Conversion of albumin into a BODIPY-like photosensitizer by a flick reaction, tumor accumulation and photodynamic therapy.

The accumulation of photosensitizers (PSs) in lesion sites but not in other organs is an important challenge for efficient image guiding in photodynamic therapy. Cancer cells are known to express a significant number of albumin-binding proteins that take up albumin as a nutrient source. Here, we converted albumin to a novel BODIPY-like PS by generating a tetrahedral boron environment via a flick reaction. The formed albumin PS has almost the same 3-dimensional structural feature as free albumin because binding occurs at Sudlow Site 1, which is located in the interior space of albumin. An i.v. injection experiment in tumor-bearing mice demonstrated that the human serum albumin PS effectively accumulated in cancer tissue and, more surprisingly, albumin PS accumulated much more in the cancer tissue than in the liver and kidneys. The albumin PS was effective at killing tumor cells through the generation of reactive oxygen species under light irradiation. The crystal structure of the albumin PS was fully elucidated by X-ray crystallography; thus, further tuning of the structure will lead to novel physicochemical properties of the albumin PS, suggesting its potential in biological and clinical applications.

Splicing by Overlap Extension PCR for the Production of Fusion Proteins.

Fusion proteins are valuable molecules to meet different demands related to the development of biopharmaceuticals and bioprocesses. In human therapy, they are used to improve the half-life of biologics by modifying the biophysical properties of the proteins. In biotechnology, the design of fusion proteins can standardize the establishment of production clones and the purification process. Analytical detection capabilities of the fusion partner and binding to affinity ligands play a crucial role. For the generation of the recombinant cell line, the maturation of the protein and the secretion are also crucial factors, which can be significantly influenced by the fusion partner and can determine the final yield of the bioprocess. Here we present a protocol to recombine the human extracellular domain of CD19 with the human serum albumin domain 2 resulting in a fusion protein CD19-AD2 including a flexible linker sequence in the interface between the C-terminus of CD19 and the N-terminus of HSA-D2 and a terminal His12-tag. The two fragments are independently amplified with primers allowing to genetically connect the two fragments in the next step by overlap extension PCR. By this strategy, the linker sequence as well as the albumin fragment can be chosen individually to be flexible in the fine-tuning of the final protein. The amplified product is then cloned into a mammalian expression vector suitable to generate a recombinant transient or stable cell culture. This workflow can be applied to any protein sequence by adapting the specific primer sequences.

Antimicrobial activity of essential oil components against Escherichia coli depends on the food components present in a food matrix.

Despite numerous studies evaluating the antimicrobial activity of essential oil components (EOCs) against different microorganisms, the effect of the composition of the matrix in which they are applied remains unexplored. Hence, the effect of different food components (i.e., proteins, lipids, carbohydrates, acids, ethanol) on vanillin antimicrobial activity was carried out by assessing the growth of E. coli at different incubation times (0, 1, 4, 8 and 24 h). Based on these outcomes, the food components that most adversely affected vanillin antimicrobial activity were subsequently tested with four other EOCs (i.e., carvacrol, eugenol, geraniol, thymol). The effective concentration of antimicrobials after coming into contact with food components was quantified. The results indicated that bovine serum albumin (BSA), sunflower oil and carbohydrates partially or completely inhibited the antimicrobial efficacy of the tested EOCs, and the inhibition rate depended on the specific EOC-food component combination. Geraniol was notably the most efficient with BSA present. Eugenol performed best with sunflower oil. Carvacrol, eugenol, geraniol and thymol were more effective than vanillin with D-lactose present. This study confirmed that loss of EOCs' effective concentration due to an interaction with food constituents is a significant cause of antimicrobial activity inhibition. These findings underscore the importance of considering matrix composition when selecting antimicrobials to combat a particular strain in real food applications.

Critical new insights into the interactions of hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) with albumin at molecular and cellular levels.

A key characteristic to be elucidated, to address the harmful health risks of environmental perfluorinated alkyl substances (PFAS), is their binding modes to serum albumin, the most abundant protein in blood. Hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) is a new industrial replacement for the widespread linear long-chain PFAS. However, the detailed interaction of new-generation short-chain PFAS with albumin is still lacking. Herein, the binding characteristics of bovine serum albumin (BSA) to GenX were explored at the molecular and cellular levels. It was found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid (PFOA). Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex. Consistent with its weaker affinity to albumin protein, the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA. In contrast to the significant effects of strong BSA-PFOA interaction, the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX. The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.

