Effects of alprostadil in β-aminopropanitrile induced aortic dissection in a murine model / 中华心血管病杂志

Objective: To investigate the protective role of alprostadil on aortic dissection. Methods: 26 C57BL6 male mice were divided into control group (normal drinking water, n=13) and model group (1 g·kg-1·d-1 BAPN via drinking water, n=13). On day 14, mRNA expression of inflammatory-related genes as well as EP receptor families were detected by RT-PCR (n=6 each) and EP4 protein levels were determined by Western blot (n=7 each). Another 88 mice were divided into 3 groups: control group (n=22), model group (n=33) and treatment group (n=33). The mice in model group and treatment group were applied with BAPN (1 g·kg-1·d-1) via drinking water. The mice in treatment group received additional intraperitoneal injection with alprostadil (80 μg·kg-1·d-1) for 28 days. The mice in the control and model group received equal volume intraperitoneal injection with 0.9% saline respectively. The body weight and systolic blood pressure, the mortality and morbidity were monitored from the beginning until the designed end of the study. On day 28, the mice were sacrificed and aorta were fixed, embedded and sliced, followed by staining with HE and Victoria Blue. The distribution of EP4 was determined by immunohistochemistry in control (n=6) and model group (n=6). Furthermore, the concentration of PGE1 were tested among model (n=3) and treatment group (n=4). EP4 protein expression was determined in model group (n=7) and treatment group (n=6). Results: On day 14, mRNA expression level of MCP-1 ((2.74±1.55) vs. (1.00±0.49),<0.05) and MMP2((1.38±0.42) vs. (1.00±0.27), P<0.05) was significantly upregulated in model group compared with control group. Protein expression of EP4 receptor also increased in aorta in model group compared with control group (1.48±0.51 vs. 1.00±0.19, P<0.05). In the dissection area, the EP4 expression was also enriched compared with non-dissection area, particularly in endothelial cells and inflammatory cells on day 28. BAPN applied in drinking water (model and treatment groups) successfully induced the aortic dissection in mice, some mice died of the rupture. The elastic fibers were fractured, and the infiltrated immune cells were visible in dissected tissue. False lumen was formed. There was no dissection and death in the control group. Compared with control group, the morbidity and mortality rates were significantly increased in the model group (60.6%, 20/33, 30.3%, 10/33) and the treatment group (72.7%, 24/33, 24.2%, 8/33). The mortality and morbidity rates were similar between model and treatment groups. There is no difference in terms of SBP among three groups (P>0.05). Further study showed that after alprostadil injection, the blood concentration of PGE1 was increased in treatment group ((0.540±0.041 vs. 0.436±0.012)μmol/L, P<0.05). Besides, the EP4 receptor expression was downregulated in the treatment group compared to model group (0.60±0.30 vs. 1.00±0.20, P<0.05). Conclusion: EP4 expression is upregulated in BAPN induced aortic dissection mouse model. No protective effects are observed post alprostadil treatment in this model probably due to the reduced expression of EP4.

Biomechanical properties study of aorta in β-aminopropionitrile-induced rat model / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate thoracic aortic longitudinal elastic strength in β-aminopropionitrile (BAPN) treated rat model of aortic dissection (AD).</p><p><b>METHODS</b>Twenty-nine young rats (Sprague-Dawley) were divided into tow groups, control group (n = 12) and BAPN group (n = 17). Seventeen rats were treated with 0.25% BAPN mixed in feed for 6 weeks. All the rats were sacrificed in the end of experiment and aorta was harvested for biomechanical and pathological study. Longitudinal elastic strength and stress were detected and analyzed by material testing machine. Elasticity modulus as well as maximum stretching length, draw ratio, maximum load, maximum strength, and maximum extensibility was calculated according to the analysis with thickness and area of aortic media.</p><p><b>RESULTS</b>Nine BAPN-treated rats died of aortic dissecting aneurysm rupture during the experiment. The diameter of the aneurysms was (6.33 ± 1.17) mm and the length was (9 ± 5) mm. The maximum diameter significantly increased in BAPN-induced rats with AD (group B2) compared with without AD (group B1) and control group ((6.49 ± 1.20) mm vs. (1.45 ± 0.11), (1.25 ± 0.26); F = 165.257, P = 0.001 and 0.000, respectively), but there was no significance between group B1 and control group (P = 0.108). Thickness and area of aortic media in BAPN-induced rats significantly increased compared with control group (F = 27.277 and 27.153, P = 0.000 and 0.000, respectively), but there was no significance of area between group B1 and B2 (P = 0.540). Maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus were significantly decreased from group B2, group B1 to control group (P < 0.01, respectively).</p><p><b>CONCLUSIONS</b>This study built a successful model of AD. Biomechanical analysis and the decrease of maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus may explain the formation of AD partly.</p>

