OBJECTIVETo compare the angiogenesis in unstable and stable plaques and to investigate the potential role of neovessels in creating vulnerable sites for atherosclerotic plaques.

METHODSSpecimens of coronary arteries were obtained from 52 autopsy cases with acute coronary syndromes. Plaque morphology was studied by use of stained slides. 922 tissue blocks of late-stage lesions were classified into two groups: (1) unstable plaque (n = 153), the plaque was characterized by a large extracellular lipid core (more than 40% of the plaque area); (2) stable plaque (n = 769), lipid core less than 40% of the plaque area. Forty blocks were selected randomly from each group and serial sections were stained immunohistochemically with a polyclonal antibody against F VIII RAg. Computer-aided planimeter was used for quantitative analysis.

RESULTSIn unstable plaques, the occurrence of neovessels was more frequent and the neovessel density (number/mm(2)) was significantly increased as compared to that of stable plaques (frequency: 80.4% vs 66.6%, P < 0.01; shoulder: 22.16 +/- 19.96 vs 10.04 +/- 11.52, base: 21.68 +/- 20.44 vs 9.68 +/- 11.52, fibrous cap: 3.80 +/- 5.32 vs 1.48 +/- 2.28, P < 0.05). Most neovessels were located in the shoulder region and at the base of plaques.

CONCLUSIONSThese findings suggest that neovessels in coronary atherosclerotic plaques are closely associated with the decreased stabilization of the plaques.

Aged ; Aged, 80 and over ; Coronary Artery Disease ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Male ; Neovascularization, Pathologic ; pathology

OBJECTIVESTo analyze the relationship between oxidized low density lipoprotein (oxLDL), angiogenesis and stabilization of atherosclerotic plaques in human coronary arteries; and to investigate the role of oxLDL in creating vulnerable sites in atherosclerotic plaques.

METHODSSamples of coronary arteries were obtained at autopsies of 42 patients with acute coronary syndrome. Eighty randomly selected blocks were studied by immunohistochemistry using antibodies against oxLDL and endothelial cells (factor VIII). Computer-aided planimeter was used for quantitative analysis.

RESULTSIn unstable plaques, percentage of immunoreactive areas for oxLDL was significantly higher than that in stable plaques. Most of the oxLDL were located in shoulder region of these plaques, as compared to the fibrous cap and basal regions. The details of distribution of oxLDL were as follows: shoulder region (20.43 +/- 3.12 for unstable plaques and 17.65 +/- 4.22 for stable plaques), fibrous cap (4.77 +/- 2.03 for unstable plaque and 2.80 +/- 0.22 for stable plaques) and basal region (5.65 +/- 1.65 for unstable plaques and 3.22 +/- 1.02 for unstable plaques). OxLDL was also a main component in the lipid core. In the shoulder region, there was a significant positive correlation between neovascularization and oxLDL (r = 0.8247, P = 0.000).

CONCLUSIONSThe amount of oxLDL is significantly higher in unstable atherosclerotic plaques, especially over the shoulder region. OxLDL in coronary atherosclerotic plaques is thus an important factor in determining stabilization of the plaques. OxLDL may induce influx of inflammatory cells which subsequently leads to decreased plaque stabilization.

Angina, Unstable ; metabolism ; pathology ; Coronary Artery Disease ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Lipoproteins, LDL ; metabolism ; Myocardial Infarction ; metabolism ; pathology ; Neovascularization, Pathologic ; metabolism ; pathology

Objective To study the influence on the metabolism of Pu-erarin on the pharmacokinetics of glipizide capsule in healthy and diabetic rabbits.Methods Healthy New Zealand rabbits randomly assigned , one group was modeled , each group had 5 rabbits.Glipizide (5 mg) was taken orally once to every rabbit.After 2 weeks of clearing stage, Puerarin (18 mg· kg -1) was administered daily by auricular vein injection qd for 3 d, then glipizide was taken orally at the same dosage on the 4 d.The blood was drawn from ear vein before and after administe-ring glipizide in every rabbit.Then the blood concentration of glipizide was measured by HPLC.The pharmacokinetic parameter was calculated with pharmacokinetic software DAS 2.0.The pharmacokinetics of glipiz-ide in rabbits administered with or without Puerarin were analyzed by auto-control.Results The concentration time -curves were fit to the one-compartment model.In healthy group , administered with Puerarin , the t1/2 were (4.2 ±0.5),(3.58 ±0.7) h,ρmax were (15.5 ±0.8), (8.4 ±0.6 ) mg· L-1 , AUC0-35 were ( 134.8 ±0.7 ) , ( 77.2 ±1.4 ) mg· h· L -1; respectively before and after.In diabetic group , t1/2 were (7.6 ±0.9),(5.6 ±0.9) h,ρmax were (13.4 ±0.8),(10.6 ±0.9) mg· L-1,AUC0-35 were (10.5 ±0.8),(7.7 ±1.6) mg· h· L-1 respectively before and after.There were notable differences on t1/2 ,ρmax , AUC values of glipizide in rabbits administered with or without Puerarin ( P <0.05 ).Conclusion Puerarin shows significant impact on the pharmacokinetics of glipizide.

