scholarly journals Rescuable effect of R-salbutamol in LPS-induced immune dysfunction of sepsis

2021 ◽  
Author(s):  
Huimin Beng ◽  
Shanping Wang ◽  
Junhua Hu ◽  
Xinglong Liang ◽  
Haolong Qin ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Inflammatory Cell ◽  
Minute Volume ◽  
Lung Damage ◽  
Racemic Mixture ◽  
Lps Challenge ◽  
Threatening Condition ◽  
Life Threatening ◽  
Alveolar Septa ◽  
Inflammatory Effect

Sepsis is a severe life-threatening condition caused by a dysregulated host response to infection. So far, there are no pharmacotherapies to stop sepsis. Salbutamol, an commonly used β2-adrenoreceptor agonist, has found to be potential in regulating immune response dysfunction and exert anti-inflammatory effect. However, salbutamol exists two isomers. R-isomer exhibits the therapeutic effect and clinical benefit, while S-isomer proves to be detrimental rather than benign. So, in this study, we investigated the preventive and therapeutic effect of R-salbutamol (R-sal), S-salbutamol (S-sal) or racemic mixture in a mouse model of lipopolysaccharide (LPS)-induced sepsis. Dexamethasone (Dex) was set as comparison. The results showed that R-sal markedly improved seven-day survival rate of septic mice both administered before or after LPS. Whereas Dex showed toxic and accelerated the death of septic mice when given before LPS injection. Lung histological examination and lung function assay revealed that LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa and congestion, and decreased minute volume in septic mice. R-sal pretreatment efficiently inhibited these changes, accompanying by markedly reduced lung MPO level, serum cytokines levels and lactate release and significantly restored the lymphocytes and suppressed the percentage of monocytes. Racemic mixture exhibited diminished effects while S-sal showed enhanced cytokines release. In addition, R-sal pretreatment showed a better improvement in prognostic pulmonary function at day4 in survived mice than that of Rac-sal. Collectively, our results indicate the potential benefit of R-sal for sepsis and sepsis-induced lung injury.

scholarly journals Lipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signaling

2021 ◽  
Author(s):  
Javier Casas ◽  
Clara Meana ◽  
José Ramón López-López ◽  
Jesús Balsinde ◽  
María A. Balboa
Keyword(s):  
Central Component ◽  
Mortality And Morbidity ◽  
Molecular Sensors ◽  
Pharmacological Inhibition ◽  
Host Immune Responses ◽  
Lps Challenge ◽  
Intracellular Sensing ◽  
Threatening Condition ◽  
Life Threatening ◽  
Lipin 1

AbstractExposure to Gram-negative bacterial LPS exacerbates host immune responses and may lead to sepsis, a life-threatening condition. Despite its high mortality and morbidity, no drugs specifically directed to treating sepsis are currently available. Using human cell genetic depletion, pharmacological inhibition, live-cell microscopy and organelle-targeted molecular sensors we present evidence that the channel TRPC3 is activated intracellularly during macrophage exposure to LPS and is essential for Ca2+ release from internal stores. In this manner, TRPC3 participates in cytosolic Ca2+ elevations, activation of the transcription factor NF-κB and cytokine upregulation. We also report that TRPC3 is activated by diacylglycerol generated by the phosphatidic acid phosphatase lipin-1. In accord with this, lipin-1-deficient cells exhibit reduced Ca2+ responses to LPS challenge. Finally, pharmacological inhibition of TRPC3 reduces systemic inflammation induced by LPS in mice. Collectively, our study unveils a central component of LPS-triggered Ca2+ signaling that involves intracellular sensing of lipin-1-derived DAG by TRPC3, and opens new opportunities for the development of strategies to treat LPS-driven inflammation.

scholarly journals Assessment of systemic inflammatory reactions and coagulopathy against the background of hormonal therapy in covid-associated lung damage

2021 ◽  
pp. 230-237
Author(s):  
V. V. Salukhov ◽  
N. I. Gulyaev ◽  
E. V. Dorokhina
Keyword(s):  
Pulse Therapy ◽  
Cardiovascular Complications ◽  
Lung Damage ◽  
Coagulation System ◽  
Inflammatory Reactions ◽  
High Incidence ◽  
Life Threatening ◽  
High Doses ◽  
Anticoagulant Prophylaxis ◽  
Inflammatory Effect

