Serum and synovial fluid levels of vascular endothelial growth factor in patients with inflammatory and degenerative arthritis

This work conducted to evaluate the clinical utility of measuring vascular endothelial growth factor [VEGF] by enzyme-linked immunosorbent assay in serum and synovial fluid [SF] samples from patients with early rheumatoid arthritis [RA], other recent-onset inflammatory arthritides, established RA and osteoarthritis [OA], as well as non-arthritic healthy controls. The study, also, investigated whether serum and SF VEGF had any relation with the standard clinical, laboratory and radiological markers of RA disease. The results showed that serum VEGF levels were elevated in patients with RA, inflammatory arthritis and OA in comparison with non-arthritic controls. Patients with recent-onset RA had the highest VEGF values both in serum and SF. In early and established RA groups, VEGF levels were higher in SF than in the serum. In the early inflammatory arthritides and the OA groups, the opposite occurred. Serum and SF VEGF were higher in active than inactive RA disease, with a positive correlation between their levels and each of ESR and disease activity grade. Moreover, values of VEGF in SF, but not in serum correlated well with the development of radiological damage in the established RA group

Serum levels of matrix metalloproteinase 9 [MMP-9] and tissue inhibitor metalloproteinase 1 [TIMP-1] in lung cancer patients: correlation with carcinoembryonic antigen [CEA] level

There is evidence of the dysregulation of the balanced interaction between matrix metalloproteinases [MMPs] and their inhibitors, tissue inhibitors of metalloproteinases [TIMPs] in cancer which is thought to facilitate tumor cell invasion and metastasis. The role of MMP-9 and TIMP-1 was evaluated in different pathological types of lung cancer. Sera were collected from 52 lung cancer patients [10 had large cell carcinoma, 9 small cell carcinoma, 19 squamous cell carcinoma and 14 metastatic adenocarcinoma] as well as from 20 healthy control subjects. MMP-9 and TIMP-1 serum levels were measured using a sandwich enzyme immunoassay technique. Serum level of carcinoembryonic antigen [CEA] was also measured in the same subjects using a one step sandwich enzyme immunoassay technique. The study revealed a significant increase in the serum level of MMP9 in lung cancer patients as compared to controls [p < 0.001], with the highest value being found in patients with large cell carcinoma. A significant increase in TIMP-1 level was also found in lung cancer patients [p < 0.001], with no marked variation amongst different pathological types. A significant increase was also found in MMP9/T1MP1 ratio in patients versus controls [p < 0.001] with the highest value being measured in patients with large cell carcinoma. A significant positive correlation was found between the serum level of MMP-9 and TIMP-1 [r = 0.3, p < 0.05] and also with MMP-9/ TIMP-1 ratio [r - 0.99, p < 0.05] in lung cancer patients. Regarding CEA level, it showed a significant increase in lung cancer patients as compared to controls [p < 0.05], with the highest value being obtained from patients with squamous cell carcinoma. No significant correlation was found between CEA serum level and either MMP9 or TIMP1 [p > 0.05]. Analysis of the diagnostic value of CEA, MMP-9 and TIMP-1 in lung cancer patients revealed that CEA had 40.38% sensitivity, 100% specificity and positive predictive value [PPV], 39.2% negative predictive value [NPV] and 56.4% diagnostic efficiency [DE]. On the other hand, MMP-9 had 90.4% sensitivity, 95% specificity, 97.9% PPV, 82.6% NPV and 91.7% DE. The sensitivity, specificity, PPV, NPV and DE of TIMP-1 were 98.1%, 95%, 98.1%, 95% and 97.2% respectively. It can be concluded that increased serum levels of MMP-9, TIMP-1 and their ratio are found in lung cancer patients independently of CEA level. Both MMP-9 and TIMP-1 may serve as tumor markers, with TIMP-1 seems to be the most efficient with the highest diagnostic efficiency

Soluble urokinase plasminogen activator receptor in plasma and synovial fluid of rheumatoid arthritis and knee osteoarthritis