Effect of lysyl oxidase on migration and adhesion of human gastric cancer HGC-27 cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effects of lysyl oxidase (LOX) on the migration and adhesion of the human gastric cancer cell line HGC-27 cells in vitro.</p><p><b>METHODS</b>The human gastric cancer cell line HGC-27 cells were cultured in vitro, and treated with different concentration of β-aminopropionitrile (BAPN). The ability of migration was assessed by wound-healing assay. The ability of adhesion was detected by homogenous and heterogeneous adhesion experiments.</p><p><b>RESULTS</b>Compared that with 0 mmol/L BAPN, the ability of migration of the cells after treatment with 0.2 mmol/L BAPN was descended at 8, 24, 32 and 48 h; the number of cells with homogeneous adhesion was increased from (6.97 ± 0.07) × 10(3)/ml to (7.78 ± 0.11) × 10(3)/ml; and the number of cells with heterogeneous adhesion was decreased from (8.98 ± 0.15) × 10(3)/ml to (8.35 ± 0.10) × 10(3)/ml, both < 0.05. Compared with that of cells treated with 0 mmol/L and 0.2 mmol/L BAPN, the migration ability of cells after treatment with 0.3 mmol/L BAPN was descended at 8, 24, 32 and 48 h; the number of cells with homogeneous adhesion was raised to (8.02 ± 0.11) × 10(3)/ml and the number of cells with heterogeneous adhesion was down to (7.93 ± 0.07) × 10(3)/ml (P < 0.05).</p><p><b>CONCLUSION</b>LOX may promote the metastasis of cancer cells by enhancing invasion, increasing heterogeneous adhesion and decreasing homogeneous adhesion.</p>

Periodontal & systemic bone changes in rats with experimental lathyrism.

BACKGROUND & OBJECTIVE: It is not clear how lathyrism affects the systemic bone metabolism. We therefore undertook a study to observe periodontal and systemic bone changes by performing radiological, metabolic, and bone densitometric evaluations in rats with experimental lathyrism. METHODS: A total of 30 rats were used. Experimental lathyrism was induced by once daily subcutaneous administration of beta-aminopropionitrile (beta-APN), at a dose of 5 mg beta-APN/0.4 ml per 100 g of body weight for 40 days. After 40 days, vertebral bone mineral density was analyzed by means of dual energy X-ray absorbtiometry in both groups. Blood was drawn by cardiac puncture and the animals were decapitated. Serum calcium levels were measured. Right mandibles were removed and radiographs were obtained. Alveolar bone level was determined in the radiographs. RESULTS: In all lathyritic rats, alveolar bone level was pathologically decreased with visible resorption. Vertebral bone mineral density values of lathyritic rats did not differ significantly from those of the control group. Compared to controls, there was a statistically significant decrease in serum calcium levels in the lathyritic group (P<0.001). INTERPRETATION & CONCLUSION: Significant alveolar bone resorption without alterations in vertebral bone mineral density indicated that lathyrogen administration for 40 days presumably has not caused systemic demineralization. This model could be used for studying the role of local and systemic agents on periodontal alveolar bone resorption.

