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Editor's Notes

• #6: §³§ç§Ö§Þ§Ñ §Ò§Ú§à-§Ú§ß§Ø§Ö§ß§Ö§â§ß§à§Û §á§à§é§Ü§Ú §á§â§à§Õ§å§è§Ú§â§å§ð§ë§Ö§Û bone morphogenic protein (BMP). §¬§â§à§Ó§î §á§Ñ§è§Ú§Ö§ß§ä§Ñ (§Ü§â§Ñ§ã§ß§à§Ô§à §è§Ó§Ö§ä§Ñ) §ã§ß§Ñ§é§Ñ§Ý§Ñ §Ó§ç§à§Õ§Ú§ä §Ó §Ô§Ö§Þ§à§æ§Ú§Ý§î§ä§â (§ã§Ý§Ö§Ó§Ñ), §Ô§Õ§Ö §Ú§Ù §Ü§â§à§Ó§Ú §à§ä§Õ§Ö§Ý§ñ§Ö§ä§ã§ñ §å§Ý§î§ä§â§Ñ§æ§Ú§Ý§î§ä§â§Ñ§ä §¬§â§à§Ó§î §Ú §å§Ý§î§ä§â§Ñ§æ§Ú§Ý§î§ä§â§Ñ§ä (§Ø§Ö§Ý§ä§í§Û), §á§à§Ü§Ú§Õ§Ñ§ð§ä §Ô§Ö§Þ§à§æ§Ú§Ý§î§ä§â, §Ú §ä§Ö§Ü§å§ä §Ó §Ò§Ú§à§â§Ö§Ñ§Ü§ä§à§â (§ã§á§â§Ñ§Ó§Ñ), §Ü§à§ä§à§â§í§Û §ã§à§Õ§Ö§â§Ø§Ú§ä §á§à§Ý§à§Ó§à§Ý§à§Ü§ß§Ú§ã§ä§í§Ö §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§í §Ù§Ñ§ã§Ö§Ý§Ö§ß§ß§í§Ö §ß§Ñ §Ó§ß§å§ä§â§Ö§ß§ß§Ú§ç §á§à§Ó§Ö§â§ç§ß§à§ã§ä§ñ§ç §Ü§Ý§Ö§ä§Ü§Ñ§Þ§Ú §ï§á§Ú§ä§Ö§Ý§Ú§ñ §á§à§é§Ö§é§ß§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó (§Ù§Ö§Ý§Ö§ß§í§Ö). §¬§Ý§Ö§ä§Ü§Ú §ã§Ö§Ü§â§Ö§ä§Ú§â§å§ð§ä BMP-7 (§æ§Ú§à§Ý§Ö§ä§à§Ó§í§Û), §Ü§à§ä§à§â§í§Û §à§Ò§à§Ô§Ñ§ë§Ñ§Ö§ä §å§Ý§î§ä§â§Ñ§æ§Ú§Ý§î§ä§â§Ñ§ä §Ó§à §Ó§â§Ö§Þ§ñ §à§Ò§â§Ñ§Ò§à§ä§Ü§Ú §Ú §á§Ö§â§Ö§ç§à§Õ§Ú§ä §Ó §Ü§â§à§Ó§î, §ä§Ö§Ü§å§ë§å§ð §ã §Ó§ß§Ö§ê§ß§Ö§Û §ã§ä§à§â§à§ß§í §Þ§Ö§Þ§Ò§â§Ñ§ß§í §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§à§Ó. §¬§â§à§Ó§î §à§Ò§à§Ô§Ñ§ë§Ö§ß§ß§Ñ§ñ BMP-7 §ä§Ö§é§Ö§ä §à§Ò§â§Ñ§ä§ß§à §Ó §à§â§Ô§Ñ§ß§Ú§Ù§Þ §á§Ñ§è§Ú§Ö§ß§ä§Ñ, §Ú §à§ä§â§Ñ§Ò§à§ä§Ñ§ß§ß§í§Û §å§Ý§î§ä§â§Ñ§æ§Ú§Ý§î§ä§â§Ñ§ä (§à§â§Ñ§ß§Ø§Ö§Ó§í§Û) §å§Õ§Ñ§Ý§ñ§Ö§ä§ã§ñ. §µ§Ó§Ö§Ý§Ú§é§Ö§ß§ß§à§Ö §ã§Ö§é§Ö§ß§Ú§Ö §á§à§Ý§à§Ô§à §Ó§à§Ý§à§Ü§ß§Ñ §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§Ñ §Ò§Ú§à§â§Ö§Ñ§Ü§ä§à§â§Ñ §á§à§Ü§Ñ§Ù§Ñ§ß§à §Ó §á§â§Ñ§Ó§à§Þ §ß§Ú§Ø§ß§Ö§Þ §å§Ô§Ý§å. §µ§Ý§î§ä§â§Ñ§æ§Ú§Ý§î§ä§â§Ñ§ä §á§â§à§ä§Ö§Ü§Ñ§Ö§ä §Ó §á§â§à§ã§Ó§Ö§ä§Ö §á§à§Ý§í§ç §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§à§Ó §Ñ §Ü§â§à§Ó§î §ä§Ö§é§Ö§ä §ã§ß§Ñ§â§å§Ø§Ú. §£§ß§å§ä§â§Ö§ß§ß§ñ§ñ §á§à§Ó§Ö§â§ç§ß§à§ã§ä§î §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§Ñ §á§à§Ü§â§í§ä§Ñ §ã§Ý§à§Ö§Þ §Ü§Ý§Ö§ä§à§Ü §Ü§Ñ§ß§Ñ§Ý§î§è§Ú§Ö§Ó§à§Ô§à §ï§á§Ú§ä§Ö§Ý§Ú§ñ §ã§Ö§Ü§â§Ö§ä§Ú§â§å§ð§ë§Ú§ç BMP-7, §Ú BMP-7 §à§Ò§à§Ô§Ñ§ë§Ñ§Ö§ä §å§Ý§î§ä§â§Ñ§æ§Ú§Ý§î§ä§â§Ñ§ä §Ú §Ü§â§à§Ó§î §Ó §Ò§Ú§à§â§Ö§Ñ§Ü§ä§à§â§Ö. BMP-7 §Ó §å§Ý§î§ä§â§Ñ§æ§Ú§Ý§î§ä§â§Ñ§ä§Ö §Ò§å§Õ§Ö§ä §â§Ö§Ô§å§Ý§Ú§â§à§Ó§Ñ§ä§î §á§â§à§Ú§Ù§Ó§à§Õ§Ú§ä§Ö§Ý§î§ß§à§ã§ä§î HPTC (Human primary renal proximal tubule cells (HPTCs), §ä§Ñ§Ü §Ü§Ñ§Ü BMP-7 §Ò§å§Õ§Ö§ä §Õ§à§ã§ä§Ñ§Ó§Ý§ñ§ä§î§ã§ñ §Ó §Ü§â§à§Ó§î §á§Ñ§è§Ú§Ö§ß§ä§Ñ. Tasnim et al. Fibrogenesis & Tissue Repair 2010 3 :14 ? Kidney Int. 2003 Jun;63(6):2037-49. Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy. http://www.ncbi.nlm.nih.gov/pubmed/12753291 Wang S, Chen Q, Simon TC, Strebeck F, Chaudhary L, Morrissey J, Liapis H, Klahr S, Hruska KA. Renal Division, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Abstract BACKGROUND: Bone morphogenic protein-7 (BMP-7), an essential developmental renal morphogen, is a secreted differentiation factor of the adult collecting duct. It activates receptors in the collecting duct, distal nephron, proximal tubule, and glomerulus. BMP-7 is therapeutic in tubulointerstitial nephritis raising the question of broader efficacy in chronic kidney disease (CKD). METHODS: Diabetes was induced in 200 g rats by a single dose of streptozotocin. After 16 weeks, glomerular hypertrophy and proteinuria were established, and therapy with BMP-7 (10, 30, or 100 microg/kg intravenously twice a week), enalapril (20 mg/kg), or vehicle was begun and continued until 32 weeks. Kidney weight, glomerular filtration rate (GFR), urine albumin excretion, blood pressure, pathology, and BMP-7 expression were measured. RESULTS: Diabetic vehicle-treated rats developed renal insufficiency by 32 weeks (GFR, 0.34 +/- 0.02 mL/min/100 g body weight vs. 0.55 +/- 0.02 in normal). In the diabetic BMP-7 high-dose-treated rats, GFR was preserved (0.70 +/- 0.08, P < 0.01 vs. vehicle), and higher than diabetic enalapril-treated rats (0.58 +/- 0.06). Kidney weights of vehicle-treated animals were not affected, but were reduced in all of the treatment groups (P < 0.001). Proteinuria was reversed to normal by BMP-7 in a dose-dependent manner. The reduction in proteinuria by the intermediate dose of BMP-7 was similar to the effect of enalapril therapy. Glomerular area and interstitial volume were significantly decreased in the BMP-7 and enalapril-treated animals. Glomerular sclerosis was prevented by BMP-7 therapy more effectively than by enalapril. Enalapril controlled hypertension throughout the course of therapy while BMP-7 did not affect blood pressure until the final 4 weeks of therapy. Diabetic vehicle-treated rats lost BMP-7 expression in the kidney. BMP-7 and enalapril therapy restored BMP-7 expression at high levels. CONCLUSION: BMP-7 partially reversed diabetic-induced kidney hypertrophy, restoring GFR, urine albumin excretion, and glomerular histology toward normal. Restoration of BMP-7 expression was associated with a successful repair reaction and a reversal of the ill-fated injury response. PMID: 12753291 [PubMed - indexed for MEDLINE] The kidney is the major source of BMP-7 in the adult body, and BMP-7 appears to be important for bone homeostasis §±§à§é§Ü§Ú §ñ§Ó§Ý§ñ§Ö§ä§ã§ñ §à§ã§ß§à§Ó§ß§í§Þ §Ú§ã§ä§à§é§ß§Ú§Ü§à§Þ BMP-7 §Ó §ä§Ö§Ý§Ö §Ó§Ù§â§à§ã§Ý§à§Ô§à §é§Ö§Ý§à§Ó§Ö§Ü§Ñ, §Ú BMP-7, §Ü§Ñ§Ü §á§â§Ö§Õ§ã§ä§Ñ§Ó§Ý§ñ§Ö§ä§ã§ñ, §Ó§Ñ§Ø§ß§í§Þ §Õ§Ý§ñ §Ü§à§ã§ä§Ö§Û §Ô§à§Þ§Ö§à§ã§ä§Ñ§Ù§Ñ [ 43 - 45 ] . [ 43 - 45 ]. Animal experiments have shown that administration of BMP-7 improves kidney recovery in models of acute and chronic renal disease §¿§Ü§ã§á§Ö§â§Ú§Þ§Ö§ß§ä§í §ß§Ñ §Ø§Ú§Ó§à§ä§ß§í§ç §á§à§Ü§Ñ§Ù§Ñ§Ý§Ú, §é§ä§à §Ñ§Õ§Þ§Ú§ß§Ú§ã§ä§â§Ñ§è§Ú§ñ BMP-7 §å§Ý§å§é§ê§Ñ§Ö§ä §â§Ñ§Ò§à§ä§å §á§à§é§Ö§Ü §Ó§à§ã§ã§ä§Ñ§ß§à§Ó§Ý§Ö§ß§Ú§ñ §Ó §Þ§à§Õ§Ö§Ý§ñ§ç §à§ã§ä§â§à§Û §Ú §ç§â§à§ß§Ú§é§Ö§ã§Ü§à§Û §á§à§é§Ö§é§ß§à§Û §ß§Ö§Õ§à§ã§ä§Ñ§ä§à§é§ß§à§ã§ä§Ú [ 44 , 100 , 102 - 107 ] . [ 44 , 100 , 102 - 107 ]. BMP-7 also has positive effects on vascular calcification and bone disease associated with chronic kidney failure in animal models BMP-7 §ä§Ñ§Ü§Ø§Ö §Ú§Þ§Ö§Ö§ä §á§à§Ý§à§Ø§Ú§ä§Ö§Ý§î§ß§à§Ö §Ó§Ý§Ú§ñ§ß§Ú§Ö §ß§Ñ §Ü§Ñ§Ý§î§è§Ú§æ§Ú§Ü§Ñ§è§Ú§Ú §ã§à§ã§å§Õ§à§Ó §Ú §Ü§à§ã§ä§Ö§Û §Ù§Ñ§Ò§à§Ý§Ö§Ó§Ñ§ß§Ú§Ö, §ã§Ó§ñ§Ù§Ñ§ß§ß§à§Ö §ã §ç§â§à§ß§Ú§é§Ö§ã§Ü§à§Û §á§à§é§Ö§é§ß§à§Û §ß§Ö§Õ§à§ã§ä§Ñ§ä§à§é§ß§à§ã§ä§î§ð §ß§Ñ §Ø§Ú§Ó§à§ä§ß§í§ç §Þ§à§Õ§Ö§Ý§ñ§ç [ 108 - 114 ] . [ 108 - 114 ]. Stryker Biotech is currently developing BMP-7-based treatments for kidney disease. Stryker Biotech §Ó §ß§Ñ§ã§ä§à§ñ§ë§Ö§Ö §Ó§â§Ö§Þ§ñ §â§Ñ§Ù§â§Ñ§Ò§Ñ§ä§í§Ó§Ñ§Ö§ä BMP-7-§à§ã§ß§à§Ó§Ñ§ß§ß§í§Ö §Ý§Ö§é§Ö§ß§Ú§ñ §Ù§Ñ§Ò§à§Ý§Ö§Ó§Ñ§ß§Ú§Û §á§à§é§Ö§Ü. It provides products consisting of a collagen sponge releasing human recombinant BMP-7 (OP-1 Putty and OP-1 Implant) for the treatment of bone disease. §°§ß §á§â§Ö§Õ§à§ã§ä§Ñ§Ó§Ý§ñ§Ö§ä §á§â§à§Õ§å§Ü§ä§í, §ã§à§ã§ä§à§ñ§ë§Ú§Ö §Ú§Ù §Ü§à§Ý§Ý§Ñ§Ô§Ö§ß§à§Ó§à§Û §Ô§å§Ò§Ü§Ú §Ó§í§á§å§ã§Ü§Ñ§ä§î §é§Ö§Ý§à§Ó§Ö§é§Ö§ã§Ü§Ú§Û §â§Ö§Ü§à§Þ§Ò§Ú§ß§Ñ§ß§ä§ß§í§Û BMP-7 (§°§±-1 Putty §Ú §°§±-1 §Ú§Þ§á§Ý§Ñ§ß§ä§Ñ§ä§à§Ó) §Õ§Ý§ñ §Ý§Ö§é§Ö§ß§Ú§ñ §Ü§à§ã§ä§ß§í§ç §Ù§Ñ§Ò§à§Ý§Ö§Ó§Ñ§ß§Ú§Û. Treatment of kidney disease would require systemic administration of BMP-7, and in this regard, the short serum half-life of the growth factor of about 30 min is a problem. §­§Ö§é§Ö§ß§Ú§Ö §Ù§Ñ§Ò§à§Ý§Ö§Ó§Ñ§ß§Ú§ñ §á§à§é§Ö§Ü §á§à§ä§â§Ö§Ò§å§Ö§ä §ã§Ú§ã§ä§Ö§Þ§ß§à§Ö §Ó§Ó§Ö§Õ§Ö§ß§Ú§Ö BMP-7, §Ú §Ó §ï§ä§à§Û §ã§Ó§ñ§Ù§Ú, §Ü§â§Ñ§ä§Ü§à§Ö §ã§í§Ó§à§â§à§ä§Ü§Ú §á§à§Ý§å§â§Ñ§ã§á§Ñ§Õ§Ñ §æ§Ñ§Ü§ä§à§â§Ñ §â§à§ã§ä§Ñ §à§Ü§à§Ý§à 30 §Þ§Ú§ß §á§â§à§Ò§Ý§Ö§Þ§í. Treatment based on frequent administration of BMP-7 to kidney patients would be associated with high