Comparison of effects of two hemoglobin-based O2carriers on intestinal integrity and microvascular leakage

2002 ◽  
Vol 283 (4) ◽  
pp. H1292-H1301 ◽  
Author(s):  
Ann L. Baldwin ◽  
Elizabeth B. Wiley ◽  
Abdu I. Alayash
Keyword(s):  
Clinical Trials ◽  
The United States ◽  
Blood Substitutes ◽  
Intestinal Epithelial ◽  
Human Hemoglobin ◽  
Sprague Dawley ◽  
Intestinal Integrity ◽  
Sprague Dawley Rats ◽  
The Mean ◽  
Epithelial Disruption

Two “blood substitutes,” a diaspirin cross-linked human hemoglobin [bis(3,5 dibromosalicyl)fumarate, DBBF-Hb] and a bovine polymerized hemoglobin (PolyHbBv), advanced to clinical trials, are used in this study. Previously, we have shown that injection of DBBF-Hb into the rat circulation produces venular leakage and intestinal epithelial disruption. The purpose of this study was to determine whether PolyHbBv, currently approved for veterinary use in the United States, shows similar effects. In anesthetized Sprague-Dawley rats, the mesenteric microvasculature was perfused with DBBF-Hb ( n = 6), PolyHbBv ( n = 5), cyanomet Hb (CNmet-DBBF-Hb), or HEPES-buffered saline with 0.5% bovine serum albumin (HBS-BSA) (controls, n = 7) for 10 min, followed by FITC-albumin for 3 min, and then fixed for microscopy. For DBBF-Hb, the mean leak number per micrometer venule length [2.41 ± 0.33 (±SE) × 10−3] was significantly greater than for PolyHbBv (0.53 ± 0.14 × 10−3), CNmet-DBBF-Hb (0.36 ± 0.14 × 10−3), and HBS-BSA (0.12 ± 0.08 × 10−3) ( P < 0.01). Corresponding quantities for leak area were 0.10 ± 0.03, 0.010 ± 0.003, 0.005 ± 0.003, and 0.02 ± 0.02 μm2/μm. In rats injected with DBBF-Hb ( n = 8), intestinal epithelial integrity was significantly compromised compared with those injected with PolyHbBv ( n = 5) or saline ( n = 6). These results indicate that intravascular PolyHbBv produces significantly less disruption of the intestinal exchange barrier than does DBBF-Hb, probably because the heme is not so easily oxidized.

Modified hemoglobins produce venular interendothelial gaps and albumin leakage in the rat mesentery

1999 ◽  
Vol 277 (2) ◽  
pp. H650-H659 ◽  
Author(s):  
Ann L. Baldwin
Keyword(s):  
Actin Cytoskeleton ◽  
Blood Substitutes ◽  
Cell Junctions ◽  
Intestinal Epithelial ◽  
Sprague Dawley ◽  
Filamentous Actin ◽  
Rat Mesentery ◽  
Sprague Dawley Rats ◽  
Albumin Leakage ◽  
Endothelial Gaps

Cross-linked hemoglobin (αα-Hb) and polyethylene glycol (PEG)-conjugated Hb have both been considered as possible “blood substitutes.” Previously, we showed that PEG-Hb extravasates rapidly in the intestinal mucosa and causes transient epithelial sloughing, resulting in temporary opening of the intestinal epithelial barrier. In the present study, the rat mesenteric preparation was used to quantify the effects of the two Hbs on microvascular leakage to albumin and to investigate possible changes in the integrity of the interendothelial cell junctions and the endothelial actin cytoskeleton. In anesthetized Sprague-Dawley rats, the microvasculature of a mesenteric window was perfused with HEPES-buffered saline (HBS) containing 0.5 mg/ml BSA and 2 mg/ml αα-Hb ( n = 16) or PEG-Hb ( n = 5) for 2 or 10 min. Controls ( n = 4) just received HBS-BSA. In some experiments ( n = 9 for αα-Hb ; n = 5 for PEG-Hb), the perfusate was then replaced by FITC-albumin in HBS-BSA for the next 3 min. The vasculature was then perfusion fixed, stained for filamentous actin and for mast cells, and viewed microscopically. In the remaining experiments, the mesenteric microvasculature was stained with silver nitrate to determine the number of endothelial junctional gaps per length of venules. Both Hbs increased the number and area of leaks per micrometer of venular length compared with control, but αα-Hb increased to a greater extent than PEG-Hb. Formation of leaks was accompanied by changes in the endothelial actin cytoskeleton and by an increased number of endothelial gaps. Mast cell degranulation was significantly greater ( P < 0.05) in Hb-treated preparations compared with controls, but there was no direct correlation between sites of degranulation and albumin leakage. These Hbs appear to induce venular leakage in the mesentery by mechanisms similar to those previously observed after treatment with histamine or nitric oxide synthase inhibitors.

