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Biomedical subjects

W Yao

Publications and source records attributed to W Yao.

At least 19 recordsLinked to original sources

Bipedal stance exercise and prostaglandin E2 (PGE2) and its synergistic effect in increasing bone mass and in lowering the PGE2 dose required to prevent ovariectomized-induced cancellous bone loss in aged rats.

Previous reports have shown that bone loss was partially prevented by bipedal stance "exercise" following ovariectomy (ovx), and it was well documented that prostaglandin E2 (PGE(2)) had an anabolic effect on the rat skeleton. The aim of this study was to determine whether lower doses of PGE(2) could prevent ovx-induced cancellous bone loss with the combination of bipedal stance exercise. Seventy-eight 10-month-old female Sprague-Dawley rats were either ovariectomized or sham-operated on day 0 and then treated with PGE(2) (0, 0.3, or 1 mg/kg per day) and/or housed in normal height cages (NC, 28 cm) or raised cages (RC, 33 cm) for 8 weeks. Bone histomorphometry was performed on the double-fluorescent-labeled proximal tibial metaphysis. In sham rats, 1 mg/kg PGE(2) + RC had synergistic effects in increasing trabecular bone area, width, and number by stimulating mineral apposition rate and bone formation rate. As expected, ovx induced cancellous bone loss, accompanied by elevated activation frequency. Without RC, PGE(2) monotherapy prevented ovx-induced bone loss at the 1 mg/kg per day dose, whereas this prevention effect was observed at the 0.3 mg/kg per day dose when combined with RC. Similar to their effects in sham rats, PGE(2) and RC had synergistic effects in augmenting cancellous bone mass and architecture and maintaining the elevated bone formation but depressing bone resorption and activation frequency. We conclude that bipedal stance exercise lowers the PGE(2) dose required to prevent ovx-induced cancellous bone loss in the proximal tibial metaphysis in aged rats.

Animals↗

Synthesis and biological evaluation of prostaglandin-F alkylphosphinic acid derivatives as bone anabolic agents for the treatment of osteoporosis.

A series of novel C(1) alkylphosphinic acid analogues of the prostaglandin-F family have been evaluated at the eight human prostaglandin receptors for potential use in the treatment of osteoporosis. Using molecular modeling as a tool for structure-based drug design, we have discovered that the phosphinic acid moiety (P(O)(OH)R) behaves as an isostere for the C(1) carboxylic acid in the human prostaglandin FP binding assay in vitro and possesses enhanced hFP receptor selectivity when compared to the parent carboxylic acid. When evaluated in vivo, the methyl phosphinic acid analogue (4b) produced a bone anabolic response in rats, returning bone mineral volume (BMV) [corrected], to intact levels in the distal femur in the ovariectomized rat (OVX) model. These results suggest that prostaglandins of this class may be useful agents in the treatment of diseases associated with bone loss.

Absorptiometry, Photon↗

Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors.

A pharmacophore model of the P1' site, specific for aggrecanase, was defined using the specificity studies of the matrix metalloproteinases and the similar biological activity of aggrecanase and MMP-8. Incorporation of the side chain of a tyrosine residue into compound 1 as the P1' group provided modest selectivity for aggrecanase over MMP-1, -2, and -9. A cis-(1S)(2R)-amino-2-indanol scaffold was incorporated as a tyrosine mimic (P2') to conformationally constrain 2. Further optimization resulted in compound 11, a potent, selective, and orally bioavailable inhibitor of aggrecanase.

Administration, Oral↗

Spectrophotometric determination of freshwater pH using bromocresol purple and phenol red.

