Understanding the role of haptoglobin in psoriasis: effects of ultraviolet B.

BACKGROUND: Haptoglobin (Hp) is one of the acute phase proteins, whose main function is to bind free haemoglobin (Hb) and transport it to the liver for degradation and iron recycling. In addition to its role as an Hb scavenger, Hp has been shown to behave as an anti-inflammatory, antioxidant and angiogenic factor. We previously investigated the role of Hp in the pathogenesis of psoriasis, and found that it displays some structural modifications that might be associated with protein function in the disease. Phototherapy is an efficacious treatment for psoriasis, although the biological mechanisms by which phototherapy improves psoriasis are still unclear. AIM: To investigate the effects of ultraviolet (UV)B on Hp to clarify the role of Hp in psoriasis. METHODS: Expression of the genes encoding Hp, interleukin (IL)-6 and IL-10 was assessed in UVB-irradiated and unirradiated HaCaT cells. The biological significance of Hp modulation of UVB treatment was confirmed by ELISA and Western blotting. The Hp gene and protein expression in the skin of patients with psoriasis was also investigated. RESULTS: In vitro results showed that UVB modulated IL-6 and IL-10 gene expression and Hp gene and protein expression in HaCaT cells. The in vivo data also showed that Hp levels were increased in the skin of patients with psoriasis compared with healthy controls. CONCLUSIONS: UVB irradiation was able to modulate Hp production in immortalized keratinocytes. The higher levels of Hp in vivo in both lesional and nonlesional skin suggest that it might have a role in the pathogenesis of the disease.

Effects of adalimumab therapy in adult subjects with moderate-to-severe psoriasis on Th17 pathway.

BACKGROUND: Until relatively recently, psoriasis has been considered to be a mainly T helper (Th)1-driven inflammatory disease; however, several findings have now assessed a major role for Th17 cells in its pathogenesis. Adalimumab is a biological agent that inhibits TNF-α, a pro-inflammatory cytokine with a pivotal role in the mechanisms of the disease. OBJECTIVE: To elucidate the in vivo effects of adalimumab therapy on Th17 pathway. METHODS: Quantitative real-time reverse transcriptase polymerase chain reaction was used to analyse levels of expression of Th17 polarizing cytokines (IL-23A, TGF-ß, IL-1ß, IL-6), Th17 cytokines (IL-17, IL-22) as well as TNF-α, Th1 polarizing cytokine (IFN-α) and Th17 downstream effector mediators, such as chemokines (IL-8, CCL-20) in skin and peripheral blood mononuclear cells before and after 16 weeks of adalimumab therapy. Similarly, gene expression of Th17 induced mediators by keratinocytes (antimicrobial peptides: HBD-2, S100A7) was investigated at skin level. In addition, cutaneous and plasma IL-17 was examined by immunohistochemistry and enzyme-linked immunosorbent assay respectively. Efficacy of the treatment was assessed by several clinical index scores as well as epidermal thickness reduction. RESULTS: Adalimumab therapy led to improvement in skin disease scores in all patients. Moreover, adalimumab treatment down-modulated Th17 pathway at skin level. Plasma IL-17 levels and IL-17-positive cells in psoriatic lesional skin were decreased by adalimumab treatment. CONCLUSIONS: Our data highlight that the immunomodulatory activity of adalimumab is associated with considerable clinical improvements as well as a potent shut down of Th17 response in patients with moderate-to-severe psoriasis.

Long-term efficacy of nitroglycerin patch in stable angina pectoris.

Subchronic and chronic efficacy of a 10 mg of nitroglycerin (NTG) patch was studied in 30 patients with stable angina pectoris. The trial consisted of 2 periods of study: 1 period of 2 months with a double-blind, crossover, placebo-controlled design and a second period of open treatment with verum patch. Two 7-day washout periods were performed at entry and at the end of the study. Efficacy was evaluated by clinical assessment of anginal attacks and NTG consumption and by means of multistage treadmill exercise testing. Exercise tests were performed at time 0 (24 hours from application of last patch), at 4 and 12 hours after dosing at the end of first 7-day washout, at the end of the first month of treatment, at the end of the second month of treatment after crossover, at the end of 3 months of treatment with active patch and at the end of the second 7-day washout period. Statistics were obtained by multivariate analysis of difference. In 27 patients whose records were available for final analysis the daily attacks of angina and NTG consumption decreased significantly during both the subchronic and chronic phases of the trial compared with placebo (p less than 0.001). Subchronic study showed significant improvement of maximal exercise duration, time to onset of angina, time to ST-segment depression of 1.0 mm, time to regression of angina and time to regression of ST depression, compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous amiodarone in acute anterior myocardial infarction: a controlled study.

