scholarly journals Serum IGF1 and linear growth in children with congenital leptin deficiency before and after leptin substitution

Author(s):  
Marianna Beghini ◽  
Stephanie Brandt ◽  
Ingrid Körber ◽  
Katja Kohlsdorf ◽  
Heike Vollbach ◽  
...  

Abstract Background Evidence from in vitro and rodent studies suggests that leptin, a key signal of long-term energy reserves, promotes IGF1 synthesis and linear growth. This effect of leptin has not been fully investigated in humans. The aim of our study was to investigate the effect of leptin substitution on growth factors and linear growth in children with congenital leptin deficiency (CLD). Methods In this cohort study we included eight pediatric patients (six males), age 0.9–14.8 years, who were diagnosed with CLD and received leptin substitution at our University Medical Center. We calculated standard deviation scores (SDS) for serum levels of IGF1 and IGFBP3, IGF1/IGFBP3 molar ratio, and height at baseline (T0) and 12 months (T12) after the initiation of substitution with metreleptin. Results All patients had severe obesity (BMI-SDS mean ± SD: 4.14 ± 1.51) at T0 and significant BMI-SDS reduction to 2.47 ± 1.05 at T12. At T0, all patients were taller than the mid-parental median, yet had low IGF1 and IGF1/IGFBP3 molar ratios (IGF1-SDS$$\overline x$$ x ¯ T0: −1.58 ± 0.92, IGF1/IGFBP3 molar ratio-SDS$$\overline x$$ x ¯ T0: −1.58 ± 0.88). At T12, IGF1-SDS increased significantly (∆T0–12: 1.63 ± 1.40, p = 0.01), and IGFBP3-SDS and IGF1/IGFBP3 molar ratio-SDS showed a trend toward an increase. In the three children within the childhood growth period (post-infancy, pre-puberty) height-SDS increased (∆height-SDST0–12: 0.57 ± 0.06, p = 0.003) despite substantial weight loss. Conclusions These results in CLD patients are contrary to observations in children with idiopathic obesity who typically have above-mean IGF1 levels that decrease with weight loss, and therefore suggest that leptin increases IGF1 levels and promotes linear growth.

2020 ◽  
Vol 21 (21) ◽  
pp. 8168
Author(s):  
Andreas Schmid ◽  
Jonas Gehl ◽  
Miriam Thomalla ◽  
Alexandra Hochberg ◽  
Anja Kreiß ◽  
...  

The adipokine CTRP-3 (C1q/TNF-related protein-3) exerts anti-inflammatory and anti-diabetic effects. Its regulation in obesity and during weight loss is unknown. Serum and adipose tissue (AT) samples were obtained from patients (n = 179) undergoing bariatric surgery (BS). Moreover, patients (n = 131) participating in a low-calorie diet (LCD) program were studied. CTRP 3 levels were quantified by ELISA and mRNA expression was analyzed in AT and in 3T3-L1 adipocytes treated with bile acids and incretins. There was a persistent downregulation of CTRP-3 serum levels during weight loss. CTRP-3 expression was higher in subcutaneous than in visceral AT and serum levels of CTRP-3 were positively related to AT expression levels. A rapid decrease of circulating CTRP-3 was observed immediately upon BS, suggesting weight loss-independent regulatory mechanisms. Adipocytes CTRP-3 expression was inhibited by primary bile acid species and GLP 1. Adipocyte-specific CTRP-3 deficiency increased bile acid receptor expression. Circulating CTRP-3 levels are downregulated during weight loss, with a considerable decline occurring immediately upon BS. Mechanisms dependent and independent of weight loss cause the post-surgical decline of CTRP-3. The data strongly argue for regulatory interrelations of CTRP-3 with bile acids and incretin system.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Byambajav Lkhagvadulam ◽  
Jung Hwa Kim ◽  
Il Yoon ◽  
Young Key Shim

Gold nanoparticles (GNPs) conjugates of water soluble ionic photosensitizer (PS), purpurin-18-N-methyl-D-glucamine (Pu-18-NMGA), were synthesized using various molar ratios between HAuCl4and Pu-18-NMGA without adding any particular reducing agents and surfactants. The PS-GNPs conjugates showed long wavelength absorption of range 702–762 nm, and their different shapes and diameters depend on the molar ratios used in the synthesis.In vitroanticancer efficacy of the PS-GNPs conjugates was investigated by MTT assay against A549 cells, resulting in higher photodynamic activity than that of the free Pu-18-NMGA. Among the PS-GNPs conjugates, the GNPs conjugate from the molar ratio of 1 : 2 (Au(III): Pu-18-NMGA) exhibits the highest photodynamic activity corresponding to bigger size (~60 nm) of the GNPs conjugate which could efficiently transport the PS into the cells than that of smaller size of the GNPs conjugate.


