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Journal of Clinical and Experimental... 2022The liver comprises both parenchymal and non-parenchymal cells with varying functions. Cirrhosis is often complicated by the development of portal hypertension and its... (Review)
Review
The liver comprises both parenchymal and non-parenchymal cells with varying functions. Cirrhosis is often complicated by the development of portal hypertension and its associated complications. Hence, assessment of liver in cirrhosis should include assessment of its structural, function of both hepatic and non-hepatic tissue and haemodynamic assessment of portal hypertension. There is no single test that can evaluate all functions of liver and assess prevalence and severity of portal hypertension. Commonly available tests like serum bilirubin, liver enzymes (alanine [ALT] and aspartate aminotransferase [AST], serum alkaline phosphatase [ALP], gamma glutamyl transpeptidase [GGT]), serum albumin and prothrombin time for assessment of liver functions partly assess liver functions. quantitative liver functions like indocyanine clearance tests [ICG-K], methacetin breath test [MBT] were developed to assess dynamic status of liver but has its own limitation and availability. Imaging based assessment of liver by transient elastography, MRI based 99 mTc-coupled asialoglycoprotein mebrofenin scan help the clinician to assess liver function, functional volume of liver left after surgery and portal hypertension [PH]. Hepatic venous pressure gradient still remains the gold standard for the assessment of portal hypertension but is invasive and not available in all centres. Combinations of blood parameters in form of various indices like fibrosis score of 4 [FIB-4], Lok index, scores like model for end stage liver disease (MELD) and Child-Turcotte Pugh score are commonly used for assessing liver function in clinical practice.
PubMed: 35677506
DOI: 10.1016/j.jceh.2021.11.004 -
Frontiers in Immunology 2019The functions of pentraxins, like C-reactive protein (CRP), serum amyloid protein P (SAP) and pentraxin-3 (PTX3), are to coordinate spatially and temporally targeted... (Review)
Review
The functions of pentraxins, like C-reactive protein (CRP), serum amyloid protein P (SAP) and pentraxin-3 (PTX3), are to coordinate spatially and temporally targeted clearance of injured tissue components, to protect against infections and to regulate related inflammation together with the complement system. For this, pentraxins have a dual relationship with the complement system. Initially, after a focused binding to their targets, e.g., exposed phospholipids or cholesterol in the injured tissue area, or microbial components, the pentraxins activate complement by binding its first component C1q. However, the emerging inflammation needs to be limited to the target area. Therefore, pentraxins inhibit complement at the C3b stage to prevent excessive damage. The complement inhibitory functions of pentraxins are based on their ability to interact with complement inhibitors C4bp or factor H (FH). C4bp binds to SAP, while FH binds to both CRP and PTX3. FH promotes opsonophagocytosis through inactivation of C3b to iC3b, and inhibits AP activity thus preventing formation of the C5a anaphylatoxin and the complement membrane attack complex (MAC). Monitoring CRP levels gives important clinical information about the extent of tissue damage and severity of infections. CRP is a valuable marker for distinguishing bacterial infections from viral infections. Disturbances in the functions and interactions of pentraxins and complement are also involved in a number of human diseases. This review will summarize what is currently known about the FH family proteins and pentraxins that interact with FH. Furthermore, we will discuss diseases, where interactions between these molecules may play a role.
