Serum Levels of Carbamylated LDL, Nitrotyrosine and Soluble Lectin-like Oxidized Low-density Lipoprotein Receptor-1 in Poorly Controlled Type 2 Diabetes Mellitus.

INTRODUCTION: Carbamylated low-density lipoprotein (cLDL) has profound proatherogenic properties. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been identified as the primary cLDL receptor. The soluble form of LOX-1 (sLOX-1) and 3-nitrotyrosine (NT) have recently been suggested as biomarkers of vascular disease. Although type 2 diabetes mellitus (T2DM) is characterised by an increased atherosclerotic risk, the clinical data on cLDL, NT and sLOX-1 levels in T2DM are limited. AIM: To explore the possible role of cLDL, NT and sLOX-1 as potential biomarkers for disease progression and complications in poorly controlled T2DM patients with and without microalbuminuria. MATERIALS AND METHODS: The serum concentrations of cLDL, NT and sLOX-1 were measured by ELISA in a cross-sectional study of 60 T2DM patients and 35 nondiabetic controls. RESULTS: Both the normoalbuminuric (n = 34) and the microalbuminuric (n = 26) patients had significantly higher serum levels of cLDL and NT than the healthy controls, but sLOX-1 was only elevated in the microalbuminuric subgroup (p < 0.05). Carbamylated LDL correlated positively with NT in the diabetic subjects (rs = 0.266, p = 0.04) while it correlated with urea only in the control group (rs = 0.475, p = 0.004). The serum concentration of sLOX-1 correlated significantly with fasting glucose (rs = 0.441, p < 0.001), HbA1c (rs = 0.328, p = 0.01) and microalbuminuria (rs = 0.272, p = 0.035) in the whole diabetic cohort. CONCLUSIONS: The present study highlights the potential of cLDL, NT and sLOX-1 as possible markers of diabetic complications.

Influence of Platelet Aggregation Modulators on Cyclic AMP Production in Human Thrombocytes.

BACKGROUND: Cyclic AMP is a powerful inhibitor of platelet aggregation. In the present study we examined the effect of platelet aggregation modulators on cyclic AMP content in human thrombocytes. Of the agents we tested, lactoferrin, wortmannin, quercetin and amiloride are platelet aggregation inhibitors, whereas ouabain is a platelet activator. AIM: To investigate the effect of lactoferrin, wortmannin, quercetin, ouabain and amiloride applied alone and in combination with lactoferrin on cyclic AMP production in human platelets. MATERIALS AND METHODS: 'Direct cAMP ELISA kit' was used for cyclic AMP determination. RESULTS: The studied modulators, individually or in combination, stimulate cyclic AMP production in platelets. CONCLUSIONS: Wortmannin, quercetin, ouabain and amiloride increase cyclic AMP level in human platelets. Lactoferrin also increases cyclic AMP level, but the effect is statistically insignificant, which shows that lactoferrin does not participate directly in the cyclic AMP signaling. Lactoferrin additionally augments the stimulating action of wortmannin, quercetin, ouabain and amiloride on the cyclic AMP production. This probably shows a synergetic interference of lactoferrin in signal pathways along with phosphatidylinositol 3-kinase (wortmannin), quercetin (control over protein kinases, the redox state of the cell and ion transport), ouabain and amiloride (mechanisms of ion transport and phosphorylation).

Pathobiochemical Mechanisms Relating Iron Homeostasis with Parameters of Inflammatory Activity and Autoimmune Disorders in Rheumatoid Arthritis.

AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies and DAS 28. RESULTS: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. CONCLUSION: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative for evaluation of the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.

Effect of Nitrates, Thiocyanates and Selenium on the Iron and Iodine Status of Postpartum Women.

AIM: To find correlations between high thiocyanate and nitrate levels and low selenium levels and the indicators of the iodine and iron status of postpartum women. MATERIALS AND METHODS: The study included 41 mothers aged 26.4±5.9 yrs from Asenovgrad and nearby villages. Urinary iodine was determined by the Sandell-Kolthoff reaction and thiocyanate - by the interaction of these ions with acidic solution of KMnO4; for serum nitrates we used the colorimetric method; serum selenium was assessed by electro-thermal atomic-absorption spectrophotometry; thyroxin (FT4), the thyroid stimulating hormone (TSH), serum ferritin (SF), and serum transferrin receptor (sTfR) were determined using ELISA; Hb levels were determined by hematology analyzer. RESULTS: Assessing the iodine status, we found a negative correlation between the levels of iodine and thiocyanates in urine (R=-0.717, р<0.0001), a positive correlation between nitrates and TSH (R=0.487, р=0.003) and a negative correlation between nitrates and FT4 (R=-0.312, р=0.06). For the iron status, we found a negative correlation between nitrates and SF (R=-0.429, р=0.009) and between nitrates and Hb (R=-0.383, р=0.021). The Mann-Whitney U-test showed that in women with nitrate levels higher than the mean value there was low FT4 level (р=0.06), high TSH level (р=0.013), low Hb concentration (р=0.061) and low SF concentration (р=0.005). The combined effects of environmental factors (elevated nitrate levels and low selenium level) on the iodine and iron status are manifested by low concentrations of FT4 (р=0.033), Hb (р=0.06) and SF (р=0.05) and high level of TSH (р=0.05). In conclusion, we found that environmental factors, especially when combined, have a negative impact on the iron and iodine status of females.

The Role of Eating Habits on the Iron Status of Pregnant Women.

OBJECTIVE: This study highlights the relationship between some eating habits and iron status during pregnancy. SUBJECTS: The study included 219 healthy pregnant women aged 27.6 ± 5.7 years from southern Bulgaria. METHODS: Subjects' iron status was assessed on the basis of the following iron indicators: hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (sTfR), and body iron index (mg/kg). RESULTS: Severe anemia among the women from southern Bulgaria was not observed. Advanced pregnancy and some eating habits are factors that deteriorate iron status. Women who had consumed fish at least 3 times a week had lower levels of sTfR (р = 0.008), higher levels of SF (р = 0.05), and lower levels of body iron (р = 0.018). Frequent legume consumption was related to increased levels of sTfR (р = 0.036). Pregnant women with a high frequency of coffee consumption had lower values of body iron (р < 0.0001). Women who had consumed cow's milk at least 3 times a week had lower levels of SF (р = 0.026) and body iron (р = 0.042). CONCLUSIONS: Regular consumption of fish and legumes, rarely drinking coffee, and milk consumption during the intervals between food intake are conditions for optimization of iron status during pregnancy.

Pathobiochemical Mechanisms Relating Iron Homeostasis to Parameters of Inflammatory Activity and Autoimmune Disorders in Rheumatoid Arthritis.

AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies, and DAS 28. RESULTS: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. CONCLUSION: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative in evaluating the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.