Peritoneal Sclerosis in a Patient on Long-term Continuous Ambulatory Peritoneal Dialysis (CAPD). : An Autopsy Case.

若年性ネフロン癆による慢性腎不全でCAPD (continuous ambulatory peritoneal dialysis)導入し, 6年6ヵ月後に死亡した20歳男性の1剖検例を報告した。CAPD導入数カ月後, 腹膜炎による除水能低下を起こしたが, 約5ヵ月後に回復した。CAPD導入1年5ヵ月以降重症な腹膜炎罹患により除水能低下状態が遷延したが, 次第に回復した。しかし, 体液貯留傾向のため, 3年2ヵ月後より高張透析液を使用し除水量の増加を得たが, 3年9ヵ月後に不可逆的な除水能低下状態となった。一方, クレアチニンの透析排液/血漿濃度比(D/P)から見た溶質除去能は, その約半年後まで保たれており, 血清クレアチニン値の上昇は軽度であった。剖検にて腹膜の線維性肥厚と高度の内腔狭窄を伴う動静脈硬化を認め, 腹膜硬化症と診断した。本例の腹膜硬化症は, 頻回の腹膜炎と高張透析液の使用が主な原因と考えられた。腹膜機能を長期に維持するためには, 腹膜炎の予防と高張透析液の使用を最小限にすることが重要と考えられた。A 20-year-old man, treated with continuous ambulatory peritoneal dialysis (CAPD) for 6.5 years because of-end-stage renal disease due to juvenile nephronophthysis, died of ultrafiltration failure, and the morphological examination of peritoneum was carried out at autopsy. Nine episodes of peritonitis developed, and ultrafiltration transiently decreased after each episodes. At 2 years after the start of CAPD, severe peritonitis occurred, and then his body weight and blood pressure gradually increased. At 4 years after the beginning of CAPD, when hyperosmotic dialysate was frequently used, ultrafiltration was irreversively deteriorated. On the other hand, creatinine dialysate/plasma ratio remained within normal limits for about several months, and the increase in the level of serum creatinine was very little. The peritoneum obtained at autopsy revealed marked fibrous thickening as well as the conspicuous luminal narrowing of arteries and veins due to intimal thickening. The development of peritoneal sclerosis seemed to be related with the frequency and severity of peritonitis and the use of hyperosmotic dialysate

Phenotypic and functional features of M1 and M2 macrophages.

<p><b>A</b>: The effect of an overnight IFNγ priming step was tested on C57Bl/6 mouse bone marrow-derived MØ subjected to M1- or M2-polarizing conditions. The expression of iNOS, ArgI, ArgII, and Ym1/2 were determined by real time RT-PCR on RNA extracted 10 hours after the induction of polarization. Data were calculated using the 2^−ΔΔCt Pfaffl formula <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008852#pone.0008852-Pfaffl1" target="_blank">[30]</a> in which experimental conditions (M1 and M2) are compared to Ct values obtained in M0 MØ and normalized to the Ct values of the HPRT house-keeping gene. <b>B</b>: Primary aortic vascular smooth muscle cells (VSMCs) from C57Bl/6 mice were cultured for 48 hours in the presence of media conditioned by C57Bl/6 M1 or M2 MØ which were polarized in the presence of the PPARγ agonist pioglitazone (Pio), the PPARγ antagonist GW9662 (GW), or the arginase inhibitor Nor-NOHA. As controls, VSMCs were also cultured with the same concentration of the polarizing agents, of the PPARγ agonists and antagonists, or of the arginase inhibitor. At the end of the assay, the number of viable cells in each condition was evaluated by the MTT assay and by using a standard curve established with known numbers of cells. *; **: p<0.05; p<0.01 vs matched medium conditioned by MØ polarized in the standard way (−). Note that the number of cells obtained with the M2-conditioned medium were significantly greater than with M1-conditioned medium (p<0.01 vs matched condition).</p

Preserved plasticity of fully polarized macrophages.

