| 1. |
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| 2. |
- Brundin, Peik, et al.
(author)
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Gene Expression of Estrogen Receptors in Pbmc From Patients With Puumala-Virus Infection
- 2012
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In: Shock. - Philadelphia : Lippincott Williams & Wilkins. - 1073-2322 .- 1540-0514. ; 37:4, s. 355-359
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Journal article (peer-reviewed)abstract
- The influence of estrogen signaling on infectious diseases is not fully known. Males seem to be more susceptible to infections than females. This has also been noted for the Scandinavian form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus (PUUV). To investigate the differences in estrogen receptors in relation to sex and clinical severity, 20 patients (10 males, 10 females) with confirmed PUUV infection were studied. Real-time polymerase chain reaction was performed for analyzing mRNA expression of estrogen receptor-alpha (ERV), ER beta, and ER beta 2 (ER beta cx) in peripheral blood mononuclear cells from patients and healthy age-and sex-matched blood donors. Blood chemistry and peripheral blood mononuclear cells sampling were performed during the acute and convalescent phases. None or very small amounts of ER beta were detected, and ER alpha and ER beta 2 mRNA were elevated in the patient group. The samples from the males were correlated with ER beta 2; the female samples, with ER alpha. Furthermore, the female and male samples are partly separated using multivariate statistic analysis (principal component analysis), supporting findings that clinical symptoms differ depending on sex.
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| 3. |
- Castegren, Markus, et al.
(author)
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Differences in Organ Dysfunction in Endotoxin Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin
- 2012
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In: Shock. - 1073-2322 .- 1540-0514. ; 37:5, s. 501-510
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Journal article (peer-reviewed)abstract
- Endotoxin tolerance is a well-studied phenomenon associated with a reduced inflammatory response. In the switch from an inflammatory to an anti-inflammatory response in clinical sepsis the concept of endotoxin tolerance is of obvious interest. However, only limited data exist regarding the effect of endotoxin tolerance on organ dysfunction and, therefore, this was investigated in a porcine intensive care sepsis model. Twenty-seven healthy pigs, including nine control animals, were included in the study. Twelve pigs pre-exposed to 24 h of intravenous endotoxin infusion and intensive care and six unexposed pigs were given either a high- or low-dose endotoxin challenge for 6 h. Inflammatory, circulatory, hypoperfusion and organ dysfunction parameters were followed. The inflammatory responses as well as parameters representing circulation, hypoperfusion, cardiac and renal function were all markedly attenuated in animals pre-exposed to endotoxin and intensive care as compared with animals not pre-exposed. In animals pre-exposed to endotoxin and given the high-dose of endotoxin challenge, deterioration in pulmonary function was equal to or even worse than in animals not pre-exposed.In contrast to the overall protective effect of endotoxin tolerance observed in other organ systems, the lungs of endotoxin tolerant animals demonstrated an increased responsiveness to high-dose endotoxin challenge.
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| 4. |
- Heinius, Goran, et al.
(author)
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HYPOTHERMIA INCREASES REBLEEDING DURING UNCONTROLLED HEMORRHAGE IN THE RAT
- 2011
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In: Shock. - : Biomedical Press. - 1073-2322 .- 1540-0514. ; 36:1, s. 60-66
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Journal article (peer-reviewed)abstract
- Trauma registers show that hypothermia (HT) is an independent risk factor for death during hemorrhagic shock, although experimental animal studies indicate that HT may be beneficial during these conditions. However, the animal models were not designed to detect the expected increase in bleeding caused by HT. In a new model for uncontrolled bleeding, 40 Sprague-Dawley rats were exposed to a standardized femoral artery injury and randomized to either normothermia or HT. Ketamine/midazolam was used to minimize hemodynamic changes due to the anesthesia. The hypothermic rats were cooled to 30 degrees C and rewarmed again at 90 min. The study period was 3 h. The incidence, onset time, duration, and volume of bleedings as well as hemodynamic and metabolic changes were recorded. There was no difference between groups with respect to the initial bleeding. Rebleedings occurred among 60% of the animals in both groups. Hypothermic rebleeders had more, larger, and longer rebleedings, resulting in a total rebleeding volume amounting to 41% of their estimated blood volume. The corresponding figure for the normothermic rebleeders was 3% (P less than 0.001). Total rebleeding volume was significantly larger in the hypothermic group, even at body temperatures greater than 35 degrees C. We conclude that the risk of rebleeding from a femoral injury is greater in the presence of cooling and HT. The larger rebleeding volumes seen even at body temperatures greater than 35 degrees C indicate that factors other than temperature-induced coagulopathy also contributed to the increased hemorrhage.
