The bone transport technique uses the principle of distraction-osteogenesis and fill bone defects with the aid of an external fixator. In order to evaluate the clinical effect of femoral internal fixation with Ortho-Bridge System after bone transport, 4 patients after femoral bone transport from October 2020 to October 2022 are studied in this paper. Among them, 3 patients ran refracture of femur after removal of the Limb reconstruction system, 1 patient just finish femoral bone transport and request internal fixation. The surgery results show that Ortho-Bridge System can be used in the situation that conventional Locking compression plate and intramedullary nail are not suitable due to anatomical variation after femoral bone transport. Key words: femoral fracture; Ortho-Bridge System; bone transport; postoperative complications of bone transport.

• MeSH
• dospělí MeSH
• externí fixátory MeSH
• femur chirurgie   MeSH
• fraktury femuru * chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteogeneze pomocí distrakčního aparátu metody   přístrojové vybavení   MeSH
• pooperační komplikace etiologie   MeSH
• vnitřní fixace fraktury metody   přístrojové vybavení   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

T-2 toxin, a major compound of trichothecenes, induces cell apoptosis and growth hormone (GH) deficiency and causes considerable growth retardation in animals and human cells. However, the mechanism underlying its growth suppression still remains unclear. Recent studies have suggested that ROS induced cell apoptosis and animal feed intake reduction, but there are limited reports on the role of RNS in T-2 toxin-mediated mitochondrial damage, cell apoptosis and growth retardation. Herein, T-2 toxin-induced GH3 cell damage and apoptosis were tested by MTT assay, LDH leakage and flow cytometry, respectively. Intracellular NO and antioxidant enzyme activity, ΔΨm, morphometric changes of mitochondria, the caspase pathway, and inflammatory factors were investigated. Free radical scavengers NAC, SOD and NO scavenger haemoglobin were used to explore the role of oxidative stress and the relationship between NO production and caspase pathway. The results clearly revealed that T-2 toxin caused significant increases in NO generation, cell apoptosis, GH deficiency, increased iNOS activity, upregulation of inflammatory factors and caspase pathway, decreases in ΔΨm and morphosis damage. These data suggest that mitochondria are a primary target of T-2 toxin-induced NO, and NO is a key mediator of T-2 toxin-induced cell apoptosis and GH deficiency via the mitochondria-dependent pathway in cells.

• MeSH
• adenohypofýza cytologie   MeSH
• apoptóza účinky léků   MeSH
• kaspasy metabolismus   MeSH
• krysa rodu rattus MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• růstový hormon nedostatek   MeSH
• signální transdukce účinky léků   MeSH
• somatotropní buňky účinky léků   metabolismus   patologie   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• T-2 toxin toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N → O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, and whether the metabolic pathway of MEQ is altered in response to the pathophysiological conditions still remain unclear. We now provide evidence that MEQ triggers oxidative damage in the liver. Moreover, using LC/MS-ITTOF analysis, two metabolites of MEQ were detected in the liver, which directly confirms the potential connection between N → O group reduction metabolism of MEQ and liver toxicity. The gender difference in MEQ-induced oxidative stress might be due to adrenal toxicity and the generation of M4 (2-isoethanol 1-desoxymequindox). Furthermore, up-regulation of the MAPK and Nrf2-Keap1 family and phase II detoxifying enzymes (HO-1, GCLC and NQO1) were also observed. The present study demonstrated for the first time the protein peroxidation and a proposal metabolic pathway after chronic exposure of MEQ, and illustrated that the MAPK, Nrf2-Keap1 and NF-кB signaling pathways, as well as the altered metabolism of MEQ, were involved in oxidative toxicity mediated by MEQ in vivo.