Regeneratable bioinspired nanochannels for highly sensitive electrochemical detection of glycated albumin.

Glycated albumin (GA) has been proposed as a reliable diabetes mellitus marker particularly useful in assessing intermediate glycemic control. Herein, we designed a bioinspired nanochannels for biochemical detection based on the host-guest interaction between ß-cyclodextrin and azobenzene. Cyclodextrin was grafted on the inner surface of nanochannels of a nanoporous membrane and azobenzene was tagged to the terminal of GA aptamer, thereby facilitating the orientation of GA aptamer in the nanochannels. The presence of GA was monitored by recording the voltammetric signal of ferricyanide that transported across the nanochannel array. The peak current exhibited a linearity relationship with the GA concentration across a broad range of 1.0 ng mL-1 to 100 µg mL-1, along with a detection limit of 0.18 ng mL-1. Notably, the aptamer could be offloaded under ultraviolet light, regenerating the cyclodextrin functionalized nanochannels for subsequent re-immobilization of the fresh aptamer. The relative standard deviation for seven cycles of regeneration treatment was no more than 1.8 %. The remarkable reusability of the nanochannels offered a cost-effective, sensitive and reproducible aptasensing platform.

Early intervention of 5% albumin shown superior control of vascular integrity and function compared to ringer's lactatein hospitalized adult with grade I & II Dengue hemorrhagic fever: a multicenter randomized controlled trial in Indonesia.

BACKGROUND: Dengue virus remains a major public health problem with one of the hallmark pathologies is the vascular leakage caused by endothelial dysfunction which can lead to Dengue Hemorrhagic Fever (DHF) manifestation. In the status quo, no specific therapy has been discovered but rather heavily relies on judicious and frequent monitoring of intravenous fluids administration. The current guideline has discussed the roles of fluid therapy during the Dengue Shock Syndrome (DSS) stage, however, administration of early fluid intervention for DHF grade I and II remains uncharted territory. In addition, the choice and timing of colloid administration remains underexplored. As one of the widely available colloids, 5% albumin has known physiological properties that potentially minimize plasma leakage. Therefore, this study aimed to evaluate the benefit of early intervention of 5% albumin in adults with DHF in the hope of preventing the lethal progression to DSS and further, shorten the length of stay (LOS) for patients. METHODS: We conducted a multicenter, open-labeled, randomized controlled trial in Jakarta and Banten to compare the effect of early intervention with 5% albumin in adult patients with DHF compared to Ringer's Lactate (RL). Statistical analyses were conducted using unpaired t-test and Mann-Whitney for normally and abnormally distributed data respectively. RESULTS: Adult patients with a diagnosis of DHF grade I and II that being hospitalized to receive the early intervention of 5% albumin had significantly lower levels of hemoconcentration 4, 12, and 24 h (p = 0.002, 0.001, 0.003, respectively), higher platelet counts 4 h (p = 0.036), higher serum albumin levels 48 h (p = 0.036), lower proteinuria 24 and 48 h post-albumin administration (p < 0.001, < 0.001, respectively), and shorter LOS (p < 0.001) when compared to the RL group. CONCLUSION: Early intervention of 5% albumin showed better control on vascular integrity and function compared to ringer lactate in hospitalized adults with grade I & II DHF, thus halting the progression of DHF into DSS and other related complications which leads to faster recovery and shorter length of stay. TRIAL REGISTRATION: The study was registered to www. CLINICALTRIAL: gov with trial registration number NCT04076254, and registration date October 31st 2016.

Can maternal inflammatory and nutritional status, evaluated by the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI) in the first trimester, predict late-onset fetal growth restriction?

