Renal artery flow alterations in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: To compare kidney blood flow and kidney function tests in infants with hypoxic ischemic encephalopathy (HIE), and the effects of therapeutic hypothermia (TH) during the first 7 days of life. METHODS: Fifty-nine infants with HIE were prospectively evaluated. Infants with moderate-severe HIE who required TH were classified as group 1 (n = 36), infants with mild HIE were classified as group 2 (n = 23), and healthy infants were classified as group 3 (n = 60). Kidney function tests were evaluated on the sixth hour, third and seventh days of life in Group 1 and Group 2, and on the sixth hour and third day of life in group 3. Renal artery (RA) Doppler ultrasonography (dUS) was performed in all infants on the first, third, and seventh days of life. RESULTS: Systolic and end diastolic blood flow in RA tended to increase and RA resistive index (RI) tended to decrease with time in group 1 (p = 0.0001). While end diastolic blood flow rates in RA on the third day were similar in patients with severe HIE and mild HIE, it was lower in patients with mild-moderate-severe HIE than healthy newborns. On the seventh day, all three groups had similar values (p > 0.05). Serum blood urea nitrogen (BUN), creatinine, uric acid, and cystatin C levels gradually decreased and glomerular filtration rate (GFR) gradually increased during TH in group 1 (p = 0.0001). Serum creatinine levels gradually decreased while GFR gradually increased during the study period in group 2. CONCLUSIONS: Therapeutic hypothermia seems to help restore renal blood flow and kidney functions during the neonatal adaptive period with its neuroprotective properties.

Metformin restores prohormone processing enzymes and normalizes aberrations in secretion of proinsulin and insulin in palmitate-exposed human islets.

AIM: To elucidate how proinsulin synthesis and insulin was affected by metformin under conditions of nutrient overstimulation. MATERIALS AND METHODS: Isolated human pancreatic islets from seven donors were cultured at 5.5 mmol/L glucose and 0.5 mmol/L palmitate for 12, 24 or 72 h. Metformin (25 µmol/L) was introduced after initial 12 h with palmitate. Proinsulin and insulin were measured. Expression of prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE), was determined by western blot. Adolescents with obesity, treated with metformin and with normal glucose tolerance (n = 5), prediabetes (n = 14), or type 2 diabetes (T2DM; n = 7) were included. Fasting proinsulin, insulin, glucose, 2-h glucose and glycated haemoglobin were measured. Proinsulin/insulin ratio (PI/I) was calculated. RESULTS: In human islets, palmitate treatment for 12 and 24 h increased proinsulin and insulin proportionally. After 72 h, proinsulin but not insulin continued to increase which was coupled with reduced expression of PC1/3 and CPE. Metformin normalized expression of PC1/3 and CPE, and proinsulin and insulin secretion. In adolescents with obesity, before treatment, fasting proinsulin and insulin concentrations were higher in subjects with T2DM than with normal glucose tolerance. PI/I was reduced after metformin treatment in subjects with T2DM as well as in subjects with prediabetes, coupled with reduced 2-h glucose and glycated haemoglobin. CONCLUSIONS: Metformin normalized proinsulin and insulin secretion after prolonged nutrient-overstimulation, coupled with normalization of the converting enzymes, in isolated islets. In adolescents with obesity, metformin treatment was associated with improved PI/I, which was coupled with improved glycaemic control.

Screening for Inflammatory Markers Identifies IL-18Rα as a Potential Link between Exenatide and Its Anti-Inflammatory Effect: New Results from the Combat-JUDO Randomized Controlled Trial.

INTRODUCTION: Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, metabolic associated fatty liver disease, and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor analogs (GLP-1RA) are clinically used to treat obesity, with known anti-inflammatory properties. How the GLP-1RA exenatide effects inflammation in adolescents with obesity is not fully investigated. METHODS: Forty-four patients were randomized to receive weekly subcutaneous injections with either 2 mg exenatide or placebo for 6 months. Plasma samples were collected at baseline and at the end of the study, and 92 inflammatory proteins were measured. RESULTS: Following treatment with exenatide, 15 out of the 92 proteins were decreased, and one was increased. However, after adjustment for multiple testing, only IL-18Rα was significantly lowered following treatment. CONCLUSIONS: Weekly injections with 2 mg of exenatide lowers circulating IL-18Rα in adolescents with obesity, which may be a potential link between exenatide and its anti-inflammatory effect in vivo. This contributes to exenatide's pharmaceutical potential as a treatment for obesity beyond weight control and glucose tolerance, and should be further studied mechanistically.