• MeSH
• antiinfekční látky aplikace a dávkování   farmakokinetika   toxicita   MeSH
• chinoxaliny aplikace a dávkování   farmakokinetika   toxicita   MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• játra účinky léků   metabolismus   MeSH
• KEAP-1 metabolismus   MeSH
• MAP kinasový signální systém * MeSH
• myši MeSH
• oxidace-redukce MeSH
• oxidační stres * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chronic exposure to low dose of T-2 toxin causes growth retardation and reduced body weight, resulting in economic losses. Excessive inflammatory cytokines and GH deficiency are important mechanisms that contribute to growth inhibition induced by T-2 toxin. However, the regulation of the inflammatory cytokines expecially IL-6, IL-1β, and TNF-α induced by T-2 toxin still remained unclear. The new transcription factor AKNA, belonging to AT-hook protein family, is closely associated with inflammation. However, it was unclear how AKNA regulate the expression of inflammatory cytokines, and there was no report on the role of AKNA in T-2 toxin mediated toxicity. Here, we investigated the role of AKNA in T-2 toxin-mediated inflammatory response and GH deficiency and the signal transduction pathway of AKNA. We showed that AKNA regulated by PKA/CREB and NF-κB pathway is a novel downstream molecular target in T-2 toxin-mediated inflammation and GH deficiency. T-2 toxin activates the PKA/CREB and NF-κB/p65 pathways, thereby promoting the direct binding of phospho-CREB and phospho-p65 to the AKNA promoter, thus inhibiting AKNA expression. GH and inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression were significantly downregulated after AKNA silencing. Furthermore, the expression of differential genes induced by T-2 toxin in the rat pituitary was further confirmed by acute toxicity tests in rats, which was consistent with the results in GH3 cells. By histopathological analysis, we confirmed the pituitary might be a novel direct target organ of T-2 toxin. These findings provided new insights into the significant role of AKNA in T-2 toxin-induced inflammatory response and growth inhibition.

• MeSH
• buněčné linie MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• down regulace MeSH
• fosforylace MeSH
• interleukin-1beta genetika   metabolismus   MeSH
• interleukin-6 genetika   metabolismus   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• NF-kappa B metabolismus   MeSH
• promotorové oblasti (genetika) MeSH
• protein vázající element responzivní pro cyklický AMP metabolismus   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   MeSH
• T-2 toxin toxicita   MeSH
• TNF-alfa genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• umlčování genů MeSH
• zánět chemicky indukované   genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a single oral administration, more than 94% of the dose was recovered within 14 d in the four species. The urine excretion was dominant in swine and rats, making up 78% of the dose. N-monodesmethyl-ADP, N-didesmethyl-ADP, and 10 new metabolites were characterized. These metabolites were biotransformed from the process of demethylation, α-hydroxylation, N-oxidation, and NH2-glucuronidation. After an oral dose for 7 d, ADP-derived radioactivity was widely distributed in tissues, and high concentrations were especially observed in bile, liver, kidney, lung, and spleen. The radioactivity in the liver was eliminated much more slowly than in other tissues, with a half-life of 4.26, 3.38, 6.69, and 5.21 d in swine, broilers, carp, and rats, respectively. ADP, N-monodesmethyl-ADP, and N-didesmethyl-ADP were the major metabolites in edible tissues. Notably, ADP was detected with the highest concentration and the longest duration in these tissues. These findings indicated that ADP is the marker residue and the liver is the residue target tissue.

• MeSH
• adenosindifosfát metabolismus   MeSH
• aplikace orální MeSH
• chromatografie kapalinová MeSH
• hmotnostní spektrometrie MeSH
• játra chemie   MeSH
• kapři moč   MeSH
• krysa rodu rattus moč   MeSH
• kur domácí moč   MeSH
• prasata moč   MeSH
• tkáňová distribuce MeSH
• trimethoprim aplikace a dávkování   analogy a deriváty   farmakokinetika   moč   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus moč   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mequindox (MEQ) is a synthetic antibacterial agent. Recent studies showed that MEQ and its primary metabolites exhibit strong genotoxicity to mammalian cells, and MEQ induced carcinogenicity in mice. These findings suggest that chronic exposure to MEQ could lead to an increased risk of cancer later in life. In the present study, four groups of Wistar rats (55 rats/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg) for 2 years. The results showed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive systems, were the main targets for MEQ. Liver toxicity mediated by MEQ was associated with apoptosis and the nuclear factor κB (NF-κB) signaling pathway. In addition, MEQ increased the incidence of tumors in rats. Phosphorylated histone H2AX (γ-H2AX) is identified as a biomarker of cellular response to DNA double-strand breaks (DSB). Our data demonstrated that γ-H2AX expression was significantly increased in tumors. Thus, high levels of DSB might be responsible for carcinogenesis in rats, and further investigation is absolutely required to clarify the exact molecular mechanisms for carcinogenicity caused by MEQ in vivo.

• MeSH
• analýza přežití MeSH
• apoptóza účinky léků   MeSH
• chinoxaliny toxicita   MeSH
• dietární expozice MeSH
• experimentální nádory metabolismus   MeSH
• fosfoproteiny biosyntéza   MeSH
• histony biosyntéza   MeSH
• imunohistochemie MeSH
• játra účinky léků   metabolismus   MeSH
• karcinogeny toxicita   MeSH
• NF-kappa B metabolismus   MeSH
• poškození DNA * MeSH
• potkani Wistar MeSH
• tělesná hmotnost účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH