scholarly journals Effect of a Low Dose of Carvedilol on Cyclophosphamide-Induced Urinary Toxicity in Rats—A Comparison with Mesna

2021 ◽  
Vol 14 (12) ◽  
pp. 1237
Author(s):  
Anna Merwid-Ląd ◽  
Piotr Ziółkowski ◽  
Marta Szandruk-Bender ◽  
Agnieszka Matuszewska ◽  
Adam Szeląg ◽  
...  
Keyword(s):  
Side Effects ◽  
Urinary Bladder ◽  
Kidney Function ◽  
Significant Interaction ◽  
Low Dose ◽  
Asymmetric Dimethylarginine ◽  
Hemorrhagic Cystitis ◽  
Adma Level ◽  
Plasma Adma ◽  
Better Than

One of the major side effects of cyclophosphamide (CPX)—an alkylating anticancer drug that is still clinically used—is urotoxicity with hemorrhagic cystitis. The present study was designed to evaluate the ability of carvedilol to protect rats from cyclophosphamide-induced urotoxicity. Rats were injected intraperitoneally (i.p.) with CPX (200 mg/kg) and administered carvedilol (2 mg/kg) intragastrically a day before, at the day and a day after a single i.p. injection of CPX, with or without mesna (40, 80, and 80 mg/kg i.p. 20 min before, 4 h and 8 h after CPX administration, respectively). Pretreatment with carvedilol partly prevented the CPX-induced increase in urinary bladder and kidney index, and completely protects from CPX-evoked alterations in serum potassium and creatinine level, but did not prevent histological alterations in the urinary bladder and hematuria. However, carvedilol administration resulted in significant restoration of kidney glutathione (GSH) level and a decrease in kidney interleukin 1β (IL-1β) and plasma asymmetric dimethylarginine (ADMA) concentrations. Not only did mesna improve kidney function, but it also completely reversed histological abnormalities in bladders and prevented hematuria. In most cases, no significant interaction of carvedilol with mesna was observed, although the effect of both drugs together was better than mesna given alone regarding plasma ADMA level and kidney IL-1β concentration. In conclusion, carvedilol did not counteract the injury caused in the urinary bladders but restored kidney function, presumably via its antioxidant and anti-inflammatory properties.

PLASMA ASYMMETRIC DIMETHYLARGININE LEVEL AND THE ASSOCIATION WITH CARDIOVASCULAR RISK FACTORS IN END STAGE CHRONIC KIDNEY DISEASE

2016 ◽  
pp. 51-60
Author(s):  
Trong Ai Quoc Hoang ◽  
Tam Vo ◽  
Viet Thang Hoang
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Cardiovascular Risk Factors ◽  
Asymmetric Dimethylarginine ◽  
Adma Level ◽  
Plasma Adma ◽  
End Stage ◽  
Esrd Patients

Objectives: we aimed to assess the levels of plasma ADMA in end stage renal disease (ESRD) patients without dialysis and its association with cardiovascular risk factors. Materials and Methods: This is a controlled cross-sectional study. Plasma ADMA level and other variables were measured in 30 patients of ESRD without dialysis and in 30 control healthy persons. Plasma ADMA levels were determined by enzyme linked immunosorbent assay (ELISA) using kits provided by immunodiagnostic AG, Germany. Data was analyzed by SPSS 19.0. Results: Mean level of ADMA in ESRD patients was 0.88 ± 0.27 µmol/L. Mean level of ADMA in healthy people was 0.49 ± 0.13 µmol/L, with significiant difference (p<0.01). There was not significiant difference of mean level of ADMA between male and female. Plasma ADMA levels were not correlated with age, serum CRP and cholesterol levels. There were correlation between ADMA level and BMI (r=-0.31, p<0.05), and Hb level (r=-0.58, p<0.01), and Hct (r=-0.60, p<0.01). It existed correlation between ADMA level and estimated glomerular filtration rate (GFR) (r=-0.63, p<0.01). Conclusion: In ESRD, mean level of ADMA is 0.88 ± 0.27 µmol/L. There is a significiant elevation of ADMA level in ESRD compared to healthy people. A negative correlation exists between ADMA level with BMI, Hb level, Hct and eGFR. Key words: Asymmetric dimethylarginine, end stage chronic kidney disease, cardiovascular risk factor, correlation.

scholarly journals Repeated Low-Dose Acrolein Triggers Irreversible Lamina Propria Edema in Urinary Bladder, Transient Voiding Behavior and Widening of Eyes to Mechanical Stimuli