The dissociation constants (KI = [H+][I2-]/[HI-]) of two sulfonephthalein indicators (bromocresol purple and phenol red) were determined as function of temperature (10-30 degrees C) at zero ionic strength. Freshwater pH, on the free hydrogen ion concentration scale (molal units), can be precisely calculated from measurements of indicator absorbance ratios (lambda2A/lambda1A) using the following equations: pH = pKI + log((R - e1)/(e2 - Re3)) and pKI = pKI(degrees) - AdeltaZ2(mu1/2 /(1 + mu1/2) - 0.3 mu), where R = lambda2A/lambda1A, pKI = -log KI, mu is the ionic strength, deltaZ2 = 4, and values of A for 283 < or = T < or = 303 can be estimated from the equation: A = 0.5092 + (T-298.15) x 8.5 x 10(-4). For bromocresol purple (lambda1 = 432 nm, lambda2 = 589 nm), pKI(degrees) = 5.226 + 378.1/T, e1 = 0.00387, e2 = 2.858, and e3 = 0.0181. For phenol red (lambda1 = 433 nm, lambda2 = 558 nm), pKI(degrees) = 5.798 + 666.7/T, e1 = 0.00244, e2= 2.734, and e3 = 0.1075. These two indicators can be used to make accurate pH measurements of freshwaters (river water, lake water, groundwater, rainwater, etc) within the range 4.5 < or =pH < or =8.5. The precision of pH measurements using phenol red in well-buffered freshwaters is on the order of +/-0.001 or better.

Acid Rain↗

Synergistic transcriptional activation of human Acyl-coenzyme A: cholesterol acyltransterase-1 gene by interferon-gamma and all-trans-retinoic acid THP-1 cells.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme involved in cellular cholesterol homeostasis and in atherosclerotic foam cell formation. Human ACAT-1 gene contains two promoters (P1 and P7), each located in a different chromosome (1 and 7) (Li, B. L., Li, X. L., Duan, Z. J., Lee, O., Lin, S., Ma, Z. M., Chang, C. C., Yang, X. Y., Park, J. P., Mohandas, T. K., Noll, W., Chan, L., and Chang, T. Y. (1999) J. Biol Chem. 274, 11060-11071). Interferon-gamma (IFN-gamma), a cytokine that exerts many pro-atherosclerotic effects in vivo, causes up-regulation of ACAT-1 mRNA in human blood monocyte-derived macrophages and macrophage-like cells but not in other cell types. To examine the molecular nature of this observation, we identified within the ACAT-1 P1 promoter a 159-base pair core region. This region contains 4 Sp1 elements and an IFN-gamma activated sequence (GAS) that overlaps with the second Sp1 element. In the monocytic cell line THP-1 cell, the combination of IFN-gamma and all-trans-retinoic acid (a known differentiation agent) enhances the ACAT-1 P1 promoter but not the P7 promoter. Additional experiments showed that all-trans-retinoic acid causes large induction of the transcription factor STAT1, while IFN-gamma causes activation of STAT1 such that it binds to the GAS/Sp1 site in the ACAT-1 P1 promoter. Our work provides a molecular mechanism to account for the effect of IFN-gamma in causing transcriptional activation of ACAT-1 in macrophage-like cells.

Base Sequence↗

Delayed stochastic differential model for quiet standing.

A physiological quiet standing model, described by a delayed differential equation, subject to a white noise perturbation, is proposed to study the postural control system of human beings. It has been found that the white noise destabilizes the equilibrium state, and inertia accelerates the destabilizing process, and that the position of a person is detected and processed by the person's nervous system with a delay. This paper focuses on the analysis of Hopf bifurcation and its stability in this context. Based on the analytical predictions confirmed by numerical simulations, it has been shown that the posture of a person is controlled in such a way that possible amplitude oscillations are minimized.

Computer Simulation↗

Lumbar vertebral cancellous bone is capable of responding to PGE2 treatment by stimulating both modeling and remodeling-dependent bone gain in aged male rats.

