Proinflammatory cytokines and leptin are increased in serum of prepubertal obese children

It has not yet been shown in prepubertal children how cytokines, leptin, and body mass, as well as parameters of obesity are interrelated. The aim of this study was to explore the relation between circulating levels of some cytokines with leptin and body mass index. A case control study was carried out in obese children of both sexes. An obese group was carried out with 63 school prepubertal children and a control group comprised the same number of nonobese children paired by age and by sex. Mean serum leptin concentration was significantly higher in the obese children at 19.9 +/- 7.4 ng/mL, than the control group (7.9 +/- 5.1 ng/mL). Serum IL-1beta, IL-6, and TNF-alpha levels were also significantly higher in the obese group than controls (33.0 +/- 8.9, 45.2 +/- 11.8, and 9.2 +/- 2.3 pg/mL, versus 3.6 +/- 1.0, 13.1 +/- 3.9, and 3.9 +/- 1.0 pg/mL, resp). In controversy, serum IL-2 level was diminished in the obese group as 0.4 +/- 0.1 versus 0.9 +/- 0.1 U/L. Obesity may be a low-grade systemic inflammatory disease. Obese prepubertal children have elevated serum levels of IL-1beta , IL-6, and TNF-alpha which are known as markers of inflammation.     

Effects of nicotine and vitamin E on carbonic anhydrase activity in some rat tissues in vivo and in vitro

Effects of nicotine, nicotine + vitamin E and nicotine + Hippophea rhamnoides L. extract (HRe-1) on muscle, heart, lungs, testicle, kidney, stomach, brain and liver carbonic anhydrase (CA; EC 4.2.1.1.) enzyme activities were investigated in vivo. Groups of rats were given nicotine (0.5 mg/kg/day, i.p.), nicotine + vitamin E (75 mg/kg/day, i.g.), nicotine + HRe-1 (250 mg/kg/day, i.g.) and a control group vehicle only. The results showed that nicotine inhibited the heart, lung, stomach and liver CA enzyme activities by approximately 80% (p < 0.001), approximately 94% (p < 0.001), approximately 47% (p < 0.001) and approximately 81% (p < 0.001) respectively, and activated muscle and kidney, but had no effects on the testicle and brain CA activities. Nicotine + vitamin E inhibited the heart and liver CA enzyme activities by approximately 50% (p < 0.001), and approximately 50% (p < 0.001), respectively, and nicotine + vitamin E activated the muscle CA activity. However, nicotine + vitamin E had no effect on lung, testicle, kidney, stomach and brain CA activities. Nicotine + HRe-1 inhibited the heart and stomach CA enzyme activities by approximately 51% (p < 0.001), and approximately 32% (p < 0.002), respectively, and activated the muscle and brain CA activities, but had no effects on the lung, testicle, kidney, and liver CA activities. In vitro CA inhibition results for similar experiments correlated well with the in vivo experimental results in lungs, testicles, kidney, stomach, brain and liver tissues.     

Health Transformation Project and Defensive Medicine Practice among Neurosurgeons in Turkey

Background

The term “Defensive” medicine was coined in the early 1970′s and has been an important topic of scientific investigation and professional debate ever since.

Objective

The aim of this study was to investigate the characteristics of defensive medicine, its reasons, and the extent to which it is practiced in the Turkish health care system. This is the first national survey to study the practice of defensive medicine among neurosurgeons in Turkey.

Methods

The present cross-sectional study on defensive medicine assessed neurosurgeons registered at the Turkish Neurosurgical Society, who are actively working in various centers and hospitals within the Turkish health care system. A 40-question survey was adapted from existing measures described in the literature and was completed by a total of 404 neurosurgeons, representing 36.7% of the neurosurgeons registered at the Turkish Neurosurgical Society.

Results

Seventy-two percent of the participants in the current study reported practicing defensive medicine. This practice was mainly reported among inexperienced neurosurgeons (74.4%). Most were younger than 40 years of age (75.2%), working in state hospitals/universities (72.7%), and living in the Marmara region (38%). Respondents reported engaging in defensive medicine by avoiding high-risk surgery (62.6%), ordering additional imaging studies (60.9%) and laboratory tests (33.7%), and referring patients to consultants (31.2%). Most participants consider every patient as a potential threat in terms of a medical lawsuit (68.3%) and do not believe the courts can distinguish malpractice from complications (89.6%).

