Role of pro-inflammatory cytokines, and matrix metalloprotinases in the pathogenesis of heart failure

Extracellular matrix remodeling is thought to play an important role in the progression of heart failure [HF]. Matrix metalloproteinases [MMPs] and tissue inhibitors of metalloproteinases [TIMPs] are matrix-degrading enzymes that have been demonstrated to influence left ventricular properties and serve as targets of potential anti-remodeling agents. It has been reported that MMPs concentration and activity are upregulated in the failing human heart. However, there are few reports describing the role of elevated level of circulating MMPs in severe congestive heart failure [CHF] patients. This study examined whether circulating MMPs are also related to the pathogenesis of CHF. The study involved 50 patients with severe CHF and 20 apparently healthy subjects, with matched age and sex were selected as a control group. Two Dimensional echocardiography, Doppler and colour flow mapping were done for the patients. Left ventricular dimensions [LVD] and cardiac size were measured. LV mass [LVM] was calculated from Interventricular septum [IVS], Left ventricular end diastolic dimensions [LVEDd], Left ventricular wall thickness [LVWT] and Left ventricular end systolic dimension [LVESd]. The serum levels of MMP-2, MMP-9 and TIMP-l as well as IL-18, TNF-alpha as pro-inflammatory cytokines were measured in patients with CHF and control subjects. The serum levels of MMP-2, MMP-9, TIMP-1, IL-18 and TNF-alpha were significantly higher in the CHF patients than control group. Moreover, MMP-2, MMP-9 and TIMP-1 serum levels were positively correlated with the levels of IL-8, TNF-alpha, cholesterol, triglyceride and CRP. Furthermore, MMP-2, MMP-9 andTIMP-1 were positively coffelated with LVM, LVED[d] and LVWT. We conclude that, the increasing serum levels of MMP-2, MMP-9 and TIMP-l were associated with increased LV diastolic dimensions and increased wall thickness in patients with CHF. These observations indicate that MMPs and TIMP- I serum levels may be markers for cardiac extracellular matrix degradation, a process involved in LV remodelling. These findings may open a new avenue for therapy that ameliorating heart failure especially high risk patients

Alteration of Serum IgF-1 and its binding proteins - 1 and - 3 in patients with chronic liver disease and their role in the prognostic scoring methods

The liver is the major source of circulating insulin-like growth factor-1 IGF-1] and at least two of the major binding proteins [IGFPPs] IGFBP-1 and -3, that modulate its bioavailability and activity. The aim of this work was to evaluate whether circulating levels of these parameters could be used for the assessment of hepatic function, reserve and in predicting the prognosis in patients with chronic liver disease [CLD]. The study included 35 patients with chronic liver disease [CLD] who were classified according to Child Pugh score [CPs] into grades A, B and C, in addition to 15 age- and sex-matched normal individuals served as controls. In conclusion, there were significant changes in the levels of circulating IGF-1 and its binding proteins [IGFBP-1 and -3] in CLD. They were closely correlated with the deterioration of liver function. Hence, they could be used as markers for the assessment of the degree of the severity of liver disease. IGFBP-3 can be used to assess the synthetic capacity of hepatocytes and seems to be a sensitive prognostic marker in CLD

Relationship between prothrombin fragment 1+2 and helicobacter pylori associated chronic gastritis

Helicohacter pylori [H. pylori] have been suggested to be an independent risk factor for cardiovascular and cerebral stroke; through the activation of clotting system following chronic inflammation. Among proinflammatory cytokines, tumour necrosis factor-alpha [TNF-alpha] and interleukin-8 [TL-8] which have been previously demonstrated to activate the clotting system in human. This study aimed to investigate: [i] if there is a difference between the circulating levels of prothromhin fragment 1+2 [F1+2]; a sensitive marker of thrombin generation in patients with chronic gastritis according to N. pylori status, [ii] the relationship between circulating and mucosal levels of TNF-alpha, IL-8 and Fl+2 and [iii] If H. pylori eradication modifies the level of these cytokins and clotting system activation. Forty-two patients with chronic gastritis were diagnosed with upper endoscopy, and enrolled in this study, divided into 2 groups on the basis of histopathological examination of gastric antral biopsies and culture. Group I: included 28 H. pylori positive patients, and group H: 14 H. pyIori negative patients chronic gastnitis. A triple eradication therapy for H. pylori [omeprazole, amoxacillin and tinidazole] was given for the 28 H. pylori positive patients [Group I] and H. pylori eradication was evaluated after 2 months. Gastric mucosal levels of TNF-alpha and IL-8 as well as plasma levels of TNF-alpha, IL-8 and F1+2 were measured in group II and before and 2 months after H. pylori eradication in group I. Our results showed that: patients with H pylori positive gastritis had a significant increase in the mean value of plasma F1+2 mucosal and plasma levels of TNF-alpha and IL-8 compared with group II [P<0.001]. There was a significant positive correlation between plasma level of F1+2 and plasma levels of TNF-alpha and IL-8 [r=0.89, p<0.00, r=0.88, p<0.000] respectively and between the plasma levels of F1+2 and gastric mucosal levels of TNF-alpha and IL-S [r=0.89, P<0.000; r=0.86 P<0.001] respectively. There was a significant reduction in the mean value of plasma levels of TNF-alpha. IL-8 and F1+2 as well as fibrinogen 2 months later after H. pylori eradication. While in-group II [H pylori negative chronic gastrius] there was no significant correlation between the studied parameters. In conclusion, the present study showed a close relationship between plasma levels of prothrombin F1+2, and both plasma and gastric mucosal values of TNF-alpha and IL-8 in cases with H. pylori associated chronic gastritis. These findings suggest that H. pylori may represent a trigger factor for clotting system activation through persistent inflammatory stimulation, cytokines production and consequently H. pylori eradication may reduce the risk of hyper-coagulability state or thrombotic events which may be associated in these patients

Clinical evaluation versus ultrasonographic findings in the diagnosis of painful shoulder

The differentiation of causes of shoulder pain is a clinical challenge. Among a wide variety of conditions that may produce similar shoulder pain and dysfunction, periarticular disorders play the main role. Accurate diagnosis is therapeutically important and early management may prevent capsulitis and rotator cuff lesions from becoming adhesive, so true frozen shoulder may be avoided. With the advent of high-resolution ultrasonography, interest in musculoskeletal sonography has increased and it can be used to evaluate the accuracy of clinical diagnosis of painful shoulder. Our aim was to compare the clinical diagnosis established by a physical examination with high frequency ultrasonographic findings in patients with painful shoulder. Twenty-seven consecutive patients were prospectively included in the study. All had a physical examination performed. Utrasonographic examination was carried out within one week of the physical examination. Ultrasonography was considered the optimal diagnostic technique. Our results showed that the clinical assessment had low accuracy in the diagnosis of periarticular shoulder lesions. Ultrasonography should be used whenever possible to improve diagnosis and treatment of painful shoulder