Pflugers Archiv : European journal of physiology最新文献_第3页

Spatially dependent tissue distribution of thyroid hormones by plasma thyroid hormone binding proteins. 血浆甲状腺激素结合蛋白对甲状腺激素空间依赖性组织分布的影响。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2025-01-03 DOI: 10.1007/s00424-024-03060-6

Anish D Bagga, Brian P Johnson, Qiang Zhang

{"title":"Spatially dependent tissue distribution of thyroid hormones by plasma thyroid hormone binding proteins.","authors":"Anish D Bagga, Brian P Johnson, Qiang Zhang","doi":"10.1007/s00424-024-03060-6","DOIUrl":"10.1007/s00424-024-03060-6","url":null,"abstract":"Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings. (1) Contrary to postulations that TTR and/or ALB are the major local T4 contributors, the three THBPs may unload comparable amounts of T4 in Liver, a rapidly perfused organ; however, their contributions in slowly perfused tissues follow the order of abundances of T4TBG, T4TTR, and T4ALB. The T3 amounts unloaded from or loaded onto THBPs in a tissue acting as a T3 sink or source respectively follow the order of abundance of T3TBG, T3ALB, and T3TTR regardless of perfusion rate. (2) Any THBP alone is sufficient to maintain spatially uniform TH tissue distributions. (3) The TH amounts unloaded by each THBP species are spatially dependent and nonlinear in a tissue, with ALB being the dominant contributor near the arterial end but conceding to TBG near the venous end. (4) Spatial gradients of TH transporters and metabolic enzymes may modulate these contributions, producing spatially invariant or heterogeneous TH tissue concentrations depending on whether the blood-tissue TH exchange operates in near-equilibrium mode. In summary, our modeling provides novel insights into the differential roles of THBPs in local TH tissue distribution.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"453-478"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Personalising dietary advice for disease prevention: concepts and experiences.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2025-01-25 DOI: 10.1007/s00424-025-03064-w

Hannelore Daniel

{"title":"Personalising dietary advice for disease prevention: concepts and experiences.","authors":"Hannelore Daniel","doi":"10.1007/s00424-025-03064-w","DOIUrl":"10.1007/s00424-025-03064-w","url":null,"abstract":"Personalised nutrition (PN) as a new endeavour emerged in the background of the human genome project with the ease to analyse genetic heterogeneity. First commercial offers with recommendations for diet and lifestyle changes, usually based on a few polymorphisms, entered markets soon after the presentation of the human genome blueprint. Although PN has seen many attempts, meanwhile, with the inclusion of other biomedical measures such as microbiome and/or continuous glucose monitoring, scientific assessments of such approaches in various settings revealed limited success. Although personalisation improved general compliance over generic advice, particular benefits in referring to biomedical measures and individual risks did, in most cases, not provide any significant advantage. Moreover, scholars criticised such approaches as of limited impact from a public health perspective by attracting mainly technology-open individuals of high social status and proper financial capabilities. Based on these experiences, new avenues for personalising dietary advice are developed, and those are going beyond pure biomedical data by assessing the entire food environment of the individual with its capabilities and constraints in the given life setting. Embedded into digital environments for data collection but also for bidirectional communication, new possibilities emerge. Artificial intelligence methods allow for the multitude of input data and highly complex decision trees to be derived to customize advice. And that can be delivered on the spot and in time in any language whenever decisions are made on what to buy or what to eat. But systems can also be employed to increase physical activity levels and for the adoption of a more healthy lifestyle in general.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"335-339"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels. 对健康年轻男性进行有控制的饮食磷酸盐负荷可提高血浆磷酸盐和 FGF23 水平。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2024-11-27 DOI: 10.1007/s00424-024-03046-4

Jennifer Scotti Gerber, Eva Maria Pastor Arroyo, Johanne Pastor, Miguel Correia, Stefan Rudloff, Orson W Moe, Daniela Egli-Spichtig, Nilufar Mohebbi, Carsten A Wagner

