Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment. 相似文献
OBJECTIVE: To investigate the sympathetic nervous system activity in Meniere's disease (MD) by recording sympathetic skin responses (SSRs) from the postauricular region (PA). METHODS: Twenty-one patients with definite unilateral MD diagnosis and 12 healthy volunteers were studied by evoking right and left PA-SSRs with electrical stimulation of the left median nerve at the wrist in attack and interval periods of MD. Mean latencies and maximum amplitudes were used in statistical analyses. RESULTS: In unilateral definite MD patients, the mean latencies were longer and the maximum amplitudes were smaller on the involved ear side than those on the normal ear side (p<0.01 for both amplitude and latency) and than those from the controls (p<0.01 and p<0.05). In three patients, there was no detectable PA-SSR on the involved ear side while there were SSRs on the healthy side. In four patients, the responses were absent bilaterally during the attack period. CONCLUSIONS: There is a marked asymmetric sympathetic hypofunction in the area of the PA region of the involved ear in MD patients. SIGNIFICANCE: The PA region is a new site for recording sympathetic skin responses. PA-SSR is a useful tool to investigate sympathetic nervous system function in MD patients. 相似文献
The purpose of this study was to design thermoreversible biomaterials for enhanced adhesion of bone morphogenetic protein-2 (BMP-2)-responsive cells. Peptides containing the arginine-glycine-aspartic acid (RGD) sequence were conjugated to N-isopropylacrylamide (NiPAM) polymers via amine-reactive N-acryloxysuccinimide (NASI) groups. In monolayer cultures, the adhesion of BMP-2-responsive C2C12 cells to RGD-grafted NiPAM/NASI surfaces was significantly higher than adhesion on ungrafted NiPAM/NASI surfaces. Although the morphology of cells adhered to RGD-grafted NiPAM/NASI surfaces was comparable to cells adhered on tissue culture polystyrene (TCPS), long-term cell growth was limited on the NiPAM/NASI surfaces, even for RGD-grafted surfaces. Treatment of C2C12 cells with recombinant BMP-2 induced dose-dependent osteoblastic differentiation as assessed by alkaline phosphatase (ALP) activity. In the absence of BMP-2, cells cultured on NiPAM/NASI polymers (either grafted with RGD peptide or not) expressed significantly higher levels of ALP activity than the cells cultured on TCPS, indicating that the polymer surfaces induced some osteoblastic activity in C2C12 cells without the need for BMP-2. We conclude that NiPAM-based thermoreversible biomaterials, despite their limited ability to support cell growth, allowed an enhanced expression of the chosen osteogenic marker (ALP) by C2C12 cells in vitro. 相似文献
An extracorporeal circulation technique was developed for use in rats to provide equilibrated blood samples for multiple hormone assays. The inclusion of the extracorporeal circulation did not significantly alter arterial blood pressure, cardiac output, heart rate or central venous pressure in either Brattleboro rats with hereditary diabetes insipidus (BDI) or normal rats of the parent Long Evans (LE) strain. Plasma adrenaline and noradrenaline levels did not alter in either BDI or LE rats following inclusion of the extracorporeal circulation but the vasopressin concentration rose significantly in the LE rats. The impaired recovery of the mean arterial blood pressure following haemorrhage in the BDI rats compared with normal LE animals was not further influenced by the inclusion of the extracorporeal circulation. Plasma vasopressin and adrenaline (but not nor-adrenaline) levels were significantly raised during, and after, haemorrhage in the LE rats while in the BDI rats only plasma adrenaline levels were significantly increased. These results show that the insertion of an extracorporeal circulation into an anaesthetized BDI or LE rat does not adversely affect the cardiovascular system despite the increase in baseline plasma vasopressin concentration in normal rats, and its subsequent removal provides an additional equilibrated blood sample for multiple hormone assay within the same animal. The increased release of both adrenaline and vasopressin (but not noradrenaline) after haemorrhage in the same animal is detected using this technique, and the importance of vasopressin to the normal recovery process confirmed. 相似文献
BACKGROUND: Our main aim was to investigate the effects of melatonin (ME), possibly the most powerful free-radical scavenger, on the prevention of i.p. adhesion formation in rat uterine horn. Our secondary aim was to determine whether different methods of administration of ME were beneficial. METHODS: Animals were randomly assigned into seven groups, each consisting of 13 rats. Measured serosal injury was created using a standard technique. While control and two sham groups were not given ME, two of the remaining four groups were given a single dose of 10 mg/kg (2 mg) of ME i.p. immediately after injury and 30 min prior to injury respectively. In the two other groups, ME treatment was continued daily for 5 days. All animals were killed 2 weeks after surgery and adhesions were determined and scored by a examiner blinded to the test. RESULTS: The extent, severity and total scores of adhesion were found to be significantly reduced in all of the ME treatment groups when compared with control and sham groups. There were no statistically significant differences between the treatment groups. CONCLUSIONS: This study showed that even single dose ME therapy was effective in the prevention of post- operative i.p. adhesion formation. 相似文献
Infertility represents a major medical, economic, and psychological problem. Stem cells therapy for infertility has a great interest nowadays especially for cancer survivors at pre-reproductive and reproductive age.