The mechanisms of COVID-19-associated coagulopathy (CAC) are complex and differ in many ways from the standard mechanisms of thrombosis in critically ill patients. This review presents the pathogenesis, diagnosis, and comparison of various types of coagulopathy with SAS. During COVID-19 infection, the number of sudden deaths outside the hospital increased. One possible reason is the high incidence of serious thrombotic events in patients with COVID-19. However, the pathogenesis of these life-threatening events is multifactorial and requires independent discussion.Deviations in laboratory studies of the hemostatic system in patients infected with SARS-CoV-2 with a severe course indicate the activation of the blood coagulation system corresponding to sepsis-induced coagulopathy (SIC) or DIC. However, hemostasis disorders in COVID-19 have characteristics that distinguish them from DIC in sepsis.The clinical and laboratory features of CAC overlap with hemophagocytic syndrome, antiphospholipid syndrome, and thrombotic microangiopathy. The review presents data on their similarities and differences.Inadequate diagnosis or inadequate treatment of hypercoagulability may explain the high incidence of unexplained deaths from COVID-19. They can be associated with potentially preventable microvascular and macrovascular thrombosis and subsequent cardiovascular complications, including myocardial injury and infarction, as well as insufficient information content of biomarkers for their assessment.Research to identify the most informative biomarkers for decision-making to intensify anticoagulant prophylaxis in patients with severe COVID-19 is progressing rapidly, with increasing focus on TEG and ROTEM.The review presents changes in CAC during hormone therapy for COVID-19-associated lung damage. Pulse therapy with high doses of GCS has a rapid anti-inflammatory effect, but at the same time increases the level of D-dimer, which increases the risk of venous thrombosis and thromboembolism. 

May-Thurner syndrome – Are we aware enough?

VASA ◽  
2019 ◽  
Vol 48 (5) ◽  
pp. 381-388 ◽  
Author(s):  
Katalin Mako ◽  
Attila Puskas
Keyword(s):  
Contraceptive Use ◽  
Iliac Vein ◽  
Common Iliac Vein ◽  
Vein Thrombosis ◽  
Compression Syndrome ◽  
Threatening Condition ◽  
Life Threatening ◽  
Iliac Vein Compression ◽  
Iliac Vein Compression Syndrome ◽  
The Right

Summary. Iliac vein compression syndrome (May-Thurner syndrome – MTS) is an anatomically variable clinical condition in which the left common iliac vein is compressed between the right common iliac artery and the underlying spine. This anatomic variant results in an increased incidence of left iliac or iliofemoral vein thrombosis. It predominantly affects young women in the second or third decades of life with preponderance during pregnancy or oral contraceptive use. Although MTS is rare, its true prevalence is underestimated but it can be a life-threatening condition due to development of pulmonary embolism (PE). In this case based review the authors present three cases of MTS. All patients had been previously confirmed with PE, but despite they were admitted to hospital, diagnosed and correctly treated for PE and investigated for thrombophilia, the iliac vein compression syndrome was not suspected or investigated. With this presentation the authors would like to emphasize that MTS is mostly underdiagnosed, and it needs to be ruled out in left iliofemoral vein thrombosis in young individuals.

Severe Alveolar Hemorrhage – What’s in it for the Gastroenterologist?

2016 ◽  
Vol 25 (4) ◽  
pp. 555-558
Author(s):  
Alina Popp
Keyword(s):  
Celiac Disease ◽  
International Normalized Ratio ◽  
Gluten Free Diet ◽  
Alveolar Hemorrhage ◽  
Severe Anemia ◽  
Gluten Free ◽  
Pulmonary Infiltrates ◽  
Pulmonary Hemosiderosis ◽  
Threatening Condition ◽  
Life Threatening

