Enhanced functional stability of plasminogen activator inhibitor-1 in patients with livedoid vasculopathy.

Livedoid vasculopathy (LV) is a chronic, recurrent, painful cutaneous disease with distinctive clinical features and an uncertain etiology. The skin lesions are recognizable by focal purpura, depigmentation and shallow ulcers. Thrombophilic conditions occur frequently in patients with LV. While no definitive treatment exists for LV, smoking cessation, antiplatelet therapy, immunosuppressive treatment, and anabolic steroids are often included in the therapeutic ladder. Recently, a possible link between LV and impaired fibrinolysis was established as cutaneous LV lesions responded to tissue plasminogen activator (t-PA) infusion suggesting that inhibition of the fibrinolysis through plasminogen activator inhibitor-1 (PAI-1) activity may determine the disease course in patients with LV. In this study, we investigated PAI-1 antigen (Ag) and activity levels in 20 patients with biopsy proven LV (mean age 26 ± 11, M/F = 7/13, median disease duration 3.5 years). All patients received antiplatelet treatment with aspirin and/or dipyrimadole and 14 patients received anabolic steroids or immunosuppressive treatment. Fasting PAI-1 Ag and activity levels were measured at 9 AM in all patients. Both Ag (34 (26) ng/ml) (median (interquartile range)) and specific activity (17 (23) IU/fmole) levels of PAI-1 were moderately elevated in LV patients compared to the controls, however, PAI-1 kinetic studies demonstrated markedly enhanced stability of PAI-1 activity in plasma from patients with LV. Specific activity at 16 h was significantly higher than expected specific activity levels (7 (11) vs. 0.07 (0.09) IU/fmole, P < 0.01). While the exact mechanism of increased stability of PAI-1 activity is not known, it may be due to post-translational modifications or increased binding affinity for a stabilizing cofactor. In conclusion, enhanced stability of PAI-1 may contribute to the pathophysiology of LV, and systemic or local treatment with PAI-1 inhibitors may offer a potential treatment alternative in patients with LV.

Evaluation of renal function in low-dose cyclosporine-treated patients using technetium-99m diaminocyclohexane: a cationic tubular excretion agent.

Technetium-99m diaminocyclohexane (DACH) is a new tubular agent excreted via a cationic transport mechanism, like cyclosporine-A (CsA). It is expected that 99mTc-DACH will permit effective assessment of tubular function in CsA-treated patients. To establish the pharmacokinetic characteristics of 99mTc-DACH and to ascertain whether this new agent is useful in CsA-treated patients, 11 healthy volunteers and 15 CsA-treated patients underwent renal imaging and clearance studies using 99mTc-DACH and chromium-51 ethylene diamine tetra-acetic acid (EDTA). 99mTc-DACH yielded satisfactory dynamic renal images in all participants. The mean plasma clearance of 99mTc-DACH was significantly greater than that of 51Cr-EDTA in volunteers (109.4¿19.7 ml/min versus 86.6 +/- 13.7 ml/min, P<0.05). However, the urinary excretion of 99mTc-DACH at 90 min was significantly lower than that of 51Cr-EDTA (46.1% +/- 9.3% versus 53.1% +/- 8.6%, P<0.05), most probably due to its partial parenchymal retention. The elimination half-life of 99mTc-DACH was significantly increased in CsA-treated patients in comparison to volunteers, and consequently the plasma clearance values were significantly suppressed in these patients, in contrast to 51Cr-EDTA and endogenous creatinine clearance values. In conclusion, our findings indicate that 99mTc-DACH, as a sensitive marker of cationic tubular function, could be used to monitor renal haemodynamics in patients receiving CsA treatment.

The HLA association of lepromatous leprosy and borderline lepromatous leprosy in Turkey. A preliminary study.

Among 50 patients with lepromatous leprosy and borderline lepromatous leprosy in Turkey, the prevalence of HLA-DR2 was 25/50 (50%). The prevalence of the same alleles among 50 healthy controls was 13/50 (26%).