PHYTOCHEMICAL POTENTIAL OF ?-SITOSTEROL, ?-AMYRIN AND EPIAFZELECHIN IN NICKEL INTOXICATED MULTIPLE ORGAN DAMAGE IN RAT

Keyword(s):  
Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001628
Author(s):  
Kamal Matli ◽  
Raymond Farah ◽  
Mario Maalouf ◽  
Nibal Chamoun ◽  
Christy Costanian ◽  
...  

Although primarily affecting the respiratory system, COVID-19 causes multiple organ damage. One of its grave consequences is a prothrombotic state that manifests as thrombotic, microthrombotic and thromboembolic events. Therefore, understanding the effect of antiplatelet and anticoagulation therapy in the context of COVID-19 treatment is important. The aim of this rapid review was to highlight the role of thrombosis in COVID-19 and to provide new insights on the use of antithrombotic therapy in its management. A rapid systematic review was performed using preferred reporting items for systematic reviews. Papers published in English on antithrombotic agent use and COVID-19 complications were eligible. Results showed that the use of anticoagulants increased survival and reduced thromboembolic events in patients. However, despite the use of anticoagulants, patients still suffered thrombotic events likely due to heparin resistance. Data on antiplatelet use in combination with anticoagulants in the setting of COVID-19 are quite scarce. Current side effects of anticoagulation therapy emphasise the need to update treatment guidelines. In this rapid review, we address a possible modulatory role of antiplatelet and anticoagulant combination against COVID-19 pathogenesis. This combination may be an effective form of adjuvant therapy against COVID-19 infection. However, further studies are needed to elucidate potential risks and benefits associated with this combination.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3135-3135
Author(s):  
Yan Leyfman ◽  
Nancy Emmanuel ◽  
Aleksey Tentler ◽  
Jared Cappelli ◽  
Timothy K Erick ◽  
...  

3135 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that causes the respiratory illness coronavirus disease 2019 (COVID-19). COVID-19 ranges in severity from an asymptomatic viral infection to life-threatening cases of pneumonia, acute respiratory distress syndrome (ARDS), multi-organ damage and sepsis. Cancer patients are at an increased risk of severe SARS-CoV-2 infection due to their immunocompromised status. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation and hypoxia-induced cellular metabolic alterations leading to cell death. Hypoxia is also induced by malignancy due to alterations in metabolism, resulting in greater IL-6 secretion. Methods: To highlight the possible effect of active cancer on the likelihood of hypoxia in COVID-19, we analyzed the correlation between cancer status and the severity of COVID-19 from the COVID-19 and Cancer Consortium data registry. For cancer status, we looked at progressive cancer and remission of cancer only -- those being the two extremes of presence and absence of uncontrolled cancer. Similar to prior studies, the severity of COVID-19 was used as an indication of hypoxia. Results: We observed a 24% positive deviation between expected and actual number of patients with actively progressing cancer who had hypoxic COVID-19 (moderate to severe), and a 26.9% negative deviation between expected and actual number of patients with active cancer who had no hypoxia with COVID-19 (p<0.0001). Conversely, for patients with cancer in remission, there was only a +5.8% and -5.1% deviation between expected and actual number of patients who did not have hypoxia and who had hypoxia, respectively. Conclusions: These results suggest that in the presence of poorly controlled malignancy, there is an increased likelihood of hypoxia in patients with COVID-19, thereby exacerbating downstream cytokine release syndrome and contributing to prolonged systemic inflammatory injury. Appreciating this pathway, future therapies can be developed to target the pathogenesis of both diseases and prevent progression, as seen with mesenchymal stem cells, which demonstrated a 91% overall survival and 100% survival in patients younger than 85 years old at one month after a single treatment.[Table: see text]


Author(s):  
Zana Stanic ◽  
Marko Vulic ◽  
Zlatko Hrgovic ◽  
Rajko Fureš ◽  
Milvija Plazibat ◽  
...  