{"title":"Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels.","authors":"Jennifer Scotti Gerber, Eva Maria Pastor Arroyo, Johanne Pastor, Miguel Correia, Stefan Rudloff, Orson W Moe, Daniela Egli-Spichtig, Nilufar Mohebbi, Carsten A Wagner","doi":"10.1007/s00424-024-03046-4","DOIUrl":"10.1007/s00424-024-03046-4","url":null,"abstract":"Increased dietary inorganic phosphate (Pi) intake stimulates renal Pi excretion, in part, by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) or dopamine. High dietary Pi may also stimulate sympathetic outflow. Rodent studies provided evidence for these regulatory loops, while controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake. The effects of controlled, isolated changes in dietary Pi intake over shorter periods are unknown. We studied the effects of a low or high Pi diet on parameters of mineral metabolism in 10 healthy young men. Participants received a standardized diet (1000 mg phosphorus equivalent/day) supplemented with either a phosphate binder (low Pi diet) or phosphate capsules (750 mg phosphorus, high Pi diet) in a randomized cross-over trial for 5 days with a 7-day washout between diets. High Pi intake increased plasma Pi levels and 24-h excretion and decreased urinary calcium excretion. High Pi intake increased intact FGF23 (iFGF23) and suppressed plasma Klotho without affecting cFGF23, PTH, calcidiol, calcitriol, Fetuin-A, dopamine, epinephrine, norepinephrine, metanephrine, or aldosterone. Higher iFGF23 correlated with lower calcitriol and higher PTH. These data support a role for iFGF23 in increasing renal Pi excretion and reducing calcitriol in healthy young men during steady-state high dietary Pi intake. High dietary Pi intake elevated blood Pi levels in healthy young subjects with normal renal function and may therefore be a health risk, as higher serum Pi levels are associated with cardiovascular risk in the general population.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"495-508"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction. 25-羟基胆固醇调节小鼠神经肌肉连接处突触囊泡内吞作用。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2025-01-09 DOI: 10.1007/s00424-024-03058-0

Eva A Kuznetsova, Guzalia F Zakirjanova, Andrei N Tsentsevitsky, Alexey M Petrov

{"title":"25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction.","authors":"Eva A Kuznetsova, Guzalia F Zakirjanova, Andrei N Tsentsevitsky, Alexey M Petrov","doi":"10.1007/s00424-024-03058-0","DOIUrl":"10.1007/s00424-024-03058-0","url":null,"abstract":"Many synaptic vesicles undergo exocytosis in motor nerve terminals during neuromuscular communication. Endocytosis then recovers the synaptic vesicle pool and presynaptic membrane area. The kinetics of endocytosis may shape neuromuscular transmission, determining its long-term reliability. Here, using fluorescent dyes, the time course of endocytosis induced by intense activity of the phrenic nerve was studied at the mouse diaphragm neuromuscular junction. It was found that a significant portion of endocytic events occurs after the end of tetanic stimulation. Pitstop 2, clathrin inhibitor, and more profoundly dynole 34-2, dynamin antagonist, suppressed endocytic FM1-43 dye uptake both during and after tetanus. Furthermore, synaptic vesicles formed in the presence of the endocytic blockers released FM-dye during subsequent evoked exocytosis at a lower rate. 25-Hydroxycholesterol (25HC) is an oxysterol, ubiquitously synthetized from excessive cholesterol. In addition, its production greatly increases by activated macrophages. 25HC accelerated FM-dye endocytosis and its sequential evoked exocytosis, and dynole (but not pitstop) prevented 25HC-mediated enhancement of endocytic FM-dye uptake. The positive effects of 25HC were interfered with chelation of cytosolic Ca2+ with a slow Ca2+ buffer EGTA-AM, Ca2+ antagonist TMB8, and sphingomyelin-hydrolyzing enzyme. In contrast to amphiphilic FM1-43 dye capture, 25HC reduced uptake of hydrophilic high molecular weight markers (labeled dextrans and toxin), which utilize bulk endocytosis to enter into nerve terminals. Thus, synaptic vesicle endocytosis had a relatively slow kinetics following the tetanic activity and can be accelerated by 25HC. The positive effect of 25HC on endocytosis engages a dynamin-dependent pathway, interconnected with cytoplasmic Ca2+ and sphingomyelin integrity.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"421-439"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of tDCS on glutamatergic pathways in epilepsy: neuroprotective and therapeutic potential. tDCS对癫痫中谷氨酸能通路的影响：神经保护和治疗潜力。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2024-12-07 DOI: 10.1007/s00424-024-03049-1

Filiz Demirdogen, Guven Akcay

{"title":"Effects of tDCS on glutamatergic pathways in epilepsy: neuroprotective and therapeutic potential.","authors":"Filiz Demirdogen, Guven Akcay","doi":"10.1007/s00424-024-03049-1","DOIUrl":"10.1007/s00424-024-03049-1","url":null,"abstract":"Epilepsy is a chronic neurological disease characterized by recurrent seizures caused by abnormal electrical activity in the brain. The aim of our study was to investigate the effect of tDCS on oxidative stress, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels in kindling-induced epilepsy model. Behavioral tests evaluated motor and cognitive functions, while assessing oxidative stress, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels in hippocampal tissue. tDCS stimulation therapy demonstrates a neuroprotective effect on motor and cognitive function postepilepsy. Our study reveals an increase in TOC, Ca2+, glutamate, GABA, AMPAR1, and NMDAR1 levels and a decline in total antioxidant capacity (TAC) following PTZ-induced seizures. However, tDCS treatment led to a significant decrease of Ca2+, total oxidant capacity (TOC), glutamate, GABA, AMPAR1, and NMDAR1 levels in the epilepsy cohorts, while simultaneously causing a spike in TAC levels. The study's results showed that tDCS treatment could have a therapeutic effect on oxidative stress, Ca2+, TOC, glutamate, GABA, AMPAR1, NMDAR1, and TAC in both acute and chronic kindling epilepsy models.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"341-348"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The lateral habenula regulates stress-related respiratory responses via the monoaminergic system. 外侧哈文脑通过单胺能系统调节与压力有关的呼吸反应。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2024-11-19 DOI: 10.1007/s00424-024-03043-7

Riko Mizukami, Masayuki Matsumoto, Tadachika Koganezawa

{"title":"The lateral habenula regulates stress-related respiratory responses via the monoaminergic system.","authors":"Riko Mizukami, Masayuki Matsumoto, Tadachika Koganezawa","doi":"10.1007/s00424-024-03043-7","DOIUrl":"10.1007/s00424-024-03043-7","url":null,"abstract":"Psychologic stress induces behavioral and autonomic responses such as acceleration of respiration. The lateral habenula (LHb) is noted to be involved in stress-induced behavioral responses. However, its involvement in stress-induced respiratory responses is unknown. In this study, we aimed to analyze whether and how the LHb regulates respiration. Electrical stimulation of the LHb of anesthetized Wistar male rats increased respiratory frequency and minute ventilation, calculated by respiratory frequency × thoracic movement amplitude. Systemic administration of a dopaminergic receptor antagonist, clozapine, suppressed the LHb-induced respiratory responses. On the other hand, administration of a serotonergic receptor antagonist, methysergide, significantly accelerated the LHb-induced increase in respiratory frequency, together with suppressing the thoracic movement amplitude. To clarify the source of dopaminergic modulation, we inhibited the ventral tegmental area (VTA), which contains dopaminergic neurons and receives inputs from the LHb, by administering microinjections of a GABAA agonist, muscimol. The bilateral inhibition of the VTA almost abolished the LHb-induced respiratory responses. These results suggest that LHb activation causes respiration acceleration, mainly mediated by dopaminergic neurons in the VTA and suppressively modulated by the serotonergic system. Neural circuits originating in the LHb may be a key modulator for respiration during psychological stress.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"441-452"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lateral hypothalamic area high-frequency deep brain stimulation rescues memory decline in aged rat: behavioral, molecular, and electrophysiological study. 下丘脑外侧区高频深部脑刺激恢复老年大鼠记忆衰退：行为学、分子和电生理研究。

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-03-01 Epub Date: 2025-01-21 DOI: 10.1007/s00424-024-03059-z

Abdelaziz M Hussein, Ahmed F Abouelnaga, Walaa Obydah, Somaya Saad, Marwa Abass, Asmaa Yehia, Eman M Ibrahim, Ahmed T Ahmed, Osama A Abulseoud

