[Ergonomic risk factors of carpal tunnel syndrome in workers of an automobile factory].

Objective: To investigate the occurrence of pain symptoms and risk factors of carpal tunnel syndrome (CTS) in automobile manufacturing workers and provide theoretical basis for the prevention of CTS. Methods: From Nov.5th to Nov.19th, 2017, 446 workers in an automobile factory whose work age was above one year participate in questionnaires by cluster sampling. Chi square test and multifactor logistics regression analysis were used to analyze the factors related to the occurrence of CTS pain symptoms in workers. Results: The incidence of CTS pain among workers in this automobile factory was 20.8%. Working in the same position for a long time (OR=2.137, 95% CI:1.183-3.862) and unable to work reasonably because of uncomfortable posture (OR =2.067, 95% CI: 1.075-3.974) were identified as the risk factors of CTS pain symptoms by multifactor logistics regression analysis. Working age (OR=0.537, 95%CI:0.311-0.926) and work break (OR= 0.489, 95% CI: 0.282-0.849) were identified as the benefit factors of CTS pain symptoms. Conclusion: The incidence of CTS pain in automobile manufacturing workers is related to the posture in the process of labor . Effective ergonomic interventions should be carried out to prevent the occurrence of CTS pain in automobile manufacturing workers.

25-hydroxyvitamin D, insulin-like growth factor-I, and bone mineral accrual during growth.

CONTEXT: The extent to which 25-hydroxyvitamin D [25(OH)D] and IGF-I influence bone mineral content (BMC) accrual from early to mid-puberty is unclear. OBJECTIVE, SETTING, AND PARTICIPANTS: This study sought to determine relationships among 25(OH)D, IGF-I, and BMC in community-dwelling prepubertal females (n = 76; aged 4-8 yr at baseline) over a period of up to 9 yr. DESIGN: The hypothesis that changes in IGF-I vs. 25(OH)D are more strongly associated with BMC accrual was formulated after data collection. 25(OH)D and IGF-I were log-transformed and further adjusted using two-way ANOVA for differences in season and race. Linear mixed modeling (including a random subject-specific intercept and a random subject-specific slope on age) was employed to analyze the proportion of variance the transformed 25(OH)D and IGF-I variables explained for the bone outcomes. RESULTS: IGF-I was more strongly associated with BMC accrual than 25(OH)D at the total body (R(2) = 0.874 vs. 0.809), proximal femur (R(2) = 0.847 vs. 0.771), radius (R(2) = 0.812 vs. 0.759), and lumbar spine (R(2) = 0.759 vs. 0.698). The rate of BMC accrual was positively associated with changes in IGF-I but negatively associated with 25(OH)D. When IGF-I and 25(OH)D were included in the same regression equation, 25(OH)D did not have a significant predictive effect on BMC accrual above and beyond that of IGF-I. CONCLUSIONS: These prospective data in early adolescent females indicate that both 25(OH)D and IGF-I have a significant impact on bone mineral accrual; however, the positive association of IGF-I and BMC accrual is greater than the negative association of 25(OH)D and BMC accrual.

Electronic transport of unimolecular devices with a group coadsorbed on one electrode surface: a density functional study.

The first-principles calculations based on the density functional theory are applied to investigate the effect of a chemical group coadsorbed on one electrode surface on the electronic transport of a molecular device. We find that the types of the coadsorbed groups and their sites on one electrode surface affect the electronic transport significantly, and the resulting shift of the molecular levels upon coadsorption depends jointly on various effects, such as the electrostatic interaction, shift of the Fermi level of the electrode, the chemical interaction, and so on. Among these factors, the chemical interaction-induced the charge transfer across metal-molecule interface is identified as a determining factor resulting in the variation of transport properties. Our findings suggest that the coadsorption may offer the novel possibility to modify the transport behaviors of a molecular device in a controlled way and can improve/add some particular functionalities or should be avoided in order to keep a stable transport for a molecular device.

Glucose-dependent insulinotropic peptide is an integrative hormone with osteotropic effects.