Topics: Animals; C-Reactive Protein; Complement Activation; Complement Factor H; Complement Membrane Attack Complex; Complement System Proteins; Humans; Serum Amyloid P-Component
PubMed: 31428091
DOI: 10.3389/fimmu.2019.01750 -
Clinical and Experimental Medicine Mar 2024Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is... (Review)
Review
Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is characterised by scar tissue formation, portal hypertension, and ascites (accumulation of fluid in the abdominal cavity) in decompensated cirrhosis. This review evaluates how albumin infusion ameliorates cirrhosis-associated complications. Since albumin is an oncotic plasma protein, albumin infusion allows movement of water into the intravascular space, aids with fluid resuscitation, and thereby contributes to resolving cirrhosis-induced hypovolemia (loss of extracellular fluid) seen in ascites. Thus, albumin infusion helps prevent paracentesis-induced circulatory dysfunction, a complication that occurs when treating ascites. When cirrhosis advances, other complications such as spontaneous bacterial peritonitis and hepatorenal syndrome can manifest. Infused albumin helps mitigate these by exhibiting plasma expansion, antioxidant, and anti-inflammatory functions. In hepatic encephalopathy, albumin infusion is thought to improve cognitive function by reducing ammonia concentration in blood and thereby tackle cirrhosis-induced hepatocyte malfunction in ammonia clearance. Infused albumin can also exhibit protective effects by binding to the cirrhosis-induced proinflammatory cytokines TNFα and IL6. While albumin administration has shown to prolong overall survival of cirrhotic patients with ascites in the ANSWER trial, the ATTIRE and MACHT trials have shown either no effect or limitations such as development of pulmonary oedema and multiorgan failure. Thus, albumin infusion is not a generic treatment option for all cirrhosis patients. Interestingly, cirrhosis-induced structural alterations in native albumin (which lead to formation of different albumin isoforms) can be used as prognostic biomarkers because specific albumin isoforms indicate certain complications of decompensated cirrhosis.
Topics: Humans; Ascites; Ammonia; Liver Cirrhosis; Albumins; Protein Isoforms
PubMed: 38551716
DOI: 10.1007/s10238-024-01315-1 -
Frontiers in Cellular and Infection... 2022This study aimed to investigate the clinical and biochemical profiles of patients with imported malaria infection between 1 January 2011 and 30 April 2022 and admitted...
OBJECTIVES
This study aimed to investigate the clinical and biochemical profiles of patients with imported malaria infection between 1 January 2011 and 30 April 2022 and admitted to the Fourth People's Hospital of Nanning.
METHODS
This cohort study enrolled 170 patients with conformed imported malaria infection. The clinical and biochemical profiles of these participants were analyzed with malaria parasite clearance, and signs and symptoms related to malaria disappearance were defined as the primary outcome. A multivariable logistic regression model was used to evaluate the odds ratios (ORs) with 95% confidence intervals (CIs) for cerebral malaria. The Cox model was used to estimate the hazard ratios (HRs) with 95% CIs for parasite clearance.
RESULTS
Adenosine deaminase and parasitemia were found to be independent risk factors for severe malaria in patients with imported malaria (OR = 1.0088, 95% CI: 1.0010-1.0167, = 0.0272 and OR = 2.0700, 95% CI: 1.2584-3.4050, = 0.0042, respectively). A 0.5-standard deviation (SD) increase of variation for urea (HR = 0.6714, 95% CI: 0.4911-0.9180), a 0.5-SD increase of variation for creatinine (HR = 0.4566, 95% CI: 0.2762-0.7548), a 0.25-SD increase of variation for albumin (HR = 0.4947, 95% CI: 0.3197-0.7653), a 0.25-SD increase of variation for hydroxybutyrate dehydrogenase (HR = 0.6129, 95% CI: 0.3995-0.9402), and a 1.0-SD increase of variation for ferritin (HR = 0.5887, 95% CI: 0.3799-0.9125) were associated with a higher risk for increased parasite clearance duration than a low-level change.
CONCLUSIONS
Aspartate aminotransferase, urea, creatinine, albumin, hydroxybutyrate dehydrogenase, and ferritin are useful biochemical indicators in routine clinical practice to evaluate prognosis for imported malaria.
Topics: Humans; Cohort Studies; Creatinine; Hydroxybutyrate Dehydrogenase; Retrospective Studies; Communicable Diseases, Imported; Malaria, Cerebral; Ferritins; Albumins; Urea
PubMed: 36439238
DOI: 10.3389/fcimb.2022.1008430 -
International Journal of Nephrology and... 2021Hypoalbuminemia results when compensatory mechanisms are unable to keep pace with derangements in catabolism/loss and/or decreased synthesis of albumin. Across many... (Review)
Review
Hypoalbuminemia results when compensatory mechanisms are unable to keep pace with derangements in catabolism/loss and/or decreased synthesis of albumin. Across many disease states, including chronic kidney disease (CKD), hypoalbuminemia is a well-established, independent risk factor for adverse outcomes, including mortality. In the setting of CKD, reduced serum albumin concentrations are often a manifestation of protein-energy wasting, a state of metabolic and nutritional alterations resulting in reduced protein and energy stores. The progression of CKD to kidney failure and the initiation of maintenance hemodialysis (HD) further predisposes an already at-risk population toward hypoalbuminemia such that approximately 60% of HD patients have albumin concentrations <4.0 g/dl. Albumin loss into the dialysate through the dialyzer appears to be a potentially modifiable cause of hypoalbuminemia in some patients. A group of newer dialyzers for maintenance HD-sometimes termed protein-leaking or medium cut-off membranes-aim to improve clearance of middle molecules (vs high flux dialyzers) but are associated with increased albumin losses. In this article, we will examine the impact of dialyzer selection on albumin losses during conventional HD, including the clinical relevance of such losses on serum albumin levels. Data on the clinical relevance of albumin losses during dialysis and current gaps in the evidence base are also discussed.
PubMed: 33505168
DOI: 10.2147/IJNRD.S291348 -
Clinical Laboratory Mar 2023The goal was to investigate the prognostic value of serum procalcitonin (PCT), procalcitonin clearance (PCTc), and procalcitonin/albumin (PCT/ALB) in patients with...
BACKGROUND
The goal was to investigate the prognostic value of serum procalcitonin (PCT), procalcitonin clearance (PCTc), and procalcitonin/albumin (PCT/ALB) in patients with sepsis.
METHODS
We conducted a retrospective study on 128 adult patients with sepsis in the Department of Intensive Care Unit (ICU) and in the Department Infectious Disease in the Affiliated Cancer Hospital of Zhengzhou University. We observed PCT, ALB, arterial blood gas analysis (ABGs) and other main indicators of patients within 5 days after admittance from June 2020 to June 2021. The acute physiological function and chronic health status system II (APACHE II) scores, sepsis related organ failure assessment (SOFA) scores, procalcitonin clearance and PCT/ALB ratio were calculated, respectively. SPSS 22.0 and Graph pad 6.0 statistical software were used for statistical analysis.
RESULTS
The septic shock group had higher PCT, lower ALB, higher PCT/ALB ratio and higher APACHE II score than the sepsis group (p = 0.01733, p = 0.0142, p = 0.0030, p = 0.0061, respectively). The 28 day mortality group had lower ALB value, higher PCT/ALB ratio and higher APACHE II score than the survival group (p = 0.0105, p = 0.0345, p = 0.0152, respectively). The PCTc-day3 and PCTc-day5 were both significantly higher in patients who survived than in the 28 day mortality group (p = 0.0159, p = 0.0042, respectively). The AUC of PCT/ ALB for predicted the septic shock was 0.8966 (95% CI: 0.8370 to 0.9562, p < 0.0001), and the cutoff value, sensitivity and specificity was 0.87, 81.25%, and 85.19%, respectively. The AUC of PCT/ALB for the predicted 28 day mortality was 0.8353 (95% CI: 0.7534 to 0.9171, p < 0.0001), and the cutoff value, sensitivity and specificity was 0.83, 70.83% and 92.59%, respectively.
CONCLUSIONS
The PCT/ALB ratio was an important indicator for predicting septic shock and 28 day mortality in sepsis patients compared to PCT or ALB alone.