costs. §­§Ö§é§Ö§ß§Ú§Ö, §à§ã§ß§à§Ó§Ñ§ß§ß§à§Ö §ß§Ñ §é§Ñ§ã§ä§í§Ö §Ñ§Õ§Þ§Ú§ß§Ú§ã§ä§â§Ñ§è§Ú§Ú BMP-7 §ß§Ñ §á§à§é§Ü§Ú §á§Ñ§è§Ú§Ö§ß§ä§à§Ó §Ò§å§Õ§Ö§ä §ã§Ó§ñ§Ù§Ñ§ß §ã §Ó§í§ã§à§Ü§Ú§Þ§Ú §Ù§Ñ§ä§â§Ñ§ä§Ñ§Þ§Ú. A BMP-7-releasing BAK, which delivers low concentrations of the growth factor to kidney patients during extended time periods (Figure BMP-7-§Ó§í§á§å§ã§Ü§Ñ§ñ §¢§¡§¬, §Ü§à§ä§à§â§Ñ§ñ §à§Ò§Ö§ã§á§Ö§é§Ú§Ó§Ñ§Ö§ä §ß§Ú§Ù§Ü§Ú§Ö §Ü§à§ß§è§Ö§ß§ä§â§Ñ§è§Ú§Ú §æ§Ñ§Ü§ä§à§â§Ñ §â§à§ã§ä§Ñ §ß§Ñ §á§à§é§Ü§Ú §á§Ñ§è§Ú§Ö§ß§ä§à§Ó §Ó §ä§Ö§é§Ö§ß§Ú§Ö §Õ§Ý§Ú§ä§Ö§Ý§î§ß§à§Ô§à §á§Ö§â§Ú§à§Õ§Ñ §Ó§â§Ö§Þ§Ö§ß§Ú (§â§Ú§ã. 3 ), might be an elegant solution for these problems. 3 ), §Þ§à§Ø§Ö§ä §Ò§í§ä§î §ï§Ý§Ö§Ô§Ñ§ß§ä§ß§í§Þ §â§Ö§ê§Ö§ß§Ú§Ö§Þ §ï§ä§Ú§ç §á§â§à§Ò§Ý§Ö§Þ. BMP-7 could either be released in a controlled manner from the membranes or other parts of the device, using, for instance, microparticle technology. BMP-7 §Þ§à§Ø§Ö§ä §Ò§í§ä§î §Ý§Ú§Ò§à §à§ã§Ó§à§Ò§à§Ø§Õ§Ö§ß §á§à§Õ §Ü§à§ß§ä§â§à§Ý§Ö§Þ §Ú§Ù §Þ§Ö§Þ§Ò§â§Ñ§ß §Ú§Ý§Ú §Õ§â§å§Ô§Ú§ç §é§Ñ§ã§ä§Ö§Û §å§ã§ä§â§à§Û§ã§ä§Ó§Ñ, §Ú§ã§á§à§Ý§î§Ù§å§ñ, §ß§Ñ§á§â§Ú§Þ§Ö§â, §Þ§Ú§Ü§â§à§é§Ñ§ã§ä§Ú§è§í §ä§Ö§ç§ß§à§Ý§à§Ô§Ú§Ú. Alternatively, HPTCs, which normally do not express BMP-7, could be genetically engineered to achieve BMP-7 secretion. §¬§â§à§Þ§Ö §ä§à§Ô§à, HPTCs, §Ü§à§ä§à§â§í§Ö §à§Ò§í§é§ß§à §ß§Ö §Ó§í§â§Ñ§Ø§Ñ§ð§ä BMP-7, §Þ§à§Ø§Ö§ä §Ò§í§ä§î §Ô§Ö§ß§Ö§ä§Ú§é§Ö§ã§Ü§Ú §Þ§à§Õ§Ú§æ§Ú§è§Ú§â§à§Ó§Ñ§ß§ß§í§ç §Õ§Ý§ñ §Õ§à§ã§ä§Ú§Ø§Ö§ß§Ú§ñ BMP-7 §ã§Ö§Ü§â§Ö§è§Ú§Ú. A third possibility would be the inclusion of additional renal cell types (eg, distal tubule cells) that express endogenous BMP-7. §´§â§Ö§ä§î§ñ §Ó§à§Ù§Þ§à§Ø§ß§à§ã§ä§î §Ò§å§Õ§Ö§ä §Ó§Ü§Ý§ð§é§Ö§ß§Ú§Ö §Õ§à§á§à§Ý§ß§Ú§ä§Ö§Ý§î§ß§í§ç §á§à§é§Ö§é§ß§à§Û §ä§Ú§á§à§Ó §Ü§Ý§Ö§ä§à§Ü (§ß§Ñ§á§â§Ú§Þ§Ö§â, §Õ§Ú§ã§ä§Ñ§Ý§î§ß§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó §Ü§Ý§Ö§ä§Ü§Ú), §Ü§à§ä§à§â§í§Ö §Ó§í§â§Ñ§Ø§Ñ§ð§ä §ï§ß§Õ§à§Ô§Ö§ß§ß§í§ç BMP-7. However, with the latter approach, it might be difficult to exactly control the amounts of BMP-7 released by the device. §°§Õ§ß§Ñ§Ü§à, §á§à§ã§Ý§Ö§Õ§ß§Ú§Û §á§à§Õ§ç§à§Õ, §ï§ä§à §Þ§à§Ø§Ö§ä §Ò§í§ä§î §ä§â§å§Õ§ß§à §ä§à§é§ß§à §Ü§à§ß§ä§â§à§Ý§Ú§â§à§Ó§Ñ§ä§î §Ü§à§Ý§Ú§é§Ö§ã§ä§Ó§à BMP-7 §Ó§í§á§å§ë§Ö§ß§Ñ §å§ã§ä§â§à§Û§ã§ä§Ó§Ñ. Apart from the beneficial effects on kidney patients treated with the BMP-7-releasing BAK, BMP-7 secretion within the device would also be expected to inhibit tubule formation and improve cell performance within the BAK. §±§à§Þ§Ú§Þ§à §Ò§Ý§Ñ§Ô§à§ä§Ó§à§â§ß§à§Ô§à §Ó§Ý§Ú§ñ§ß§Ú§ñ §ß§Ñ §á§à§é§Ü§Ú §á§Ñ§è§Ú§Ö§ß§ä§à§Ó §ã BMP-7-§Ó§í§á§å§ã§Ü§Ñ§ñ §¢§¡§¬, BMP-7 §ã§Ö§Ü§â§Ö§è§Ú§Ú §Ó §å§ã§ä§â§à§Û§ã§ä§Ó§à §Ò§å§Õ§Ö§ä §ä§Ñ§Ü§Ø§Ö §à§Ø§Ú§Õ§Ñ§ä§î §Ú§ß§Ô§Ú§Ò§Ú§â§å§ð§ä §à§Ò§â§Ñ§Ù§à§Ó§Ñ§ß§Ú§Ö §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó §Ú §å§Ý§å§é§ê§Ú§ä§î §á§â§Ö§Õ§ã§ä§Ñ§Ó§Ý§Ö§ß§Ú§Ö §Ü§Ý§Ö§ä§Ü§Ú §Ó §¢§¡§¬. However, we would like to point out that the benefit of BMP-7 release by BAKs is still speculative at this point, and the discussion above reflects our personal view. §°§Õ§ß§Ñ§Ü§à, §Þ§í §ç§à§ä§Ö§Ý§Ú §Ò§í §à§ä§Þ§Ö§ä§Ú§ä§î, §é§ä§à §Ó §Ú§ß§ä§Ö§â§Ö§ã§Ñ§ç BMP-7-§â§Ö§Ý§Ú§Ù §¢§Ñ§Ü§ã §Ö§ë§Ö §ã§á§Ö§Ü§å§Ý§ñ§ä§Ú§Ó§ß§í§ç §ß§Ñ §Õ§Ñ§ß§ß§í§Û §Þ§à§Þ§Ö§ß§ä, §Ú §à§Ò§ã§å§Ø§Õ§Ö§ß§Ú§Ö §Ó§í§ê§Ö §à§ä§â§Ñ§Ø§Ñ§Ö§ä §ß§Ñ§ê§Ö §Ý§Ú§é§ß§à§Ö §Þ§ß§Ö§ß§Ú§Ö. It is also worth mentioning that secretion of active proteins into the bloodstream is one possible application of BAKs, and the use of BMP-7 is one possible example of such an application. §³§ä§à§Ú§ä §ä§Ñ§Ü§Ø§Ö §à§ä§Þ§Ö§ä§Ú§ä§î, §é§ä§à §Ó§í§Õ§Ö§Ý§Ö§ß§Ú§Ö §Ñ§Ü§ä§Ú§Ó§ß§í§ç §Ò§Ö§Ý§Ü§à§Ó §Ó §Ü§â§à§Ó§Ú §ñ§Ó§Ý§ñ§Ö§ä§ã§ñ §à§Õ§ß§Ú§Þ §Ú§Ù §Ó§à§Ù§Þ§à§Ø§ß§í§ç §á§â§Ú§Þ§Ö§ß§Ö§ß§Ú§Ö Baks, §Ú §Ú§ã§á§à§Ý§î§Ù§à§Ó§Ñ§ß§Ú§Ö BMP-7 §ñ§Ó§Ý§ñ§Ö§ä§ã§ñ §à§Õ§ß§Ú§Þ §Ú§Ù §Ó§à§Ù§Þ§à§Ø§ß§í§ç §á§â§Ú§Þ§Ö§â§à§Ó §ä§Ñ§Ü§Ú§ç §á§â§Ú§Ý§à§Ø§Ö§ß§Ú§Û.
