The ultra-photostable and electrically modulated Stimulated Emission in perylene-based dye doped liquid crystal.

One of the most important drawback of organic dyes is their low photo-stability which reduces possibility of their commercial utilization. In this article we employ the strategy of dye re-crystallization from oversaturated matrix in order to enhance material's durability. One of the main advantages of perylene derivative is ability to form emissive j-aggregates, good miscibility and incorporation into liquid crystalline matrix. Investigation of perylene-based dye and LC matrix brought as the result very efficient light amplification modulation by applied external electric field. In our article we show that Stimulated Emission (STE) is possible to achieve from perylene-derivative based system, at typical fluence thresholds for laser dyes: 3.9 mJ/cm2. Moreover, presented system proves ultra-high photostability, showing lack of STE reduction even after 12 000 excitation laser pulses. Furthermore, we proved the possibility of light emission intensity control using external electric field.

Elevated percentage of HLA-DR⁺ and ICAM-1⁺ conjunctival epithelial cells in active Graves' orbitopathy.

BACKGROUND: To evaluate if conjunctival epithelial cells' expression of HLA-DR and ICAM-1 could be helpful as early topical markers of inflammation in Graves' orbitopathy (GO). METHODS: The ocular examination evaluated a clinical activity score (CAS) by assessment of clinical features, (e.g., eyelid or conjunctival inflammation, lid width, lid closure, proptosis, ocular motility). Conjunctival epithelial cell specimens for flow-cytometric evaluations of ICAM-I and HLADR expression were collected by impression cytology from ten eyes with active GO (CAS ≥ 4 and duration ≤ 12 months), from 15 eyes with Graves' disease (GD) without active GO (CAS 0-2) and from 15 normal specimens without any ocular disorders. RESULTS: The percentage of HLA-DR + conjunctival epithelial cells was significantly elevated in patients with active GO comparing to GD without active GO and healthy controls, 10.7 % (8.5-17.7) and 7.78 % (3.92-10.1) (p < 0.05) vs. control 4.89 % (3.5-5.5) (p < 0.005), respectively. The expression of ICAM - 1+ conjunctival epithelial cells was greater only in patients with GO vs. controls, 5.5 % (4.8-7.03) and 1.46 % (0.69-2.51) (p < 0.005), respectively. CONCLUSION: The percentage of HLA-DR⁺ and ICAM-1⁺ conjunctival epithelial cells in patients with the active GO may serve as a topical inflammation marker in Graves' orbitopathy.

Circulating CXCL9 and CXCL10 as markers of activity of Graves' orbitopathy during treatment with corticosteroids and teleradiotherapy.

The aim of the study was to assess the usefulness of circulating chemokines CXCL9 and CXCL10 measurements as surrogate markers of GO activity and as a guideline in therapeutic decision-making. Forty-two individuals were divided into 4 groups: 1. 15 euthyroid patients with clinical symptoms of orbitopathy (GO) who underwent corticosteroid therapy consisting of intravenous infusions of methylprednisolone (MP) and teleradiotherapy (TR); 2. 10 patients with hyperthyroid GD (Gtx); 3. 10 patients with GD in euthyreosis (Geu); and 4. 7 healthy volunteers age and sex-matched to groups 1-3. The serum samples were collected 24 h before MP, 24 h after first dose of MP, before TR and at the end of therapy. Serum CXCL9 and CXCL10 were determined by ELISA and TSH-Rab by RIA. There were significant reductions in CXCL9 and CXCL10 serum concentrations during CS and TR treatment as compared both to control group and to basal values in GO patients. Moreover, CXCL9 concentration was significantly diminished in comparison to controls in GO patients who were identified later as corticosteroid-respondent (p<0.001). In this latter group of patients, CXCL9 was also found to be significantly reduced 24 h after first dose of MP as compared to non-respondents (p<0.02). The high-degree positive correlation between CXCL9 and CXCL10 was found (R=0.8; p<0.001). Our results suggest that the increased concentrations of CXCL9 (and CXCL10), at least in part, reflect the activity of orbital inflammation and therefore these chemokines could serve as a guideline in therapeutic decision-making in patients with Graves' orbitopathy.

