Assessment of angiogenic factor, vascular endothelial growth factor, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical Bacillus Calmette-Guerin

<b>Background and Aim:</b> Bladder tumor is one of the most common genitourinary tumors. Management of non-muscle invasive (NMI) bladder tumors is primarily by transurethral resection (TURBT) followed by intravesical immunotherapy or chemotherapy. Bacillus Calmette-Guerin (BCG) is the most effective adjuvant therapy in NMI bladder tumor. Since angiogenesis is an essential factor in solid tumor progression and vascular endothelial growth factor (VEGF) is an important factor in angiogenesis, the aim of this study is the assessment of angiogenic factor, VEGF, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical BCG. <b>Materials and Methods:</b> A total of 23 patients with bladder transitional cell carcinoma (TCC) in stage Ta/T1 or carcinoma <i>insitu</i> (CIS), low or high grade, which passed a 2-4 week period from TURBT participated in this study. Blood and urine samples were obtained at first and sixth sessions before instillation of BCG. Enzyme-linked immunosorbent assay (ELISA) method was used to obtain VEGF level in samples. <b>Results:</b> Urine and serum VEGF levels did not change significantly before and after BCG therapy. Changes in VEGF level were significantly different neither in low grade against high grade tumors nor in stage T1 against stage Ta tumors. A significant difference in VEGF level was seen between low grade and high grade tumors in serum after BCG therapy (<i>P</i>=0.007); but not in urine samples. <b>Conclusion:</b> Although intravesical BCG possesses anti-angiogenic activity, it seems that it exerts its effect through pathways other than VEGF, especially in low grade tumors

Optimizing Anesthetic Selection in Transcatheter Aortic Valve Replacement: Striking a Delicate Balance between Efficacy and Minimal Intervention

Patients with severe calcific native aortic valve stenosis (AS) who require valve replacement have two options, surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). TAVR was approved in late 2011 for extremely high-risk patients and was subsequently approved for high-risk (2012), intermediate-risk (2016), and low-risk (2019) patients. In 2019, TAVR procedures surpassed SAVR procedures for the first time in the United States. The approach to anesthesia for this procedure has also evolved. Initially, general anesthesia (GA) was preferred, but currently, conscious sedation (CS) is favored. This review aims to clarify the indications and contraindications for both approaches, as well as the advantages of one approach over the other. Recent studies show that conscious sedation has better outcomes in terms of all-cause mortality, procedure complications such as stroke, myocardial infarction, infection requiring antibiotics, acute kidney injury, and the need for inotropes or vasopressors

Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure - Fig 6

<p>Photomicrograph of proximal tubular cells (PTC) purified from primary cell cultures that were originally derived from NK kidneys (A) and CKD kidneys (B) at passage 1 (P1) original magnification x10. Consolidated growth curve of proximal tubular cells isolated from NK and CKD human renal cells (C). Proximal tubular cells from different age donors were counted after achieving confluency, had the same behavior in culture.</p

Ultrastructural analysis of renal proximal tubular cells using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM).

<p>SEM analysis showing long microvilli on the apical surface membrane of a Proximal tubular cells derived from a NK kidney at passage 3 (A) and passage 6 (C) and the same cell type from a CKD kidney at passage 3 (B) and passage 6 (D); Upper panel shows the cellular morphology magnified x630. TEM analysis showing the integrity of tight junction (arrow) in proximal tubular cells isolated from primary renal NK kidneys (E) and CKD kidney cells (F) at passage 3 (P3) magnified x4780; TEM micrograph showing the ultrastructure of nucleus “N” and other intracellular components in proximal tubular cells of NK (G) and CKD (H) kidneys are similar morphology, magnified x11000.</p

Histology of donor human kidney tissue derived from normal kidneys (NK) and chronic kidney disease-affected kidneys (CKD).

<p>H&E staining,(A & D); Periodic acid-Schiff (PAS) staining, (B & E); Masson’s-Trichrome staining (C & F). No major histological abnormalities were seen in the NK tissues. H&E staining of the CKD kidneys revealed a fibrotic cortex with sclerotic glomeruli and scattered chronic infiltration of inflammatory cells. The arterial walls appeared thickened, and the tubules were dilated and filled with pink casts, illustrating renal thyroidization (D). The PAS staining of CKD tissues showed sclerotic glomeruli with collagen deposition and interstitial fibrosis (E). Tubular atrophy and hyalinosis were also observed (D-E). MT staining of the CKD tissues showed collagen deposition in glomeruli (glomerulosclerosis) and interstitium, as well as a thickening of arterial walls (F). Original magnification x40.</p

Quantitative uptake analysis of primary proximal tubular cells (PTC) derived from NK and CKD kidneys confirms specific uptake of Na⁺ by the cells with no significant difference.

<p>Ouabain treatment increases sodium uptake by inhibiting Na/K ATPase. FACS analysis of Intracellular Na⁺ uptake using the cell permeant Sodium Green Tetra-acetate in (PTC) cells from NK and CKD kidneys (B-C) were similar.</p

Characterization of specific renal cells among the total renal cells isolated from NK and CKD kidneys.

<p>Cell-type specific antibodies and FACS was used to isolate proximal tubular cells (A-B), distal tubular cells (D-E) and podocytes (G-H) in different passages (P3 and P9) of cultured renal cells from NK and CKD kidneys. FACS-based quantification percentage of proximal tubular cells in passage 3 and 9 cells (C), percentage of distal tubular cells (F), percentage of podocytes (I). The result highlights that there is no significant difference between the groups.</p

Oxidative Stress in NK and CKD kidney derived tissues.

<p>Immunohistochemical staining to detect Superoxide dismutase 1 (SOD1) expression in human renal tissues from NK (A) and CKD (B) kidneys. Quantitation of oxidative stress in primary renal cells derived from NK and CKD kidneys using a Glutathione (GSH) assay that utilizes a fluorescent dye Monochlorobimane (MCB), (C). GSH was assayed in cells of passage 3 (P3) to (P9) and 12. The Glutathione levels in renal cells derived from both NK and CKD kidneys were almost similar during the entire cell culture</p