Hemorrhagic shock induces G-CSF expression in bronchial epithelium

1997 ◽  
Vol 273 (5) ◽  
pp. L1058-L1064 ◽  
Author(s):  
Christian Hierholzer ◽  
Edward Kelly ◽  
Katsuhiko Tsukada ◽  
Eric Loeffert ◽  
Simon Watkins ◽  
...  
Keyword(s):  
Lung Injury ◽  
Hemorrhagic Shock ◽  
Fold Increase ◽  
Bronchial Epithelium ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Inflammatory Processes ◽  
Csf Levels

Hemorrhagic shock (HS) initiates a series of inflammatory processes that includes the activation of polymorphonuclear granulocytic neutrophils (PMN). We tested the hypothesis that HS induces granulocyte colony-stimulating factor (G-CSF), a cytokine that augments PMN effector functions, in the lungs of rats. Sprague-Dawley rats were subjected to compensated or decompensated HS followed by resuscitation and death at 4 or 8 h. Animals subjected to HS demonstrated acute lung injury with PMN infiltration, edema, and hypoxia. Using semiquantitative reverse transcriptase-polymerase chain reaction, we detected a 1.9- to 7.1-fold increase in G-CSF mRNA levels in the lung of animals subjected to HS compared with sham controls. Levels of G-CSF mRNA increased with increased duration of the ischemic phase of resuscitated shock. In situ hybridization revealed that bronchoepithelial cells were the major cellular site of G-CSF mRNA. Thus production of G-CSF mRNA by bronchoepithelial cells is dramatically increased in a rat model of HS that also demonstrated lung injury. Increased local G-CSF levels may contribute to PMN recruitment and activation and resultant lung injury in HS.

Modulation of central glucocorticoid receptors in short- and long-term experimental hypothyroidism

2015 ◽  
Author(s):  
Elena Nikolopoulou ◽  
Dimitris Mytilinaios ◽  
Dimitris Spinos ◽  
Nikitas – Apollon Panagiotopoulos ◽  
George P. Chrousos
Keyword(s):  
Glucocorticoid Receptor ◽  
Binding Affinity ◽  
Glucocorticoid Receptors ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Receptor Number ◽  
Short And Long Term

Aim: Normal adrenocortical responsiveness to stress involves glucocorticoid negative feedback to terminate hypothalamic-pituitary-adrenal (HPA) axis activation. Hypothyroidism is associated with a centrally mediated adrenal insufficiency associated. The aim of this study was to examine whether this may be explained by a disturbed glucocorticoid feedback through specific brain receptors: the mineralocorticoid (MR) and glucocorticoid receptor (GR). Methods: Cytosolic receptor binding and gene expression was assessed in male Sprague-Dawley rats (350gm) with short- (7 days) and long-standing (60 days) hypothyroidism (thyroidectomy). Glucocorticoid receptor number and binding affinity in the hippocampus were measured using radioreceptor assay. In situ hybridization was employed to examine GR and MRmRNA levels in the hippocampus and the pituitary. Results: No differences in receptor number or affinity were observed after 7days and 60days treatment. Increased GRmRNA expression in the anterior pituitary was observed in 7day hypothyroid rats under basal conditions compared to euthyroid rats (122.77+4.93 vs 99.65+4.83 DPM/mg; p<0.05), which was associated with significantly decreased GRmRNA levels after osmotic stress (100.82+2.8 vs 110.48+4.1 DPM/mg; p<0.05). No differences were observed at 60days. No effect on MR mRNA expression in the hippocampus was seen in basal condition after both 7- and 60days hypothyroidism. MRmRNA was significantly decreased in 60 days-hypothyroid rats compared to euthyroid after normal saline (3995.67+131.54 vs 5121.00+505.2 DPM/mg; p<0.05). Conclusion: Hypothyroidism resulted in significant changes in GR and MR mRNA levels, in the hippocampus and the pituitary, without changes in receptor number and binding affinity.