Conclusion

Concerns and perceptions about medical liability lead neurosurgeons to practice defensive medicine. By avoiding high-risk surgery, ordering unnecessary diagnostic tests, and referring the patients to consultants, neurosurgeons try to minimize the risk of malpractice and protect themselves from legal risks, resulting in higher healthcare expenditure and longer treatment periods.     

Bile acid derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide as new carbonic anhydrase inhibitors: synthesis and investigation of inhibition effects

Bile acid amides (cholan-24-amides) of 5-substituted 1,3,4-thiadiazole-2-sulfonamide have been prepared from lithocholic, deoxycholic, cholic and dehydrocholic acids. Besides, the alcohol functional groups on the cholane ring systems were protected with acetyl group. Amides of the protected cholanes of lithocholic and cholic acids were also synthesized. Later, inhibition effects of these compounds on human carbonic anhydrase isozymes (HCA-I and II) have been investigated in vitro. For the most active compounds, inhibition constants ranged from 66 to 190nM for HCA-II with I(50) (molarity of inhibitor producing a 50% inhibition of CA activity). In addition, in vivo studies were performed for the synthesized compounds in Sprague-Dawley rats. The compounds (11 and 18) showed especially significant inhibition efficacy (p<0.001).     

CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice

More humans have died of tuberculosis (TB) than any other infectious disease and millions still die each year. Experts advocate for blood-based, serum protein biomarkers to help diagnose TB, which afflicts millions of people in high-burden countries. However, the protein biomarker pipeline is small. Here, we used the Diversity Outbred (DO) mouse population to address this gap, identifying five protein biomarker candidates. One protein biomarker, serum CXCL1, met the World Health Organization’s Targeted Product Profile for a triage test to diagnose active TB from latent M.tb infection (LTBI), non-TB lung disease, and normal sera in HIV-negative, adults from South Africa and Vietnam. To find the biomarker candidates, we quantified seven immune cytokines and four inflammatory proteins corresponding to highly expressed genes unique to progressor DO mice. Next, we applied statistical and machine learning methods to the data, i.e., 11 proteins in lungs from 453 infected and 29 non-infected mice. After searching all combinations of five algorithms and 239 protein subsets, validating, and testing the findings on independent data, two combinations accurately diagnosed progressor DO mice: Logistic Regression using MMP8; and Gradient Tree Boosting using a panel of 4: CXCL1, CXCL2, TNF, IL-10. Of those five protein biomarker candidates, two (MMP8 and CXCL1) were crucial for classifying DO mice; were above the limit of detection in most human serum samples; and had not been widely assessed for diagnostic performance in humans before. In patient sera, CXCL1 exceeded the triage diagnostic test criteria (>90% sensitivity; >70% specificity), while MMP8 did not. Using Area Under the Curve analyses, CXCL1 averaged 94.5% sensitivity and 88.8% specificity for active pulmonary TB (ATB) vs LTBI; 90.9% sensitivity and 71.4% specificity for ATB vs non-TB; and 100.0% sensitivity and 98.4% specificity for ATB vs normal sera. Our findings overall show that the DO mouse population can discover diagnostic-quality, serum protein biomarkers of human TB.     

Leptin Does Not Play a Major Role in Platelet Aggregation in Obesity and Leptin Deficiency

