scholarly journals Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Chian-Yuh Lin ◽  
Mao-Tsun Lin ◽  
Ruei-Tang Cheng ◽  
Sheng-Hsien Chen
Keyword(s):  
Heat Stress ◽  
Core Temperature ◽  
Neuronal Damage ◽  
Organ Damage ◽  
Multiple Organ ◽  
Testosterone Replacement ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Beneficial Effects ◽  
Multiple Organs ◽  
Induced Apoptosis

When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15) and reduced the hypothermia (core temperature,37.3∘C). The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

scholarly journals Relationship Between Serum Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid and Organ Damage in Coronavirus 2019 Patients: A Cohort Study

2020 ◽  
Author(s):  
Dan Xu ◽  
Fuling Zhou ◽  
Wenbo Sun ◽  
Liangjun Chen ◽  
Lan Lan ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Troponin I ◽  
Demographic Data ◽  
Organ Damage ◽  
Multiple Organ ◽  
Serum Samples ◽  
Cardiac Damage ◽  
Multiple Organs ◽  
Laboratory Biomarkers

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. Methods Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. Results Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. Conclusions In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.

scholarly journals Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB

2021 ◽  
Vol 22 (12) ◽  
pp. 6249
Author(s):  
Jaewoong Jang ◽  
Jaewon Song ◽  
Inae Sim ◽  
Young V. Kwon ◽  
Yoosik Yoon
Keyword(s):  
Wnt Signaling ◽  
Organ Dysfunction ◽  
Proinflammatory Cytokines ◽  
Host Response ◽  
Organ Damage ◽  
Suppressive Effect ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Multiple Organs

Sepsis is characterized by multiple-organ dysfunction caused by the dysregulated host response to infection. Until now, however, the role of the Wnt signaling has not been fully characterized in multiple organs during sepsis. This study assessed the suppressive effect of a Wnt signaling inhibitor, Wnt-C59, in the kidney, lung, and liver of lipopolysaccharide-induced endotoxemic mice, serving as an animal model of sepsis. We found that Wnt-C59 elevated the survival rate of these mice and decreased their plasma levels of proinflammatory cytokines and organ-damage biomarkers, such as BUN, ALT, and AST. The Wnt/β-catenin and NF-κB pathways were stimulated and proinflammatory cytokines were upregulated in the kidney, lung, and liver of endotoxemic mice. Wnt-C59, as a Wnt signaling inhibitor, inhibited the Wnt/β-catenin pathway, and its interaction with the NF-κB pathway, which resulted in the inhibition of NF-κB activity and proinflammatory cytokine expression. In multiple organs of endotoxemic mice, Wnt-C59 significantly reduced the β-catenin level and interaction with NF-κB. Our findings suggest that the anti-endotoxemic effect of Wnt-C59 is mediated via reducing the interaction between β-catenin and NF-κB, consequently suppressing the associated cytokine upregulation in multiple organs. Thus, Wnt-C59 may be useful for the suppression of the multiple-organ dysfunction during sepsis.

scholarly journals Clinical and morphological features of SARS-COV-2 associated acute hemorrhagic necrotizing encephalopathy: case report

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Victor Vladimirovich Ermilov ◽  
Nikita Alexeevich Dorofeev
Keyword(s):  
Nervous System ◽  
Case Report ◽  
Neuronal Damage ◽  
Organ Damage ◽  
Multiple Organ ◽  
Fatal Complication ◽  
Current Case ◽  
Case Presentation ◽  
Hemorrhagic Necrosis ◽  
Similar Combination

Abstract Background The current case report presents acute hemorrhagic necrotizing encephalopathy (AHNE) as an example of a fatal complication, the etiology of which could be coronavirus disease 2019 (COVID-19) with multiple organ damage along with the existing respiratory tuberculosis. Case presentation A male in his 20s had severe symptoms of central nervous system lesion, which developed against the background of COVID-19 and respiratory tuberculosis, for which he was treated in the intensive care unit. Autopsy confirmed that he died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated AHNE in adults with severe fatal endothelial dysfunction and respiratory tuberculosis. The main morphological signs of brain damage were desquamative endotheliitis, thrombosis, parenchymal hemorrhagic necrosis, encephalitis, severe necrobiotic neuronal damage. Conclusion The defeat of endothelial cells with the development of generalized endotheliitis in COVID-19, especially in conjunction with comorbid pathology, in particular tuberculosis, can lead to a fatal complication that affects the nervous system—AHNE. Therefore, it is worth paying close attention to the appearance of neurological symptoms in patients with a similar combination of diseases.

A 3-D mathematical model to identify organ-specific risks in rats during thermal stress

2013 ◽  
Vol 115 (12) ◽  
pp. 1822-1837 ◽  
Author(s):  
Vineet Rakesh ◽  
Jonathan D. Stallings ◽  
Bryan G. Helwig ◽  
Lisa R. Leon ◽  
David A. Jackson ◽  
...  
Keyword(s):  
Heat Stress ◽  
Core Temperature ◽  
Three Dimensional ◽  
Blood Perfusion ◽  
Adverse Outcomes ◽  
Maximum Temperature ◽  
Blood Temperature ◽  
Multiple Organs ◽  
Organ Specific

Early prediction of the adverse outcomes associated with heat stress is critical for effective management and mitigation of injury, which may sometimes lead to extreme undesirable clinical conditions, such as multiorgan dysfunction syndrome and death. Here, we developed a computational model to predict the spatiotemporal temperature distribution in a rat exposed to heat stress in an attempt to understand the correlation between heat load and differential organ dysfunction. The model includes a three-dimensional representation of the rat anatomy obtained from medical imaging and incorporates the key mechanisms of heat transfer during thermoregulation. We formulated a novel approach to estimate blood temperature by accounting for blood mixing from the different organs and to estimate the effects of the circadian rhythm in body temperature by considering day-night variations in metabolic heat generation and blood perfusion. We validated the model using in vivo core temperature measurements in control and heat-stressed rats and other published experimental data. The model predictions were within 1 SD of the measured data. The liver demonstrated the greatest susceptibility to heat stress, with the maximum temperature reaching 2°C higher than the measured core temperature and 95% of its volume exceeding the targeted experimental core temperature. Other organs also attained temperatures greater than the core temperature, illustrating the need to monitor multiple organs during heat stress. The model facilitates the identification of organ-specific risks during heat stress and has the potential to aid in the development of improved clinical strategies for thermal-injury prevention and management.

scholarly journals Inhibition of Cerebral High-Mobility Group Box 1 Protein Attenuates Multiple Organ Damage and Improves T Cell-Mediated Immunity in Septic Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Ren ◽  
Xiu-hua Li ◽  
Yao Wu ◽  
Ning Dong ◽  
Ya-lin Tong ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
High Mobility ◽  
Organ Damage ◽  
Multiple Organ ◽  
High Mobility Group ◽  
Organ Injury ◽  
Cell Mediated Immunity ◽  
Functional Changes ◽  
Multiple Organs ◽  
Major Factors

Sepsis remains one of the leading causes of mortality in intensive care units, but there is a shortage of effective treatments. A dysregulated host immune response and multiple organ injury are major factors for the pathogenesis and progression of sepsis, which require specific mechanism and treatment. In the present study, we performed an intracerebroventricular (ICV) injection of BoxA, a specific antagonist of high-mobility group box 1 protein (HMGB1), in septic rats that were produced by cecal ligation and puncture surgery; we further assessed the functional changes of multiple organs and splenic T lymphocytes. We found that the inhibition of cerebral HMGB1 significantly alleviated multiple organ damage under septic exposure, including damage to the heart, liver, lungs, and kidneys; reversed the immune dysfunction of T cells; and increased the survival of septic rats. These data suggest that central HMGB1 might be a potential therapeutic target for septic challenge and that inhibition of brain HMGB1 can protect against multiple organ dysfunction induced by sepsis.

scholarly journals Lipopolysaccharide Induces Disseminated Endothelial Apoptosis Requiring Ceramide Generation

1997 ◽  
Vol 186 (11) ◽  
pp. 1831-1841 ◽  
Author(s):  
Adriana Haimovitz-Friedman ◽  
Carlos Cordon-Cardo ◽  
Shariff Bayoumy ◽  
Mark Garzotto ◽  
Maureen McLoughlin ◽  
...  
Keyword(s):  
Endotoxic Shock ◽  
Organ Damage ◽  
Multiple Organ ◽  
Acid Sphingomyelinase ◽  
Endothelial Apoptosis ◽  
Tnf Α ◽  
Normal Increase ◽  
Induced Apoptosis ◽  
Ceramide Generation ◽  
Necrosis Factor

