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91.
Low muscle strength is observed during the peri-and postmenopausal periods, when the secretion of ovarian hormones is drastically
reduced. It is also a predictive of adverse health events as well as incident mobility limitation and disability. The objective
of the present study is to study the biochemical and the histological changes in the skeletal muscle of premature menopause-induced
rats and the possible protective role of L-carnitine. Ovariectomized (OVX) rats were gavaged with L-carnitine (100 mg/kg)
daily for 60 days starting from the second post-operative day. Serum levels of estradiol and markers of skeletal muscle damage
(creatine kinase and lactic dehydrogenase activities) were determined. Light and electron microscopic study of the quadriceps
femoris muscle (QFM) specimens were done. OVX rats showed significant decrease in the serum estradiol level with significant
increase the markers for skeletal muscle damage. Histopathological examination of the QFM showed degenerated myofibers, apoptotic
changes and compensatory hypertrophy. Degenerated mitochondria, multiple lysosomes and lipid droplets among the damaged myofibrils
were also noticed. L-carnitine administration to the OVX rats resulted in non-significant change in the serum estradiol level
with significant attenuation of skeletal muscle damage either biochemically or histopathologically. In conclusion, L-carnitine
administration recovered muscle degeneration after ovariectomy. This finding suggested that L-carnitine could be recommended in the management of post-menopausal myopathy. 相似文献
92.
Al-Garawi A Husain M Ilieva D Humbles AA Kolbeck R Stampfli MR O'Byrne PM Coyle AJ Jordana M 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(2):832-843
Respiratory viral infections have been associated with an increased incidence of allergic asthma. However, the mechanisms by which respiratory infections facilitate allergic airway disease are incompletely understood. We previously showed that exposure to a low dose of house dust mite (HDM) resulted in enhanced HDM-mediated allergic airway inflammation, and, importantly, marked airway hyperreactivity only when allergen exposure occurred during an acute influenza A infection. In this study, we evaluated the impact of concurrent influenza infection and allergen exposure at the genomic level, using whole-genome microarray. Our data showed that, in contrast to exposure to a low dose of HDM, influenza A infection led to a dramatic increase in gene expression, particularly of TLRs, C-type lectin receptors, several complement components, as well as FcεR1. Additionally, we observed increased expression of a number of genes encoding chemokines and cytokines associated with the recruitment of proinflammatory cells. Moreover, HDM exposure in the context of an influenza A infection resulted in the induction of unique genes, including calgranulin A (S100a8), an endogenous damage-associated molecular pattern and TLR4 agonist. In addition, we observed significantly increased expression of serum amyloid A (Saa3) and serine protease inhibitor 3n (Serpina3n). This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying the ensuing immune-inflammatory response. We propose that influenza A infection primes the lung environment in such a way as to lower the threshold of allergen responsiveness, thus facilitating the emergence of a clinically significant allergic phenotype. 相似文献
93.
Chapoval SP Al-Garawi A Lora JM Strickland I Ma B Lee PJ Homer RJ Ghosh S Coyle AJ Elias JA 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(10):7030-7041
IL-13 is a major Th2 cytokine that is capable of inducing inflammation, excessive mucus production, airway hyperresponsiveness, alveolar remodeling, and fibrosis in the murine lung. Although IL-13 through its binding to IL-4Ralpha/IL-13Ralpha1 uses the canonical STAT6-signaling pathway to mediate these tissue responses, recent studies have demonstrated that other signaling pathways may also be involved. Previous studies from our laboratory demonstrated that IL-13 mediates its tissue effects by inducing a wide variety of downstream genes many of which are known to be regulated by NF-kappaB. As a result, we hypothesized that NF-kappaB activation plays a critical role in the pathogenesis of IL-13-induced tissue alterations. To test this hypothesis, we compared the effects of transgenic IL-13 in mice with normal and diminished levels of NF-kappaB activity. Three pharmacologic approaches were used to inhibit NF-kappaB including 1) PS1145, a small molecule inhibitor of IkappaBalpha kinase (IKK2), 2) antennapedia-linked NF-kappaB essential modulator-binding domain (NBD) peptide (wild-type NBD), and 3) an adenoviral construct expressing a dominant-negative version of IKK2. We also crossed IL-13-transgenic mice with mice with null mutations of p50 to generate mice that overproduced IL-13 in the presence and absence of this NF-kappaB component. These studies demonstrate that all these interventions reduced IL-13-induced tissue inflammation, fibrosis and alveolar remodeling. In addition, we show that both PS1145 and wild-type NBD inhibit lung inflammatory and structural cell apoptosis. PS1145 inhibits caspase activation and up-regulates inhibitor of apoptosis protein cellular-inhibitor of apoptosis protein 1 (c-IAP-1). Therefore, NF-kappaB is an attractive target for immunotherapy of IL-13-mediated diseases. 相似文献
94.
PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing 总被引:6,自引:0,他引:6
Wang L Manji GA Grenier JM Al-Garawi A Merriam S Lora JM Geddes BJ Briskin M DiStefano PS Bertin J 《The Journal of biological chemistry》2002,277(33):29874-29880
PYRIN-containing Apaf1-like proteins (PYPAFs) are members of the nucleotide-binding site/leucine-rich repeat (NBS/LRR) family of signal transduction proteins. We report here that PYPAF7 is a novel PYPAF protein that activates inflammatory signaling pathways. The expression of PYPAF7 is highly restricted to immune cells, and its gene maps to chromosome 19q13.4, a locus that contains a cluster of genes encoding numerous PYPAF family members. Co-expression of PYPAF7 with ASC results in the recruitment of PYPAF7 to distinct cytoplasmic loci and a potent synergistic activation of NF-kappa B. To identify other proteins involved in PYPAF7 and ASC signaling pathways, we performed a mammalian two-hybrid screen and identified pro-caspase-1 as a binding partner of ASC. Co-expression of PYPAF7 and ASC results in the synergistic activation of caspase-1 and a corresponding increase in secretion of interleukin-1 beta. In addition, PYPAF1 induces caspase-1-dependent cytokine processing when co-expressed with ASC. These findings indicate that PYPAF family members participate in inflammatory signaling by regulating the activation of NF-kappa B and cytokine processing. 相似文献
95.