OBJECTIVE: The aim of this study was to evaluate the potential of immunonutritional markers, specifically the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI), in predicting late-onset fetal growth restriction (LO-FGR) during the first trimester. MATERIALS AND METHODS: This retrospective study was conducted at a tertiary care center between October 2022 and August 2023. The study included a total of 213 singleton pregnancies, with 99 women in the LO-FGR group and 114 in the healthy control group, matched by maternal age and gestational age at delivery. All blood samples were collected between 11 and 14 weeks of gestation (during the first-trimester screening test). We analyzed first-trimester laboratory parameters, specifically focusing on hemoglobin levels, white blood cells (WBCs), lymphocytes, platelets, and albumin levels. Afterwards, we calculated the HALP score and PNI, and then compared the values of both groups. RESULTS: Both HALP score (3.58 ± 1.31 vs. 4.19 ± 1.8, p = 0.012) and PNI (36.75 ± 2.9 vs. 39.37 ± 3.96, p < 0.001) were significantly lower in the FGR group than in the control group. The HALP score cut-off value of < 3.43 in predicting FGR had a sensitivity of 62.3% and specificity of 54.5% (AUC = 0.600, 95% CI: 0.528-0.672, p = 0.012). The PNI cut-off value of < 37.9 in predicting FGR had a sensitivity of 65.8% and specificity of 62.9% (AUC = 0.707, 95% CI: 0.632-0.778, p < 0.001). While the HALP score was not a significant predictor of composite adverse neonatal outcomes in the FGR group, PNI showed a cut-off value of < 37.7 with a sensitivity of 60.9% and specificity of 59.7% (AUC = 0.657, 95% CI: 0.581-0.733, p < 0.001). CONCLUSION: The HALP score and PNI are valuable prognostic tools for predicting the risk of FGR in the first trimester. Low PNI values are also associated with composite adverse neonatal outcomes in pregnancies complicated by FGR.

Diuretic responses to Ringer's solution and 20% albumin at different arterial pressures.

Intravenous volume loading is a common treatment when hypovolemia is a potential cause of oliguria. We studied whether the effectiveness of Ringer's solution and 20% albumin in inducing diuresis differs depending on the mean arterial pressure (MAP). For this purpose, volume kinetic analysis was performed based on urine output and hemoglobin-derived plasma dilution obtained during and after 136 infusions of Ringer and 85 infusions of 20% albumin. Covariance analysis quantified the diuretic response at different arterial pressures. The results show that the diuretic response to a known plasma volume expansion was greater for Ringer's solution above a MAP of 70 mmHg, while 20% albumin was significantly more effective at lower pressures (p < 0.03). Simulations of the urinary output in response to infusion of a predefined fluid volume yielded superior efficacy for 20% albumin when the MAP was low, while Ringer's was similarly effective when the MAP averaged 100 mmHg. In conclusion, urine output in response to plasma volume expansion with 20% albumin was similar to, or even stronger, than that of Ringer's solution when the MAP was below 70 mmHg.

Efficient purification of soluble receptor for advanced glycation end-products from Sus scrofa lung tissue and synthesis of its binding ligand, glycated bovine serum albumin.

A receptor for advanced glycation end products (RAGE) has emerged as a crucial player in various pathological conditions due to its involvement in inflammation and cellular dysfunction. Its soluble isoform, sRAGE, has garnered significant attention for its competitive inhibitory effects and potential therapeutic applications. However, obtaining sRAGE with appropriate glycosylation patterns for binding to glycated proteins has been challenging, often requiring costly expression systems. Here, we present a novel approach for producing and purifying sRAGE from Sus scrofa lungs, bypassing the need for expensive expression systems. Previous protocols for sRAGE extraction faced reproducibility issues due to high viscosity and haemoglobin content of the solution. To address this, we developed a method for selective haemoglobin precipitation using a zinc-containing buffer, enabling purification via various chromatographic methods. Through a combination of chromatographic techniques, we obtained sRAGE in suitable purity, identified using HPLC-MS/MS. Additionally, producing glycated proteins for RAGE receptor activation often involved lengthy protocols or inadequate separation from reactants. Thus, we devised a rapid method for producing and purifying pure BSA glycated with ribose, addressing a critical gap in the field. Functional studies, conducted using Native PAGE, demonstrated the capability of purified proteins to bind to each other.

Formulation Strategies to Overcome Amphotericin B Induced Toxicity.