Spatiotemporal electrophysiology of cerebral ischemia observed using chronic electrode array in auditory cortex

2008 ◽  
Vol 2 (1) ◽  
Author(s):  
M.T. Huberty ◽  
P. Tek ◽  
P.J. Rousche
Keyword(s):  
Auditory Cortex ◽  
Time Course ◽  
Electrode Array ◽  
The United States ◽  
Stroke Recovery ◽  
Sprague Dawley ◽  
Stroke Research ◽  
Sprague Dawley Rats ◽  
The Mean

Stroke research is of considerable societal value in an age in which the scourge is a leading cause of disability and the third-leading cause of death in the United States. While previous studies investigate the electrophysiology of stroke, none examine the long-term time-course of stroke recovery in the auditory cortex, the objective of this study. An electrode was implanted in the auditory cortex of two anesthetized Sprague-Dawley rats, stroke was induced in one of the subjects using photothrombosis, and daily electrical recordings were made while each subject was presented with a click stimulus every 500 ms. Peri-stimulus time histograms reveal that in the control subject, the second stimulus-evoked bursts peak decreased the day following implantation (Day 1) but returned almost to its Day 0 (day of surgery) value by Day 5, representing recovery from implantation trauma. The mean firing rate decreased logarithmically from its Day 0 value of 90 Hz to 10 Hz by Day 8, revealing decreasing electrode viability. In the stroke subject, the second stimulus-evoked bursts peak was undetected Day 1, but was detected again on Day 4, elucidating that the rat auditory cortex regains function as stroke recovery progresses.

scholarly journals Preclinical Characterization of the Distribution, Catabolism, and Elimination of a Polatuzumab Vedotin-Piiq (POLIVY®) Antibody–Drug Conjugate in Sprague Dawley Rats

2021 ◽  
Vol 10 (6) ◽  
pp. 1323
Author(s):  
Victor Yip ◽  
M. Violet Lee ◽  
Ola M. Saad ◽  
Shuguang Ma ◽  
S. Cyrus Khojasteh ◽  
...  
Keyword(s):  
B Cell Lymphoma ◽  
The United States ◽  
Clinical Development ◽  
Sprague Dawley ◽  
Antibody Drug Conjugate ◽  
Post Dose ◽  
Drug Conjugate ◽  
Sprague Dawley Rats ◽  
A Minor ◽  
Antibody Drug

Polatuzumab vedotin (or POLIVY®), an antibody–drug conjugate (ADC) composed of a polatuzumab monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable dipeptide linker, has been approved by the United States Food and Drug Administration (FDA) for the treatment of diffuse large B-cell lymphoma (DLBCL). To support the clinical development of polatuzumab vedotin, we characterized the distribution, catabolism/metabolism, and elimination properties of polatuzumab vedotin and its unconjugated MMAE payload in Sprague Dawley rats. Several radiolabeled probes were developed to track the fate of different components of the ADC, with 125I and 111In used to label the antibody component and 3H to label the MMAE payload of the ADC. Following a single intravenous administration of the radiolabeled probes into normal or bile-duct cannulated rats, blood, various tissues, and excreta samples were collected over 7–14 days post-dose and analyzed for radioactivity and to characterize the metabolites/catabolites. The plasma radioactivity of polatuzumab vedotin showed a biphasic elimination profile similar to that of unconjugated polatuzumab but different from unconjugated radiolabeled MMAE, which had a fast clearance. The vast majority of the radiolabeled MMAE in plasma remained associated with antibodies, with a minor fraction as free MMAE and MMAE-containing catabolites. Similar to unconjugated mAb, polatuzumab vedotin showed a nonspecific distribution to multiple highly perfused organs, including the lungs, heart, liver, spleen, and kidneys, where the ADC underwent catabolism to release MMAE and other MMAE-containing catabolites. Both polatuzumab vedotin and unconjugated MMAE were mainly eliminated through the biliary fecal route (>90%) and a small fraction (<10%) was eliminated through renal excretion in the form of catabolites/metabolites, among which, MMAE was identified as the major species, along with several other minor species. These studies provided significant insight into ADC’s absorption, distribution, metabolism, and elimination (ADME) properties, which supports the clinical development of POLIVY.

scholarly journals Pengaruh Pemberian Kurma Muda (Phoenix dactylifera) Terhadap Kadar FSH dan Reseptor FSH Ovarium Tikus Putih (Rattus norvegicus)

2019 ◽  
Vol 7 (1) ◽  
pp. 117-121
Author(s):  
Herlambang Herlambang ◽  
Ave Olivia Rahman ◽  
Erny Kusdiyah
Keyword(s):  
Ovarian Tissue ◽  
Scientific Evidence ◽  
Phoenix Dactylifera ◽  
Group Iv ◽  
Sprague Dawley ◽  
Female Reproduction ◽  
Group I ◽  
Sprague Dawley Rats ◽  
Vaginal Swabs ◽  
The Mean

ABSTRACT Background: Infertility may give an impact on psychosocial. In Indonesia, the habit of consuming young dates is often done by couples to increase fertility. FSH is one of the factors that play a role in folliculogenesis. The lack of scientific evidence of young dates consumption effects on female reproduction has led to this study. This study aims to determine the levels of FSH hormone and the picture of ovarian tissue in mice after administration of young dates. Method: This study used an experimental design using 28 female Sprague-Dawley rats which were randomly divided into 4 groups. Group I to III was given young dates in successive doses: 17 mg, 34 mg, 68 mg per 200 grams of body weight and group IV was given distilled water. The treatment was carried out for 28 days. FSH levels were examined before treatment during the proestrus phase which was known from microscopic examination of rat vaginal swabs. The treatment begins during the proestrus phase. Result: The mean baseline and post-treatment FSH levels were 0.08 and 0.09 respectively Conclusion: There is no significant increase of FSH levels and FSH receptors as the effect of giving young dates (Phoenix Dactylifera) to female Sprague-Dawley rats Keywords: Dates, FSH, FSH receptors, Rats   ABSTRAK Latar Belakang: Infertilitas dapat memberikan dampak psikososial. Di Indonesia, kebiasaan mengkonsumsi kurma muda sering dilakukan oleh pasangan untuk meningkatkan kesuburan. Hormon FSH merupakan salah satu faktor yang berperan dalam folikelgenesis.  Belum adanya bukti ilmiah efek konsumsi buah kurma muda terhadap reproduksi wanita mendorong dilakukannya studi ini. Studi ini bertujuan mengetahui kadar hormon FSH dan gambaran jaringan ovarium pada tikus setelah pemberian kurma muda. Metode: Penelitian ini menggunakan desain ekperimental menggunakan tikus Sprague dawney betina sebanyak 28 ekor yang dibagi secara acak menjadi 4 kelompok. Kelompok I-III diberikan kurma muda dosis berturut -turut 17 mg, 34 mg, 68 mg per 200 gram BB dan kelompok IV diberikan aquadest. Perlakuan dilakukan selama 28 hari. Kadar hormon FSH diperiksa sebelum perlakuan saat fase proestrus yang diketahui dari pemeriksaan mikroskopis swab vagina tikus. Perlakuan dimulai saat fase proestrus. Hasil: Rerata kadar FSH baseline dan paska perlakuan adalah 0,08 dan 0,09 Kesimpulan: Tidak terdapat peningkatan yang signifikan kadar FSH dan reseptor FSH terhadap efek pemberian buah kurma muda (Phoenix Dactylifera) pada uterus tikus Spague Dawney Kata kunci : kurma, FSH, Reseptor FSH, tikus