Topics: Adult; Humans; Procalcitonin; Prognosis; Shock, Septic; Retrospective Studies; ROC Curve; Sepsis; Albumins; Intensive Care Units
PubMed: 36912300
DOI: 10.7754/Clin.Lab.2022.220613 -
Scientific Reports Jul 2022The aim of this study was to evaluate the prognostic value of the Lactate to Albumin (L/A) ratio compared to that of lactate and lactate clearance in predicting outcomes... (Comparative Study)
Comparative Study Observational Study
Comparison of lactate/albumin ratio to lactate and lactate clearance for predicting outcomes in patients with septic shock admitted to intensive care unit: an observational study.
The aim of this study was to evaluate the prognostic value of the Lactate to Albumin (L/A) ratio compared to that of lactate and lactate clearance in predicting outcomes in patients with septic shock. This was a multi-center observational study of adult patients with septic shock, who admitted to intensive care units (ICUs) at Shohada and Imam Reza Hospitals, Tabriz, Iran, between Sept 2018 and Jan 2021. The area under the curve (AUC) of receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were used to explore associations of the L/A ratio, lactate and lactate clearance on the primary (mortality) and secondary outcomes [ICU length of stay (LOS), duration of mechanical ventilation (MV), need of renal replacement therapy (RRT) and duration of using vasopressors] at baseline, 6 h and 24 h of septic shock recognition. Best performing predictive value for mortality were related to lactate clearance at 24 h, L/A ratio at 6 h and lactate levels at 24 h with (AUC 0.963, 95% CI 0.918-0.987, P < 0.001), (AUC 0.917, 95% CI 0.861-0.956, P < 0.001), and (AUC 0.904, 95% CI 0.845-0.946, P < 0.001), respectively. Generally, the lactate clearance at 24 h had better prognostic performance for mortality and duration of using vasopressor. However, the L/A ratio had better prognostic performance than serum lactate and lactate clearance for RRT, ICU LOS and MV duration.
Topics: Adult; Albumins; Humans; Intensive Care Units; Lactic Acid; Prognosis; ROC Curve; Retrospective Studies; Shock, Septic
PubMed: 35906231
DOI: 10.1038/s41598-022-14764-z -
Drug Metabolism and Disposition: the... Sep 2023Understanding the extended clearance concept and establishing a physiologically based pharmacokinetic (PBPK) model are crucial for investigating the impact of changes in... (Review)
Review
A 20-Year Research Overview: Quantitative Prediction of Hepatic Clearance Using the In Vitro-In Vivo Extrapolation Approach Based on Physiologically Based Pharmacokinetic Modeling and Extended Clearance Concept.
Understanding the extended clearance concept and establishing a physiologically based pharmacokinetic (PBPK) model are crucial for investigating the impact of changes in transporter and metabolizing enzyme abundance/functions on drug pharmacokinetics in blood and tissues. This mini-review provides an overview of the extended clearance concept and a PBPK model that includes transporter-mediated uptake processes in the liver. In general, complete in vitro and in vivo extrapolation (IVIVE) poses challenges due to missing factors that bridge the gap between in vitro and in vivo systems. By considering key in vitro parameters, we can capture in vivo pharmacokinetics, a strategy known as the top-down or middle-out approach. We present the latest progress, theory, and practice of the Cluster Gauss-Newton method, which is used for middle-out analyses. As examples of poor IVIVE, we discuss "albumin-mediated hepatic uptake" and "time-dependent inhibition" of OATP1Bs. The hepatic uptake of highly plasma-bound drugs is more efficient than what can be accounted for by their unbound concentration alone. This phenomenon is referred to as "albumin-mediated" hepatic uptake. IVIVE was improved by measuring hepatic uptake clearance in vitro in the presence of physiologic albumin concentrations. Lastly, we demonstrate the application of Cluster Gauss-Newton method-based analysis to the target-mediated drug disposition of bosentan. Incorporating saturable target binding and OATP1B-mediated hepatic uptake into the PBPK model enables the consideration of nonlinear kinetics across a wide dose range and the prediction of receptor occupancy over time. SIGNIFICANCE STATEMENT: There have been multiple instances where researchers' endeavors to unravel the underlying mechanism of poor in vitro-in vivo extrapolation have led to the discovery of previously undisclosed truths. These include 1) albumin-mediated hepatic uptake, 2) the target-mediated drug disposition in small molecules, and 3) the existence of a trans-inhibition mechanism by inhibitors for OATP1B-mediated hepatic uptake of drugs. Consequently, poor in vitro-in vivo extrapolation and the subsequent inquisitiveness of scientists may serve as a pivotal gateway to uncover hidden mechanisms.