OBJECTIVETo investigate the influence of ICAM-1 469K/E gene polymorphisms on the risk of atrophic gastritis and dysplasia.

METHODSThe ICAM-1 469K/E gene polymorphisms in a total of 372 subjects were detected by polymerase chain reaction-direct sequencing. All of the subjects were from Linqu County, a high risk area of gastric cancer in Shandong Province of northern China. All cases were initially diagnosed as normal or superficial gastritis at the beginning of this study. After a 5-year follow-up, the cases were subdivided into no progression group (no histological progression, n=137), progression group I (progressed to severe chronic atrophic gastritis, n=194) and progression group II (progressed to low-grade dysplasia, n=41).

RESULTSIn all 372 subjects, the frequencies of KK, KE or EE genotype of ICAM-1 K469E were 50.5%, 39.2% and 10.2%, respectively. No significant differences were observed in the ICAM-1 469K/E genotype frequencies between the progression group I and no progression group (P>0.05). The frequencies of KK genotype (68.3%) were significantly higher in the progression group II than in the no progression group (49.6%, P=0.035), and also than in the progression group I (47.4%, P=0.015). An increased risk of the progressing to dysplasia from normal or superficial gastritis was found in the individuals with ICAM-1 469KK genotype [odds ratio (OR)=2.21, 95%CI, 1.10-4.42].

CONCLUSIONICAM-1 469K/E gene polymorphisms are significantly associated with the risk of gastric low-grade dysplasia, but not related with severe chronic atrophic gastritis in a population with high risk of gastric cancer in Linqu County, Shandong Province, China.

Adult ; Female ; Follow-Up Studies ; Gastritis ; genetics ; pathology ; Gastritis, Atrophic ; genetics ; pathology ; Genotype ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Genetic ; Precancerous Conditions ; genetics ; pathology ; Risk ; Stomach Neoplasms ; genetics ; pathology

A randomized crossover study was performed to compare the effects of low glycemic index diets (LGI)and high glycemic index diets(HGI)on blood glucose,lipid profile and control of body weight in patients with type 2 diabetes.Compared with HGI group,the fasting serum insulin,Homa-IR,LDL-C and body weight significantly decreased in LGI group(P

BACKGROUNDChromosome 13q14 deletion (del13q14), chromosome 1q21 gain (amp1q21) and chromosome 17p13 deletion (del17p13) are the most frequent chromosomal aberrations in multiple myeloma (MM). They play an important role in prognosis. The aim of this study was to investigate the clinical significance of the chromosomal changes in Chinese MM patients.

METHODSInterphase fluorescence in situ hybridization (FISH) on bone marrow (BM) cells was performed in 72 enrolled MM patients. Relationships between chromosomal abnormalities and clinical features, response to therapies and prognosis were analyzed.

RESULTSAs a result of interphase FISH, 77.8% (56/72) patients had chromosome changes. The incidences of each probe were RB1 51.4% (37/72), D13S319 47.2% (34/72), 1q21 45.8% (33/72) and p53 22.2% (12/72). Osteolytic lesion, BM plasma cells index, serum calcium and serum M component were significantly correlated to del13q14. BM plasma cells and hemoglobin were correlated to amp1q21. Serum lactate dehydrogenase (LDH) was correlated with del17p13. Patients with del13q14 treated with bortezomib had a notably higher overall response rate than the patients treated with traditional chemotherapies (93% vs. 65%, P = 0.048). Patients carrying amp1q21 or/and del17p13 did not achieve satisfactory response to bortezomib. The median progression-free survival (PFS) for patients with amp1q21 was 5 months and patients without amp1q21 got 9-month PFS (P = 0.001). The median PFS for patients with del13q14 was 5 months (vs. 8 months, P = 0.026). The median PFS for patients with del17p13 was 3 months (vs. 8 months, P = 0.002). Patients with β(2)-microglobulin > 5.5 mg/L also had a worse outcome, whose median PFS was 5 months (vs. 8 months, P = 0.016).

CONCLUSIONSThe prevalence of chromosomal abnormalities of MM patients was similar in Chinese and Caucasian people. Genetic changes were associated with patients' responses to therapies and prognosis.

Adult ; Aged ; Asian Continental Ancestry Group ; Chromosome Aberrations ; Chromosome Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Interphase ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; genetics ; Prognosis

BACKGROUNDEnamel demineralization occurs frequently during orthodontic treatment. In this study, we evaluated the changes of the density of mutans streptococcus (MS) in plaque after bracket bonding and using fluoride adhesive on maxillary incisors by real time fluorescence-quantitative polymerase chain reaction (RT-FQ PCR).

METHODSThe study was designed as a self-paired test. Brackets were bonded with fluoride adhesive on the left side, while non-fluoride adhesive on the right side for each patient. Plaque samples were taken from the surfaces around the brackets of four maxillary incisors before brackets bonding and after the bonding 4 weeks later. The amount of MS was measured by RT-FQ PCR. The data obtained were analyzed statistically using the SPSS 11.5 version and the alpha level was set at 0.05 (2-tailed).

