BELTOWSKI, JERZY, GRAŻ YNA WÓ JCICKA, AND EWA BORKOWSKA. Human leptin stimulates systemic nitric oxide production in the rat. Obes Res. 2002;10: 939 -946. Objective: Apart from having an effect on energy balance, leptin is also involved in cardiovascular regulation and in the pathogenesis of obesity-associated hypertension. We investigated the effect of leptin on nitric oxide (NO) production. Research Methods and Procedures: Wistar rats were placed in metabolic cages, and urine was collected in 2-hour periods. After the control period, leptin (1 mg/kg intraperitoneal) was administered, and urine collection was continued for up to 6 hours. Blood was obtained 0.5, 1, 2, 4, and 6 hours after hormone injection. Results: Leptin increased plasma concentrations of NO metabolites (nitrates ϩ nitrites, NO x ) by 32.5%, 58.0%, and 29.7% at 1, 2, and 4 hours, respectively. Urinary NO x excretion increased by 28.8% in the first and by 20.1% in the second 2-hour period after injection. The plasma concentration of the NO second messenger, cyclic guanosine 3Ј,5Ј-monophosphate (cGMP), increased by 83% and 50.6% at 2 and 4 hours after leptin administration, respectively. Urinary excretion of cyclic GMP increased by 36.1% in the first and by 43.1% in the second 2-hour period. Leptin had no effect on the plasma concentration of atrial natriuretic peptide (ANP). The effect of leptin on plasma and urinary NO x was abolished by the NO synthase inhibitor, N G -nitro-L-arginine methyl ester (L-NAME) (30 mg/kg intraperitoneal) administered 15 minutes before leptin injection. L-NAME alone caused a 32.2% increase in systolic blood pressure, but this increase was not observed in rats receiving L-NAME and leptin. Discussion:The results indicate that leptin stimulates systemic NO production; leptin prevents blood pressure elevation induced by acute NO blockade, suggesting that leptin also triggers additional hypotensive mechanisms; and ANP is not involved in renal and vascular effects of leptin.

Introduction: Infliximab (IFX) is a monoclonal antibody that binds to and neutralizes TNF-α. IFX (Remicade) was approved by the U.S. Food and Drug Administration in 2006 for the treatment of severe plaque psoriasis. In 2013 two infliximab biosimilars: Remsima and Inflectra were also registered. The introduction of biosimilar drugs is associated with a significant reduction in treatment costs. Aim: To evaluate the efficacy of treatment with biosimilar IFX with non-medical switch option in patients with plaque psoriasis under the drug program "Treatment of moderate and severe plaque psoriasis" of the Ministry of Health in Poland. Material and methods: The group of 91 adult patients with moderate to severe plaque psoriasis, unresponsive or with contraindications to the standard treatment were qualified to the drug program (in 2016-2018). Efficacy of treatment with biosimilar IFX was evaluated using the Psoriasis Area and Severity Index, body surface area and Dermatology Life Quality Index scoring performed at week 0, 14, 46 and 94. Results: The mean change in PASI, DLQI, and BSA scores at week 14 was 89.92%, 93.75% and 90.91%, respectively. By week 14, 83.52% of patients achieved PASI75, 49.45% PASI ≥ 90 and 26.37% PASI100. At week 46, 84.62% of patients achieved PASI75, 54.95% PASI ≥ 90, and 21.98% PASI100. At week 94 of therapy, 80.22% of patients achieved PASI75, 48.35% PASI ≥ 90, and 18.68% PASI100. At week 94 of therapy, PASI100 was maintained by 37.5% of patients who achieved PASI100 at week 14. Conclusions: 94-week therapy with biosimilar infliximab results in high and sustained clinical efficacy in patients with moderate to severe psoriasis.