Previously we found that PGE2 3 mg/kg in 20-month-old male rats induced massive bone formation mainly by modeling dependent bone gain in cortical bone. It is not known whether cancellous bone will respond similarly; thus, we evaluated the effect of PGE2 on cancellous bone of the same aged rats. Thirty-four 20-month-old Wistar male rats were given PGE2 (3 mg/kg/day) or vehicle subcutaneously for 10 and 30 days. Double fluorescent labels were injected 9 and 2 days prior to the sacrifice. Histomorphometry was performed on 1% toluidine blue stained and unstained sagittal sections of lumbar vertebral bodies. The results demonstrated that 10-day PGE2 treatment increased osteoprogenitor cells, osteoblasts (x 2-fold), osteoid (x 4.5-fold), woven bone formation (0.04%), and 40% more trabecular area; it stimulated modeling (x 2-fold) and remodeling-dependent (x 1.5-fold) bone formation with increase of mineralization lag time (MLT, x 7.5-fold). Thirty-day treatment sustained increases in osteoblast numbers, modeling and remodeling-dependent bone formation and further stimulated woven bone formation (6.6%), turnover (x 3-fold), and trabecular area and number (x 2-fold). Osteoprogenitor cells were undetectable along with 70% less osteoid area compared with 10-day treatment but still was 1.5-fold higher than aging controls. MLT returned to aging control level. It was concluded that the aged cancellous bone of 20-month-old male Wistar rat retains a capability of responding to the anabolic effect of PGE2. Osteoblastogenesis and enhanced modeling and remodeling-dependent woven or lamellar formation contribute to this anabolic action. Bone formation differed in that the endocortical surface of cortical bone was stimulated mainly by modeling whereas both modeling and remodeling-dependent bone gain were equally stimulated at the trabecular surface of the lumbar vertebral body.

Animals↗

Cancellous bone of aged rats maintains its capacity to respond vigorously to the anabolic effects of prostaglandin E2 by modeling-dependent bone gain.

The present study examined the early effects of prostaglandin (PG)E2 on proximal tibial metaphyses of 20-month-old Wistar male rats. PGE, was given to intact rats for 10 and 30 days at 3mg/kg/day. After multiple in vivo fluorochrome labeling, undecalcified longitudinal sections were subjected to analysis of bone histomorphometry and classification of the contour of the cement line in bone formation units. The latter was used to classify bone formation units into modeling, remodeling and uncertain units. After 10 days of treatment, there was a 2% increase in woven bone formation with the appearance of osteoprogenitor cells and increases in the number of osteoblasts (649%) and osteoid (375%) surfaces. Remodeling and modeling units increased by 56% and 429%. respectively. After 30 days of treatment, there was an increase of 212% of total trabecular bone mass, 60% of which was woven bone. In addition, there were increases in labeling surface (147%), mineral apposition rate (760%), bone formation rates tissue area (BFR/T.Ar, 1920%; BFR/B.Pm, 343%), and bone turnover (BFR/B.Ar, 426%). Osteoblasts and osteoid production at 30 days were 29% and 58% less than at 10 days post-treatment. Modeling and remodeling activity did not differ from that seen at 10 days. In addition, PGE2 treatment tended to stimulate the closing of growth plates and decrease the fatty marrow area. We conclude that the aged skeleton was able to respond vigorously to PGE2 treatment. Massive osteoprogenitors cells, and osteoid and osteoblast formations were observed within 10 days. and dramatic woven and lamellar bone formation was seen at 30 days post-treatment. The anabolic effects were driven mainly by modeling.

Aging↗

Low viscosity Ektacytometry and its validation tested by flow chamber.

The flow chamber was used to observe the orientation and small deformation of red blood cells (RBCs) in a shear flow of low viscosity. With the aid of computer software, the percentage of RBCs oriented to the C=0 orbit (OI)(F) and the degree of deformation (DI)(F) of such RBCs were calculated by processing the photographs. It was found that these parameters were highly correlated, respectively, to the orientation index (OI)(E) and the small deformation index (DI)(E) obtained by our low viscosity Ektacytometry (LVE). Thus, our flow chamber research has provided direct evidence to validate the use of this low viscosity Ektacytometry. Although there are relative merits for the flow chamber method using low viscosity medium, the LVE is more likely to be applied in clinic for its simplicity and convenience.

Animals↗

Bipedal stance exercise enhances antiresorption effects of estrogen and counteracts its inhibitory effect on bone formation in sham and ovariectomized rats.

In this study we employed a raised cage model in combination with estrogen to observe their effects on the proximal tibial metaphysis (PTM) and tibial shaft (TX) in sham-operated or ovariectomized rats. A total of 105 6-month-old female Sprague-Dawley rats were used in the study. Bilateral sham ovariectomy or ovariectomy was performed at day 0 and the rats were housed in normal height or raised cages (RCs) and injected subcutaneously twice per week with 10 microg/kg of 17beta-estradiol (E2) or vehicle for 4 and 8 weeks. Because the time course of bone loss or bone gain distribution was not uniform in the metaphyses of the tibia, we subdivided the PTM into three zones (medial, central, and lateral) to observe the different bone loss or bone gain patterns after ovariectomy and/or raised cages. We found that: (1) E2 alone did not alter bone area or architecture in sham rats, whereas RC alone increased trabecular thickness and area of PTM, but had no effects on TX; (2) Ovx induced most bone loss from the central zone of the PTM and endocortical surface of TX, accompanied by decreased trabecular number and increased bone resorption; (3) E2 alone prevented ovx-induced bone loss by preserving trabecular number and depressing bone resorption; (4) RC alone partially compensated for bone loss following ovx by thickening the surviving trabeculae in lateral and medial zones, and tended to stimulate bone formation and decrease bone resorption; and (5) RC plus E2 increased trabecular bone area by having an additive effect on bone resorption and bone turnover. RCs helped to prevent the depressive effect of estrogen on periosteal bone formation. In conclusion, early and rapid bone loss occurred in the central zone of the metaphysis and endocortical surface after ovx. Estrogen replacement therapy prevented this loss. Raised cages partially compensated for bone loss following ovx by thickening the trabeculae in the lateral area of the metaphysis and decreased endocortical erosion. Combination treatment added bone to the PTM and prevented the decrease of periosteal bone formation after estrogen administration.

Animals↗

Ultrasonographic texture analysis of parenchymatous organs by the four-neighborhood-pixels algorithm: clinical experiment.

OBJECTIVE: The parenchyma of organs such as liver, thyroid, and mammary gland during climacterium have common ultrasonographic textural features, which together form what we call small-dot-structure texture. To study this texture we designed the 4-neighborhood-pixels algorithm, an ultrasonographic texture analysis algorithm. The objective of this study was to confirm whether the 4-neighborhood-pixels algorithm can reflect the features of small-dot-structure texture. METHODS: A changed small-dot-structure texture and 3 other textures were compared with the normal small-dot-structure texture in 4 groups, and a histogram algorithm was used for contrast with the 4-neighborhood-pixels algorithm. RESULTS: The 4-neighborhood-pixels algorithm could reflect all the textural differences, but the histogram algorithm could reflect only some of them. CONCLUSIONS: The 4-neighborhood-pixels algorithm is a good algorithm for analyzing ultrasonographic small-dot-structure texture. Not only can it reflect changes in the small-dot-structure texture, but it can also differentiate between small-dot-structure and non-small-dot-structure textures.

Adipose Tissue↗

[Effect of radiation with 60Co on RBC membrane elastic shear modulus and membrane viscosity].

RBC membrane shear elastic modulus and membrane viscosity are two important indexes reflecting RBC membrane viscoelasticity. Their variation was investigated in this study after rabbits were radiated with 60Co. With a new ektacytometer, we measured the small deformation index (DId) and the half-time of deformation relaxation (t0.5) of RBC in flow field then we calculated RBC membrane shear elastic modulus and membrane viscosity. We found that the value of RBC membrane shear elastic modulus and membrane viscosity continuously increased from 0 to 16th day then continuously decreased and tended to be stable on 60th day or so. The reason may lie in the variation of proportion of new and old RBC in blood and variation of microconformation of RBC membrane after rabbits were radiated with 60Co.