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3477
Author(s):  
Sanghee Lee ◽  
Jiwoo Lee ◽  
Chandresh Khimji ◽  
Jaebeom Lee ◽  
Shelle Malkmus ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Lamina Propria ◽  
Low Dose ◽  
Clinical Symptoms ◽  
Hemorrhagic Cystitis ◽  
Behavioral Assessment ◽  
High Volume ◽  
Mechanical Stimuli ◽  
Therapeutic Benefits ◽  
Wide Range

Acrolein is a metabolite of cyclophosphamide (CYP), an alkylating agent used for a wide range of benign and malignant diseases. CYP treatments are known to trigger hemorrhagic cystitis in patients and animals. Significant effort has been made to prevent CYP/acrolein-induced cystitis, while still maintaining its therapeutic benefits. As a result, supplementary therapeutic options to mediate the protective role against CYP/acrolein and lower doses of CYP are currently given to targeted patients, as compared to past treatments. There is still a need to further study the effects of the repeated low-dose CYP/acrolein on the pathophysiology of the urinary bladder. In our study, a one-time treatment of acrolein and repeated low-dose acrolein triggered the thickening of the smooth muscle and lamina propria in the urinary bladder of C57BL/6J mice, respectively. The first dose of acrolein did not trigger voiding dysfunction, but the second dose triggered high-volume low-frequency voiding. Interestingly, our new scoring criteria and concurrent behavioral assessment revealed that mice with repeated low-dose acrolein had a wider opening of eyes in response to mechanical stimuli. Our study suggests that clinical symptoms among patients undergoing prolonged low-dose CYP may differ from previously reported symptoms of CYP-induced hemorrhagic cystitis.

Removal of inelastically scattered electrons substantially increases phase contrast on frozen-hydrated molecules

1987 ◽  
Vol 45 ◽  
pp. 652-653
Author(s):  
John P. Langmore ◽  
Brian D. Athey
Keyword(s):  
Electron Diffraction ◽  
Phase Contrast ◽  
Low Dose ◽  
Dark Field ◽  
Biological Structure ◽  
Bright Field ◽  
Low Contrast ◽  
Negative Stain ◽  
The Difference ◽  
Better Than

Although electron diffraction indicates better than 0.3nm preservation of biological structure in vitreous ice, the imaging of molecules in ice is limited by low contrast. Thus, low-dose images of frozen-hydrated molecules have significantly more noise than images of air-dried or negatively-stained molecules. We have addressed the question of the origins of this loss of contrast. One unavoidable effect is the reduction in scattering contrast between a molecule and the background. In effect, the difference in scattering power between a molecule and its background is 2-5 times less in a layer of ice than in vacuum or negative stain. A second, previously unrecognized, effect is the large, incoherent background of inelastic scattering from the ice. This background reduces both scattering and phase contrast by an additional factor of about 3, as shown in this paper. We have used energy filtration on the Zeiss EM902 in order to eliminate this second effect, and also increase scattering contrast in bright-field and dark-field.

A Developmental Study of Intonation Recognition

1968 ◽  
Vol 11 (4) ◽  
pp. 825-832 ◽  
Author(s):  
Marilyn M. Corlew
Keyword(s):  
Significant Interaction ◽  
Multiple Choice ◽  
Semantic Content ◽  
First Grade ◽  
Choice Test ◽  
Developmental Study ◽  
Multiple Choice Test ◽  
The Third ◽  
Matching Test ◽  
Better Than

Two experiments investigated the information conveyed by intonation from speaker to listener. A multiple-choice test was devised to test the ability of 48 adults to recognize and label intonation when it was separated from all other meaning. Nine intonation contours whose labels were most agreed upon by adults were each matched with two English sentences (one with appropriate and one with inappropriate intonation and semantic content) to make a matching-test for children. The matching-test was tape-recorded and given to children in the first, third, and fifth grades (32 subjects in each grade). The first-grade children matched the intonations with significantly greater agreement than chance; but they agreed upon significantly fewer sentences than either the third or fifth graders. Some intonation contours were matched with significantly greater frequency than others. The performance of the girls was better than that of the boys on an impatient question and a simple command which indicates that there was a significant interaction between sex and intonation.

CONTRACEPTION IN DIABETIC PATIENTS

1974 ◽  
Vol 77 (3_Suppl) ◽  
pp. S87-S94 ◽  
Author(s):  
J. Wiese ◽  
M. Osler
Keyword(s):  
Side Effects ◽  
Contraceptive Method ◽  
Low Dose ◽  
Unplanned Pregnancy ◽  
Intrauterine Device ◽  
Diabetic Patients ◽  
Intrauterine Contraception ◽  
Unwanted Pregnancies ◽  
Unreliable Method ◽  
Retrospective Investigation

ABSTRACT A retrospective investigation was made of contraception in diabetic women delivered in our department in 1969 and 1970. Seventy-nine (69 per cent) answered the questionnaires. About one third had found the contraceptive instruction insufficient. A shift from conventional to intrauterine contraception and sterilization was seen, but nearly 25% of the patients were still using conventional methods, mainly the condom. The patients consider this an unreliable method. Thirty-three patients were using intrauterine contraception. Although 10 of them had bleeding irregularities, all were satisfied with the method. Sterilization had been performed on 17 patients, all of whom were fully satisfied and had experienced no side effects. Four of 11 insulin-requiring diabetics, who have used combined oestrogen-progesterone medication have had difficulties in the regulation of the diabetes. Of 24 unwanted pregnancies 12 occurred since the hospitalization in 1969 and 1970. In diabetic women the contraceptive method should either be sterilization, intrauterine device or low dose progestagens, and only in a few cases conventional. A thorough contraceptive instruction as well as a close control of the diabetic women are of importance in order to avoid unplanned pregnancy. The best way to achieve this is by having an out-patient clinic in connection with the obstetrical department to supervise contraception in all diabetic women in the area.

scholarly journals Molecularly imprinted membrane for transport of urea, creatinine, and vitamin B12 as a hemodialysis candidate membrane

2021 ◽  
Vol 19 (1) ◽  
pp. 806-817
Author(s):  
Muhammad Cholid Djunaidi ◽  
Nabilah Anindita Febriola ◽  
Abdul Haris
Keyword(s):  
Polyethylene Glycol ◽  
Vitamin B12 ◽  
Kidney Function ◽  
Cross Linking ◽  
Vitamin B ◽  
Molecularly Imprinted ◽  
Selective Transport ◽  
Molecularly Imprinted Membrane ◽  
Better Than ◽  
Imprinted Membrane

Abstract High levels of urea and creatinine in the blood are a sign of decreased kidney function. To remove these substances from the blood, hemodialysis which utilizes membranes could be used. In this study, a molecularly imprinted membrane (MIM) was synthesized for the selective transport of urea. The synthesis is initiated with the polymerization of eugenol into polyeugenol and then into polyeugenoxy acetate (PA). The PA is then contacted with urea and then used as the functional polymer in the synthesis of MIM with polysulfone as the membrane base, and polyethylene glycol as the cross-linking agent. The result was later analyzed with FTIR and SEM-EDX. The membrane is then used in the transport of urea, creatinine, and vitamin B12 and then compared with the non-imprinted membrane (NIM) performance. By using UV-Vis spectrophotometry, the results showed that the membrane with 10 h heating variation is able to transport more urea and is more selective than NIM; this proves that the urea template on the MIM enables it to recognize urea molecules better than creatinine and vitamin B12. The order of transport from the best results is urea > creatinine > vitamin B12.

scholarly journals Combined low-dose everolimus and low-dose tacrolimus after Alemtuzumab induction therapy: a randomized prospective trial in lung transplantation

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alberto Benazzo ◽  
Ara Cho ◽  
Anna Nechay ◽  
Stefan Schwarz ◽  
Florian Frommlet ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Lung Transplantation ◽  
Kidney Function ◽  
Induction Therapy ◽  
Low Dose ◽  
Prospective Trial ◽  
Control Group ◽  
Long Term Outcomes ◽  
Maintenance Immunosuppression

