Abstract P234: Pre- And Post-treatment Analysis Of Pendrin In The Urinary Exosome In Primary Aldosteronism

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Fumika Ochiai ◽  
Kenichi Ishizawa ◽  
Yuya Tsurutani ◽  
Tetsuo Nishikawa ◽  
Shigeru Shibata

Background and Aim: Pendrin is a Cl/HCO3 exchanger that is selectively present at the apical membrane in non-α intercalated cells of the renal tubules in the kidney. Besides its role in acid/base homeostasis, accumulating studies provided evidence that pendrin regulates extracellular fluid volume and electrolyte balance. Experimental studies using animal models also indicate that pendrin is upregulated in a high aldosterone state, along with the induction of NaCl cotransporter and epithelial Na channel. However, the regulation of pendrin in human is unclear. The present study was conducted to examine the levels of pendrin in subjects with primary aldosteronism. Methods: Sixteen patients who were diagnosed as primary aldosteronism at Teikyo University Hospital and Yokohama Rosai Hospital were enrolled in this study. We isolated exosomes from pre- and post-treatment urine samples by the ultracentrifugation method, and the levels of pendrin was evaluated by Western blotting. The loading amount was adjusted by creatinine concentration. Purification of exosomal fraction was confirmed by electron microscopy and also by the presence of alix, a marker of exosome. Results and Discussion: Among 16 patients, six received unilateral adrenalectomy and 10 received MR antagonist as the treatment. Mean aldosterone-to renin ratio was 1085. We excluded two subjects because alix was not detected in the pre-treatment samples, and the analysis was done in 14 subjects. In human urine, pendrin was detected at ~110kDa and ~220kDa, the latter likely representing a dimer. We found that pendrin abundance was significantly reduced by 49.8% (P<0.01) in post-treatment samples compared with pre-treatment samples. Therefore, pendrin is altered in primary aldosteronism, likely contributing to the pathophysiology of aldosterone excess in humans.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Michele Provenzano ◽  
Raffaele Serra ◽  
Ashour Michael ◽  
Giuseppina Crugliano ◽  
Alessandra Urso ◽  
...  

