TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-β, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-β-driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-β in fibrosis, highlighting mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation.

https://rupress.org/jem/article-pdf/217/3/e20190103/1050682/jem_20190103.pdf

Transforming growth factor–β in tissue fibrosis

The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is charged with reviewing, updating and categorizating indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence‐based approach in the grading and categorization of indications. This Sixth Edition of the ASFA Special Issue has further improved the process of using evidence‐based medicine in the recommendations by consistently applying the category and GRADE system definitions, but eliminating the “level of evidence” criteria (from the University HealthCare Consortium) utilized in prior editions given redundancy between GRADE and University HealthCare Consortium systems. The general layout and concept of a fact sheet that was utilized in the Fourth and Fifth Editions, has been largely maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. This article consists of 78 fact sheets (increased from 2010) for therapeutic indications in ASFA categories I through IV, with many diseases categorized having multiple clinical presentations/situations which are individually graded and categorized. J. Clin. Apheresis 28:145–284, 2013. © 2013 Wiley Periodicals, Inc.

Guidelines on the use of therapeutic apheresis in clinical practice - Evidence-based approach from the writing committee of the american society for apheresis

Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant–important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele–associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

/pdf/focal-segmental-glomerulosclerosis-b7nhhet8lx.pdf

Focal Segmental Glomerulosclerosis

Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%-90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis.

Minimal Change Disease

Change your habit to hang or waste the time to only chat with your friends. It is done by your everyday, don't you feel bored? Now, we will show you the new habit that, actually it's a very old habit to do that can make your life more qualified. When feeling bored of always chatting with your friends all free time, you can find the book enPDF renal pathology with clinical and functional correlations and then read it.

http://ajcp.oxfordjournals.org/content/ajcpath/102/6/861.1.full.pdf

Renal Pathology with Clinical and Functional Correlations

A focalis segmentalis glomerulosclerosis fenymikroszkopos vizsgalattal lathato jellegzetes morfologiaju glomeruluskarosodas, tobbfele szovettani altipussal es valtozo klinikai keppel. A kulonboző szovettani variansokat ujabban rendszereztek (Columbia-klasszifikacio). A glomeruluskarosodas mindegyik variansnal a podocytakat erinti, ezert ujabban a focalis segmentalis glomerulosclerosist a podocytopathiak fő tipusanak tartjak. A primer (ismeretlen eredetű) formak mellett egyre nő a secunder focalis segmentalis glomerulosclerosisok szama is. A terapias lehetősegek kozott uj elem az altalanos vesevedő kezeles kiterjedt alkalmazasa es egyes primer idiopathias esetekben a szteroidkezeles megnyujtasa.

Focal segmental glomerulosclerosis

ObjectivesTo analyse the effect of an organized, nationwide breast cancer screening programme on non-organized mammography activities in Hungary.SettingThe nationwide dataset of the Hungarian National Health Insurance Fund Administration covering the years 2000-2005.MethodsData derived from the nationwide database of the Hungarian National Health Insurance Fund Administration. The study includes all women undergoing mammography before (2000-2001) and after (2002-2003/2004-2005) the introduction of organized screening.ResultsThe number of women having non-organized (opportunistic/diagnostic) mammograms was around 250,000 in 2000-2001, but increased to 350,000 in 2005. In the age group 45-64 years in 2000-2001, only 27.4% of all women undergoing mammography were examined within locally-organized programmes. After the introduction of the nationwide programme, this percentage increased to 61.0% in 2002-2003, and 56.3% in 2004-2005. After the introduction of the nationwide organized programme (2002-2003), the ...

https://journals.sagepub.com/doi/pdf/10.1258/jms.2008.007070

The effect of an organized, nationwide breast cancer screening programme on non-organized mammography activities

/pdf/age-group-specific-gap-between-treatment-cost-of-and-1p458uqtgs.pdf

Age Group–Specific Gap Between Treatment Cost of and Mortality Due to Breast and Colorectal Cancer

Background. The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. Methods. Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n ¼ 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. Results. Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). Conclusions. Phenacetin should be banned. Our study results support the need for longitudinal cohort and case–control studies in Hungary.

/pdf/analgesic-nephropathy-in-hungary-the-hans-study-1obdo81y0z.pdf

Analgesic nephropathy in Hungary: the HANS study

Contrast medium induced nephropathy. The wide-spread use of invasive diagnostic and therapeutic procedures makes the use of contrast media more common. Acute renal failure may develop following their intravascular administration, referred as contrast medium induced nephropathy or briefly contrast nephropathy. It develops especially in patients with diabetic nephropathy, in cases of volume depletion and in chronic renal insufficiency. Contrast nephropathy is the third most common cause of acute renal failure acquired in hospital. In their present work current literature, pathogenesis, clinical characteristics and potential ways of prevention are reviewed.

Contrast medium induced nephropathy

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