RESULTSThe amount of MS in plaque increased significantly after bracket bonding (P < 0.01), whereas no significant differences were observed among four maxillary incisors both before and after brackets bonding (P > 0.05), and among the incisors using and not using fluoride adhesive (P > 0.05).

CONCLUSIONSThe increase of the density of MS in plaque after bracket bonding is one of the etiological factors for enamel demineralization in orthodontic patients. The result of this study did not support what we observed clinically that the incidence of enamel demineralization for lateral incisors was higher than that for central incisors. Using fluoride adhesive for bonding did not affect the amount of MS in plaque in our study. Further study is needed.

Adhesives ; Adolescent ; Dental Bonding ; Dental Plaque ; microbiology ; Female ; Fluorescence ; Fluorides ; administration & dosage ; Humans ; Male ; Orthodontic Brackets ; Polymerase Chain Reaction ; methods ; Streptococcus mutans ; genetics ; isolation & purification ; Tooth Demineralization

BACKGROUNDThere are few reports of a biological role for glycosyltransferases in the infiltration of osteoarthritic synovitis. The aim of this research was to investigate the expression and cellular location of β-1,4-galactosyltransferase I (β-1,4-GalT-I) in a surgically-induced rat model of knee osteoarthritis (OA), and explore the role of β-1,4-GalT-I in the pathogenesis of OA.

METHODSMale Sprague-Dawley rats were randomly divided into three groups: OA group, sham group and normal group. The model of OA was established in the right knees of rats by anterior cruciate ligament transaction (ACLT) with partial medial meniscectomy. Fibroblast-like synoviocytes (FLSs) obtained from normal rat synovial tissue were cultured. The expression of β-1,4-GalT-I mRNA in the synovial tissue, articular cartilage and FLSs treated with tumor necrosis factor-α (TNF-α) were assayed by real-time PCR. Western-blotting and immunohistochemisty were used to observe the expression of β-1,4-GalT-I at the protein level. Double immunofluorescent staining was used to define the location of the β-1,4-GalT-I with macrophage-like synoviocytes, FLSs, neutrophils, and TNF-α in the OA synovium. The alteration of TNF-α in FLSs which were treated with lipopolysaccharide (LPS) and β-1,4-GalT-I-Ab were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSThe mRNA and protein expression of β-1,4-GalT-I increased in synovial tissue of the OA group compared with the normal and sham groups at two and four weeks after the surgery, however, no significant difference appeared in the articular cartilage. Immunohistochemistry also indicated that the β-1,4-GalT-I expression in OA synovium at four weeks after surgery increased sharply compared with the control group. β-1,4-GalT-I co-localized with macrophage-like synoviocytes, FLSs, neutrophils and TNF-α in rat OA synovitis. Moreover, in vitro β-1,4-GalT-I mRNA in FLSs was affected in a dose- and time-dependent manner in response to TNF-α stimulation. ELISA revealed that the expression of TNF-α was attenuated in FLSs in vitro when treated with anti β-1,4-GalT-I antibody.

CONCLUSIONβ-1,4-GalT-I may play an important role in the inflammation process of rat OA synovial tissue which would provide the foundation for further researching into the concrete mechanism of β-1,4-GalT-I in OA synovitis.

Animals ; Blotting, Western ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Galactosyltransferases ; genetics ; metabolism ; Immunohistochemistry ; Knee Joint ; enzymology ; pathology ; surgery ; Male ; Osteoarthritis, Knee ; enzymology ; genetics ; pathology ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; enzymology ; Synovitis ; enzymology ; etiology

Aged ; Coronary Angiography ; Coronary Restenosis ; diagnostic imaging ; etiology ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Sirolimus ; administration & dosage ; Stents

Objective To investigate Notch1 protein expression of leukemic cells in children with pediatric Bcell acute lymphoblastic leukemia(B-ALL) and its effect on prognosis.Methods The expression of Notch1 protein of leukemic cells in bone marrow smears was detected by immunohistochemistry(SABC) in primarily diagnosed childhood ALL,including 63 cases of B-ALL and 14 cases of T-ALL,a group of 34 children with no malignancy served as controls.Reverse transcription-ploymerase chain reaction was used to assay Notch1 mRNA expression in ALL patients.Results The incidence of Notch1 expression was 31.7％ in B-ALL patients,71.4％ in T-ALL patients,and 8.8％ in control group,respectively.Notch1 protein was aberrantly expressed in both B-ALL and T-ALL compared with the controls(P ＜ 0.05,P ＜ 0.001).Multivariate analysis revealed that the expression of Notch1 protein in B-ALL was not associated with patients' age,gender,WBC count at diagnosis(all P ＞ 0.05),it had no influence on the early treatment response.Nevertheless,the Kaplan-Meier curve of event-free survival showed that,in the patients without Notch1 protein expression,the long-term event-free survival rate was as high as 92.7 ％,in contrast,in the children with Notch 1 expression,the event-free survival was only 54.5 ％ (P =0.0054).Conclusions The expression of Notch 1 protein in pediatric B-ALL may predict a poor prognosis,and interfering with Notch1 signaling could be employed as a potential therapeutic target for those patients with Notch1 expression.