Optimization of liquid crystal structures for real time holography applications.

In this paper we present results of experiments designed to increase our understanding of the photorefractive effect occurring during processes of dynamic hologram generation in Hybrid Photorefractive Liquid Crystal Structures (HPLCS). We also propose equivalent mathematical model which can be used to optimize those structures in order to obtain the highest diffraction efficiency in possibly shortest time.

Estrogens modulate RANKL-RANK/osteoprotegerin mediated interleukin-6 effect on thyrotoxicosis-related bone turnover in mice.

Interleukin-6 has been shown to cause imbalance between bone resorption and formation in thyrotoxicosis. The aim of the present study was an attempt to estimate the influence of estrogens on thyrotoxicosis-related disturbances in bone turnover in relation to RANKL-RANK/osteoprotegerin system in IL-6 deficient mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6J (IL6-/-Kopf) (IL-6 knock-out; IL6KO). The mice were randomly divided into 8 groups with 7 mice in each one: 1. WT controls, 2. IL6KO controls, 3. WT mice with thyrotoxicosis, 4. IL6KO mice with thyrotoxicosis, 5. WT ovariectomized, 6. IL6KO ovariectomized, 7. WT ovariectomized mice with thyrotoxicosis, and 8. IL6KO ovariectomized mice with thyrotoxicosis. Experimental model of menopause was evoked by bilateral ovariectomy carried out in 8-9 weeks old mice. Thyrotoxicosis was induced by intraperitoneal injection of levothyroxine at a dose of 1 µg/g daily over 21 days. The serum levels of TRACP5b, osteocalcin, OPG, and RANKL were determined by ELISA. RANKL serum concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, however, in a minor degree in IL6KO thyrotoxic mice as compared to wild-type animals. Osteoprotegerin serum levels were significantly increased in all thyrotoxic groups of mice except ovariectomized IL6KO animals. To sum up, the results of the present study suggest that IL-6 plays a key role in stimulation of RANKL-RANK/OPG system and this effect is strongly enhanced in conditions of accelerated bone turnover such as thyrotoxicosis and/or estrogen depletion.

A crucial role of interleukin-6 in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in mice.

Interleukin-6 (IL-6) has been shown to be involved in the pathogenesis of several bone diseases characterized by a negative balance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b) reflecting resorption, and osteocalcin as a marker of bone formation in IL-6 knock-out mice to assess the role of IL-6 in the pathogenesis of thyrotoxicosis-related disturbances of bone metabolism. The study was performed on forty, 14-15 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6J (IL6-/-Kopf) (IL-6 knock-out; IL6KO). The mice were randomly divided into 4 groups with 10 mice in each one: 1. WT mice in thyrotoxicosis (WT-thx), 2. WT controls (WT-ctrl), 3. IL6KO mice with thyrotoxicosis (IL6KO-thx), and 4. IL6KO controls. Experimental model of hyperthyroidism was induced by intraperitoneal injection of levothyroxine at a dose of 1 microg/g, daily over 21 days. The serum levels of TRACP 5b and osteocalcin were determined by ELISA. Serum concentration of TRACP 5b (median and interquartile ranges) were significantly increased in both groups of mice with thyrotoxicosis: WT [28.2(18.8-41.6) U/l] and IL6KO [26.4(23.0-31.2) U/l] as compared to the respective controls. Osteocalcin serum levels in IL6KO-thx mice [111.9(103.1-175.6) ng/ml] were significantly elevated in comparison to WT-thx animals [46.1(32.5-58.9) ng/ml]. In summary, the results of the present study suggest that IL-6 plays a crucial role in thyrotoxicosis-related disturbances of bone turnover in mice, determining the imbalance between bone resorption and bone formation caused by excess of thyroid hormones predominantly by inhibition of bone formation.

Soluble CD40 and its ligand CD154 in patients with Graves' ophthalmopathy during combined therapy with corticosteroids and teleradiotherapy.

