A makro-TSH diagnosztikus és terápiás jelentősége Hashimoto-thyreoiditises betegekben | Diagnostic and therapeutical significance of macro-TSH in patients with Hashimoto’s thyroiditis

Absztrakt: Bevezetés: A makro-TSH szerkezete, incidenciája és klinikai szerepe pajzsmirigybetegekben nem tisztázott. Célkitűzés: A makro-TSH előfordulási gyakoriságának, tulajdonságainak meghatározása Hashimoto-thyreoiditises betegek savójában. Módszer: A Hashimoto-thyreoiditises betegek vérmintáiban a makro-TSH-t meghatározták polietilén-glikol precipitációs módszerrel és protein G agaróz abszorpciós, illetve gélfiltrációs kromatográfiával. A makro-TSH biológiai aktivitását TSH-receptorral transzfektált CHO bioassay módszerével mérték. A betegek L-tiroxin-kezelésben részesültek (átlagosan 66,5 µg/nap), a betegek fele pedig szelént is kapott (átlagosan 60 µg/nap). Eredmények: 880 Hashimoto-thyreoiditises beteget (728 nő, átlagéletkor 44,8 év) vontak be a vizsgálatba. A makro-TSH-t 41 betegben (4,6%) mutatták ki, az átlagos TSH-szint a PEG-precipitáció előtt 185,4 ± 35 IU/l volt, a precipitáció után pedig 5,55 ± 1,8 IU/l. Az anti-TPO-szint 445 ± 51 IU/l volt és fokozatosan csökkent 212 ± 51 IU/l-re egyéves tiroxin- és szelénkezelés után. Mind a PEG-precipitációs, mind a protein G abszorpciós módszerrel, illetve gélkromatográfiás eljárással a TSH elleni antitest jelenlétét mutatták ki a makro-TSH-immunkomplexben. A makro-TSH biológialag inaktívnak bizonyult, mivel a CHO-sejteket nem stimulálta. A makro-TSH a szelénnel nem kezelt csoportban 18 ± 3,2 hónapig, a szelénnel kezeltben 12 ± 1,9 hónapig volt kimutatható. Következtetés: A TSH elleni antitestek fő komponensei a makro-TSH-nak és diagnosztikus, illetve terápiás nehézségeket okozhatnak. A PEG-precipitációs eljárás alkalmas szűrőmódszer a makro-TSH bizonyítására. A szelén képes nemcsak az anti-TPO-, hanem a makro-TSH-szint csökkentésére egyaránt. Amikor a TSH-szint 40,0 IU/l feletti a hypothyreosis jelei nélkül, gondolnunk kell a makro-TSH jelenlétére. Orv Hetil. 2017; 158(34): 1346–1350. | Abstract: Introduction: Structure, importance and incidence and clinical role of macro-TSH not clarified in thyroid diseases. Aim: This study was undertaken to determine the incidence and biological role of macro-TSH in patients with Hashimoto’s thyroiditis. Method: Blood samples taken from patients with Hashimoto’s thyroiditis were screened for the presence of macro-TSH with the polyethylene glycol method and confirmed with protein G agarose absorption test and gel filtration chromatography. Stimulatory capacity of macro-TSH was measured by CHO cells bio-assay. Patients were treated with L-thyroxine (mean 66.5 µg/day) and half of them with selenium (mean 60 µg/day), respectively. Results: 880 patients (728 female, aged 44.8 yr) with Hashimoto’s thyroiditis was involved in the study. Macro-TSH was found in the serum of 41 patients (4.6%), the mean TSH 185.4 ± 35 IU/l was before PEG precipitations and after 5.55 ± 1.8 IU/l. Titre of anti-TPO proved to be 445 ± 51 IU/l and gradulally decreased to 212 ± 51 IU/l after one year therapy. Both the precipitation, protein G absorption and gel chromatography supported the presence of anti-TSH antibody in the macro-TSH complex. Stimulatory capacity of macro-TSH on CHO bio-assay was not proved. The macro-TSH was detected in the selenium not treated group for 18 ± 3.2 months, selenium-treated for 12 ± 1.9 months. Conclusion: It is concluded that anti-human TSH autoantibodies are a major components of macro-TSH and may cause diagnostic and therapeutical difficulties. The PEG precipitation is a suitable screening method for detection of macro-TSH. Selenium is able to decrease of anti-TPO antibodies and macro-TSH, respectively. When the TSH level is greater than 40.0 IU/l, without the signs of hypothyroidism, the presence of macro-TSH is to be considered. Orv Hetil. 2017; 158(34): 1346–1350

Data_Sheet_1_Transient Receptor Potential Melastatin 8 (TRPM8)-Based Mechanisms Underlie Both the Cold Temperature-Induced Inflammatory Reactions and the Synergistic Effect of Cigarette Smoke in Human Bronchial Epithelial (16HBE) Cells.PDF

