Biomedical subjects

Jingbo Zhao

Publications and source records attributed to Jingbo Zhao.

At least 19 recordsLinked to original sources

PubMed2007

Biomechanical remodeling of the chronically obstructed Guinea pig small intestine.

Small intestinal obstruction is a frequently encountered clinical problem. To understand the mechanisms behind obstruction and the clinical consequences, data are needed on the relation between the morphologic and biomechanical remodeling that takes place in the intestinal wall during chronic obstruction. We sought to determine the effect of partial obstruction on mechanical and morphologic properties of the guinea pig small intestine. Partial obstruction was created surgically in 2 groups of animals living for 2 and 4 weeks. Controls were sham operated and lived for 4 weeks. A combined impedance planimetry-high-frequency ultrasound system was designed to measure the luminal cross-sectional area and wall thickness. These measures were used to compute the circumferential stress and strain of the excised intestinal segments. The incremental elastic modulus was obtained by using nonlinear fitting of the stress-strain curve. Histologic analysis and the measurements of total wall collagen were also performed. The luminal cross-sectional area, wall thickness, and elastic modulus in circumferential direction increased in a time-dependent manner proximal to the obstruction site (P < 0.01), whereas no differences in these parameters were found distal to the obstruction site (P > 0.25). The circumferential stress-strain curves of the proximal segments in 2- and 4-week groups shifted to the left, indicating the intestinal wall became stiffer. Histologic examination revealed a massive increase in the thickness of the muscle layer especially the circular smooth muscle layer (P < 0.05). The collagen content proximal to the obstruction site was significantly larger in the partially obstructed animals compared to controls (P < 0.05). No difference was found distal to the obstruction site. Strong correlation was found between the collagen content and the elastic modulus at stress levels of 70 kPa stress (P < 0.01) and 10 kPa (P < 0.05) proximal to the obstruction site suggesting that the alteration of collagen has great impact on the mechanical remodeling. The morphologic and biomechanical remodeling likely influence the function of the intestine affected by partial obstructed intestine.

Animals↗

PubMed2006

Manual pressure distension of the human saphenous vein changes its biomechanical properties-implication for coronary artery bypass grafting.

Patency rates of saphenous vein grafts following coronary artery bypass grafting (CABG) depend on multiple factors. Information regarding the impact of biomechanical properties of vein grafts on patency rates is not available. The objective of the present study was to evaluate whether uncontrolled manual pressure distension during routine preparation of the saphenous vein in CABG-induced changes in the biomechanical properties of the vein. The morphometric and stress-strain properties were studied in isolated segments of the saphenous vein from 12 patients undergoing elective CABG. Six segments were manually distended without pressure control and six were not distended. The mechanical test was performed as a ramp inflation using syringe pump. The vein dimensions were obtained from digitised images at different pressures as well as at the no-load and zero-stress states. The circumferences, the wall and lumen area, the wall thickness, and the outer diameter as function of the applied pressure were largest in the segments with uncontrolled manual distension compared to those without distension (P<0.05). The opening angle and the absolute value of the residual strains were lower (P<0.01) and the circumferential stress-strain curve shifted to the left, indicating the wall became stiffer with uncontrolled manual distension compared to those without distension (P<0.05). In conclusion, manual pressure distension changed the morphometric and biomechanical properties of the saphenous vein. The perspective is that studies on biomechanical properties on the saphenous vein may guide surgeons how to handle graft material without causing major changes of the biomechanical properties during harvesting and preparation.

Aged↗

PubMed2006

Longitudinal residual strain and stress-strain relationship in rat small intestine.

BACKGROUND: To obtain a more detailed description of the stress-free state of the intestinal wall, longitudinal residual strain measurements are needed. Furthermore, data on longitudinal stress-strain relations in visceral organs are scarce. The present study aims to investigate the longitudinal residual strain and the longitudinal stress-strain relationship in the rat small intestine. METHODS: The longitudinal zero-stress state was obtained by cutting tissue strips parallel to the longitudinal axis of the intestine. The longitudinal residual stress was characterized by a bending angle (unit: degrees per unit length and positive when bending outwards). Residual strain was computed from the change in dimensions between the zero-stress state and the no-load state. Longitudinal stresses and strains were computed from stretch experiments in the distal ileum at luminal pressures ranging from 0-4 cmH2O. RESULTS: Large morphometric variations were found between the duodenum and ileum with the largest wall thickness and wall area in the duodenum and the largest inner circumference and luminal area in the distal ileum (p < 0.001). The bending angle did not differ between the duodenum and ileum (p > 0.5). The longitudinal residual strain was tensile at the serosal surface and compressive at the mucosal surface. Hence, the neutral axis was approximately in the mid-wall. The longitudinal residual strain and the bending angle was not uniform around the intestinal circumference and had the highest values on the mesenteric sides (p < 0.001). The stress-strain curves fitted well to the mono-exponential function with determination coefficients above 0.96. The alpha constant increased with the pressure, indicating the intestinal wall became stiffer in longitudinal direction when pressurized. CONCLUSION: Large longitudinal residual strains reside in the small intestine and showed circumferential variation. This indicates that the tissue is not uniform and cannot be treated as a homogenous material. The longitudinal stiffness of the intestinal wall increased with luminal pressure. Longitudinal residual strains must be taken into account in studies of gastrointestinal biomechanical properties.

Animals↗

PubMed2006

The geometric configuration and morphometry of the rabbit oesophagus during luminal pressure loading.

The aim of the present study was to determine the geometric configuration and morphometric dimensions in the rabbit oesophagus during luminal pressure loading. The geometric configuration is of fundamental importance because it is related to stress and strain and determines the resistance to flow. The oesophagus was excised from rabbits, transferred to an organ bath and stretched to the in vivo length. Cannulas were inserted into both ends and each oesophagus was subjected to a luminal pressure up to 0, 1, 2, 5 and 10 cm H(2)O. After equilibrium was reached, the oesophagus was snap-frozen in liquid nitrogen. Sections were cut from five locations in the oesophagus and videotaped in the frozen state. Geometric and morphometric data including perimeter, circularities, area, thickness, buckles and strains in different layers were obtained from the video images. These variables did not show axial variation in the oesophagus. All variables changed as a function of the pressure. The whole wall thickness decreased as an inverse function of the pressure. The thickness decrease was mainly due to thinning of the submucosa and muscle. The number of buckles decreased from 4.05 +/- 0.34 at 0 cm H(2)O pressure to 0.07 +/- 0.07 at 10 cm H(2)O. Circumferential Green strain-pressure curves for the various layers all showed an exponential pattern. The curve obtained at the submucosa-muscle layer interface was located to the right of the other curves, indicating that the muscle layer was softest. The data obtained in this study will be useful for further modelling of the mechanics of the oesophagus.

Animals↗

PubMed2006

Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus.

Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed.

Autonomic Nervous System↗

PubMed2006

Three-dimensional surface model analysis in the gastrointestinal tract.

The biomechanical changes during functional loading and unloading of the human gastrointestinal (GI) tract are not fully understood. GI function is usually studied by introducing probes in the GI lumen. Computer modeling offers a promising alternative approach in this regard, with the additional ability to predict regional stresses and strains in inaccessible locations. The tension and stress distributions in the GI tract are related to distensibility (tension-strain relationship) and smooth muscle tone. More knowledge on the tension and stress on the GI tract are needed to improve diagnosis of patients with gastrointestinal disorders. A modeling framework that can be used to integrate the physiological, anatomical and medical knowledge of the GI system has recently been developed. The 3-D anatomical model was constructed from digital images using ultrasonography, computer tomography (CT) or magnetic resonance imaging (MRI). Different mathematical algorithms were developed for surface analysis based on thin-walled structure and the finite element method was applied for the mucosa-folded three layered esophageal model analysis. The tools may be useful for studying the geometry and biomechanical properties of these organs in health and disease. These studies will serve to test the structure-function hypothesis of geometrically complex organs.

