Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction

2004 ◽  
Vol 96 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Patricia A. Rothenbach ◽  
Benny Dahl ◽  
Jason J. Schwartz ◽  
Grant E. O'Keefe ◽  
Masaya Yamamoto ◽  
...  
Keyword(s):  
Burn Injury ◽  
Plasma Concentrations ◽  
Early Time ◽  
Microvascular Dysfunction ◽  
Microvascular Permeability ◽  
Lung Model ◽  
Actin Binding ◽  
Sprague Dawley ◽  
Plasma Gelsolin ◽  
Perfused Lung

Reduced plasma concentrations of the extracellular actin-binding proteins gelsolin and Gc-globulin correlate with pulmonary failure and death in humans after injury. The purpose of this study was to investigate the role of plasma gelsolin in the pathophysiology of inflammation-induced lung injury. We postulated that plasma gelsolin levels decrease at an early time point after burn injury and that the intravenous infusion of gelsolin prevents burn-induced pulmonary microvascular dysfunction. Adult Sprague-Dawley rats were randomized to undergo a 40% body surface area thermal injury (Burn) or manipulation without burn (Sham). Plasma gelsolin and Gc-globulin concentrations were determined at various times during the first 6 days of injury by Western blotting. Other animals were randomized to receive either recombinant human gelsolin (0.078, 0.78, or 7.8 mg) or albumin (7.8 mg) before and 8 h after Burn or Sham. Twenty-four hours later, pulmonary microvascular permeability was assessed by measuring the capillary filtration by use of an isolated, perfused lung model. We found that plasma gelsolin levels of burn-injured rats decreased to 10% of normal levels within 12 h and remained below normal levels for up to 6 days postinjury. Gc-globulin values also fall, but to a lesser extent and only transiently. Treatment of burned animals with intravenous infusions of recombinant human gelsolin prevented the increase in pulmonary microvascular permeability that accompanies this injury. Our findings are consistent with the hypothesis that plasma gelsolin depletion contributes to the pathophysiology of pulmonary microvascular dysfunction during inflammation.

scholarly journals Oral absorption and drug interaction kinetics of moxifloxacin in an animal model of weightlessness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Liang ◽  
Jing Ma ◽  
Bo Wei
Keyword(s):  
Oral Dose ◽  
Oral Absorption ◽  
Jugular Vein ◽  
Plasma Concentrations ◽  
Pharmacokinetic Data ◽  
Simulated Weightlessness ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Interaction Kinetics ◽  
Kinetics Of

AbstractTo investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.

The Effect of Tumor Necrosis Factor-?? on Microvascular Permeability in an Isolated, Perfused Lung

Shock ◽  
2002 ◽  
Vol 18 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Carl I. Schulman ◽  
Joseph K. Wright ◽  
Fiemu Nwariaku ◽  
George Sarosi ◽  
Richard H. Turnage
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Microvascular Permeability ◽  
Isolated Perfused Lung ◽  
Perfused Lung ◽  
Necrosis Factor

scholarly journals Pharmacokinetics of α-Pyrrolidinovalerophenone in Male Rats with and without Vaccination with an α-Pyrrolidinovalerophenone Vaccine

2021 ◽  
Vol 24 ◽  
pp. 267-276
Author(s):  
Samantha McClenahan ◽  
Melinda Gunnell ◽  
Michael Owens
Keyword(s):  
Treatment Time ◽  
Area Under The Curve ◽  
Early Time ◽  
Volume Of Distribution ◽  
Male Rats ◽  
Serum Concentrations ◽  
Sprague Dawley ◽  
Serum Samples ◽  
Maximum Serum ◽  
The Brain

PURPOSE: α-Pyrrolidinovalerophenone (α-PVP) is a second-generation synthetic cathinone which acts as an inhibitor at the dopamine and norepinephrine transporters in the brain. These novel studies determined the pharmacokinetics (PK) of α-PVP in rats and then evaluated the effects of an α-PVP vaccine on the PK profile. METHODS: Adult male Sprague-Dawley rats were randomly divided into treatment groups (n = 24/group) in which the vaccinated rats received an initial and two booster immunizations of the α-PVP vaccine at 0, 3, and 9 wks. Control rats received saline injections. α-PVP (0.56, 1, 3 mg/kg, sc) was then administered to both groups between 11-12 weeks and serum samples were collected for determination of α-PVP serum concentrations by LC-MS/MS (n=6 rats/treatment/time). At 13 weeks, brain, heart and kidney concentrations of α-PVP were determined by LC-MS/MS after administration of 1 mg/kg α-PVP (n=4-5 rats/treatment/time). RESULTS: PK values in control rats showed dose-dependent increases in maximum serum concentrations (Cmax) and area under the curve (AUCinf) values with an elimination half-life (t1/2) of approximately 2.1 h. α-PVP exhibited linear PK profile in control rats. Vaccinated rats had significantly (p<0.05) higher serum Cmax and AUCinf values than controls, and significantly reduced total body clearance, volume of distribution and t1/2 values. Vaccinated rats had significantly lower α-PVP concentrations in the brain, heart, and kidney in comparison to control rats at early time points. CONCLUSION: Vaccination with the novel α-PVP vaccine significantly altered serum PK leading to a time-dependent reduction in brain, kidney and heart concentrations of α-PVP compared to controls.

134 The Effect of Adipose Derived Stromal Vascular Fraction on Stasis Zone in an Experimental Burn Model on Streptozocin – Induced Diabetic Rats

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S89-S90
Author(s):  
Cagri A Uysal ◽  
Burak Ozkan ◽  
Abbas Najimaldin Muhsun Al Bayati ◽  
Gonca Ozgun ◽  
Kadri Akinci ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Cell Density ◽  
Inflammatory Cell ◽  
Burn Injury ◽  
Stromal Vascular Fraction ◽  
Vascular Density ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats

Abstract Introduction Stasis zone is the encircling area of the coagulation zone which is a critical area determining the depth and width of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF). Methods Intraperitoneal Streptozotocin was administered for the induction of diabetes mellitus (DM) and the development of DM was confirmed by the measurement of blood glucose levels in the blood samples with blood glucometer weekly 48 hours after injection. Rats with blood glucose levels above 200 mg/dl were accepted as diabetic. The diabetic animals were followed for 4 weeks before the intervention. Thermal injury was applied on dorsum of diabetic Sprague – Dawley rats (n=20) according to the previously described ‘‘comb burn’’ model. After the burn injury (30 minutes) on Sprague - Dawley rats; rat dorsum was separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each pair. ADSVF cells harvested from inguinal fat pads of diabetic Sprague - Dawley rats (n=5) were injected on the right side while same amount of phosphate buffered saline (PBS) injected on the left side of the same animal. One week later, average vital tissue on the statis zone was determined by macroscopy, angiography and microscopy. Vascular density, inflammatory cell density and gradient of fibrosis were determined via immunohistochemical assay. Results Macroscopic stasis zone tissue survivability percentage (32 ± 3.28 %, 57 ± 4.28 %), average number of vessels (10.28 ± 1.28, 19.43 ± 1.72), capillary count (15.67 ± 1.97, 25.35 ± 2.15) and vascular density (1.55 ± 0.38, 2.14 ± 0.45) were higher on ADSVF side. Fibrosis gradient (1.87 ± 0.51, 1.50 ± 0.43) and inflammatory cell density (1.33 ± 0.40, 1.20 ± 0.32) were higher on the PBS side. Conclusions Macroscopic and microscopic findings determined that ADSVF has a statistically significant benefit for salvaging stasis zone on acute burn injuries in DM.

Dissociation between plasma renin and plasma aldosterone induced by dietary glycine hydrochloride

1988 ◽  
Vol 254 (2) ◽  
pp. E187-E192
Author(s):  
T. A. Kotchen ◽  
G. P. Guthrie ◽  
L. D. Boucher ◽  
J. N. Lorenz ◽  
C. E. Ott
Keyword(s):  
Plasma Renin Activity ◽  
Indirect Effect ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Elevated Plasma ◽  
Sprague Dawley ◽  
Low Sodium ◽  
High Chloride ◽  
Stimulation Of

We evaluated the effects of selective dietary chloride loading (without sodium) on plasma renin activity (PRA) and plasma aldosterone in the sodium-deprived Sprague-Dawley rat. Three groups of animals were fed one of the following diets for 13 days: 1) low NaCl; 2) high NaCl; or 3) low sodium, high chloride, provided as glycine hydrochloride. Compared with NaCl-deprived animals, PRA and plasma aldosterone were lower (P less than 0.01) in animals fed low sodium high chloride, whereas aldosterone in animals fed glycine hydrochloride was higher (P less than 0.01) than that of NaCl-deprived animals. In contrast, plasma concentrations of corticosterone and 18-hydroxycorticosterone were not increased by selective chloride loading. Glycine chloride-fed animals were acidotic and had elevated plasma concentrations of potassium and ionized calcium. Thus stimulation of aldosterone by selective chloride loading is not related to PRA or ACTH but may be due to a direct effect of acidosis or an indirect effect of acidosis on potassium and/or calcium. Additionally, selective chloride loading appears to stimulate the conversion of 18-hydroxycorticosterone to aldosterone.

scholarly journals Pharmacokinetic Profile of μSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Rosario Russo ◽  
Angelo Mancinelli ◽  
Michele Ciccone ◽  
Fabio Terruzzi ◽  
Claudio Pisano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sprague Dawley ◽  
Time Curve ◽  
Maximum Plasma Drug Concentration

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (μSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t1/2), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with μSMIN Plus™ compared with animals treated with micronized diosmin. In particular, μSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for μSMIN Plus™, which may represent a new tool for CVI management.

Juxtamedullary microvascular dysfunction during the hyperfiltration stage of diabetes mellitus

1994 ◽  
Vol 267 (1) ◽  
pp. F99-F105 ◽  
Author(s):  
K. Ohishi ◽  
M. I. Okwueze ◽  
R. C. Vari ◽  
P. K. Carmines
Keyword(s):  
Diabetes Mellitus ◽  
Microvascular Dysfunction ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats ◽  
Vasoconstrictor Response ◽  
Wide Range ◽  
Single Nephron

This study was designed to identify and localize defects in renal microvascular function during the hyperfiltration stage of diabetes mellitus. Male Sprague-Dawley rats were injected intravenously with 65 mg/kg streptozotocin (IDDM rats) or vehicle (sham rats). IDDM rats received insulin (3 U.kg-1.day-1) via an osmotic minipump; sham rats received diluent. During the ensuing 2-wk period, blood glucose levels averaged 89 +/- 2 mg/dl in 33 sham rats and 290 +/- 13 mg/dl in 37 IDDM rats. At the end of this period, inulin clearance was elevated in eight IDDM rats (1.43 +/- 0.17 ml.min-1.g kidney wt-1) compared with six sham rats (0.78 +/- 0.05 ml.min-1.g kidney wt-1). The remaining animals served as tissue donors for study of the renal microvasculature using the in vitro blood-perfused juxtamedullary nephron technique. Kidneys from sham and IDDM rats were perfused with homologous blood at a renal arterial pressure of 110 mmHg. Juxtamedullary single-nephron glomerular filtration rate was higher in IDDM rats (41.5 +/- 5.4 nl/min) than in sham rats (25.4 +/- 2.4 nl/min). Afferent arteriolar inside diameter was greater in IDDM rats (34 +/- 2 microns) than in sham rats (22 +/- 1 microns); however, efferent arteriolar diameter did not differ between groups. The afferent arteriolar vasoconstrictor response to norepinephrine (NE) was attenuated in IDDM rats, relative to sham rats, over a wide range of NE concentrations. In contrast, NE evoked similar degrees of efferent vasoconstriction in IDDM and sham rats.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Gelsolin variant (Asn-187) in familial amyloidosis, Finnish type

1990 ◽  
Vol 272 (3) ◽  
pp. 827-830 ◽  
Author(s):  
J Ghiso ◽  
M Haltia ◽  
F Prelli ◽  
J Novello ◽  
B Frangione
Keyword(s):  
Amyloid Fibrils ◽  
Corneal Dystrophy ◽  
Binding Activity ◽  
Actin Binding ◽  
Cranial Neuropathy ◽  
Protein Subunit ◽  
Plasma Gelsolin ◽  
Sequence Identity ◽  
Finnish Type ◽  
Repetitive Motif

Familial amyloidosis, Finnish type (FAF), is an inherited form of systemic amyloidosis clinically characterized by cranial neuropathy and lattice corneal dystrophy. We have demonstrated that the protein subunit isolated from amyloid fibrils shows considerable sequence identity with gelsolin, an actin-binding protein. We have purified the amyloid subunit from a second case and further analysed different fractions from the previous one. Sequence analysis shows that, in both cases, the amyloid subunit starts at position 173 of the mature molecule; it has a heterogeneous N-terminus and contains one amino acid substitution, namely asparagine for aspartic acid, at position 15 (gelsolin residue 187), that is due to a guanine-to-adenine transversion corresponding to nucleotide-654 of human plasma gelsolin cDNA. The substitution maps in a fragment with actin-binding activity and is located in a repetitive motif highly conserved among species. Thus FAF is the first human disease known to be caused by an internal abnormal degradation of a gelsolin variant. We designate this variant of gelsolin-associated amyloidosis ‘Agel Asn-187’.

Sign in / Sign up

Export Citation Format

Share Document