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Biomedical subjects

C Bonifati

Publications and source records attributed to C Bonifati.

At least 37 records · Page 2Linked to original sources

The serum levels of sE-selectin are increased in patients with bullous pemphigoid or pemphigus vulgaris. Correlation with the number of skin lesions and recovery after corsticosteroid therapy.

Soluble E (sE)-selectin represents the soluble isoform of cellular E-selectin, an adhesion molecule synthesized only by endothelial cells. As a consequence, it may be considered a marker of endothelial activity. The aim of this study was therefore to evaluate the serum levels of sE-selectin in nine patients affected with pemphigus vulgaris (PV) and in 15 patients with bullous pemphigold (BP). Higher amounts of sE-selectin, median 40.3 ng/mL, range 30-109.6 were found in the patients when compared with 20 healthy individuals, median 28.5 ng/mL, range 6.4-48; P < 0.01, matched for sex and age. These levels were also significantly correlated with the number of detectable lesions (r = 0.63, P < 0.001) when the patient data were considered at the time of the first observation. Thirteen subjects were followed over time for a maximum of 3 months (from three to seven observations). During therapy, the number of lesions and the serum sE-selectin values decreased concomitantly. Differently from sE-selectin, the serum soluble intercellular adhesion molecule-1 (sICAM-1) values were not significantly different in the patients from the controls and showed no correlation with the serum sE-selectin concentrations or with the number of lesions. The data presented point to the possible use of sE-selectin determinations as a non-specific follow-up marker, suitable to gauge disease intensity over time and emphasize that endothelial activation is present in BP as well as in PV.

Administration, Topical↗

Cytokines in the sera of patients with pemphigus vulgaris: interleukin-6 and tumour necrosis factor-alpha levels are significantly increased as compared to healthy subjects and correlate with disease activity.

Cytokine serum levels, when detectable, are currently measured in many disease states, both to evaluate a possible pathogenetic involvement of such molecules and for clinical purposes. No data are currently available on the cytokine levels in the sera of patients with pemphigus vulgaris (PV), a rare bullous disease of autoimmune origin. This study presents data concerning the levels of 13 different cytokines assayed in the sera of 25 patients affected with PV as compared with 20 healthy subjects using high sensitivity ELISA kits. Of the 13 molecules analyzed, no differences in the levels of most cytokines were observed between pemphigus and control sera, with the exception of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Serum TNF-alpha and IL-6 levels were found to be significantly higher in PV patients than in normal controls (p < 0.001). Furthermore, the levels of the two cytokines decreased after one month of corticosteroid therapy. A significant correlation was found between the serum levels of both TNF-alpha and IL-6 and the number of lesions for each patient (p < 0.001). The data presented support an involvement of at least IL-6 and TNF-alpha in the biological modifications associated with PV manifestations.

Adult↗

CD4 Lymphocyte enumeration: comparison between flow cytometry and enzyme immunoassay.

Assessment of the CD4 lymphocyte number, currently performed by flow cytometry, is one of the main laboratory tests for establishing progression to acquired immunodeficiency syndrome (AIDS). An enzyme immunoassay has recently been commercialized which can be very useful for counting CD4 cells in laboratories where flow cytometers are not available. In the present study, a comparative evaluation of CD4 positive lymphocytes with flow cytometry and the enzyme assay was made in healthy subjects (N = 30, R = 0.88, P < 0.0001), human immunodeficiency virus (HIV)-infected individuals (N = 80, R = 0.91, P < 0.0001), and patients with autoimmune diseases (N = 28, R = 0.82, P < 0.001) or psoriasis (N = 18, R = 0.76, P = 0.01). A correlation between the two methodologies was not found in psoriatic patients under treatment with cyclosporin A (N = 7, R = 0.05, not significant). Some differences could be found at low CD4 lymphocyte levels since the influence of CD4 antigen eluted from monocytes or soluble CD4 in the whole blood sample could cause overestimation of CD4 cell numbers by the enzyme assay.

Acquired Immunodeficiency Syndrome↗

Correlation of lesional skin corneometry values with serum E-selectin levels and disease severity in patients affected by plaque-type psoriasis: recovery after effective therapy.