• #8: §¬§Ý§Ö§ä§Ü§Ú §ã§à§Ò§Ñ§é§î§Ú§ç §á§à§é§Ö§Ü §®§Ñ§Õ§Ú§ß-§¥§Ñ§â§Ò§Ú (MDCK) §à§Ò§â§Ñ§Ù§å§ð§ä §á§à§Ý§ñ§â§Ú§Ù§à§Ó§Ñ§ß§ß§í§Û §ï§á§Ú§ä§Ö§Ý§Ú§Û §ß§Ñ §Ó§ß§å§ä§â§Ö§ß§ß§Ö§Û §á§à§Ó§Ö§â§ç§ß§à§ã§ä§Ú §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§à§Ó §Ú§Ù §á§à§Ý§Ú§ï§æ§Ú§â§ã§å§Ý§î§æ§à§ß§Ñ / §á§à§Ý§Ú§Ó§Ú§ß§Ú§Ý§á§Ú§â§â§à§Ý§Ú§Õ§à§ß§Ñ (§¡) §³§Ý§Ú§Ó§Ñ§ð§ë§Ú§Û§ã§ñ §Þ§à§ß§à§ã§Ý§à§Û MDCK §Ü§Ý§Ö§ä§à§Ü §ß§Ñ §Ó§ß§å§ä§â§Ö§ß§ß§Ö§Û §á§à§Ó§Ö§â§ç§ß§à§ã§ä§Ú §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§Ñ. §´§â§Ö§ë§Ú§ß§í §Ó §Þ§à§ß§à§ã§Ý§à§Ö (§å§Ü§Ñ§Ù§Ñ§ß§í §ã§ä§â§Ö§Ý§Ü§Ñ§Þ§Ú) §ñ§Ó§Ý§ñ§ð§ä§ã§ñ §Ñ§â§ä§Ö§æ§Ñ§Ü§ä§Ñ§Þ§Ú §Ó §â§Ö§Ù§å§Ý§î§ä§Ñ§ä§Ö §á§à§Õ§Ô§à§ä§à§Ó§Ü§Ú §à§Ò§â§Ñ§Ù§è§Ñ (§ê§Ü§Ñ§Ý§Ñ: §Õ§Ö§Ý§Ö§ß§Ú§Ö = 100 ¦Ìm). (§¢) §±§à§Ó§Ö§â§ç§ß§à§ã§ä§î §ã§Ý§à§ñ §Ü§Ý§Ö§ä§à§Ü MDCK §ß§Ñ §Ó§ß§å§ä§â§Ö§ß§ß§Ö§Û §á§à§Ó§Ö§â§ç§ß§à§ã§ä§Ú §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§à§Ó (§ê§Ü§Ñ§Ý§Ñ: §Õ§Ö§Ý§Ö§ß§Ú§Ö = 1 ¦Ì §Þ). §±§à§Ó§Ö§â§ç§ß§à§ã§ä§î §Ü§Ý§Ö§ä§à§Ü §á§Ý§à§ä§ß§à §á§à§Ü§â§í§ä§Ñ §Þ§Ú§Ü§â§à§Ó§à§â§ã§Ú§ß§Ü§Ñ§Þ§Ú. §¯§Ñ §Ó§ã§ä§Ñ§Ó§Ü§Ö §á§â§Ú §Ò§à§Ý§î§ê§à§Þ §å§Ó§Ö§Ý§Ú§é§Ö§ß§Ú§Ú §á§à§Ü§Ñ§Ù§Ñ§ß§í §Þ§Ú§Ü§â§à§Ó§à§â§ã§Ú§ß§Ü§Ú, §á§à§Ü§â§í§Ó§Ñ§ð§ë§Ú§Ö §á§à§Ó§Ö§â§ç§ß§à§ã§ä§Ú (§ê§Ü§Ñ§Ý§Ñ: §Õ§Ö§Ý§Ö§ß§Ú§Ö = 1 ¦Ì§Þ).. §£§ã§Ö §Ú§Ù§à§Ò§â§Ñ§Ø§Ö§ß§Ú§ñ §Ò§í§Ý§Ú §á§à§Ý§å§é§Ö§ß§í §ã §á§à§Þ§à§ë§î§ð §ã§Ü§Ñ§ß§Ú§â§å§ð§ë§Ö§Ô§à §ï§Ý§Ö§Ü§ä§â§à§ß§ß§à§Ô§à §Þ§Ú§Ü§â§à§ã§Ü§à§á§Ñ. Tasnim et al. Fibrogenesis & Tissue Repair 2010 3 :14 ?
• #13: Clinical trials are scheduled to start simultaneously in Los Angeles, California and Singapore at the start of 2011. David B. N. Lee and Martin Roberts:? A peritoneal-based automated wearable artificial kidney.? Clinical and Experimental Nephrology:? 12:171-180, 2008. Abstract- Work on wearable kidneys has evolved around the technology of hemodialysis or hemofiltration, which call for continuous anticoagulation of the extracoporeal circulation and are encumbered with potential immunologic and non-immunologic complications of continuous blood¨Cartificial membrane interactions. A peritoneal-based automated wearable artificial kidney (AWAK) requires no extracorporeal circulation and is therefore ¡°bloodless.¡± Because AWAK is designed to continuously regenerate and reuse the spent dialysate in perpetuity, it is also ¡°waterless.¡± A sorbent-based assembly regenerates both the aqueous and the protein components (AqC and PrC) of the spent dialysate, producing a novel, autologous protein-containing dialysate. The regenerated AqC has the same composition as the commercially available peritoneal dialysate, but contains bicarbonate instead of lactate and has a more physiological pH. The regenerated PrC is recycled back into the peritoneal cavity, thereby ameliorating or eliminating protein loss. Depending on the steady-state protein concentrations that can be achieved (under the condition of continuous dialysate regeneration and recycling), the PrC also has the potential of both augmenting ultrafiltration and mediating the removal of protein-bound toxins. Additional sorbents can be incorporated into AWAK for the removal of middle molecular weight uremic toxins. At a regeneration rate of 4?l/h, AWAK provides a dialysate flow of 96?l/day (8¨C12 times the current rate). Round-the-clock dialysis and ultrafiltration provide steady-state metabolic-biochemical and fluid balance regulation, thereby eliminating ¡°shocks¡± of abrupt changes in these parameters that characterize the current dialytic modalities. Dialysis-on-the-go, made possible by AWAK¡¯s ¡°wearability¡± and automation, frees end-stage renal failure patients from the servitude that is demanded by the current dialytic regimentations. Keywords-??Automated wearable artificial kidney,?AWAK,Peritoneal dialysis. Martin Roberts and David B. N. Lee:? Wearable Artificial Kidney: A Historical Perspective.? Proceedings of the World Congress on Medical Physics and Biomedical Engineering, 11th International Congress of the IUPESM, September 7-12, 2009, Munich, Germany.? Abstract- A wearable artificial kidney (WAK) allows the patient to have a more normal life style and provides continuous fluid and electrolyte balance.? Only four WAKs have been tested in patients and none marketed.? Two hemofiltration WAKs used the heart as the blood pump. Neff required the patient to drink 450 ml of dialysate every hour to replace the fluid lost.? Murisasco regenerated the ultrafiltrate with a miniature REDY cartridge.? In both instances the artificial kidneys clotted within 5 days.? Two WAKs were based on hemodialysis. Bazzato used the heart to pump the blood through a dialyzer without a casing, placed in a plastic bag.? The patient changed the dialysate in the bag periodically.? Gura uses a blood pump and regenerates the used hemodialysate with a REDY type cartridge.? His unit has been clinically tested for only 8 hours.? To develop an extracorporeal WAK, problems of clotting and possible accidental fatal disconnects need to be solved. A number of WAKs are under development.? Lande presented a hemodialysis unit on the arm, which uses the heart as a pump by intermittently blocking the fistula.? Nissenson has proposed a kidney based upon a G membrane and T membrane. The G membrane filters the blood.? The T ¡®smart¡± membrane blocks undesired substances while passing desirable substances.? Humes and also Saito have proposed a hybrid kidney but have not formulated a wearable configuration. Two peritoneal-based kidneys are under development. Ronco uses activated carbon and polystyrene resins for the removal of creatinine, b2 microglobulin and angiogenin from used dialysate.? Other metabolites such as urea and phosphate were not addressed.??? Lee and Roberts use a REDY type cartridge for complete regeneration of used peritoneal dialysate. Use of peritoneal dialysis eliminates the problem of clotting and accidental fatal disconnects. Keywords- Peritoneal Dialysis, Wearable kidney, Wearable Artificial Kidney, Hemodialysis, Hemofiltration.