Abstract Background and Aims Measurement of urine proteins, mainly through the 24-hour excretion or the albumin-to-creatinine ratio (ACR) has become crucial in current clinical practice in Nephrology. Besides being a biomarker of injury, albuminuria also exerts direct pro-inflammatory and pro-fibrotic effects on renal tubules. Hence, a large number of intervention studies have been aimed at lowering albuminuria levels in patients with Chronic Kidney Disease (CKD). However, albuminuria is a measure characterized by a random variability that has been evaluated in several mechanistic and experimental studies and may be influenced by several factors, such as posture, exercise and dietary factors. The aim of the present study was to evaluate the within-day variability, specifically in a cohort of CKD outpatients who were on Renin-Angiotensin-Aldosterone-System inhibitors (RAASi) therapy. Method We enrolled consecutive CKD patients referred to the Nephrology Unit at Magna Graecia University Hospital of Catanzaro between January 1st and March 30th 2020. Inclusion criteria were: age &gt; 18 years, diagnosis of CKD from any cause, presence of albuminuria in the range 150-3500 mg/g at screening. Patients already treated with RAASi, patients with active malignancy/signs of glomerulonephritis requiring immunosuppressive therapies, were excluded. At screening visit, patients with increased albuminuria were started with an Angiotensin Converting Enzyme inhibitor (ACEi) or an Angiotensin II Receptor Blocker (ARB). A second ambulatory visit was scheduled 1 month after start of RAASi therapy. During this visit, patients were asked to stay in the Renal Unit for 12 hours. They collected urine void for ACR, protein-to-creatinine ratio (PCR) and urine creatinine (Ucreat) assessment at 8am,1pm and 6pm. For each patient, comparisons between ACR, PCR and Ucreat were assessed by Kruskal-Wallis test and Friedman post-hoc, using the Benjamini-Hochberg as adjustment method. Coefficients of variation (CV,standard deviation/mean) were also computed. Results Final analysis included 43 patients (46.5% of males). Mean age was 59.6±16.7 years and median eGFR 41 [21-74] mL/min/1.73m2. A high cardiovascular (CV) risk profile was testified by the prevalence of type 2 diabetes (30.2%) and previous CV disease (34.8%). When patient characteristics were compared across ACR categories (&lt;30, 30-300, &gt;300 mg/g), systolic blood pressure was increased (p=0.020) and mean age decreased from 68.0 to 54.8 years on average (p=0.038). ACR values collected were 189 [38-759], 252 [51-1685] and 229 [56-1185] mg/g at 8am, 1pm and 6pm, respectively, with a CV of 24.6% (95%CI 12.4-39.1). 8am ACR was significantly different from 1pm ACR (p&lt;0.001) and from 6pm ACR (p&lt;0.001). 1 pm ACR was significantly different from 6pm ACR (p=0.002). Median PCR were 335 [115-932], 429 [146-1811] and 447 [151-1465] mg/g respectively at 8am, 1pm and 6pm, with CV being 17.8% (95%CI 9.0-26.6). 8am PCR differed significantly from 1pm and 6pm PCR (p&lt;0.001 for both), while 1pm ACR was lower than 6pm ACR (p&lt;0.001). Ucreat was 66 [53-103], 63 [47-96] and 69 [50-90] mg/dL respectively at 8am, 1pm and 6pm with no significant variation trend. Individual within-day ACR and PCR trends are depicted in the Figure . Conclusion The present analysis showed a significant individual within-day variability of albuminuria, measured as both ACR and PCR, suggesting that another parameter, in addition to those already known, may be responsible for the day-by-day albuminuria variation. Moreover, the absence of variability in Ucreat, namely the denominator of the ACR/PCR formula, suggests that the true variation is likely dependent on the urine protein values. Thus, albuminuria reduction in response to RAASi treatment should be carefully evaluated by measuring ACR/PCR preferentially at a similar time of the day for each patient. This would allow to avoid under- or overestimation of the actual treatment effect.


2014 ◽  
Vol 84 (3-4) ◽  
pp. 0140-0151 ◽  
Author(s):  
Thilaga Rati Selvaraju ◽  
Huzwah Khaza’ai ◽  
Sharmili Vidyadaran ◽  
Mohd Sokhini Abd Mutalib ◽  
Vasudevan Ramachandran ◽  
...  

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.


1972 ◽  
Vol 69 (1) ◽  
pp. 67-76
Author(s):  
Rolf Plesner

ABSTRACT Twenty-two fertile women were treated cyclically in from 4–30 cycles (mean 15.5) with a total of 341 injections of Deladroxate®, an injectable, long-acting oestrogen-progestogen. The injections were administered on the 8th (7th–9th) day of each cycle. Before treatment, the last pre-treatment cycle was controlled by means of daily recordings of the basal body temperature (BBT), urinary excretion of pregnanediol and total pituitary gonadotrophins at certain intervals, and by endometrial biopsies obtained late in the cycle. The effects of Deladroxate® on ovulation, on pituitary gonadotrophic function, and on the endometrium were controlled by the above mentioned parameters during cycles 1, 3, and 6, and all assessments were repeated after discontinuation of treatment. During treatment, there was a statistically significant fall in gonadotrophin excretion values (as compared with the pre-treatment values), and the fall was found to be gradually progressive during treatment. After discontinuation of treatment, there seemed to be a tendency towards an increase in the excretion values. Suppression of ovulation as determined by means of the pregnanediol excretion during treatment, was effective in nearly all of the treatment cycles checked. The fall in pregnanediol excretion was also gradually progressive during treatment, while there was a slight increase in excretion values in the post-treatment period. During treatment, 79 BBT curves were recorded. Nearly 50 % were monophasic, indicating anovulatory cycles, 17 curves were biphasic, but with the rise in temperature occurring at non-characteristic times in the cycles, 18 curves were classified as thermogenic because of a rise in temperature occurring within 24 hours after the injection, and 5 curves were not assessable. During the first month after discontinuation of treatment, 8 out of 10 recorded curves were monophasic. Out of 53 endometrial biopsies obtained around the 23rd day of the cycle, 31 were of the mixed phase type, but showing a predominance of proliferative patterns, 15 were of the secretory type, and 7 were purely proliferative. Out of 15 biopsies obtained in the post-treatment period, only two were of the mixed phase type, 12 were proliferative and one was purely secretory.