Ten subjects with plaque-type psoriasis (5 females, 5 males, median age 47, range 20-71 years, median psoriasis area and severity index [PASI] score = 15.5, range 8.1-23.0) were observed before (week 0) and at the second and sixth week after starting treatment (PASI = 10.5, range 7.8-14.6; PASI = 8.5, range 1.6-11.6, respectively). At each of these times, the patients were evaluated for both lesional and unlesional skin corneometry and serum E-selectin values, previously shown to be increased in psoriatic subjects. At time 0, both the corneometry and the E-selectin values were significantly correlated with the PASI, infiltration and desquamation scores. As expected, the corneometry was statistically higher in the unlesional than in the lesional areas (p < 0.001). After therapy, the lesion improvement was related both to the PASI scores and E-selectin level decreases (from median levels of 15.5 to 8.5 and from 18 to 13.2 ng/ml, respectively, p < 0.05) as well as to the corneometric level increases (from a median value of 34.5 to 42, p < 0.05). Considering the data obtained at all of these times, significant correlations were found between the PASI scores, lesional skin corneometry and serum E-selectin levels. In conclusion, lesional corneometry seems to represent an objective alternative method for reliably monitoring psoriatic patients.

Adult↗

Soluble E-selectin and soluble tumour necrosis factor receptor (60 kD) serum levels in patients with psoriasis.

BACKGROUND: Increased tumour necrosis factor alpha has been found in psoriatic skin. This cytokine activates endothelial cells and induces the membrane E-selectin molecule (E-selectin or endothelial leucocyte adhesion molecule 1); the same cytokine is able to induce its own receptors. Since the soluble forms of E-selectin and tumour necrosis factor receptor (TNF-R, 60 kD) may be reliably measured in body fluids, these determinations have been performed in the sera of psoriatic patients. OBJECTIVE: To evaluate endothelial activation in psoriatic patients, sE-selectin has been determined in patient sera and compared with those of a control group. sTNF-R (60 kD) was also measured in the same samples. METHODS: Two commercially available enzyme immunoassay methods have been used to determine sE-selectin and sTNF-R (60 kD) in the sera of 19 patients with plaque-type psoriasis; 22 healthy subjects were used as controls. CONCLUSIONS: Significantly increased amounts of sE-selectin serum levels were found in psoriatic patients as compared to healthy controls. Moreover, a direct correlation between sE-selectin and PASI scores was observed. On the contrary, sTNF-R (60 kD) serum levels presented no increases. These data suggest that sE-selectin serum levels are a reliable marker of disease activity in psoriatic patients.

Adolescent↗

Correlated increases of tumour necrosis factor-alpha, interleukin-6 and granulocyte monocyte-colony stimulating factor levels in suction blister fluids and sera of psoriatic patients--relationships with disease severity.

Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF) were measured in serum and involved and uninvolved skin blister fluids of 20 psoriatic patients and 10 healthy subjects, by enzyme immunoassay. TNF-alpha and IL-6 were always detectable in involved skin blister fluids, while GM-CSF was detected only in 45% of these samples. TNF-alpha, IL-6 and GM-CSF were detected in 95, 100 and 10% of uninvolved skin blister fluid samples, respectively. TNF-alpha and IL-6 were found in 50 and 30% of control blister fluids, while GM-CSF was never detected. In serum, TNF-alpha was detected in 75% of patients and in 70% of controls; IL-6 in 45% of patients and in no controls; and GM-CSF in 35% of patients and in 20% of the controls. The median TNF-alpha and IL-6 levels in involved skin were statistically higher than those of both uninvolved and control skin blister fluids. TNF-alpha and IL-6 levels in blister fluids obtained from both involved and uninvolved skin were higher than those of the patients' sera. GM-CSF, when present in involved skin blister fluids, showed correlated levels with the other cytokines (TNF-alpha: R = 0.85, P = 0.004; IL-6: R = 0.72, P = 0.03). TNF-alpha was highly correlated with IL-6 (R = 0.78, P < 0.00001) in involved skin blister fluids. TNF-alpha and IL-6 levels of involved skin blister fluids showed significant correlations with the psoriasis area and severity index scores in the patients, suggesting a direct relationship between these cytokines and the clinical manifestations of the disease. Moreover, the TNF-alpha levels were particularly related to the erythema scores in the patients, further supporting evidence of their role in the pathogenesis of the disease.

Adolescent↗

Interleukin-6 and tumour necrosis factor levels decrease in the suction blister fluids of psoriatic patients during effective therapy.

