Asthma control affects school absence, achievement and quality of school life: a multicenter study.

INTRODUCTION AND OBJECTIVES: Asthma may have a detrimental effect on school attendance and achievement. Friend relations, attendance to school activities, quality of life (QOL) of asthmatic children may be negatively affected. The aim of this study was to evaluate factors influencing school functioning for asthmatic school-age children. MATERIALS AND METHODS: From January to May 2019, parents and school-age children who were followed by a diagnosis of asthma for more than one year, from seven pediatric allergy centers, were given a standard questionnaire including questions about child's disease, school performance, absenteeism, home-family-school conditions. A pediatric QOL questionnaire was filled out by children. For evaluating control in the previous year, children who had more than two exacerbations and/or had any exacerbations needing systemic corticosteroids in the previous year were defined as inadequate control. School absence over nine days was taken into account as this has been shown to bring a risk for successful school life. RESULTS: 507 patients were included. Asthma control status was found to be effective on school absence (p < 0.001), on school success (especially math scores) (p < 0.001), on friend relations (p = 0.033), QOL (p < 0.001), attendance to school activities (p < 0.001). Regular follow-up (p < 0.001), regular use of asthma medication (p = 0.014), tobacco smoke exposure (p < 0.001), heating with stove at home (p = 0.01) affected asthma control. School conditions such as crowdedness (p = 0.044), humidity of the class (p = 0.025), knowledge of teacher about child's asthma (p = 0.012) were effective on asthma control independent of home conditions and asthma treatment parameters. CONCLUSION: School interventions are important to improve asthma management.

The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults?

OBJECTIVE: Hypertrophic obesity correlates with metabolic complications of obesity. We evaluated adipocyte volume and its relationship with tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), adiponectin and high sensitivity C-reactive protein (hs-CRP) levels. SUBJECTS AND METHODS: Patients were divided into 4 groups; lean healthy controls [body mass index (BMI): 24.2+/-1.4 kg/m2], non-diabetic obese patients (30.2+/-2.9), obese (30.1+/-3.2) and non-obese (22.2+/-1.5) Type 2 diabetic patients. TNF-alpha, hs-CRP, adiponectin and IL-6 levels were measured preoperatively and sc fat specimens were obtained during operation. Semi-thin sections were stained with toluidine-blue and evaluated by light microscopy. Fat volumes were calculated by Goldrick's formulation. RESULTS: Mean adipocyte volumes were higher in obese diabetic patients than in other groups (p<0.0001). Mean TNF-alpha, hs-CRP and IL-6 levels were higher in obese diabetic patients than in control subjects, obese non-diabetic and non-obese diabetic patients (p<0.0001, p<0.02 and p<0.01, respectively). Mean TNF-alpha levels of non-diabetic obese patients were higher than the control group (p<0.05). Mean IL-6 levels of diabetic and non-diabetic obese patients were higher than control subjects (p<0.02 and p<0.0001, respectively). Mean adiponectin levels of control subjects were higher than non-diabetic obese, non-obese diabetic and obese-diabetic subjects (p<0.0001). Mean adiponectin levels of obese diabetic patients were lower than non-diabetic obese subjects (p<0.008). Mean hs-CRP levels were higher in diabetic patients whether they were obese or not. There was a positive correlation between adipocyte size and TNF-alpha (p<0.01), IL-6 (p<0.03) and hs-CRP levels (p<0.004), and negative correlation between adipocyte size, adiponectin levels (p<0.0001). CONCLUSIONS: TNF-alpha, IL-6 and hs-CRP levels were positively, adiponectin negatively correlated with adipocyte size. Therefore, adiposity may be an inflammatory condition.

A novel electron-conformational approach to molecular modeling for QSAR by identification of pharmacophore and anti-pharmacophore shielding.

