Objective To profile the expression of all known members of the matrix metalloproteinase ( MMP ), a disintegrin and metalloproteinase with thrombospondin motifs ( ADAMTS ), and tissue inhibitor of metalloproteinases ( TIMP s) gene families in normal cartilage and that from patients with osteoarthritis (OA). Methods Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur. Total RNA was purified and expression of genes assayed using quantitative real-time PCR. Results Several members of the above gene families were regulated in OA. Genes increasing in expression in OA were: at P < 0.001, MMP-13 , MMP-28 , ADAMTS-16 ; at P < 0.01, MMP-9 , MMP-16 , ADAMTS-2 , ADAMTS-14 and at P < 0.05, MMP-2 , TIMP-3 , ADAMTS-12 . Genes decreasing in expression in OA were: at P < 0.001, MMP-1 , MMP-3 , ADAMTS-1 ; at P < 0.01, MMP-10 , TIMP-1 , ADAMTS-9 and at P < 0.05, TIMP-4 , ADAMTS-5 , ADAMTS-15 . Correlation analysis revealed that groups of genes across the gene families are co-expressed in cartilage. Conclusion This is the first comprehensive expression profile of all known MMP , ADAMTS and TIMP genes in cartilage. Patterns of expression provide a foundation on which to understand mechanisms of gene regulation in OA and potentially for refining the specificity of anti-proteolytic therapies. 相似文献
Background: For nitrous oxide, a preconditioning effect on the heart has yet not been investigated. This is important because nitrous oxide is commonly used in combination with volatile anesthetics, which are known to precondition the heart. The authors aimed to clarify (1) whether nitrous oxide preconditions the heart, (2) how it affects protein kinase C (PKC) and tyrosine kinases (such as Src) as central mediators of preconditioning, and (3) whether isoflurane-induced preconditioning is influenced by nitrous oxide.
Methods: For infarct size measurements, anesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Rats received nitrous oxide (60%), isoflurane (1.4%) or isoflurane-nitrous oxide (1.4%/60%) during three 5-min periods before index ischemia (each group, n = 7). Control animals remained untreated for 45 min. Additional hearts (control, 60% nitrous oxide alone%, and isoflurane-nitrous oxide [0.6%/60%, in equianesthetic doses]) were excised for Western blot of PKC-[varepsilon] and Src kinase (each group, n = 4).
Results: Nitrous oxide had no effect on infarct size (59.1 +/- 15.2% of the area at risk vs. 51.1 +/- 10.9% in controls). Isoflurane (1.4%) and isoflurane-nitrous oxide (1.4%/60%) reduced infarct size to 30.9 +/- 10.6 and 28.7 +/- 11.8% (both P < 0.01). Nitrous oxide (60%) had no effect on phosphorylation (2.3 +/- 1.8 vs. 2.5 +/- 1.7 in controls, average light intensity, arbitrary units) and translocation (7.0 +/- 4.3 vs. 7.4 +/- 5.2 in controls) of PKC-[varepsilon]. Src kinase phosphorylation was not influenced by nitrous oxide (4.6 +/- 3.9 vs. 5.0 +/- 3.8; 3.2 +/- 2.2 vs. 3.5 +/- 3.0). Isoflurane-nitrous oxide (0.6%/60%, in equianesthetic doses) induced PKC-[varepsilon] phosphorylation (5.4 +/- 1.9 vs. 2.8 +/- 1.5; P < 0.001) and translocation to membrane regions (13.8 +/- 13.0 vs. 6.7 +/- 2.0 in controls; P < 0.05). 相似文献
Background: Acetaminophen (paracetamol) is widely used for postoperative analgesia. Its mechanism of action is inhibition of prostaglandin synthesis in the central nervous system, and acetaminophen is traditionally not considered to influence platelet function. The authors studied the dose-dependent inhibition of platelet function by acetaminophen in healthy volunteers.
Methods: Thirteen healthy male volunteers (aged 19-26 yr) were given placebo or 15, 22.5, or 30 mg/kg acetaminophen intravenously in a double-blind, crossover study. Ten and 90 min after infusion, platelet function was assessed by photometric aggregometry and by measuring release of thromboxane B2, analgesia by cold pressor test, and plasma acetaminophen concentrations by high-performance liquid chromatography.
Results: When triggered with 500 [mu]m arachidonic acid, median platelet aggregation (area under the curve) was 25.7, 22.8, 4.1, or 3.6 x 103 area units (P < 0.001) 10 min after placebo or 15, 22.5, or 30 mg/kg acetaminophen, respectively. An increasing concentration of arachidonic acid attenuated the antiaggregatory effect. After 90 min, platelet function was recovering. Release of thromboxane B2 was also dose-dependently inhibited by acetaminophen. Although plasma concentration of acetaminophen increased linearly with the dose, no analgesic effect was detected in the cold pressor test. 相似文献
Background: Inhaled administration of milrinone reduces pulmonary artery pressure. Pulmonary hypertension (PH) and right heart failure are associated with difficult separation from cardiopulmonary bypass (CPB). Therefore, inhaled milrinone could facilitate separation from CPB. Objective: To determine the impact and timing of administration of inhaled milrinone. Methods: A retrospective analysis of our experience on high-risk patients receiving inhaled milrinone was conducted to evaluate the postoperative course after administration of the drug. Results: Seventy-three patients received inhaled milrinone from June 2002 to February 2005. Mean age was 64 ± 13 years, with a mean preoperative Parsonnet score of 27 ± 14. Inhaled milrinone (5 mg) was administered before (n = 30) or after (n = 40) CPB, three patients had off-pump procedures and were excluded. CPB time was 145 ± 78 min with cross-clamping times of 91 ± 56 min without any significant difference between groups. Fifty-four patients (74%) had difficult separation from CPB, 14 patients (19%) required an intra-aortic balloon pump and 10 patients (14%) needed emergency reinitiation of CPB for hemodynamic instability. Ten patients died in the perioperative period (13.7%). Patients receiving inhaled milrinone prior to CPB initiation had a lowering pulmonary artery pressure after CPB (p < .01) and had less emergency reinitiation of CPB after weaning (3% vs 23%, p = .02) as compared to those with administration after CPB. No detectable side effects were directly linked to the administration of the drug. Conclusion: In this high-risk cohort, use of inhaled milrinone was well tolerated. Administration before initiation of CPB could help weaning from CPB. 相似文献
Integrated surveillance of infectious multi-source diseases using a combination of epidemiology, ecology, genetics and evolution can provide a valuable risk-based approach for the control of important human pathogens. This includes a better understanding of transmission routes and the impact of human activities on the emergence of zoonoses. Until recently New Zealand had extraordinarily high and increasing rates of notified human campylobacteriosis, and our limited understanding of the source of these infections was hindering efforts to control this disease. Genetic and epidemiological modeling of a 3-year dataset comprising multilocus sequence typed isolates from human clinical cases, coupled with concurrent data on food and environmental sources, enabled us to estimate the relative importance of different sources of human disease. Our studies provided evidence that poultry was the leading cause of human campylobacteriosis in New Zealand, causing an estimated 58–76% of cases with widely varying contributions by individual poultry suppliers. These findings influenced national policy and, after the implementation of poultry industry-specific interventions, a dramatic decline in human notified cases was observed in 2008. The comparative-modeling and molecular sentinel surveillance approach proposed in this study provides new opportunities for the management of zoonotic diseases. 相似文献
OBJECTIVE: Esophagectomy is an operation with high morbidity and mortality. Its adoption as a minimally invasive operation worldwide has been slow, but the potential benefits of reducing the trauma of surgery need to be considered. Our 30-month experience with transhiatal esophagectomy in a district general hospital is presented herein. METHODS: Patients were considered for surgery after radiological staging had excluded inoperable disease. Laparoscopic staging was initially performed. Patients with tumors of the esophagus and high-grade dysplasia in a Barrett's esophagus were included. RESULTS: Twenty-nine patients were referred for consideration for resectional surgery. Nine underwent outpatient laparoscopy only. Twenty patients (age range, 34 to 78, 15 males:5 females) underwent resectional surgery. Seventeen transhiatal resections were completed, 2 were converted to open procedures, and 1 transhiatal resection of a benign tumor was performed. Median time of surgery was 415 minutes (range, 320 to 480) and blood loss was 300 mL (range, 200 to 350). The median length of post-operative ventilation and critical care stay were 1 (range, 1 to 4) and 4 (range, 2 to 8) days. Median duration of hospitalization was 17 days (range, 10 to 28). Thirty-day mortality was 0; 1 patient who was converted to an open procedure died after a cerebrovascular event on day 34. CONCLUSION: A zero mortality rate for laparoscopic resection and a low-morbidity rate compare well with morbidity and mortality in reported series using this method and open surgery. Laparoscopic transhiatal esophagectomy is an advanced, complex procedure that can be performed safely in a district general hospital setting. 相似文献