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| 5. |
- Johannisson, Anders
(author)
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Bronchial microdialysis of cytokines in the epithelial lining fluid in experimental intestinal ischemia and reperfusion before onset of manifest lung injury
- 2010
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In: Shock. - 1073-2322 .- 1540-0514. ; 34, s. 517-524
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Journal article (peer-reviewed)abstract
- Today, there is no continuous monitoring of the bronchial epithelial lining fluid. This study used microdialysis as a method of continuous monitoring of early lung cytokine response secondary to intestinal ischemia-reperfusion in pigs. The authors aimed to examine bronchial microdialysis for continuous monitoring of IL-1 beta, TNF-alpha, IL-8, and fluorescein isothiocyanate Dextran 4,000 Da (FD-4). The superior mesenteric artery was cross-clamped for 120 min followed by 240 min of reperfusion (ischemia group, n = 8). Four sham-operated pigs served as controls. The pigs were anesthetized and normoventilated (peak inspiratory pressure, <20 cm H(2)O; positive end-expiratory pressure, 7 cm H(2)O). Samples from bronchial and luminal intestinal and arterial microdialysis catheters (flow-rate of 1 mu L/min) were collected during reperfusion in 60-min fractions. Samples were analyzed for TNF-alpha, IL-1 beta, IL-8, and FD-4. Data are presented as median (interquartile range). A lung biopsy was collected at the end of the experiment. During reperfusion, there was an increase in bronchial concentrations of both IL-8 (3.70 [1.47-8.93] ng/mL per h vs. controls, 0.61 [0.47-0.91] ng/mL per h; P < 0.001) and IL-1 beta (0.32 [0.05-0.56] ng/mL per h vs. controls, 0.07 [0.04-0.10] ng/mL per h; P = 0.008). In the intestinal lumen, IL-8 was increased in the ischemia group (6.33 [3.13-9.23] ng/mL per h vs. controls, 0.89 [0.21-1.86] ng/mL per h; P < 0.001). The FD-4 did not differ between groups. Pulmonary vascular resistance and pulmonary shunt increased versus controls. During reperfusion, PaO(2)/FiO(2) ratio decreased in the ischemia group. Histology was normal in both groups. Bronchial microdialysis detects altered levels of cytokines in the epithelial lining fluid and can be used for continuous monitoring of the immediate local lung cytokine response secondary to intestinal ischemia-reperfusion.
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| 6. |
- Lindenberger, Marcus, 1975-, et al.
(author)
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Reduced defense of central blood volume during acute hypovolemic circulatory stress in aging women
- 2012
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In: Shock. - : Lippincott Williams & Wilkins. - 1073-2322 .- 1540-0514. ; 37:6, s. 579-585
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Journal article (peer-reviewed)abstract
- Elderly men respond with decreased defense of central blood volume during hypovolemic stress, but this response has not been evaluated with age in women. The aim was to examine the compensatory mechanisms to defend central blood volume during experimental hypovolemia in elderly compared to young women. Cardiovascular responses in 34 women, 12 elderly (66.4±1.4 yr) and 22 young (23.1±0.4 yr) were studied during experimental hypovolemic circulatory stress induced by lower body negative pressure (LBNP) of 11-44 mmHg. Volumetric technique was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as to assess net capillary fluid transfer from tissue to blood in the arm. LBNP created comparable hypovolemia in elderly and young women. Heart rate increased less in elderly women (LBNP of 44 mmHg: 20±2 vs. 37±4 %, P < 0.01), but with similar decrease in forearm vascular conductance (FVC). Mobilization of capacitance blood from the peripheral circulation was both slower and decreased by ~60 % in elderly, and net capillary fluid absorption from surrounding tissues was reduced by ~40 % (LBNP of 44 mmHg). In conclusion, during acute hypovolemic circulatory stress elderly women responded with less increase in heart rate but with an equal change in FVC, implying decreased cardiovagal baroreceptor sensitivity. Furthermore, both capacitance response and net capillary fluid absorption were reduced, indicating less efficiency to defend central blood volume in elderly than in young women.
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| 7. |
- Semenas, Egidijus, et al.
(author)
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Neuroprotective effects of 17-beta-estradiol after hypovolemic cardiac arrest in immature piglets: the role of nitric oxide and peroxidation
- 2011
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In: Shock. - 1073-2322 .- 1540-0514. ; 36:1, s. 30-37
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Journal article (peer-reviewed)abstract
- We recently reported that cerebral and cardiac injuries are mitigated in immature female piglets after severe hemorrhage with subsequent cardiac arrest (CA) Female sex was also associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (nNOS). In the current study, we tested the hypothesis that exogenously administered 17β-estradiol (E2) can improve neurological outcome by NOS modulation. Thirty nine sexually immature piglets were bled to a mean arterial pressure of 35 mmHg over 15 min. Fifty μg/kg of E2 was then administered to 10 male and 10 female animals (estradiol group), while control animals (n=10 males and 9 females) received equal volume of normal saline. The animals were then subjected to ventricular fibrillation (4 min) followed by up to 15 min of open chest CPR. Vasopressin 0.4 U/kg and amiodarone 0.5 mg/kg were given and 3 ml/kg of 7.5% saline with 6% dextran was administered over 20 min. All surviving animals were euthanized after 3hr and their brains examined for histological injury and NOS expression. No significant differences were observed in survival or hemodynamics between the groups. Compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was a significant correlation between nNOS and iNOS levels and neuronal injury. Interestingly estradiol attenuated cerebral damage (including lower activation of nNOS and iNOS) both in male and female piglets. In conclusion, in our immature piglets model of hypovolemic cardiac arrest, E2 down-regulates iNOS and nNOS expression and results in decreased BBB permeability disruption and smaller neuronal injury.
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| 8. |
- Wang, Shuyun, et al.
(author)
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THE P38 alpha AND P38 delta MAP KINASES MAY BE GENE THERAPY TARGETS IN THE FUTURE TREATMENT OF SEVERE BURNS
- 2010
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In: Shock. - : Biomedical Press. - 1073-2322 .- 1540-0514. ; 34:2, s. 176-182
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Journal article (peer-reviewed)abstract
- Microvascular barrier damage, induced by thermal injury, imposes life-threatening problems owing to the pathophysiological consequences of plasma loss and impaired perfusion that finally may lead to multiple organ failure. The aim of the present study was to define the signaling role of selected mitogen-activated protein kinases (MAPKs) in general vessel hyperpermeability caused by burns and to look for a potential gene therapy. Rearrangement of cytoskeletons and cell tight junctions were evaluated by phalloidin labeling of actin and immunocytochemical demonstration of the ZO-1 protein, whereas blood vessel permeability was evaluated by a fluorescence ratio technique. The p38 MAPK inhibitor SB203580 largely blocked burn serum-induced stress-fiber formation and tight-junction damage. Using the adenoviral approach to transfect dominant negative forms of p38 MAPKs, we found that p38 alpha and p38 delta had similar effects. The in vivo part of the study showed that transfection of these two constructs significantly lowered general venular hyperpermeability and enhanced the survival of burned animals. Because the p38 MAPK pathway seems to play a crucial role in burn-induced vascular hyperpermeability, general transfection with p38 MAP dominant negative constructs might become a new therapeutic method to block burn-induced plasma leakage.
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| 9. |
- Wu, Wei, et al.
(author)
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Roles of Mitogen-Activated Protein Kinases in the Modulation of Endothelial Cell Function Following Thermal Injury
- 2011
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In: Shock. - : Biomedical Press. - 1073-2322 .- 1540-0514. ; 35:6, s. 618-625
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Journal article (peer-reviewed)abstract
- Several mitogen-activated protein kinases (MAPKs) are activated during thermal injury, and the p38 MAPK is specifically involved in endothelial cell (EC) actin and myosin rearrangement (stress-fiber formation) with ensuing cellular contraction and enhanced vessel permeability. Inhibition of p38 MAPK and extracellular signal-related kinase MAPK by their inhibitors SB203580 and PD98059, respectively, significantly reduces burn serum-induced EC stress-fiber formation, whereas SB203580 also inhibits burn serum-induced EC tight-junction damage and thereby general blood vessel hyperpermeability. The JNK MAPK inhibitor, SP600125, on the contrary, influences neither stress-fiber formation nor EC tight-junction damage. Extracellular signal-related kinase MAPK inhibition significantly decreases burn serum-induced Monocyte chemotactic protein-1 (MCP-1) release, whereas SB203580 and SP600125 have only limited such effects. Western blotting, real-time reverse transcriptase-polymerase chain reaction, and confocal laser scanning microscopy proved that SP600125 significantly inhibits burn serum-induced intercellular adhesion molecule 1 expression, whereas SB203580 depresses the expression of P selectin. In vivo studies, using the dominant negative adenoviral approach of MAPK kinase 3b and MAPK kinase 6b to block p38 MAPKs, and MKK4 and MKK7 to block JNK MAPKs, show that the latter MAPKs are involved in the regulation of P selectin and intercellular adhesion molecule 1 expression, respectively, following thermal injury. Taken together, the results suggest that several MAPKs play important, although different, roles in general EC alterations following burn injuries.
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