YPTB3816 of Yersinia pseudotuberculosis strain IP32953 is a virulence-related metallo-oligopeptidase.

BACKGROUND: Although bacterial peptidases are known to be produced by various microorganisms, including pathogenic bacteria, their role in bacterial physiology is not fully understood. In particular, oligopeptidases are thought to be mainly involved in degradation of short peptides e.g. leader peptides released during classical protein secretion pathways. The aim of this study was to investigate effects of inactivation of an oligopeptidase encoding gene opdA gene of Yersinia pseudotuberculosis on bacterial properties in vivo and in vitro, and to test dependence of the enzymatic activity of the respective purified enzyme on the presence of different divalent cations. RESULTS: In this study we found that oligopeptidase OpdA of Yersinia pseudotuberculosis is required for bacterial virulence, whilst knocking out the respective gene did not have any effect on bacterial viability or growth rate in vitro. In addition, we studied enzymatic properties of this enzyme after expression and purification from E. coli. Using an enzyme depleted of contaminant divalent cations and different types of fluorescently labelled substrates, we found strong dependence of its activity on the presence of particular cations. Unexpectedly, Zn2+ showed stimulatory activity only at low concentrations, but inhibited the enzyme at higher concentrations. In contrast, Co2+, Ca2+ and Mn2+ stimulated activity at all concentrations tested, whilst Mg2+ revealed no effect on the enzyme activity at all concentrations used. CONCLUSIONS: The results of this study provide valuable contribution to the investigation of bacterial peptidases in general, and that of metallo-oligopeptidases in particular. This is the first study demonstrating that opdA in Yersinia pseudotuberculsosis is required for pathogenicity. The data reported are important for better understanding of the role of OpdA-like enzymes in pathogenesis in bacterial infections. Characterisation of this protein may serve as a basis for the development of novel antibacterials based on specific inhibition of this peptidase activity.

Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.

Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: Real-world experience from Turkey (ARNi-TR).

OBJECTIVE: Heart failure (HF) is a growing public health problem with high morbidity and mortality. Recently, angiotensin receptor neprilysin inhibitor (ARNi) has emerged as a promising treatment for HF with reduced ejection fraction (HFrEF). Here, we shared our experience with the use of ARNi in HFrEF from multiple centers in Turkey. METHODS: The ARNi-TR is a multicenter, noninterventional, retrospective, observational study. Overall, 779 patients with HF from 22 centers in Turkey who were prescribed sacubitril/valsartan were examined. Initial clinical status, biochemical and echocardiographic parameters, and New York Heart Association functional class (NYHA-FC) values were compared with follow-up values after 1 year of ARNi use. In addition, the effect of ARNi on number of annual hospitalizations was investigated, and the patients were divided into 2 groups, depending on whether ARNi was initiated at hospitalization or under outpatient clinic control. RESULTS: N-terminal pro-brain natriuretic peptide (NT-proBNP), left-ventricle ejection fraction (LV-EF), and NYHA-FC values improved significantly in both groups (all parameters, p<0.001) within 1-year follow-up. In both groups, a decrease in hemoglobin A1c (HbA1c) values was observed in ARNi use (p<0.001), and a decrease in daily diuretic doses and hospitalizations owing to HF were observed after ARNi use (all comparisons, p<0.001). Hypotension (16.9%) was the most common side effect in patients using ARN. CONCLUSION: The ARNi-TR study offers comprehensive real-life data for patients using ARNi in Turkey. The use of ARNi has shown significant improvements in FC, NT-proBNP, HbA1c levels, and LV-EF. Likewise, reductions in the number of annual hospitalizations and daily furosemide doses for HF were seen in this study.

DNA damage in children with asthma bronchiale and its association with oxidative and antioxidative measurements.

