Immunomodulating treatment with low dose interleukin-4, interleukin-10 and interleukin-11 in psoriasis vulgaris.

Psoriasis is a chronic inflammatory skin disease affecting approximately 2-3 percent of the world population; it is characterised by hyperproliferation and hyperplasia of the superficial layers of the epidermis. Inappropriate signals released by the immune system determine an altered keratinocyte differentiation, resulting in the formation of desquamating, thickened, inflamed and erythematous plaques. The aim of this investigation was to study the pharmacological activity and safety of three low dose cytokines, Guna-Interleukin 4, Guna-Interleukin 10 and Guna-Interleukin 11 at the concentration of 10 fg/ml in patients affected by moderate to slight psoriasis vulgaris. The multicenter, double-blind, randomized, placebo-controlled clinical trial involved 48 patients who were enrolled and followed up according to a 8-month experimental project. All patients received, according to a cross-over model, either the experimental treatment or placebo, alternatively. Globally, in the 41 evaluated patients it was observed a PASI significant reduction (Friedman test: p=0.00960). The DLQI too decreased significantly in all subjects compared to baseline (Friedman test: p=0.00007). The safety of the treatment with three low dose cytokines administered simultaneously was proved; no adverse event was reported during the whole trial.

Hemorheology in complicated hypertension.

During essential and secondary arterial hypertension it is possible to observe changes in microcirculation perfusion associated with a reduction in tissue oxygenation due in part to hemorheological changes such as an increase in blood viscosity or the formation of the red blood cell "rouleaux" which favour an increase in peripheral resistance and can cause or worsen arterial hypertension. We studied 21 healthy subjects (11 male and 10 female aged 42 +/- 4) and 26 hypertensive subjects (14 male and 12 female aged 49 +/- 3). The patients were non smokers and non suffering from respiratory or haemathological pathologies. They were not undergoing antihypertensive or vasodilatory pharmaceutical treatment. The patients suffered from mild hypertension (II WHO) with Peripheral Occlusive Arterial Disease (POAD II "a" acc. to Leriche-Fontaine class.). The patients showed an increase in cholesterolaemia (6.42 +/- 0.81 mmol/l) and trygliceridaemia (2.73 +/- 0.09 mmol/l) at an average level. The patients were studied in standard conditions with a constant temperature of 22 degrees C. We measured SBP, DBP, MBP, and the HR. We also measured the elongation index (EI) (with shear stress range 0.30 to 30 pascals) using LORCA, acc. to Hardeman method (1994), in order to study the erythrocyte deformability and aggregation kinetics in dynamic condition. To evaluate deformability in static conditions we calculated the Erythrocyte Morphologic Index (EMI), acc. to Forconi method, via the bowl/discocyte ratio (for 100 red blood cells fixed in glutaraldehyde at 0.3% and observed with an optical microscope under immersion in glycerol). Peripheral oxygenation was taken transcutaneously (TcpO2). To establish the level of vascular disease we used the Regional Perfusion Index (RPI = TcpO2 foot/TcpO2 subclavean) and doppler guided Winsor Index (WI). The Student "t" test and linear regression were used for the statistical analysis. Our data confirm a reduction in peripheral tissue oxygenation in hypertensives especially if suffering from vascular disease which correlates significantly (p < 0.01) with a reduction in red blood cell deformability. This itself can increase peripheral resistances and favour the onset of hemorheological complications, at a cerebral-vascular level, which are frequent in hypertensives.

Hemorheological aspects in hypertensive menopausal smoker women treated with female hormones.

In postmenopausal hypertensive women (PostMHW) the erythrocyte deformability (ED) is reduced if compared with premenopausal hypertensive women (PreMHW). This might partially explain the increased incidence of cardiovascular diseases (CD) in hypertensive women after menopause. Moreover a positive correlation exists between estradiol and rheological patterns in women. If PostMHW smoke cigarettes, there is an important decrease in hemorheological parameters. On the other hand if PostMHW are submitted to an hormonal replacement therapy (HRT) they can show controversial results with an impairment if hemorheological parameters. The aim of this study was to evaluate the influence of smoking and HRT on PostMHW. We studied four groups of subjects: Group 1: PreMHW (10 F aged 35 +/- 3 years) non smokers; Group 2: PostMHW (8 F aged 45 +/- 2 years) non smokers; Group 3: PostMHW (14 F aged 48 +/- 4 years) smokers (20 cigarettes per day); Group 4: PostMHW (16 F aged 50 +/- 2 years) smokers (20 cigarettes per day) submitted to HRT. We evaluated Elongation Index of erythrocytes under torsion force of 30 pascals (EI--30 Pa) using a new computerized instrument Laser assisted Optical rotational Red Cell Analyzer (LORCA) (Mechatronics, Hoorn, NL) acc. to Hardeman (1994) and, also with the same LORCA, Aggregation Index (AI), t(1/2). We measured the transcutaneous oxygen partial pressure (TcpO2) in subclavicular standard area using a Transcutaneous Oximeter (Microgas 7650 Kontron Instruments with Combi Sensor) and total cholesterolaemia. In PostMHW our data showed a significant (p < 0.01) impairment of hemorheological patterns and tissue oxygenation if compared with PreMHW (Group 1). In Group 3 there is a significant (p < 0.01) decrease in EI, a significant (p < 0.01) increase in AI, a significant (p < 0.01) decrease in t(1/2) and TcpO2 if compared with Control Group 1 and Group 2. Finally a further significant (p < 0.01) impairment in hemorheology and tissue oxygenation showed Group 4. In conclusion, it seems necessary, that many studies will be performed to understand really protective action of HRT on cardiovascular diseases in PostMHW and it is necessary to suppress cigarette smoking to prevent cardiovascular complications in these patients.