Thirty-two adult male albino rats were used, divided equally into four groups; Group I (Control group) received isotonic saline intraperitoneally (i.p.) as vehicle. Group II (Cisplatin-treated group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, and then were sacrificed after 5 days. Group III (Stem-cell-treated group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, then after 5 days received adipose-derived mesenchymal stem cells (ADMSCs) (1 × 106). Cells were injected in the rete testis, then after 60 days, the animals were sacrificed. Group IV (Auto healing group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, and then left for 65 days then the animals were sacrificed. Cisplatin administration resulted in degenerative changes in the testicular architecture in the form of thickened irregular BM of seminiferous tubules. The germinal epithelium showed disorganization and marked reduction in the thickness, associated with Sertoli cells preservation. Features of apoptosis assured by elevated caspase-3 expression were noticed. The interstitium showed cellular infiltration and distorted Leydig cells. Injection of (ADMSCs) resulted in great improvement of testicular architecture and increase in the testosterone level associated with strong immune reaction of the CD-44. ADMSCs are recommended as a new treatment modality for male infertility.
Cardiovascular disease is one of the major causes of mortality in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Metabolic syndrome (MetS) is associated with increased cardiovascular risk in the normal population. However, MetS in AAV has not been adequately investigated. We aimed to determine MetS prevalence and associated factors in AAV patients.
Methods
Thirty-seven AAV patients and 42 healthy controls were enrolled. MetS was determined by International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. The relationship between clinical features of AAV and MetS was also investigated.
Results
MetS was significantly higher in AAV patients than controls by NCEP-ATPIII (51.4% vs. 26.2%, p 0.022) and IDF (62.2% vs. 35.7%, p 0.020). When AAV patients with MetS were compared to those without, there were significant differences in age, CRP, GFR and NT-pro-BNP. Age [58 (13) vs. 50 (8) years p: 0.028], CRP [4.0 (3.6) vs. 3.2 (1.0) mg/l, p 0.021] and NT-pro-BNP [173.5 (343.7) vs. 106.0 (103.0) pg/ml, p 0.013] were significantly higher in AAV patients with MetS than those without; GFR was significantly lower [38 (46) vs. 83 (51) ml/min/1.73 m2, p 0.004]. ROC curve analysis showed NT-pro-BNP?>?58.0 ng/ml predicted MetS with 87.1% sensitivity and 46.7% specificity (Area under curve: 0.71, CI 0.536–0.902, p 0.041). Multivariate analysis revealed age [OR (95% CI): 1.180 (1.010–1.370), p 0.039] and NT-pro-BNP?>?58 pg/ml [OR (95% CI): 5.5 (1.02–30.1) p 0.047] were independent predictors of MetS in AAV patients.
Conclusion
MetS is significantly higher in AAV patients than controls and is associated with age and NT-pro-BNP. Screening and treating MetS may improve prognosis in AAV patients.