Fungal infection poses a major global threat to public health because of its wide prevalence, severe mortality rate, challenges involved in diagnosis and treatment, and the emergence of drug-resistant fungal strains. Millions of people are getting affected by fungal infection, and around 3.8 million people face death per year due to fungal infection, as per the latest report. The polyene antibiotic AmB has an extensive record of use as a therapeutic moiety against systemic fungal infection and leishmaniasis since 1960. AmB has broad-spectrum fungistatic and fungicidal activity. AmB exerts its therapeutic activity at the cellular level by binding to fungal sterol and forming hydrophilic pores, releasing essential cellular components and ions into the extracellular fluid, leading to cell death. Despite using AmB as an antifungal and antileishmanial at a broad scale, its clinical use is limited due to drug-induced nephrotoxicity resulting from binding the aggregated form of the drug to mammalian sterol. To mitigate AmB-induced toxicity and to get better anti-fungal therapeutic outcomes, researchers have developed nanoformulations, self-assembled formulations, prodrugs, cholesterol- and albumin-based AmB formulations, AmB-mAb combination therapy, and AmB cochleates. These formulations have helped to reduce toxicity to a certain extent by controlling the aggregation state of AmB, providing sustained drug release, and altering the physicochemical and pharmacokinetic parameters of AmB. Although the preclinical outcome of AmB formulations is quite satisfactory, its parallel result at the clinical level is insignificant. However, the safety and efficacy of AmB therapy can be improved at the clinical stage by continuous investigation and collaboration among researchers, clinicians, and pharmaceutical companies.

Combined influence of physical activity and C-reactive protein to albumin ratio on mortality among older cancer survivors in the United States: a prospective cohort study.

BACKGROUND: Although a high C-reactive protein-to-albumin ratio (CAR) is believed to increase mortality risk, the association between the physical activity (PA), CAR, and mortality among cancer survivors has not been investigated. This study aimed to examine this association among cancer survivors in the United States. METHODS: This cohort study used data from the National Health and Nutrition Examination Survey from 1999 to 2010. PA was self-reported using the Global Physical Activity Questionnaire, and C-reactive protein and albumin levels were obtained from laboratory data files. Mortality data were obtained by linkage of the cohort database to the National Death Index as of December 31, 2019. The analysis was conducted from November 1 to December 31, 2023. We used Cox proportional hazards multivariable regression to assess hazard ratios (HRs) and 95% confidence interval (CIs) for total and cancer-specific mortality risks attributable to PA and CAR. RESULTS: Among 2,232 cancer survivors, 325 (14.6%) reported no PA with a high CAR. During a follow-up of up to 20.75 years (median, 12.3 years; 27,453 person-years), 1,174 deaths occurred (cancer, 335; other, 839). A high CAR was observed to be consistently associated with the highest risks of total (HR, 1.59; 95% CI, 1.37-1.85) and cancer-specific (HR, 2.06; 95% CI, 1.55-2.73) mortality compared with a low CAR in a series of adjusted models. Multivariable models showed that PA was associated with a lower risk of all-cause (HR, 0.60; 95% CI, 0.52-0.69) and cancer-specific (HR, 0.64; 95% CI, 0.49-0.84) mortality compared with no PA. In the joint analyses, survivors with PA ≥ 600 metabolic equivalent min/wk and a low CAR were more likely to reduce the risk of total (HR, 0.41; 95% CI, 0.32-0.51) and cancer-specific (HR, 0.32; 95% CI, 0.20-0.50) mortality by 59% and 68% compared with those with no PA and a high CAR. CONCLUSION: The pairing of adequate PA and a low CAR was significantly associated with reduced all-cause and cancer-related mortality risks.

Elevated serum albumin-to-creatinine ratio as a protective factor on clinical outcomes among critically ill patients with sepsis: a retrospective study.