Increased production of reactive oxygen species leading to an imbalance between the oxidative forces and the antioxidant defense systems favoring an oxidative injury has been implicated in the pathogenesis of asthma. The aim of the study was to investigate the peripheral DNA damage, and its association with oxidative and antioxidative measurements in children with asthma bronchiale. The study population contained 42 children with asthma bronchiale and 32 healthy controls. DNA damage was assessed by alkaline comet assay in peripheral lymphocytes. Plasma levels of total antioxidant status (TAS), total peroxide concentration (LOOHs), and total oxidant status (TOS) were determined. In asthma bronchiale patients, DNA damage was significantly higher than in controls (17.9 +/- 11.8 AU vs. 1.2 +/- 2.0 AU, p < 0.001). Plasma TOS and LOOHs were higher in patients than in healthy controls (13.4 +/- 7.0 vs. 9.0 +/- 3.5, p = 0.002; 9.9 +/- 3.4 vs. 4.4 +/- 1.5, p < 0.001, respectively). Plasma TAS level in patients was higher than in healthy controls (5.5 +/- 2.5 vs. 1.0 +/- 0.6, p < 0.001). DNA damage was correlated with TOS (r = 0,616, p < 0.001). The findings indicated that lymphocyte DNA damage level increases in children with asthma bronchiale. Elevated DNA damage may be related to increased oxidative stress. However, the mechanism of this association, and whether it is direct or indirect, remains to be explored.

Severe osteoporosis and high level TSH in a child before the diagnosis of acute lymphoblastic leukemia.

Osteoporosis in children is rare and mostly secondary to such conditions as prolonged immobilization, malabsorption syndromes, corticosteroid excess, osteogenesis imperfecta, celiac disease, Turner syndrome, and malignancy. Idiopathic juvenile osteoporosis (IJO) is a very rare condition of primary bone demineralization that presents in childhood. IJO, a disease of unknown etiology, manifests typically by pain, bone deformities, and fractures. Diagnosis of IJO was made by excluding other common causes of osteoporosis in this age. Bisphosphonates, calcitriol, fluoride, and calcitonin have been administered therapeutically, but the results were equivocal. Usually the disease remits by itself. Patient that has serious osteoporosis and high thyroid stimulating hormone level was diagnosed as IJO by eliminating secondary reasons. We report this case, whose symptoms were disappeared after parenteral pamidronat treatment, and he was reexamined owing to anemia and trombositopenia, and diagnosed as B-cell acute lymphoblastic leukemia, just to emphasis the importance of close follow-ups of IJO patients.

Oxidative status and paraoxonase activity in children with asthma.

OBJECTIVE: To compare paraoxonase activity and changes in oxidative status in asthmatic children and healthy children by determining serum paraoxonase activity and total oxidative status, total antioxidant capacity and lipid hydroperoxidation. METHODS: Forty two asthmatic children were compared with 32 healthy children of similar age and sex. To evaluate the paraoxonase and oxidative status, total antioxidant capacity and lipid hydroperoxidation were examined. Serum paraoxonase activity was evaluated by measuring the rate of paraoxon hydrolosis. Oxidative status was evaluated by the method developed by Erel. Lipid hydroperoxide was measured by an iodometric method. RESULTS: In comparison with the healthy control group, the paraoxonase activity of the asthmatic children was found to be low (163.7 +/- 73.0 (U/L) and 349.2 +/- 153.9 (U/L), P = 0.002) and total oxidant status (9.0 +/- 3.5 micromol H2O2 Eq/L and 13.4 +/- 7.0 micromol H2O2 Eq/L, P =0.002), total antioxidant capacity (5.5 +/- 2.5 micromol Trolox Eq/L and 1.0 +/- 0.6 micromol Trolox Eq/L, P < 0.001), and lipid hydroperoxidation values (9.9 +/- 3.4 micromol H2O2 Eq/L and 4.4 +/- 1.5 micromol H2O2 Eq/L, P < 0.001) were found to be high. The high density lipoprotein (HDL) concentration of the asthmatic children was lower than that in the control group (40.1 +/- 9.2 mg/dl and 54.5 +/- 15.9 mg/dl, P < 0.001) CONCLUSION: In asthmatic children, when total oxidant status, total antioxidant capacity and lipid hydroperoxidation levels increase, paraoxonase activity decreased.

Serum prolidase activity and oxidative status in patients with bronchial asthma.