Abstract Background Long-term outcomes of lung transplantation are severely affected by comorbidities and development of chronic rejection. Among the comorbidities, kidney insufficiency is one of the most frequent and it is mainly caused by the cumulative effect of calcineurin inhibitors (CNIs). Currently, the most used immunosuppression protocols worldwide include induction therapy and a triple-drug maintenance immunosuppression, with one calcineurin inhibitor, one anti-proliferative drug, and steroids. Our center has pioneered the use of alemtuzumab as induction therapy, showing promising results in terms of short- and long-term outcomes. The use of alemtuzumab followed by a low-dose double drug maintenance immunosuppression, in fact, led to better kidney function along with excellent results in terms of acute rejection, chronic lung allograft dysfunction, and survival (Benazzo et al., PLoS One 14(1):e0210443, 2019). The hypothesis driving the proposed clinical trial is that de novo introduction of low-dose everolimus early after transplantation could further improve kidney function via a further reduction of tacrolimus. Based on evidences from kidney transplantation, moreover, alemtuzumab induction therapy followed by a low-dose everolimus and low-dose tacrolimus may have a permissive action on regulatory immune cells thus stimulating allograft acceptance. Methods A randomized prospective clinical trial has been set up to answer the research hypothesis. One hundred ten patients will be randomized in two groups. Treatment group will receive the new maintenance immunosuppression protocol based on low-dose tacrolimus and low-dose everolimus and the control group will receive our standard immunosuppression protocol. Both groups will receive alemtuzumab induction therapy. The primary endpoint of the study is to analyze the effect of the new low-dose immunosuppression protocol on kidney function in terms of eGFR change. The study will have a duration of 24 months from the time of randomization. Immunomodulatory status of the patients will be assessed with flow cytometry and gene expression analysis. Discussion For the first time in the field of lung transplantation, this trial proposes the combined use of significantly reduced tacrolimus and everolimus after alemtuzumab induction. The new protocol may have a twofold advantage: (1) further reduction of nephrotoxic tacrolimus and (2) permissive influence on regulatory cells development with further reduction of rejection episodes. Trial registration EUDRACT Nr 2018-001680-24. Registered on 15 May 2018

scholarly journals Low-dose IL-2 therapy limits the reduction in absolute numbers of circulating regulatory T cells in rheumatoid arthritis

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110113
Author(s):  
Sheng-Xiao Zhang ◽  
Jia Wang ◽  
Cai-Hong Wang ◽  
Rui-Huan Jia ◽  
Ming Yan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Side Effects ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Immune Tolerance ◽  
Low Dose ◽  
Fold Increase ◽  
Plain Language ◽  
T Subsets

Background: Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4+T subsets and the clinical feasibility of IL-2 therapies in patients with RA. Methods: The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment with 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment. Results: RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs ( p < 0.05). Patients treated with low-dose IL-2 had a three-fold increase in absolute anti-inflammatory Treg counts, as well as a two-fold increase in the other CD4+T subsets. Moreover, post-treatment levels of markers of disease activity in RA patients treated with IL-2 were significantly lower than the baseline values ( p < 0.001), with no apparent side effects. Conclusion: Decreased absolute counts of circulating CD4+T lymphocyte subsets were observed in patients with RA. Circulating Tregs, which mediate immune tolerance, may be involved in the pathogenesis and progression of RA; however, this was ameliorated by low-dose IL-2, without obvious side effects. Plain language summary Low-dose IL-2 treatment for rheumatoid arthritis • Circulating Tregs may be involved in the pathogenesis and progression of RA. • The absolute count of Tregs was significantly correlated with disease activity measures. • Low-dose IL-2 was able to effectively expade Tregs and help for RA patients’ symptoms remission without evaluated side effects.

scholarly journals Acute Childhood Cardiorenal Syndrome and Impact of Cardiovascular Morbidity on Survival

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Wasiu A. Olowu
Keyword(s):  
Risk Factors ◽  
Kidney Function ◽  
Preventive Measures ◽  
Cardiorenal Syndrome ◽  
Cardiovascular Morbidity ◽  
Acute Glomerulonephritis ◽  
Cumulative Mortality ◽  
All Cause Mortality ◽  
Type 3 ◽  
Better Than

Cardiorenal syndrome (CRS) clinical types, prevalence, aetiology, and acute cardiovascular morbidity impact on the outcome of acute kidney function perturbation were determined. Forty-seven of 101 (46.53%) patients with perturbed kidney function had CRS. Types 3 and 5 CRS were found in 10 and 37 patients, respectively. Type 3 CRS was due to acute glomerulonephritis (AGN; ), captopril (), frusemide (), and hypovolaemia (). Malaria-associated haemoglobinuria (), septicaemia (), lupus nephritis (), tumour lysis syndrome (), and acute lymphoblastic leukaemia () caused Type 5 CRS. The cumulative mortality in hypertensive CRS was similar to nonhypertensive CRS (51.4% versus 40.9%; ). Mortality in CRS and non-CRS was similar (45.7% versus 24.5%; ). Type 5 survived better than type 3 CRS (66.7% versus 12.5%; ). Risk factors for mortality were Type 3 CRS (), AGN-associated CRS (), dialysis requiring CRS (), and heart failure due to causes other than anaemia (). All-cause-mortality was 34.2%. Preventive measures aimed at the preventable CRS aetiologies might be critical to reducing its prevalence.

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