Pelvic and breast ultrasound abnormalities and associated metabolic disturbances in girls with premature pubarche due to adrenarche.

OBJECTIVE: Premature adrenarche (PA) has been suggested as a risk factor for future health problems, such as metabolic syndrome and early menarche. However, not all girls with PA have these features and it is not certain who will develop them. We propose that these abnormalities might be identified earlier, even before they are visible. DESIGN: Case-control study. SETTING: Tertiary care hospital. PARTICIPANTS: Forty-eight girls with premature pubarche due to PA and age (mean age 7.6 ± 1.0 years), weight, body mass index (BMI), birth weight and gestational age-matched 49 girls with no palpable breast tissue. MEASUREMENTS: Early pubertal pelvic and breast ultrasonographic changes and their associations with obesity and metabolic parameters were evaluated. Blood samples were collected, breast and pelvic ultrasound examinations were performed and bone ages were assessed. RESULTS: Girls with PA were taller and their bone ages were higher (p = .049 and p = .005). Fasting blood glucose, insulin, triglycerides, high-density lipoprotein and low-density lipoprotein cholesterol were not different between the groups. Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol were not different either. Ultrasonography revealed breast gland tissue in 30% of girls with PA and 5% of controls (p = .006). Uterine volume and endometrial thickness were higher in girls with PA (p = .03 and p = .04). Endometrial thickness was positively associated with serum insulin levels in the whole study group and after adjusting for age, diagnosis, BMI, mean ovarian volume and LH, FSH, estradiol levels, this association remained with a borderline p-value (R2 = 0.486, p = .050). CONCLUSIONS: We found early changes in uterus and breast glands of girls with PA and endometrial thickness was positively associated with insulin levels.

Cross-talk of cholinergic and ß-adrenergic receptor signalling in chronic myeloid leukemia K562 cells.

In many studies on breast, skin and intestinal cancers, ß-adrenergic receptor antagonists have been shown to inhibit cell proliferation and angiogenesis and increase apoptosis in cancers. Carbachol inhibits chronic myeloid leukaemia K562 cell proliferation. Beta-blockers are known to inhibit cell progression. The aim of this study is to explain the mechanism of action of ß-adrenergic receptors agonists and antagonists on apoptosis in chronic myeloid leukaemia cells. We tried to determine the effect of combined treatment of ß-adrenergic and cholinergic drugs on adrenergic ß1 and ß2 gene expression, cell proliferation and apoptosis in chronic myeloid leukaemia K562 cells. Cell proliferation was evaluated by the 5-bromo-2-deoxy-uridine (BrdU) incorporation kit. Caspase 3, 8, 9 activities were measured by the caspase assay kit. Protein expression level was detected by western blotting. We found that exposure to propranolol either by combination with carbachol facilitates additive effects on inhibition of caspase 3 and 8 expression in chronic myeloid leukaemia K562 cells. However, caspase 9 expression level was increased by propranolol alone or with propranolol and carbachol combination. The combined therapy of cholinergic and adrenergic receptor drugs will decrease cell proliferation in K562 cells. This decrease in cell proliferation may be mediated by the mitochondrial-dependent intrinsic apoptosis pathway.

Decreased Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Activity in a Rat Model of Absence Epilepsy and the Effect of ZD7288, an Ih Inhibitor, on the Spike-and-Wave Discharges.