BACKGROUND: Involvement of various cytokines in psoriasis pathomechanisms has previously been reported. OBJECTIVE: To better define the relationship between the disease severity and interleukin-6 and tumour necrosis factor alpha skin levels, these two cytokines were measured in suction blister fluids obtained from involved and uninvolved skin areas of psoriatic patients treated with UVB, beta-methasone dipropionate and salicylic acid ointment. METHODS: Determinations were performed by ELISA in fluids obtained from 6 patients with the Kiistala method, every 1-2 weeks for at least 1 month. RESULTS: During the observation period, all the patients showed disease improvement (median PASI score declined from 13.4 to 3.9) and significant decreases in the cytokine levels in all samples. CONCLUSION: These results are in agreement with a functional involvement of these two cytokines in the pathogenesis of the disease and their possible use as follow-up markers.

Administration, Topical↗

Soluble intercellular adhesion molecule-1 and procollagen III peptide are reliable markers of disease severity in psoriasis.

Levels of soluble intercellular adhesion molecule-1 (sICAM-1) and procollagen III peptide (PIIIP) were measured respectively by enzyme immunoassay (EIA) and radioimmunoassay (RIA) methods in sera from 14 patients affected with psoriasis. The same determinations were also performed on suction blister fluids (BFs) obtained from lesional and non-lesional skin. Fourteen normal subjects were used as controls. Significant correlations were found between the serum levels and psoriasis area and severity index (PASI), (R = 0.62 for sICAM-1 and R = 0.73 for PIIIp, respectively). Of the PASI components, infiltration and erythema represented the variables most closely related to PIIIP (R = 0.85; R = 0.72 respectively). Differently from PIIIP, whose levels were significantly lower in the sera than in skin BFs (serum: median value 1.05, range 0.7-2.3 vs. lesional skin fluid: 11.8, 4.8-30 U/ml), sICAM-1 molecules were found predominantly in the sera (serum: median 316, range 117-579 vs lesional skin fluid: median 70, range 31-252 ng/ml). These data cannot exclude that sICAM-1 molecules detected in suction BFs may derive from serum contamination.

Adolescent↗

Interleukin-1-beta, interleukin-6, and interferon-gamma in suction blister fluids of involved and uninolved skin and in sera of psoriatic patients.

Interleukin-1-beta (IL-1-beta), Interleukin-6 (IL-6) and Interferon-gamma (IFN-gamma) were measured by enzyme immunoassay (EIA) methods in blister fluids (BFs) obtained from both involved (ISBF) and non-involved skin (USBF) and in sera from 14 psoriatic patients. The same determinations were carried out in 14 sera and in 5 suction blister fluids from 14 normal subjects. IL-6 was always detectable in all skin fluids and in 3 psoriasis sera. IL-1-beta was measured only in 5 ISBFs and in 5 sera from the same patients. IFN-gamma was present in 11 ISBFs, in 5 USBFs and in 5 sera. The analysis of the levels found in the samples shows: 1) a local production of these cytokines, 2) the presence of detectable amounts of IL-6 and IFN-gamma in USBFs, and 3) a significant correlation between the IL-6 levels in the ISBFs and erythema score.

Adolescent↗

GangliosideGM1 expression during human spinal cord and neural crest development.

GangliosideGM1 represents a widespread component of the neural cell plasma membranes. Cholera toxin-B subunit binds selectively to GM1. Human spinal cords at post-conception (PC) weeks 6 to 11 were examined and early GM1 expression shown on the cell plasma membrane in the developing grey matter at PC week 6. GM1 was demonstrated also in the marginal layer (white matter); on neural crest derivative plasma membrane, i.e. dorsal root (DRG) and sympathetic ganglia; along emerging fibres from DRG and neurite terminals innervating skeletal muscle. GangliosideGM1 is highly expressed in spinal cord primary cultures and is a stringent neural cell marker. GangliosideGM1 represents an early marker of neural differentiation in both spinal cord and neural crest derivatives.

Cell Membrane↗

Cyclosporin A: preliminary results in the treatment of psoriasis.

