Peritubular capillary permeability and intravascular RBC aggregation after ischemia: effects of neutrophils

1990 ◽  
Vol 258 (4) ◽  
pp. F1018-F1025 ◽  
Author(s):  
P. O. Hellberg ◽  
O. T. Kallskog ◽  
G. Ojteg ◽  
M. Wolgast

The influence of neutrophils on peritubular capillary permeability and intravascular red blood cell (RBC) aggregation after renal ischemia was studied in anesthetized Sprague-Dawley rats. Intraperitoneal administration of antineutrophil serum (ANS) reduced the number of neutrophils in the blood to 3% of normal. The control group received an equal volume of inactive serum. Renal macromolecular capillary permeability was studied from 1) extravasation of albumin and 2) plasma to lymph transport of plasma proteins and of neutral and negatively charged lactate dehydrogenase (LDH). The net driving force (NDF) for fluid transfer over the peritubular capillary membrane was determined by the micropuncture technique. The intrarenal distributions of neutrophils and RBC were measured by a histochemical method and 51Cr-labeled RBC, respectively. Under preischemic control conditions neither macromolecular permeability nor renal clearance of inulin was affected by ANS. However, the steep increase in the macromolecular transport from plasma to lymph resulting from 45 min of ischemia and reperfusion was blunted by ANS, and preischemic control values were restored after 1 h of recirculation. In the control group the mass transport of plasma proteins increased twofold and that of both neutral and negatively charged LDH fourfold. NDF was equal in the two groups. In the ANS-treated animals the intrarenal neutrophil content was only 2% of the control. Neutrophils were found mainly in the cortex, whereas RBC aggregation was observed only in the renal medulla. It is concluded that neutrophils mediate postischemic capillary leakage. It is suggested that this leakage underlies RBC aggregation and incomplete return of blood flow in the renal medulla after ischemia.

1997 ◽  
Vol 8 (12) ◽  
pp. 1915-1920
Author(s):  
T Wang ◽  
C Chen ◽  
O Heimbürger ◽  
J Waniewski ◽  
J Bergström ◽  
...  

Hyaluronan, exhibiting a high resistance against water flow, acts in the tissue as a barrier against rapid changes in water content. To test whether hyaluronan has any effect on the peritoneal fluid and solute transport, and, in particular, on the peritoneal fluid absorption, a 4-h dwell study with an intraperitoneal volume marker (radiolabeled human serum albumin [RISA]) was conducted in 21 male Sprague Dawley rats (three groups, seven rats in each group). Each rat was injected intraperitoneally with 25 ml of 1.36% glucose solution alone (control group), with 0.005% hyaluronan (HA1 group), or with 0.01% hyaluronan (HA2 group). Dialysate and blood samples were taken frequently for analyses of fluid and solute (urea, glucose, and protein) transport. The intraperitoneal volume was calculated from the dilution of RISA with a correction for RISA disappearance from the peritoneal cavity. This study shows that adding hyaluronan to peritoneal dialysis solution significantly (P < 0.01) increased the net peritoneal fluid removal, mainly due to a significant decrease in the peritoneal fluid absorption rate (P < 0.01). The diffusive mass transfer coefficients for glucose, urea, and protein did not differ between the three groups. The peritoneal clearance of urea increased significantly in the two hyaluronan groups compared with the control group, due to the increased net fluid removal in the hyaluronan groups. These results suggest that intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption.


2004 ◽  
Vol 12 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Katica Bajin-Katic ◽  
Karmen Stankov ◽  
Zoran Kovacevic

BACKGROUND: Rapidly proliferating crypt cells of the intestinal epithelium, the precursors of the mature enterocytes, are extremely sensitive to the effects of cytostatic agents. We investigated the effects of the methotrexate on rat intestinal mucosa in order to get the information on biochemical indicators of intestinal damage. METHODS: Biochemical parameters were investigated in isolated intestinal mucosa of Sprague-Dawley rats, previously treated with methotrexate by intraperitoneal administration. Glutamine was dissolved in water and administered orally. RESULTS: The activity of glutaminase and alkaline phosphatase showed the enzymatic response to different doses of methotrexate. The activity of both enzymes was significantly lower in the mucosa of treated animals, compared to control group. CONCLUSION: Minimal mucosal damage and regeneration time is dose dependent and influenced by the dosage schedule of antitumor therapy.


2009 ◽  
Vol 79 (6) ◽  
pp. 1169-1174 ◽  
Author(s):  
Tatsunori Shibazaki ◽  
Joseph H. Yozgatian ◽  
Jorge L. Zeredo ◽  
Carmen Gonzales ◽  
Hitoshi Hotokezaka ◽  
...  