Transient receptor potential melastatin 8 (TRPM8) is a major receptor of cold environment. Recently, we found that cigarette smoke extract (CSE) upregulated TRPM8 mRNA and protein expression in bronchial tissues that made them more sensitive to cold stimuli. In our present study, we found that cold temperature (18°C)-induced activation of TRPM8 in 16HBE (human bronchial epithelial) cells facilitated Ca2+ influx and subsequently led to the increased expression of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α via the upregulation of p-extracellular signal-regulated kinase (ERK) and the activation of NF-κB. In addition, 16HBE cells that co-stimulated with 18°C and CSE were used to explore the synergistic effect of CSE on cold temperature-induced inflammatory cytokine production as well as the possible involved signaling pathway. RT-PCR and western blot analysis revealed that CSE upregulated TRPM8 mRNA and protein level in 16HBE cells. Ca2+ imaging, western blot, and luciferase assay showed more robust increase in intracellular Ca2+ and promoted phosphorylated ERK, P38, and NF-κB activity, respectively, in 16HBE cells co-stimulated with CSE and cold temperature, and such alteration was attenuated by TRPM8 short hairpin RNA (shRNA) transfection and BCTC pretreatment. Furthermore, enhanced levels of IL-6, IL-8, and TNF-α showed by enzyme-linked immunosorbent assay (ELISA) were reduced by specific inhibitors of ERK and NF-κB. Collectively, our results suggest that mitogen-activated protein kinase (MAPK)/NF-κB signaling is involved in TRPM8-mediated cold temperature-induced inflammatory cytokine expression. In addition, CSE synergistically amplifies cold temperature-induced inflammatory factors release via upregulating TRPM8 expression and enhancing MAPK/NF-κB signaling pathway.</p

Synthesis and Application of Silane-Modified Castor Oil-Based Waterborne Polyurethane as a Fluorine-Free and Durable Water Repellent

As petroleum resources diminish and public environmental consciousness increases, biobased, fluorine-free waterproof agents have become a research hotspot. However, most reported waterproof agents still suffer from poor water resistance and have the drawback of hardening the fabric’s hand feel. To address these issues, silanated castor oil (SiCO) was synthesized by castor oil and trimethoxysilane and used to prepare a series of biobased waterborne polyurethanes (SiCO-WPU). Then, SiCO-WPU was finished on the polyamide fabric using a pad–dry–cure procedure. The finishing process was optimized by using the Minitab software. The water repellency tests showed that when the SiCO content was 19.92%, the water contact angle of the SiCO-WPU film increased from 74.8° to 95.8°, and the treated polyamide fabric achieved a contact angle of 138.5° along with a water repellency rating of level 4. In addition, the treated fabric exhibited an 11% decrease in the sliding friction coefficient and a 20% enhancement in the crease recovery angle. Even after 20 washes, the treated fabric still maintained good water repellency and improved the smooth and elastic hand feel. This work holds significant importance for the design and application of sustainable, fluorine-free waterproofing agents in the textile industry

Synthesis of Silica Particles Grafted with Well-Defined Living Polymeric Chains by Combination of RAFT Polymerization and Coupling Reaction

A combinatorial approach based on reversible addition−fragmentation chain transfer (RAFT) polymerization and coupling reaction was used to prepare well-defined silica−polymer hybrids. Chain-end-functionalized homopolymers were synthesized by RAFT polymerization of vinyl monomers such as methyl acrylate, butyl acrylate, N,N-dimethylacrylamide, N-isopropylacrylamide, N-acrylomorpholine, methyl methacrylate, and styrene mediated by S-methoxycarbonylphenylmethyl S′-trimethoxysilylpropyltrithiocarbonate in toluene or dioxane at 60 °C, and di-, tri-, and tetrablock copolymers were further synthesized by successive chain extension polymerization. These polymers comprising a trimethoxysilane functionality in the chain end were then grafted to the surface of flash silica by coupling reaction between trimethoxysilane and hydroxyl groups. IR and thermogravimetric analyses results indicated the grafting ratios of polymeric chains on the surface of silica were relatively high. The grafted polymeric chains were cleaved from the surface of silica by aminolysis, and gel permeation chromatography results revealed all the grafted polymers possessed low polydispersity (typically less than 1.2) and molecular weight similar to that of the “as-prepared” polymers. Furthermore, the solid-supported polymeric chains were almost 100% living, evident from highly efficient chain extension polymerization to prepare well-defined block copolymers grafted onto silica particles

Clinical Characteristics of the Study Population.

<p>AST≥40 IU/L or ALT≥40 IU/L were defined as Transaminase elevation;Serum PA levels≤170 mg/L were defined as PA decreased.</p>*<p><i>P<</i>0.05, compared to both TB and healthy individuals groups.</p>***<p><i>P<</i>0.001, compared to both lung cancer patients and health individuals groups.</p>**<p><i>P<</i>0.01, compared to both lung cancer patients and health individuals groups.</p

The serum PA levels in different subgroups of TB patients.

<p>There were significant differences in the serum PA levels between following subgroups: pleuritis and lung tuberculosis, TB patients with higher ESR (≥20 mm/h) and normal ESR (<i><</i>20 mm/h), TB patients with higher smoking status (≥20 year×pack) (<i>P<</i>0.01).</p

Correlation analysis of the DCE-MRI and SUV parameters in primary tumors of NSCLC and its subtypes.

<p>The statistically significant correlations are indicated with an asterisk.</p

Influencing factors of PA decrease in patients with TB.

<p>Serum PA levels≤170 mg/L were defined as PA decreased;</p><p>Patients were divided into two types:lung TB(pulmonary tuberculosis patients without pleuritis) and with pleuritis(incluing both pulmonary tuberculosis patients with pleuritis and simple pleuritis patients).</p>**<p><i>P<</i>0.01.a: age≥60 compared to other subgroups; b: smoking status≥20 compared to other subgroups.</p

Graph shows the correlation between ADCmean and tumour cellularity of lung cancer.

<p>AC, adenocarcinoma; SqCC, squamous cell carcinoma; SLCC, small cell lung cancer.</p

Scatter matrix of the PET/CT and DCE-MRI metrics in AC of the lung.

<p>Scatter matrix of the PET/CT and DCE-MRI metrics in AC of the lung.</p