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Krücken J Dkhil MA Braun JV Schroetel RM El-Khadragy M Carmeliet P Mossmann H Wunderlich F 《Infection and immunity》2005,73(1):436-443
Testosterone induces a lethal outcome in otherwise self-healing blood-stage malaria caused by Plasmodium chabaudi. Here, we examine possible testosterone effects on the antimalaria effectors spleen and liver in female C57BL/6 mice. Self-healing malaria activates gating mechanisms in the spleen and liver that lead to a dramatic reduction in trapping activity, as measured by quantifying the uptake of 3-mum-diameter fluorescent polystyrol particles. However, testosterone delays malaria-induced closing of the liver, but not the spleen. Coincidently, testosterone causes an approximately 3- to 28-fold depression of the mRNA levels of nine malaria-responsive genes, out of 299 genes tested, only in the liver and not in the spleen, as shown by cDNA arrays and Northern blotting. Among these are the genes encoding plasminogen activator inhibitor (PAI1) and hydroxysteroid sulfotransferase (STA2). STA2, which detoxifies bile acids, is suppressed 10-fold by malaria and an additional 28-fold by testosterone, suggesting a severe perturbation of bile acid metabolism. PAI1 is protective against malaria, since disruption of the PAI1 gene results in partial loss of the ability to control the course of P. chabaudi infections. Collectively, our data indicate that the liver rather than the spleen is a major target organ for testosterone-mediated suppression of resistance against blood-stage malaria. 相似文献
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Swiedler SJ Beck M Bajbouj M Giugliani R Schwartz I Harmatz P Wraith JE Roberts J Ketteridge D Hopwood JJ Guffon N Sá Miranda MC Teles EL Berger KI Piscia-Nichols C 《American journal of medical genetics. Part A》2005,(2):144-150
A cross-sectional survey in individuals affected with the lysosomal storage disease Mucopolysaccharidosis VI (MPS VI) was conducted to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of the disease. The survey evaluated 121 bona fide MPS VI-affected individuals over the age of 4 years from 15 countries across the Americas, Europe, and Australasia representing greater than 10% of the estimated world prevalence of the disease. A medical history, complete physical exam, urinary GAG determination, and assessment of several clinical measures related to physical endurance, pulmonary function, joint range of motion, strength, and quality of life were completed for each participant. Although a wide variation in clinical presentation was observed, several general findings were obtained reflecting progression of the disease. Impaired physical endurance, as measured by the distance achieved in a 6-min walk, could be demonstrated across all age groups of MPS VI-affected individuals. High urinary GAG values (>200 mug/mg creatinine) were associated with an accelerated clinical course comprised of age-adjusted short stature and low body weight, impaired endurance, compromised pulmonary function, and reduced joint range of motion. An unexpected result was the predominance of urinary GAG values <100 mug/mg creatinine for those participants over the age of 20 years. Pending the collection of longitudinal data, these results suggest that urinary GAG levels predict clinical morbidity, and longer-term survival is associated with urinary GAG levels below a threshold of 100 mug/mg creatinine. 相似文献
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Fatina W. Dahadhah Mayyas Saleh Jaweesh Mazhar Salim Al Zoubi Manal Issam Abu Alarjah Mohamad Eid Hammadeh Houda Amor 《Andrologia》2021,53(8):e14139
Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation. 相似文献
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Failure of voluntary activation of the quadriceps femoris muscle after patellar contusion 总被引:1,自引:0,他引:1
Manal TJ Snyder-Mackler L 《The Journal of orthopaedic and sports physical therapy》2000,30(11):655-60; discussion 661-3
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Wael H. Roshdy Mohamed K. Khalifa James Emmanuel San Houriiyah Tegally Eduan Wilkinson Shymaa Showky Darren Patrick Martin Monika Moir Amel Naguib Nancy Elguindy Mokhtar R. Gomaa Manal Fahim Hanaa Abu Elsood Amira Mohsen Ramy Galal Mohamed Hassany Richard J. Lessells Ahmed A. Al-Karmalawy Rabeh EL-Shesheny Ahmed M. Kandeil Mohamed A. Ali Tulio de Oliveira 《Viruses》2022,14(9)
COVID-19 was first diagnosed in Egypt on 14 February 2020. By the end of November 2021, over 333,840 cases and 18,832 deaths had been reported. As part of the national genomic surveillance, 1027 SARS-CoV-2 near whole-genomes were generated and published by the end of July 2021. Here we describe the genomic epidemiology of SARS-CoV-2 in Egypt over this period using a subset of 976 high-quality Egyptian genomes analyzed together with a representative set of global sequences within a phylogenetic framework. A single lineage, C.36, introduced early in the pandemic was responsible for most of the cases in Egypt. Furthermore, to remain dominant in the face of mounting immunity from previous infections and vaccinations, this lineage acquired several mutations known to confer an adaptive advantage. These results highlight the value of continuous genomic surveillance in regions where VOCs are not predominant and the need for enforcement of public health measures to prevent expansion of the existing lineages. 相似文献
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Gomaa Mostafa-Hedeab Manal Ewaiss Hassan Taher F. Halawa Farooq Ahmed Wani 《Saudi Pharmaceutical Journal》2022,30(9):1293
Chronic liver disease is a worldwide health problem. Carbon tetra hydrochloride is an environmental toxin which is regarded as highly toxic and a potential human carcinogen. It can cause liver damage through the generation of metabolites and production of free radicals. Green tea contains catechins such as Epigallocatechin gallate which has been found to reduce the inflammation, oxidative stress, and fibrosis in experimental animal models. Hence, it represents a good source to prevent or ameliorate several chronic diseases. Silymarin is extracted from milk thistle seeds and has been found to be an effective agent to reduce the oxidative stress and free radical production and thereby exert protective effects in chronic liver conditions. The present study was planned to keep in view the above-mentioned facts. We included thirty rats in our study and divided them into five groups, each having six rats and the study continued for 8 weeks. Group I received normal saline; Group 2 received i.p. CCl4 injections; Group 3 received CCl4 i.p. injection and Epigallocatechin gallate (EGCG) oral gavage, Group 4 received CCl4 i.p. injection and silymarin by oral gavage; and Group 5 received CCl4 i.p. injection and combined EGCG + silymarin by oral gavage. The study found that in group 2, CCl4 induced significant elevation of ALT and MDA and reduced GSH thereby signifying increased oxidative stress. CCl4 also significantly increased inflammatory (TNFα, NFκB, IL1β, and TGFβ) as well as fibrotic markers (p-ERK and p-Smad1/2 protein expression). EGCG and silymarin significantly reversed the previously mentioned parameters either alone or in combination; however, the effect was more pronounced in case of EGCG. We conclude that EGCG and silymarin possess liver protective effects through their antioxidant, anti-inflammatory, and antifibrotic action. 相似文献
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Noah Zafran Manal Massalha Abeer Suleiman Refaat Massalha Lila Mahagna Scott A. Weiner Shabtai Romano Eliezer Shalev Raed Salim 《CTS Clinical and Translational Science》2022,15(10):2528
The recommended fixed dosage of betamethasone for pregnancies at risk of preterm birth was determined in the 1970s, regardless of gestational age (GA), number of fetuses, and maternal weight. We aimed to examine the association between maternal and neonatal betamethasone serum levels and neonatal respiratory distress syndrome (RDS) and to examine whether levels correlate with maternal weight, GA, or number of fetuses. A prospective study was conducted at a single academic medical center between August 2016 and February 2019. Women received betamethasone and delivered between 28+0 and 34+6 weeks were included. Maternal serum levels (MSLs), and neonatal serum levels (NSLs) of betamethasone at delivery were analyzed using Corticosteroid enzyme‐linked immunosorbent assay kit. RDS was diagnosed according to clinical and radiographic findings. We assumed that the sensitivity of NSLs to detect RDS is 95%; hence, 150 neonates were needed (power 80%, alpha 0.05). Overall, 124 women were included; including 96 (77.4%) singletons, 26 (21.0%) twins, and 2 (1.6%) triplets, corresponding to 154 neonates. RDS was diagnosed in 35 neonates (22.7%). After adjusting for GA, time elapsed from the last dose, and number of doses, NSLs were associated with RDS (relative risk: 0.97, 95% confidence interval: 0.94–0.99, p = 0.011). A level of 6.00 ng/ml predicted RDS with a sensitivity of 80.0% and specificity of 64.7%. Adjusted MSLs were not associated with RDS. Both maternal and neonatal serum levels were not associated with the number of fetuses and maternal weight. In conclusion, NSLs are associated with RDS whereas MSLs are not. Study Highlights
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
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