effect of pioglitazone on matrix metalloproteinase-9, matrix metalloproteinase-2, tumor necrosis factor-a, vascular endothelial growth factor and E-selectin in skin lesions in psoriatic patients with and without psoriatic arthritis

Psoriasis is a common inflammatory skin disease characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation. The aim of the present study was to investigate the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients with and without psoriatic arthritis, the association of MMP-9 with the activity of the disease, the relationship between MMP-9 and TNF-alpha production as well as to evaluate the effect of pioglitazone [one of the agents thiazolidinediones] on TNF- alpha, MMP-9, MMP-2, VEGF and E-selectin production and in treatment of psoriasis. Thirty-five psoriatic patients [28 males, 7 females] were included in this study. They were divided into 2 groups. Group I [PsA] included 15 psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease [PsA]. Group II [Ps] included 20 psoriatic patients, clinically presenting cutaneous disease without psoriatic arthritis [PsA]. Each psoriatic patient received pioglitazone 30 mg/day orally for 10 weeks. Lesional tissue specimens were taken, in the same skin area before and after 10 weeks pioglitazone treatment. Tissues were kept in short term cultures and production soluble mediators such as TNF- alpha, MMP-9, MMP-2, VEGF and E-selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by ELISA. MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index [PAST]. Clinical and laboratory assessment indicated that all patients had a significant improvement of the PAS1 score after 10 weeks of pioglitazone therapy. The clinical improvement was associated to a significant decrease of TNF- alpha, MMP-9, MMP-2, VEGFand E-selectin levels [P < 0.05], spontaneously released by lesional biopsies before and after therapy. A significant decrease of MMP-9 [P < 0.01] in the sera, associated to the clinical improvement was also found. In addition, significant positive correlations [P < 0.01] were found between the TNF- alpha and PASI score, MMP-9, MMP-2, VEGFand E-selectin [r = 0.85, 0.84, 0.58, 0.63, 0.67 respectively], as well as between the MMP-9 and PASI, MMP-2, VEGFand E-selectin [r = 0.82, 0.39, 0.69, 0.41 respectively] of patients with PsA after pioglitazone treatment. In psoriatic patients without psoriatic arthritis after pioglitazone treatment there were also significant positive correlations between the TNF- alpha and PASI score, MMP-9, MMP-2, VEGF and E-selectin [r =.0.87, 0.68, 0.53, 0.61, 0.51 respectively], as well as between MMP-9 and PASI, MMP-2, VEGF and E-selectin [r = 0.95, 0.51, 0.58, 0.45 respectively]. The current study shows the existence of a direct relationship between MMP-9 and TNF- alpha production strongly suggesting that MMP-9 may play a key role in the skin inflammatory process. Our findings also demonstrated that pioglitazone could be considered as an efficacious and safe agent for the treatment of psoriasis. The optimum dose and duration of pioglitazone therapy remain to be determined

Influences of short-term aerobic exercise and supplementation of carnitine with or without choline on body weight, serum leptin and carnitine as well as lipid status in male rats

Carnitine is essential for fatty acids translocation, muscles function and exercise performance. Choline is a lipotropic agent that prevents deposition of fat in the liver. The studies concerning the effects of carnitine and choline supplementation with exercise on carnitine status and serum leptin are rare. The aim of the present study was to study the effect of carnitine and its combination with choline, with or without exercise on body and total fat pad [TFP] weights, serum carnitine, leptin, P-hydroxy butyric acid [beta-HBA], triacylglycerols [TAG] and Free Fatty acids [FFA]. Also, total lipids [TL] and TAG content of TFP and urinary carnitine were investigated. 48 male rats were equally divided to the following groups: control [C], carnitine [5 g/Kg diet] supplemented, carnitine plus choline [5 and 11.5 g/Kg diet respectively] supplemented. Half of each group was subjected to short term aerobic exercise on manual treadmill, in which the speed and duration were gradually increased via the course of the experiment, to be 10 m/min for 20 min/day, 5 days/week in the last 2 weeks. Body weights were recorded weekly. After 6 weeks, The 24 hours urine was collected then the fasted rats were sacrificed and blood and the total fat pad [TFP] were collected for analysis. Carnitine supplementation, tended to decrease body weight, TFP, TAG content and serum FFA, and significantly decreased the TL content, serum leptin, TAG [P < 0.0005]. Carnitine feeding resulted in a significant elevation of serum carnitine, P-HBA and urinary carnitine [P < 0.0005], compared to sedentary control rats. These values became more pronounced on choline addition to the diet except for serum and urinary carnitine that reversed [i.e. decreased] by choline addition. Exercise intervention resulted in a significant decrease in body weight, TFP, TL content and serum leptin, TAG and FFA. These values were more pronounced in both supplements with exercise, specially serum carnitine. However, exercise caused reduction of urinary carnitine in non-supplemented and carnitine supplemented groups and this was reversed by choline and exercise. Our study demonstrated that the beneficial effects of carnitine supplements is promoted by choline with or without mild exercise to reduce body weight, body fat, serum leptin and promote fat loss by increasing lipolysis as indicated by increased serum beta-HBA. These results may or may not be applicable to humans, so further research is recommended to determine whether similar effects would result in humans or not