Tuberculous Pneumonia and Bacterial Pneumonia in Diabetic Patients: Comparison of CT Findings

PURPOSE: To compare the CT findings of tuberculous pneumonia (TBPN) with those of bacterial pneumonia (BAPN) in diabetic patients and to evaluate the usefulness of CT in the differential diagnosis of these two diseases. MATERIALS AND METHODS: The chest CT scans of 23 diabetic patients with TBPN (M:F=21:2; mean age, 59 yrs.) and of 37 diabetic patients with BAPN (M:F=21:16; mean age, 63 yrs.) were evaluated by two radiologists with regard to low attenuation areas in regions of consolidation, cavities, air bronchogram, volume changes, ground-glass attenuation, findings of bronchogenic spread, and other associated findings. The involvement of each segment was recorded in all patients. RESULTS:The frequencies of multiple small low-attenuation areas in regions of consolidation (52%, 0%), multiple cavities (35%, 3%), loss of volume (70%, 30%) and findings of bronchogenic spread (96%, 30%) were significantly higher in TBPN than in BAPN (p<.05). Low-attenuation masses and bizarre-shaped cavities were noted only in TBPN. Large areas of ground-glass attenuation (4%, 38%) and bilateral pleural effusions (0%, 19%) were more common in BAPN, while air-bronchogram was common in both groups (96%, 86%). The involvement of the superior segment was significantly more common in TBPN (p<.05). CONCLUSION: In the diabetic patients with pulmonary consolidation, CT findings of multiple small low-attenuation areas, multiple cavities, bizarre-shaped cavities, low attenuation masses in cavities, volume loss, and findings of bronchogenic spread are more suggestive of TBPN, while large areas of ground-glass attenuation and bilateral pleural effusions are more suggestive of BAPN. CT may be useful in the differential diagnosis between TBPN and BAPN.

EFFECTS OF BONE MORPHOGENETIC PROTEIN ON THE HEALING OF PERIODONTIUM AFTER TOOTH REPLANTATION OF THE RAT / 대한치주과학회지

The purpose of this study is to evaluate the influences of the bone morphogenetic protein (BMP) on the healing of periodontal ligament and alveolar bone after replantation of tooth, and to examine the possibility of its clinical application. 45 Sprague Dawley rats weighted about 100 gram were divided into 3 experimental groups by different dose of BMP. All the upper right and left 1st molar were extracted after 5 days feeding of 0.4% beta-aminopropionitrile, and right molar were used as experimental group and left molar were used as control group. The root surface of experimental molar were treated with 25, 50 and 100ng/ml of human recombinant Bone morphogenetic protein-4 (rh-BMP-4) with micropipet, and 1M Sodium hypochloride were used on control root surface. All the experimental animals were sacrificed as 1, 2, 4, 7 and 14 days after autoreplantation of upper 1st molar into their own position. The maxilla were disected included both side of 1st molar. The collected tissue were processed from demineralization to paraffin embeding as usual procedure, and the specimens were prepared with Hematoxylin-Eosin stain for the light microscopic evaluation. The results of this study were as follows : 1. There was no significant differences between control and experimental site on 1 and 2 days after replantation of tooth. In the case of 4th days, the evidence of tissue regeneration were observed on experimental site to compare the controls. New osteoid were revealed on high concentration of BMP at 7 days after replantation, and it became more obvious at 14 days. 2. The effect of the rh-BMP-4 coated on root surface was revealed slight influences for the prolifertion of cells of periodontium and tissue regeneration as dose-dependent pattern. 3. Bony ankylosis was observed between alveolar bone and root surface due to the remarkable amount of osteoid formation on the 14 days after replantation of root. In the conclusion, it was suggested that topical application of the rhBMP-4 on the root surface has influence on the periodontal ligament and alveolar bone. The application method of BMP on the root should be designed with calculation of proper concentration.