Glucose-dependent insulinotropic peptide (GIP) is a gut-derived hormone known to be important in modulating glucose-induced insulin secretion. In addition, GIP receptors are widely distributed and may have effects on multiple other tissues: fat cells, adrenal glands, endothelium and brain. We have demonstrated recently that GIP also has anabolic effects on bone-derived cells. We now demonstrate that GIP administration prevents the bone loss associated with ovariectomy. We propose that GIP plays a unique role in signaling the bone about nutrient availability, indicating the importance of the gut hormones in directing absorbed nutrients to the bone, and suggesting the concept of an 'entero-osseous axis'. Thus, GIP plays an integrative role helping coordinate efficient and targeted nutrient absorption and distribution.

Functional analysis of glucose-dependent insulinotropic polypeptide fusion proteins.

To generate functional fluorescently tagged glucose-dependent insulinotropic polypeptide (GIP), a series of GIP expression constructs were devised. These included G1 (complete preprohormone), G2 (lacking the C-terminal extension), G3 (lacking both N- and C-terminal extensions), G4 (G2 fused to green fluorescent protein, GFP), and G5 (G3 fused to GFP). Expression of G5 in bacteria generated immunopositive GIP together with GFP fluorescence, while G4 generated only fluorescence without immunoreactivity. Transfection of NIH3T3 cells with cDNAs of G1, G3, G5, but not G2, G4, and EGFP, resulted in immunologically detectable GIP formation, although fluorescence could be detected in the latter two. GIP as well as GIP-GFP secreted by NIH3T3 cells significantly stimulated intracellular cAMP accumulation and Ca(2+) mobilization in SaOS2 cells. The GIP receptor antagonist GIP(7-30) abolished these responses. These results suggest that a GIP-GFP fusion protein seven times larger than the native peptide retains function and may be used as an in vivo probe to detect GIP receptor distribution and to explore GIP's biological roles.

Glucose-dependent insulinotropic peptide signaling pathways in endothelial cells.

Glucose-dependent insulinotropic peptide (GIP) potentiates glucose-induced insulin secretion. In addition, GIP has vasoconstrictive or vasodilatory properties depending on the vascular bed affected. In order to assess whether this effect could be related to differences in GIP receptor expression, several different endothelial cell types were examined for GIP receptor expression. GIP receptor splice variants were detected and varied depending on the endothelial cell type. Furthermore, stimulation of these cells with GIP led to cell type dependent differences in activation of the calcium and cAMP signaling pathways. To our knowledge this is the first physiological characterization of receptors for GIP in endothelial cells.

Functional parathyroid hormone receptors are present in an umbilical vein endothelial cell line.

Acute parathyroid hormone exposure induces vascular smooth muscle relaxation. In contrast, continuous infusion of parathyroid hormone leads to vasoconstriction and an elevation of blood pressure. Despite the known effects of parathyroid hormone on vascular smooth muscle, possible direct effects on the vascular endothelium have not previously been investigated. Using a human umbilical vein endothelial cell line, we found that parathyroid hormone increased both intracellular calcium and cellular cAMP content in these endothelial cells. Furthermore, exposure of these cells to increasing concentrations of parathyroid hormone stimulated both [(3)H]thymidine incorporation and endothelin-1 secretion. Parathyroid hormone/parathyroid hormone-related peptide receptor mRNA could be detected at low levels in these cells. In summary, these data demonstrate that endothelium-derived cells contain functional parathyroid hormone receptors. The potential physiological role of these receptors remains to be determined.

Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors.

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid peptide synthesized and secreted from endocrine cells in the small intestine. The role of GIP in coupling nutrient intake and insulin secretion, the incretin effect, is well known. We report that GIP receptor messenger RNA and protein are present in normal bone and osteoblast-like cell lines, and that high affinity receptors for GIP can be demonstrated by [125I]GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated increases in cellular cAMP content and intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I messenger RNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblast-like cells and that GIP modulates the function of these cells.

Atrial natriuretic peptide provokes a dramatic increase in cyclic GMP formation and markedly inhibits muscarinic-stimulated Ca2+ mobilisation in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells.

