (IMG) was investigated by intracellular recording. Repetitive stimulation of the colon nerves (1 ms, 25 Hz, 4 s) elicited a burst of action potentials, which was followed by a long-lasting depolarization in 74.3% (52/70) of the IMG neurons. The depolarization was not blocked by nicotinic (d-tubocurarine, 100 micromol/L) and muscarinic (atropine, 1 micromol/L) antagonists, but was eliminated in a low Ca(2+)/high Mg(2+) Krebs solution, indicating that the depolarization was due to the release of non-cholinergic transmitters. Superfusing the ganglia with BOM (10 micromol/L, 1 min) induced a slow depolarization in 66.5% (109/164) neurons tested. The BOM response was not appreciably changed in low Ca(2+)/high Mg(2+) Krebs solution (n=6, P>0.05), suggesting that BOM depolarized the neurons by acting directly on the postsynaptic membrane rather than via a release of other endogenous depolarizing substances. In a total of 102 cells that exhibited late slow excitatory postsynaptic potential (ls-EPSP), superfusion of the ganglia with BOM produced a membrane depolarization in 82 neurons (80%), while the remaining 20 cells (20%) exhibited no response to BOM. In 18 neurons with ls-EPSP, 4 (22%) neurons were sensitive to both BOM and SP; 6 (33%) and 5 (28%) neurons were only sensitive to BOM and SP, respectively. The remaining 3 (17%) neurons were insensitive to both BOM and SP. Membrane resistance (Rm) had no apparent change in 47.3%, 59.5 % of the neurons tested during the ls-EPSP (n=55) and BOM depolarization (n=84), respectively, but had a marked decrease in 38.2%, 27.4%, and a marked increase in the remaining 14.5%, 13.1% of the neurons. However, when the Rm change accompanying ls-EPSP was compared with that accompanying BOM depolarization (n=20) in the same neuron, the changes in Rm were always parallel. Moreover, ls-EPSP (n=6) and BOM depolarization (n=8) were all augmented by conditioning hyperpolarization. The extrapolated values of the reversal potentials of ls-EPSP and BOM depolarization were 46.0+/-8.0 and 50.0+/-7.0 mV (n=8, P>0.05), respectively. In 14 BOM-sensitive neurons, a ls-EPSP was elicited by repetitive colon nerve stimulation. Superfusion of BOM (10 micromol/L) in these cells initially caused a large depolarization and then membrane potential gradually subsided to resting level in the continuous presence of BOM. Stimulation of the presynaptic nerves at this time failed to elicit a detecable ls-EPSP in 2 neurons and induced a much smaller one in 10 cells, while the ls-EPSP in the remaining 2 neurons was not appreciably affected. On the other hand, prolonged superfusion of BOM had no effect on the amplitude and duration of ls-EPSP in 6 BOM-insensititive neurons studied (P>0.05). The amplitude and duration of SP-induced depolarization were not altered by prolonged superfusion of BOM (n=4, P>0.05) Superfusion of tyr(4) D-phe(12) bombesin (1 micromol/L, 10 15 min), a BOM receptor antagonist, did not cause any noticeable changes in passive membrane properties nor block nicotinic f-EPSPs, but markedly suppressed (n=5) or completely abolished (n=11) BOM depolarization in all 16 neurons tested Similarly, tyr(4) D-phe(12) bombesin partially or completely antagonized the ls-EPSP in 9 out of a total of BOM sensitive neurons (n=11). The ls-EPSP elicited in the remaining two neurons was insignificantly affected by this drug. However, following 10 20 min of wash with Krebs solution the ls-EPSP was reversed. In contrast, superfusion of the ganglia with tyr(4) D-phe(12) bombesin did not change the amplitude and duration (P>0.05) of ls-EPSP in 10 BOM-insensitive cells. Similarly, the amplitude and duration of SP-induced depolarization were not appreciably affected by tyr(4) D-phe(12) bombesin (n=6, P>0.05). In conclusion, our results indicate that BOM may be another transmitter mediating the ls-EPSP in the guinea pig IMG and that there is no cross-desensitization of BOM receptors and SP receptors.