Tacrolimus intracellular kinetics.

<p>Intracellular accumulation of tacrolimus (0.05 μM) after 15, 30 sec, 1, 5, 10, 30 or 60 min of efflux (N = 6) in (<b>A</b>) CTL HEK293, CTL HEKpcDNA3.1, HEK_1199G and HEK_1199A and (<b>B</b>) CTL K562, CTL K562pcDNA3.1, K562_1199G and K562_1199A. Cells were pre-loaded with tac for 120 min before efflux. The intracellular accumulation of Tac in each cell line was normalized by reporting the absolute amounts of Tac (in ng) on the total amount of proteins in cell extracts, expressed in mg. * compared to CTL pcDNA3.1 *p<0.05 **p<0.01 ***p<0.001, # compared to 1199G/WT #p<0.05 ##p<0.01 ###p<0.001.</p

DRV plasma concentration according to <i>CYP3A5*3</i> polymorphism.

<p>DRV plasma concentration according to <i>CYP3A5*3</i> polymorphism.</p

Influence of <i>ABCB1</i> 1199G>A polymorphism on drug transport and/or efficacy.

<p>*Compared to 1199G wild-type; n.a.: not available.</p><p>See text for details.</p

The <i>ABCB1</i> 1199A variant differentially affects Tac and CsA efflux.

<p>Intracellular accumulation of tacrolimus after 120 min of incubation (N = 3) (<b>A</b>) at six different concentrations (0.0015–0.5 μM) in CTL HEK293, CTL HEKpcDNA3.1, HEK_1199G and HEK_1199A and (<b>B</b>) at 0.05 μM in CTL K562, CTL K562 pcDNA3.1, K562_1199G and K562_1199A. Intracellular accumulation of CsA after 120 min of incubation (N = 3) (<b>C</b>) at six different concentrations (0.015–5 μM) in CTL HEK, CTL HEKpcDNA3.1, HEK_1199G and HEK_1199A and (<b>D</b>) at 0.5 μM in CTL K562, CTL K562pcDNA3.1, K562_1199G and K562_1199A. The intracellular accumulation of Tac or CsA in each cell line was normalized by reporting the absolute amounts of Tac or CsA (in ng) on the total amount of proteins in cell extracts, expressed in mg. * compared to 1199G/WT *p<0.05 **p<0.01 ***p<0.001.</p

Intracellular accumulation of Rhodamine123 is not influenced by <i>ABCB1</i> 1199A variant.

<p>Intracellular accumulation of Rhodamine123 (5 μM) in presence (0.1 and 0.2 μM) or absence of ABCB1 inhibitor (LY335979) (N = 6) in (<b>A</b>) CTL HEK293, CTL HEKpcDNA3.1, HEK_1199G and HEK_1199A and (<b>B</b>) CTL K562, CTL K562pcDNA3.1, K562_1199G and K562_1199A. * compared without inhibitor *p<0.05 **p<0.01 ***p<0.001, # compared to CTL pcDNA3.1 #p<0.05 ##p<0.01 ###p<0.001.</p

Patients characteristics at day of sampling.

<p>Patients characteristics at day of sampling.</p

Darunavir plasma concentration according to <i>CYP3A5*3</i> polymorphism in patients co-treated with darunavir and etravirine.

<p>Values are reported on the Y-axis using a box and whisker plot. Bottom and top of the boxes indicate the 25th and 75th percentiles, respectively and the inside-line represents the 50th percentile (median). Whiskers show maximal and minimal observed values.</p

Data_Sheet_1_Case report: Motor neuron disease phenotype associated with symptomatic copper deficiency: Challenging diagnosis and treatment.PDF

Copper deficiency is an acquired condition that can lead to neurologic dysfunctions, such as myelopathy, motor neuron impairment, polyneuropathy, cognitive impairment, and optic nerve neuropathy. Associated biological findings are low serum copper and ceruloplasmin levels with low copper urinary excretion. We report the case of a previously healthy 59-year-old man who presented a complex neurological picture starting with symptoms and radiological signs consistent with degenerative myelopathy in the presence of persisting low serum copper and ceruloplasmin despite oral and intravenous copper supplementation. Over time, his symptoms evolved into a motor neuron disease evocating an amyotrophic lateral sclerosis (ALS) phenotype. The potential role of copper deficiency is discussed, together with the difficulties in biomonitoring copper supplementation.</p

Distribution of the <i>CYP3A5</i> genotypes in the study cohort and according to the ethnicity (Caucasian versus African origin).

<p>Distribution of the <i>CYP3A5</i> genotypes in the study cohort and according to the ethnicity (Caucasian versus African origin).</p

ABCB1 expression analysis by fluorescence microscopy.

<p>(<b>A</b>) Untransfected (CTL) HEK293, (<b>B</b>) transfected with empty plasmid (CTL pcDNA3.1) HEK pcDNA3.1 (<b>C</b>) HEK_1199G and (<b>D</b>) HEK_1199A cells were stained with anti-ABCB1 antibodies (green fluorescence) as described in materials and methods. DAPI was used to stain nuclei (blue).</p