INTRODUCTION: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents of Ih and absence epilepsy seizures are associated, but studies reveal differential results. OBJECTIVE: In our study, we aimed to investigate the role of the HCN channels on the expression of spike-and-wave discharges (SWDs) using the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model. METHODS: HCN isoform levels from isolated brains of both naïve nonepileptic Wistar and GAERS groups were evaluated by enzyme-linked immunosorbent assay. ZD7288, an Ih inhibitor as well as an HCN channel antagonist, was administered intracerebroventricularly to the adult GAERS groups, and to evaluate their SWD activities, electroencephalography was recorded. The effect of ZD7288 on the cumulative total duration and number of SWDs and the mean duration of each SWD complex was evaluated. RESULTS: The HCN2 levels in the cortex and hippocampus of the GAERS group were lower compared to the naïve nonepileptic Wistar group (p < 0.05). ZD7288 increased the number of SWDs at the 20th and 120th min with the highest administered dose of 7 µg (p < 0.05). CONCLUSION: The Ih inhibitor ZD7288 increased the number of SWDs in a genetic absence epilepsy rat model, although this increase may not be significant due to the inconsistent time-dependent effects. In GAERS, the cortical and hippocampal HCN2 channel levels were significantly lower compared to the control group. Further studies are needed with higher doses of ZD7288 to determine if the effects will increase drastically.

Studies on the role of alpha 7 nicotinic acetylcholine receptors in K562 cell proliferation and signaling.

The results we obtained from this study gave information about the determination of alpha 7 nicotinic acetylcholine receptor (α7-nACh) expression in human erythroleukemia cells, as well as whether it has a role in calcium release and cell proliferation in the presence of nicotinic agonist, antagonists. Determining the roles of α7 nicotinic receptors in erythroleukemia cells will also contribute to leukemia-related signal transduction studies. This study is primarily to determine the role of nicotinic agonists and antagonists in cell proliferation, α7 nicotinic acetylcholine receptor expression, and calcium release. The aim of this study, which is a continuation and an important part of our previous studies on the cholinergic system, has contributed to the literature on the human erythroleukemia cell signaling mechanism. Cell viability was evaluated by the trypan blue exclusion test and Bromodeoxyuridine/5-Bromo-2'-deoxyuridine (BrdU) labeling. Acetylcholine, nicotinic alpha 7 receptor antagonist methyllycaconitine citrate, and cholinergic antagonist atropine were used to determine the role of α7-nACh in K562 cell proliferation. In our experiments, the fluorescence spectrophotometer was used in Ca2+ measurements. The expression of nicotinic alpha 7 receptor was evaluated by western blot. The stimulating effect of acetylcholine in K562 cell proliferation was reversed by both the α7 nicotinic antagonist methyllycaconitine citrate and the cholinergic antagonist, atropine. Methyllycaconitine citrate inhibited K562 cell proliferation partially explained the roles of nicotinic receptors in signal transduction. While ACh caused an increase in intracellular Ca2+, methyllycaconitine citrate decreased intracellular Ca2+ level in K562 cell. The effects of nicotinic agonists and/or antagonists on erythroleukemic cells on proliferation, calcium level contributed to the interaction of nicotinic receptors with different signaling pathways. Proliferation mechanisms in erythroleukemic cells are under the control of the α7 nicotinic acetylcholine receptor via calcium influx and different signalling pathway.

Is it necessary to give calcium infusion during the exchange transfusion in newborns?

OBJECTIVES: We aimed to evaluate total serum calcium (TSC) and ionized serum calcium (ISC) levels and their effects on clinical outcomes in neonates underwent exchange transfusion (ET). METHOD: In this study, the data of newborn infants who underwent ET due to hyperbilirubinemia in a third level neonatal intensive care unit (NICU) were retrospectively analyzed. The patients were monitored by electrocardiogram during ET. Cardiac and respiratory rates, peripheral oxygen saturation, blood pressure values ​​and clinical findings as convulsion, tremor, hypertonia, laryngospasm, cyanosis and apnea were recorded in ET observation forms. The infants with no symptoms of hypocalcemia during the procedure were not routinely given IV calcium gluconate. TSC and ISC measured at the beginning, at the end and 24 h after the end of ET were evaluated retrospectively. RESULTS: Data of 36 newborn patients were evaluated. Median gestational age was 39 (35-40) weeks, mean birthweight was 2840 ± 841 (mean ± SD) grams. During the ET, desaturation was observed in five patients(13.9 %), sinus bradycardia in six(16.7 %), tachypnea in two(5.5 %), sinus tachycardia in one(2.8 %), and rare ventricular extrasystoles in one(2.8 %). Hypocalcaemia was not detected in any of the patients at the beginning of ET. Hypocalcemia was observed in two cases (5.5 %) at the end of ET. There was no statistically significant difference between the TSC and ISC levels at the beginning of ET, at the end and at the end of 24 h. CONCLUSION: As a result, routine intravenous (IV) calcium administration seems to be unnecessary provided that vital signs and neurological status are closely monitored during ET.

Role of cholinergic agents in proliferation and caspase activity of hemin-induced erythroid differentiated K562 cells.

Background: Muscarinic receptors have many functions in the cells and tissues. Acetylcholine (ACh) plays an important role in cellular physiology. ACh also acts at the different parts of the central nervous system and nonneuronal cells. Cholinergic receptors also have different functions in many cell types and tissues. Caspases (cysteine aspartic proteases and cysteine aspartases) are cysteine dependent aspartate-specific proteases. They are an important role in necrosis and cell death and inflammation signaling pathways. They are also the primary mediators of apoptosis. During apoptosis, different caspase types participate in different functions. We have previously shown that carbachol (CCh) inhibits K562 cell proliferation. This study was performed to investigate the anti-tumor efficacy of cholinergic drugs in hemin-induced erythroid differentiated K562 cells. The aim of this study was to address the mechanism of cholinergic drugs on hemin-induced erythroid differentiated K562 cell proliferation and caspase activities. We detected M3 muscarinic receptor expression in erythroid differentiated K562 cell line.Methods: K562 cells were differentiated with hemin (50 µM). The expression of the M3 muscarinic receptor was detected by the western blotting technique. Erythroid differentiated K562 cells treated with CCh (100 µM). After 24 and 48 h, cells were counted by BrdU cell proliferation kit. Caspase 3,8, and 9 activities were measured by enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions.Results: Erythroid differentiated K562 cell proliferation was not significantly increased after CCh treatment. In the meantime, caspases 8 and 9 activities in erythroid differentiated K562 cell line was significantly higher than undifferentiated K562 cells (p < .05).

Atipamezole, a specific α2A antagonist, suppresses spike-and-wave discharges and alters Ca2⁺ /calmodulin-dependent protein kinase II in the thalamus of genetic absence epilepsy rats.

OBJECTIVE: The role of α2A adrenergic receptors (α2A ARs) in absence epilepsy is not well characterized. Therefore, we investigated the outcomes of the specific antagonism of α2A ARs on the spike-and-wave discharges (SWDs) in genetic absence epilepsy rats from Strasbourg (GAERSs), together with its influence on the behavior and second messenger systems, which may point to the mechanisms to which a possible SWD modulation can be related. METHODS: Atipamezole, an α2A AR antagonist, was administered intracerebroventricularly to the adult GAERSs, and electroencephalography (EEG) was conducted. The cumulative duration and number of SWDs, and the mean duration of each SWD complex were counted. The relative power of the EEG frequency bands and behavioral activity after the acute application of two doses (12 and 31 µg/5 µL) of atipamezole were evaluated. The levels of cyclic adenosine monophosphate and calcium/calmodulin-dependent kinase II (CaMKII) were measured in the cortex, thalamus, and hippocampus of naive Wistar rats and GAERSs, administered with artificial cerebrospinal fluid (aCSF) as a vehicle, or either acute or chronic atipamezole (12 µg), the latter being administered for 5 consecutive days. RESULTS: Atipamezole significantly suppressed SWDs dose-dependently, without affecting the relative power values of EEG frequency spectrum. The stereotypic activity was significantly lower in both naive Wistar rats and GAERSs receiving the highest dose (31 µg) of atipamezole compared to GAERSs receiving aCSF. In GAERSs, CaMKII levels were found to be higher in the thalamus after the acute and chronic application of SWD-suppressing doses of atipamezole (12 and 31 µg) compared to aCSF. SIGNIFICANCE: This study emphasizes the α2 AR-related modulation of absence epilepsy and particularly the significance of α2 AR antagonism in suppressing SWDs. Atipamezole's SWD-suppressive actions may be through CaMKII-mediated second messenger systems in the thalamus.