Cyclosporin A (CYA) has recently attracted the attention of the dermatologists with regard to its use in the treatment of severe psoriasis. We report four cases of psoriasis resistant to conventional therapy. Three patients were affected by chronic plaque psoriasis and one by erythrodermic psoriasis. The initial dosage of CYA was 5 mg/kg/day per os, and was gradually reduced according to the course of the disease. The drug was administered for a period of 6 weeks. All patients showed a significant improvement of the clinical picture. No remarkable clinical side effects were observed. During the trial we took skin biopsies on which we conducted histological and immunohistochemical studies. The efficacy of CYA in the treatment of psoriasis demonstrates the important role of the cell mediated immunity in the pathogenesis of psoriasis.

Adult↗

Spontaneous release of leukemia inhibitory factor and oncostatin-M is increased in supernatants of short-term organ cultures from lesional psoriatic skin.

Several cytokines are increased in psoriatic skin, mainly at the lesional level. Some of these mediators seem to be very important in the pathogenesis of psoriasis since they are thought to stimulate keratinocyte proliferation and/or to drive the inflammatory changes associated with psoriasis. Among the proinflammatory modulators, hematopoietins, which are a family of cytokines sharing a receptor component (the gp130 subunit), have been under intensive investigation in recent years. The hematopoietin family includes interleukin-6 (IL-6), interleukin-11 (IL-11,) leukemia inhibitory factor (LIF), oncostatin-M (OSM), granulocyte colony-stimulating factor (G-CSF), ciliary neurotrophic factor (CNTF) and cardiotrophin. Amounts of two of these molecules, IL-6 and IL-11, have been found to be increased in psoriatic lesions. The present study adds new information concerning the spontaneous release of two hematopoietins, namely LIF and OSM, in 48-h culture supernatants of lesional and nonlesional skin punch biopsies from psoriatic patients and normal subjects. The cytokine determinations were performed using commercially available ELISA kits. The results are expressed as picograms per milligram of tissue, after weight normalization. The levels of LIF released by lesional skin (median 2.4 pg/mg, range 0.05-13.4 pg/mg) were significantly higher than from nonlesional (median 0.4 pg/mg, range under detection limit (UDL)-4.4 pg/mg; P = 0.001) and normal skin (median 0.4 pg/mg, range UDL-0.9 pg/mg; P = 0.005). The OSM levels were also significantly higher in supernatants of lesional skin (median 0.9 pg/mg, range 0.4-5.2 pg/mg) than in supernatants of nonlesional (median 0.2 pg/mg, range UDL-0.8 pg/mg; P = 0.001) and normal skin (median 0.1 pg/mg, range UDL-0.4 pg/mg; P = 0.0001). In addition, interleukin-8 (IL-8), a cytokine involved in the pathomechanisms of psoriasis, showed a similar behaviour when measured in the same samples. Lesional skin showed a median value of 752.5 pg/mg, range 98.8-2063.8 pg/mg, nonlesional skin a median value of 58.3 pg/mg, range UDL-1252.5 pg/mg (P = 0.007) and normal skin a median value of 44.6 pg/mg, range UDL-176.7 pg/mg (P = 0.004). No significant differences were found between nonlesional and normal skin for the three molecules analyzed. Taken together with the fact that at least two other hematopoietins (namely IL-6 and IL-11) are also increased in supernatants of lesional psoriatic skin, these data point to a possible involvement of the hematopoietins in inflammatory processes associated with psoriasis.

Adult↗

IL-10 levels are decreased in psoriatic lesional skin as compared to the psoriatic lesion-free and normal skin suction blister fluids.

IL-10 is a cytokine produced by B and T-cells, monocytes and keratinocytes with pleiotropic effects, some of which are directed towards suppressing monocyte activities (anti-inflammatory cytokine). No information at the protein level is available concerning IL-10 in suction blister fluids from psoriatic skin, even if contrasting data have been reported on IL-10 mRNA of psoriatic biopsies and on the cytokine patterns of the T-cell clones, isolated from psoriatic skin. The IL-10 blister fluid concentrations in psoriatic lesions were compared to those found in the non-lesional skin of 14 patients effected with plaque-type psoriasis, and to those found in the skin of healthy controls (9 subjects sharing sex ratio and age with psoriatic patients). No difference in the IL-10 levels was found between non-lesional and control skin. In contrast, lower IL-10 levels were observed in blister fluids obtained from lesional psoriatic skin (p < 0.0005). The possible meanings of these results have been evaluated in the context of the mechanisms activating or maintaining the chronic inflammatory components of psoriasis.

Adult↗