Surfactant protein A expression is delayed in fetuses of streptozotocin-treated rats

1992 ◽  
Vol 262 (4) ◽  
pp. L489-L494 ◽  
Author(s):  
S. H. Guttentag ◽  
D. S. Phelps ◽  
W. Stenzel ◽  
J. B. Warshaw ◽  
J. Floros
Keyword(s):  
Protein A ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Female Rats ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Normal Expression

The content and distribution of the 26-to 38-kDa surfactant protein (SP-A) and its mRNA were determined in fetuses of control and streptozotocin (STZ)-treated Sprague-Dawley rats using immunohistochemistry, RNA blotting, and in situ hybridization. Female rats were treated with 50 mg/kg STZ before mating, and the fetuses were killed at fetal days 18-21 or on neonatal days 1 and 2 (day of birth = end of day 22). SP-A was barely detectable on fetal day 18 in controls and easily detected by fetal day 21. In the STZ group, SP-A was decreased compared with controls at fetal days 18-21. However, by neonatal days 1–2, there were no significant differences in SP-A levels between groups. SP-A mRNA was detectable at fetal day 18 in controls, but it was decreased in the STZ group at day 18-21 (P less than 0.02) and differences were no longer detected by neonatal days 1–2. SP-A and SP-A mRNA accumulated with advancing gestational age in both groups until neonatal days 1–2. The differences in SP-A and SP-A mRNA levels in the two groups diminished with advancing age but remained significant at fetal day 21. These data suggest that STZ-induced diabetes interferes with normal expression of SP-A in the developing fetal lung.

C5-blocking antibody reduces fluid requirements and improves responsiveness to fluid infusion in hemorrhagic shock managed with hypotensive resuscitation

2007 ◽  
Vol 102 (2) ◽  
pp. 673-680 ◽  
Author(s):  
Russell M. Peckham ◽  
Michael T. Handrigan ◽  
Timothy B. Bentley ◽  
Michael J Falabella ◽  
Andrew D. Chrovian ◽  
...  
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Fold Increase ◽  
Sprague Dawley ◽  
Blocking Antibody ◽  
Fluid Infusion ◽  
Hypotensive Resuscitation ◽  
Sprague Dawley Rats ◽  
Prolonged Hypotension

Hypotensive resuscitation strategies and inhibition of complement may both be of benefit in hemorrhagic shock. We asked if C5-blocking antibody (anti-C5) could diminish the amount of fluid required and improve responsiveness to resuscitation from hemorrhage. Awake, male Sprague-Dawley rats underwent controlled hemorrhage followed by prolonged (3 h) hypotensive resuscitation with lactated Ringer’s or Hextend, with or without anti-C5. Anti-C5 treatment led to an estimated 62.3 and 58.5% reduction in the volume of Hextend and lactated Ringer’s, respectively. In the subgroup of animals with a positive mean arterial pressure (MAP) response to fluid infusion following prolonged hypotension, anti-C5 treatment led to an estimated 4.7- and 4.1-fold increase in mean arterial pressure response per unit Hextend and lactated Ringer’s infused, respectively. We observed no significant postresuscitation metabolic differences between the anti-C5 groups and controls. Whether anti-C5 could serve as a volume-sparing adjunct that improves responsiveness to fluid administration in humans deserves further study.