To determine the level of soluble urokinase plasminogen activator receptor [suPAR] in the plasma and synovial fluid of rheumatoid arthritis [RA] patients and osteoarthritis [OA] patients in comparison to normal healthy subjects, in order to find out its possible role in the pathogenesis of these diseases and to detect whether it can be used as a marker of disease activity and severity. Our study was conducted on 53 subjects. 23 rheumatoid arthritis [RA] patients, 20 patients having knee osteoarthritis [OA] and 10 healthy subjects served as the control group. suPAR level in plasma and synovial fluid of all subjects was measured by ELISA technique. The mean value of soluble urokinase plasminogen activator receptor [suPAR] in plasma and synovial fluid of RA patients was highly significantly increased in comparison to OA patients and healthy subject [p<0.001]. The mean value of plasma suPAR level was also higher in OA patients than healthy subjects but no significant difference was found between them [p>0.05]. While its value in the synovial fluid was significantly increased in OA patients than healthy subjects. Also, no significant difference was found between plasma and synovial fluid suPAR level in RA, and the control group [p>0.05]. While a highly significant difference in its level was found between them in OA patients. There was a significant positive correlation between plasma and synovial fluid level of suPAR and age, duration of disease and disease severity in RA patients. While no significant correlation was found in RA patients between both plasma and synovial fluid level of suPAR and sex, rheumatoid factor sero reactivity, tenderness, swelling [or any of the clinical data], ESR, disease activity index and type of drug received. Also no significant correlation was found between synovial fluid level of suPAR in OA patients and age, and disease severity. A significant positive correlation was found between plasma and synovial fluid level of suPAR in RA patients. The highly significant in crease in the level of suPAR in both plasma and synovial fluid of RA patients compared to other studied groups and the significant correlation between both plasma and synovial fluid suPAR level and disease severity may clarify its possible role in the pathogenesis of RA and may reflect the destructive and erosive nature of this disease. So suPAR appears to be a useful marker that reflects disease severity in RA patients. Also the significant increase in the synovial fluid suPAR level in OA patients in comparison to the control group suggest that alterations in the PA/PAR system also occur in OA and thus might contribute to the pathogenesis of this disease. Since there was no significant difference in the level of suPAR between plasma and synovial fluid, therefore we suggest measuring plasma suPAR only. Also no correlation was found between plasma and synovial fluid suPAR level and disease activity. This needs further extended studies to confirm this result, as it will determine the value of suPAR as a marker of disease activity

Granulocyte macrophage - colony stimulating factor [GM- CSF] in bronchial asthma

This study included 41 subjects classified into 3 groups. Group 1: Twenty-one asthmatic patients [6 with mild and 15 with moderate asthma]; Group 2: Ten patients with other inflammatory lung diseases [bronchiectasis, COPD, IDF] and Group 3: Ten normal controls. FOB and BAL were done for groups 1 and 2; and blood sample was collected from all groups. GM-CSF levels in serum and BAL were measured. The results showed a significantly higher GM-CSF level in serum and BAL of the asthmatics compared to the other inflammatory diseases. A highly significant level was also found in the serum of asthmatic patients compared to the normal subjects. There was a significant negative correlation between the mean FEV 1% and mean levels of GM-CSF in both serum and BAL of the asthmatic patients. In light of these findings, we would recommend measurement of this important cytokine, GM-CSF in the serum and airways secretions in different asthmatic patients and this should contribute to monitoring the status of asthma and selecting the most appropriate anti-inflammatory therapy

Cross - linked teleopepetide of type I collagen [bone turnover marker] inpatients with rheumatoid arthritis in correlation with disease activity

In this study Radioimmunoassay was used to measure the serum concentration of corss-linked carboxy terminal telopeptide of type I collagen [ICTP] as a serum marker for bone collagen degradation in rheumatoid arthritis [RA] patients. 30 patients having [RA] were subdivided into two subgroups according to disease activity. One subgroup concluded 15 patients having active rheumatoid, the other subgroup concluded 15 patients having inactive [RA]. The 30 patients were also divided according to steroid therapy administration, where 14 patients received steroid and 16 patients did not receive steroid at all. In addition to 15 patients healthy control subjects. All patients and control were females, the mean age was 38.1 +/- 3.8 years old and 36.9 +/- 3.5 years old respectively [P>0.05] i.e. statistically insignificant. Our results showed that s. [ICTP] was increased in patients in comparison to control, the mean was 6.7 +/- 2.3 mg/L and 3.5 +/- 0.5 mg/L respectively [P< 0.001] which is highly significant. Higher levels of [ICTP] were found in active [RA] group than inactive group, the mean was 8.30 +/- 2.3 mg/L and 5.14 +/- 0.6 mg/L respectively [P< 0.00 1] which is highly significant. There was no, significant differences in s.[ICTP] between patients on steroid therapy and that who were not, the mean was 7.7 +/- 2.8 mg/L and 5.8 +/- 1.3 mg/L [P> 0.05] which is not significant. In conclusion, serum [ICTP] level was elevated in patients having rheumatoid arthritis and correlated positively with disease activity, serum [ICTP] however, is not influenced by steroid intake in those patients

Study of non-fibrinolysis-related role of plasminogen activator inhibitor-1 activity in chronic hepatitis C

The plasminogen activator inhibitor-1 [PAI-1] activity was investigated in chronic hepatitis C in relation to disease severity and some associated metabolic changes. The study included 30 patients with chronic hepatitis C compared to 30 control subjects. Disease severity was assessed using prothrombin time and serum albumin as parameters. Plasma plasminogen, PAI-1 and tissue plasminogen activator PAI-1 complex were determined, as well as serum lipid parameters and blood glucose level. We found decrease in PAI-1 activity, reflected by complex, more expressed in severe cases, with inadequate rise of PAI-1 level, associated with decreased VLDL, raised cholesterol and triglycerides and insignificant correlation to blood glucose level. We conclude that apart from its fibrinolysis-related role in chronic liver disease, PAI-1 activity is altered in chronic hepatitis C, resulting from chronic inflammation and associated lipid disturbances. This alteration contributes to the progression of the disease and its complications. Therapy directed at regulation of hepatic stellate cell function and control of lipid metabolism needs detailed investigation in order to regulate PAI-1 activity