2018 ◽  
Vol 75 (4) ◽  
pp. 44-48
Author(s):  
A. Mukhina ◽  
◽  
I. Boichuk ◽  
L. Zhuravliova ◽  
◽  
...  

2008 ◽  
Vol 59 (5) ◽  
Author(s):  
Mirela Dulama ◽  
Nicoleta Deneanu ◽  
Cristian Dulama ◽  
Margarit Pavelescu

The paper presents the experimental tests concerning the treatment by membrane techniques of radioactive aqueous waste. Solutions, which have been treated by using the bench-scale installation, were radioactive simulated secondary wastes from the decontamination process with modified POD. Generally, an increasing of the retention is observed for most of the contaminants in the reverse osmosis experiments with pre-treatment steps. The main reason for taking a chemical treatment approach was to selectively remove soluble contaminants from the waste. In the optimization part of the precipitation step, several precipitation processes were compared. Based on this comparison, mixed [Fe(CN)6]4-/Al3+/Fe2+ was selected as a precipitation process applicable for precipitation of radionuclides and flocculation of suspended solid. Increased efficiencies for cesium radionuclides removal were obtained in natural zeolite adsorption pre-treatment stages and this was due to the fact that volcanic tuff used has a special affinity for this element. Usually, the addition of powdered active charcoal serves as an advanced purifying method used to remove organic compounds and residual radionuclides; thus by analyzing the experimental data (for POD wastes) one can observe a decreasing of about 50% for cobalt isotopes subsequently to the active charcoal adsorption.. The semipermeable membranes were used, which were prepared by the researchers from the Research Center for Macromolecular Materials and Membranes, Bucharest. The process efficiency was monitored by gamma spectrometry.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshimi Sugiura ◽  
Fumiki Okamoto ◽  
Tomoya Murakami ◽  
Shohei Morikawa ◽  
Takahiro Hiraoka ◽  
...  

AbstractTo evaluate the effects of intravitreal ranibizumab injection (IVR) on metamorphopsia in patients with branch retinal vein occlusion (BRVO), and to assess the relationship between metamorphopsia and inner retinal microstructure and other factors. Thirty-three treatment-naïve eyes of 33 patients with macular edema caused by BRVO with at least 12 months of follow-up were included. The degree of metamorphopsia was quantified using the M-CHARTS. Retinal microstructure was assessed with spectral-domain optical coherence tomography. Disorganization of the retinal inner layers (DRIL) at the first month after resolution of the macular edema (early DRIL) and at 12 months after treatment (after DRIL) was studied. Central retinal thickness (CRT), and status of the external limiting membrane as well as ellipsoid zone were also evaluated. IVR treatment significantly improved best-corrected visual acuity (BCVA) and CRT, but the mean metamorphopsia score did not improve even after 12 months. Post-treatment metamorphopsia scores showed a significant correlation with pre-treatment metamorphopsia scores (P < 0.005), the extent of early DRIL (P < 0.05) and after DRIL (P < 0.05), and the number of injections (P < 0.05). Multivariate analysis revealed that the post-treatment mean metamorphopsia score was significantly correlated with the pre-treatment mean metamorphopsia score (P < 0.05). IVR treatment significantly improved BCVA and CRT, but not metamorphopsia. Post-treatment metamorphopsia scores were significantly associated with pre-treatment metamorphopsia scores, the extent of DRIL, and the number of injections. Prognostic factor of metamorphopsia was the degree of pre-treatment metamorphopsia.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3256
Author(s):  
Adam Brewczyński ◽  
Beata Jabłońska ◽  
Agnieszka Maria Mazurek ◽  
Jolanta Mrochem-Kwarciak ◽  
Sławomir Mrowiec ◽  
...  