Tissular oxygenation and erythrocyte deformability in haemodialyzed patients using different dialytic membranes.

We studied the effect of some dialytic membrane on tissular oxygenation (TO) and erythrocyte deformability (ED). Sixteen patients (10 M and 6 F, aged 59 +/- 12 years) have been submitted to bicarbonate dialysis (BD) and subdivided into four groups (GR) of 4 patients each: GR 1 (hemophan membrane, 35 BD), GR 2 (polyacrylonitrile, PAN AN 69, 42 BD), GR 3 (polysulphone, 38 BD) and GR 4 (polycarbonate, 37 BD). The TO has been detected with the transcutaneous oxygen pressure (Tc pO2) using a transcutaneous oxymeter and the ED has been evaluated with the EMI (Erythrocyte Morphometric Index), which results from the ratio between deformable erythrocytes (bowl shape) and rigid erythrocytes (discocyte shape), for every 100 red cells fixed in vitro with 0.3% glutaraldehyde. The ED was also evaluated using a laser instrument: Laser Optical Rotational Cell Analyser. During BD was observed a significant decrease of Tc pO2 in the 1st hour only in the 1st and 2nd GR and, in contrast with results obtained in the 3rd and 4th GR, in the same GRs the EMI showed a significant reduction of ED at the end of BD. Finally the LORCA results, showing a significant decrease of ED only in the 1st and 2nd GR, confirmed the data obtained with EMI. In conclusion, our study has suggested that hemophan and PAN AN 69 are less biocompatible than polysulphone and polycarbonate membranes according to effects on ED and TO.

Hemorheology and tissue oxygenation in hypertensives with lipoidoproteinosis and peripheral occlusive arterial disease (POAD) treated with sulodexide and pravastatine and evaluated with laser assisted optical rotational red cell analyzer (LORCA) and transcutaneous oxymetry.

BACKGROUND: During arterial hypertension it is often possible to find other factors like lipoidoproteinosis and peripheral arterial disease (POAD), which can accentuate blood rheological abnormalities in hypertensive subjects. A group of hypertensives with lipoidoproteinosis (LP) and POAD were therefore examined to evaluate the relationship between these factors and blood rheological disorders and, if possible, to correct it. METHODS: We studied a group of 27 hypertensives with LP and POAD (15 males and 12 females in menopause for at least 1 year, aged 48 +/- 4 years), with WHO stage I hypertension, obesity (BMI = 30 +/- 2), stage II type "a" POAD, class 2 type "b" lipoidoproteinosis (acc. to Fredrick-son's classification) and hyperfibrinogenemia. All patients received oral medication with 500 lipidic units (ULS) sulodexide a day, 20 mg pravastatin o.d. orally, and were put on a low-salt and low-calorie diet (1400 kcal/day) during a follow-up of 60 days. Blood rheology status was evaluated before and after treatment (red blood cell--RBC--deformability and aggregability) using a new computerized instrument, which uses laser rays: the laser assisted optical rotational red cell analyzer (LORCA) (acc. to Hardeman) and RBC deformability using optical microscopy under immersion (acc. to Zipursky and Forconi). Transcutaneous oxymetry was also used to evaluate tissue oxygenation. RESULTS AND CONCLUSIONS: At the end of the study a significant improvement (p < 0.01) was noted in the blood rheological patterns of peripheral perfusion and tissue oxygenation. This underlined the positive influence of sulodexide with pravastatin in improving hemorheological patterns and modulating hypercholesterolemia and hyperfibrogenemia in hypertensives with POAD II "a" and LP 2 "b" and blood rheology disorders.