Objective: A recent study suggested that high concentrations of leptin enhance platelet aggregations. Therefore, the aim of this study was to investigate whether platelet aggregation is altered in patients with leptin gene mutations compared with obese subjects or controls. Research Methods and Procedures: Four men (one homozygous man and his three heterozygous brothers) carrying a leptin gene mutation; 20 age‐matched, healthy, unrelated men; and 18 age‐matched obese men were enrolled in the study. Adenosine diphosphate (ADP)‐, collagen‐, and epinephrine‐induced platelet aggregation were evaluated in all individuals. Results: Our results show that patients with the leptin gene mutation (both the homozygous and heterozygous patients) had significantly higher ADP‐induced (78.3 ± 3.4% vs. 57.9 ± 9.3%, p = 0.001), collagen‐induced (78.1 ± 2.9% vs. 56.7 ± 9.3%, p = 0.007), and epinephrine‐induced (76.5 ± 9.2% vs. 59.5 ± 7.70%, p = 0.003) platelet aggregation compared with controls. However, ADP‐, collagen‐, or epinephrine‐induced platelet aggregations were similar to those in obese patients. Platelet aggregation responses to a combination of pretreatment with leptin at concentrations of 20, 50, 100, or 500 ng/mL for 5 minutes and ADP at concentrations of 2 μmol/liter also were evaluated. However, we did not find significant increases in platelet aggregation even at high concentrations of leptin (100 or 500 ng/mL) in leptin‐deficient patients, obese subjects, or controls. Discussion: Our data show that similar to findings in obese humans, homozygous or heterozygous leptin deficiency is associated with increased platelet aggregation compared with controls, and that higher concentrations of leptin do not increase platelet aggregation.     

Serum IL-18 levels in patients with type 1 diabetes: relations to metabolic control and microvascular complications

The study was designed to examine serum IL-18 level and its relation to metabolic control parameters and microvascular complications in type 1 diabetes mellitus (DM). Sixty two patients with type 1 DM and 30 healthy individuals were enrolled in the study. Serum IL-18 levels of patients with type 1 DM were significantly increased compared to controls (293.4+/-133.4 vs 211.2+/-63.9 pg/ml, P=0.003). Patients with poor glycemic control had higher levels of IL-18 than patients with well glycemic control (329.9+/-141.0 vs 226.3+/-89.6 pg/ml, P=0.02). There was no significant difference between the serum IL-18 levels of patients with microvascular complications and those of patients without microvascular complications (307.6+/-127.6 vs 293.2+/-145.6 pg/ml, P>0.05). IL-18 correlated positively with HbA(1c) (r=0.32, P=0.01) and postprandial blood glucose (PPBG) (r=0.26, P=0.02); and negatively with HDL-cholesterol (HDL-C) (r=-0.38, P=0.007). By linear regression analysis, PPBG was determined as the most explanatory parameter for the alterations in serum IL-18 levels (P=0.02). High levels of IL-18 in patients with type 1 DM is related to short and long term glycemic control and HDL-C levels but not to microvascular complications.     

Large-scale purification of viroid RNA using Cs2SO4 gradient centrifugation and high-performance liquid chromatography

A procedure for the purification of viroid RNA from tomato plants is described which yields up to a milligram of viroid RNA of gel electrophoretic homogeneity within 2 days. This technique is at least three times as fast as previous methods and is generally applicable to other RNA species. Plant material was homogenized and phenol extracted. In a Cs₂SO₄ density gradient, viroid RNA together with low-molecular-weight RNA, was separated from large single-stranded RNA, DNA, polysaccharides, polyphenols, and other compounds. The separation is based on the differences in the buoyant density and on the selective precipitation of large single-stranded RNA in Cs₂SO₄. Further purification of viroid RNA was achieved by HPLC over a weak anion exchanger linked to silica gel of optimized pore size. The elution was carried out by a salt gradient with complete exclusion of divalent metal ions. The procedures were applied to whole plants, leaves, stems, roots, cells, and protoplasts. The yields of nucleic acids at the different steps of purification are given for leaves, stems, and roots.     

Comparison of dose distributions and organs at risk (OAR) doses in conventional tangential technique (CTT) and IMRT plans with different numbers of beam in left-sided breast cancer

Aim

Our aim was to improve dose distribution to the left breast and to determine the dose received by the ipsilateral lung, heart, contralateral lung and contralateral breast during primary left-sided breast irradiation by using intensity modulated radiotherapy (IMRT) techniques compared to conventional tangential techniques (CTT). At the same time, different beams of IMRT plans were compared to each other in respect to CI, HI and organs at risk (OAR) dose.