AbstractThe majority of patients with simultaneous pancreas and kidney transplant (SPKT) required transplantation owing to a long-standing history of insulin-dependent diabetes mellitus (IDDM). The disease causes multiple organ damage, impairs fertility, and affects quality of life. A successful kidney and pancreas transplant can improve health, ameliorate the consequences of pre-existent diabetes, and restore fertility. Good graft function, without any sign of rejection, and stable doses of immunosuppressant drugs are of utmost importance prior to the planned pregnancy. SPKT recipients who become pregnant may be at an increased risk for an adverse outcome and require meticulous multidisciplinary surveillance. We present experiences with SPKT pregnancies, traditional approaches, and recent considerations. In light of complex interactions between new anatomic relations and the impact of developing pregnancy and immunosuppressive medications, special stress is put on the risk of graft rejection, development of pregnancy complications, and potential harmful effects on fetal development. Recent recommendations in management of SPKT recipients who wish to commence pregnancy are presented as well. Key words: transplantation, pregnancy, pancreas, kidney, simultaneous pancreas and kidney transplantation (SPKT)


Author(s):  
C. Welzl ◽  
A.L. Leisewitz ◽  
L.S. Jacobson ◽  
T. Vaughan-Scott ◽  
E. Myburgh

This study was designed to document the systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS) in dogs with complicated babesiosis, and to assess their impact on outcome. Ninety-one cases were evaluated retro-spectively for SIRS and 56 for MODS. The liver, kidneys, lungs, central nervous system and musculature were assessed. Eighty-seven percent of cases were SIRS-positive. Fifty-two percent of the cases assessed for organ damage had single-organ damage and 48 % had MODS. Outcome was not significantly affected by either SIRS or MODS, but involvement of specific organs had a profound effect. Central nervous system involvement resulted in a 57 times greater chance of death and renal involvement in a 5-fold increased risk compared to all other complications. Lung involvement could not be statistically evaluated owing to co-linearity with other organs, but was associated with high mortality. Liver and muscle damage were common, but did not significantly affect outcome. There are manysimilarities between the observations in this study and previous human and animal studies in related fields, lending additional support to the body of evidence for shared underlying pathophysiological mechanisms in systemic inflammatory states.


2020 ◽  
Vol 4 (2) ◽  
pp. 21-28
Author(s):  
Jonathan S Chávez-Iñiguez ◽  
Jose Said Cabrera-Aguilar ◽  
Guillermo Garcia-Garcia ◽  
Juan Armendáriz-Borunda

Leptospirosis is considered a zoonosis acquired predominantly from contaminated surfaces and water, more commonly in emerging countries with limited sanitary conditions. Leptospira in the host unleashes an immune response that explains the symptoms and clinical signs; once it reaches the kidney and liver tissue, it can manifest with alterations that lead to acute and chronic diseases in both organs. Weil’s syndrome is the best known clinical manifestation with jaundice and acute kidney injury that could lead to multiple organ failure and death. For its diagnosis, there are simplified scores such as the SPiRO score, the microbiological criteria by microscopy or serological tests; the treatment focuses on antibiotics and, if necessary, provides organic support until the infection is curtailed. The purpose of this review was to address the impact of Lep-tospira infection on the kidney and liver, the mechanisms of organ damage, the clinical presentation, and diagnosis and management of this disease.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jun Soma ◽  
Daisuke Ishii ◽  
Hisayuki Miyagi ◽  
Seiya Ishii ◽  
Keita Motoki ◽  
...  

Abstract Background Intra-abdominal hemorrhage caused by blunt hepatic injury is a major cause of morbidity and mortality in patients with abdominal trauma. Some of these patients require laparotomy, and rapid decision-making and life-saving surgery are essential. Damage control (DC) surgery is useful for treating children in critical situations. We performed this technique to treat an 8-year-old boy with grade IV blunt hepatic injury and multiple organ damage. This is the first report of the use of the ABTHERA Open Abdomen Negative Pressure Therapy System (KCI, now part of 3 M Company, San Antonio, TX, USA) for DC surgery to rescue a patient without neurological sequelae. Case presentation An 8-year-old boy was brought to the emergency department of our hospital after being run over by a motor vehicle. He had grade IV blunt hepatic injury, thyroid injury, and bilateral hemopneumothorax. Although he was hemodynamically stable, the patient’s altered level of consciousness, the presence of a sign of peritoneal irritation, and suspicion of intestinal injury led us to perform exploratory laparotomy. As part of a DC strategy, we performed gauze packing to control hemorrhage from the liver and covered the abdomen with an ABTHERA Open Abdomen Negative Pressure Therapy System to improve the patient’s general condition. Eighteen days after admission, the patient was diagnosed with a biliary fistula, which improved with percutaneous and external drainage. He had no neurological sequelae and was discharged 102 days after injury. Conclusion The DC strategy was effective in children with severe blunt hepatic injury. We opted to perform DC surgery because children have less hemodynamic reserve than adults, and we believe that using this strategy before the appearance of trauma triad of death could save lives and improve outcomes. During conservative management, it is important to adopt a multistage, flexible approach to achieve a good outcome.