Asthma is a disease where there is an accumulation of collagen in the reticular basal membrane of the airway leading to chronic inflammation. The enzyme prolidase plays an important role in the breakdown of collagen and the breakdown of intracellular protein especially in the final stage when peptides and dipeptides contain a high level of proline. To evaluate the relationship between prolidase activity and oxidative status in asthma patients. Comparison was made between 42 patients diagnosed with bronchial asthma and 32 healthy children of similar age and gender. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total antioxidant capacity (TAC) and total oxidant status (TOS) measurement. The prolidase activity of the asthma patient group was statistically significant compared with the control group (P< or =0.001). TAC and TOS levels in the asthma patient group were higher than the control group (P< or =0.001, P< or =0.002, respectively). No correlation was found between the prolidase and oxidative levels of the two groups. A positive correlation was determined between the prolidase activity and TAC in the asthma patient group (P< or =0.001, r=0.501). The prolidase enzyme activity, which plays a role in the collagen turnover, was low in the asthma patients; therefore, their collagen metabolism had undergone a change and this indicates that there may be an effect on the accumulation of collagen in the reticular basal membrane. Moreover, the high level of TOS indicates that these patients were exposed to severe oxidative stress with an increased TAC response.

A comparison of multiple daily insulin therapy with continuous subcutaneous insulin infusion therapy in adolescents with type 1 diabetes mellitus: a single-center experience from Turkey.

AIM: To compare the long-term outcomes of continuous subcutaneous insulin infusion (CSII) pump therapy with the clinical and metabolic parameters recorded during multiple daily insulin (MDI) therapy. PATIENTS AND METHODS: CSII pump was used by volunteer adolescents, who had a duration of diabetes mellitus (DM) longer than one year, regularly attended periodic examinations for the last year, measured and recorded blood glucose levels on average 3 to 4 times a day, and did not achieve the preferred metabolic control even though the use of MDI therapy. Carbohydrate counting and flexible MDI therapy was taught to these patients before CSII pump implantation. The metabolic and clinical parameters of the patients for the post-CSII pump period were compared with the data of flexible and non-flexible MDI periods. RESULTS: The mean CSII pump implantation age of the 17 adolescents enrolled in the study was 15.53 +/- 1.8 years, duration of DM 6.77 +/- 4.05 years, flexible MDI injection duration 0.70 +/- 0.20 years, and duration of CSII pump use 2.07 +/- 1.12 years. A decrease was detected in HbA(1c) levels of the patients with transition to CSII pump compared to flexible and non-flexible MDI injection periods; however, this decrease was not statistically significant (7.71%, 8.21%, and 8.71%, respectively, p = 0.105). No statistically significant difference was detected in frequency of hypoglycemia, lipid profiles, total daily insulin requirement, and BMI SDS values of the patients when data of the post-CSII pump state were compared with that of flexible and non-flexible MDI therapy groups. CONCLUSION: In adolescents, it was found that CSII pump therapy is efficient and safe without any increased risk for weight gain and hypoglycemia compared to flexible and non-flexible MDI injection periods. The present study also demonstrated that flexible MDI injection therapy might be efficiently and safely used in patients who cannot receive CSII pump therapy due to social and/or financial factors.

Can haptoglobin be an indicator for the early diagnosis of neonatal jaundice?

Neonatal jaundice is the result of an imbalance between bilirubin production and elimination. Bilirubin conjugation in newborns is significantly impaired in the first few days; even a small increase in the rate of production can contribute to the development of hyperbilirubinemia. Hemolysis has a significant role in bilirubin increase in newborns. Intrauterine is tolerated by the maternal metabolism in life. When hemolysis takes place, a decrease is accepted in the haptoglobin and hemopoexin blood levels binding hemoglobin in the environment. Therefore, it may be considered that haptoglobin and hemopoexin from the early period umbilical cord (UC) blood in newborns may be an indicator in determining jaundice likely to develop in later stages. Babies were called to the control polyclinic in the third and fifth days. Eighty-four babies with normal term birth were included in the study. Gestational age of the mothers was 39.5+/-1.5 weeks in average. A significant negative correlation was found between the haptoglobin level from the UC taken during delivery and the bilirubin value in the fifth day (r=-0.345; P=0.001). The haptoglobin value from the blood of the UC can be used as a guiding indicator to demonstrate the future occurrence of jaundice in newborns. This way, the babies with high jaundice risk may be detected earlier and closer follow-up of these babies can be obtained. As a result, the haptoglobin level of the blood from the UC during delivery allows us to make an early prediction on whether neonatal jaundice will occur.

Effect of routine postdilatation on final coronary blood flow in primary percutaneous coronary intervention patients without angiographic stent expansion problems.