Background

Conventional early breast cancer treatment consists of lumpectomy followed by whole breast radiation therapy. CTT is a traditional method used for whole breast radiotherapy and includes standard wedged tangents (two opposed wedged tangential photon beams). The IMRT technique has been widely used for many treatment sites, allowing both improved sparing of normal tissues and more conformal dose distributions. IMRT is a new technique for whole breast radiotherapy. IMRT is used to improve conformity and homogeneity and used to reduce OAR doses.

Materials and methods

Thirty patients with left-sided breast carcinoma were treated between 2005 and 2008 using 6, 18 or mixed 6/18 MV photons for primary breast irradiation following breast conserving surgery (BCS). The clinical target volume [CTV] was contoured as a target volume and the contralateral breast, ipsilateral lung, contralateral lung and heart tissues as organs at risk (OAR). IMRT with seven beams (IMRT7), nine beams (IMRT9) and 11 beams (IMRT11) plans were developed and compared with CTT and among each other. The conformity index (CI), homogeneity index (HI), and doses to OAR were compared to each other.

Results

All of IMRT plans significantly improved CI (CTT: 0.76; IMRT7: 0.84; IMRT9: 0.84; IMRT11: 0.85), HI (CTT: 1.16; IMRT7: 1.12; IMRT9: 1.11; IMRT11: 1.11), volume of the ipsilateral lung receiving more than 20 Gy (>V_20 Gy) (CTT: 14.6; IMRT7: 9.08; IMRT9: 8.10; IMRT11: 8.60), and volume of the heart receiving more than 30 Gy (>V_30 Gy) (CTT: 6.7; IMRT7: 4.04; IMRT9: 2.80; IMRT11: 2.98) compared to CTT. All IMRT plans were found to significantly decrease >V_20 Gy and >V_30 Gy volumes compared to conformal plans. But IMRT plans increased the volume of OAR receiving low dose radiotherapy: volume of contralateral lung receiving 5 and 10 Gy (CTT: 0.0–0.0; IMRT7: 19.0–0.7; IMRT9: 17.2–0.66; IMRT11: 18.7–0.58, respectively) and volume of contralateral breast receiving 10 Gy (CTT: 0.03; IMRT7: 0.38; IMRT9: 0.60; IMRT11: 0.68). The differences among IMRT plans with increased number of beams were not statistically significant.

Conclusion

IMRT significantly improved conformity and homogeneity index for plans. Heart and lung volumes receiving high doses were decreased, but OAR receiving low doses was increased.     

Optimization based tumor classification from microarray gene expression data

Background

An important use of data obtained from microarray measurements is the classification of tumor types with respect to genes that are either up or down regulated in specific cancer types. A number of algorithms have been proposed to obtain such classifications. These algorithms usually require parameter optimization to obtain accurate results depending on the type of data. Additionally, it is highly critical to find an optimal set of markers among those up or down regulated genes that can be clinically utilized to build assays for the diagnosis or to follow progression of specific cancer types. In this paper, we employ a mixed integer programming based classification algorithm named hyper-box enclosure method (HBE) for the classification of some cancer types with a minimal set of predictor genes. This optimization based method which is a user friendly and efficient classifier may allow the clinicians to diagnose and follow progression of certain cancer types.

Methodology/Principal Findings

We apply HBE algorithm to some well known data sets such as leukemia, prostate cancer, diffuse large B-cell lymphoma (DLBCL), small round blue cell tumors (SRBCT) to find some predictor genes that can be utilized for diagnosis and prognosis in a robust manner with a high accuracy. Our approach does not require any modification or parameter optimization for each data set. Additionally, information gain attribute evaluator, relief attribute evaluator and correlation-based feature selection methods are employed for the gene selection. The results are compared with those from other studies and biological roles of selected genes in corresponding cancer type are described.

Conclusions/Significance

The performance of our algorithm overall was better than the other algorithms reported in the literature and classifiers found in WEKA data-mining package. Since it does not require a parameter optimization and it performs consistently very high prediction rate on different type of data sets, HBE method is an effective and consistent tool for cancer type prediction with a small number of gene markers.