Dysregulation of arcuate nucleus preproneuropeptide Y mRNA in diet-induced obese rats

1997 ◽  
Vol 272 (5) ◽  
pp. R1365-R1370 ◽  
Author(s):  
B. E. Levin ◽  
A. A. Dunn-Meynell
Keyword(s):  
Arcuate Nucleus ◽  
High Energy ◽  
Energy Restriction ◽  
Dopamine Turnover ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Hypothalamic Arcuate Nucleus

Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) produce metabolic and physiological effects that promote the development and maintenance of obesity. In turn, NPY metabolism in these neurons is inhibited by dopamine release. In this study, ARC prepro-NPY mRNA and ARC/median eminence (ME) dopamine turnover were assessed in chow-fed male Sprague-Dawley rats prone to develop diet-induced obesity (DIO) or to be diet resistant (DR) when fed a high-energy (HE) diet. By in situ hybridization, DIO-prone rats had 39% more ARC NPY mRNA expression than DR-prone rats under chow-fed conditions. DIO-prone rat ARC/ME dopamine levels were 14% higher, but dopamine half-life was 176% longer and turnover was 59% less than DR-prone rats. Neither a 48-h fast nor 50% energy intake restriction for 5 days affected the already increased ARC NPY mRNA levels in DIO-prone rats. Both manipulations increased NPY expression to the level of DIO-prone rats in DR-prone rats by 23 and 35%, respectively. Finally, when fed HE diet for 2 wk, neither DIO- nor DR-prone rats altered their ARC NPY expression despite the development of obesity and hyperinsulinemia in DIO rats. Thus DIO-prone rats overexpress and fail to regulate ARC NPY mRNA to energy restriction or hyperinsulinemia. This dysregulation is possibly secondary to reduced inhibition because of defective ARC/ME dopamine turnover. Both may be important predisposing factors in the development of DIO.

Intracellular EDEMA does not adversely affect the ability to cryopreserve intact hearts

1993 ◽  
Vol 51 ◽  
pp. 278-279
Author(s):  
CL Hastings ◽  
RD Carlton ◽  
FG Lightfoot ◽  
AF Tryka
Keyword(s):  
Cell Injury ◽  
Median Sternotomy ◽  
Left Ventricular ◽  
Ventricular Free Wall ◽  
Hypoxic Cell ◽  
Free Wall ◽  
Sprague Dawley ◽  
Left Ventricular Free Wall ◽  
Sprague Dawley Rats

The earliest ultrastructural manifestation of hypoxic cell injury is the presence of intracellular edema. Does this intracellular edema affect the ability to cryopreserve intact myocardium? To answer this guestion, a model for anoxia induced intracellular edema (IE) was designed based on clinical intraoperative myocardial preservation protocol. The aortas of 250 gm male Sprague-Dawley rats were cannulated and a retrograde flush of Plegisol at 8°C was infused over 90 sec. The hearts were excised and placed in a 28°C bath of Lactated Ringers for 1 h. The left ventricular free wall was then sliced and the myocardium was slam frozen. Control rats (C) were anesthetized, the hearts approached by median sternotomy, and the left ventricular free wall frozen in situ immediately after slicing. The slam frozen samples were obtained utilizing the DDK PS1000, which was precooled to -185°C in liguid nitrogen. The tissue was in contact with the metal mirror for a dwell time of 20 sec, and stored in liguid nitrogen until freeze dry processing (Lightfoot, 1990).

scholarly journals Differential Effects of Refeeding on Melanocortin-Responsive Neurons in the Hypothalamic Paraventricular Nucleus

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4329-4335 ◽  
Author(s):  
Edith Sánchez ◽  
Praful S. Singru ◽  
Runa Acharya ◽  
Monica Bodria ◽  
Csaba Fekete ◽  
...  
Keyword(s):  
Gene Expression ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Early Action ◽  
Sprague Dawley Rats ◽  
Melanocortin Signaling ◽  
Agouti Related Protein ◽  
Serum Tsh