<p>MØ^ApoE (white) and MØ^B6 (black) were primed and subjected to a first M1 or M2 polarization. After ten hours, the culture conditions were switched during 10 additional hours in order to induce the opposite phenotype. Expression of iNOS, Arg I and ArgII was evaluated by real time PCR and normalized by HPRT (au: arbitrary unit). Results are representative of three distinct experiments.</p

Macrophages of early atherosclerotic lesions in ApoE KO mice express Arg I while Arg II predominates in late stages.

<p><b>A</b>: Immunofluorescence of atherosclerotic lesions from 20 and 55 week-old ApoE KO mice. MØ were identified as Mac3⁺ (red) cells. Co-expression of Mac3 and Arg I (violet) and/or Arg II (green) were identified by image overlay. Merge: overlay of bright field, DAPI, Mac3, Arg I and Arg II stainings. Inset: magnification of the zone delimited in the “Merge” frame. <b>B</b>: Arg I, Arg II and Arg I⁺ Arg II⁺ double positive surface areas within 3 random fields/plaque of 20 (white) and 55 (grey) week-old mice. <b>C, D</b>: Regression analysis between the surface area of plaques (X-axis) and total MØ area (Mac3, C) or the Arg I⁺/Arg II⁺ ratio (D). R²: regression correlation coefficient. <b>E</b>: Expression of IL-4 and IFNγ transcripts on microdissected atherosclerotic lesions from 20 and 55 week-old ApoE KO mice determined by real time PCR and normalized by HPRT (au: arbitrary unit). **; ***: p<0.001; p<0.0001 vs 20 w. <b>F–I</b>: Microdissection of aortic atherosclerotic lesions. Lesions can be detected (delimited by black dashes) through the vascular wall in the dissected aortic root (white dashes). The vascular wall was opened longitudinally to expose the luminal side of the vessel (G). The aortic cusps are readily identified. Arrow heads indicate the plane of fracture at the lesion/media interface, which allows the separation of the lesion from the media. The arrows in H indicate the movement performed with tweezers to detach the lesion. Appearance of the vessel after the dissection of the lesion is shown in I.</p

Kinetic expression of M1 and M2 markers.

<p>Bone marrow-derived MØ from C57BL/6 mice (MØ^B6, closed circles) and ApoE KO mice (MØ^ApoE, open circles) were differentiated, primed with IFNγ and polarized or not (No polarization) towards the M1 (M1 polarization) or the M2 phenotype (M2 polarization). Expression of Arg I, iNOS, Arg II were determined by real time PCR and normalized by HPRT (au: arbitrary unit). IL-6 was monitored in cell culture supernatant by ELISA. Results are representative of three independent experiments.</p

ApoE modulates the expression of PPARγ.

<p><b>A</b>: Expression of IL-4Rα1 and of IL-13Rα1 in non-polarized MØ^B6 and MØ^ApoE determined by real time PCR and normalized by HPRT (au: arbitrary unit). <b>B</b>: Expression of PPARγ in non-polarized MØ from MØ^B6 (black) and MØ^ApoE (white) mice with increasing doses of recombinant ApoE (rApoE) determined by real time PCR and normalized by HPRT (au: arbitrary unit). **: p<0.001; ***: p<0.0001 vs MØ^B6. <b>C</b>: Expression of ArgI in M1 and M2 MØ^B6 (black) and MØ^ApoE (white) mice polarized with or without (−) pioglitazone (Pio) or GW9662 (GW) determined by real time PCR. The Results are expressed as 2^−ΔΔCt<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008852#pone.0008852-Pfaffl1" target="_blank">[30]</a>. *: p<0.05; **: p<0.001 vs matched MØ^B6 condition; †: p<0.05; ††: p<0.01 vs matched M1 condition.</p

Table <b>1.</b> Baseline characteristics of patients.

<p>Table <b>1.</b> Baseline characteristics of patients.</p

DFX/VD association induces myeloid differentiation and increases overall survival in elderly AML patients.

<p>(A) Kaplan-Meier estimated OS in DFX/VD and BSC treated patients (B) Multivariate analysis. Forest plot of the odds ratio. (C) OS within subgroups presenting normal VD levels (≥50 nmol/L) or VD deficiency (≤50 nmol/L). (D) Monocytes numbers in VD/DFX treated patients (F) Creatinine levels in treated patients.</p