Leptin Replacement Improves Cognitive Development

Leptin changes brain structure, neuron excitability and synaptic plasticity. It also regulates the development and function of feeding circuits. However, the effects of leptin on neurocognitive development are unknown.To evaluate the effect of leptin on neurocognitive development.A 5-year-old boy with a nonconservative missense leptin gene mutation (Cys-to-Thr in codon 105) was treated with recombinant methionyl human leptin (r-metHuLeptin) at physiologic replacement doses of 0.03 mg/kg/day. Cognitive development was assessed using the Differential Ability Scales (DAS), a measure of general verbal and nonverbal functioning; and selected subtests from the NEPSY, a measure of neuropsychological functioning in children.Prior to treatment, the patient was morbidly obese, hypertensive, dyslipidemic, and hyperinsulinemic. Baseline neurocognitive tests revealed slower than expected rates of development (developmental age lower than chronological age) in a majority of the areas assessed. After two years, substantial increases in the rates of development in most neurocognitive domains were apparent, with some skills at or exceeding expectations based on chronological age. We also observed marked weight loss and resolution of hypertension, dyslipidemia and hyperinsulinemia.We concluded that replacement with r-metHuLeptin is associated with weight loss and changes in rates of development in many neurocognitive domains, which lends support to the hypothesis that, in addition to its role in metabolism, leptin may have a cognitive enhancing role in the developing central nervous system.ClinicalTrials.gov NCT00659828

The effect of bilirubin on long-term mortality in patients with chronic total coronary occlusion

Cetin, Mustafa/0000-0001-6342-436X; TURAN, Oguzhan Ekrem/0000-0003-3557-1682WOS: 000497971500010PubMed: 31747768AIM: We intended to investigate the association of bilirubin with total mortality in patients with chronic total coronary occlusion (CTO). METHODS: We included 172 patients who underwent coronary angiography due to stable angina pectoris and had CTO. We checked the viability of patients after 9 years of follow-up. RESULTS: Direct bilirubin levels were significantly lower in the non-viable group. We revealed age (OR = 1.045, 95% C.I: 1.009.1.083; p = 0.015) and direct bilirubin concentrations (OR = 0.029, 95% C.I: 0.002.0.435; p = 0.029) as independent predictors of mortality. Direct bilirubin value of > 0.2 mg/dL was associated with decreased mortality with a sensitivity of 85 %, and a specificity of 46 %. CONCLUSION: Serum direct bilirubin concentrations independently predict total mortality in patients with chronic total occlusion over 9 years of follow-up (Tab. 1, Fig. 2, Ref. 23)

Relationship between leukocyte and subtype counts, low-grade inflammation and slow coronary flow phenomenon in patients with angiographically normal coronary arteries

Background: Slow coronary flow (SCF) is an angiographic finding characterized by delayed opacification of epicardial coronary arteries in the absence of obstructive coronary disease. Leukocytes and low-grade inflammation play a major role in atherosclerotic vascular processes and may be important in other coronary pathologies. Therefore, we aimed to investigate whether there is a positive correlation between leukocyte counts, high-sensitive C-reactive protein (hsCRP) and SCF determined by frame rates. Methods: Seventy-seven individuals who underwent coronary angiography with suspected CAD, and had angiographically normal coronary arteries (NCA) of varying coronary flow rates were enrolled. From the original 77 study participants, forty-seven patients with NCA and SCF in all three coronary vessels and 30 sex- and age-matched control participants with NCA but without SCF were investigated. The quantification of the coronary flow was assessed by use of the TIMI frame count method (TFC) in all coronary arteries. The normal flow was defined as TFC < 28 frames and slow flow as TFC ? 28 frames. Results: HsCRP was significantly positively correlated with mean TFC (r = 0.522, p < 0.001). In addition, leukocytes, neutrophils and monocytes were significantly positively related to mean TFC (r = 0.353, p = 0.002; r = 0.298, p = 0.009 and r = 0.511, p < 0.001, respectively). In multivariate analyses, only hsCRP (?: 0.324, p = 0.003) and monocyte count (?: 0.354, p = 0.003) were related to SCF as determined by TFC. Conclusion: Our results showed that circulating monocytes and low-grade inflammation are related to SCF. Although we cannot make conclusive assumptions about the underlying pathologic process of SCF, we believe that these findings may be pivotal for further studies which seek to ascertain the specific roles of monocytes and hsCRP on SCF phenomenon in coronary vasculature

Protective effects of hyperbaric oxygen and iloprost on ischemia-reperfusion injury in rabbit kidneys