Inadequate expansion of coronary stents is associated with stent thrombosis in early stage and with stent restenosis in later stages. Postdilatation (postD) performed using non-compliant balloons improves stent expansion. However, use of this ballooning strategy in primary percutaneous coronary intervention (PPCI) has not been evaluated adequately. Patients who presented with ST segment elevation myocardial infarction (STEMI) and underwent PPCI were included in the present study. Patients were randomized into two groups as those for whom postD was performed (n=62) and those for whom postD was not performed (n=62). Coronary blood flow was evaluated using the thrombolysis in myocardial infarction (TIMI) flow and TIMI frame count (TFC). Total of 124 patients with STEMI were included in the study. There was no difference with respect to baseline TIMI flow, culprit coronary artery and MI localization. However, slow-reflow rate (14.5% vs 35.5%, p=0.007) and final corrected TFC (28.9±16.9 vs 37.0±23.1, p=0.028) were significantly higher in the postD group. Multivariate regression analysis showed postD as an independent variable for slow reflow (OR 11.566, 95% CI 1.633 to 81.908, p=0.014). In our study, routine postD during PPCI was found to be associated with an increased risk of slow reflow in patients without angiographic stent expansion problems.

Complex urogenital malformation associated with female pseudohermaphroditism: caudal dysgenesis syndrome.

Caudal dysgenesis syndrome is a rare cause of female pseudohermaphroditism. This syndrome consists of absent perineal and anal openings in association with ambiguous genitalia, urogenital, colonic, and lumbosacral anomalies. We report a case of caudal dysgenesis syndrome in an infant who had non-palpable testes, bifid scrotum, a phallus-like structure and urethral atresia. Radiological evaluation revealed bilateral hydronephrosis, bifid uterus, cervix and vagina. Caudal dysgenesis syndrome should be considered in any female infant presenting with bilateral streak ovaries, and Müllerian and genito-urinary anomalies.

Evaluation of Pre-Treatment and Post-Treatment S100B, Oxidant and Antioxidant Capacity in Children with Diabetic Ketoacidosis.

OBJECTIVE: The study aimed to evaluate the pre-treatment and post-treatment oxidant capacity, antioxidant capacity and S100B protein levels in cases of diabetic ketoacidosis (DKA). METHODS: The study included 49 pediatric patients diagnosed with DKA and a control group comprising 49 healthy children. Blood samples were obtained after confirmation of the DKA diagnosis and also after treatment. S100B, total oxidant (TOL) and total antioxidant levels (TAL) were measured and the oxidative stress index (OSI) was calculated. RESULTS: When the pre-treatment and post-treatment values of patients with DKA were compared with those of the healthy control group, the S100B level, TOL, TAL and OSI were found to be significantly higher in the diabetes group (p<0.001). Pre-treatment TOL and TAL were also significantly higher than post-treatment levels (p<0.001), while no statistically significant difference was found in the S100B levels or the OSI (p>0.05). CONCLUSION: We believe that long-term exposure to high blood glucose concentrations leads to an increase in TOL in patients with DKA and that the neurotransmitter changes that develop in response to this exposure lead to an increase in S100B levels, which is an indicator of neuronal damage.

Turner syndrome and associated problems in Turkish children: a multicenter study.

OBJECTIVE: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. METHODS: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. RESULTS: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. CONCLUSION: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan.

Growth curves for Turkish Girls with Turner Syndrome: Results of the Turkish Turner Syndrome Study Group.

OBJECTIVE: Children with Turner syndrome (TS) have a specific growth pattern that is quite different from that of healthy children. Many countries have population-specific growth charts for TS. Considering national and ethnic differences, we undertook this multicenter collaborative study to construct growth charts and reference values for height, weight and body mass index (BMI) from 3 years of age to adulthood for spontaneous growth of Turkish girls with TS. METHODS: Cross-sectional height and weight data of 842 patients with TS, younger than 18 years of age and before starting any therapy, were evaluated. RESULTS: The data were processed to calculate the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for defined ages and to construct growth curves for height-for-age, weight-for-age and BMI-for-age of girls with TS. The growth pattern of TS girls in this series resembled the growth pattern of TS girls in other reports, but there were differences in height between our series and the others. CONCLUSION: This study provides disease-specific growth charts for Turkish girls with TS. These disease-specific national growth charts will serve to improve the evaluation of growth and its management with growth-promoting therapeutic agents in TS patients.