1987 ◽  
Author(s):  
E J Pilger ◽  
J Lammer ◽  
H Bertuch ◽  
H Steiner

In order to predict usefulness of streptokinase (SK), urokinase (UK) and streptokinase-glutamin-plasminogen (SK-Glu-Plg) for intraarterial fibrinolysis, an in vitro test was designed. Fibrin plates with and without plasminogen were incubated with SK, UK and SK-Glu-Plg (in molar ratios of 1:1, 2:1 and 1:2). On the fibrin plates containing plasminogen the highest fibrinolytic activity was observed with UK; on the fibrin plates without plasminogen, SK-Glu-Plg in a molar ratio of 1:2 was superior. We concluded, that plasmin would be synthesized by SK and Glu-Plg. In order to examine the in vivo efficacy of these different fibrinolytic agents, 120 patients suffering from peripheral artery occlusion were randomized into three treatment groups for local thrombolysis. The technique of Hess and coworkers was used for local thrombolytic therapy. In group I local fibrinolysis was performed with SK (2500 IU/5 min), in group II UK (4000 IU/5 min) was used and in group III the lytic agent consisted of SK-Glu-Plg (2500 IU/5 min). The primary recanalization rate was equal in all groups: 86%, 89% and 83% in group I, II and III respectively. However the duration required for the procedure and thus the total amount of fibrinolytic agent used was significantly different (p < 0,001) between the three groups: 2,3 ± 1,4; 2,1 ± 1,2 and 1,1 ±0,8 hours for groups I,II and III, respectively (mean ± SEM) . We conclude that SK-Glu-Plg or plasmin itself has the highest efficacy as a fibrinolytic agent for intraarterial thrombolysis. Since the intra-thrombotic concentration of Pig is unknown in an individual patient an empirically chosen dose of SK of UK may either be to high or to low for optimal thrombolysis.


Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2185
Author(s):  
Mohamed Dellali ◽  
Camelia Elena Iurciuc (Tincu) ◽  
Corina Lenuța Savin ◽  
Nawel Spahis ◽  
M’hamed Djennad ◽  
...  

Cross-linked chitosan (CS) films with aldehyde groups obtained by oxidation of carboxymethyl cellulose (CMC) with NaIO4 were prepared using different molar ratios between the CHO groups from oxidized carboxymethyl cellulose (CMCOx) and NH2 groups from CS (from 0.25:1 to 2:1). Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy demonstrated the aldehyde groups’ presence in the CMCOx. The maximum oxidation degree was 22.9%. In the hydrogel, the amino groups’ conversion index value increased when the -CHO/-NH2 molar ratio, cross-linking temperature, and time increased, while the swelling degree values decreased. The hydrogel films were characterized by scanning electron microscopy (SEM) and FTIR analysis. The curcumin encapsulation efficiency decreases from 56.74% to 16.88% when the cross-linking degree increases. The immobilized curcumin release efficiency (REf%) and skin membrane permeability were evaluated in vitro in two different pH solutions using a Franz diffusion cell, and it was found to decrease when the molar ratio -CH=O/NH2 increases. The curcumin REf% in the receptor compartment was higher at pH = 7.4 (18%- for the sample with a molar ratio of 0.25:1) than at pH = 5.5 (16.5%). The curcumin absorption in the skin membrane at pH = 5.5 (47%) was more intense than at pH = 7.4 (8.6%). The curcumin-loaded films’ antioxidant activity was improved due to the CS presence.