2021 ◽  
Vol 22 (22) ◽  
pp. 12520
Author(s):  
Manigandan Krishnan ◽  
Joonhyeok Choi ◽  
Ahjin Jang ◽  
Young Kyung Yoon ◽  
Yangmee Kim

Carbapenem-resistant A. baumannii (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.


2021 ◽  
Vol 9 ◽  
Author(s):  
Birte Weber ◽  
Ina Lackner ◽  
Christian Karl Braun ◽  
Miriam Kalbitz ◽  
Markus Huber-Lang ◽  
...  

Severe trauma is the most common cause of mortality in children and is associated with a high socioeconomic burden. The most frequently injured organs in children are the head and thorax, followed by the extremities and by abdominal injuries. The efficient and early assessment and management of these injuries is essential to improve patients' outcome. Physical examination as well as imaging techniques like ultrasound, X-ray and computer tomography are crucial for a valid early diagnosis. Furthermore, laboratory analyses constitute additional helpful tools for the detection and monitoring of pediatric injuries. Specific inflammatory markers correlate with post-traumatic complications, including the development of multiple organ failure. Other laboratory parameters, including lactate concentration, coagulation parameters and markers of organ injury, represent further clinical tools to identify trauma-induced disorders. In this review, we outline and evaluate specific biomarkers for inflammation, acid-base balance, blood coagulation and organ damage following pediatric polytrauma. The early use of relevant laboratory markers may assist decision making on imaging tools, thus contributing to minimize radiation-induced long-term consequences, while improving the outcome of children with multiple trauma.


2020 ◽  
Author(s):  
Min Xu ◽  
Lili Luo ◽  
Mengyi Du ◽  
Lu Tang ◽  
Jie Zhou ◽  
...  

Abstract Background: Disseminated intravascular coagulation (DIC) is characterized by extensive endothelial injury and coagulation activation that is primarily caused by infection and can be aggravated by the gut due to increased permeability and bacterial translocation. Studies have shown that statins play an important role in reducing inflammation, protecting the endothelium and improving coagulation. In addition, statins regulate tight junction (TJ) proteins and gut microbes. Therefore, we aimed to investigate whether simvastatin improves DIC prognosis by regulating the intestinal microenvironment. Methods: Mice were administered 20 mg/kg simvastatin by gavage for 2 weeks and then intraperitoneally injected with 50 mg/kg endotoxin. Twelve hours later, cytokine release, coagulation dysfunction, multiple organ damage and survival were assessed. In addition, intestinal barrier and permeability and bacteria and bacteria translocation were evaluated. Results: We found that the severity of endotoxin-induced DIC was significantly improved in simvastatin-pretreated mice, who showed attenuated depletion of coagulation factors and platelets, decreased plasminogen activator inhibitor-1 (PAI-1) expression, reduced organ fibrin deposition and an improved survival rate. In addition, simvastatin reduced epithelial apoptosis, increased TJ gene expression, and upregulated antimicrobial peptides, lysozyme and mucins. Simvastatin-pretreated mice showed increased Lactobacillales counts, while the LPS group had increased numbers of Desulfovibrio and Mucispirillum, which produce harmful toxins and damage the intestinal epithelium and mucosa. Finally, with the decreased intestinal permeability in the simvastatin group, bacterial translocation in the organs and blood was significantly reduced, both in quantity and species. Conclusions: Simvastatin improves DIC prognosis, and the intestinal microenvironment participates in this process.


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