Background: The aim of this study was to examine the prognostic significance of serum albumin-to-creatinine ratio (ACR) in critically ill patients with sepsis. Methods: This retrospective study analyzed sepsis cases admitted to the Affiliated Hospital of Jiangsu University between January 2015 and November 2023. The patients were divided into four groups based on their ACR upon admission to the intensive care unit (ICU). Laboratory data were collected at the time of ICU admission, and the primary outcome measure was in-hospital all-cause mortality. Kaplan-Meier survival curves were generated to illustrate the differences in 30-/60-day mortality among the various groups. Multivariate Cox regression models and restricted cubic splines (RCS) were utilized to explore the association between ACR and all-cause mortality in sepsis patients. Subgroup analyses were conducted to examine the impact of other covariates on the relationship between ACR and all-cause mortality. Results: A total of 1,123 eligible patients were included in the study, with a median ACR of 0.169. The in-hospital mortality rate was 33.7%, the ICU mortality rate was 31.9%, and the 30-day mortality rate was 28.1%. Kaplan-Meier survival analysis demonstrated that patients with higher ACR had a significantly lower risk of 30-/60-day mortality (log-rank p < 0.001). Multivariable Cox proportional hazards analyses revealed that ACR was an independent predictor of in-hospital death (HR: 0.454, 95% CI 0.271-0.761, p = 0.003), ICU death (HR: 0.498, 95% CI 0.293-0.847, p = 0.010), and 30-day death (HR: 0.399, 95% CI 0.218-0.730, p = 0.003). For each 1-unit increase in ACR, there was a 1.203-fold decrease in the risk of death during the hospital stay. The RCS curve illustrated a non-linear negative correlation between ACR and in-hospital mortality (p for non-linear =0.018), ICU mortality (p for non-linear =0.005), and 30-day mortality (p for non-linear =0.006). Sensitivity analysis indicated consistent effect sizes and directions in different subgroups, confirming the stability of the results. Conclusion: Low ACR levels were identified as independent risk factors associated with increased in-hospital, ICU, and 30-day mortality in sepsis patients. ACR can serve as a significant predictor of the clinical outcome of sepsis.

Association of urinary albumin excretion with all-cause and cardiovascular mortality among patients with rheumatoid arthritis: a national prospective study.

Background: Rheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients. Methods: National Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves. Results: The Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically non-significant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR<300mg/g). ACR≥300mg/g was associated with an increase in all-cause mortality (HR 2.62, 95% CI 1.55-4.45) and CVD mortality (HR 5.67, 95% CI 1.96-16.39). RCS demonstrated a nonlinear correlation between ACR and all-cause mortality in RA patients with microalbuminuria. Subgroup analysis showed that CVD mortality was higher in RA patients with microalbuminuria characterized by the following features: female, other ethnicity, eGFR≥60 ml/min/1.73 m2, hypertension or hyperlipidemia. Compared with eGFR, ACR provided better prognostic efficacy than eGFR with higher values of the area under the curve (AUC) for all-cause mortality (AUC=0.683, 95% CI 0.613-0.754) and CVD mortality (AUC=0.681, 95% CI 0.541-0.820). Conclusion: ACR is an independent risk factor affecting the prognosis of RA patients. The all-cause mortality was increased in RA patients with albuminuria. There was an upward trend in the CVD mortality of those with macroalbuminuria when ACR increased.

Tissue-Adaptive BSA Hydrogel with Dual Release of PTX and bFGF Promotes Spinal Cord Injury Repair via Glial Scar Inhibition and Axon Regeneration.

Spinal cord injury (SCI) is a severe clinical disease usually accompanied by activated glial scar, neuronal axon rupture, and disabled motor function. To mimic the microenvironment of the SCI injury site, a hydrogel system with a comparable mechanical property to the spinal cord is desirable. Therefore, a novel elastic bovine serum albumin (BSA) hydrogel is fabricated with excellent adhesive, injectable, and biocompatible properties. The hydrogel is used to deliver paclitaxel (PTX) together with basic fibroblast growth factor (bFGF) to inhibit glial scar formation as well as promote axon regeneration and motor function for SCI repair. Due to the specific interaction of BSA with both drugs, bFGF, and PTX can be controllably released from the hydrogel system to achieve an effective concentration at the wound site during the SCI regeneration process. Moreover, benefiting from the combination of PTX and bFGF, this bFGF/PTX@BSA system significantly aided axon repair by promoting the elongation of axons across the glial scar with reduced reactive astrocyte secretion. In addition, remarkable anti-apoptosis of nerve cells is evident with the bFGF/PTX@BSA system. Subsequently, this multi-functionalized drug system significantly improved the motor function of the rats after SCI. These results reveal that bFGF/PTX@BSA is an ideal functionalized material for nerve repair in SCI.

