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In Reinke's space of human vocal fold, type III collagen forms a three dimensional network and this contains numerous minute chambers in between these fibers. These compartments are occupied by glycosaminoglycans and glycoproteins. In laryngeal fold lesions, such as Reinke's edema and vocal fold polyps, proteoglycan (PG)/hyaluronic acid (HA) components of extracellular matrix increased. We investigated the size and quantity of the minute chambers within Reinke's space, filled with PG/HA with the aid of transmission electron microscopy. Eight vocal fold polyps and 10 mucosal biopsies (as control group) were all evaluated by light microscopy and electron microscopy. We detected that PG/HA in extracellular matrix had been increased in vocal fold lesions when compared with control group, by Alcian Blue-pH 2.5 stain. The mean volume of the chambers in Reinke's space of normal larynx was measured as 0.040233 µm2 whereas the mean volume of these chambers in vocal fold polyps was measured as 6.420221 µm2. The difference between the volumes of these chambers in vocal fold polyps and in control group was statistically significant (P = 0.001). Within these chambers PG/HA were found and PG/HA filling these chambers were increased in vocal fold polyps. We think proteoglycan and glycosaminoglycans, especially HA, play an important role in determining biochemical properties of vocal fold lesions.

The aim of this study was to investigate the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the glomerulus through the evaluation of podocyturia in patients with diabetic kidney disease (DKD).The study population was composed of 40 male patients with type 2 diabetes mellitus; 22 of them received SGLT2i (SGLT2i group), and the others who did not were the control. The DKD-related parameters of patients were monitored before SGLT2i initiation, and then in the third and sixth month of the follow-up period. Patients' demographic, clinical, laboratory, and follow-up data were obtained from medical charts. Microalbuminuria was measured in 24-h urine. The number of podocytes in the urine was determined by immunocytochemical staining of two different markers, namely podocalyxin (podx) and synaptopodin (synpo). Concentrations of urine stromal cell-derived factor 1a and vascular endothelial growth factor cytokines were quantified with an enzyme-linked immunosorbent assay kit.At the end of the follow-up period, decreases in glycosylated hemoglobin, glucose, systolic and diastolic blood pressure, uric acid level, and microalbuminuria, and improvement in body mass index level and weight loss were significant for the SGLT2i group. On the other hand, there was no significant difference in terms of these parameters in the control group. The excretion of synaptopodin-positive (synpoAt the end of the follow-up period, male patients receiving SGLT2i had better DKD-related parameters and podocyturia levels compared to baseline and the control group. Our data support the notion that SGLT2i might have structural benefits for glomerular health.背景: 本研究旨在通过对糖尿病肾病(DKD)患者尿足细胞的评估, 探讨钠葡萄糖共转运体2抑制剂(SGLT2i)对肾小球的影响。 方法: 研究对象为40例男性2型糖尿病患者, 其中22例接受SGLT2i治疗(SGLT2i组), 另22例未接受SGLT2i治疗作为对照组。在SGLT2i治疗前、随访期第3个月和第6个月监测患者的DKD相关参数。从病历中获得患者的人口学、临床、实验室和随访数据。24小时中测定尿微量白蛋白。通过两种不同的标记物, 即Podocalyxin (podx)和Synaptopodin (synpo)的免疫细胞化学染色来确定尿足细胞的数量。用酶联免疫吸附分析试剂盒检测尿基质细胞衍生因子1a和血管内皮生长因子细胞因子的浓度。 结果: 在随访结束时, SGLT2i组糖化血红蛋白、血糖、收缩压、舒张压、尿酸水平、微量白蛋白尿均显著下降, 体重指数和体重减轻明显改善。另一方面, 对照组的这些参数没有显著差异。SGLT2i组synpo+和podx+的排泄量在随访期结束时显著减少, 而对照组无明显变化。 结论: 在随访期结束时, 接受SGLT2i治疗的男性患者与基线和对照组相比, 有更好的DKD相关参数和尿足细胞水平。我们的数据支持SGLT2i对肾小球健康有结构性益处的观点。.

Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors which are a class of oral anti-diabetic drugs are being used in the treatment of type 2 diabetes (T2D). Basically these drugs reduce blood glucose by blocking glucose reabsorption of primary sodium-coupled glucose transporter in the proximal tubules. Diabetic nephropathy (DN) is a progressive disease with the pathology of glomerular filtration barrier damage and loss of podocytes. In this respect, podocyturia which is the case characterized with presence of podocytes in urine have recently been considered to be a candidate marker for glomerular damage. Therefore, we aimed to investigate effects of SGLT2 inhibitors on glomerulus through the evaluation of podocyturia in DN patients. Method Our study population was composed of two T2D patient groups; one of which received SGLT2 inhibitor (SGLT2 group) and the other one is control which did not received. Patients with T2D for at least 5 years, diagnosed with DN and having microalbuminuria >30 mg/day, glomerular filtration rate (GFR) >60 ml/min and HbA1c< 8.5 were involved. In addition, all patients had received angiotensin converting enzyme inhibitor or angiotension receptor blocker for at least 6 months. Nephrologic parameters of patients were monitored before and 3rd and 6th month of follow up period. Patients’ age, sex, diabetes duration and HbA1c value were obtained from medical charts. GFR was calculated using the abbreviated MDRD formula. Microalbuminuria was measured in 24 hour urine. Number of podocytes in the urine was determined by immunocytochemical staining of two different markers as podocalyxin (podx) and synaptopodin (synp). Statistical analyses were carried out using Statistical Package for the Social Sciences version (SPSS) 24.0 and statistical significance was set as p Results We evaluated a total of 29 patients (mean age: 57.59 ± 9.66). The number of patients for SGLT2 and control groups are 18 (mean age: 54.89 ± 7.73) and 11 (mean age: 62.00 ± 11.60) respectively. Between these two groups, there was no statistical difference with respect to durations of diabetes (p=0.875) and HbA1c (p=0.05) values except for age (p=0.023) in which control group is statistically higher than the SGLT receiving group. Among the patients receiving SGLT2 inhibitor, podocyturia and microalbuminuria (mca) levels in the 6th month of follow up period were statistically lower than the initial ones [p=0.039 (synp), p=0.016 (podx) and p=0.011 (mca) respectively] while there was no statistical difference for creatinine clearance rate between the initial and follow up period (p:0.371 and ;p=0.111) (Figure-1). For control group, although podocyturia was significantly reduced in the 6th month of follow up period [p=0.013 (synp) and p:0.005 (podx)], microalbuminuria (p=0.263) in addition to creatinine clearance (p:0.214; p=0.173) did not change significantly (p=0.263). Furthermore, while there was no significant difference for initial microalbuminuria level between the control and SGLT2 groups (p=0.353); in the 3rd and 6th month follow up period, microalbuminuria was significantly lower than the control group accordingly (p=0.011 and p=0.015 respectively). Conclusion According to our preliminary results; patients receiving SGLT2 inhibitors had better microalbuminuria levels than the ones did not and this parameter was correlated with podocyturia. However, even though microalbuminuria of the control group did not change during the follow up period, podocyturia was found out as reduced in the 6th month of follow up period. This discrepancy in the podocyturia level could be resulted from lower number of patients in control so that there is need for evaluation of more patients to emphasize podocyte protective effect of SGLT2 inhibitors.

BACKGROUND: Monopolar electrocautery is an important tool for harvesting the pedicular internal thoracic artery (ITA) in cardiac surgery. The different power outputs of cautery may affect graft integrity and long-term patency. This study aimed to identify the optimal threshold of electrocautery power for ITA harvest. METHODS: This prospective study included 30 patients who underwent elective coronary artery bypass surgery at the Medipol Mega University Hospital. The ITA was harvested by monopolar electrocautery after a median sternotomy. The output of cautery was adjusted at 20 W in group A and 40 W in group B. Three to 4 cm of a distal ITA sample from each patient was examined under a light microscope by two independent pathologists. RESULTS: The ITA harvest time was longer in group A (21.2 ± 7.5 vs 10.3 ± 8.1 min, p < 0.001) than in group B. ITA free flow was similar in the two groups (43.6 ± 48.7 vs 51.7 ± 45.0 Ml/min, p = 0.762). Mild to moderate injury in the endothelial and sub-endothelial sample was more frequent in the low-cautery group (p = 0.0037). CONCLUSIONS: ITA endothelial integrity was found to be better preserved with 40W electrocautery. Moreover, 20W of monopolar electrocautery may not be safe in pedicular ITA harvesting.