We investigated the effects of cGMP-elevating agents, including atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) and sodium nitroprusside (SNP), on cGMP accumulation and on carbachol (CCh)-stimulated intracellular calcium ([Ca2+]i) mobilisation in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells and in primary cultured cat iris sphincter smooth muscle (CISM) cells. The stimulatory effects of the natriuretic peptides on cGMP production correlated well with their inhibitory effects on CCh-induced [Ca+1]i mobilisation, and these effects were significantly more pronounced in the SV-CISM-2 cells than in the CISM cells. Thus, ANP (1 microM) increased cGMP production in the SV-CISM-2 cells and CISM cells by 487- and 1.7-fold, respectively, and inhibited CCh-induced [Ca2+]i mobilisation by 95 and 3%, respectively. In the SV-CISM-2 cells, ANP and CNP dose dependently inhibited CCh-induced [Ca2+]i mobilisation with IC50 values of 156 and 412 nM, respectively, and dose dependently stimulated cGMP formation with EC50 values of 24 and 88 nM, respectively, suggesting that the inhibitory actions of the peptides are mediated through cGMP. Both ANP and CNP stimulated cGMP accumulation in a time-dependent manner. The potency of the cGMP-elevating agents were in the following order: ANP>>CNP>>SNP; these agents had no effect on cAMP accumulation. The inhibitory effects of the natriuretic peptides were mimicked by 8-Br-cGMP, a selective activator of cGMP-dependent protein kinase. LY83583, a soluble guanylyl cyclase inhibitor, significantly inhibited SNP-induced cGMP formation but had no effect on those of ANP and CNP. The basal activities of the guanylyl cyclase and the dissociation constant (Kd) and total receptor density (Bmax) values of the natriuretic peptide receptor for [125I]ANP binding were not significantly different between the two cell types. The cGMP system, as with the cAMP system, has a major inhibitory influence on the muscarinic responses in the iris sphincter smooth muscle cells, and SV-CISM-2 cells can serve as an excellent model for investigating the cross talk between cGMP and the Ca2+ signalling system.

Activation of particulate guanylyl cyclase by endothelins in cultured SV-40 transformed cat iris sphincter smooth muscle cells.

We investigated the effects of endothelins (ETs) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ET-3 increased cGMP formation in a concentration-dependent manner (EC50 = 98nM), which was 2.5 times higher than that of ET-1. The ET(B)receptor agonists sarafotoxin-S6c and IRL 1620 also increased cGMP production, mimicking the effects of the ETs. The ET(B) receptor antagonist BQ 788, but not the ET(A) receptor antagonist BQ610, dose-dependently blocked ET-3-stimulated cGMP formation (IC50=10nM). The phorbol ester, Phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylyl cyclase in smooth muscle, dose-dependently inhibited ET-3-stimulated cGMP accumulation (IC50=66nM). LY83583 and ODQ, inhibitors of soluble guanylyl cyclases, as well as inhibitors of the nitric oxide cascade and of intracellular Ca2+ elevation had no appreciable effect on ET-3-induced cGMP production. ET-3 markedly inhibited carbachol-induced intracellular Ca2+ mobilization. We conclude that ET-3 increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ET(B) receptor subtype and subsequent stimulation of the membrane-bound guanylyl cyclase. Elevation of cGMP by ET and the subsequent inhibition of muscarinic stimulation of intracellular Ca2+ mobilization by the cyclic nucleotide could serve to modulate the contractile effects of Ca2+-mobilizing agonists in the iris sphincter smooth muscle.

Scattering of electromagnetic waves from dense distributions of spheroidal particles based on Monte Carlo simulations.

In a dense discrete random medium, the propagation and scattering of waves are affected not only by the individual properties of the particles such as size, shape, and permittivity, but also by group properties such as the statistics of relative particle positions and relative orientations. We use Monte Carlo simulations to investigate the interactions of electromagnetic waves with a dense medium consisting of spheroidal particles for cases of random orientation and for cases of aligned orientation. A shuffling process is used to generate the positions of densely packed spheroids. Multiple-scattering equations are formulated by means of the volume integral equation and are solved numerically. The scattering results are averaged over realizations. Numerical results are presented for the extinction rates and the phase matrices. Salient features of the numerical results indicate that (1) the extinction rates of densely packed small spheroids are smaller than those of independent scattering; (2) for aligned spheroids, the extinction rates are polarization dependent; and (3) the co-polarized part of the phase matrix for densely packed spheroids is smaller than that of independent scatering, while the cross-polarized part is larger than that for independent scattering. This means that the ratio of cross-polarization to co-polarization is significantly higher than that of independent scattering.

Actions of C-type natriuretic peptide and sodium nitroprusside on carbachol-stimulated inositol phosphate formation and contraction in ciliary and iris sphincter smooth muscles.

PURPOSE: To investigate the effects of C-type natriuretic peptide (CNP) and sodium nitroprusside (SNP) on cyclic guanosine monophosphate (cGMP) accumulation and on carbachol (CCh)-stimulated inositol 1,4,5-triphosphate (IP3) production and contraction in ciliary muscle (CM) and iris sphincter (Sph) isolated from bovine and other mammalian species. METHODS: Ciliary muscle and sphincter isolated from cows, cats, dogs, rabbits, monkeys, and humans were used. Bovine specimens were used in the present work. Accumulation of cGMP and cyclic adenosine monophosphate (cAMP) in tissue extracts was measured by radioimmunoassay, IP3 production was measured by ion-exchange chromatography, and changes in tension were recorded isometrically. RESULTS: In general, CNP and SNP exerted differential inhibitory effects on muscarinic-receptor-induced responses in CM and Sph isolated from the various species. Thus in bovine CM, SNP stimulated cGMP formation in a time- and concentration-dependent manner and dose dependently inhibited CCh-induced IP3 production and contraction. These effects were inhibited by LY 83583, a soluble guanylyl cyclase inhibitor, and mimicked by 8-Br-cGMP, a cell-membrane permeable analogue of cGMP. The inhibitory effects of the soluble cGMP analogue are tissue and species specific. Sodium nitroprusside had no effect on the muscarinic responses in bovine Sph, but it attenuated CCh-induced contractions in Sph isolated from cats, dogs, and rabbits. In bovine Sph, CNP increased cGMP accumulation in a time- and dose-dependent manner and dose dependently inhibited CCh-induced IP3 production and contraction. LY 83583 had no effect on the muscarinic responses. C-type natriuretic peptide attenuated CCh-induced contraction in CM isolated from monkey and human, but it had no influence on this response in CM isolated from cows, cats, and dogs. CONCLUSIONS: In bovine CM, SNP effects are probably mediated through soluble guanylyl cyclase, whereas in Sph the CNP effects are mediated through membrane-bound guanylyl cyclase, which is associated with the type-B natriuretic peptide receptor. Agents that strongly increase intracellular cGMP levels, including SNP and CNP, produce significant inhibition of CCh-induced IP3 production and contraction. These effects are tissue and species specific. The results indicate that the cGMP signaling system, similar to the cAMP system, has a major inhibitory influence on the muscarinic responses in smooth muscles of the iris-ciliary body. The agents CNP and SNP, which stimulate cGMP accumulation in the ocular smooth muscles, could reduce intraocular pressure, presumably by increasing uveoscleral outflow induced by relaxation of the CM. However, the relationships between the CNP- and SNP-induced inhibition of the muscarinic stimulation and the reported intraocular pressure-lowering effects of the cGMP-elevating agents remain to be determined.

Inhibition of muscarinic-stimulated polyphosphoinositide hydrolysis and Ca2+ mobilization in cat iris sphincter smooth muscle cells by cAMP-elevating agents.

The effects of carbachol (CCh) on inositol 1,4,5-trisphosphate (IP3) production and intracellular calcium ([Ca2+]i) mobilization, and their regulation by cAMP-elevating agents were investigated in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. CCh produced time- and dose-dependent increases in IP3 production; the t1/2 and EC50 values were 68 s and 0.5 microM, respectively. The muscarinic agonist provoked a transient increase in [Ca2+]i which reached maximum within 77 s, and increased [Ca2+]i mobilization in a concentration-dependent manner with an EC50 of 1.4 microM. Thapsigargin, a Ca(2+)-pump inhibitor, caused a rapid rise in [Ca2+]i and subsequent addition of CCh was without effect. Both CCh-induced IP3 production and CCh-induced [Ca2+]i mobilization were more potently antagonized by 4-DAMP, an M3 muscarinic receptor antagonist, than by pirenzepine, an M1 receptor antagonist, suggesting that both responses are mediated through the M3 receptor subtype. Treatment of the cells with U73122, a phospholipase C (PLC) inhibitor, resulted in a concentration-dependent decrease in both CCh-stimulated IP3 production and [Ca2+]i mobilization. These data indicate close correlation between enhanced IP3 production and [Ca2+]i mobilization in these smooth muscle cells and suggest that the CCh-stimulated increase in [Ca2+]i could be mediated through increased IP3 production. Isoproterenol (ISO) inhibited CCh-induced IP3 production (IC50 = 80 nM) and [Ca2+]i mobilization (IC50 = 0.17 microM) in a concentration-dependent manner. Microsomal fractions isolated from SV-CISM-2 cells contained phospholipase C (PLC) which was stimulated by CCh (10 microM) and GTP gamma S (0.1 microM). Pretreatment of the cells with ISO or forskolin, 5 microM each, produced membrane fractions in which CCh-stimulated PLC activity was significantly attenuated. Furthermore, when microsomal fractions isolated from SV-CISM-2 cells were phosphorylated with Protein kinase A (PKA), the CCh- and GTP gamma S-stimulated IP3 production were significantly inhibited. It can be concluded from these studies that in SV-CISM-2 cells, activation of M3 muscarinic receptors results in stimulation of PLC-mediated PIP2 hydrolysis, generating IP3 which mobilizes [Ca2+]i. Furthermore, elevation of cAMP may inhibit IP3 production and [Ca2+]i mobilization through mechanisms involving PKA-dependent phosphorylation of PLC, G-proteins, IP3 receptor and/or IP3 metabolizing enzymes.