A randomized, single-blind controlled study intended to assess the potential benefits of intravenous amiodarone in anterior myocardial infarction is presented. Three hundred nineteen patients entered the study, 159 received amiodarone infusion, and 160 received glucose-insulin-potassium (GIK) infusion. Basal characteristics were similar in the two experimental groups, who were randomized on a consecutive basis. Exclusion criteria were shock or pulmonary edema, hypotension, inferoposterior infarction, bradycardia, antrioventricular block, severe diabetes, and other major diseases. Patients aged 27 to 70 years, with a Q-wave anterior infarction, initiated 12-40 hours earlier at the time of admission, entered the trial. Other entry criteria were heart rate higher than 80 beats/min and systolic blood pressure higher than 100 mmHg. Amiodarone was administered in saline infusion 10-20 mg/kg, within 4 to 10 hours, through a central vein. GIK infusion consisted of 150-300 g of glucose, 25-50 IU of insulin, and 80-120 mEq of KCl in 1000 cc of water at a rate of 1.5-2.0 ml/g/hour. Both groups received digitalis, nitrates, sedatives, and diuretics as needed. Although individually the major endpoints of death, reinfarction, and sustained supraventricular and ventricular arrhythmias did not differ significantly, each was less in the amiodarone group than in the control, and the sum of all adverse events was significantly lower for the amiodarone patients (p less than 001). Heart failure and conduction disturbances were not different in the two groups. This study shows that amiodarone, with its vasodilating and antiarrhythmic properties, may be beneficial in acute anterior infarction, but further studies on larger populations will be necessary in order to show a reduction of mortality rate.

Efficacy of a new transdermal nitroglycerin patch (Deponit 10) for stable angina pectoris.

In this double-blind randomized placebo-controlled crossover study, the antianginal and anti-ischemic effect of a new transdermal system, releasing 10 mg of nitroglycerin (NTG) over 24 hours, was assessed in 19 outpatients with stable exercise-induced angina pectoris. The trial consisted of a 3-day washout: a 1-week period with verum or placebo patch followed by a second 1-week period with the other patch. During the study only sublingual NTG was allowed, and its consumption and the number of attacks recorded. Treadmill exercise tests were performed at the end of washout before patch application (baseline test) and 3 and 24 hours, respectively, after each period of 7 days of application of 1 patch daily. Systolic blood pressure and heart rate did not vary significantly at rest in the 17 patients who completed the trial. Angina was reduced 31.3% and NTG consumption 34.3% (p less than 0.01) during the week with Deponit 10 as compared with placebo. Exercise duration increased 29 and 16.1% (p less than 0.001 and p less than 0.1, respectively) at 3 and 24 hours with a verum patch as compared with placebo. ST-segment depression at comparable loads decreased 69 and 40.5% (p less than 0.01) at 3 and 24 hours, respectively, after application of Deponit. Onset of angina was delayed and maximal heart rate-blood pressure product significantly increased at 3 and 24 hours of treatment. It is concluded that Deponit 10 patch is effective in reducing anginal attacks and in increasing exercise capacity up to 24 hours after application.

[Long-term (10 years) predictive value of the exercise test after myocardial infarct and significance of the longitudinal repetition of the test during follow-up]. / Valore predittivo a lungo termine (10 anni) della prova da sforzo nel post-infarto e significato della ripetizione del test longitudinalmente nel corso del follow-up.

Our follow-up after myocardial infarction consists of 321 patients followed for 10 years or until death. 147 patients, free of clinical features associated with high risk of subsequent events, underwent a late exercise test at cycloergometer 6 to 17 months after infarction. Ten year mortality was 48.3% and 10.3% in patients with a positive or a negative test respectively (p less than 0.0001). Incidence of nonfatal reinfarction was 4.6% and 33.3% respectively (p less than 0.001). 108 patients underwent a second test later in the follow-up (2.8 +/- .9 years): in 27 patients who were positive at first test the second test was also positive and mortality was 33.3%. Sixteen out of 81 patients with a former negative test resulted positive at a repeat test and mortality was 37.5% vs a 3% mortality rate among 65 patients who were negative at both tests. Thus long-term prognostic significance of exercise stress testing after acute myocardial infarction is confirmed and extended, despite limitation of a late test. Moreover, the second test along the follow-up allows further stratification. In conclusion, patients with a negative test and without clinical features predictive of poor prognosis constitute a very low risk group who need not undergo invasive testing, whereas patients with a positive result or who become positive at following test deserve further evaluation and may become bypass candidates in the ensuing years.