2000 ◽  
Vol 84 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Elisabeth Wisker ◽  
Martina Daniel ◽  
Gerhard Rave ◽  
Walter Feldheim

It was studied whether the type of bread (i.e. a low-fibre wheat–rye mixed bread and coarse or fine wholemeal rye bread) either as part of a diet or alone, had an influence on the short-chain fatty acids (SCFA) produced during in vitro fermentation. Fermentation substrates were dietary fibre residues obtained from diets and breads. In addition, it was investigated whether the faecal SCFA pattern in the inoculum donors, who ingested the experimental diets, could be predicted by in vitro fermentation. Yields of SCFA in vitro were 0·51–0·62 g/g fermented polysaccharide. In vitro, the molar ratios of butyrate were higher for the two high-fibre diets containing coarse or fine wholemeal bread than for the low fibre diet containing wheat–rye mixed bread; the difference was significant for the coarse (P < 0·01), but not for the fine bread diet (P = 0·0678). The coarse wholemeal bread alone produced a higher molar ratio of butyrate than the fine wholemeal bread (P < 0·05) and the wheat–rye mixed bread (P < 0·01). Ingestion by the inoculum donors of the diets containing wholemeal bread led to higher faecal butyrate ratios (molar ratios: coarse bread diet 19·6, fine bread diet 17·7) compared with the wheat–rye mixed bread-containing diet (14·9), but the differences between the diets were not significant. For the diets investigated, there were no significant differences between faecal and in vitro SCFA patterns.


2014 ◽  
Vol 487 ◽  
pp. 121-126 ◽  
Author(s):  
Tian Yu Wang ◽  
Xing Xiang Zhang ◽  
Na Han

A series of acrylonitrile (AN)-methacrylate (MA)-dimethyl maleate (DMM) terpolymers with different molar ratios were fabricated by emulsion polymerization. The feeding ratio agrees well with the composition of AN-MA-DMM terpolymer. With increasing the molar ratio of DMM in terpolymer, glass transition temperature (Tg) increases to higher temperature at first and then decreases. Tgdrops to the lowest value-78.6 °C when the feeding ratio is 85/13/2 mol%. The melting temperature (Tm) of 85/11/4 AN-MA-DMM terpolymer is the lowest at-137.2 °C, while its resistant temperature (5 wt% weight loss, T0.05) rises up to the highest value, -314.9 °C. DMM plays an important role in improving the melt flowability of PAN based copolymer. The cross sections of 85/14/1 AN-MA-DMM fiber are compact and the outer surfaces of the fiber are smooth. Tensile strength of AN-MA-DMM fiber is 3.4 cN/dtex.


2018 ◽  
Vol 8 (5-s) ◽  
pp. 175-183 ◽  
Author(s):  
Mangesh D Godbole ◽  
Vijay B Mathur

The present investigation was aimed to compare various phospholipids and different methods that would be appropriate to produce liposomes having vesicle size in the range of 200-300 nm, PDI less than 0.500, maximum entrapment and delayed release of lamivudine. The phospholipids employed were Phospholipon® 90G, Phospholipon® 90H, 1,2-Dimyristoyl-sn-glysero-3-phosphocholine (DMPC) and 1,2-Dipalmitoyl-sn-glysero-3-phosphocholine (DPPC). They were used in various molar ratio with cholesterol and blank liposomes were prepared initially by thin film hydration and ether injection method. The thin film hydration method was only found to be appropriate to produce liposome of desired size and PDI. Hence, the molar ratios of employed phospholipids:cholesterol that produced liposomes as per the expected parameters was then used to load lamivudine. The method of preparation, phospholipid: cholesterol molar ratio, hydrations above transition temperature and hydration time were showed direct influence on vesicle size, PDI, percentage encapsulation and in-vitro release. Phospholipon® 90H: cholesterol: lamivudine in the molar ratio 1:2:1 produced liposomes having desired vesicle size and PDI with maximum drug entrapment and sustained release. The encapsulation efficiency of drug in liposomes was in the order of Phospholipon® 90H> Phospholipon® 90G > DPPC > DMPC. Keywords: Liposomes, Lamivudine, Phospholipid, Thin film hydration method, Ether injection method, encapsulation efficiency