• #16: §±§à§é§Ö§é§ß§í§Ö §Ü§Ñ§ß§Ñ§Ý§î§è§í, §Ü§à§ä§à§â§í§Ö §à§Ò§â§Ñ§Ù§å§ð§ä§ã§ñ §ã§á§à§ß§ä§Ñ§ß§ß§à §ß§Ñ 2-§Þ§Ö§â§ß§í§ç §á§à§Ó§Ö§â§ç§ß§à§ã§ä§ñ§ç §Ó §á§â§à§Ò§Ú§â§Ü§Ö. §±§à§é§Ö§é§ß§í§Ö §Ü§Ý§Ö§ä§Ü§Ú §Ü§å§Ý§î§ä§Ú§Ó§Ú§â§à§Ó§Ñ§Ý§Ú §ß§Ñ §Õ§ß§Ö §ñ§é§Ö§Û§Ü§Ú (§Þ§ß§à§Ô§à§ñ§é§Ö§Ú§ã§ä§Ñ§ñ §á§Ý§Ñ§ã§ä§Ú§ß§Ñ) §Ó §ä§Ö§é§Ö§ß§Ú§Ö §ß§Ö§ã§Ü§à§Ý§î§Ü§Ú§ç §Õ§ß§Ö§Û, §á§à§Ü§Ñ §ß§Ö §á§â§à§Ú§ã§ç§à§Õ§Ú§Ý§à §ã§á§à§ß§ä§Ñ§ß§ß§à§Ô§à §æ§à§â§Þ§Ú§â§à§Ó§Ñ§ß§Ú§ñ §ä§â§å§Ò§à§é§Ü§Ú. (§¡) §¹§Ñ§ã§ä§î §á§à§é§Ö§é§ß§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó §à§Ò§â§Ñ§Ù§à§Ó§Ñ§ß§ß§í§ç §é§Ö§Ý§à§Ó§Ö§é§Ö§ã§Ü§Ú§Þ§Ú §Ü§Ý§Ö§ä§Ü§Ñ§Þ§Ú §á§Ö§â§Ó§Ú§é§ß§í§ç §á§à§é§Ö§é§ß§í§ç §á§â§à§Ü§ã§Ú§Þ§Ñ§Ý§î§ß§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó (HPTCs). §­§Ö§Ó§í§Û §Ü§à§ß§Ö§è §ä§â§å§Ò§à§é§Ü§Ú §Ü§â§Ö§á§Ú§ä§ã§ñ §Ü §Ü§â§Ñ§ð §ñ§é§Ö§Û§Ü§Ú (§ä§Ö§Þ§ß§Ñ§ñ §Ù§à§ß§Ñ §Ó §Ý§Ö§Ó§à§Þ §ß§Ú§Ø§ß§Ö§Þ §å§Ô§Ý§å). §¿§á§Ú§ä§Ö§Ý§Ú§Û §ß§Ñ §Õ§ß§Ö §Ò§í§Ý §é§Ñ§ã§ä§Ú§é§ß§à §ß§Ñ§â§å§ê§Ö§ß §Ó §á§â§à§è§Ö§ã§ã§Ö §æ§à§â§Þ§Ú§â§à§Ó§Ñ§ß§Ú§ñ §ä§â§å§Ò§à§é§Ü§Ú (§á§Ý§à§ë§Ñ§Õ§î §Ý§Ú§ê§Ö§ß§ß§Ñ§ñ §Ü§Ý§Ö§ä§à§Ü §Ó §Ó§Ö§â§ç§ß§Ö§Þ §Ý§Ö§Ó§à§Þ §å§Ô§Ý§å).. §ª§Ù§à§Ò§â§Ñ§Ø§Ö§ß§Ú§Ö §Ò§í§Ý§à §á§à§Ý§å§é§Ö§ß§à §á§â§Ú §Þ§Ú§Ü§â§à§ã§Ü§à§á§Ú§Ú §Ó §ñ§â§Ü§à§Þ §á§à§Ý§Ö, §Ú §á§à§ñ§Ó§Ý§Ö§ß§Ú§Ö §à§Ò§Ý§Ñ§ã§ä§Ö§Û §ã §ñ§â§Ü§Ú§Þ§Ú §Ú §ä§Ö§Þ§ß§í§Þ§Ú §à§ã§Ó§Ö§ë§Ö§ß§Ú§ñ §ã§Ó§ñ§Ù§Ñ§ß§à §ã §à§á§ä§Ú§é§Ö§ã§Ü§Ú§Þ§Ú §ï§æ§æ§Ö§Ü§ä§Ñ§Þ§Ú §Ò§Ý§Ú§Ù§Ü§à §Ü §Ü§â§Ñ§ð §ñ§é§Ö§Û§Ü§Ú §Ú §Ó§à§Ü§â§å§Ô §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó. (§¢) §é§Ñ§ã§ä§î §á§à§é§Ö§é§ß§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó §à§Ò§â§Ñ§Ù§å§ð§ä§ã§ñ LLC-PK 1 §Ü§Ý§Ö§ä§Ü§Ñ§Þ§Ú. The cell nuclei were stained with 4', 6'-diamidino-2'-phenylindole (DAPI, blue). §Á§Õ§â§Ñ §Ü§Ý§Ö§ä§à§Ü §à§Ü§â§Ñ§ê§Ö§ß§í 4 ', 6'-diamidino-2'-phenylindole (DAPI, §Ô§à§Ý§å§Ò§à§Û). §ª§Ù§à§Ò§â§Ñ§Ø§Ö§ß§Ú§Ö §Ò§í§Ý§à §á§à§Ý§å§é§Ö§ß§à §ï§á§Ú§æ§Ý§å§à§â§Ö§ã§è§Ö§ß§ä§ß§í§Þ §Þ§Ú§Ü§â§à§ã§Ü§à§á§à§Þ. §º§Ü§Ñ§Ý§Ñ: §Õ§Ö§Ý§Ö§ß§Ú§Ö= (§¡) 400 ¦Ì§Þ §Ú (B) 100 ¦Ì§Þ. Tasnim et al. Fibrogenesis & Tissue Repair 2010 3 :14 ?
• #17: §´§â§Ñ§ß§ã§á§Ý§Ñ§ß§ä§Ñ§è§Ú§Ú §á§à§é§Ü§Ú §Õ§Ý§ñ §Ý§Ö§é§Ö§ß§Ú§ñ §ä§Ö§â§Þ§Ú§ß§Ñ§Ý§î§ß§à§Û §ã§ä§Ñ§Õ§Ú§Ú §á§à§é§Ö§é§ß§à§Û §Ò§à§Ý§Ö§Ù§ß§Ú §ç§à§â§à§ê§à §å§ã§ä§Ñ§ß§à§Ó§Ý§Ö§ß§ß§à§Þ §á§à§â§ñ§Õ§Ü§Ö §ã §à§ä§Ý§Ú§é§ß§í§Þ §Ü§Ý§Ú§ß§Ú§é§Ö§ã§Ü§Ú§Þ §Ú§ã§ç§à§Õ§à§Þ, §Ó §ß§Ñ§ã§ä§à§ñ§ë§Ö§Ö §Ó§â§Ö§Þ§ñ, §á§Ö§â§Ö§ã§Ñ§Õ§Ü§Ú §á§à§é§Ü§Ú §ã§à§ã§ä§Ñ§Ó§Ý§ñ§Ö§ä 70% §Ó§ã§Ö§ç §ä§â§Ñ§ß§ã§á§Ý§Ñ§ß§ä§Ñ§è§Ú§Û §à§â§Ô§Ñ§ß§à§Ó. In 2003, more than 2,000 patients received a kidney transplant as their first therapy, and the number of patients needing a kidney transplant grows steadily. §£ 2003 §Ô§à§Õ§å §Ò§à§Ý§Ö§Ö 2000 §á§Ñ§è§Ú§Ö§ß§ä§à§Ó §á§à§Ý§å§é§Ú§Ý§Ú §á§à §á§Ö§â§Ö§ã§Ñ§Õ§Ü§Ö §á§à§é§Ü§Ú §Ó §Ü§Ñ§é§Ö§ã§ä§Ó§Ö §á§Ö§â§Ó§à§Ô§à §ä§Ö§â§Ñ§á§Ú§Ú, §Ñ §é§Ú§ã§Ý§à §á§Ñ§è§Ú§Ö§ß§ä§à§Ó, §ß§å§Ø§Õ§Ñ§ð§ë§Ú§ç§ã§ñ §Ó §á§Ö§â§Ö§ã§Ñ§Õ§Ü§Ö §á§à§é§Ü§Ú §â§Ñ§ã§ä§Ö§ä. However, the shortage of kidney donors is an unsolved problem that creates a transplant crisis. §°§Õ§ß§Ñ§Ü§à, §ß§Ö§ç§Ó§Ñ§ä§Ü§Ñ §Õ§à§ß§à§â§à§Ó §á§à§é§Ö§Ü §ñ§Ó§Ý§ñ§Ö§ä§ã§ñ §ß§Ö§â§Ö§ê§Ö§ß§ß§Ñ§ñ §á§â§à§Ò§Ý§Ö§Þ§Ñ, §Ü§à§ä§à§â§Ñ§ñ §ã§à§Ù§Õ§Ñ§Ö§ä §á§Ö§â§Ö§ã§Ñ§Õ§Ü§Ú §Ü§â§Ú§Ù§Ú§ã§Ñ. According to data from United Network for Organ Sharing, kidney patients account for 65,000 of the approximately 90,000 patients on the waiting list for all organ transplantation. §±§à §Õ§Ñ§ß§ß§í§Þ §°§â§Ô§Ñ§ß§Ú§Ù§Ñ§è§Ú§Ú §°§Ò§ì§Ö§Õ§Ú§ß§Ö§ß§ß§í§ç §ã§Ö§ä§Ú §Õ§Ý§ñ §ã§à§Ó§Þ§Ö§ã§ä§ß§à§Ô§à §Ú§ã§á§à§Ý§î§Ù§à§Ó§Ñ§ß§Ú§ñ §à§â§Ô§Ñ§ß§à§Ó, §á§à§é§Ö§Ü §á§Ñ§è§Ú§Ö§ß§ä§à§Ó §ã§à§ã§ä§Ñ§Ó§Ý§ñ§ð§ä 65000 §Ú§Ù §á§â§Ú§Þ§Ö§â§ß§à 90.000 §á§Ñ§è§Ú§Ö§ß§ä§à§Ó §Ó §Ý§Ú§ã§ä§Ö §à§Ø§Ú§Õ§Ñ§ß§Ú§ñ §Õ§Ý§ñ §Ó§ã§Ö§ç §ä§â§Ñ§ß§ã§á§Ý§Ñ§ß§ä§Ñ§è§Ú§Ú §à§â§Ô§Ñ§ß§à§Ó. Besides transplants, other strategies, such as extracorporeal dialysis, are in clinical