Distribution and metabolism of corticotropin-releasing factor in the rat

1986 ◽  
Vol 64 (6) ◽  
pp. 683-688 ◽  
Author(s):  
Bernard Candas ◽  
Josée Lalonde ◽  
Maurice Normand
Keyword(s):  
Time Course ◽  
Corticotropin Releasing Factor ◽  
Metabolic Clearance ◽  
Sprague Dawley ◽  
Rapid Injection ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
The Mean ◽  
The Moment ◽  
The One

To develop a mathematical model of the distribution and metabolism of rat corticotropin-releasing factor (rCRF), the time course of 125I-labelled rCRF in plasma was measured in male Sprague–Dawley rats (i) following a rapid injection of 24 ng rCRF/100 g body weight (BW), or (ii) following a rapid injection of 424 ng rCRF/100 g BW, or (iii) during an infusion at a rate ranging from 0.28 to0.73 ng rCRF∙min−1∙100 g BW−1. The comparison of the one-, two-, and three-compartment models shows that the two-pool structure fits better to the dynamics of CRF in plasma as measured in each rat. Following a rapid injection the decay curve occurs in a biphasic manner; the early phase of disappearance is 25 times faster than the late one. There is no significant difference between the estimates of the metabolic clearance rate following both amplitudes of injection (0.40 ± 0.06 and 0.48 ± 0.05 mL∙min−1∙100 g BW−1). The volume of the first pool, 16.8 ± 1.1 mL/100 g BW, is four times larger than the plasma volume. It would thus appear that CRF is rapidly distributed from plasma into several tissues which are represented in the first pool of the model. The mean residence time of every CRF molecule in the second compartment, from the moment of secretion to its elimination, is from three to four times longer than in the first one. It stays, on average, between 140 min and 3 h in the system before an irreversible exit. At steady state, the disposal rate represents only 3% of the CRF mass of the first compartment every minute. These results could explain the prolonged effects of CRF on pituitary-adrenocortical secretion.

Effect of Gasohol on The Rat Liver

1997 ◽  
Vol 3 (S2) ◽  
pp. 49-50
Author(s):  
B.A. MacDuff ◽  
A. Singh ◽  
I. Chu
Keyword(s):  
United States ◽  
Body Weight ◽  
Adverse Effects ◽  
Rat Liver ◽  
Corn Oil ◽  
The United States ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Although there are a variety of gasoline ethanol mixtures proposed as neat fuels (ethanol 85% + gasoline 15% = E85; E95) for automobiles, gasohol (gasoline 90% + ethanol 10%) is presently used as a fuel in the United States. The adverse effects, if any, of gasohol ingestion are unknown; effects on the liver of rats administered gasohol are examined in this study.Twenty-four female Sprague-Dawley rats received daily, via gavage, one of the three concentrations of gasohol for 28 days; LD50/20, LD50/100 and LD50/1000, where LD50 = 1.5g ethanol / kg body weight (bw) and 14g gasoline / kg bw. The LD50 was based on that of gasoline, which was obtained from literature value.1 The amount of ethanol added to stock gasohol was only 1/10 its LD50, required to maintain the gasoline ethanol proportion of 9:1. Gasohol was administered in corn oil with total volume 10 ml. Animals that received only corn oil served as controls.

scholarly journals A Novel Technique to Perform Microvascular Anastomosis Revisions without Clamps

2018 ◽  
Vol 03 (02) ◽  
pp. e58-e61
Author(s):  
Amro Harb ◽  
Maxwell Levi ◽  
Yelena Akelina ◽  
Rajendra Kadiyala ◽  
Jeffrey Ascherman
Keyword(s):  
Operating Time ◽  
Microvascular Anastomosis ◽  
Sprague Dawley ◽  
Surgical Experience ◽  
Novel Technique ◽  
Technical Errors ◽  
Sprague Dawley Rats ◽  
Leakage Site ◽  
The Mean ◽  
And Training