Abstract A novel method of pharmacophore identification and activity prediction in structure-activity (structure-property) relationships is worked out as an essential extension and improvement of previous publications. In this method each conformation of the molecular systems in the training set of the SAR problem is presented by both electronic structure and geometry parameters arranged in a matrix form. Multiple comparisons of these matrices for the active and inactive compounds allows one to separate a smaller number of matrix elements that are common for all the active compounds and are not present in the same arrangement in the inactive ones. This submatrix of activity represents the pharmacophore (Pha). By introducing the Anti-Pharmacophore Shielding (APS) defined as molecular groups and competing charges outside the Pha that hinder the proper docking of the Pha with the bioreceptor, the procedure of Pha identification is essentially reduced to the treatment of a smaller number of simplest in structure most active and inactive compounds. A simple empirical scheme is suggested to estimate the APS numerically, while the contributions of different conformations of the same compound are taken into account by means of Boltzmann distribution. This enables us to make approximate quantitative predictions of activities. In application to rice blast activity we reached an approximately 100% (within experimental error) prediction probability of the activity qualitatively (yes, no), and with r (2) = 70% quantitatively.

Protective effect of ethyl pyruvate on liver injury in streptozotocin-induced diabetic rats.

BACKGROUND AND AIMS: Diabetes Mellitus, leading to an increase in oxidative stress, can cause liver damage. Our aim was to investigate the antioxidant effects of Ethyl Pyruvate (EP) on the liver tissue in diabetic rats. MATERIALS AND METHODS: Thirty-two Wistar albino rats were separated into four equal groups. Groups were assigned as follows: (1) Non-diabetic group; (2) EP-treated non-diabetic group; (3) diabetic group; and (4) EP-treated diabetic group. In order to induce diabetes mellitus, 45 mg/kg b.w. streptozotocin was administered intraperitoneally to the rats in groups 3 and 4. On the 3rd day, blood glucose was assessed. Rats with blood glucose levels higher than 300 mg/dl were considered to be diabetic. The EP solution was administered intraperitoneally at a dose of 50 mg/kg b.w. twice daily for 14 days to the rats in groups 2 and 4. The other rats were simultaneously given the same amount of Ringer's lactate solution intraperitoneally. Liver tissue was obtained for malondialdehyde (MDA) analyses and histopathological examination. RESULTS: In group 4, Total Antioxidant Status (TOS) and MDA levels were significantly lower as compared to group 3. Also, morphological abnormalities occurred in group 3 when compared with non-diabetic groups (groups 1 and 2), whereas the disorders resulting from diabetes improved significantly in group 4. CONCLUSIONS: These findings show that EP has protective effects against diabetes-induced liver injury.

Improved electron-conformational method of pharmacophore identification and bioactivity prediction. Application to angiotensin converting enzyme inhibitors.

The electron-conformational (EC) method of pharmacophore (Pha) identification and bioactivity prediction, suggested earlier, is given here two major improvements. First, an atomic index of orbital and charge controlled interaction is introduced to better represent the ligand (substrate) in its interaction with the bioreceptor. Second, the multiconformational problem is considered in view of ligand-receptor binding states, resulting in essential simplification of the expression of bioactivity. The details of the improved EC method are demonstrated in application to the problem of angiotensin converting enzyme (ACE) inhibitors. The Pha of the latter is identified by separation of the heavily populated conformations of the chosen 51 compounds (the training set), calculation of the electronic structure, construction of their EC matrixes of congruity, and processing of the latter in comparison with the activities to reveal a common submatrix of all the active only compounds that describes the Pha. The latter contains three oxygen atoms plus a fourth atom X = S, N, O at certain interatomic distances and with restricted electronic parameters (within assumed tolerances), the position of the atom X being more changeable from one active compound to another. For quantitative prediction of the bioactivity, an expression is deduced which takes into account the duly parametrized influence of auxiliary groups (AG) which, being positioned outside the Pha, either diminish the activity (antipharmacophore shielding) or enhance it. It is shown that in case of many conformations of the same compound only one of them, that of the lowest energy which has the Pha, should be parametrized. The 15 parameters chosen to represent the AG in case of ACE inhibitors are weighted by variational (adjustable) coefficients which are determined from a regression treatment of the calculated versus known activities in the training set. Then the formulas with known coefficients are used to validate the method by calculating the bioactivity of other compounds not used in the training set. The prediction of the activity proved to be more than 90% (within experimental error and available compounds) qualitatively (yes, no) and about 60%-70% quantitatively.

Is hyperprolactinemia associated with insulin resistance in non-obese patients with polycystic ovary syndrome?