AIM: To assess the role of CD40/CD154 interaction in GO pathogenesis and to estimate usefulness of soluble CD40 (sCD40) and CD154 (sCDI54) measurements as markers of GO activity. MATERIAL AND METHODS: 61 individuals in 4 groups: (1) 15 euthyroid patients with clinical symptoms of ophthalmopathy (GO) who underwent corticosteroid therapy consisting of intravenous infusions of methylprednisolone (MP) and subsequent treatment with oral prednisone (P) and teleradiotherapy (TR); (2) 14 patients with hyperthyroid GD (GDtox); (3) 22 patients with GD in euthyreosis treated with methimazol (GDeu); (4) 10 healthy volunteers age and sex-matched to group 1-3. The serum samples were collected 24 hours before MP, 24 hours after MP, after TR and at the end of therapy. Serum CD40, CD154 and TPOab were determined by ELISA and TSHRab by RIA. RESULTS: Serum concentrations of CD40 (in pg/ml) and CD154 (in ng/ml) were increased in GO patients: 84.9 (74.7-93.9) and 4.0 (2.5-7.3) respectively in comparison to controls (p < 0.001 and p < 0.05 respectively). Serum CD154 in GO group was elevated as compared to both hyperthyroid and euthyroid GD without clinical ophthalmopathy (p < 0.001 both). The sCD40/sCD154 quotient was significantly elevated during GO therapy with CS and TR in nonresponders after MP (p < 0.05) and at the end of the study (p < 0.01). SUMMARY: Our data suggest an important role of CD40/ CD154 interaction in the pathogenesis of autoimmune process leading to inflammatory infiltration in Graves' ophthalmopathy, however usefulness of sCD40 and sCD154 measurements in prediction of effects of GO treatment and its monitoring needs further investigations.

Liver transplantation for fulminant hepatic failure without venovenous bypass and without portacaval shunting.

Preservation of the caval vein during liver transplantation (OLT) has gained wide acceptance but portosystemic bypass or temporary portocaval shunt is still believed to be indicated in patients with fulminant hepatic failure. Herein we have described our initial experience with piggyback OLT without venovenous bypass and without portocaval shunting in five such patients. Division of the portal vein was always delayed until the native liver was completely dissected off the caval vein. The donor hepatic artery was anastomosed to the recipient aorta via an iliac interposition graft placed in the supraceliac position in two and at an infrarenal site in three patients. The ahepatic phase urinary output was low in the two patients in whom we applied supraceliac cross-clamping of the aorta. The mean ahepatic phase was 53 (45 to 67) minutes in four recipients who remained hemodynamically stable throughout surgery and prolonged to 5 hours in one patient due to a complicated supraceliac aortic anastomosis. Its repair resulted in hemodynamic instability, multiorgan failure, and death at 4 days following OLT. Four (80%) patients are alive in good condition with normal liver function after a mean of 12 (5 to 25) months of follow-up. In summary, liver transplantation for fulminant hepatic failure may be safely performed without venovenous bypass and without temporary portocaval shunting if the ahepatic phase is minimized and portal flow to the liver maintained up to the moment of hepatic excision. Arterial anastomosis with the supraceliac aorta prolongs the ahepatic phase and may impair kidney function: therefore, it should be avoided in these patients.

Soluble Fas, Fas ligand and Bcl-2 in autoimmune thyroid diseases: relation to humoral immune response markers.