Thrombolytic treatment (alteplase; rt-Pa) in acute massive pulmonary embolism and cardiopulmonary arrest.

Patients with pulmonary thromboembolism (PE) often decompensate suddenly, and once hemodynamic compromise has developed, mortality is extremely high. Currently, thrombolytic therapy for PE is still controversial. We retrospectively evaluated 34 patients with PE between January 2010 and December 2013 in the Department of Pulmonary Medicine, Medical Park Samsun Hospital, Samsun, Turkey. The demographic and disease characteristics of patients who received thrombolytic treatment were retrospectively analyzed. The female to male ratio was 19/15 and the mean age was 63.1±13.2 years. PE diagnosis was made using echocardiography (64.7%) or contrast-enhanced thorax computed tomography with echocardiography (32.4%). Twenty-two (64.7%) patients went into the cardiopulmonary arrest due to massive PE and 17 (50%) patients recovered without sequelae. Eleven (32.4%) patients were diagnosed with massive PE during cardiopulmonary arrest with clinical and echocardiographic findings. Alteplase (recombinant tissue plasminogen activator [rt-PA]) was administered during cardiopulmonary resuscitation (CPR) and four (36.3%) patients responded and survived without sequelae. The complications of rt-PA treatment were hemorrhage in five (14.7%) patients and allergic reactions in two (5.9%) patients. There was no mortality due to rt-PA treatment complications. In conclusion, mortality due to massive PE is much more than estimated and alteplase can be used safely in patients with massive PE. This thrombolytic treatment was not associated with any fatal hemorrhage complication. If there is any sign of acute PE, echocardiography should be used during cardiopulmonary arrest/instability. Alteplase should be given to patients with suspected massive PE.

Monitoring and prognostic evaluation of patients with congenital hypothyroidism treated in a pediatric endocrinology unit.

In this study, the etiological factors, diagnostic approaches, dose, and duration of treatment were compared between cases with transient and permanent congenital hypothyroidism (CH) with respect to prognosis. One hundred and twenty-two patients who received treatments with the diagnosis of CH in the last 10 years were included in the study. The records of the patients were reviewed retrospectively. Serum thyroid- stimulating hormone (TSH) levels at the time of diagnosis were found to be significantly higher, and total thyroxine (TT4) levels were found to be significantly lower in the permanent CH group in comparison to the transient CH group. A statistically significant difference was present between the groups regarding treatment doses, the time needed for TSH decrease to <5 mIU/ml and the TSH and free thyroxine (FT4) levels obtained one month after discontinuation of the treatment. The association between age at the time of initiation of treatment and results of Denver Developmental Test was noted to be statistically significant. The high frequency of transient CH in our region leads to the result that some of the patients had to be unnecessarily treated with L-thyroxine for a long time.

Paraoxonase activity in athletic adolescents.

Regular physical activity may play a protective role against cardiovascular disease in adults, and paraoxonase activity may serve to mediate this effect. This study compared paraoxonase activity and that of other antioxidative agents in adolescent athletes compared with inactive youth. Paraoxonase level was 177.32 +/- 100.10 (U/L) in children with regular physical activity and 98.11 +/- 40.92 (U/L) in the control group (P < 0.0001). The levels of total antioxidative capacity, total oxidative status, oxidative stress index, and lipid hydroperoxide were significantly higher in the athlete group compared with controls (P < 0.0001). Paraoxonase activity was found to be greater in adolescent athletes, suggesting that regular exercise might provide a cardio-protective effect by this means.

Comparative study between the Ves-matic and microerythrocyte sedimentation rate method.

In this study, Ves-matic erythrocyte sedimentation rate and micro-erythrocyte sedimentation rate methods were compared on 96 subjects mean age 4.9+/-4.3 years. Ves-matic erythrocyte sedimentation rate an automated method, and micro-erythrocyte sedimentation rate method required minimal bloods are various approaches on the erythrocyte sedimentation rate. An important relationship between that the Ves-matic and micro-erythrocyte sedimentation rate was revealed. Although there was significantly correlation between these two methods, they are different to use interchangeably. Our study implies that "Micro-Automated Erythrocyte Sedimentation Rate Systems" could be developed which require a few amounts of blood and study automatically.