Insulin resistance is common in polycystic ovary syndrome (PCOS). Moderate elevations in serum PRL concentration may contribute to insulin resistance in PCOS. The aim of this study was to determine PRL on development of insulin resistance in non-obese hyperprolactinemic patients with PCOS. Ninety-eight non-obese subjects with PCOS and 100 non-obese healthy control were accepted in the study. Serum glucose, lipids, androgens, free androgen index (FAI), gonadotropins, fat mass and percentage, SHBG, and insulin levels were measured. Homeostasis model assessment (HOMA) was used as index of pancreatic beta-cell function and tissue insulin sensitivity. Independent t-test was used in comparison of results. In patients with PCOS, FAI and mean HOMA-(%B) level were higher than in the control group (p<0.0001), whereas mean HOMA-(%S) in subjects with PCOS was lower than in the control group (p<0.0001). Patients with PCOS were divided into subgroups according to their serum prolactin level (< 24 or > or = 24 ng/ml). Although FAI was not different, mean insulin and HOMA-(%B) levels in hyperprolactinemic patients were higher than in normoprolactinemic subjects (p<0.001). HOMA-(%S) in hyperprolactinemic patients with PCOS was lower than in normoprolactinemic patients (p<0.002). In conclusion, PCOS is associated with insulin resistance; non-obese hyperprolactinemic PCOS patients may be more insulin-resistant than normoprolactinemics and there may be an association between hyperprolactinemia and insulin resistance in PCOS.

The comparison of insulin sensitivity in non-diabetic hemodialysis patients treated with and without recombinant human erythropoietin.

BACKGROUND: Patients with end-stage renal disease (ESRD) are known to have insulin resistance. Treatment with EPO is associated with improvement in insulin sensitivity in uremic patients. The aim of this study was to compare insulin sensitivity and pancreatic B cell function in adult non-diabetic uremic hemodialysis patients treated with or without rHuEPO. SUBJECTS AND METHODS: Three groups of subjects were included to the study: hemodialysis patients treated with rHuEPO [EPO(+) group] or without rHuEPO [EPO(-) group], and healthy controls. Anthropometrical parameters, lipid levels, fasting glucose and insulin levels were measured in all subjects. Homeostasis Model Assessment (HOMA) was used to compare insulin sensitivity. ANOVA, independent t-test, and Pearson correlation were used for statistical analysis. RESULTS: Mean insulin level of control group (20.04 +/- 7.2 pmol/l) was significantly lower than EPO(+) group (p < 0.04) and EPO(-) group (p < 0.0001). HOMA-(%B) levels in the EPO(+) group were significantly lower than in the EPO(-) group (106 +/- 42, 140 +/- 63 respectively, p < 0.02). HOMA-(%B) levels in the control group (66 +/- 17) were significantly lower than in the EPO(+) and EPO(-) group (p < 0.005 and p < 0.0001 respectively). HOMA-(%S) levels in the EPO(+) groups was significantly higher than in the EPO(-) group (91 +/- 40, 56 +/- 26, respectively; p < 0.01). HOMA-(%S) levels of control group (125 +/- 24 ) was significantly higher than EPO(+) and EPO(-) groups (p < 0.02, p < 0.0001 respectively). We found a positive correlation between duration of erythropoietin treatment and insulin sensitivity (r = 0.484, p < 0.002). CONCLUSIONS: Firstly, patients treated with EPO are insulin sensitive compared to patients not treated with EPO. Secondly, duration of erythropoietin treatment is positively correlated with insulin sensitivity in hemodialysis patients.

Serum prostate specific antigen levels in women with polycystic ovary syndrome and the effect of flutamide+desogestrel/ethinyl estradiol combination.

BACKGROUND: Prostate-specific antigen (PSA) is expressed in many female tissues and its concentrations were higher in hirsute subjects. We aimed to determine serum PSA level in hirsute women and evaluate the effect of flutamide+desogestrel/ethynil estradiol combination. SUBJECTS AND STUDY DESIGN: Thirty patients with polycystic ovary syndrome (PCOS) and 30 healthy controls were studied. Hirsutism was defined by modified Ferriman-Gallwey score (FGS). Free androgen index (FAI) was used for hyperandrogenism. Patients received flutamide (500 mg/d) and oral contraceptive (desogestrel+ethinyl estradiol) for 9 months. RESULTS: Mean FGS (p<0.0001), insulin (p<0.01), FAI (0.0001), androstenedione (p<0.0001), LH (p<0.05), and free testosterone (p<0.003) levels of patients with PCOS were higher than the control group. Mean serum total and free PSA level of PCOS patients were higher than the control group (p<0.0001 and p<0.0001). We found a positive correlation between total PSA levels and FGS (r=0.568, p<0.001), FAI and FGS (r=0.456 and p<0.01). There was also a positive correlation between FAI and total PSA (r=0.503 and p<0.005). At the end of treatment, FGS, androstenedione, free and total testosterone, FAI, serum PSA and LH levels decreased significantly [serum total PSA was 0.0208 +/- 0.0178 ng/ml at baseline and 0.0061 +/- 0.0044 ng/ml after treatment (p<0.0001)]. CONCLUSIONS: 1. Serum prostate specific antigen level is higher in patients with PCOS; 2. There is a positive correlation among FGS, FAI and PSA levels; 3. Serum PSA levels decrease with antiandrogen treatment; 4. Serum PSA measurement might be a marker for hirsutism.