Bozok, Sahin/0000-0002-1256-5055; DURAKOGLUGIL, MURTAZA EMRE/0000-0001-5268-4262WOS: 000322943900006Aim. the aim of the study was to demonstrate protective effects of hyperbaric oxygen (HBO) and iloprost (IL) on renal ischemia-reperfusion (IR) injury using histopathological and biochemical methods. Methods. Fourty New Zealand white male rabbits were randomly allocated into one of four study groups. HBO group (N.=10) received a single session of HBO treatment (120 min at 2.5 atm); IL group (N.=10) received an infusion of 25 ng/kg/min IL; HBO+IL group (N.=10) received both HBO and IL; control group (N.=10) received only 0.9% saline. Renal ischemia-reperfusion was established by clamping abdominal aorta for 1h. Levels of pH, PO2, PCO2, HCO3, Na+, K+, lactate dehydrogenase, blood urea nitrogen and creatinine, plasma and renal malondialdehyde, myeloperoxidase, glutathione and superoxide dismutase were measured at onset, the end of ischemia period and the 24th hour of reperfusion. the kidneys of the sacrificed rabbits were evaluated histopathologically. Results. Even though blood urea nitrogen and creatinine levels were significantly higher in control group, there were not any differences between other groups. Blood PO2, pH, and HCO3 concentrations were significantly elevated and malondialdehyde levels were lower in control group compared to HBO, IL and BBO+IL groups. Histopathological changes including tubular necrosis, atrophy, hydropic degeneration and regenerative atypia that reflect renal injury were also significantly higher in control group. Conclusion. We suggested that both HBO and IL, either alone or in combination significantly reduced biochemical and histopathological signs of renal ischemia-reperfusion injury

INCREASED CIRCULATING SOLUBLE CD40 LEVELS IN PATIENTS WITH SLOW CORONARY FLOW PHENOMENON

WOS: 000317946500063[No abstract available

Evaluation of serum apelin-13 and apelin-36 concentrations in preeclamptic pregnancies

onal, ozgur/0000-0001-6514-2120; GURLEK, BERIL/0000-0002-4050-3193WOS: 000505271900006PubMed: 31595589Aim Recent studies suggest that apelin can be a novel potential therapeutic mediator to improve the diagnosis, and treatment of preeclampsia. This study aimed to investigate the association of serum apelin-13 and apelin-36 with preeclampsia and to detect their relationship with preeclampsia-associated perinatal morbidity. Methods Forty-four women with preeclampsia were included as the study group. Forty-four healthy pregnant women, at similar gestational week with similar gravidity, formed the control group. the clinical findings, biochemical indicators, maternal and perinatal outcomes, and the serum concentrations of apelin-36 and apelin-13 were evaluated. the levels of apelin-13 and apelin-36 were determined with commercial kits using a competition-based enzyme-linked immunosorbent assay method. Results the mean gestational age at sampling was 35.77 +/- 2.515 weeks in the preeclamptic group, 36.45 +/- 2.057 weeks in the control group (P = 0.270). Maternal serum apelin-36 and apelin-13 concentrations were significantly lower in patients with preeclampsia compared to the individuals in the control group (P = 0.030 and P = 0.005, respectively). the optimal cut-off points of apelin-36 and apelin-13 measurements for discriminating between preeclampsia and controls were evaluated by the receiver-operator curve analysis. the results showed that apelin-13 and apelin-36 are moderately successful markers to differentiate subjects with preeclampsia from healthy pregnant women. the concentrations of apelin-13 and apelin-36 in both groups were not statistically different in cases with and without adverse fetal/neonatal outcomes. Conclusion in conclusion, we investigated serum apelin-13 and apelin-36 concentrations in preeclamptic patients and demonstrated markedly lower maternal concentrations compared to healthy pregnant women.Recep Tayyip Erdogan University Scientific Research CommitteeRecep Tayyip Erdogan University [TSA-2017-785] Funding Source: Medlin

Lrp4 domains differentially regulate limb/brain development and synaptic plasticity.

Apolipoprotein E (ApoE) genotype is the strongest predictor of Alzheimer's Disease (AD) risk. ApoE is a cholesterol transport protein that binds to members of the Low-Density Lipoprotein (LDL) Receptor family, which includes LDL Receptor Related Protein 4 (Lrp4). Lrp4, together with one of its ligands Agrin and its co-receptors Muscle Specific Kinase (MuSK) and Amyloid Precursor Protein (APP), regulates neuromuscular junction (NMJ) formation. All four proteins are also expressed in the adult brain, and APP, MuSK, and Agrin are required for normal synapse function in the CNS. Here, we show that Lrp4 is also required for normal hippocampal plasticity. In contrast to the closely related Lrp8/Apoer2, the intracellular domain of Lrp4 does not appear to be necessary for normal expression and maintenance of long-term potentiation at central synapses or for the formation and maintenance of peripheral NMJs. However, it does play a role in limb development

Limb and bone structure of different <i>Lrp4</i> KI mutants.

<p><b>A</b>: Illustration of the different Lrp4 protein products of all KI mutants. Panels are aligned to paw images in B and C to indicate genotypes. <b>B</b>: Ventral view of fore and hind limbs of <i>Lrp4</i> KI mutants. Homozygous mutant mice for each allelic variant (<i>KI/KI</i>) and compound mutant mice that carry one allelic variant and one KO allele (<i>KO/KI</i>) are shown. Note that there are strong defects in the limb pattering of <i>Lrp4</i>^{<i>ECD/ECD</i>}, intermediate defects in <i>Lrp4</i>^{<i>ΔICD/ΔIC</i>}, and only mild defects in <i>Lrp4</i>^{<i>LDLR-ICD/LDLR-ICD</i>} (red arrows). <b>C</b>: Ventral view of alizarin red (stains bones) and alcian blue (stains cartilage) of different <i>Lrp4</i> KI mutants. A WT-KI allele (2^nd panel in A and B) was generated to control for the lack of introns in the ICD-cassette in the other KI mutants. Black arrowheads: ectopic bone or bony fusion; red arrowheads: soft-tissue fusion. (modified from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116701#pone.0116701.ref022" target="_blank">22</a>]).</p