Renal involvement can develop before detection of microalbuminuria in type 2 diabetes. There is an interest in finding biomarkers to detect diabetic nephropathy (DN) earlier and identify progression risk. Podocyturia emerge as a marker for early kidney damage however standardization problems hamper its widespread use. We aimed to investigate the value of podocyturia for the detection of early DN. Herein we report our preliminary results. Our study population was composed of three type 2 diabetic patient groups and a healthy control group. Diabetic groups were defined as follows; group 1: patients without microalbuminuria who had HbA1c 8.5%; group 3: patients with diabetic retinopathy who had proteinuria >1g/day and/or microalbuminuria >300 mg/day and group 4: healthy volunteers without any known disease. Patients with glomerular filtration rate (GFR) below 30 ml/min were excluded. GFR was calculated using the abbreviated MDRD formula. Microalbuminuria was measured in 24 hour urine. Number of podocytes in the urine was determined by immunocytochemical staining of podocalyxin. Due to the known expression of podocalyxin in the female genital tract, only males were included. Statistical analyses were carried out using Statistical Package for the Social Sciences version (SPSS) 24.0 and statistical significance was set as p We examined a total of 119 patients (mean age 57.35 ± 12.75 yrs.). Patient distribution in each group was as follows; group 1: 24(20%); group 2: 26(22%); group 3: 24(20%) and group 4: 45(38%) patients. There was no significant difference in mean age (p=0.582) and duration of diabetes (p=0.517) between the diabetic groups. The mean GFR was significantly lower in group 3 than in group 1 and 2 (p According to our preliminary results; podocyturia assessed by podocalyxin immunostaining does not seem to be increased in male diabetic patients without proteinuria. Further studies on larger patient groups and using different podocyte markers might clarify the value of podocyturia as an early marker of DN.

Recent studies showed that JAK/STAT pathway plays role in glomerular damages. The fact that STAT3 could be activated also by oxidative stress make Puromycin Aminonucleoside (PAN) Nephrosis model very appropriate for examination of STAT3 expression changes in glomerular pathology. Along with a control group, three PAN groups sacrificed on different days were formed by the i.p. injection of PAN for 5 consecutive days. Throughout the experiment, 24-hour-urines were collected on specific days and proteinuria levels were monitored. At the end of the experiments, tissue specimens were stained immunohistochemically for both total and phosphorylated STAT3 and evaluated subjectively. They were also examined ultrastructurally in transmission electron microscope. The proteinuria levels did not increase significantly on 5th day but showed a dramatic increase on 10th and 15th days. On 20th and 25th days, urinary protein levels gradually decreased. Ultrastructural examinations showed glomerular damages such as significant decrease in slit pore number, a significant gradual increase in glomerular basement membrane thickness and podocyte hypertrophy on 5th and 15th days; besides significant increase in mesangial matrix. The first significant increases in phosphorylated and total STAT3 levels occurred in 5th day and 15th day groups respectively. These increases diminished in 25th day group. Regarding all the findings, it was deduced that STAT3 is one of the active factors in glomerular pathologies.

Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed by massive proteinuria, severe damage on endocytotic activity of epithelial cells and postmodification of endocytosed compounds. However, total PA nephrosis (PAN) mechanism cannot be understood. We aimed to study glomerular function, foot process degeneration and transport pathways of podocytes in pre-proteinuria and acute PAN rats. Eighteen male Wistar albino rats were divided into three groups: control, pre-proteinuria and acute nephrosis groups (n=6). PA was injected into pre-proteinuria group for three times and acute group for nine times. Proteinuria levels in urine, creatinine and albumin levels in blood were detected 24 hours after PA injections. Renal cortex samples were prepared for transmission electron microscopy. Proteinuria levels in acute group significantly elevated, whereas creatinine clearance, serum albumin levels and urine volumes diminished compared to control and pre-proteinuria groups. In pre-proteinuria group, hypertrophy and structurally rich cytoplasm were detected only within podocytes. Acute group had various protein absorption granules secreted from podocyte cytoplasm to the urinary space through exocytosis after lysosomal digestion; but not observed in pre-proteinuria group. The number of slit pores in pre-proteinuria group decreased, particularly related to fusion of foot processes, subsequently leading to proteinuria. We concluded that foot process fusion begins prior to development of proteinuria although their serum albumin and creatinine clearance levels do not differ significantly. Additionally, we suggested that in acute PAN, first affected glomerular cells could be podocytes and there could be a correlation between glomerular function and number of slit pores.