Prevalence and extent of subclinical atherosclerosis in patients with psoriasis.

OBJECTIVE: Patients with psoriasis are prone to premature atherosclerosis and increased risk of cardiovascular disease events. However, the prevalence and extent of atherosclerosis in patients with psoriasis are unknown. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: The prevalence and extent of coronary and carotid atherosclerosis were compared in 70 patients with psoriasis (46 ± 9 years, 71% male) without known cardiovascular disease or joint involvement and 51 age- and gender-matched healthy control subjects (45 ± 7 years, 71% male). Systemic inflammation was assessed by the level of high-sensitivity C-reactive protein (hs-CRP). Coronary atherosclerosis was determined by the coronary calcification score (CCS) measured by multi-detector computed tomography. Carotid atherosclerosis was assessed by high-resolution ultrasound-derived carotid intima-media thickness (cIMT). RESULTS: Patients with psoriasis had a higher prevalence of coronary atherosclerosis (CCS > 0; 28.6% vs. 3.9%, P < 0.01), and a higher degree of coronary atherosclerosis estimated by the mean CCS (67.4 ± 349.2 vs. 0.5 ± 3.0, P < 0.05) compared with controls. Similarly, cIMT was significantly greater in patients with psoriasis than in control subjects (0.73 ± 0.11 mm vs. 0.67 ± 0.08 mm, P < 0.01). Multiple logistic regression revealed that psoriasis [odd ratio (OR): 10.54, 95% confidence interval (CI) 1.89-58.67, P < 0.01] and serum total cholesterol level (OR 2.10, 95% CI 1.01-4.37) were associated with the presence of coronary atherosclerosis (CCS > 0). By contrast, only age was independently associated with increased cIMT. Amongst participants with no traditional cardiovascular disease risk factors, hs-CRP level was higher in patients with psoriasis than in controls. CONCLUSION: The present results demonstrate early-onset, diffuse arterial atherosclerosis in coronary and carotid arteries in patients with psoriasis, but not in age- and gender-matched control subjects. Low-grade inflammation could explain the presence of premature atherosclerosis in patients with psoriasis.

Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation.

BACKGROUND: Psoriasis is associated with premature atherosclerosis although the underlying mechanism remains unclear. OBJECTIVES: We sought to investigate the relationship between disease activity and systemic inflammation in patients with psoriasis, and macrovascular and microvascular function. METHODS: Fifty-two patients with psoriasis (mean ± SD age 44 ± 8 years; 38 men) were compared with 50 age- and sex-matched controls. Baseline demographics and high-sensitivity C-reactive protein (hs-CRP) level were recorded for each subject. Psoriatic disease activity was assessed using the Psoriasis Area and Severity Index (PASI). Arterial stiffness and endothelial function were assessed using brachial to ankle pulse wave velocity (baPWV) and digital hyperaemic response measured using the peripheral arterial tonometry (PAT) index. RESULTS: Patients with psoriasis had significantly higher hs-CRP (mean ± SD 5·3 ± 5·1 vs. 1·9 ± 1·6 mg L(-1), P < 0·01) and baPWV (mean ± SD 14·5 ± 2·5 vs. 13·2 ± 1·6 m s(-1) , P < 0·01) but not PAT index (mean ± SD 2·06 ± 0·59 vs. 2·10 ± 0·44, P = 0·70) than controls. There was significant correlation of hs-CRP with baPWV (r = 0·51, P < 0·01) and with PASI (r = 0·48, P < 0·01). Multiple linear regression analysis demonstrated that baPWV is independently correlated with age, fasting glucose and hs-CRP (P < 0·05), but does not predict PAT index. Each mg L(-1) increase in hs-CRP accounted for an increase in baPWV of +0·12 m s(-1) (95% confidence interval 0·01-0·22, P = 0·03). CONCLUSIONS: Young patients with psoriasis have increased arterial stiffness but not microvascular dysfunction compared with healthy controls. More importantly, hs-CRP positively correlated with, and independently predicted, arterial stiffness. This suggests that systemic inflammation in patients with psoriasis is associated with premature atherosclerosis.

[Early ultrastructural evolution of murine malaria merozoites after entering red cells].