Determinants of Increased Aortic Diameters in Young Normotensive Patients With Turner Syndrome Without Structural Heart Disease.

Factors associated with aortic dilation and dissection in patients with Turner syndrome (TS) remain unclear. We assessed magnetic resonance imaging-based aortic diameters at nine predefined anatomic positions and examined associations of increased aortic diameters with B-type natriuretic peptide (BNP), A-type NP (ANP), growth hormone treatment, insulin-like growth factor 1 (IGF1), and estrogen status. Forty-seven patients with TS aged 7.3-21 years and 34 healthy peers were enrolled in this study. Aortic diameters were higher in patients with TS at three positions than in controls (p < 0.05). History of GH treatment, pubertal status, and serum estradiol levels were not associated with increased aortic diameters. Patients with TS had higher plasma BNP and ANP levels than controls. BNP and IGF1 were independently associated with the increase in aortic diameters in TS at three positions of the ascending aorta (R2 = 0.361-0.458, p < 0.05 for all). At two positions of the descending aorta, only BNP emerged as an independent variable (R2 = 0.130-0.139, p < 0.05). We conclude that young, normotensive patients with TS had greater aortic diameters at several positions than healthy controls. BNP and IGF1 were independently associated with increased aortic diameters in TS.

The relationship between infancy growth rate and the onset of puberty in both genders.

BackgroundIn this study, we examined the hypothesis that weight gain and linear growth during the first years of life influence the onset of puberty both in girls and in boys.MethodsA cohort of 157 healthy children, aged 6-9 years, was evaluated and their growth patterns were analyzed retrospectively. Repeated measures mixed model was used to examine the longitudinal anthropometric data.ResultsGirls with pubertal signs were heavier than their peers starting at 9 months of age (P=0.02), and the difference became more evident over time (P<0.001). Accelerated weight gain between 6 and 15 months of age was found to increase the odds of having a pubertal sign at the study visit (odds ratio (OR)=34.5) after adjusting for birth weight, gestational age and current age, height, weight, and BMI (P=0.004). Anthropometric indices of boys with or without pubertal signs were not significantly different at the study visit, but boys with accelerated height gain between 9 and 15 months of age were more likely to have pubertal signs (OR=15.8) after adjusting for birth weight, gestational age and current age, height, weight, and BMI (P=0.016).ConclusionEarly growth acceleration might be important for the timing of puberty in both genders.

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.

The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants.

OBJECTIVE: To test the efficacy of probiotic and prebiotic, alone or combined (synbiotic), on the prevention of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. STUDY DESIGN: A prospective, randomized, controlled trial was conducted at 5 neonatal intensive care units in Turkey. VLBW infants (n = 400) were assigned to a control group and 3 study groups that were given probiotic (Bifidobacterium lactis), prebiotic (inulin), or synbiotic (Bifidobacterium lactis plus inulin) added to breastmilk or formula for a maximum of 8 weeks before discharge or death. The primary outcome was NEC (Bell stage ≥2). RESULTS: The rate of NEC was lower in probiotic (2.0%) and synbiotic (4.0%) groups compared with prebiotic (12.0%) and placebo (18.0%) groups (P < .001). The times to reach full enteral feeding were faster (P < .001), the rates of clinical nosocomial sepsis were lower (P = .004), stays in the neonatal intensive care unit were shorter, (P = .002), and mortality rates were lower (P = .003) for infants receiving probiotics, prebiotics, or synbiotic than controls. The use of antenatal steroid (OR 0.5, 95% CI 0.3-0.9) and postnatal probiotic (alone or in synbiotic) (OR 0.5, 95% CI 0.2-0.8) decreased the risk of NEC, and maternal antibiotic exposure increased this risk (OR 1.9, 95% CI 1.1-3.6). CONCLUSIONS: In VLBW infants, probiotic (Bifidobacterium lactis) and synbiotic (Bifidobacterium lactis plus inulin) but not prebiotic (inulin) alone decrease NEC.

