Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study evaluates coagulation profiles of single ventricle (SV) patients in relationship to liver function, hemodynamic variables and outcome. Twenty-six children with SV anatomy were included. Advanced coagulation profiles, invasive preoperative hemodynamic parameters and clinical course were retrospectively analyzed. Median (interquartile range) age and weight at the time of blood sampling was 25.5 (31) months and 10.5 (6.9) kg. Sixteen patients (16/26; 62%) showed decreased antithrombin and/or protein C (PC) and/or free protein S (PS) function and/or free PS antigen. Two patients showed abnormal activated PC resistance ratio due to heterozygous factor V Leiden mutation and 1 heterozygous prothrombin G20210A mutation. Group comparison (abnormal coagulation profile [group 1; n = 16] versus normal coagulation profile [group 2; n = 10]) showed longer postoperative hospitalization time (p = .04), longer postoperative catecholamine support (p = .01), a higher incidence of thromboembolic events (p = .04), and chylothoraxes (p = .007) in group 1. In 5 (31%) of 16 group 1 patients, thromboembolic complications occurred: cerebral stroke (n = 1), intestinal ischemia (n = 2), thrombus formation in inferior caval vein (n = 1), and pulmonary vein (n = 1). Abnormalities in coagulation parameters are common in SV patients. Coagulation abnormalities constitute a preoperative risk factor and affect postoperative course.
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PMID:Single Ventricle Physiology Patients and Coagulation Abnormalities: Is There a Relationship With Hemodynamic Data and Postoperative Course? A Pilot Study. 3182 12

Prohibitin (PHB) is a critical protein involved in many cellular activities. In brain, PHB resides in mitochondria, where it forms a large protein complex with PHB2 in the inner TFmembrane, which serves as a scaffolding platform for proteins involved in mitochondrial structural and functional integrity. PHB overexpression at moderate levels provides neuroprotection in experimental brain injury models. In addition, PHB expression is involved in ischemic preconditioning, as its expression is enhanced in preconditioning paradigms. However, the mechanisms of PHB functional regulation are still unknown. Observations that nitric oxide (NO) plays a key role in ischemia preconditioning compelled us to postulate that the neuroprotective effect of PHB could be regulated by NO. Here, we test this hypothesis in a neuronal model of ischemia-reperfusion injury and show that NO and PHB are mutually required for neuronal resilience against oxygen and glucose deprivation stress. Further, we demonstrate that NO post-translationally modifies PHB through protein S-nitrosylation and regulates PHB neuroprotective function, in a nitric oxide synthase-dependent manner. These results uncover the mechanisms of a previously unrecognized form of molecular regulation of PHB that underlies its neuroprotective function.SIGNIFICANCE STATEMENT Prohibitin (PHB) is a critical mitochondrial protein that exerts a potent neuroprotective effect when mildly upregulated in mice. However, how the neuroprotective function of PHB is regulated is still unknown. Here, we demonstrate a novel regulatory mechanism for PHB that involves nitric oxide (NO) and shows that PHB and NO interact directly, resulting in protein S-nitrosylation on residue Cys69 of PHB. We further show that nitrosylation of PHB may be essential for its ability to preserve neuronal viability under hypoxic stress. Thus, our study reveals a previously unknown mechanism of functional regulation of PHB that has potential therapeutic implications for neurologic disorders.
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PMID:Prohibitin S-Nitrosylation Is Required for the Neuroprotective Effect of Nitric Oxide in Neuronal Cultures. 3215

Background: Thromboembolic events are rare but critical complications in childhood nephrotic syndrome. The veins are more commonly affected, while arterial thrombosis is extremely rare but often life-threatening. Herein, we describe the clinical course of a 10-years-old girl with catastrophic multiple arterial thrombosis at the primary onset of nephrotic syndrome who underwent bilateral above-knee amputation. Case diagnosis/treatment: A previous healthy 10-years-old girl contracted the influenza B virus. Five days later, she suddenly developed severe ischemia in both legs. Physical examination showed eyelid and leg edema, and laboratory tests revealed hypoalbuminemia and acute kidney injury. After undergoing contrast-enhanced computed tomography, the patient was diagnosed with multiple arterial thrombosis (including the bilateral iliac arteries) due to nephrotic syndrome. Despite the performance of surgical thrombectomies, fasciotomy, and systematic heparinization, she required bilateral above-knee amputation. The patient achieved spontaneous remission of nephrotic syndrome, and her renal function fully recovered. There were no findings suggestive of secondary nephrotic syndrome and antiphospholipid syndrome. Her protein C and protein S concentrations were slightly decreased at admission. However, whole-exome sequencing revealed a thrombotic risk variant (T630I) in the PROS1 gene encoding protein S. This missense variant is often reported in patients with thrombosis or protein S deficiency, and may result in a thrombotic predisposition in some situations, such as nephrotic syndrome. Conclusions: Arterial thrombosis is a rare complication; however, it must be considered, especially in patients with new-onset nephrotic syndrome. Early recognition is important for early intervention and prevention of serious sequelae.
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PMID:Childhood Nephrotic Syndrome Complicated by Catastrophic Multiple Arterial Thrombosis Requiring Bilateral Above-Knee Amputation. 3226 86

The outbreak of novel coronavirus disease 2019 (COVID-19) has now become a global pandemic. Coagulopathy has been reported widely in critically ill COVID-19 patients and was related to high mortality. However, the comprehensive coagulation profiles have not been examined and the underlying mechanism of the coagulopathy in COVID-19 patients is unclear. To study the coagulation profiles of routine hemostasis tests, natural anticoagulants, coagulant factors and antiphospholipid antibodies in critically ill COVID-19 patients. This single-center and cross-section study included 19 patients with COVID-19, who were admitted to intensive care unit (ICU) at Tongji hospital in Wuhan, China, from Feb 23 to Mar 3, 2020. Demographic data, laboratory parameters, treatments and clinical outcomes of the patients were collected and analyzed. The final date of follow-up was Mar 31, 2020. In this study, 12 thrombotic events occurred in 9 patients, including 4 cerebral infarctions, 7 acro-ischemia and 1 internal jugular vein thrombosis. The common abnormalities of routine coagulation tests included evelated D-Dimer level (100%), prolonged prothrombin time (73.7%) and hyperfibrinogenemia (73.7%). The median activities of natural anticoagulants including protein C, protein S and antithrombin were all below the normal range. Factor VIII activities were significantly above normal range (median value 307%, IQR 198-441) in all patients. Factor V and factor VII activities were significantly lower in near-terminal stage patients. Anti-phospholipid antibodies were present in 10 patients. Strikingly, 4 cerebral infarction events were in patients had anti-phospholipid antibodies of multiple isotypes. Sustained hypercoagulable status and thrombotic events were common in critically ill patients with COVID-19. The low activities of natural anticoagulants, elevated factor VIII level and the presence of antiphospholipid antibodies, together, may contribute to the etiopathology of coagulopathy in COVID-19 patients.
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PMID:Profile of natural anticoagulant, coagulant factor and anti-phospholipid antibody in critically ill COVID-19 patients. 3264 93


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