Search results for "binding"
showing 10 items of 3896 documents
Active recovery shows favorable IGF-I and IGF binding protein responses following heavy resistance exercise compared to passive recovery
2019
IGF-I and IGFBPs have important physiological modulatory effects and this study sought to examine the influence of active vs. passive recovery following a heavy resistance exercise on IGF-I and IGF binding protein (IGFBP) recovery responses. It was hypothesized that increased IGF-I and decreased inhibitory IGFBPs during active recovery may be reflective of cascades promoting physiological recovery. 18 untrained men ((AR n = 7, PR n = 11), age: 26 ± 4 years, height: 174 ± 8 cm, body mass: 75 ± 13 kg) performed either a protocol-specific 10 × 10 × 30% 1RM active (AR) or passive recovery (PR) session following a heavy resistance exercise session performed on a leg press device (10 × 10 1RM). M…
Microdialysis-Assessed Exercised Muscle Reveals Localized and Differential IGFBP Responses to Unilateral Stretch Shortening Cycle Exercise
2020
Microdialysis allows for a preview into local muscle metabolism and can provide physiological insight that blood measurements cannot. Purpose: To examine the potential differential IGF-I system regulation in interstitial fluid during unilateral stretch shortening cycle exercise. Methods: 10 men (26 ± 7 year) performed unilateral jumping [stretch shortening cycle (SSC) exercise at 50% of optimal jump height] until volitional fatigue on a sled apparatus. Biological sampling took place using a catheter inserted into an antecubital vein (serum), and 100 kDa microdialysis probes inserted into the thigh muscle of each exercise/control leg (dialysate). Serum was drawn before (Pre; −3 h) and after …
Lomitapide affects HDL composition and function
2016
Abstract Background Lomitapide reduces low-density lipoprotein-cholesterol (LDL-C) but also high-density lipoprotein-cholesterol (HDL-C) levels. The latter may reduce the clinical efficacy of lomitapide. We investigated the effect of lomitapide on HDL-C levels and on cholesterol efflux capacity (CEC) of HDL in patients with homozygous familial hypercholesterolemia (HoFH). Methods and results Four HoFH patients were treated with increasing dosages of lomitapide. Lomitapide decreased LDL-C (range −34 to −89%). Total HDL-C levels decreased (range −16 to −34%) with a shift to buoyant HDL. ABCA1-mediated CEC decreased in all patients (range −39 to −99%). The changes of total, ABCG1- and SR-BI-me…
Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans – Implications for the evaluation of …
2013
Quercetin has been shown to inhibit intestinal P-glycoprotein-mediated drug efflux. A crossover clinical study was performed in 10 healthy volunteers to assess the effect of single-dose and repeated quercetin intake on the pharmacokinetics of talinolol, a substrate of intestinal P-glycoprotein. Unexpectedly, mean area under the plasma concentration-time curve (AUC0-48h) and maximal plasma concentration (cmax) were slightly decreased following concomitant and short-term quercetin administration (3186.0 versus 2468.3 and 2527.7 ng h/ml, p>0.05; 309.7 versus 212.0 and 280.6 ng/ml, p>0.05). Individual analysis revealed that talinolol AUC0-48h was lowered by 23.9% up to 60.6% in 5 subjects and c…
Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene
2019
Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by the inability to discriminate colors, nystagmus, photophobia, and low-visual acuity. Six genes have been associated with this rare autosomal recessively inherited disease, including the GNAT2 gene encoding the catalytic α-subunit of the G-protein transducin which is expressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independent families diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patients with ACHM from 19 independent families with likely causative mutations in GNAT2, representing 1.7% of our large ACHM cohort. In total 22 different potentially disease-causing…
Effects of controlled-release on the pharmacokinetics and absorption characteristics of a compound undergoing intestinal efflux in humans
2006
Abstract Objective The number of active pharmaceutical ingredients (API) undergoing inhibitable and saturable intestinal efflux is considerable. As a consequence, absorption and bioavailability may depend on the intestinal concentration profile of the drug and may vary as a function of dose and release rate of the drug from the dosage form. The impact of controlled versus immediate-release on the absorption of P-glycoprotein substrates is currently unknown. Thus, the main focus of the present study was a comparison of the pharmacokinetics of the P-gp model substrate talinolol following administration of immediate-release (IR) and controlled-release (CR) tablets to healthy human volunteers w…
Characterization of 14 novel deletions underlying Rubinstein–Taybi syndrome: an update of the CREBBP deletion repertoire
2015
Rubinstein–Taybi syndrome (RSTS) is a rare, clinically heterogeneous disorder characterized by cognitive impairment and several multiple congenital anomalies. The syndrome is caused by almost private point mutations in the CREBBP (~55 % of cases) and EP300 (~8 %) genes. The CREBBP mutational spectrum is variegated and characterized by point mutations (30–50 %) and deletions (~10 %). The latter are diverse in size and genomic position and remove either the whole CREBBP gene and its flanking regions or only an intragenic portion. Here, we report 14 novel CREBBP deletions ranging from single exons to the whole gene and flanking regions which were identified by applying complementary cytomolecu…
Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome.
2012
Background: Rubinstein-Taybi syndrome (RSTS) is a congenital neurodevelopmental disorder defined by postnatal growth deficiency, characteristic skeletal abnormalities and mental retardation and caused by mutations in the genes encoding for the transcriptional co-activators with intrinsic lysine acetyltransferase (KAT) activity CBP and p300. Previous studies have shown that neuronal histone acetylation is reduced in mouse models of RSTS. Methods: The authors identified different mutations at the CREBBP locus and generated lymphoblastoid cell lines derived from nine patients with RSTS carrying distinct CREBBP mutations that illustrate different grades of the clinical severity in the spectrum …
Phenotype associated with TAF2 biallelic mutations: a clinical description of four individuals and review of the literature
2021
International audience; Transcription factor IID is a multimeric protein complex that is essential for the initiation of transcription by RNA polymerase II. One of its critical components, the TATA-binding protein-associated factor 2, is encoded by the gene TAF2. Pathogenic variants of this gene have been shown to be responsible for the Mental retardation, autosomal recessive 40 syndrome. This syndrome is characterized by severe intellectual disability, postnatal microcephaly, pyramidal signs and thin corpus callosum. Until now, only three families have been reported separately. Here we report four individuals, from two unrelated families, who present with severe intellectual disability and…
High progesterone levels are associated with family history of premature coronary artery disease in young healthy adult men.
2019
Background & aimsThe offspring of patients with premature coronary artery disease (P-CAD) are at higher risk for cardiovascular disease, compared with subjects without a family history (FH) of P-CAD. The increased risk for cardiovascular disease in subjects with FH of early-onset CAD results from unfavorable genetic variants as well as social, behavioral and environmental factors, which are more prevalent in this group. Previous studies have shown that specific sex hormone levels may be associated with the risk of cardiovascular disease. The aim of this study was to compare wide range of biochemical marker levels including i.e. the levels of luteinizing hormone (LH), follicle-stimulating ho…