The impact of anti-TNF treatment on Wnt signaling, noggin, and cytokine levels in axial spondyloarthritis.

INTRODUCTION: Anti-tumor necrosis factor (anti-TNF) agents are commonly used in treatment of axial spondyloarthritis (axSpA), but clinical and radiological improvement is not achieved in all patients. We aimed to investigate the impact of anti-TNFs on inflammatory and noninflammatory parameters in patients with axSpA. METHODS: In this longitudinal study, 30 biologic naïve axSpA patients with high disease activity and 30 healthy controls were enrolled. All patients were treated with anti-TNF agents for 6 months. ASDAS-CRP, BASDAI, BASFI, BASMI, patient and physician global assessments were evaluated. C-reactive protein, COX2, TNF-α IL-6, IL-17, IL-22, IL-23, IL-33, sclerostin, dickkopf-1, and noggin levels were evaluated at baseline and at 6 months of anti-TNF treatment. RESULTS: At baseline, axSpA patients had significantly higher median (IQR) TNF-α levels, 34.4 (31.4-37.03) vs. 18.1 (12.1-28.4) pg/ml (p < 0.001), and lower DKK1, 446.7 (356.9-529.3) vs. 1088.7 (951.7-1244.4) pg/ml, and sclerostin, 312.4 (140.8-412.7) vs. 412.3 (295.4-512.8) pg/ml, compared to healthy controls (all p < 0.001). The median (IQR) serum levels of IL-17, IL-22, and IL-33 increased significantly after 6 months of anti-TNF treatment, from 93.3 (85.1-104.8) to 102.1 (86.6-114.6) pg/ml (p = 0.026), 159.2 (151.9-178.4) to 183.5 (156.3-304.6) pg/ml (p = 0.033), and 127.8 (106.6-186.1) to 147.06 (128.5-213.4) pg/ml (p = 0.016), respectively. Sclerostin and DKK-1 levels increased significantly after anti-TNF treatment from 312.4 (140.8-412.7) to 405.1 (276.3-452.5) pg/ml (p = 0.018) and 446.7 (356.9-529.3) to 881.3 (663.1-972.2) pg/ml (p < 0.001), while there was no significant change in noggin level. CONCLUSIONS: Many inflammatory cytokines increase after anti-TNF treatment and noggin is not affected by anti-TNF treatment in AxSpA. Noggin might be a therapeutic target in patients with axSpA. KEY POINTS: • Anti-TNF therapy is not sufficient for complete blockage of the inflammatory process in axial spondyloarthritis. • The increase in IL-17, IL-22, and IL-33 may decrease the efficiency of anti-TNF therapy. • Noggin might be a therapeutic target as a complementary or alternative approach to anti-TNF therapy in axial spondyloarthritis.

The effect of the anticoagulant on the cellular composition and growth factor content of platelet-rich plasma.

BACKGROUND: The cellular and biochemical composition of the platelet rich plasma (PRP) may impact its regenerative capacity. PRP composition have been shown to vary substantially among different separation systems and protocols. The type and the dose of anticoagulant might affect the content of PRP. OBJECTIVE: The objective of this study was to evaluate the effect of anticoagulant use, on cellular composition and the amount of growth factors in fresh PRP. METHODS: Three different methods were used to prepare PRP from 12 healthy participants. The protocol 1 included standart dose sodium citrate (SC) (0.9 ml, 3.8%), protocol 2 included 0.5 ml SC and no anticoagulant was used in protocol 3. The PRP's were compared in regards to cellular content, capture efficiency of platelets (CE), concentrations and total doses of fresh studied vascular endothelial growth factor (VEGF), platelet derived growth factor -BB, (PDGF-BB), transforming growth factor ß1 (TGF-ß1) levels. RESULTS: The CE and total platelet count were highest in protocol 1. The white blood cells (WBC) and VEGF were highest in protocol 3. The highest total TGF-ß1 and total PDGF levels were obtained with protocol 1, while the highest total VEGF levels were obtained with protocol 3. CONCLUSION: The results of this study revealed that the use and the dose of SC affects the cellular content of PRP and GFs measured in fresh PRP. The CE and platelet dose increases while the WBC and VEGF decreases with the use of SC.

The lethality, histological, haematological and biochemical alterations in mice envenomated with Aegaeobuthus nigrocinctus venom.

There is currently no data regarding the toxicity or the in vivo effects of the venom the Aegaeobuthus nigrocinctus species, since it has not been studied thus far according to the best of our knowledge. In the present study, and for the first time, the median lethal dose, the in vivo toxic effects, the histological changes in some of the vital organs were all determined as well as an assessment was made of the histological, biochemical and haematological changes which were caused by the venom injected in mice. The median lethal dose (LD50) of the scorpion venom for mice was found to be 0.38 mg/kg in terms of body weight. The results of the study show that the A. nigrocintus is a potentially lethal scorpion. The evidence related to the venom indicated that it could cause tissue injury in some vital organs. In conclusion, this scorpion venom could cause significant medical complications, and may lead to death, regarding at-risk patients. Therefore, health professionals should be aware of the various scorpion species in their regions and should follow current medical approaches concerning scorpion envenomation.

The effects of lipoprotein(a) and homocysteine on prognosis and risk factors in acute ischemic stroke.