Abstract Objective: To test the efficacy of an animal model of pain and stress and evaluate the effects of celecoxib administered when orthodontic force is applied. Materials and Methods: A 20-g reciprocal force was applied via an orthodontic appliance to the maxillary left first and second molars of 7-week-old male Sprague-Dawley rats. Rat behavior was evaluated at 5, 24, and 48 hours after the appliance was set. Behavior was assessed in a test field by the number of lines crossed in the first 30 seconds and 5 minutes following force application; number of lines crossed to the center; rearing time; and facial grooming time. Experimental group 1 received intraperitoneal administration of 30 mg/kg celecoxib before every behavioral test. Experimental group 2 received 90 mg/kg before the first behavioral test, and physiologic saline was administered before the remaining behavioral tests. Control groups received saline before every behavioral test and were given passive (passive control group) and active (active control group) appliances, respectively. Results: Parameters related to pain increased in the active controls, whereas the parameters in the experimental groups decreased to the level seen in the passive controls. Statistically significant differences in pain-related behavior between control and experimental groups were found at 5 and 24 hours after placing the appliance. Stress-related behavior was significantly less in the experimental groups compared to the active control group during experimental periods. Conclusions: The administration of celecoxib relieves pain- and stress-related behavior evoked by orthodontic tooth movement in the rat. This model might be a useful tool for the evaluation of pain and stress.


1997 ◽  
Vol 17 (2) ◽  
pp. 179-185 ◽  
Author(s):  
Sang-Eun Park ◽  
Zbylut J. Twardowski ◽  
Harold L. Moore ◽  
Ramesh Khanna ◽  
Karl D. Nolph

Objective To determine the influence of chronic iron dextran administrations into the peritoneal cavity of rats on function and anatomy of the peritoneal membrane, as well as on erythropoiesis and serum iron. Design Prospective randomized animal study. Setting Animallaboratory. Animals: 36 Sprague-Dawley rats. Interventions The rats were divided into three groups (n = 12). The animals were given standard 1.5% Dianeal (control group) or 1.5% Dianeal containing iron dextran in a concentration of 2 mg/L [Iow-dose group (LDG)] or 10 mg/L [high-dose group (HDG)]. Main outcome measures On the 8th day, at 3 months, and at 6 months a 2-hour peritoneal equilibration test (PET) and blood tests including hematocrit, serum iron, and total iron-binding capacity (TIBC) were done. After the final PET at 6 months, the peritoneal membrane was evaluated by gross inspection and by light microscopy. Results Hematocrit and serum iron levels increased only in the HDG and LDG. Peritoneal transport of small solutes decreased significantly in the HDG compared to baseline. All cases of the HDG group revealed peritoneal adhesions and fibrosis around the peritoneal catheter as well as massive iron deposits on the peritoneum. Similar but less pronounced changes were found in the LDG. Conclusions These findings suggest an efficient absorption of iron from the peritoneal cavity of rats, however, dialysate iron dextran concentrations of 2 mg/L or greater are toxic to the peritoneal membrane. Therefore, future studies should be performed to determine the minimal effective and nontoxic iron dextran concentrations for intraperitoneal administration.


1979 ◽  
Author(s):  
B. Lacaze ◽  
C. Ferrand ◽  
O. Pepin

The intraperitoneal administration of the LD50 dose of Russell’s viper venom to Sprague Dawley rats induces a DIC with consumption coagulopathy. The PT, TT and APTT are increased and the recalcification time and platelet count is considerably decreased. Also the thromboelastogram is quite perturbed. In order to follow the modifications of the coagulation parameters induced by the venom in the presence and absence of Ticlopidine. Four groups of each eight animals are investigated : Control, Ticlopidine 150 mg/kg/d. P.O. 4 days, Venom LD5O of Russell’s venom viper (Sigma), i.e. 400 μg/kg by I.P. route, 15 hrs before sacrifice, Ticlopidine + Venom T. 150 mg/kq/d. P.O. 4 days and the LD50 venom 15 hrs before sacrifice. The venom showed versus control a significant increase of PT, and APTT a significant decrease of Recalcification time and platelet count. The prevention of the DIC by Ticlopidine is characterized by the normalization of the coagulation factors. In comparison with the venom the Ticlopidine group has an increase of rocalci-fication time and PT, TT, APTT and platelet count were identical with the control group. The fibrinogen level increase significantly. The histopathological examination of kidneys and lunqs show the characteristic lesions of DIC in the venom animals, and the protective activity of Ticlopidine versus the intravascular aggregats in the Ticlopidine venom group. No protection by Ticlopidine however, was shown against the neurotoxicity of the venom. The inhibition of platelet aggregats and the antithrombotic activity of a drug can be evaluated by this experimental model of an acute DIC.


2012 ◽  
Vol 46 (3) ◽  
pp. 200-206 ◽  
Author(s):  
Mariana Abreu ◽  
Delia Aguado ◽  
Javier Benito ◽  
Ignacio A Gómez de Segura

This study aimed to estimate the reduction in the minimum alveolar concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane ( n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.


