Relationship of serum osteoprotegerin with arterial stiffness,preclinical atherosclerosis,and disease activity in patients with ankylosing spondylitis

Patients with ankylosing spondylitis (AS) reportedly have a higher mortality and morbidity risk. Osteoprotegerin (OPG) was recently defined as an important cardiovascular (CV) marker in the general population. We aimed to assess the relationship of serum OPG levels with arterial stiffness, carotid intima media thickness (CIMT), and clinical and laboratory data in AS patients. We examined 60 AS patients without CV disease or risk factors and 50 healthy controls. Disease activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS), whereas functional capacity was evaluated using the Bath Ankylosing Spondylitis Functional Index (BASFI). Serum OPG levels were measured with the enzyme-linked immunosorbent assay. Carotid-femoral pulse wave velocity (PWV) was used as an indicator of arterial stiffness, whereas CIMT (examined via carotid ultrasonography) was used to evaluate preclinical atherosclerosis. The mean serum OPG level, PWV, and CIMT were significantly higher in AS patients than in controls (106.7?±?50.9 vs. 58.1?±?12.7 pg/mL; 7.4?±?1.8 vs. 6.2?±?1.2 m/s; 0.72?±?0.13 vs. 0.57?±?0.07 mm, respectively; P?<?0.001 for all). In AS patients, the serum OPG levels were not significantly correlated with PWV and CIMT but were significantly correlated with erthrocyte sedimentation rate, BASFI, and ASDAS. AS patients without CV disease or risk exhibited high OPG levels and increased PWV and CIMT values. Although OPG levels were not significantly correlated with PWV or CIMT, future long-term follow-up studies will help define the predictive value of OPG in these patients.     

Differential expression of microRNAs in plasma of patients with laryngeal squamous cell carcinoma: potential early-detection markers for laryngeal squamous cell carcinoma

Purpose

Altered microRNA (miRNA) expression has been found in many cancers, including lung, breast, prostate, bladder and colorectal cancer. Many recent studies have demonstrated that aberrant plasma miRNAs were also found in various types of cancers. However, the alteration in plasma miRNA expressions in laryngeal squamous cell carcinoma (LSCC) remains unclear. The present study aimed to investigate the alterations in plasma miRNAs in LSCC.

Methods

In the present study, the expression profiles of 738 miRNAs in plasma from 20 patients and 44 healthy subjects were evaluated using high-throughput real-time quantitative polymerase chain reaction.

Results

Our results demonstrated that expression levels of 17 miRNAs were significantly upregulated in patients with LSCCs when compared to control group (p < 0.05). Expression levels of nine miRNAs were found significantly downregulated in LSCC patients (p < 0.05). In addition, 17 miRNAs were expressed only in LSCC group, and five of these miRNAs (miR-331-3p, 603, 1303, 660-5p and 212-3p) are LSCC specific and never seen before in plasma of any human subject.

Conclusion

In conclusion, our study suggests that detecting these LSCC-specific miRNAs in plasma might serve as novel noninvasive biomarkers for LSCC.     

Hematology Morphology Forum

Introduction: Thrombotic thrombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, mainly as a consequence of autoimmunity. Plasma exchange (PEx) is standard, achieving complete remission (CR) in 77–83% of cases, but rates are variable depending on ADAMTS-13 activity and relapse is frequent in patients with <10%. Thus, an effective front-line immunosuppressive treatment is needed.

Materials and methods: We administered PEx daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks to 10 patients with a first TTP episode and 1 relapsed patient (8 females (72%) and 3 males (28%)). Median age was 34 years (15–46) and laboratory parameters at diagnosis were as follows: platelets 11?×?10⁹/l (range 7–27.4?×?10⁹/l), lactate dehydrogenase 1822?U/l (range 705–8220?U/l, normal 70–180?U/l), and haemoglobin 6?g/dl (range 4.2–11.8?g/dl). ADAMTS-13 activity was determined in eight patients and was <10% in all. ADAMTS-13 autoantibody titre was determined in seven patients and was >15?units/ml in all (ref: negative <12, undetermined 12–15, positive >15?units/ml); Shiga toxin was negative in all patients. The median number of PEx until CR was 7 (range 4–12); prednisone 1?mg/kg was administered to six patients.

Results: The median follow-up was 22 months (range 4–49) and the estimated 2-year relapse-free survival was 89%; one HIV+ patient relapsed at 8 months follow-up. No complications related to PEx or rituximab were reported.

Conclusions: Our study suggests that low-dose rituximab and PEx are effective as front-line treatment for acute TTP; however, a prospective trial is needed to demonstrate whether low-dose rituximab is as effective as the conventional dose.     