{"title":"Lateral hypothalamic area high-frequency deep brain stimulation rescues memory decline in aged rat: behavioral, molecular, and electrophysiological study.","authors":"Abdelaziz M Hussein, Ahmed F Abouelnaga, Walaa Obydah, Somaya Saad, Marwa Abass, Asmaa Yehia, Eman M Ibrahim, Ahmed T Ahmed, Osama A Abulseoud","doi":"10.1007/s00424-024-03059-z","DOIUrl":"10.1007/s00424-024-03059-z","url":null,"abstract":"To examine the effect of DBS of the lateral hypothalamic area (LHA) on age-related memory changes, neuronal firing from CA1, oxidative stress, and the expression of Hsp70, BDNF, and synaptophysin. 72 male rats were randomly allocated into 6 equal groups: a) normal young group (8 W), b) sham young group, c) DBS young group, d) normal old group (24 months), e) sham old group and f) DBS old group. Memory tests (passive avoidance and Y maze), oxidative stress markers (MDA, catalase, and GSH) and expression of Nrf2, HO-1, Hsp70, BDNF, and synaptophysin were measured by the end of the experiment. Also, in vivo recording of the neuronal firing of the CA1 region in the hippocampus was done. Old rats show significant decline in memories, antioxidant genes (Nrf2 and HO-1), antioxidants (GSH and catalase), Hsp70, BDNF, and synaptophysin with significant increase in MDA in hippocampus (p < 0.05) and DBS for LHA caused a significant improvement in memories in old rats, with significant rise in fast gamma and theta waves in CA1 region in old rats (p < 0.05). This was associated with a significant increase in antioxidants (GSH and CAT), antioxidant genes (Nrf2, HO-1), Hsp70, BDNF, and synaptophysin with significant reduction in MDA in hippocampus (p < 0.05). DBS for LHA ameliorates the age-induced memory decline. This might be due to increase in fast gamma in CA1, attenuation of oxidative stress, upregulation of Nrf2, HO-1, Hsp70, BDNF, and synaptophysin in the hippocampus.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"371-391"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Obituary: Stefan Silbernagl - physiologist, gentleman, aesthete.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-02-28 DOI: 10.1007/s00424-025-03070-y

Michael Gekle

引用次数: 0

Emerging roles of PCSK9 in kidney disease: lipid metabolism, megalin regulation and proteinuria.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-02-18 DOI: 10.1007/s00424-025-03069-5

Sandra Hummelgaard, Jean-Claude Kresse, Michael Schou Jensen, Simon Glerup, Kathrin Weyer

{"title":"Emerging roles of PCSK9 in kidney disease: lipid metabolism, megalin regulation and proteinuria.","authors":"Sandra Hummelgaard, Jean-Claude Kresse, Michael Schou Jensen, Simon Glerup, Kathrin Weyer","doi":"10.1007/s00424-025-03069-5","DOIUrl":"https://doi.org/10.1007/s00424-025-03069-5","url":null,"abstract":"Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD). Key features of CKD include proteinuria and reduced glomerular filtration rate, both of which are linked to disease progression and adverse outcomes. Dyslipidemia, a major CVD risk factor, often correlates with CKD severity and is inadequately addressed by conventional therapies. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in lipid metabolism by modulating low-density lipoprotein receptor (LDLR) levels and has emerged as a therapeutic target for managing dyslipidemia. PCSK9 inhibitors, including monoclonal antibodies and siRNA, effectively lower LDL cholesterol levels and have demonstrated safety in patients with mild to moderate CKD. Recent findings indicate that PCSK9 aggravates proteinuria by interacting with and downregulating megalin, a proximal tubule receptor essential for protein reabsorption in the kidney. Inhibition of PCSK9 has been shown to preserve megalin levels, reduce proteinuria, and improve the disease phenotype in experimental models. However, conflicting data from preclinical studies underscore the need for further research to clarify the mechanisms underlying PCSK9's role in kidney disease. This review highlights the potential of PCSK9 inhibition in addressing proteinuria and dyslipidemia in CKD, emphasizing its promise as a therapeutic strategy, while addressing current challenges and future directions for research.","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The obesity pandemic and its impact on non-communicable disease burden.

IF 2.9 4区医学

Pflugers Archiv : European journal of physiology Pub Date : 2025-02-10 DOI: 10.1007/s00424-025-03066-8

Staffan Hildebrand, Alexander Pfeifer

引用次数: 0