An electron-conformational method of identification of pharmacophore and anti-pharmacophore shielding: application to rice blast activity.

In extension and improvement of previous results, a novel method is worked out for pharmacophore identification and activity prediction in structure-activity relationships. In this method, as in our previous works, each molecular system (conformation) of the training set is described by a matrix with both electron structural parameters (atomic charges, bond orders, etc.) and interatomic distances as matrix elements. This description includes a rather full geometry of charge and/or reactivity distribution thus providing a much better representation of the molecular properties in their interaction with the target. By multiple comparison of these matrices for the active and inactive compounds of the training set, a relatively small number of matrix elements are revealed that are common for all the active compounds and are not present in the same combination in the inactive ones. In this way a set of electronic and geometry parameters is obtained that characterize the pharmacophore (Pha). A major improvement of this scheme is reached by introducing the anti-pharmacophore shielding (APS) and a proper treatment of the conformational problem. The APS is defined as molecular groups and competing charges outside the basic skeleton (the Pha plus the inert neighbor atoms that do not affect the activity) that hinder the proper docking of the Pha with the bioreceptor thus diminishing (partially or completely) the activity. A simple empirical formula is derived to estimate the relative contribution of APS numerically. Two main issues are most affected by the APS: (1) the procedure of Pha identification is essentially simplified because only a small number of molecular systems with the highest activity and simplest structures (systems without APS) should be tried for this purpose; (2) with the APS known numerically, we can make a quantitative (or semiquantitative) prediction of relative activities. The contributions of different conformations (of the same molecular system) that possess the Pha and different APS is taken into account by means of a Boltzmann distribution at given temperatures. Applied to an example, rice blast activity, this approach proved to be rather robust and efficient. In validation of the method, the screening of 39 new compounds yields approximately 100% (within experimental error) prediction probability of the activity qualitatively (yes, no), and with r2 = 0.66 quantitatively.

Insulin sensitivity and hyperprolactinemia.

It has been shown that prolactin (PRL) induces glucose intolerance, hyperinsulinemia and insulin resistance in several animal species. In women with microprolactinomas, the sensitivity to insulin is lower in hyperprolactinemia than in normoprolactinemia. Thirty non-obese women with hyperprolactinemia and 30 healthy non-obese women were included into the study. Age, body weight (bw), height, body mass index (BMI), waist circumference, hip circumference and waist to hip ratio of both patients with hyperprolactinemia and control subjects were not different. Mean serum prolactin level was higher in hyperprolactinemic patients than in control group (84.5 +/- 51.1 ng/ml and 13.8 +/- 5.3 ng/ml respectively, p<0.002). Mean HOMA-(%B) index of hyperprolactinemic patients was higher than in control subjects (121 +/- 49 and 84 +/- 38, respectively, p<0.02). Mean HOMA-(%S) index was lower in hyperprolactinemic patients (56 +/- 39 and 105 +/- 55, respectively, p<0.006). Serum total testosterone, free testosterone, androstenedione, estradiol, cortisol, sex hormone binding globulin and DHEA-S levels in both hyperprolactinemic women and healthy subjects, statistically did not show any difference between the two groups. The present data indicate that hyperprolactinemia is associated with an insulin-resistant state. This resistant state may not be a result of obesity, androgenic hormones, and SHBG or pregnancy. It may be the result of serum free fatty acids (FFA) levels, decrement in the number of insulin receptors (by a down-regulation of insulin receptors) or post-binding defect in insulin action or more.