Topics: Hepatocytes; Kinetics; Models, Biological; Liver; Albumins
PubMed: 37407092
DOI: 10.1124/dmd.123.001344 -
Current Opinion in Chemical Biology Aug 2021The field of nuclear imaging and therapy is rapidly progressing with the development of targeted radiopharmaceuticals that show rapid targeting and rapid clearance with... (Review)
Review
The field of nuclear imaging and therapy is rapidly progressing with the development of targeted radiopharmaceuticals that show rapid targeting and rapid clearance with minimal background. Unfortunately, they are often reabsorbed in the kidneys, leading to possible nephrotoxicity, limiting the therapeutic dose, and/or reducing imaging quality. The blocking of endocytic receptors has been extensively used as a strategy to reduce kidney radiation. Alternatively, the physicochemical properties of radiotracers can be modulated to either prevent their reuptake or promote the excretion of radiometabolites. Other interesting strategies focus on the insertion of a cleavable linker between the radiolabel and the targeting moiety or pretargeting approaches in which the targeting moiety and radiolabel are administered separately. In the context of this review, we will discuss the latest advances and insights on strategies used to reduce renal retention of low- to moderate-molecular-weight radiopharmaceuticals.
Topics: Albumins; Animals; Contrast Media; Dose-Response Relationship, Radiation; Humans; Kidney; Molecular Weight; Radioisotopes; Radiopharmaceuticals; Single Photon Emission Computed Tomography Computed Tomography; Structure-Activity Relationship
PubMed: 34325089
DOI: 10.1016/j.cbpa.2021.06.008 -
Cellular and Molecular Bioengineering Apr 2022Short interfering RNAs (siRNAs) are potent nucleic acid-based drugs designed to target disease driving genes that may otherwise be undruggable with small molecules....
INTRODUCTION
Short interfering RNAs (siRNAs) are potent nucleic acid-based drugs designed to target disease driving genes that may otherwise be undruggable with small molecules. However, therapeutic potential of siRNA is limited by poor pharmacokinetic properties, including rapid renal clearance and nuclease degradation. Backpacking on natural carriers such as albumin, which is present at high concentration and has a long half-life in serum, is an effective way to modify pharmacokinetics of biologic drugs that otherwise have poor bioavailability. In this work, we sought to develop albumin-binding aptamer-siRNA chimeras to improve the bioavailability of siRNA.
METHODS
A Systematic Evolution of Ligands through Exponential Enrichment (SELEX) approach was used to obtain modified RNA-binding aptamers, which were then fused directly to siRNA via transcription. Molecular and pharmacokinetic properties of the aptamer-siRNA chimeras were subsequently measured and .
RESULTS
assays show that albumin-binding aptamers are stable in serum while maintaining potent gene knockdown capabilities in the chimera format. , the absolute circulation half-life of the best-performing aptamer-siRNA chimera (Clone 1) was 1.6-fold higher than a scrambled aptamer chimera control.
CONCLUSIONS
Aptamer-siRNA chimeras exhibit improved bioavailability without compromising biological activity. Hence, this albumin-binding aptamer-siRNA chimera approach may be a promising strategy for drug delivery applications.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12195-022-00718-y.
PubMed: 35401842
DOI: 10.1007/s12195-022-00718-y