Animals↗

[Effects of the alterations of membrane shear elastic modulus and viscosity on the deformation and orientation of RBCs].

Neuraminidase can partly remove the surface charge of RBCs through a biochemical interaction; thus it can give rise to alterations in the microstructure of membrane, the shear elastic modulus (E) and the viscosity(micron) of membrane. Changing the time of treatment and the dose of neuraminidase and using a new ektacytometry that can separate deformation index DI into orientation index (DI)or and small deformation index (DI)d for RBCs in shear flow field of low viscosity, we measured (DI)d and the half time t0.5 when the DI recovered to half of the maximum in the process of relaxation for every treated sample. (DI)d and t0.5 were put respectively into the RBC membrane shear elastic modulus formula and the membrane viscosity formula which were put forward by Wen Zong-yao and Yan Zong-yi et al[1]. The rules of the alterations of E and micron were obtained. We also measured DI and (DI)or. It was found that E and micron increased greatly but DI and (DI)or decreased when the dose of neuraminidase and the time of treatment were increased. There was a contrary correlation between them. These data demonstrated that the increase of E and micron weakened the deformability and the ability of orientation of RBCs.

Animals↗

Effect of Cr(VI) exposure on sperm quality: human and animal studies.

The semen status of male workers occupationally exposed to hexavalent chromium(VI) was investigated. Sperm counts from exposed workers were 47.05+/-2.13 x 10(6)/ml and those from control group 88.96+/-3.40 x 10(6)/ml. Sperm motility decreased from 81.92+/-0.41% for the control group to 69.71+/-0.93% for the exposed workers. The levels of zinc, lactate dehydrogenase (LDH), and lactate dehydrogenase C4 isoenzyme (LDH-x) in seminal plasma for the exposed workers were 1.48+/-0.07 micromol/ml, 1.05+/-0.02 x 10(3) U, and 0.47+/-0.01 x 10(3) U, respectively, which were significantly lower than those of 5.72+/-0.15 micromol/ml, 1.49+/-0.02 x 10(3) U, and 0.78+/-0.15 x 10(3) U for the control group, respectively. Follicle stimulating hormone (FSH) (7.34+/-0.34 x 10(-3) IU/ml) in serum from the exposed workers was significantly higher than that (2.41+/-0.08 x 10(-3) IU/ml) from the control group. On the other hand, there were no significant differences in semen volume, semen liquefaction time, luteinizing hormone (LH) level in serum, and Cr concentration in both serum and seminal plasma between the exposed workers and the control group. Feeding Cr(VI) to rats significantly reduced the epididymal sperm counts from 87.40+/-3.85 x 10(6)/g epididymis in control group to 21.40+/-1.20 x 10(6)/g epididymis at a CrO(3) dose of 10 mg/kg body weight and to 17.48+/-1.04 x 10(6)/g epididymis at a CrO(3) dose of 20 mg/kg body weight. Exposure of rats to Cr(VI) also significantly increased the sperm abnormality from 2.75+/-0.06% in the control group to 6.68+/-0.32% in the exposed group at a CrO(3) dose of 10 mg/kg body and to 7.6+/-0.15% at a CrO(3) dose of 20 mg/kg body weight. In exposed rats, there was visible disruption in germ cell arrangement near the walls of the seminiferous tubules. The diameters of seminiferous tubules in exposed rats were smaller. These results suggest that occupational exposure to chromium(VI) leads to alteration of semen status and may affect the reproductive success of exposed workers.

Animals↗

Effect of ipratropium bromide on airway and pulmonary muscarinic receptors in a rat model of chronic obstructive pulmonary disease.

OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.

Animals↗

Effect of 60Co irradiation on characteristics of hemorheology in rabbits.