A STUDY OF TGF-Beta EXPRESSION DURING PALATOGENESIS IN RATS WITH CLEFT PALATE INDUCED BY BAPN

A study of TGF-beta expression patterns in cleft palate formed rats induced by BAPN / 대한치과교정학회지

Cleft palate has been studied with epidemiologic and molecular methods, and many etiologic factors have been examined closely. Among the research methods, biologic molecule research has been the most important method for cleft palate formation study. The TGF-beta played an important role in cell migration, epithelial-mesenchymal transdifferentiation, extracellular matrix synthesis and deposition. But there was not much research on the correlation cleft palate induced by beta-aminonitroproprionitrile(BAPN) and TGF-beta expression. The purpose of the present study was to examine how TGF-beta is expressed in cleft palate rats. 4 Timed-pregnant Sprague-Dawley rats were obtained on the 10th gestation day. On the 13th day of gestation, BAPN-monofumarate salts ((C3H6N2)2.C4H4O4) were individually, orally administered to 3 pregnant rats at a ratio of 1g/kg body weight. And 4 pregnant rats were sacrificed on day 20 post coitus (p.c.). The TGF-beta expression in the cleft formed rats fetuses showed the following patterns : 1. Osteoblast and mesenchymal cells of the cleft palate rats were of low expression compared with those of the control rats. 2. The cleft palate rats didn't show any difference in the TGF-beta expression of osteocyte from the control rats. 3. In western blot analysis, the thickness of band of TGF-beta in the cleft palate rats was thinner and more diluted than that of the control rats.

Impact of antifibrotic treatment on the course of Schistosoma mansoni infection in murime model

Administration of an antifibrotic agent as an adjunct to antihelmintic treatment with the objective of morbidity reduction was investigated in the nurine schistosomiasis mansoni model. Antifibrotic, ß-aminopropionitrile treatment has a profound effect on the cellular composition of the liver granuloma of Schistosoma mansoni infected mice when given alone, resulting in increase macrophage infiltration. These macrophages, in response to stimulation with soluble egg antigen or lipopolysaccharide produced elevated levels of nitric oxide but low levels of tumor necrosis factor alpha compared to untreated infected mice. This also correlated with reduced liver granuloma size. In spite of low numbers of eggs in the liver, mice receiving a combine treatment had a high level of resistance to a challenge infection compared with mice receiving only praziquantel. Those mice also exhibited a reduced lymphocyte proliferative response, similar to that of infected untreated mice. Antifibrotic treatment has an impact on the dynamic of the cellular nature of granulomas and impacts on the host immunity to infection.

Experimental Study on the Adhesion of the Flexor Tendon in Chickens / 대한정형외과학회잡지

Peritendinous adhesions which develop in the flexor tendons of the digits after injury or operation are still a major problem in the surgery of the hand. The adhesions that are part of the healing process constitute an almost inevitable functional disability during the biological response of the tissue to injury. To achive better gliding function of flexor tendons, continuous efforts are being made to reduce peritendinous adhesions without adversely affecting the healing process itself. To reduce peritendinous adhesions, an aqueous solution of beta-aminopropionitrile (BAPN) was added to a solution of enriched native collagen (E.C.S.) and applied to the cut tendons of one group: untreated controls and controls treated with collagen solution alone comprised the other groups. Chickens from each group were sacrificed one, three and five weeks after operation. Tn he results were evaluated grossly and pathologically. The results of this experiment were as follows. 1. The collagen solution alone had the same lathylogenic effect as the beta-aminopropionitrile. 2. There were no systemic complications with beta-aminopropionitrile. 3. The beta-aminopropionitrile collagen solutions had the adverse effect on the tendon healings.

A study on the metabolic alteration of periodontal tissue on orthodontic tooth movement in rats / 대한치과교정학회지

in the present study orthodontic force was applied to the molars of control group and experimental group treated with the lathyrogen beta-aminopropionitrile (BAPN). Observation resulted in the following conclusions; 1) New alveolar bone formation in response to orthodontic force in BAPN-treated rats exceeded corresponding bone formation in control group when measured at two tension sites in the periodontal ligament. 2) BAPN administration produced disorganization of the collagenous fibers of the periodontium of experimental group. Multiple eosinophilic cell-free areas were found distributed throughout the radicular portions of affected periodontal ligaments. 3) The areas of periodontium surrounding orthodontically treated teeth exhibited relatively normal organization under these conditions, while the periodontium of adjacent nonorthodontically treated teeth was disorganized. 4) The present results suggest that the typical histologic response to orthodontic force application can occur in the presence of a chemically and physically altered periodontium.