Correlations among serum leptin levels, complete blood count parameters and peripheral CD34(+) cell count in prepubertal obese children

Leptin is a hormone produced by adipocytes that helps reduce body weight by depressing appetite and increasing metabolic activity. Leptin also promotes early hematopoiesis. The main aim of this study was to compare complete blood count (CBC) parameters and peripheral blood CD34(+) cell counts in prepubertal obese and nonobese children. Relationships between leptin levels and CBC parameters and peripheral CD34(+) progenitor cell counts in the obese group were also investigated. Thirty one healthy, prepubertal, obese children and 30 nonobese, age-matched prepubertal controls were included in the study. A fasting blood sample was collected from each subject, and CBC findings, serum leptin level, and peripheral blood CD34(+) progenitor cell count were recorded. In the obese group, the mean results for body mass index (BMI), BMI standard deviation score (BMI SDS), and serum leptin level were significantly higher than the corresponding control findings. There were no significant differences between the groups with respect to CBC parameters and CD34(+) cell percentage. In both the obese and control groups, the girls serum leptin levels were significantly higher than the boys. In the obese group, serum leptin level was strongly correlated with BMI and with BMI SDS (Pearson correlation coefficients r=0.70, p<0.001, and r=0.59, p<0.001, respectively) in both girls and boys. None of the CBC parameters nor CD34(+) progenitor cell percentage was correlated with leptin, BMI, or BMI SDS. The results indicate that serum leptin levels in obese children are positively correlated with BMI. However, in contrast to adults, high leptin level in childhood obesity does not seem to be associated with altered CBC parameters or increased peripheral CD34(+) progenitor cell count.     

NephroCheck data compared to serum creatinine in various clinical settings

Background

Acute kidney injury is frequently observed at the intensive care unit, after surgery, and after toxic drug administration. A rise in serum creatinine and a fall in urine output are consequences of much earlier injury to the most sensitive part of tubular cells located at the proximal tubule. The aim of the present study was to investigate the course of two cell-cycle arrest urinary biomarkers compared to serum creatinine in four clinical settings: ischemic reperfusion injury, cardiac failure, severe acute kidney injury, and chemotherapy-induced kidney injury.

Methods

A recently developed bedside test known as NephroCheck measures two urinary parameters: insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The test is based on a sandwich immunoassay technique. The final test output, labeled AKIRisk, is shown as a numeric result.

Results

This report revealed that [IGFBP7]?·?[TIMP-2] in urine rise rapidly prior to any change in serum creatinine. A unique feature of all four clinical settings is that a rapid decline predicts the recovery of kidney function. Besides, a subclinical kidney injury might be detected by the test.

Conclusion

This bedside test detects biomarkers of renal injury. A rapid decline in AKIRisk was associated with the restoration of kidney function, whereas a prolonged high AKIRisk score was associated with end-stage renal disease. However, the dynamics seem to differ, depending on the cause and the extent of injury. Further studies will be needed to clarify the issue.

     

Immunohistochemical profile of transforming growth factor-beta1 and basic fibroblast growth factor in sciatic nerve anastomosis following pinealectomy and exogenous melatonin administration in rats.

Collagen scar formation at the cut end of a peripheral nerve, an important problem in clinical practice for neurosurgeons, obstructs sprouting of axons into appropriate distal fascicles, and thereby limits the regeneration process. Researchers have attempted to control collagen accumulation and neuroma formation with various physical and chemical methods, but with limited functional success. Recently, it has been demonstrated that transforming growth factor (TGF)-beta and basic fibroblast growth factor (bFGF) play an important role in collagen production by fibroblasts and in Schwann cell activity. In our study, rats were divided into a control group, a melatonin-treated group, a surgical pinealectomy group, and a group treated with melatonin following pinealectomy. They then underwent a surgical sciatic nerve transection and primary suture anastomosis. At 2 months after anastomosis, the animals were sacrificed and unilateral sciatic nerve specimens, including the anastomotic region, were removed and processed for immunohistochemical study from two animals in each group. For each antibody, immunoreactivity was assessed using a semiquantitative scoring system. Strong TGF-beta1 and/or bFGF expression was observed in the epineurium of animals that underwent pinealectomy, but no or weak staining was observed in animals in the control and melatonin treatment groups. Based on these data, we suggest that both TGF-beta1 and bFGF have important roles in control of collagen accumulation and neuroma formation at the anastomotic site, and that the pineal neurohormone melatonin has a beneficial effect on nerve regeneration.     

The role of adipokines in the improvement of diabetic and cardiovascular risk factors within a 52-week weight-loss programme for obesity

BackgroundObesity is an independent risk factor for cardiovascular disease and diabetes weight reduction not only reduces the risk for these diseases but leads to an alteration of the circulating adipokine levels. The aim of our study was to evaluate the effect of weight loss and lifestyle changes implemented in the form of the interdisciplinary weight management programme Optifast52® on cardiovascular and diabetic risk factors and on key adipokines.Methods72 morbidly obese patients were included in the programme, which consisted of a very low-calorie diet followed by incremental food introduction and dietary stabilisation, accompanied by medical surveillance, physical activity, dietary counselling and psychological support. At baseline, and after 14, 26 and 49 weeks, risk factor profiles and adipokine levels were evaluated.Results43 patients completed the programme with an average weight reduction of about 20%. Significant improvement was observed in the lipid and diabetic laboratory panels of all patients. In addition, adiponectin levels increased significantly (7.79 vs. 12.38 μg/ml, p < 0.001), while leptin levels decreased (7.29 vs 3.09 ng/ml, p < 0.001) during the course of the programme.ConclusionIn this study, Optifast52®, a multidisciplinary programme focusing on diet and lifestyle changes, was found not only to affect a decrease in parameters associated with diabetes and cardiovascular disease, but also to ameliorate in part the obesity-related imbalance of pro- and anti-inflammatory adipokines.