To explore the effect of refeeding on recovery of TRH gene expression in the hypothalamic paraventricular nucleus (PVN) and its correlation with the feeding-related neuropeptides in the arcuate nucleus (ARC), c-fos immunoreactivity (IR) in the PVN and ARC 2 h after refeeding and hypothalamic TRH, neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels 4, 12, and 24 h after refeeding were studied in Sprague-Dawley rats subjected to prolonged fasting. Despite rapid reactivation of proopiomelanocortin neurons by refeeding as demonstrated by c-fos IR in ARC α-MSH-IR neurons and ventral parvocellular subdivision PVN neurons, c-fos IR was present in only 9.7 ± 1.1% hypophysiotropic TRH neurons. Serum TSH levels remained suppressed 4 and 12 h after the start of refeeding, returning to fed levels after 24 h. Fasting reduced TRH mRNA compared with fed animals, and similar to TSH, remained suppressed at 4 and 12 h after refeeding, returning toward normal at 24 h. AGRP and NPY gene expression in the ARC were markedly elevated in fasting rats, AGRP mRNA returning to baseline levels 12 h after refeeding and NPY mRNA remaining persistently elevated even at 24 h. These data raise the possibility that refeeding-induced activation of melanocortin signaling exerts differential actions on its target neurons in the PVN, an early action directed at neurons that may be involved in satiety, and a later action on hypophysiotropic TRH neurons involved in energy expenditure, potentially mediated by sustained elevations in AGRP and NPY. This response may be an important homeostatic mechanism to allow replenishment of depleted energy stores associated with fasting.

scholarly journals Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock

2016 ◽  
Vol 311 (1) ◽  
pp. G180-G191 ◽  
Author(s):  
Geeta Rao ◽  
Vivek R. Yadav ◽  
Shanjana Awasthi ◽  
Pamela R. Roberts ◽  
Vibhudutta Awasthi
Keyword(s):  
Oxidative Stress ◽  
Hemorrhagic Shock ◽  
Multiorgan Failure ◽  
Sprague Dawley ◽  
Barrier Dysfunction ◽  
Protective Mechanisms ◽  
Unfolded Protein ◽  
Sprague Dawley Rats ◽  
Markers Of Oxidative Stress ◽  
Protein Response

Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms.

Activated Kupffer cells cause a hypermetabolic state after gentle in situ manipulation of liver in rats

2001 ◽  
Vol 280 (6) ◽  
pp. G1076-G1082 ◽  
Author(s):  
Peter Schemmer ◽  
Nobuyuki Enomoto ◽  
Blair U. Bradford ◽  
Hartwig Bunzendahl ◽  
James A. Raleigh ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Kupffer Cells ◽  
Cell Function ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Hypermetabolic State ◽  
Hypoxia Marker ◽  
Factor Α ◽  
Necrosis Factor

Harvesting trauma to the graft dramatically decreases survival after liver transplantation. Since activated Kupffer cells play a role in primary nonfunction, the purpose of this study was to test the hypothesis that organ manipulation activates Kupffer cells. To mimic what occurs with donor hepatectomy, livers from Sprague-Dawley rats underwent dissection with or without gentle organ manipulation in a standardized manner in situ. Perfused livers exhibited normal values for O2 uptake (105 ± 5 μmol · g−1 · h−1) measured polarigraphically; however, 2 h after organ manipulation, values increased significantly to 160 ± 8 μmol · g−1 · h−1 and binding of pimonidazole, a hypoxia marker, increased about threefold ( P < 0.05). Moreover, Kupffer cells from manipulated livers produced three- to fourfold more tumor necrosis factor-α and PGE2, whereas intracellular calcium concentration increased twofold after lipopolysaccharide compared with unmanipulated controls ( P < 0.05). Gadolinium chloride and glycine prevented both activation of Kupffer cells and effects of organ manipulation. Furthermore, indomethacin given 1 h before manipulation prevented the hypermetabolic state, hypoxia, depletion of glycogen, and release of PGE2 from Kupffer cells. These data indicate that gentle organ manipulation during surgery activates Kupffer cells, leading to metabolic changes dependent on PGE2 from Kupffer cells, which most likely impairs liver function. Thus modulation of Kupffer cell function before organ harvest could be beneficial in human liver transplantation and surgery.