[Volume therapy: which preparation for which situation?] / Volumentherapie ­ welches Präparat in welcher Situation?

The most commonly used fluids for volume therapy are crystalloids and colloids. Crystalloids comprise 0.9% sodium chloride and balanced crystalloids (BC). Colloids can be divided into artificial colloids and human albumin (a natural colloid). Large studies show advantages for BC over 0.9% NaCl with respect to renal endpoints, probably due to the unphysiologically high chloride content of 0.9% NaCl. However, other studies, such as the BaSICS and PLUS trials, showed no significant differences in mortality in a heterogeneous population. Despite this, meta-analyses suggest advantages for BC. Therefore, BC should be preferred, especially in patients at increased risk of acute kidney injury, with acidemia and/or hyperchloremia. Except for specific indications (e.g., in patients with cirrhosis, sepsis resuscitation after initial volume therapy with BC), albumin should not be used. There is clear evidence of harm from hydroxyethyl starch in intensive care patients.

Does serum albumin at the onset of necrotising enterocolitis predict severe disease in preterm infants?

OBJECTIVE: To investigate whether laboratory markers obtained at the onset of necrotising enterocolitis (NEC) predict the severity of the disease in preterm infants. METHODS: Prospective cohort study conducted in a tertiary referance hospital. A total of 88 preterm infants were included in the study. Of those, 60 infants had the diagnosis of severe NEC, while the remaining 28 infants constituted the non-severe NEC group. Severe NEC was defined as surgical NEC or NEC-related mortality. Infants with and without severe NEC were compared in terms of demographic, clinical and laboratory characteristics. RESULTS: At the onset of disease, infants with severe NEC noted to have lower platelet count and serum ALB levels (p = 0.011, p = 0.004; respectively), whereas higher CRP, and serum lactate levels (p = 0.009, p = 0.008; respectively). Multiple binary logistic regression analyses showed that CRP (1.03(1.01-1.05), p = 0.024) and serum albumin level (0.16(0.04-0.64), p = 0.010) were statistically significant independent risk factors for severe NEC. The optimal cut-off value for the serum ALB level was found to be 23 g/L with 52% sensitivity (95%CI: 37-68%) and 84% specificity (95%CI: 60-97%) (AUC 0.727; p = 0.002). CONCLUSION: Serum ALB level at NEC onset might be a reliable biomarker for severe disease in preterm infants.

Fluid bolus resuscitation with hypertonic saline albumin solution in critically ill children: a prospective observational pilot study.

To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p < 0.05). Moreover, the amount of fluid requirements decreased significantly in the 6 h following HSA infusion [8.7 ml/kg (SD 9.6) vs. 15.1 ml/kg (SD 13.6) in the previous 6 h (p < 0.05)]. Serum levels of sodium and chloride increased after the infusion, reaching their peak concentration after one hour (143 mEq/L (SD 3.5) and 109.7 mEq/L (SD 6) respectively). HSA-related metabolic acidosis or acute kidney injury were not observed in this study. Hypertonic saline albumin is safe and effective when infused at a dose of 5 ml/kg in critically ill children. However, further research is required to confirm our findings.

Minimal mathematical model for glycation of albumin.

BACKGROUND: Glycated albumin (GA) is often described as a reflection of glucose exposure over the past 2-4 weeks. We examined the scale of the operative interval for changes in %GA from the perspective of a theoretical model for GA formation, by simulating the time course of changes in %GA after changes in glucose. METHODS: Probability of survival of albumin (A) was according to first-order elimination based on t1/2 of 17 days. Probability of formation of GA from A per unit time was proportional to glucose (G) and a glycation rate constant, k, deduced from reference values for %GA vs. G. We then simulated the kinetics of changes in %GA for conditions in which a prior steady-state (constant G) was followed by a step change in G. RESULTS: The glycation rate constant k was 9.79e-4/d/(mmol/L). We simulated changes in %GA for two scenarios involving step changes in G at time = 0: A. from 10 mmol/L to 15 mmol/L (%GA ultimately moves from 19.3% to 26.4%); B. from 15 mmol/L to 10 mmol/L (%GA ultimately moves from 26.4% to 19.3%). For both scenarios, the fractional transition of %GA between respective starting points and ultimate endpoints was after 30 days approximately 80% of the ultimate full transition. CONCLUSIONS: Model-based calculations support the description of %GA as a reflection of G over the past 4-6 weeks, longer than the period of 2-4 weeks that is commonly cited.