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1685
Author(s):  
Antonino Grassadonia ◽  
Vincenzo Graziano ◽  
Laura Iezzi ◽  
Patrizia Vici ◽  
Maddalena Barba ◽  
...  

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.


Author(s):  
Gamze Akkus ◽  
Barış Karagun ◽  
Hilal Nur Yaldız ◽  
Mehtap Evran ◽  
Murat Sert ◽  
...  

AbstractObjectivesProlactinoma is the most common cause of pituitary tumours. Current medical guidelines recommend dopamine agonists (cabergoline or bromocriptine) as the initial therapy for prolactinoma. However, surgical removal can also be considered in selected cases, such as patients with macroadenomas with local complications (bleeding or optic chiasm pressure) or those not responding to medical treatment.MethodsThe present retrospective study included patients with prolactinomas (n=43; female, 24; male, 19) who were primarily managed with medical (n=32) or surgical (n=11) treatment.ResultsMacroadenoma (n=29.67%) was commonly detected in both genders (female, 54%; male, 84%). Moreover, the mean pre-treatment prolactin levels were similar in both genders (female, 683.3 ± 1347 ng/mL; male, 685.4 ± 805 ng/mL; p=0.226). Surgically treated patients had a greater reduction in tumour size (27.7 ± 17.9 mm pre-treatment vs. 8.72 ± 14.2 mm post-treatment) than non-surgically treated ones (12.5 ± 7.5 mm pre-treatment vs. 4.1 ± 4.2 mm post-treatment; p=0.00). However, the decrease in prolactin levels was similar between the two patient groups (p=0.108). During the follow-up period (10.6 ± 7.0 years), the average cabergoline dose of the patients was 1.42 ± 1.47 mcg/week.ConclusionsAlthough a surgical approach was considered for selected cases of prolactinoma, the average dose used for medical treatment was highly inadequate for the patients in the present study.


2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Alaa Mouminah ◽  
Austin J. Borja ◽  
Emily C. Hancin ◽  
Yu Cheng Chang ◽  
Thomas J. Werner ◽  
...  

Abstract Background 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used in the clinical management of oncologic and inflammatory pathologies. It may have utility in detecting radiotherapy (RT)-induced damage of oral tissues. Thus, the aim of the present study was to use FDG-PET/CT to evaluate parotid gland inflammation following RT in patients with head and neck cancer (HNC). Methods This retrospective study included patients with HNC treated with photon, proton, or combined photon/proton RT, in addition to chemotherapy. All patients received FDG-PET/CT imaging pre-treatment and 3 months post-treatment. The average mean standardized uptake value (Avg SUVmean) and the average maximum standardized uptake value (Avg SUVmax) of the left and right parotid glands were determined by global assessment of FDG activity using OsiriX MD software. A two-tailed paired t test was used to compare Avg SUVmean and Avg SUVmax pre- and post-RT. Results Forty-seven HNC patients were included in the study. Parotid gland Avg SUVmean was significantly higher at 3 months post-treatment than pre-treatment (p < 0.05) in patients treated with photon RT, but no significant differences were found between pre- and post-treatment Avg SUVmean in patients treated with proton RT or combined photon/proton RT. Conclusion Our results suggest that photon RT may cause radiation-induced inflammation of the parotid gland, and that proton RT, which distributes less off-target radiation, is a safer treatment alternative.


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