Search

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.

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.

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.