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Catalog of Herbs
Published in James A. Duke, Handbook of Medicinal Herbs, 2018
Contains three highly active cardiac glycosides, bovocides A, B, and C, all about as toxic as ouabain. As much as 10% sinistrin is reported. Nabigenin, isolated from the bulb, is a mixture largely composed of scilliglaucosidin; hellebrigenin is also reported. Other complex compounds and their derivatives occur.3,33
Rodent Autosomal Dominant Polycystic Kidney Disease Models
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Sara J. Holditch, Raphael A. Nemenoff, Katharina Hopp
The principal measurement of disease progression or treatment effect in ADPKD patients is glomerular filtration rate (GFR) or serum creatinine based estimated GFR (eGFR) as a marker of renal function. Similarly, noninvasive measurements of kidney function such as blood urea nitrogen (BUN) and creatinine measurements (serum, plasma, urine) are ubiquitously used in rodent models of ADPKD. BUN is typically evaluated using a colorimetric assay designed to detect urea nitrogen levels in plasma obtained either sequentially from cheek or retro-orbital bleeds, or terminally by cardiac puncture. Creatinine levels are also determined by either colorimetric assay or HPLC using plasma or sequentially collected urine (e.g., spot urine or 24 h urine collected in metabolic cages). As in patients, BUN and creatinine levels are influenced by age and gender. Further, small animal model BUN levels are also influenced by mouse strain and thus require age-, sex-, and strain-matched controls (Figure 10.2e). Jackson Laboratory provides a physiological data summary sheet for each of their wildtype strains, which includes normal BUN and creatinine values for male and female mice at different ages as a reference and guideline for assay accuracy. However, as for ADPKD patients, BUN and creatinine levels in rodents lack the sensitivity to detect changes in early disease progression as their values only change once significant renal damage has occurred.17,58 An alternative and likely more sensitive way of determining renal function is through transdermal measurements of the clearance of fluorescein isothiocyanate (FITC)-labeled sinistrin. This method has been evaluated once in an ADPKD rodent model using an optical imaging protocol.59 Here, FITC-labeled sinistrin was injected via tail-vein and fluorescence clearance was monitored by acquiring images of the anesthetized rats’ ear every two minutes. To date, MediBeacon has developed a wearable monitor utilizing the same principle of monitoring fluorescence clearance but allows longitudinal measurements without restraining the animal. This continuous renal function monitor has shown high sensitivity in many rodent AKI and CKD studies.60,61 However, its ability to detect changes in renal function in early versus late stage PKD has not been evaluated in murine ADPKD models.
Noninvasive assessment of radiation-induced renal injury in mice
Published in International Journal of Radiation Biology, 2021
Anis Ahmad, Junwei Shi, Saba Ansari, Jumana Afaghani, Judith Molina, Alan Pollack, Sandra Merscher, Youssef H. Zeidan, Alessia Fornoni, Brian Marples
A major advantage of the FITC-sinistrin technique is that measurements of GFR are made on non-restrained and conscious animals over a prolonged time period in a single event, and repeated measurements can be made within a short-time period over a number of days without the necessity for blood sampling. In contrast, the toxicity associated with the use of some X-ray contrast agents and the prolonged anesthesia needed for X-ray imaging are less conducive to making daily measurements or multiple assessments with a single week. Also, the CT imaging is also prone to measurement artifacts from animal motion and respiration, although this can be minimized by calculating GFR values from captured images. However, the FITC-sinistrin technique is not without limitations. Skin edema and excessive pigmentation may reduce the efficacy of the detector, factors that do not impact GFR measurements by CT imaging. Also, the FITC-sinistrin methodology bilaterally assessed GFR, from both kidneys simultaneously, whereas both the left and right kidneys can be independently assessed using CT imaging. This latter distinct between the two approaches allows GFR measurements to be made after unilateral disease or damage, or combined injury modeling in which systemic nephrotoxic agents are given and then compared with concurrent irradiation on a single kidney such that CT can be compared with chemotherapy plus irradiation in separate kidneys within the same animal.
Inhibitors of the renin-angiotensin system ameliorates clinical and pathological aspects of experimentally induced nephrotoxic serum nephritis
Published in Renal Failure, 2018
M. E. Ougaard, H. E. Jensen, I. D. Thuen, E. G. Petersen, P. H. Kvist
The glomerular filtration rate (GFR) was measured by a preclinical transdermal GFR monitor (Medibeacon GmBH, Mannheim, Germany) as previously described [11]. In short, two times two centimeters fur on the back of the mice were depilated 24 h prior to GFR measurements. FITC-sinistrin (Medibeacon GmBH, Mannheim, Germany) was dissolved in physiological saline, and a stock of 15 mg/ml was prepared and stored at –20 °C away from light. Mice were shortly anesthetized while the GFR monitor was adhered to the depilated area. Subsequently, the mice were injected with 7.5 mg/100g BW of FITC-sinistrin intravenously into the tail vein. The mice were placed for one hour in a single-cage. Afterward the tape was removed and the GFR data were transferred and GFR was calculated.
Simulated vehicle exhaust exposure (SVEE) in rats impairs renal mitochondrial function
Published in Clinical and Experimental Hypertension, 2020
Camila Kochi, Indira Pokkunuri, Ankita Salvi, Mohammad Asghar, Samina Salim
The glomerular filtration rate (GFR) was measured in the CON and SVEE rats using fluorescein-isothiocyanate (FITC) conjugated sinistrin and a transdermal GFR measurement device (MediBeacon, St. Louis, MO) (27). The amount of FITC-Sinistrin was calculated and prepared for each rat according to their body weight per the manufacturer’s instructions, 5 mg FITC-Sinistrin/100 g body weight. The transdermal device was placed on a depilated region on the back of the rat and the appropriate dose of FITC-Sinistrin was administered intravenously. The rat was then housed individually for 2 hours and the read-out data from the transdermal device were recorded. The excretion half-life was used to determine the GFR using the following equation: