Irene Rebelo

The inflammatory response in mild and in severe psoriasis

Background  Psoriasis is a chronic and recurrent inflammatory skin disease. The inflammatory response represents a fundamental ability of the organism to protect itself from infectious agents and from injury.

Dislipidemia and oxidative stress in mild and in severe psoriasis as a risk for cardiovascular disease

Psoriasis is a common chronic and recurrent inflammatory skin disorder that has been associated with oxidative stress, abnormal plasma lipid metabolism and with high frequency of cardiovascular events. This prevalence seems to be related to the severity of psoriasis, as it occurs more frequently in patients presenting large areas of the body affected with psoriasis lesions. The aim of our work was to evaluate the development of oxidative stress and of dislipidemia in psoriasis, and to look for a correlation between their levels and worsening of psoriasis. We evaluated lipid profile, total antioxidant capacity, antioxidant vitamins A and E, and lipoperoxidation products. The study was performed in controls and in patients presenting mild and severe psoriasis. Patients presented risk changes in lipid profile (a rise in cholesterol (P<0.01), triglycerides (P<0.001), low density lipoprotein cholesterol (P<0.01), very low density lipoprotein cholesterol (P<0.01), apolipoprotein B (P<0.001) and lipoprotein(a) (P<0.001); and a reduction in high density lipoprotein cholesterol (P<0.001)), a rise in lipoperoxidation products (P<0.001) and a reduction in total antioxidant capacity (P<0.001) and in antioxidant vitamins A (P<0.001) and E (P<0.05). Moreover, we found that the worsening of psoriasis was associated with the enhancement of oxidative stress and of the lipid risk changes. Our data suggest that psoriasis patients must be considered as a group at risk for cardiovascular disease and that this risk seems to be higher in severe psoriasis. In addition, a possible benefit of an enriched diet or of a supplement of vitamins A and E in psoriasis patients should be further studied.

Neutrophil Activation and C‐Reactive Protein Concentration in Preeclampsia

Preeclamptic pregnancies seem to be associated with a higher extent of inflammation compared with normal ones. We intended to test this proposal and also to clarify the contribution of some variables in such inflammatory process. We measured total and differential leukocyte count, serum C‐reactive protein (CRP), and plasma levels of lactoferrin, elastase, and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Uric acid was also evaluated and used as an indicator of the severity of the disease. A cross‐sectional study was performed by evaluating healthy and preeclamptic women in the third trimester of gestation (n = 67 and n = 51, respectively) and 24 to 48 h postpartum (n = 32 and n = 26, respectively). When comparing the third trimester of normal and preeclamptic pregnancies, we found significantly higher levels of uric acid, CRP, and elastase, and a significantly higher elastase to neutrophil ratio in the pathologic group. However, for CRP, statistical significance was lost after adjustment for maternal weight. No significant differences were found in total leukocyte count, plasma levels of GM‐CSF, and lactoferrin between groups. In preeclampsia, a significant positive correlation was found between elastase and lactoferrin and these neutrophil activation products correlated positively with uric acid level. Considering the analysis of all variables in the postpartum period, only CRP and uric acid levels were significantly elevated in the pathologic group. However, CRP differences obtained in the puerperium seem to be influenced by the increased number of dystocic deliveries in the preeclamptic group. In conclusion, our data suggest that inflammation is further pronounced in preeclampsia and that the extent of neutrophil activation correlates with the severity of this syndrome.

Inflammatory Disturbances in Preeclampsia: Relationship between Maternal and Umbilical Cord Blood

Preeclampsia (PE) is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB), in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin), proinflammatory cytokines (IL-6 and TNF-α), leukocyte activation (elastase, lactoferrin, sL-selectin, sVCAM, sPECAM), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation.

Elevated tissue plasminogen activator as a potential marker of endothelial dysfunction in pre-eclampsia: correlation with proteinuria

Objective To clarify the role played by endothelial cell production of fibrinolytic factors in normal pregnancy and pre‐eclampsia.

Erythrocyte damage in mild and severe psoriasis

Background  Psoriasis is a common chronic and recurrent inflammatory skin disorder. Oxygen metabolites and proteases released by activated inflammatory cells may induce oxidative and proteolytic damage to plasma constituents and red blood cells (RBCs). RBCs have a limited biosynthesis capacity and poor repair mechanisms.

Erythrocyte damage and leukocyte activation in ischemic stroke

BACKGROUND The traditional lipid risk factors can only predict some of the cardiovascular events. Our work has focused on new potential biological markers of risk, namely leukocyte activation and erythrocyte membrane damage, in ischemic stroke cases. METHODS Besides the traditional lipid profile, we evaluated the plasma levels of elastase and lactoferrin as markers of leukocyte activation, and membrane band 3 protein profile and membrane bound hemoglobin as markers of erythrocyte damage. Total and differential leukocyte counts and erythrocyte counts, hematocrit and hemoglobin concentrations were also evaluated. The lipid study included the evaluation of triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), apolipoprotein AI (Apo AI) and B (Apo B), and lipoprotein (a) (Lp(a)). The work was performed in a control group (n=29) with no history of cardiovascular events, presenting normal hematological and lipid values, and in a pathologic group (n=21) of ischemic stroke cases diagnosed by computed tomographic imaging. RESULTS We found that ischemic stroke was associated with significantly higher values of leukocytes, which seem to be activated, as shown by significant higher levels of elastase and lactoferrin. This activation seems to impose erythrocyte damage, as suggested by a significant increase in membrane bound hemoglobin and by a different band 3 profile. CONCLUSIONS Our data suggest that plasma levels of elastase and lactoferrin, together with levels of erythrocyte membrane bound hemoglobin and band 3 profile, could be used as powerful new markers of risk for cardiovascular events.

Comparative study of lactoferrin and other blood markers of inflammatory stress between preeclamptic and normal pregnancies

OBJECTIVE To test lactoferrin as a blood discriminator of neutrophil activation between normal and preeclamptic pregnancy. DESIGN Comparative study between normal (n = 40) and preeclamptic women receiving treatment (n = 42) in the third trimester of pregnancy and in the post partum period (30 women with normal pregnancy and 22 with preeclampsia). METHODS Blood, serum or plasma measurements of neutrophils, lactoferrin, vitamin C, vitamin E, lipid peroxidation products, elastase, C-reactive protein (CRP), gamma-glutamyltranspeptidase (gamma GT), haptoglobin, osmotic fragility, urea, creatinine, uric acid, transaminases (ASAT, ALAT), lactic dehydrogenase (LDH), platelets, red and white blood cells. RESULTS In preeclamptic women the ratios of lactoferrin per neutrophil or per erythrocyte are higher before delivery than in normal women but decrease after delivery. Delivery induces a greater inflammatory response in normal pregnancy as detected by blood concentrations of inflammatory markers and hepatic and renal parameters. CONCLUSION Whereas in normal pregnant women neutrophil activation increases with delivery, in preeclamptic women the opposite occurs.

Lactoferrin as a sensitive blood marker of neutrophil activation in normal pregnancies

OBJECTIVE To test lactoferrin as a marker of neutrophil activation during pregnancy. DESIGN Cross-sectional study in normal pregnant (n = 100), nonpregnant (n = 11) and post partum women (n = 30). METHODS Serum or plasma measurements of neutrophils, lactoferrin, vitamin C, vitamin E, lipid peroxide, elastase, C-reactive protein gamma-glutamyltranspeptidase, haptoglobin and osmotic fragility. RESULTS During normal pregnancy all markers of neutrophil-activation increase. CONCLUSION Neutrophil-activation compromises the antioxidant defense mechanism during normal pregnancy.

Apolipoprotein E and cholesteryl ester transfer protein polymorphisms in normal and preeclamptic pregnancies

OBJECTIVES To evaluate the association of apolipoprotein (apo) E polymorphism and a cholesteryl ester transfer protein (CETP) polymorphism (CETP/TaqIB) with preeclampsia and with lipid/lipoprotein profile in pregnancy. MATERIALS AND METHODS A group of 144 normal pregnant women (67 in the third trimester) were compared with 51 cases of preeclampsia in the third trimester of gestation. Apo E and CETP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Serum lipids, lipoproteins and apolipoproteins were evaluated using commercially available kits. LDL size was assessed by gradient gel electrophoresis. RESULTS No differences were found in the distribution of subjects with respect to genotypes, in the apo E and CETP polymorphisms, between control and pathologic groups. In the third trimester of gestation (both control and case groups considered), apo E polymorphism, but not CETP polymorphism, was associated with different lipid and lipoprotein levels. Patients carrying the E2 allele (E2+) presented with significantly lower values of LDL cholesterol (LDLc) compared with carriers of E4 (E4+) and E3/3 individuals. E2+ also presented with the highest triglyceride (TG) level, although this was not statistically significant. On the other hand, HDL cholesterol (HDLc) and apo A-I levels were significantly reduced in E4+, compared with E3/3. Furthermore, E4+ presented with the highest total cholesterol and LDL and therefore LDLc/HDLc and apo B/apo A-I ratios were significantly higher in this group compared with the other two. CONCLUSIONS Neither of our candidate genes showed association with preeclampsia. However, apo E genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.