2020 ◽  
Author(s):  
Emre Kayalar ◽  
Gul Tas Deynek ◽  
Olgu Enis Tok ◽  
Sevim Kucuk

ABSTRACT Objectives To determine the effects of Salvianolic acid B (Sal B) on new bone formation in the orthopedically expanded premaxillary sutures in rats. Materials and Methods The sample consisting of Sprague Dawley rats (male, n = 14) was split in half by random selection: the experiment group (Sal B) and the control group. The premaxillary suture of each rat was expanded by bonding an open-loop spring to two maxillary incisors, each end to one tooth. A 5-day expansion period followed by a 12-day retention period was conducted. The 17-day intraperitoneal administration of Sal B was performed daily for the experiment group at a dose of 40 mg/kilo. The trial was completed after sacrificing the rats and dissection of the premaxillae for histological analysis. The amount of new bone, quantity of capillaries and intensity of inflammatory cells were histomorphometrically determined while the quantities of osteoblasts and osteoclasts were determined immunohistochemically. Results The Sal B group was significantly different from the control group and had greater quantities of new bone, capillaries, inflammatory cells, osteoblasts, and osteoclasts. Conclusions Salvianolic acid B displays a positive effect during premaxillary expansion with a greater number of capillaries potentially in association with higher bone formation and improved angiogenesis in rats.


Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.


2020 ◽  
Vol 21 (6) ◽  
pp. 471-478
Author(s):  
Shenjia Huang ◽  
Qingqing Xu ◽  
Linsheng Liu ◽  
Yicong Bian ◽  
Shichao Zhang ◽  
...  

Background: Green tea can inhibit OATPs, so it may interact with the substrate of OATPs, such as rosuvastatin. Objective: This study aimed to investigate the effects of green tea on the pharmacokinetics of rosuvastatin and its mechanism. Methods: Male Sprague-Dawley rats received different doses of green tea extract (GTE) and (-)- epigallocatechin-3- gallate (EGCG). Caco-2 cells and OATP1B1-HEK293T cells were used in drug uptake and transport assay. The matrix concentrations of rosuvastatin and catechins were determined by ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). Results: GTE and EGCG were both found to increase the area under the plasma concentration-time curve (AUC0-∞) of rosuvastatin ((p<0.050). In the Caco-2 cell model, the uptake and transport of rosuvastatin in the GTE groups were 1.94-fold (p<0.001) and 2.11-fold (p<0.050) higher, respectively, than those of the control group. However, in the EGCG group, the uptake and transport of rosuvastatin were decreased by 22.62% and 44.19%, respectively (p<0.050). In the OATP1B1- HEK293T cell model, the OATP1B1-mediated rosuvastatin uptake was decreased by GTE to 35.02% of that in the control (p<0.050) and was decreased by EGCG to 45.61% of that in the control (p<0.050). Conclusion: GTE increased the systemic rosuvastatin exposure in rats. The mechanism may include an increase in rosuvastatin absorption and a decrease in liver distribution by inhibiting OATP1B1. EGCG may be the main ingredient of green tea that affects the pharmacokinetic parameters of rosuvastatin. Our results showed the importance of conducting green tea-rosuvastatin study.


2019 ◽  
Vol 18 (1) ◽  
pp. 52-62 ◽  
Author(s):  
Antonio Ibarra ◽  
Erika Mendieta-Arbesú ◽  
Paola Suarez-Meade ◽  
Elisa García-Vences ◽  
Susana Martiñón ◽  
...  

Background: The chronic phase of Spinal Cord (SC) injury is characterized by the presence of a hostile microenvironment that causes low activity and a progressive decline in neurological function; this phase is non-compatible with regeneration. Several treatment strategies have been investigated in chronic SC injury with no satisfactory results. OBJECTIVE- In this proof-of-concept study, we designed a combination therapy (Comb Tx) consisting of surgical glial scar removal plus scar inhibition, accompanied with implantation of mesenchymal stem cells (MSC), and immunization with neural-derived peptides (INDP). Methods: This study was divided into three subsets, all in which Sprague Dawley rats were subjected to a complete SC transection. Sixty days after injury, animals were randomly allocated into two groups for therapeutic intervention: control group and animals receiving the Comb-Tx. Sixty-three days after treatment we carried out experiments analyzing motor recovery, presence of somatosensory evoked potentials, neural regeneration-related genes, and histological evaluation of serotoninergic fibers. Results: Comb-Tx induced a significant locomotor and electrophysiological recovery. An increase in the expression of regeneration-associated genes and the percentage of 5-HT+ fibers was noted at the caudal stump of the SC of animals receiving the Comb-Tx. There was a significant correlation of locomotor recovery with positive electrophysiological activity, expression of GAP43, and percentage of 5-HT+ fibers. Conclusion: Comb-Tx promotes motor and electrophysiological recovery in the chronic phase of SC injury subsequent to a complete transection. Likewise, it is capable of inducing the permissive microenvironment to promote axonal regeneration.


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