Loss of hypoxic pulmonary vasoconstriction in chronic pneumonia is not mediated by nitric oxide

1993 ◽  
Vol 265 (5) ◽  
pp. H1523-H1528 ◽  
Author(s):  
D. G. McCormack ◽  
N. A. Paterson
Keyword(s):  
Nitric Oxide ◽  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Sprague Dawley ◽  
Absolute Increase ◽  
Pulmonary Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Inflammatory Processes ◽  
The Difference

In pulmonary inflammatory processes such as pneumonia there is diminished hypoxic pulmonary vasoconstriction (HPV). We investigated whether the attenuated HPV in pneumonia is a due to excess nitric oxide (NO) release. Sprague-Dawley rats were anesthetized, and a slurry (0.06 ml) of infected agar beads (containing 6 x 10(5) Pseudomonas aeruginosa organisms) or control (sterile) beads was then injected into a distal bronchus through a tracheotomy. After the establishment of a chronic P. aeruginosa pneumonia (7-10 days later) animals were instrumented for hemodynamic monitoring, and the response to exposure to hypoxic gas (fraction of inspired O2 = 0.08) was recorded before and after the administration of NG-monomethyl-L-arginine (L-NMMA; 50 mg/kg), an inhibitor of NO synthesis. The hypoxic pressor response, as assessed by the absolute increase in pulmonary arterial pressure (PAP) and total pulmonary resistance (TPR), was reduced in infected animals compared with control animals. The change in PAP and TPR was 8.5 +/- 0.7 and 0.053 +/- 0.007, respectively, in control animals compared with 5.9 +/- 0.5 and 0.041 +/- 0.011 in infected animals. After L-NMMA the increase in PAP and TPR during hypoxia was greater in both control and infected animals. However, treatment with L-NMMA did not affect the difference between control and infected animals. We conclude that excess release of NO does not account for the attenuated hypoxic pressor response in pneumonia.

Cortical collecting duct Na-K pump in obstructive nephropathy

1990 ◽  
Vol 258 (5) ◽  
pp. F1320-F1327 ◽  
Author(s):  
H. Kimura ◽  
S. K. Mujais
Keyword(s):  
Ureteral Obstruction ◽  
Turnover Rate ◽  
Collecting Duct ◽  
Obstructive Nephropathy ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Irreversible Damage ◽  
Sprague Dawley Rats ◽  
Collecting Tubule

The present study examined the alterations in the cortical collecting tubule (CCT) Na-K pump that occur after unilateral ureteral obstruction and their consequences on electrolyte excretion. In male Sprague-Dawley rats, unilateral ureteral ligation led to a progressive decrease in intact CCT Na-K pump in situ turnover worsening with the duration of the obstruction: control, 20.1 +/- 0.4; obstructed kidney: 3 h, 14.6 +/- 0.3; 12 h, 12.7 +/- 0.6; 24 h, 12.8 +/- 0.5; 48 h, 11.6 +/- 0.5; and 96 h, 10.6 +/- 0.4 pmol Rb.mm-1.min-1 (all P less than 0.001 vs. control). CCT diameter increased with the duration of obstruction. Release of ureteral obstruction was associated with restitution of pump turnover rate. With 3 h of obstruction, recovery of pump in situ turnover was complete (19.7 +/- 0.4 pmol Rb.mm-1.min-1) by 24 h after release. With more prolonged obstruction (24 h) recovery was partial by 24 h postrelease (16.2 +/- 0.5 pmol Rb.mm-1.min-1) and complete (19.8 +/- 0.7 pmol Rb.mm-1.min-1) by 48 h, suggesting a delay in recovery without the occurrence of irreversible damage. The impairment in Na-K pump in situ turnover was paralleled by an impairment in the ability of the obstructed kidney to excrete an acute potassium load. This parallelism of functional and biochemical studies favors the notion that impairment of CCT Na-K pump in situ turnover contributes significantly to the abnormal potassium excretion that accompanies obstructive damage.

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