Algorithms↗

PubMed2006

Biomechanical properties of the layered oesophagus and its remodelling in experimental type-1 diabetes.

Passive biomechanical properties in term of the stress-strain relationship and the shear modulus were studied in separated muscle layer and mucosa-submucosa layer in the oesophagus of normal and STZ (streptozotocin)-induced diabetic rats. The mucosa-submucosa and muscle layers were separated using microsurgery and studied in vitro using a self-developed test machine. Stepwise elongation and inflation plus continuous twist were applied to the samples. A constitutive equation based on a strain energy function was used for the stress-strain analysis. Five material constants were obtained for both layers. The mucosa-submucosa layer was significantly stiffer than the muscle layer in longitudinal, circumferential and circumferential-longitudinal shear direction. The mechanical constants of the oesophagus show that the oesophageal wall was anisotropic, the stiffness in the longitudinal direction was higher than in the circumferential direction in the intact oesophagus (P < 0.001) and in the muscle layer (P < 0.05). Diabetes-induced pronounced increase in the outer perimeter, inner perimeter and lumen area in both the muscle and mucosa-submucosa layer. The growth of the mucosa-submucosa layer (P < 0.001) was more pronounced than the muscle layer (P < 0.05). Furthermore, the circumferential stiffness of the mucosa-submucosa layer increased 28 days after STZ treatment. In conclusion, the oesophagus is a non-homogeneous anisotropic tube. Thus, the mechanical properties differed between layers as well as in different directions. Morphological and biomechanical remodelling is prominent in the diabetic oesophagus.

Animals↗

PubMed2005

Structure and function of the upstream promotor of the human Mafbx gene: the proximal upstream promotor modulates tissue-specificity.

Muscle loss has been linked to increased expression of an ubiquitin ligase termed muscle atrophy F-box (MAFbx), a nuclear protein involved in degradation of MyoD. To gain insights into mechanisms by which the human MAFbx gene is controlled, the structure of its upstream promotor were studied, and its expression in cultured cells was characterized. Expression of MAFbx was found only in cells of muscle lineage. A reporter gene controlled by 948 bases of human MAFbx upstream promotor displayed similar cell-type selectivity. MAFbx levels were greatly enhanced upon myogenic differentiation of C2C12 myoblasts, and differentiation markedly increased activity of a reporter gene constructed with 400 bp of upstream promotor from the MAFbx gene. The core promotor spanned approximately 160 bases beginning at -241 bp upstream of the first codon, included potential binding sites for MyoD and myogenin, and was highly conserved among mouse, rat, and humanMAFbx genes. The major transcription start site for the human MAFbx gene was 340 bases upstream of the ATG and was localized the highly conserved region of 140 bp. The findings indicate an important role for the immediate upstream promotor of the human MAFbx gene in mediating its developmental expression and tissue specificity.

Animals↗

PubMed2005

Three-dimensional geometry analysis of the stomach in type II diabetic GK rats.

AIMS/HYPOTHESIS: The stomach is affected in more than half of all diabetic patients. The present study aims to investigate 3D geometry, 3D tension distribution and the elasticity in the stomach and its non-glandular and glandular regions in five non-diabetic and five Goto-Kakizaki (GK) rats (type 2 diabetic model). METHODS: The stomachs were distended in vitro using a pressure range from 0 to 8 cm H2O. Gastric compliance curves, the surface principal radii of curvature, the surface tension, and circumferential and longitudinal deformation-pressure curves were calculated based on 3D non-diabetic and the diabetic stomach models. RESULTS: Diabetes lowered the gastric compliance in the non-glandular stomach and the whole stomach (P<0.02). The radii of curvature and tension distribution were non-homogeneous in both the diabetic and the non-diabetic stomach due to the complex geometry. Furthermore, diabetes increased the circumferential stiffness in the non-glandular part (P<0.001). CONCLUSIONS: The diabetic stomach exhibited lower material compliance not only in the proximal stomach but also in the entire stomach. The biomechanical properties differed between regions and in different directions in both the non-diabetic and the diabetic stomach. The changes due to diabetes may contribute to the delayed gastric emptying and the symptoms in diabetic patients.