Effect of therapeutic hypothermia on C-reactive protein levels in patients with perinatal asphyxia.

OBJECTIVE: To determine the changes in serum C-reactive protein (CRP) levels during therapeutic hypothermia. STUDY DESIGN: Between January 2011 and June 2013, 133 hypoxic-ischemic encephalopathy patients being followed up in the neonatal intensive care unit of Dr. Sami Ulus Maternity and Children's Hospital are prospectively evaluated. Group 1; patients that received therapeutic hypothermia (n = 74) and group 2; patients that did not required therapeutic hypothermia (n = 59). All the patients underwent serial complete blood cell count and CRP assessments; blood cultures were obtained from all the cases at the time of admission and when CRP levels were elevated. RESULTS: Positive blood cultures were encountered in five cases (6.7%) in group 1 while no blood culture-proven septicemia was encountered in group 2. The CRP levels elevated gradually reaching a peak level on the 4th day and then decreased during the therapeutic hypothermia in patients with no blood culture-proven septicemia in group 1. The CRP levels showed statistically significant changes reaching a peak level on the 7th day in patients with blood culture-proven septicemia in group 2. Also, the CRP levels showed no alteration with time in group 2. CONCLUSION: Therapeutic hypothermia itself might be associated with CRP elevation rather than an actual infection.

Blood levels of polychlorinated biphenlys and organochlorinated pesticides in women from Istanbul, Turkey.

The human body is not a chemically uncontaminated system. Every simple action that humans undertake, such as drinking water, eating, nursing, and even breathing air, puts the system under environmental xenobiotic exposure stress. Environmental chemicals have been shown to produce unwanted effects on health and remove the right to healthy living, starting from the first encounter in utero to geriatrics, throughout the lifespan. Organochlorine pesticides (OCPs) and polychlorinated biphenyl (PCB) levels, important members of the persistent organic pollutants (POPs), have been detected before in human breast milk and also in the adipose tissue of women from different regions of Turkey; however, there was no information about the blood levels of these chemicals. This study generated the first information that evaluates OCP and PCB contamination levels in the blood of the women living in Turkey. The current study measured the blood concentrations of OCPs and PCBs in 58 healthy women (age 20-41 years; mean age 28 years) who were living in Istanbul, Turkey, in the years 2010-2012. Samples were analyzed for 29 OCPs and 18 PCB congeners using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). PCB 153 was the predominant congener (643.2 pg/g lipid), followed by PCB 138 and PCB 180. 4,4'-DDE (24872.8 pg/g lipid) was the most common organochlorinated pesticide contaminant in studied blood samples. Results for analyzed chlorinated compounds were as follows: ∑PCB 2682 ± 3300 pg/g lipid; ∑DDT 25,938 ± 28,644 pg/g lipid; and ∑HCH 2930 ± 2222 pg/g lipid, respectively. The mean concentration of ∑WHOPCB-TEQ was 0.037 pg/g on a lipid basis. This information will be important base data during the assessment of the general health concerns of women, as well as for studies about how endocrine disruptors affect humans for forthcoming studies.

An interesting newborn case of fructose 1-6 diphosphatase deficiency triggered after thyme juice ingestion.

Herbs have been used for centuries to prevent and control many diseases. The biggest challenge and problem is lack of information about the effect of herbs and its side effects. Thyme (thymus vulgaris) is a small shrubby plant with a strong, spicy taste, and odor. Thyme has carminative, diaphoretic, expectorant, sedative, antibacterial and antifungal properties. It also has antispasmodic effects; tea made by infusing the herb in water or thyme juice ready-to-use is traditionally frequently used for infantile colic in our country. A fourteen-day-old male newborn was admitted to the emergency department with severe respiratory distress. There was a history of 50 mL of thyme juice (added table sugar) ingestion given for his infantile colic two hours before admission. He had hypoglycemia, hyperuricemia, and lactic acidosis. Further investigation confirmed fructose 1-6 diphosphatase deficiency in the patient. We thought that lactic acidosis may have been triggered by fructose added to the thyme water to sweeten its taste. However, phenolic compounds of thyme juice may also cause acidosis.