1988 ◽  
Vol 119 (2) ◽  
pp. 203-212
Author(s):  
H. Edward Grotjan

Abstract. The release of uncombined gonadotropin subunits by rat anterior pituitaries during an in vitro incubation as well as intracellular concentrations were assessed. Uncombined subunits and native gonadotropins were quantitated by radioimmunoassays after samples were subjected to gel filtration on Sephadex G-100 Superfine. Small, but detectable, amounts of uncombined rat LH β subunit were released under basal conditions. GnRH increased the absolute amount of rLHβ released but did not alter the rLHβ/rLH molar ratio (≈ 0.02). Tissue extracts prepared in aqueous buffer (100 000 × g supernatants) and 0.5% Triton X-100 extracts of the 100 000 × g pellets from the initial homogenization ('pellet extracts') contained larger quantities of uncombined rLHβ as well as elevated rLHβ/rLH molar ratios (≈ 0.10 and ≈ 0.20, respectively). Significant amounts of uncombined rLHα were released and were present in both tissue and pellet extracts. However, when FSH β subunit was quantitated in tissue extracts after gel filtration, all of the immunoreactive materials eluted in the position of native rFSH (FSHβ/rFSH molar ratio < 0.0025). Pellet extracts contained significant amounts of rLHβ, rLH and rLHα but lesser amounts of rFSH suggesting that intracellular gonadotropins are not completely extracted when homogenization is performed in aqueous buffers. Thus, rat anterior pituitaries contain and release significant amounts of the uncombined α subunit, relatively small amounts of uncombined rLHβ and extremely small amounts of uncombined FSHβ, if any.


Author(s):  
Alexandra Hochberg ◽  
Marissa Patz ◽  
Thomas Karrasch ◽  
Andreas Schäffler ◽  
Andreas Schmid

AbstractCAMP (Cathelicidin antimicrobial peptide) is synthesized and secreted by adipocytes and involved in adipose tissue (AT) innate immune response and host defense of subcutaneous AT against Gram positive bacteria. Data on the regulation of CAMP in obesity and during weight loss are scarce and reference values do not exist. Serum CAMP levels (ELISA) and AT gene expression levels (quantitative real time PCR) were investigated in two large and longitudinal (12 months) cohorts of severely obese patients undergoing either a low calorie diet (LCD; n=79) or bariatric surgery (BS; n=156). The impact of metabolic factors on CAMP expression in vitro was investigated in differentiated 3T3-L1 adipocytes. CAMP serum levels significantly increased after BS but not during LCD. Females had lower CAMP serum levels and lower gene expression levels in subcutaneous AT. CAMP was positively correlated to unfavorable metabolic factors/adipokines and negatively to favorable factors/adipokines. CAMP gene expression was higher in subcutaneous than in visceral AT but serum CAMP levels were not correlated to levels of AT gene expression. While certain bile acids upregulated CAMP expression in vitro, high glucose/insulin as well as GLP-1 had an inhibitory effect. There exist gender-specific and AT compartment-specific effects on the regulation of CAMP gene expression. Weight loss induced by BS (but not by LCD) upregulated CAMP serum levels suggesting the involvement of weight loss-independent mechanisms in CAMP regulation such as bile acids, incretins and metabolic factors. CAMP might represent an adipokine at the interface between metabolism and innate immune response.


Author(s):  
Ihsan K. Jasim ◽  
Shaimaa N. Abd Alhammid ◽  
Alaa A. Abdulrasool

  CD-nanosponges were prepared by crosslinking B-CD with diphenylcarbonate (DPC) using ultrasound assisted technique. 5-FU was incorporated with NS by freeze drying, and the phase solubility study, complexation efficiency (CE) entrapment efficiency were performed. Also, the particle morphology was studied using SEM and AFM. The in-vitro release of 5-FU from the prepared nanosponges was carried out in 0.1N HCl. 5-FU nanosponges particle size was in the nano size. The optimum formula showed a particle size of (405.46±30) nm, with a polydispersity index (PDI) (0.328±0.002) and a negative zeta potential (-18.75±1.8). Also the drug entrapment efficiency varied with the CD: DPC molar ratio from 15.6 % to 30%. The SEM and AFM showed crystalline and porous nature of the nanosponges. The in vitro drug release study of the selected formula 5-FUNS2 exhibited the fastest dissolution rate which is 56% in the first hr. Different molar ratios of (cyclodextrin to crosslinker) (CD: DPC) has a proficient effect on complexation efficiency (CE), apparent stability constant (Kst) and entrapment efficiency of 5-FU. 5-FUNS2 with (1:4) molar ratio showed the best result of CE, Kst and entrapment efficiency. 5-FUNS2 gave a higher release rate than the 5-FU-BCD inclusion complex and 5-FU solution. Surface morphology of the prepared nanosponges by SEM, AFM indicate that nanosized and highly porous nanosponges was obtained. The overall results suggest that cyclodextrin nanosponges could be a promising 5-FU delivery system utilizing the suitable formula.


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