PURPOSE: To compare soluble Fas, FasL and Bcl-2 in Graves' disease (GD) and Hashimoto's thyroiditis (HT) to the markers of humoral response: aTPO, aTG and aTSHR. MATERIAL AND METHODS: 5 groups of subjects: 1) 14 patients with GD in euthyreosis on methimazol (euGD); 2) 20 patients with hyperthyroid GD (hrGD); 3) 15 patients with HT in euthyreosis on levothyroxine (euHT); 4) 16 patients with hypothyroid HT (hoHT); 5) 12 healthy volunteers age and sex-matched to group 1-4. Serum concentrations of Fas, FasL, Bcl-2, aTPO and aTG were determined by ELISA and aTSHR by RIA. RESULTS: Levels of sFas were the highest in hoHT: 8.7 (7.2-9.8) ng/ml as compared to the controls (p < 0.01) and euHT (p < 0.05). We found positive correlations between sFas and aTPO in all studied groups (r = 0.25, p < 0.05) and between sFas and TSH in HT (r = 0.4, p < 0.05). In GD there was a positive correlation between sFasL and aTG (r = 0.5, p < 0.01) and negative correlations between sFasL and Fas (r = -0.39, p < 0.01) and between sFasL and period of methimazol administration (r = -0.32, p < 0.05). Levels of sBcl-2 were significantly increased in euHT: 31.0 (13.5-44.1) ng/ml as compared to the controls (p < 0.05) and euGD (p < 0.05). CONCLUSIONS: Fas/FasL mediated apoptosis plays an important role in the active stage of the autoimmune process of both Hashimoto's thyroiditis and Graves' disease, however, in Hashimoto's thyroiditis they contribute to irreversible damage of thyreocytes. Early detection of Hashimoto's and Graves' diseases allows for the initiation of the proper treatment that probably leads to the reduction of the autoimmune process intensity.

Serum Th1 and Th2 profile cytokine level changes in patients with Graves' ophthalmopathy treated with corticosteroids.

The aim of this study was to estimate the influence of corticosteroids on Th1 and Th2 serum cytokine balance in patients with GO: IFNgamma, TNFalpha, IL-4 and IL-10. Further, we tested the hypothesis of an up-regulation of Th2 immune response during successful treatment with corticosteroids to explain their beneficial effect in Graves' ophthalmopathy. Serum cytokines were detected in three groups of subjects: 20 patients with Graves' disease without ophthalmopathy (Gd), 16 patients with clinical symptoms of ophthalmopathy (GO) (CAS over 3 points, last consultation record for GO less than a year old) and 16 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) (2 series, 3 g each time) and subsequent treatment with oral prednisone (60 mg per day) in a tapering schedule. The serum samples were collected 24 hours before MP, 24 hours after MP, 14 days of treatment with prednisone and at the end of corticosteroid therapy. The levels of IFNgamma, TNFalpha, IL-4 and IL-10 in the serum were determined using ELISA. Statistical significance was estimated by the Mann-Whitney U-test. Our findings show a deviation to systemic Th2 profile cytokines in Graves' disease. In patients with GO, we found a significantly increased serum IL-10 concentration. In corticosteroid-responsive patients, the balance of serum cytokines IL-4/IFNgamma, IL-4/TNFalpha, IL-10/IFNgamma and IL-10/TNFalpha increased and remained upregulated until the end of the study. In non-responders, the balance of serum cytokines studied increased after methylprednisolone but declined markedly during continuation of the therapy with prednisone. In summary, our results show that efficient corticosteroid therapy may be related to its influence on Th2/Th1 profile cytokine balance. The upregulation of serum IL-4 and IL-10 during successful treatment with corticosteroids indicate the possibility of using these cytokines as predictors of the beneficial effect of corticosteroids in Graves' ophthalmopathy.

Serum L-selectin and ICAM-1 in patients with Graves' ophthalmopathy during treatment with corticosteroids.

UNLABELLED: Circulating forms of L-selectin were found to be elevated in several autoimmune diseases. ICAM-1 has been suggested a predictor of the onset of GO. The aim of the study was an estimation of serum L-selectin and ICAM-1 in patients with Graves' disease with ophthalmopathy during treatment with corticosteroids to assess their potential as a guideline of immunosuppressive therapy. We detected serum L-selectin and ICAM-1 in three groups of subjects: 20 patients with Graves' disease without ophthalmopathy (Gd), 17 patients with clinical symptoms of ophthalmopathy (CAS> or =3, anamnesis of GO> or =1 year) and 24 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methyloprednisolone (MP) and subsequent treatment with oral prednisone (P). The serum samples were collected 24 h before MP, 24 h after MP, 12+/-2 days of treatment with prednisone and after the end of the corticosteroid therapy. The levels of soluble L-selectin and ICAM-1 in the serum were determined by the ELISA method. The statistical significance was estimated by the Mann-Whitney U-test. Serum L-selectin and ICAM-1 were significantly increased in patients with GO (respectively 1182+/-222 and 438+/-68 ng/ml) and in patients with Graves' disease without ophthalmopathy (respectively: 1168+/-130 and 343+/-109) in relation to the controls. After MP treatment in corticosteroid-responsive patients (improvement in CAS < or =1) serum concentration of L-selectin and ICAM-1 decreased significantly and gradually increased during subsequent treatment with prednisone. In corticosteroid-responsive patients serum L-selectin was significantly higher before MP administration and after P treatment in relation to corticosteroid-resistant subjects. CONCLUSIONS: 1. Serum L-selectin and ICAM-1 were elevated in patients with active GO 2. Methyloprednisolone decreased levels of the studied adhesion molecules in corticosteroid-responsive patients with GO 3. Lack of clinical results in corticosteroid therapy in patients with a low starting L-selectin level would suggest the possibility of serum L-selectin estimation as a prognostic for immunotherapy efficacy.

In vitro interleukin-13 production by peripheral blood in patients with newly diagnosed insulin-dependent diabetes mellitus and their first degree relatives.

It is generally accepted that proinflammatory cytokines secreted by macrophages/monocytes as well as cytotoxic T cells are responsible for pancreatic B-cell destruction in animal models of autoimmune diabetes and presumably in insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to evaluate the production of interleukin (IL)-13-a Th2 cells derived anti-inflammatory cytokine, by peripheral blood of newly diagnosed IDDM patients and their first degree relatives with a low or high risk of IDDM development. The study was carried out in 20 patients with a recent onset of type 1 diabetes, their first degree relatives with high (with DRB1*03 and/or DRB1*04 HLA class II alleles and two or more autoantibodies directed against pancreatic B-cell antigens) (n = 20) or a low (with DQB1*0602 allele) risk of type 1 diabetes development (n = 10) and a control age matched group of healthy volunteers (n = 18). IL-13 concentrations in supernatant of 72 h cultures of peripheral blood after incubation with phytohemagglutinin (PHA) or PHA+ insulin were quantified by enzyme-linked immunosorbent assay (ELISA). The levels of IL-13 in the supernatants were significantly lower in at high risk of IDDM first degree relatives of diabetic patients (P < 0.02), higher in subjects with low genetic risk of diabetes type 1 (P < 0.02), and normal in IDDM patients in comparison to the control group. We have also observed that the adding of human insulin to the cultures resulted in a significant increase of in vitro IL-13 production in prediabetics, but not in the other studied groups. In conclusion our findings suggest that the IL-13 alterations could play an important role in the pathogenesis of type 1 diabetes. We would speculate that IL-13 as an anti-inflammatory cytokine and a mediator of the Th2 pathway could be the potential therapeutic approach in the prevention of type 1 diabetes.

Abnormal distribution of gammadelta T lymphocytes in Graves' disease and insulin-dependent diabetes type 1.

There is an increasing evidence that CD3+ cells, bearing gammadelta T cell receptors representing a minor subpopulation of T cells in the peripheral blood of humans are involved in the development of autoimmunity. The aim of the present study was determination of the gammadelta T cell subpopulation levels in the peripheral blood of subjects with Graves' disease and newly diagnosed type 1 diabetes in comparison to age-matched healthy controls. The percentages of CD3+, CD8+, gammadelta TCR+CD8+, gammadelta TCR+CD8- lymphocyte subsets were measured by flow cytometry. In the peripheral blood of newly diagnosed Graves' disease patients we showed a significant decrease of gammadelta TCR+ cells and gammadelta TCR+CD8- subset content in comparison to the percentages observed in subjects after methimazole treatment and in healthy controls. We also found a significant increase of gammadelta TCR+CD8+ cells in the peripheral blood of subjects with insulin-dependent diabetes, treated with insulin for 3-6 months. The present findings confirm our previous hypothesis that gammadelta TCR+CD8+ lymphocyte subset could play a role in the pathogenesis of diabetes type 1, probably as regulatory T cells and could be induced by delivery of exogenous insulin. Our results suggest that gammadelta T cells (gammadelta TCR+CD8- subset) could also play an important role in the development of Graves' disease and that their levels are modulated by thyreostatic treatment.