Background: Alveolar hemorrhage is a potentially life-threatening condition which is usually managed by the pulmonologist. When considering its etiology, there is a rare association that sets the disease into the hands of the gastroenterologist. Case presentation: We report the case of a 48 year-old female who was admitted to the intensive care unit for severe anemia and hemoptysis. On imaging, diffuse pulmonary infiltrates suggestive of alveolar hemorrhage were detected and a diagnosis of pulmonary hemosiderosis was made. She received cortisone therapy and hematologic correction of anemia, with slow recovery. In search of an etiology for the pulmonary hemosiderosis, an extensive workup was done, and celiac disease specific serology was found positive. After confirmation of celiac disease by biopsy, a diagnosis of Lane-Hamilton syndrome was established. The patient was recommended a gluten-free diet and at 6 months follow-up, resolution of anemia and pulmonary infiltrates were observed. Conclusion: Although the association is rare, celiac disease should be considered in a patient with idiopathic pulmonary hemosiderosis. In our case, severe anemia and alveolar infiltrates markedly improved with glucocorticoids and gluten-free diet. Abbreviations: APTT: activated partial thromboplastin time; BAL: bronchoalveolar lavage; CD: celiac disease; Cd: crypt depth; GFD: gluten-free diet; GI: gastrointestinal; IEL: intraepithelial lymphocyte; INR: international normalized ratio; IPH: idiopathic pu

LAPAROSCOPIC CHOLECYSTECTOMY IN ACUTE CHOLECYSTITIS: A PROSPECTIVE STUDY.

2019 ◽  
Author(s):  
Madan Goyal ◽  
R K Goel
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Acute Cholecystitis ◽  
Open Cholecystectomy ◽  
Critical View Of Safety ◽  
Recent Onset ◽  
Conversion To Open Cholecystectomy ◽  
Threatening Condition ◽  
Life Threatening ◽  
Fluid Collections ◽  
A Prospective Study

Acute cholecystitis (AC) is a potentially life-threatening condition. LC was initially considered to be a relative contraindication for laparoscopic cholecystectomy (LC), but with increase in general expertise, early LC was recommended in selected patients1. Aprospective study of LC in grade 1 and 2 AC patients with mild to moderate inflammatory changes in the gallbladder and no significant organ dysfunction, was performed during October 2016 to July 2019. A total of 78 patients, out of 408 cholecystectomies performed during this period, were included in this study. Criteria for diagnosing AC was, recent onset of pain in right hypochondrium, fever, leucocytosis, pericholecystic fluid collections, subserosal oedema on ultrasound, pyocele and other pathological evidence of AC. Patients presented and operated within 4 days of onset of symptoms showed better results as compared to those who could be operated after 4 days and within 14 days. Five patients required conversion to open cholecystectomy because of complex adhesions in 2, critical view of safety was unachievable in 2 and in 1 for troublesome bleeding.

PRO–CF–MED, Clinical Proof of concept for a RNA–targeting Oligonucleotide for a Cystic fibrosis–F508del MEDication, Horizon2020

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 52-54
Author(s):  
Nicolas Lamontagne
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Rna Targeting ◽  
Threatening Condition ◽  
Life Threatening ◽  
Cftr Protein ◽  
Disease Modifying ◽  
Cystic Fibrosis Transmembrane ◽  
Specific Challenge

Cystic fibrosis (CF) is a progressive life–shortening disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene leading to a dysfunctional CFTR protein. The disease affects over 70,000 patients worldwide and while many mutations are known, the F508del mutation affects 90% of all patients. The absence of CFTR in the plasma membrane leads to a dramatic decrease in chloride efflux, resulting in viscous mucus that causes severe symptoms in vital organs like the lungs and intestines. For CF patients that suffer from the life threatening F508del mutation only palliative treatment exist. PRO–CF–MED addresses the specific challenge of this call by introducing the first disease modifying medication for the treatment of the CF patients with F508del mutation. The PRO–CF–MED project has been designed to assess the potential clinical efficacy of QR–010, an innovative disease modifying oligonucleotide–based treatment for F508del patients. Partners within PRO–CF–MED have generated very promising preclinical evidence for QR–010 which allows for further clinical assessment of QR–010 in clinical trials. PRO–CF–MED will enable the fast translation of QR–010 towards clinical practice and market authorisation. PRO–CF–MED has the potential to transform this life–threatening condition into a manageable one.

Advanced care planning: thinking ahead for parents, carers, children, and young people

2018 ◽  
Author(s):  
Angela Thompson
Keyword(s):  
Spiritual Needs ◽  
Care Planning ◽  
Best Interest ◽  
Social Emotional ◽  
Children And Young People ◽  
Adult Services ◽  
Active Approach ◽  
Threatening Condition ◽  
Life Threatening ◽  
Advance Care

Advance care planning (ACP) in paediatrics applies from the diagnosis of a life-limiting/life-threatening condition onwards. It encompasses the management of intermittent potentially reversible episodes through to end-of-life care in keeping with the child’s best interest. It is an active approach to managing care and acknowledges the child’s and family’s broader social, emotional, and spiritual needs and keeps the child central and paramount to all planning. It requires transparent discussions and effectively documented agreements that are well communicated, readily accessible, and immediately identifiable. It is essential to regularly review and amend as necessary. They describe the care agreed at that point in time in the child’s best interest, in line with RCPCH guidance. Challenges may particularly occur at the time of transition to adult services.

scholarly journals A Case of Exertional Heat Stroke Complicated by Hypoxic Hepatitis

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Bertram K. Woitok ◽  
Shawki Bahmad ◽  
Gregor Lindner
Keyword(s):  
Supportive Care ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Multiorgan Failure ◽  
Heat Stroke ◽  
Exertional Heat Stroke ◽  
Hypoxic Hepatitis ◽  
Threatening Condition ◽  
Life Threatening ◽  
Delayed Referral

Background.Exertional heat stroke is a life-threatening condition often complicated by multiorgan failure. We hereby present a case of a 25-year-old male presenting with syncope after a 10  km run in 28°C outside temperature who developed acute liver failure. Case Presentation. Initial temperature was found to be 41.1°C, and cooling measures were rapidly applied. He suffered from acute renal failure and rhabdomyolysis and proceeded to acute liver failure (ASAT 6100 U/l and ALAT 6561 U/l) due to hypoxic hepatitis on day 3. He did not meet criteria for emergency liver transplantation and recovered on supportive care. Conclusions. Acute liver failure due to heat stroke is a life-threatening condition with often delayed onset, which nevertheless resolves on supportive care in the majority of cases; thus, a delayed referral to transplant seems to be reasonable.

Ultrasound diagnosis of dissecting thoracic aortic aneurysms: procedure with a handheld device and a video-illustrated case

2021 ◽  
Vol 51 (1) ◽  
pp. 10-15
Author(s):  
Kenneth V Iserson ◽  
Sri Devi Jagjit ◽  
Balram Doodnauth
Keyword(s):  
Aortic Dissection ◽  
Correct Diagnosis ◽  
Signs And Symptoms ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Aneurysms ◽  
Handheld Device ◽  
Thoracic Aortic Dissection ◽  
Threatening Condition ◽  
Life Threatening ◽  
Handheld Ultrasound

Acute thoracic aortic dissection is an uncommon, although not rare, life-threatening condition. With protean signs and symptoms that often suggest more common cardiac or pulmonary conditions, it can be difficult to diagnose. Ultrasound has proven useful in making the correct diagnosis. This case demonstrates that training gained using standard ultrasound machines can be easily and successfully adapted to newer handheld ultrasound devices. The examination technique using the handheld device is illustrated with photos and a video.

scholarly journals Trauma-Induced Coagulopathy: Overview of an Emerging Medical Problem from Pathophysiology to Outcomes

Medicines ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 16
Author(s):  
Gabriele Savioli ◽  
Iride Francesca Ceresa ◽  
Luca Caneva ◽  
Sebastiano Gerosa ◽  
Giovanni Ricevuti
Keyword(s):  
Major Trauma ◽  
Management Strategies ◽  
Medical Problem ◽  
Current Evidence ◽  
Potential Drug ◽  
The Past ◽  
Trauma Induced Coagulopathy ◽  
Threatening Condition ◽  
Life Threatening ◽  
Trauma Mortality

Coagulopathy induced by major trauma is common, affecting approximately one-third of patients after trauma. It develops independently of iatrogenic, hypothermic, and dilutive causes (such as iatrogenic cause in case of fluid administration), which instead have a pejorative aspect on coagulopathy. Notwithstanding the continuous research conducted over the past decade on Trauma-Induced Coagulopathy (TIC), it remains a life-threatening condition with a significant impact on trauma mortality. We reviewed the current evidence regarding TIC diagnosis and pathophysiological mechanisms and summarized the different iterations of optimal TIC management strategies among which product resuscitation, potential drug administrations, and hemostatis-focused approaches. We have identified areas of ongoing investigation and controversy in TIC management.

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