Plasma adiponectin and resistin levels in type 2 diabetic obese female patients with and without hypertension and retinopathy

In the past, adipose tissue was largely regarded as a depot for fuel storage in the form of triglyceride. However, adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. The adipocyte is now known to secrete a variety of proteins such as tumour necrosis factor [TNF]-alpha, adipsin, plasminogen activator inhibitor-1, leptin, resistin, and adiponectin. Adipose tissue regulates insulin sensitivity via the circulating adipocytokines, resistin and adiponectin. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance and type 2 diabetes [DM]. The objective of this study was to compare the levels of resistin and adiponectin in type 2 diabetic obese female patients with and without hypertension and retinopathy. In this study the plasma adiponectin and resistin concentrations were investigated, in 20 control obese non-diabetic females and 40 obese female patients with type 2 diabetes mellitus. The diabetic females were divided into 2 groups. G[I] included 20 controlled uncomplicated diabetics and GII included 20 diabetic patients with hypertension and retinopathy. The plasma concentration of adiponectin was significantly lower [P< 0.01] in diabetic females in G[I] and G[II] than non-diabetic control females. In diabetic patients with hypertension and retinopathy [G[II]] there was a significant decrease in plasma adiponectin levels [P< 0.01] as compared to their levels in diabetic females in G and control females. Our results also show that there were non-significant changes in plasma resistin in diabetic patients in both groups G[I] and G[II] as compared to their levels in control group. These results suggest that adiponectin may play a key role in pathophysiology of type 2 diabetes mellitus and its microangiopathy and macrovascular complications

Assessment of anticardiolipin antibodies, circulating lupus anticoagulant, protein C, protein S, antithrombin III and activated protein C resistance and their relation to thomboembolic and other clinical manifestations in Behcet's disease

Venous and arterial thrombosis occurs in patients with Behcet's disease and is associated with significant morbidity and mortality. Studies on a possible association between the occurrence of thrombosis and thrombophilia in patients with this disease have been controversial. The objective of this study was to assess the frequency and clinical relevance of anticardiolipin antibodies [aCL] and other thrombophilic factors and their relationship to thromboembolic and clinical manifestations in Behcet's disease [BD]. IgG, IgM and IgA anticardiolipin antibodies [aCL] isotypes, presence of circulating lupus anticoagulant [LAC], protein C, protein S, antithrombin III and activated protein C resistance were investigated in 25 patients with BD and 25 patients with various rheumatic diseases not known to be associated with venous or arterial thromboembolic phenomena served as controls. Twelve of the patients with BD [48%] had either deep vein thrombosis [8 patients], arterial thromboembolic phenomena [4 patients], or both [2 patients]. The IgA aCL elevated in14 [56%] patients with BD compared with one [4%] patient in the control group [P<0.01]. IgG aCL levels were elevated in 13 [52%] patients with Behcet's disease [BD] compared with one [4%] patient in the control group [P<0.01].Also patients with BD do not have decreased protein S, or antithrombin III activity, activated protein C resistance, circulating lupus anticoagulant [LAC], or elevated LgM aCL. No significant differences were found between any variable in both groups. No association between elevated IgMaCL levels and venous or arterial thrombosis and no statistical correlation was found between any factor and clinical manifestations of the disease. A significant number of patients have elevated levels of IgA and IgG aCL but they are not associated with venous or arterial thrombosis. These results do not suggest a primary role for aCL in BD and do not support the role of coagulation abnormalities in the pathogenesis of thromboembolic complications of Behcet's disease but suggest vascular inflammation as the main pathogenetic event in the vascular lesions in Behcet's disease