Nicotinamide inhibits enhanced in vitro production of interleukin-12 and tumour necrosis factor-alpha in peripheral whole blood of people at high risk of developing type 1 diabetes and people with newly diagnosed type 1 diabetes.

Macrophages and T lymphocytes are the first cells to appear in pancreatic islets in the development of autoimmune diabetes. It has been suggested that cytokines released by monocytes/macrophages, including interleukin-1beta (IL-1beta), interleukin-12 (IL-12) and tumour necrosis factor-alpha (TNF-alpha) could have an initial role in islet B-cell damage. The aim of the present study was to estimate the effect of human insulin and nicotinamide on the levels of monocyte/ macrophage derived cytokines in the peripheral blood of humans at risk of Type 1 diabetes, and in patients with newly diagnosed Type 1 diabetes compared to healthy control subjects. The study was carried out on three groups of subjects: 20 first degree relatives of people with Type 1 diabetes (with two or more antibodies against pancreatic B-cell antigens); 22 patients with recent onset of Type 1 diabetes (duration of the disease 3-6 months); and 25 age- and sex-matched healthy subjects. Cytokine levels (IL-1beta, IL-12, and TNF-alpha) in the supernatants of whole blood cultures incubated with PHA alone (10 microg/ml), or PHA + human insulin (50 microg/ml), or PHA + nicotinamide (100 micromol/l) were quantified by ELISA. In the cultures with nicotinamide the concentration of IL-12 and TNF-alpha was significantly lower in the prediabetic group, diabetic patients, and the healthy controls than in the cultures with PHA only or with PHA + insulin. There were no significant differences in IL-1beta production in the cultures after incubation with the different stimuli in the studied groups and healthy controls. No significant influence of human insulin on macrophage/monocyte cytokines secretion in in vitro cultures of the peripheral blood was found. This suggests that nicotinamide could influence monocyte/macrophage function in peripheral blood by inhibiting production of IL-12 and TNF-alpha.

[Clinical classification of diabetic foot as a guideline for selection of treatment]. / Kliniczne klasyfikacje owrzodzenia w zespole stopy cukrzycowej jako przewodnik w wyborze sposobu leczenia.

Foot ulceration in patients with diabetes mellitus is always a serious risk factor for lower limb amputation. To amputate or to continue conservative treatment is usually a very difficult decision and not without mistakes. The main objective of the study was assessment of the diabetic wound depth as a clinical guideline for decision-making of conservative or aggressive surgical treatment. Local foot ulceration and results of management of 62 diabetics were analysed. Lower leg amputations were performed in 40% of the patients. The foot wound was evaluated according to University of San Antonio or Wagner's scoring system. Conservative treatment resulted in failure in 19% of patients of grade I, 54% of grade II, 60% of grade III and 87% of grade IV according to Wagner's. Using the San Antonio classification there were 20% of amputations in grade I, 58% in grade II and 65% in grade III. Taking into account infection and peripheral vascular disease there were 37% of amputations in stage B, 41% in stage C and 80% in stage D. Data analysis of the study suggests better clinical usefulness of the San Antonio classification system in prognosis of limb salvage. There is high probability of failure in conservative treatment of diabetic foot lesion of grade II and III and in stage D according to University of San Antonio scoring system.

[Graves-Basedow's disease: effect of treatment methods for hyperthyroidism on the course of ophthalmopathy]. / Choroba Gravesa-Basedowa: wplyw metody leczenia nadczynnosci tarczycy na przebieg oftalmopatii.