use. §¬§â§à§Þ§Ö §ä§à§Ô§à §ä§â§Ñ§ß§ã§á§Ý§Ñ§ß§ä§Ñ§è§Ú§Ú, §Õ§â§å§Ô§Ú§Ö §ã§ä§â§Ñ§ä§Ö§Ô§Ú§Ú, §ä§Ñ§Ü§Ú§Ö §Ü§Ñ§Ü §ï§Ü§ã§ä§â§Ñ§Ü§à§â§á§à§â§Ñ§Ý§î§ß§à§Ô§à §Õ§Ú§Ñ§Ý§Ú§Ù§Ñ, §Ó §Ü§Ý§Ú§ß§Ú§é§Ö§ã§Ü§à§Û §á§â§Ñ§Ü§ä§Ú§Ü§Ö. However, in current hemodialysis or hemofiltration, synthetic semipermeable membranes are utilized only to substitute for the small solute clearance functions of the renal glomerulus; this does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. §°§Õ§ß§Ñ§Ü§à, §Ó §ä§Ö§Ü§å§ë§Ú§ç §Ô§Ö§Þ§à§Õ§Ú§Ñ§Ý§Ú§Ù§Ñ §Ú§Ý§Ú §Ô§Ö§Þ§à§æ§Ú§Ý§î§ä§â§Ñ§è§Ú§Ú, §ã§Ú§ß§ä§Ö§ä§Ú§é§Ö§ã§Ü§Ú§Ö §á§à§Ý§å§á§â§à§ß§Ú§è§Ñ§Ö§Þ§à§Û §Þ§Ö§Þ§Ò§â§Ñ§ß§í §Ú§ã§á§à§Ý§î§Ù§å§ð§ä§ã§ñ §ä§à§Ý§î§Ü§à §Õ§Ý§ñ §Ù§Ñ§Þ§Ö§ß§í §Þ§Ñ§Ý§í§ç §Ó§Ö§ë§Ö§ã§ä§Ó§Ñ §æ§å§ß§Ü§è§Ú§Ú §à§æ§à§â§Þ§Ý§Ö§ß§Ú§ñ §á§à§é§Ö§é§ß§í§ç §Ü§Ý§å§Ò§à§é§Ü§à§Ó, §ï§ä§à §ß§Ö §Ù§Ñ§Þ§Ö§ß§ñ§Ö§ä §ä§â§Ñ§ß§ã§á§à§â§ä§Ñ, §Þ§Ö§ä§Ñ§Ò§à§Ý§Ú§é§Ö§ã§Ü§Ú§ç §Ú §ï§ß§Õ§à§Ü§â§Ú§ß§à§Ý§à§Ô§Ú§é§Ö§ã§Ü§Ú§ç §æ§å§ß§Ü§è§Ú§Û §ä§â§å§Ò§é§Ñ§ä§í§ç §Ü§Ý§Ö§ä§à§Ü. Although researchers tried to combine a synthetic hemofiltration device with renal tubule cells derived from porcine kidney to replace certain physiologic function of kidney in acutely uremic animals,? extracorporeal perfusion still has significant limitations in terms of morbidity, mortality, and cost. §·§à§ä§ñ §Ú§ã§ã§Ý§Ö§Õ§à§Ó§Ñ§ä§Ö§Ý§Ú §á§í§ä§Ñ§Ý§Ú§ã§î §à§Ò§ì§Ö§Õ§Ú§ß§Ú§ä§î §ã§Ú§ß§ä§Ö§ä§Ú§é§Ö§ã§Ü§Ú§Ö §å§ã§ä§â§à§Û§ã§ä§Ó§Ñ §Ô§Ö§Þ§à§æ§Ú§Ý§î§ä§â§Ñ§è§Ú§ñ §ã §á§à§é§Ö§é§ß§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó §Ü§Ý§Ö§ä§Ü§Ú, §á§à§Ý§å§é§Ö§ß§ß§í§Ö §Ú§Ù §ã§Ó§Ú§ß§í§ç §á§à§é§Ü§Ú §Ù§Ñ§Þ§Ö§ß§Ú§ä§î §à§á§â§Ö§Õ§Ö§Ý§Ö§ß§ß§í§Ö §æ§å§ß§Ü§è§Ú§Ú §æ§Ú§Ù§Ú§à§Ý§à§Ô§Ú§é§Ö§ã§Ü§à§Û §á§à§é§Ö§Ü §Ó §à§ã§ä§â§à§Û §å§â§Ö§Þ§Ú§é§Ö§ã§Ü§Ú§Û §Ø§Ú§Ó§à§ä§ß§í§ç, §ï§Ü§ã§ä§â§Ñ§Ü§à§â§á§à§â§Ñ§Ý§î§ß§à§Û §á§Ö§â§æ§å§Ù§Ú§Ú §á§à-§á§â§Ö§Ø§ß§Ö§Þ§å §Ú§Þ§Ö§Ö§ä §ã§å§ë§Ö§ã§ä§Ó§Ö§ß§ß§í§Ö §à§Ô§â§Ñ§ß§Ú§é§Ö§ß§Ú§ñ §Ó §á§Ý§Ñ§ß§Ö §Ù§Ñ§Ò§à§Ý§Ö§Ó§Ñ§Ö§Þ§à§ã§ä§Ú, §ã§Þ§Ö§â§ä§ß§à§ã§ä§Ú §Ú §ã§ä§à§Ú§Þ§à§ã§ä§Ú. Therefore, extracorporeal dialysis is a partial, temporary treatment, not a radical solution for this problem. §´§Ñ§Ü§Ú§Þ §à§Ò§â§Ñ§Ù§à§Þ, §ï§Ü§ã§ä§â§Ñ§Ü§à§â§á§à§â§Ñ§Ý§î§ß§à§Ô§à §Õ§Ú§Ñ§Ý§Ú§Ù§Ñ §é§Ñ§ã§ä§Ú§é§ß§à§Ö, §Ó§â§Ö§Þ§Ö§ß§ß§à§Ö §Ý§Ö§é§Ö§ß§Ú§Ö, §ß§Ö §â§Ñ§Õ§Ú§Ü§Ñ§Ý§î§ß§à§Ö §â§Ö§ê§Ö§ß§Ú§Ö §ï§ä§à§Û §á§â§à§Ò§Ý§Ö§Þ§í. Engineering of a living, functional human kidney can solve this problem permanently. §´§Ö§ç§ß§Ú§Ü§Ñ §Ø§Ú§Ù§ß§Ú, §æ§å§ß§Ü§è§Ú§à§ß§Ñ§Ý§î§ß§í§Ö §é§Ö§Ý§à§Ó§Ö§é§Ö§ã§Ü§à§Û §á§à§é§Ü§Ú §Þ§à§Ô§å§ä §ß§Ñ§Ó§ã§Ö§Ô§Õ§Ñ §â§Ö§ê§Ú§ä§î §ï§ä§å §á§â§à§Ò§Ý§Ö§Þ§å. However, this is no established technology to tissue-engineer functional human kidney yet. §°§Õ§ß§Ñ§Ü§à, §ï§ä§à §ß§Ö §ç§à§â§à§ê§à §Ù§Ñ§â§Ö§Ü§à§Þ§Ö§ß§Õ§à§Ó§Ñ§Ó§ê§Ñ§ñ §ã§Ö§Ò§ñ §ä§Ö§ç§ß§à§Ý§à§Ô§Ú§ñ §Õ§Ý§ñ §ä§Ü§Ñ§ß§Ö§Û §Ú§ß§Ø§Ö§ß§Ö§â-§æ§å§ß§Ü§è§Ú§à§ß§Ñ§Ý§î§ß§í§ç §é§Ö§Ý§à§Ó§Ö§é§Ö§ã§Ü§à§Û §á§à§é§Ü§Ú §Ö§ë§Ö. To this end, we recently initiated Charleston Bioengineered Kidney Project . §¥§Ý§ñ §ï§ä§à§Ô§à, §Þ§í §ß§Ö§Õ§Ñ§Ó§ß§à §á§â§Ú§ã§ä§å§á§Ú§Ý§Ú §¹§Ñ§â§Ý§ã§ä§à§ß §¢§Ú§à§Ú§ß§Ø§Ö§ß§Ö§â§ß§í§Ö §á§à§é§Ü§Ú §á§â§à§Ö§Ü§ä§Ñ . The goal of this translational multidisciplinary project is to bioengineer a living, functional human kidney suitable for clinical transplantation. §¸§Ö§Ý§î §ï§ä§à§Û §ä§â§Ñ§ß§ã§Ý§ñ§è§Ú§à§ß§ß§à§Û §Þ§Ö§Ø§Õ§Ú§ã§è§Ú§á§Ý§Ú§ß§Ñ§â§ß§à§Ô§à §á§â§à§Ö§Ü§ä§Ñ §Ù§Ñ§Ü§Ý§ð§é§Ñ§Ö§ä§ã§ñ §Ó §Ò§Ú§à§Ú§ß§Ø§Ö§ß§Ö§â §Ø§Ú§Ù§ß§Ú, §æ§å§ß§Ü§è§Ú§à§ß§Ñ§Ý§î§ß§í§Ö §é§Ö§Ý§à§Ó§Ö§é§Ö§ã§Ü§à§Û §á§à§é§Ü§Ú §á§â§Ú§Ô§à§Õ§ß§í§Û §Õ§Ý§ñ §Ü§Ý§Ú§ß§Ú§é§Ö§ã§Ü§à§Ô§à §ä§â§Ñ§ß§ã§á§Ý§Ñ§ß§ä§Ñ§è§Ú§Ú. There are five major components in mammal nephrons: the renal corpuscle consists of a thin capsule of epithelial tissue (Bowman's Capsule) surrounding a ball of capillaries (glomerulus), the proximal convoluted tubule, the Loop of Henle, the distal convoluted tubule, and the collecting ducts. §¦§ã§ä§î §á§ñ§ä§î §à§ã§ß§à§Ó§ß§í§ç §Ü§à§Þ§á§à§ß§Ö§ß§ä§à§Ó §Ó §Þ§Ý§Ö§Ü§à§á§Ú§ä§Ñ§ð§ë§Ú§ç §ß§Ö§æ§â§à§ß§à§Ó: §á§à§é§Ö§é§ß§Ñ§ñ §ä§Ö§Ý§î§è§Ö §ã§à§ã§ä§à§Ú§ä §Ú§Ù §ä§à§ß§Ü§à§Û §Ü§Ñ§á§ã§å§Ý§à§Û §Ú§Ù §ï§á§Ú§ä§Ö§Ý§Ú§Ñ§Ý§î§ß§à§Û §ä§Ü§Ñ§ß§Ú (§Ó §Ü§Ñ§á§ã§å§Ý§í §¢§à§å§Þ§Ö§ß§Ñ), §à§Ü§â§å§Ø§Ñ§ð§ë§Ú§Ö §ê§Ñ§â §Ü§Ñ§á§Ú§Ý§Ý§ñ§â§à§Ó (§Ü§Ý§å§Ò§à§é§Ö§Ü), §á§â§à§Ü§ã§Ú§Þ§Ñ§Ý§î§ß§í§ç §Ú§Ù§Ó§Ú§ä§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó, §á§Ö§ä§Ý§Ú §¤§Ö§ß§Ý§Ö, §Õ§Ú§ã§ä§Ñ§Ý§î§ß§í§ç §Ú§Ù§Ó§Ú§ä§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó, §Ñ §ä§Ñ§Ü§Ø§Ö §ã§à§Ò§Ú§â§Ñ§ä§Ö§Ý§î§ß§í§ç §ä§â§å§Ò§à§Ü. We demonstrated that kidney epithelial cells can form a cyst-like structure and then fuse into a renal tubule-like structure? with appropriate polarity]. §®§í §á§à§Ü§Ñ§Ù§Ñ§Ý§Ú, §é§ä§à §á§à§é§Ü§Ú §ï§á§Ú§ä§Ö§Ý§Ú§Ñ§Ý§î§ß§í§Ö §Ü§Ý§Ö§ä§Ü§Ú §Þ§à§Ô§å§ä §à§Ò§â§Ñ§Ù§à§Ó§í§Ó§Ñ§ä§î §Ü§Ú§ã§ä§í, §Ü§Ñ§Ü §ã§ä§â§å§Ü§ä§å§â§Ñ, §Ñ §Ù§Ñ§ä§Ö§Þ §ã§Ý§Ú§Ó§Ñ§ð§ä§ã§ñ §Ó §á§à§é§Ö§é§ß§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó-§á§à§Õ§à§Ò§ß§å§ð §ã§ä§â§å§Ü§ä§å§â§å §ã §ã§à§à§ä§Ó§Ö§ä§ã§ä§Ó§å§ð§ë§Ú§Þ§Ú] §á§à§Ý§ñ§â§ß§à§ã§ä§Ú. Using phase inversion technology, we fabricated biodegradable, elastic, hollow-fiber membranes from biocompatible polyurethane and seeded the membranes with kidney epithelial cells. §ª§ã§á§à§Ý§î§Ù§à§Ó§Ñ§ß§Ú§Ö §ä§Ö§ç§ß§à§Ý§à§Ô§Ú§Ú §Ú§ß§Ó§Ö§â§ã§Ú§Ú §æ§Ñ§Ù§í, §Ò§í§Ý§Ú §Ú§Ù§Ô§à§ä§à§Ó§Ý§Ö§ß§í §Ò§Ú§à§Ý§à§Ô§Ú§é§Ö§ã§Ü§Ú, §å§á§â§å§Ô§à§Û, §á§à§Ý§í§Ö §Ó§à§Ý§à§Ü§ß§Ñ §Þ§Ö§Þ§Ò§â§Ñ§ß §Ú§Ù §Ò§Ú§à§ã§à§Ó§Þ§Ö§ã§ä§Ú§Þ§í§ç §á§à§Ý§Ú§å§â§Ö§ä§Ñ§ß§à§Ó§í§ç §Ú §ã§Ö§Þ§Ö§ß§Ñ§Þ§Ú §Þ§Ö§Þ§Ò§â§Ñ§ß §ã §á§à§é§Ö§é§ß§à§Û §ï§á§Ú§ä§Ö§Ý§Ú§Ñ§Ý§î§ß§í§ç §Ü§Ý§Ö§ä§à§Ü. Using laser micro-fabrication, we then created holes of controlled size and demonstrated that epithelial cyst-like structure can fuse with the epithelialized hollow fiber through those laser-drilled holes. §ª§ã§á§à§Ý§î§Ù§à§Ó§Ñ§ß§Ú§Ö §Ý§Ñ§Ù§Ö§â§ß§à§Û §Þ§Ú§Ü§â§à-§Ú§Ù§Ô§à§ä§à§Ó§Ý§Ö§ß§Ú§Ö, §Þ§í §ä§à§Ô§Õ§Ñ §ã§à§Ù§Õ§Ñ§Ý§Ú §à§ä§Ó§Ö§â§ã§ä§Ú§ñ §Ü§à§ß§ä§â§à§Ý§Ú§â§å§Ö§Þ§à§Ô§à §â§Ñ§Ù§Þ§Ö§â§Ñ §Ú §á§à§Ü§Ñ§Ù§Ñ§ß§à, §é§ä§à §ï§á§Ú§ä§Ö§Ý§Ú§Ñ§Ý§î§ß§í§Ö §Ü§Ú§ã§ä§í-§á§à§Õ§à§Ò§ß§à§Û §ã§ä§â§å§Ü§ä§å§â§í §Þ§à§Ô§å§ä §ã§Ý§Ú§Ó§Ñ§ä§î§ã§ñ §ã epithelialized §á§à§Ý§à§Ö §Ó§à§Ý§à§Ü§ß§à §é§Ö§â§Ö§Ù §ï§ä§Ú §Ý§Ñ§Ù§Ö§â§ß§à§Û §á§Ö§â§æ§à§â§Ñ§è§Ú§Ö§Û. Thus, we can create a seamless epithelial transition from hybrid synthetic-epithelial tubes (macro-structure of bioengineered kidney) to regenerated renal tubules in the permissive hydrogel system (micro-structure of regenerated renal tissue). §´§Ñ§Ü§Ú§Þ §à§Ò§â§Ñ§Ù§à§Þ, §Þ§í §Þ§à§Ø§Ö§Þ §ã§à§Ù§Õ§Ñ§Ó§Ñ§ä§î §Ò§Ö§ã§ê§à§Ó§ß§í§Ö §ï§á§Ú§ä§Ö§Ý§Ú§Ñ§Ý§î§ß§í§ç §á§Ö§â§Ö§ç§à§Õ §à§ä §Ô§Ú§Ò§â§Ú§Õ§ß§í§ç §ã§Ú§ß§ä§Ö§ä§Ú§é§Ö§ã§Ü§Ú§ç §ï§á§Ú§ä§Ö§Ý§Ú§Ñ§Ý§î§ß§í§ç §ä§â§å§Ò§à§Ü (§Þ§Ñ§Ü§â§à-§ã§ä§â§å§Ü§ä§å§â§í §Ò§Ú§à§Ú§ß§Ø§Ö§ß§Ö§â§ß§í§ç §á§à§é§Ü§Ú), §é§ä§à§Ò§í §â§Ö§Ô§Ö§ß§Ö§â§Ú§â§à§Ó§Ñ§ä§î §á§à§é§Ö§é§ß§í§ç §Ü§Ñ§ß§Ñ§Ý§î§è§Ö§Ó §Ó §â§Ñ§Ù§â§Ö§ê§Ú§ä§Ö§Ý§î§ß§à§Û §ã§Ú§ã§ä§Ö§Þ§Ö §Ô§Ú§Õ§â§à§Ô§Ö§Ý§ñ (§Þ§Ú§Ü§â§à-§ã§ä§â§å§Ü§ä§å§â§Ñ §â§Ö§Ô§Ö§ß§Ö§â§Ú§â§à§Ó§Ñ§ß§ß§à§Ô§à §á§à§é§Ö§é§ß§à§Û §ä§Ü§Ñ§ß§Ú). We demonstrated the feasibility of fabricating four out of five essential components of a kidney nephron using animal cells. §®§í §á§â§à§Õ§Ö§Þ§à§ß§ã§ä§â§Ú§â§à§Ó§Ñ§Ý§Ú §Ó§à§Ù§Þ§à§Ø§ß§à§ã§ä§î §Ú§Ù§Ô§à§ä§à§Ó§Ý§Ö§ß§Ú§ñ §é§Ö§ä§í§â§Ö §Ú§Ù §á§ñ§ä§Ú §à§ã§ß§à§Ó§ß§í§ç §Ü§à§Þ§á§à§ß§Ö§ß§ä§à§Ó §á§à§é§Ü§Ú §ß§Ö§æ§â§à§ß§Ñ §Ú§ã§á§à§Ý§î§Ù§à§Ó§Ñ§ß§Ú§Ö§Þ §Ø§Ú§Ó§à§ä§ß§í§ç §Ü§Ý§Ö§ä§à§Ü. The glomerulus is the only element in the renal corpuscle that remains to be developed. §¬§Ý§å§Ò§à§é§Ö§Ü §ñ§Ó§Ý§ñ§Ö§ä§ã§ñ §Ö§Õ§Ú§ß§ã§ä§Ó§Ö§ß§ß§í§Þ §ï§Ý§Ö§Þ§Ö§ß§ä§à§Þ §Ó §á§à§é§Ö§é§ß§à§Û §ä§Ö§Ý§î§è§Ö, §é§ä§à §Ö§ë§Ö §á§â§Ö§Õ§ã§ä§à§Ú§ä §â§Ñ§Ù§â§Ñ§Ò§à§ä§Ñ§ä§î.