Background For surgeons learning microsurgery, uneven spacing between sutures while performing microvascular arterial anastomoses is one of the most common technical errors made that can lead to leakage. Based on the previous surgical experience and training of these surgeons, the first option chosen to prevent bleeding is to place a vascular clamp proximal to the anastomosis and an additional suture at the site of the leak. Because this technique may have technical and thrombosis concerns, our study proposes an alternative technique of performing post-anastomotic revisions without the use of clamps. Methods Our technique involves placing a cotton-tipped applicator under the artery and lifting it to partially occlude flow within the vessel as an additional suture is placed at the leakage site to complete the revision. One-hundred eighty-four microvascular anastomoses were performed on the femoral arteries of 92 Sprague-Dawley rats, and of the 184 anastomoses, 147 had a leak and required a post-anastomotic revision. All revisions were completed using our technique, and no clamps were used during any of the revisions. Results Of the 147 post-anastomotic revisions completed using our technique, 141 (95.9%) were patent 2 hours post-revision. The mean operating time for the revisions was 5:03 minutes (range, 1:44–6:30 minutes). Conclusion Our technique of partially occluding an artery with a cotton-tipped applicator while performing a post-anastomotic revision is a safe and effective alternative to using vascular clamps. Our technique may also reduce technical errors and have a low risk of causing thrombosis when completing post-anastomotic revisions.

scholarly journals Absorption, Distribution, Excretion, and Pharmacokinetics ofC-Pyronaridine Tetraphosphate in Male and Female Sprague-Dawley Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Hyun Park ◽  
Kannampalli Pradeep
Keyword(s):  
Clinical Trials ◽  
Small Intestine ◽  
Oral Administration ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Phase Ii Clinical Trials ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Peak Value

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) ofC-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion ofC-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that theCmax, AUC (0-inf), andTmaxvalues were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.

scholarly journals Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Yi Tao ◽  
Hongliang Zhang ◽  
Bing Gao ◽  
Jiao Guo ◽  
Yinming Hu ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Chitosan Nanoparticles ◽  
Plasma Viscosity ◽  
Water Soluble ◽  
Lipid Lowering ◽  
Sprague Dawley ◽  
High Fat ◽  
Sprague Dawley Rats ◽  
Mean Size ◽  
The Mean

Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC) has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs) on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800 nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD) activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia.

scholarly journals BODY WEIGHT PROFILEAND MORTALITY RATEOF MALE SPRAGUE DAWLEY RATS DURING THE FORMATION OF FIBROSARCOMA INDUCED BY BENZO(A)PYRENE

2021 ◽  
Vol 10 (1) ◽  
pp. 1-11
Author(s):  
Palagan Senopati Sewoyo ◽  
Anak Agung Ayu Mirah Adi ◽  
Ida Bagus Oka Winaya
Keyword(s):  
Body Weight ◽  
Mortality Rate ◽  
The Body ◽  
Sprague Dawley ◽  
Patients With Cancer ◽  
Sprague Dawley Rats ◽  
Polycyclic Aromatic ◽  
The Mean ◽  
Average Body ◽  
Average Body Weight

Benzo(a)pyrene (BaP) is one of several examples of polycyclic aromatic hydrocarbons that come from incomplete combustion of organic materials.BaP compound is used in research to induce fibrosarcoma.In general, patients with cancer will experience a reduction in body weight. This study aims to determine the body weight profile, the time it takes to cause fibrosarcoma, and the mortality rate of male Sprague Dawley rats after injection with BaP. In this study, 18 rats were used with two treatments.Rats in treatment 0 (P0) were not treated, while rats in treatment I (PI) were injected with BaP 0.3% in 0.1 mL oleum olivarumten times given gradually at two-day intervals via subcutaneous. There were six and 12 rats, respectively, P0 and PI. BaP solution is prepared by dissolving in oleum olivarum, mixing, and stirring until homogeneous. The rats were weighed at the beginning of the study and then carried out routinely once a weekfor 19 weeks of research. At the beginning of the study, the average body weight of rats at P0 and PI were 121.43 ± 7.04 g and 131.49 ± 16.31 g, respectively. The mean body weight of the rats at P0 and PI from the first week to the 19th were178.53 ± 29.97 g and 159.20 ± 14.24 g, respectively. The time taken to inducefibrosarcoma was 85.5 ± 17.6 days. The mortality rate in treatment P0 was 0% and PI treatment was 8.33%.From the results of this study, it can be concluded that giving BaP significantly reduces the body weight profile of rats and has a mortality rate of 8.33%.

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