Efficient and permanent restoration of euthyreosis is an important factor in the therapy of Graves' ophthalmopathy (GO). The choice for a treatment method of thyreotoxicosis (thyreostatic drugs, radioiodine, strumectomy) may influence the natural course of the coexistent ophthalmopathy. Some forms of therapy seem to facilitate the withdrawal of the ophthalmic symptoms, while the others may worsen or even increase the risk of the reveal of GO. This paper includes the discussion of the influence of a chosen treatment of hyperthyreoidism on the course of GO.

CD11a expression and soluble ICAM-1 levels in peripheral blood in high-risk and overt type 1 diabetes subjects.

A pair of correspondent adhesion molecules: LFA-1 (CD11aCD18) and ICAM-1 (CD54) was shown to be involved in autoimmune insulitis in animal models. Anti-LFA-1 or anti-ICAM-1 monoclonal antibodies administered in vivo had a very strong preventive effect on the development of spontaneous diabetes with a marked reduction of insulitis. On the other hand elevated levels of the soluble form of ICAM-1 (sICAM-1) were documented in subjects at risk for type 1 diabetes. Recently sICAM-1 was shown to play an immunoregulatory role as an inhibitor of islet insulitis. The aim of the present study was to evaluate CD11a + mononuclear cells (lymphocytes and monocytes) and soluble sICAM-1 levels in the peripheral blood of subjects with preclinical and overt type 1 diabetes to assess their role in the development of the autoimmune process and their possible associations with the humoral autoimmune markers. The study was carried out in three groups of subjects: 26 first degree relatives of type 1 diabetes patients (prediabetics) with the combinations of autoantibodies against pancreatic B cells (ICA, GADA, IA-2A, IAA), 22 patients with a recent onset of type 1 diabetes and age and sex-matched 24 healthy volunteers (control group). We observed an increased fluorescence intensity of CD11a on mononuclear cells in overt diabetes subjects and a positive correlation between CD11a fluorescence intensity on monocytes and ICA titre. The highest sICAM-1 levels we obtained in the peripheral blood in the prediabetics in comparison to patients with clinical diabetes and the healthy controls. We found a positive correlation between slCAM-1 and values of ICA, GADA and a total number of antibodies present. In conclusion our study suggests that LFA-1 and sCAM-1 play an important role in the pathogenesis of type 1 diabetes. The assessment of the CD11a bearing monocytes and sICAM-1 levels are potential markers of the preclinical stage of the autoimmune diabetes, but further prospective studies in high risk diabetes type 1 subjects are needed.

Gammadelta T-cells alterations in the peripheral blood of high risk diabetes type 1 subjects with subclinical pancreatic B-cells impairment.

There is increasing evidence that CD3 + cells bearing gammadelta T-cell receptor (represent the minor subpopulation of the T-cells in the peripheral blood in humans) are involved in autoimmunity development. Gammadelta T-cell receptor (TCR)+ /CD8+ T-cells have been recently found to play a critical role in the pathogenesis and prevention of autoimmune diabetes in the animal model. The aim of the present study was the estimation the gammadelta T-cell subpopulation levels in the peripheral blood of subjects with preclinical and overt type 1 diabetes and their possible associations with the humoral immunity, metabolic parameters and pancreatic B-cells function. The study was carried out in three groups of subjects: 26 first degree relatives of type 1 diabetes patients (prediabetics) with the combinations of autoantibodies against pancreatic B-cells (ICA, GADA, IA-2A, IAA), 22 patients with a recent onset of type 1 diabetes and age and sex-matched 24 healthy volunteers (control group). A decrease was observed in the absolute numbers and percentages of gammadelta+ /CD8+ and gammadelta+ /CD8- T-cell subpopulations in peripheral blood in the prediabetics with the impaired first phase of insulin secretion in comparison to relatives with autoantibodies but still with normal B-cells function, patients with clinical diabetes and healthy controls. In conclusion, the study suggests that the gammadelta T-cells play an important role in the development of insulin-dependent diabetes mellitus (IDDM). It is possible that their levels in the peripheral blood could be an additional marker of preclinical detection of the disease, but further prospective studies in high risk of IDDM subjects are needed.