The endotoxic shock syndrome is characterized by systemic inflammation, multiple organ damage, circulatory collapse and death. Systemic release of tumor necrosis factor (TNF)-α and other cytokines purportedly mediates this process. However, the primary tissue target remains unidentified. The present studies provide evidence that endotoxic shock results from disseminated endothelial apoptosis. Injection of lipopolysaccharide (LPS), and its putative effector TNF-α, into C57BL/6 mice induced apoptosis in endothelium of intestine, lung, fat and thymus after 6 h, preceding nonendothelial tissue damage. LPS or TNF-α injection was followed within 1 h by tissue generation of the pro-apoptotic lipid ceramide. TNF-binding protein, which protects against LPS-induced death, blocked LPS-induced ceramide generation and endothelial apoptosis, suggesting systemic TNF is required for both responses. Acid sphingomyelinase knockout mice displayed a normal increase in serum TNF-α in response to LPS, yet were protected against endothelial apoptosis and animal death, defining a role for ceramide in mediating the endotoxic response. Furthermore, intravenous injection of basic fibroblast growth factor, which acts as an intravascular survival factor for endothelial cells, blocked LPS-induced ceramide elevation, endothelial apoptosis and animal death, but did not affect LPS-induced elevation of serum TNF-α. These investigations demonstrate that LPS induces a disseminated form of endothelial apoptosis, mediated sequentially by TNF and ceramide generation, and suggest that this cascade is mandatory for evolution of the endotoxic syndrome.

scholarly journals Multiple Organ Dysfunction Reduces In-Hospital Survival in COVID-19 Patients

2020 ◽  
Vol 5 (09) ◽  
pp. 389-394
Author(s):  
Najiba Abdulrazzaq ◽  
Kashif Bin Naeem ◽  
Abdalla Alhajiri ◽  
Ayman Chkhis ◽  
Vinod Choondal ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Organ Dysfunction ◽  
Distress Syndrome ◽  
Cardiac Injury ◽  
Kidney Injury ◽  
Organ Damage ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Hospital Survival ◽  
Multiple Organs

Background: Although primarily a respiratory illness, COVID-19 involves multiple organs when the disease is severe or critical. Hence, we conducted this study to evaluate the incidence of multiple organ dysfunction in COVID-19 patients and its implications on survival. Methods: A retrospective analysis of laboratory-confirmed COVID-19 patients presenting to our center in Dubai, UAE between April 2020 and July 2020. Data was collected from the electronic medical records and analyzed to evaluate multiple organ damage observed during hospital admission. Findings: Five-hundred patients were studied. Overall mean age was 49.5 years (range 13-94), 76% males, 33% diabetics, 31% hypertensives. 97/500 (19.4%) had evidence of single organ damage; 37/500 (7.4%) had two organ damage; and 105/500 (21%) had more than two organ damage. Acute respiratory distress syndrome was the most prevalent organ damage,153/500 (30.6%); followed by acute cardiac injury, 120/500 (24%); acute kidney injury 107/500 (21.4%); acute liver injury 96/500 (19.2%); septic shock 93/500 (18.6%); disseminated intravascular coagulation 27/500 (5.4%), and heart failure 17/500 (3.4%). We found that in-hospital survival reduced as the number of organs involved increased; only 20% patients survived who had more than 2 organ damage. Also, the chances of survival reduced considerably once other organs were involved in addition to the acute respiratory distress syndrome (91.6% survival in ARDS alone vs. 28.6% survival in ARDS with acute kidney injury vs. 10.4% survival in ARDS with shock/acute cardiac injury/acute kidney injury). Conclusion: Multiple organ dysfunction is common in COVID-19 as 21% had evidence of more than two organ damage in our study. The survival in COVID-19 reduces significantly once multiple organs are involved. Early monitoring and recognition of multiple organ dysfunction is necessary to prevent adverse outcomes and improve survival.

scholarly journals Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricia Soriano Roque ◽  
Mehdi Hooshmandi ◽  
Laura Neagu-Lund ◽  
Shelly Yin ◽  
Noosha Yousefpour ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
General Anesthesia ◽  
Preventive Treatment ◽  
Intranasal Insulin ◽  
Translational Repressor ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

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