Animals↗

PubMed2005

Differential effects of the organochlorine pesticide DDT and its metabolite p,p'-DDE on p-glycoprotein activity and expression.

1,1-Bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT) is an organochlorine pesticide. Its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethene (p,p'-DDE) is a persistent environmental contaminant and both compounds accumulate in animals. Because multidrug resistance transporters, such as p-glycoprotein, function as a defense against xenobiotic exposure, we analyzed the ability of DDT and p,p'-DDE to act as efflux modulators. Using a competitive intact cell assay based on the efflux of the fluorescent dye rhodamine 123, we found that DDT, but not p,p'-DDE, stimulated dye retention. Subsequent studies using verapamil as competitor suggested that DDT is a weak p-glycoprotein inhibitor. Further studies addressed the ability of DDT and p,p'-DDE to induce MDR1, the gene encoding p-glycoprotein. In HepG2 cells, we found that both compounds induced MDR1 by twofold to threefold. Similar results were observed in mouse liver after a single dose of p,p'-DDE, although some gender-specific induction differences were noted. By contrast, p,p'-DDE failed to induce MDR1 in HeLa cells, indicating some cell-specific effects for induction. Further expression studies demonstrated increased levels of the endoplasmic reticulum molecular chaperone, Bip, in response to DDT, but not p,p'-DDE. These results suggest that DDT, but not p,p'-DDE, induces an endoplasmic reticulum stress response.

Animals↗

PubMed2005

Regional surface geometry of the rat stomach based on three-dimensional curvature analysis.

A better understanding of gastric accommodation and gastric perception requires knowledge of regional gastric geometry and local gastric tension throughout the stomach. An analytic method based on medical imaging data was developed in this study to describe the three-dimensional (3D) rat stomach geometry and tension distribution. The surface principal radii of curvatures were simulated and the surface tension was calculated in the glandular and non-glandular region of the stomach at pressures from 0 Pa to 800 Pa. The radii of curvature and tension distribution in the stomach were non-homogeneous. The radii of curvature in the glandular stomach were larger than those in the non-glandular region at pressures less than 100 Pa (P < 0.001). When the pressure increased to more than 200 Pa, the radii of curvature in the non-glandular stomach was larger than in the glandular stomach (P < 0.05). The curvature and tension distribution mapping using medical imaging technology and 3D models can be used to characterize and distinguish the physical behaviour in separate regions of the stomach.

Anatomy, Cross-Sectional↗

PubMed2005

The effect of digestion of collagen and elastin on histomorphometry and the zero-stress state in rat esophagus.

To understand the physiology and pathology of the esophagus, it is necessary to know the mechanical properties and their dependence on the structural components. The aim of this study was to investigate the effect of collagenase and elastase on the morphological and biomechanical properties in the no-load and zero-stress states in the rat esophagus. Twenty tissue rings from each esophagus of seven normal rats were sectioned in an organ bath containing calcium-free Krebs solution with dextran and EGTA. After the rings were photographed in the no-load state, 8 of the 20 rings were separated into mucosa-submucosa and muscle rings and the rings were transferred to four different solutions containing collagenase, elastase, or corresponding control solutions. The rings were cut radially to obtain the zero-stress state and photographed again. The thickness, area, and opening angle were measured from the digitized images. The collagen and elastin area fractions were determined from histological slides with Van Gieson and Weigert's elastic stain. The opening angles and residual strain did not differ in the nonseparated enzyme-treated rings and control rings. However, in the separated mucosa-submucosa ring the opening angle was significantly smaller after treatment than that in control rings (P < 0.01). Collagenase and elastase reduced collagen and elastin in the mucosa-submucosa layer about 40% in the nonseparated wall and 54% in the separated mucosa-submucosa layer (P < 0.01). Collagenase and elastase increased the thickness in the separated mucosa-submucosa layer compared to the control (P < 0.05). Disconnection between the epithelia and the lamina propria was histologically observed after elastase digestion. In conclusion, collagenase and elastase caused the opening angle and the residual strain in the separated mucosa-submucosa layer to decrease. The opening angle of the separated mucosa-submucosa layer depended to some extent on the fraction of collagen and elastin.