Safaa I. Elewa Mansour Eman Nassar Ibrahim F. Mekawey Amal A. I. 《Russian Journal of Bioorganic Chemistry》2020,46(3):382-392
Russian Journal of Bioorganic Chemistry - 3-(2-Thienyl)-5-aryl-1-thiocarbamoyl-2-pyrazolines were reacted with chloroacetone derivatives and hydrazonyl chloride derivatives in ethanol to afford the... 相似文献
96.
97.
Ayyad SE Sowellim SZ el-Hosini MS Abo-Atia A 《Zeitschrift für Naturforschung. C, Journal of biosciences》2003,58(5-6):333-336
An investigation of the natural products chemistry of the brown alga Sargassum asperifolium from the red sea yielded a new steroidal metabolite, 24-vinyl cholest-4-ene-24-ol-3-one, saringosterone (3), a known steroidal metabolite, 24-vinyl cholest-5-ene-3b,24-diol, saringosterol (4), and known diterpene with a hydroazulene skeleton, dictyone (1). The identification of the isolated metabolites was established mainly by spectral methods and chemical transformation of the dictyone (1) to its acetate (2). 相似文献
98.
Boland JL Corbeij HA Van Der Giessen W Seabra-Gomes R Suryapranata H Wijns W Hanet C Suttorp MJ Buller C Bonnier JJ Colombo A Van Birgelen C Pieper M Mangioni JA Londero H Carere RG Hamm CW Bonan R Bartorelli A Kyriakides ZS Chauhan A Rothman M Grinfeld L Oosterwijk C Serruys PW Cumberland DC 《International journal of cardiovascular interventions》2000,3(4):215-225
AIMS: The BiodivYsio trade mark stent (Biocompatibles Ltd, Farnham, UK) is coated with a phosphorylcholine (PC)-containing copolymer to confer biocompatibility. The SOPHOS (Study Of PHosphorylcholine coating On Stents) study was designed to assess the safety and efficacy of this novel coronary stent and by indirect comparison to indicate equivalence with other formal stent studies. METHODS AND RESULTS: Patients with angina and a single short (#x2A7F;12 mm) de novo lesion in a native coronary artery of >/=2.75 mm diameter were included. A total of 425 patients were allocated in 24 centers. Clinical data were collected at one-, six- and nine-month follow-up. Angiography was performed before and after the stent implantation. In addition, in the first 200 patients (SOPHOS A) angiography was routinely performed at six months. The following 225 patients (SOPHOS B) were merely followed up clinically. The primary end-point of the study, the six-month MACE-rate (MACE = Major Adverse Cardiac Events) was 13.4% (two cardiac death; five Q-wave/nine non-Q-wave myocardial infarctions (MI); nine CABG and 32 target lesion revascularization (TLR), which is similar to the calculated 15% MACE-rate in comparable reference studies. Secondary end-points included among others restenosis at six months in the SOPHOS A population. The target vessel diameter was 2.98 +/- 0.48 mm. Minimal lumen diameter pre/post procedure and at follow-up was 1.00 +/- 0.32, 2.69 +/- 0.37, 1.91 +/- 0.71 mm, respectively. The binary restenosis rate (>/=50% diameter stenosis at follow-up) was 17.7%. CONCLUSION: The coronary BiodivYsio stent is safe and effective as a primary device for the treatment of native coronary artery lesions in patients with stable or unstable angina pectoris. Clinical and angiographic results are in the statistical range of equivalence with comparable studies with other current stents. 相似文献
99.
Yvet E Noordman Patrick AM Jansen Wiljan JAJ Hendriks 《Journal of molecular signaling》2006,1(1):1-11
Background
Spatio-temporal control of extracellular signal-regulated kinase (ERK) activity, a critical determinant of the cell's response to growth factors, requires timely dephosphorylation of its regulatory tyrosine and/or threonine residue by MAPK phosphatases. We studied the physiological role of kinase interaction motif (KIM)-containing protein tyrosine phosphatases (PTPs) in the control of EGF- and NGF-induced ERK activity in neuroendocrine PC12 cells.Results
We found a single KIM-containing PTP to be endogenously expressed in rat PC12 cells: the transmembrane PTPRR isoform termed PCPTP1. Protein knock-down of PCPTP1, or fourfold overexpression of its mouse orthologue, PTPBR7, left EGF- and NGF-induced ERK1/2 activity in PC12 cells unaltered. Ectopic expression of cytosolic PTPRR isoforms, however, resulted in reduced EGF-induced ERK1/2 activity, an effect that was dependent on the phosphatase activity and the KIM-domain of these PTPs.Conclusion
The finding that robust changes in tyrosine-specific MAPK phosphatase expression levels have minor effects on temporal ERK1/2 activity control in PC12 cells suggests that dual-specificity MAPK phosphatases may act as major regulators of growth factor-induced ERK1/2 signaling in these cells. 相似文献100.