A TEM study of murine malaria parasites, Plasmodium berghei and P. yoelii was performed by consecutive sampling in vivo to look into the early sequential changes in the ultrastructure of the merozoites after entering red cells. The results showed that once finishing invasion, the merozoite resided in the peripheral cytoplasm of the red cell, creating a bulge at the invasion site, with an additional unit membrane around it (parasitophorous vacuole); apical structures disappeared; the spherical body was degenerative or atrophic and separated from the mitochondrion and nucleus. The mitochondrion became more extended and the nucleus elongated and curved. There were more Er vesicles in the cytoplasm, taking a dilated polyangular shape. The inner double membrane was separated from the outer membrane and got into incomplete, winding, finally disappeared. Sometimes multimembranous bodies could be seen in the peripheral spaces. Once the dedifferentiation process was over, the merozoite was transformed into an early trophozoite, with a single plasma membrane and decreased density. Individual large Er vesicle with acute angles was found in the cytoplasm, and small food pills appeared beneath the plasma membrane; then the shape of the parasite changed from a ball-like one to a pie-like one, gradually the flat cell body rolled up, with its edges met and fused, resulting in the formation of a large food vacuole, with digestive vacuoles and pigment granules around it. Thus, it grew into a middle-aged trophozoite.

Anti-allergic effects of scoparone on mast cell-mediated allergy model.

Scoparone is known to have a wide range of pharmacological properties in vitro. However, the roles of scoparone in immediate-type allergic reactions have not yet been investigated. In this study, we demonstrated that scoparone attenuated IgE-mediated allergic response in mast cells. Oral administration of scoparone inhibited passive cutaneous anaphylaxis in rats. Presence of scoparone dose-dependently decreased histamine release from rat peritoneal mast cells (RPMC) stimulated by anti-dinitrophenyl IgE. Moreover, scoparone reduced the expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 in RPMC. Pretreatment with scoparone inhibited the calcium uptake and p38 mitogen-activated protein kinase (MAPK) activity. Furthermore, scoparone blocked translocation of nuclear factor-kappa B (NF-kappaB) p65 subunit by suppressing IkappaBalpha phosphorylation in RPMC. Reduced calcium uptake as well as the suppressed activity of p38 MAPK and NF-kappaB might be involved in the inhibitory effect of scoparone on the secretory response. Our findings suggest that scoparone may serve as an effective therapeutic agent for allergic diseases.

[Effects of alpha-dimethylamino-cyclohexoxyl-dimethyl gallium on ultrastructure of erythrocytic stage of Plasmodium berghei and P yoelii].

The effects of alpha-dimethylamino-cyclohexoxyl-dimethyl gallium (DCDG), a new antimalarial drug developed in China, on the ultrastructure of murine malaria parasites in vivo was studied in comparison with those of chloroquine (CQ) and artemisinin (Art). All these 3 antimalarials were administered ig to mice at dosages of 1-3, 40-80, and 200-400 mg.kg-1 for DCDG, CQ, and Art respectively, based on a similar intensity of morphological changes in the parasites. Blood samples were collected for electron microscopy from 15 min to 48 h after medication. The results showed that DCDG killed the malaria parasites (both asexual and sexual forms) rapidly. The most prominent changes in DCDG-treated parasites were serious dilation of perinuclear space, endoplasmic reticulum, mitochondrion and some other vesicles or intermembranous spaces. These led to the formation of large autophagic vacuoles containing some membranous materials, which were subsequently extruded. Then the parasite cells became more concentrated, finally pyknotic and died. The mode of action was very different from that of CQ and Art.

[Cloning, expression and preliminary application of a alpha-hydroxynitrile lyase from cassave].

alpha-Hydroxynitrile lyase (ME-HNLs, E.C. 4.1.2.3.37) from the cyanogenic crop cassava(Manihot esculentz, Crantz) catalyze the condensation of hydrocyanic acid and aldehydes or ketone into (s)-cyanohydrins, which are valuable starting material for various optically active compounds, such as pharmaceuticals and agrochemicals. The cDNA of a ME-HNL were obtained by RT-PCR and cloned. The sequencing result for the cDNA showed that the sequence encoded for the ME-HNL was inconsistent with all those which are published, such as hnl10, hnl24, hnl4. The full sequence analysis demonstrated that the cloned cDNA was about 75.2%, 79.8%, 99.2% homologous to other three reported HNL genes from cassava, respectively, among which the last was the same to the cloned gene except the five base substitution at the site 142, 337, 476, 634 and 636, respectively. The two base substitutions lead to change the amino acid sequence, i.e., Ser113-->Gly113, Phe158-->Tyr158. To construct the recombinant plasmid pET30a-hnl, the cDNA was inserted into an expression vector pET30a. After transformation of pET30a-hnl and induction with IPTG, the ME-HNL was efficiently expressed in E. coli. BL21 (DE3) and reached over 2100 units/L of culture with the specific activity 8.5 u/mg protein. By one simple treatment, incubating 10 minutes at 70 degrees C, the recombinant ME-HNL may be used as an catalyst for production of (S)-mandelonitrile with enantiomeric excess of 95.2% and 98.2% yield.