Animals↗

PubMed2005

Small intestinal morphometric and biomechanical changes during physiological growth in rats.

Changes in small intestinal geometry, residual strain and stress-strain properties during physiological growth were studied in rats ranging from 1 to 32 weeks of age. Small intestinal mass and dimensions increased many-fold with age, e.g. the weight per unit length increased five-fold with age and the wall cross-sectional area increased four-fold. The opening angle of duodenum obtained at zero-stress state was approximately 220 degrees and 290 degrees during the first and second week after birth and decreased to 170 degrees at other ages (p < 0.005). The opening angle of ileum ranged between 120 degrees and 150 degrees . The residual strain of duodenum at the mucosal surface did not vary with age (p > 0.05) whereas the residual strain of ileum at the mucosal surface decreased with age (p < 0.001). The circumferential and longitudinal stress-strain curves fitted well to a mono-exponential function. At a given circumferential stress, the corresponding strain values increased during the first 8 weeks of age (p < 0.05) where after no further change was observed. Hence, the small intestine became more compliant during early life. At a given longitudinal stress, the corresponding strains of ileum and duodenum became larger during the first 2-4 weeks of age (p < 0.05) where after no further change was observed. The small intestine was stiffer in longitudinal direction compared to the circumferential direction. In conclusion, pronounced morphometric and biomechanical changes were observed in the rat small intestine during physiological growth. Such data may prove useful in the understanding of the functional changes of the digestive tract during early life.

Age Factors↗

PubMed2004

Quantitative analysis of collagen fiber angle in the submucosa of small intestine.

It is of interest to know how distension changes the angle and content of collagen in the submucosa of small intestine. We describe the application of a two-dimensional quantitative analysis technology to determine the angles between collagen fibers in the submucosa using digital image processing. A polarization microscope was used to obtain a series of animal intestinal slice images. The images were studied by analyzing the relationship between the pixel values of each of the polarized angles to obtain the collagen fiber angle. The statistical distribution of the angle as function of the degree of distension can be analyzed.

Animals↗

PubMed2004

Two-layered quasi-3D finite element model of the oesophagus.

Analysis of oesophageal mechanoreceptor-dependent responses requires knowledge about the distribution of stresses and strains in the layers of the organ. A two-layered and a one-layered quasi-3D finite element model of the rat oesophagus were used for simulation. An exponential pseudo-strain energy density function was used as the constitutive equation in each model. Stress and strain distributions at the distension pressures 0.25 and 1.0 kPa were studied. The stress and strain distributions depended on the wall geometry. In the one-layered model, the stress ranged from -0.24 to 0.38 kPa at a pressure of 0.25 kPa and from -0.67 to 2.57 kPa at a pressure of 1.0 kPa. The stress in the two-layered model at the pressure of 0.25 and 1.0 kPa varied from -0.52 to 0.64 kPa and from -1.38 to 3.84 kPa. In the two-layered model, the stress was discontinuous at the interface between the muscle layer and the mucosa-submucosa layer. The maximum stress jump was 1.67 kPa at the pressure of 1.0 kPa. The present study provides a numerical simulation tool for characterising the mechanical behaviour of a multi-layered, complex geometry organ.

Animals↗

PubMed2004

Oxandrolone blocks glucocorticoid signaling in an androgen receptor-dependent manner.