• #20: §ª§Ù §Ü§å§ã§Ü§Ñ §Ü§à§Ø§Ú §á§Ñ§è§Ú§Ö§ß§ä§à§Ó, §Ú§ã§ã§Ý§Ö§Õ§à§Ó§Ñ§ä§Ö§Ý§Ú §Ó§í§â§Ñ§ã§ä§Ú§Ý§Ú §Ü§â§à§Ó§Ö§ß§à§ã§ß§í§ç §ã§à§ã§å§Õ§à§Ó §Ó §Ý§Ñ§Ò§à§â§Ñ§ä§à§â§Ú§Ú, §Ñ §Ù§Ñ§ä§Ö§Þ §å§ã§á§Ö§ê§ß§à §Ú§Þ§á§Ý§Ñ§ß§ä§Ú§â§à§Ó§Ñ§Ý§Ú §Ú§ç §à§Ò§â§Ñ§ä§ß§à §Ó §ä§Ö§Ý§à, §é§ä§à§Ò§í §á§à§Þ§à§é§î §Ó§à§ã§ã§ä§Ñ§ß§à§Ó§Ú§ä§î §á§â§Ú§ä§à§Ü §Ü§â§à§Ó§Ú §Ü §á§à§Ó§â§Ö§Ø§Õ§Ö§ß§ß§í§Þ §Ñ§â§ä§Ö§â§Ú§ñ§Þ §Ú §Ó§Ö§ß§Ñ§Þ §á§Ñ§è§Ú§Ö§ß§ä§Ñ§Þ. §¥§à§Ü§ä§à§â §®§Ñ§Ü§Ñ§Ý§Ý§Ú§ã§ä§Ö§â §Ú§Ù Cytograft §à§è§Ö§ß§Ú§Ý §ã§ä§à§Ú§Þ§à§ã§ä§î §á§â§à§è§Ö§Õ§å§â§í §à§ä $ 15000 §Õ§à $ 25000, §ß§à §Õ§à§Ò§Ñ§Ó§Ú§Ý, §é§ä§à §è§Ö§ß§Ñ §Ò§å§Õ§Ö§ä §ã§Ü§à§â§Ö§Ö §Ó§ã§Ö§Ô§à §á§Ñ§Õ§Ñ§ä§î §ã §Ò§à§Ý§Ö§Ö §ê§Ú§â§à§Ü§à§Ô§à §Ú§ã§á§à§Ý§î§Ù§à§Ó§Ñ§ß§Ú§ñ.
• #21: §²§Ö§Ó§à§Ý§ð§è§Ú§à§ß§ß§à§Ö §å§ã§ä§â§à§Û§ã§ä§Ó§à, §Ü§à§ä§à§â§à§Ö §Ò§í§Ý§à §â§Ñ§Ù§â§Ñ§Ò§à§ä§Ñ§ß§à §ã §Ú§ã§á§à§Ý§î§Ù§à§Ó§Ñ§ß§Ú§Ö§Þ §ß§Ñ§ß§à§ä§Ö§ç§ß§à§Ý§à§Ô§Ú§Û, §ã§à§ã§ä§à§Ú§ä §Ú§Ù §Þ§Ú§Ý§Ý§Ú§à§ß§à§Ó §Ú§ß§ß§à§Ó§Ñ§è§Ú§à§ß§ß§í§ç §ê§Ú§á§Ñ§Þ§Ú, §Ü§à§ä§à§â§í§Ö §á§â§Ú§Ó§Ý§Ö§Ü§Ñ§ð§ä §ã§ä§Ó§à§Ý§à§Ó§í§Ö §Ü§Ý§Ö§ä§Ü§Ú, §á§â§Ú§ã§å§ä§ã§ä§Ó§å§ð§ë§Ú§Ö §Ó §Ü§â§à§Ó§Ú. These stem cells then blend completely with endothelial linings of the blood vessels which prevents clot formation. §¿§ä§Ú §ã§ä§Ó§à§Ý§à§Ó§í§Ö §Ü§Ý§Ö§ä§Ü§Ú, §ä§à §ã§Þ§Ö§ã§î §á§à§Ý§ß§à§ã§ä§î§ð §ã §ï§ß§Õ§à§ä§Ö§Ý§Ú§Ñ§Ý§î§ß§à§Û §ß§Ñ§Ü§Ý§Ñ§Õ§Ü§Ú §Ú§Ù §Ü§â§à§Ó§Ö§ß§à§ã§ß§í§ç §ã§à§ã§å§Õ§à§Ó, §á§â§Ö§Õ§à§ä§Ó§â§Ñ§ë§Ñ§Ö§ä §à§Ò§â§Ñ§Ù§à§Ó§Ñ§ß§Ú§Ö §ã§Ô§å§ã§ä§Ü§à§Ó. Professor Alexander Seifalian of University College London, who led the research adds that around 30 percent of heart patients lack the proper vein that can be incorporated during a heart bypass surgery. §±§â§à§æ§Ö§ã§ã§à§â §¡§Ý§Ö§Ü§ã§Ñ§ß§Õ§â Seifalian §Ú§Ù §µ§ß§Ú§Ó§Ö§â§ã§Ú§ä§Ö§ä§ã§Ü§à§Ô§à §Ü§à§Ý§Ý§Ö§Õ§Ø§Ñ §Ó §­§à§ß§Õ§à§ß§Ö, §Ó§à§Ù§Ô§Ý§Ñ§Ó§Ý§ñ§Ó§ê§Ú§Û §Ú§ã§ã§Ý§Ö§Õ§à§Ó§Ñ§ß§Ú§Ö §Õ§à§Ò§Ñ§Ó§Ý§ñ§Ö§ä, §é§ä§à §à§Ü§à§Ý§à 30 §á§â§à§è§Ö§ß§ä§à§Ó §á§Ñ§è§Ú§Ö§ß§ä§à§Ó §ã §Ù§Ñ§Ò§à§Ý§Ö§Ó§Ñ§ß§Ú§ñ§Þ§Ú §ã§Ö§â§Õ§è§Ñ §à§ä§ã§å§ä§ã§ä§Ó§Ú§Ö §ß§Ñ§Õ§Ý§Ö§Ø§Ñ§ë§Ö§Ô§à §Ó§Ö§ß§í, §Ü§à§ä§à§â§í§Ö §Þ§à§Ô§å§ä §Ò§í§ä§î §Ó§Ü§Ý§ð§é§Ö§ß§í §Ó§à §Ó§â§Ö§Þ§ñ §à§á§Ö§â§Ñ§è§Ú§Ú §ê§å§ß§ä§Ú§â§à§Ó§Ñ§ß§Ú§ñ §ã§Ö§â§Õ§è§Ñ. Thus, this ground-breaking invention is expected to be hugely beneficial for patients suffering from life threatening coronary heart diseases. §´§Ñ§Ü§Ú§Þ §à§Ò§â§Ñ§Ù§à§Þ, §ï§ä§à §ß§à§Ó§Ñ§ä§à§â§ã§Ü§à§Ö §Ú§Ù§à§Ò§â§Ö§ä§Ö§ß§Ú§Ö, §Ü§Ñ§Ü §à§Ø§Ú§Õ§Ñ§Ö§ä§ã§ñ, §Ò§å§Õ§Ö§ä §é§â§Ö§Ù§Ó§í§é§Ñ§Û§ß§à §á§à§Ý§Ö§Ù§ß§í§Þ §Õ§Ý§ñ §á§Ñ§è§Ú§Ö§ß§ä§à§Ó, §ã§ä§â§Ñ§Õ§Ñ§ð§ë§Ú§ç §à§ä §å§Ô§â§à§Ø§Ñ§ð§ë§Ú§ç §Ø§Ú§Ù§ß§Ú §Ú§ê§Ö§Þ§Ú§é§Ö§ã§Ü§à§Û §Ò§à§Ý§Ö§Ù§ß§Ú §ã§Ö§â§Õ§è§Ñ. Meanwhile, the scientists have been granted ?500,000 by medical research charity, Wellcome Trust to perform the first human trials, which is likely to commence later this year. §®§Ö§Ø§Õ§å §ä§Ö§Þ, §å§é§Ö§ß§í§Ö §á§à§Ý§å§é§Ú§Ý§Ú ? 500,000 §Þ§Ö§Õ§Ú§è§Ú§ß§ã§Ü§à§Û §Ò§Ý§Ñ§Ô§à§ä§Ó§à§â§Ú§ä§Ö§Ý§î§ß§à§Û §Ú§ã§ã§Ý§Ö§Õ§à§Ó§Ñ§ß§Ú§Û, Wellcome Trust, §é§ä§à§Ò§í §Ó§í§á§à§Ý§ß§Ú§ä§î §á§Ö§â§Ó§í§Ö §Ú§ã§á§í§ä§Ñ§ß§Ú§ñ §ß§Ñ §é§Ö§Ý§à§Ó§Ö§Ü§Ö, §Ü§à§ä§à§â§í§Û, §Ó§Ö§â§à§ñ§ä§ß§à, §ß§Ñ§é§Ñ§ä§î §Ó §Ü§à§ß§è§Ö §ï§ä§à§Ô§à §Ô§à§Õ§Ñ.