Adherence to growth hormone therapy: results of a multicenter study.

OBJECTIVE: To evaluate the adherence to growth hormone (GH) therapy and identify the influencing factors and outcomes in children. METHODS: A total of 217 GH-naïve patients in 6 pediatric endocrinology clinics were enrolled in the study. Structured questionnaires were filled out and patients were evaluated at the initiation and 3rd, 6th, and 12th months of therapy. Patients were categorized into 4 adherence segments based on percentage of doses omitted at each evaluation period, classified as excellent if 0%, good if 5%, fair if 5 to 10%, and poor if > 10%. RESULTS: There was a decrement in adherence to GH therapy during the study period (P = .006). Patients who showed excellent and good adherence to therapy had better growth velocity and growth velocity standard deviation scores (SDSs) (P = .014 and P = .015, respectively). A negative correlation between growth velocity SDS and number of missed injections was also observed (r = -.412; P = .007). A positive correlation between delta insulin-like growth factor-1 (IGF-1) SDS and growth velocity was demonstrated (r = .239; P = .042). IGF-1 levels were significantly higher in patients who showed excellent and good adherence to therapy (P = .01). Adherence was better in boys than in girls (P = .035), but adherence rates were not associated with age, cause of GH treatment, socioeconomic status, person who administered the injections, type of injection device, or GH product. CONCLUSION: Poor adherence to GH therapy was common in our group of patients and was one of the factors underlying suboptimal growth during therapy. Before considering other problems that can affect growth, clinicians should confirm good adherence to therapy.

Netherton syndrome associated with growth hormone deficiency.

Netherton syndrome (NS) is a rare autosomal recessive disorder characterized by ichthyosiform scaling, hair abnormalities, and variable atopic features. Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS. Growth retardation is a classic feature of NS, but growth hormone (GH) deficiency with subsequent response to GH therapy is not documented in the literature. It is proposed that a lack of inhibition of proteases due to a deficiency of LEKTI in the pituitary gland leads to the overprocessing of human GH in NS. Herein we report three patients with NS who had growth retardation associated with GH deficiency and responded well to GH therapy.

Evaluation of endocrine function in children admitted to pediatric intensive care unit.

BACKGROUND: Although studied widely in adulthood, little is known about endocrinological disorders during critical illnesses in childhood. The aims of this study were to define the endocrinological changes in patients admitted to pediatric intensive care unit (PICU) and to identify their effects on prognosis. METHODS: Forty patients with a mean age of 5.1 years admitted to PICU were enrolled in the study. Blood samples were taken at admission and at 24 and 48 h to measure cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor-binding protein-3 (IGFBP-3) and interleukin-6 (IL-6). The severity of the patient's condition was assessed using pediatric risk of mortality (PRISM) and pediatric logistic organ dysfunction (PELOD) scores. RESULTS: PRISM and PELOD scores were significantly higher in non-survivors. Cortisol, ACTH, prolactin, GH, GHBP, IGFBP-3 and IL-6 were not significantly different between the survivors and non-survivors. There was a negative correlation between baseline IGFBP-3 and PRISM scores. A positive correlation was seen between cortisol level at 24 h and PRISM score. On multivariate linear regression analysis, PRISM score was best explained by ACTH and cortisol at 24 h. A positive weak correlation was detected between IL-6 at 24 h and PELOD scores. CONCLUSIONS: Although there was no difference between survivors and non-survivors regarding the studied endocrine parameters, there were associations between cortisol, ACTH, IL-6 and IGFBP-3 and risk assessment scores, and, given that these scores correlated with mortality, these parameters might be useful as prognostic factors.