Effects of endothelin on phospholipases and generation of second messengers in cat iris sphincter and SV-CISM-2 cells.

In both immortalized cat iris sphincter smooth muscle cells (SV-CISM-2 cells) and cat iris sphincter, endothelin-1 (ET-1) markedly increased the activities of phospholipase A2 (PLA2), as measured by the release of arachidonic acid (AA), phospholipase C (PLC), as measured by the production of inositol trisphosphate (IP3), and phospholipase D (PLD), as measured by the formation of phosphatidylethanol (PEt). In SV-CISM-2 cells, ET-1 induced AA release, IP3 production and PEt formation in a dose- and time-dependent manner. The dose-response studies showed that the peptide is more potent in activating PLD (EC50 = 1.2 nM) than in activating PLC (EC50 = 1.5 nM) or PLA2 (EC50 = 1.7 nM). The time course studies revealed that ET-1 activated the phospholipases in a temporal sequence in which PLA2 was stimulated first (t1/2 = 12 s), followed by PLC (t1/2 = 48 s) and lastly PLD (t1/2 = 106 s). In SV-CISM-2 cells, in contrast to the intact iris sphincter, sarafotoxin-c, an ETB receptor agonist, had no effect on the phospholipases, and indomethacin, a cyclooxygenase inhibitor, had no effect on the stimulatory effect of ET-1 on the phospholipases. These results suggest that in this smooth muscle cell line, ET-1 interacts with the ETA receptor subtype to activate, via G proteins, phospholipases A2, C and D in a temporal sequence.

Inhibition of 5'-chloro-5'-deoxyadenosine on phosphoinositide and protein phosphorylation in swine platelets.

AIM: To study the effects of adenosine on the phosphorylation of phosphoinositides and proteins in platelets. METHODS: In the presence of Mg2+ and/or Ca2+, swine thrombocytic membranes were incubated with [gamma-32P]ATP at 30 degrees C for 3 min and the incorporations of 32P into phospholipids or proteins were measured. RESULTS: 5'-Chloro-5'-deoxyadenosine decreased the formation of phosphatidylinositol 4-phosphate and phosphatidylinositol 4, 5-bisphosphate [IC50 71 and 75 (95% confidence limits 60-85 and 62-90) mumol.L-1, respectively], behaving as a competitive inhibitor to ATP, and inhibited the phosphorylation of pleckstrin (the major protein kinase C substrate) and myosin light chain [IC50 75 and 82 (95% confidence limits 62-90 and 66-102) mumol.L-1, respectively]. CONCLUSION: Adenosine affects the phosphoinositide signaling pathway in platelets, which helps to clarify the inhibition of adenosine on platelet activation.

[Effects of spermine on phosphorylation of phosphoinositide and 47 K protein in platelet membranes of pig].

In the presence of Mg2+ and exogenous phosphatidylinositol-4-phosphate, swine thrombocytic membranes were incubated with [gamma-32P]ATP at 30 degrees C for 3 min and the incorporations of 32P into phospholipids and proteins were measured. Spermine stimulated the formation of phosphatidylinositol-4,5-bisphosphate (optimal concentration 0.25 mmol.L-1) and inhibited the phosphorylation of 47 K protein (IC50 1 mmol.L-1). This helps to clarify the effect of spermine on cell growth and proliferation.