Prognostic importance of preoperative albumin-to-alkaline phosphatase ratio in colorectal cancer patients.

<b>Introduction:</b> Colorectal cancer (CRC) prognosis is typically determined based on clinical stage and histopathological findings, yet patients with the same stage and histological structure can exhibit varying survival outcomes. This highlights the need for additional prognostic biomarkers. Serum biomarkers are gaining increasing significance due to their affordability and accessibility. The albumin-alkaline phosphatase ratio (AAPR) has been associated with prognosis in hepatocellular and gastric cancers, but its role in CRC remains underexplored.<b>Aim:</b> This study aimed to evaluate the effect of the albumin-alkaline phosphatase ratio (AAPR) on the prognosis of patients with colorectal cancer (CRC).<b>Material and method:</b> Data from 358 patients who had undergone surgery for CRC were analyzed retrospectively to identify factors that could predict overall survival (OS). The Roc-Curve test was applied to determine the power of the preoperative AAPR in predicting mortality. Kaplan Meier and log-rank tests were used to examine the survival times of the patients.<b>Results:</b> Our findings revealed that an albumin-alkaline phosphatase cut-off ratio above 0.67 predicted mortality with a sensitivity of 17.54% and a specificity of 92.22%. Although patients with a lower AAPR exhibited a slightly shorter mean survival time compared to those above the cut-off value, this difference did not reach statistical significance (P = .112).<b>Conclusions:</b> The results of this study did not provide evidence to support the AAPR as a potential prognostic factor in patients with colorectal cancer.

Pregnancy cholestasis typically occurs in the third trimester of pregnancy and is a significant clinical condition.

AIM: The aim of this study is to determine the albumin/bilirubin ratio index and the aspartate aminotransferase (AST)/alanine aminotransferase ratio (ALT) index in patients diagnosed with cholestasis during pregnancy, and to demonstrate their correlation with liver damage. Additionally, potential strategies to prevent liver damage will be elucidated. MATERIALS AND METHOD: Our study is a retrospective study. A total of 4019 pregnant women aged between 18 and 40 years, presenting with itching complaints at 32-36 weeks of gestation, were screened at the Department of Obstetrics and Gynecology, Istanbul Training and Research Hospital of Health Sciences University between January 1, 2018, and December 31, 2023. Among them, 104 pregnant women without any other accompanying diseases were diagnosed with Gestational Cholestasis. Among the 104 diagnosed women, 78 met the inclusion criteria and were included in the study. Twenty-six women were excluded from the study due to missing albumin and total bilirubin values or due to blood samples being taken at different times. The serum albumin/bilirubin ratio index and the alanine aminotransferase/aspartate aminotransferase ratio index were calculated and statistically compared between pregnant women diagnosed with cholestasis and healthy pregnant women at the same gestational week. FINDINGS: We found that AST, ALT, albumin, and total bilirubin levels were significantly higher in pregnant women diagnosed with cholestasis compared to the control group (p < 0.05). The AST/ALT index in the case group was significantly lower compared to the control group. However, there were no significant differences found between the case and control groups regarding the albumin/total bilirubin index and ALBI grade. When comparing ALBI grades in cases, no significant differences were found in terms of patients' age, gestational week, AST, ALT, and AST/ALT index. When compared according to ALBI grades, the albumin level was higher in patients with ALBI grade I compared to grade II, and in patients with grade II compared to grade III. The total bilirubin level was significantly higher in patients with ALBI grade III compared to grades I and II, but there was no significant difference between grades I and II. No significant differences were found among the groups separated according to ALBI grades when FBA values were compared. CONCLUSION: In this study, the negative correlation between lower AST/ALT ratio and FBA values in patients with severe cholestasis suggests the need for careful consideration regarding future liver damage. The lack of difference in ALBI score between the case and control groups, as well as the absence of correlation with FBA values, indicates the necessity to evaluate ALBI score based on patients' long-term prognosis.