A high-dose (7 Gy) whole-body 60Co irradiation for a short period caused disturbances of hematopoietic function. A decrease in the hematocrit of the circulating blood lasted for about 15 days, thus forming an anemic animal model. We studied the influence of high-dose 60Co irradiation on hemorheologic parameters: percentage of reticulocytes, RBC deformability, sedimentation rate and plasma fibrinogen concentration in the rabbit. It was found that the plasma fibrinogen concentration increased to twice more than control level and that percentage of reticulocytes in circulation disappeared immediately after irradiation. The deformation index of RBCs in shear flow decreased from a value of 58% down to a value of 42% in the first two weeks and gradually returned to control levels about 40 days after 60Co irradiation. Our results showed that a short period of high-dose 60Co irradiation caused severe and relatively long-lasting damage of hematopoietic system in animals' body.

Animals↗

[Image analysis of airway remodeling and responsiveness in asthmatic guinea pig].

OBJECTIVE: To observe the mechanism of airway remodeling and changes of airway responsiveness in guinea pig model of asthma. METHODS: 40 guinea pigs were randomly divided into two groups: control (20) and asthmatic group (20). After incubating with different stimulus, bilateral lung tissue section were stained with HE. Using image analysis system to measure the airway internal perimeter, wall area, external perimeter, etc. and calculate percentage of muscle shortening (PMS) according to formula. RESULTS: (1) The airway wall thickness (WA/Pi) in asthmatic group and control group were (10.0 +/- 2.0) and (7.9 +/- 2.1) micrometer(2)/micrometer, respectively. The bronchial smooth muscle thickness in asthmatic group and control group were (4.8 +/- 1.5) and (3.1 +/- 2.0) micrometer(2)/micrometer, respectively. Both were statistically significant (P < 0.01). The number of bronchial smooth muscle nucleus in asthmatic group (0.012 3 +/- 0.002 7/micrometer) was higher compared with control (0.010 +/- 0.003/micrometer) (P < 0.05). (2) Responsiveness of airway smooth muscle to adenosine (represented by PMS) in asthmatic group and control were 0.34 +/- 0.07 and 0.29 +/- 0.08, respectively (P < 0.05). When combined with aminophyline, PMS in asthmatic group was 0.26 +/- 0.07. There was statistically significant difference when compared with adenosine alone (0.34 +/- 0.07) (P < 0.01). (3) PMS to acetylcholine in asthmatic group and control were 0.24 +/- 0.04 and 0.19 +/- 0.06, respectively (P < 0.05). When combined with heparin, PMS in asthmatic group was 0.20 +/- 0.04. There was statistically significant difference when compared with acetylcholine alone (0.24 +/- 0.04) (P < 0.05). CONCLUSIONS: The main reason of airway remodeling in asthma is due to bronchial smooth muscle hyperplasia. Aminophylline and heparin may inhibit the responsiveness of airway to adenosine and acetylcholine respectively.

Acetylcholine↗

[Study on the muscarinic receptor and its subtypes in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the M receptor and its subtypes in the lung tissue of patients with chronic obstructive pulmonary disease (COPD). METHODS: Muscarinic cholinergic receptors have been identified and characterized by radioligand binding assay in the lung tissue specimens of patients with COPD. Competitive binding experiments with pirenzepine and methoctramine were used to characterize muscarinic subtypes. RESULTS: The contents of M-receptor were (64 +/- 10), (42 +/- 18) fmol/mg. protein in normal group and COPD patients respectively. No significant difference was observed in antagonist affinity (K(D)) among normal group and COPD patients. The ratio of subtype M(1) was higher in COPD patients (67.2 +/- 2.7)% than in normal group (74.2 +/- 4.8)%, M(2) was lower [(29.3 +/- 1.7)% vs (16.8 +/- 4.4)%] and M(3) was higher [(3.6 +/- 2.9) % vs (9.3 +/- 4.1)%] respectively. CONCLUSION: The number of muscarinic cholinergic receptors is decreased in COPD patients, but the ratios of subtype M(1) and M(3) are increased and the subtype M(2) is decreased. The changes of the distribution of the subtypes of M-receptors is an important pathophysiologic change of COPD.

Female↗