The anabolic steroid oxandrolone is increasingly used to preserve or restore muscle mass in those with HIV infection or serious burns. These effects are mediated, in part, by the androgen receptor (AR). Anti-glucocorticoid effects have also been reported for some anabolic steroids, and the goal of our studies was to determine whether oxandrolone had a similar mechanism of action. Studies with in vitro translated glucocorticoid receptor (GR), however, showed no inhibition of cortisol binding by oxandrolone. Conversely, experiments in cell culture systems demonstrated significant antagonism of cortisol-induced transcriptional activation by oxandrolone in cells expressing both the AR and GR. Inhibition was not overcome by increased cortisol concentration, and no inhibition by oxandrolone was observed in cells expressing GR alone, confirming that non-competitive mechanisms were involved. AR-dependent repression of transcriptional activation by oxandrolone was also observed with the synthetic glucocorticoids dexamethasone and methylprednisolone. Furthermore, the AR antagonists 2-hydroxyflutamide and DDE also repressed GR transactivation in an AR-dependent manner. A mutant AR lacking a functional nuclear localization signal (AR(4RKM)) was active in oxandrolone-mediated repression of GR even though oxandrolone-bound AR(4RKM) failed to enter the nucleus and did not affect nuclear import of GR. These data indicate a novel action of oxandrolone to suppress glucocorticoid action via crosstalk between AR and GR.

Androgens↗

PubMed2004

Physiological growth is associated with esophageal morphometric and biomechanical changes in rats.

Esophageal geometry and biomechanical changes were studied during physiological growth in rats aged 1-32 weeks. Histological examination was done after the biomechanical study. The esophageal dimensions increased many-fold from 1-32 weeks, e.g. the weight per unit length increased six-fold and the wall cross-sectional area increased eight-fold. The inner and outer circumferential length of the mucosa and muscle, and the thickness and area of the layers increased as function of age. The opening angle was approximately 140 degrees at age 1 and 2 weeks and gradually decreased to approximately 80 degrees after 16 weeks. The circumferential and longitudinal stress-strain curves were exponential. The circumferential stress-strain curves shifted from left to the right up to 4 weeks of age (P < 0.001) where after no further change was observed, i.e. the esophagus became more compliant during the first 4 weeks of life. The longitudinal stress-strain curves shifted from left to the right up to 16 weeks of age (P < 0.001), i.e. the esophagus became more compliant longitudinally during the first 16 weeks of life. Bi-axial stress-strain analysis with determination of mechanical tissue constants showed that the esophagus was stiffer in the longitudinal direction than in the circumferential direction. In conclusion, a pronounced morphometric and biomechanical remodelling was observed in the rat esophagus during physiological growth. The observed changes likely reflect the development of the physiological function of the esophagus since for other tissues the function dictates the form of the tissue, and growth and remodelling depend on the mechanical loading.

Animals↗

PubMed2004

Shear modulus of elasticity of the esophagus.

Experimental and diagnostic procedures like distension of a balloon catheter, bougie, and esophagogastroduodenoscopy can induce shear deformation in the esophageal wall. However, the shear modulus of the esophagus is yet unknown. The aim of this study was to determine the esophageal shear modulus and its dependence on the circumferential and longitudinal stresses and strains in the rat. The constitutive equation including the shear deformation based on a pseudo-strain-energy function was generated. Results were obtained using a new triaxial instrument to perform simultaneous torsion, inflation, and longitudinal stretching tests. The shear modulus varied with the inflation pressure and the longitudinal stretch ratio. The shear modulus at the longitudinal stretch ratio of 1.5 and between inflation pressures of 0 and 2.0 kPa ranged from 5.43 to 185.01 kPa. The mechanical constant of the esophagus showed that the esophageal wall was anisotropic with different stiffness in the circumferential, longitudinal, and the shear directions. The stiffness in the longitudinal direction was higher than in the circumferential direction (P < 0.001). This test can be extended for further mechanical remodeling experiments and for other tubular organs such as the small intestine or blood vessels.

Animals↗