The role of atherosclerosis in ischemic stroke has been intensively investigated in recent years, and homocysteine (Hcy) and lipoprotein(a) Lp(a) were found to have roles during the process. This study aims to investigate the relationship between acute ischemic stroke and Lp(a) and Hcy levels and to determine the prognosis and functional disability. Forty-one patients with acute ischemic stroke and 33 controls were included in the study. Lp(a) and Hcy levels were examined in both groups. The modified Rankin scale (MRS) scores at discharge and in the first and third months were determined to establish the functional disability and prognosis of stroke patients. In patients with acute ischemic stroke, Hcy levels were significantly higher than the controls (p = 0.003). There was no significant difference between Lp(a) levels in patients with acute ischemic stroke and controls (p = 0.150). Because there was a significant difference in terms of Hcy levels between the groups, it will be suitable to routinely monitor the Hcy levels of individuals who are known to have risk factors for stroke. Neither Lp(a) nor Hcy levels had any correlations with functional disability; therefore, it can be concluded that the Lp(a) and Hcy levels are inexpressive in predicting the functional disability and prognosis for ischemic stroke patients.

Role of mean platelet volume in diagnosis of childhood acute appendicitis.

Introduction. Acute appendicitis is the leading cause of abdominal pain in children requiring emergency surgical intervention. The aim of this study is to investigate the diagnostic value of MPV in early diagnosis of acute appendicitis cases in pediatric age group. Methods. This study was performed retrospectively. Three hundred five patients operated on with the diagnosis of appendicitis and pathologically found to be acute appendicitis were classified as Group 1 and 305 healthy children were classified as control Group 2. Results. One hundred ninety-seven of 305 cases in Group 1 are males (64.6%), in Group 2, 151 of 305 cases are males (49.5%). The mean MPV in Group 1 was 7.9 ± 0.9 (fL), and whereas in Group 2 was 7.7 ± 0.8 (fL). There was no statistically significant difference regarding MPV values (P > 0.05). Conclusion. In our study we detected that mean platelet volume has no diagnostic value in pediatric acute appendicitis cases.

Value of IGF-I levels in the evaluation of response to treatment with levosimendan in patients with severe heart failure.

OBJECTIVE: Levosimendan treatment has inotropic, anti-stunning, and cardioprotective effects in the setting of acute decompensated heart failure (HF). Among studies conducted on the treatment of heart failure, those based on the growth hormone axis are of particular interest. The aim of this study was to determine the value of baseline insulin-like growth factor 1 (IGF-I) measurements in predicting response to levosimendan treatment. METHODS: The study population included patients on standard heart failure treatment who presented with functional capacity NYHA class 3-4 and left ventricular (LV) ejection fraction less than 35% were enrolled in this prospective, cohort study. Pre- and post-treatment symptoms of patients (72 hours after the completion of levosimendan infusion) and echocardiographic parameters were evaluated and blood samples were collected. Mann-Whitney U, Pearson Chi-square and Wilcoxon Sign Rank tests were used for statistical analysis. Correlations were determined using Spearman correlation analysis. RESULTS: Thirty patients were enrolled in this study, 83.3% of whom were male and 16.7% were female, with a mean age of 62.6 ±10.1 years. Mean baseline IGF-I level was 106.9±47.0 µg/L. Statistically significant improvements were observed in NYHA class, mean brain natriuretic peptide (BNP) levels, LV ejection fraction and LV end-systolic volume values following treatment with levosimendan (respective pre-treatment and post-treatment values: 3.5±0.5 vs. 2.5±0.7, p<0.001; 1209.8±398.6 pg/ml vs. 704.1±344.6 pg/ml, p<0.001, and 25.7±6.6% vs. 29.0±6.8%, p=0.021, and 164.1±45.7 ml vs. 152.8±50.6 ml, p=0.012). Fourteen patients (46.7%) had low IGF-I levels, taking into consideration variations due to age and gender. Patients with normal baseline IGF-I values showed more significant decreases in BNP levels in response to treatment compared to those with low baseline IGF-I levels (650.5±367.2 pg/ml vs. 340.1±269.0 pg/ml, p=0.014). CONCLUSION: Baseline IGF-I levels may be used to predict response to levosimendan treatment in patients hospitalized for decompensated HF.

Trace and toxic element patterns in nonsmoker patients with noninsulin-dependent diabetes mellitus, impaired glucose tolerance, and fasting glucose.

PROJECT: Noninsulin dependent diabetes mellitus is supposed to be associated with fluctuations in the plasma levels of several trace elements. There is accumulating evidence that the metabolism of several trace elements is altered in patients with noninsulin dependent diabetes mellitus and that these nutrients might have specific roles in the pathogenesis and progression of this disorder. PROCEDURE: The aim of the present study is to compare the levels of essential trace and toxic elements including lead (Pb), arsenic (As), cadmium (Cd), chromium (Cr), aluminium (Al), nickel (Ni), cobalt (Co), iron (Fe), copper (Cu), selenium (Se), zinc (Zn), vanadium (V), manganese (Mn), barium (Ba), silver (Ag), and mercury (Hg) in patients with noninsulin dependent diabetes mellitus (n = 31), impaired glucose tolerance (n = 20), impaired fasting glucose (n = 14), and healthy controls (n = 22). Plasma concentrations of the elements were measured by using inductively coupled plasma mass spectrometry. RESULTS: The results indicated that values of lead, nickel, aluminium, copper, and chromium were significantly higher, but not above toxic levels, in the plasma of nonsmoker patients with noninsulin dependent diabetes mellitus (P < 0.05). The values for these elements were found to be significantly higher (P < 0.05) in patients with impaired fasting glucose than in controls. Moreover, a statistically significant correlation was found between plasma levels of glycated hemoglobin and of some trace elements like lead, nickel, aluminium, copper, chromium, cadmium, and mercury. CONCLUSIONS: Thus, it was concluded that chronic complications of glucose metabolism disorders might be associated with alterations in the levels of some trace elements. Nevertheless, some more timely and extensive studies are required to clarify the exact mechanisms of each of these changes.