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Clinical Biochemistry Oct 2023Multiple previously published studies have shown a weak to medium, negative correlation between BMI and glycated albumin (GA). However, many of these studies were in...
BACKGROUND AND AIMS
Multiple previously published studies have shown a weak to medium, negative correlation between BMI and glycated albumin (GA). However, many of these studies were in populations with a narrow range of BMI. It is unknown whether this trend exists if a wider BMI range is used. This is an important question for proper interpretation of GA levels in obese populations.
MATERIALS AND METHODS
A retrospective analysis of clinical trial data (NCT02519309) was performed. After appropriate exclusions, 334 subjects remained. These included 73.7% with type 2 diabetes (T2D) diagnosis and 26.3% with prediabetes. BMI ranged from 24.8-86.9 kg/m. Laboratory data were measured in a CLIA-certified laboratory using commercially available, automated methods.
RESULTS
No significant, negative correlation was seen between GA and BMI. However, individual components (glycated serum proteins and albumin) as well as the GA/HbA1c ratio show a weak, negative correlation with BMI for all subjects and those with T2D. The strongest negative correlation was with albumin. Examination by traditional BMI subgroups also showed statistically significant differences for those with T2D, but not for the prediabetic cohort. Correlations between BMI and C-reactive protein were similar in those with diabetes and prediabetes; however, correlation between BMI and insulin was stronger in those with diabetes.
CONCLUSION
Negative correlations between BMI and albumin or BMI and glycated serum proteins persist in diabetic populations that are obese and overweight, even when a statistically significant negative correlation is not observed between BMI and GA. Inflammation or insulin-mediated changes in protein synthesis could be contributors to these negative correlations, but BMI-related changes to the glomerulus could also affect clearance of albumin or glycated proteins and should be examined.
Topics: Humans; United States; Diabetes Mellitus, Type 2; Glycated Serum Albumin; Prediabetic State; Glycated Serum Proteins; Overweight; Body Mass Index; Retrospective Studies; Glycated Hemoglobin; Glycation End Products, Advanced; Serum Albumin; Obesity; Insulin; Blood Glucose
PubMed: 37757966
DOI: 10.1016/j.clinbiochem.2023.110654 -
Annals of Hepatology 2024Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVES
Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and safety compared to albumin and noradrenaline in adult hepatorenal disease patients.
MATERIALS AND METHODS
Clinical trials from four databases were included. Cochrane's approach for calculating bias risk was utilized. We rated the quality evaluation by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included the following outcomes: serum creatinine (mg/dl), urine output (ml/24 h), mean arterial pressure (mmHg), reversal rate of HRS, mortality rate, blood plasma renin activity (ng/ml/h), plasma aldosterone concentration (pg/ml), urine sodium (mEq/l), and creatinine clearance (ml/min).
RESULTS
Our analysis of nine clinical studies revealed that the noradrenaline group was associated with higher creatinine clearance (MD = 4.22 [0.40, 8.05]), (P = 0.03). There were no significant differences in serum creatinine levels (MD = 0.03 [-0.07, 0.13]), urinary sodium (MD = -1.02 [-5.15, 3.11]), urine output (MD = 32.75 [-93.94, 159.44]), mean arterial pressure (MD = 1.40 [-1.17, 3.96]), plasma renin activity (MD = 1.35 [-0.17, 2.87]), plasma aldosterone concentration (MD = 55.35 [-24.59, 135.29]), reversal rate of HRS (RR = 1.15 [0.96, 1.37]), or mortality rate (RR = 0.87 [0.74, 1.01]) between the two groups (p-values > 0.05).
CONCLUSIONS
Noradrenaline is a safe alternative medical therapy for HRS.
Topics: Humans; Terlipressin; Hepatorenal Syndrome; Norepinephrine; Albumins; Treatment Outcome; Vasoconstrictor Agents; Adult; Creatinine; Lypressin
PubMed: 38460713
DOI: 10.1016/j.aohep.2024.101495 -
Journal of Controlled Release :... Nov 2021Developing new therapeutic strategies that damage tumour cells without harming normal tissues is among the primary obstacles in chemotherapy. In this study, a novel...
Developing new therapeutic strategies that damage tumour cells without harming normal tissues is among the primary obstacles in chemotherapy. In this study, a novel β-glucuronidase-sensitive albumin-binding prodrug was designed and synthesized to selectively deliver the drug SN38 to tumour sites and maximize its efficacy. After intravenous administration, the prodrug Mal-glu-SN38 covalently bound to plasma albumin through the Michael addition, enabling it to accumulate in the tumour and release SN38 when triggered by extracellular β-glucuronidase. Compared to irinotecan, Mal-glu-SN38 displayed a slower plasma clearance and increased drug exposure over time. Moreover, Mal-glu-SN38 caused an increase in tumour-site accumulation of both the albumin-prodrug conjugate and free SN38 released from albumin conjugate when compared with irinotecan. After administration of multiple doses, Mal-glu-SN38 also significantly delayed the tumour growth, resulting in an impressive reduction or even disappearance of tumours (67% of mice cured) without causing any observable side effects.
Topics: Albumins; Animals; Camptothecin; Cell Line, Tumor; Drug Delivery Systems; Irinotecan; Mice; Neoplasms; Prodrugs
PubMed: 34619226
DOI: 10.1016/j.jconrel.2021.09.040 -
Clinical and Experimental Nephrology May 2022The present study investigates cardiovascular risk and kidney damage in patients with solitary kidneys.
BACKGROUND
The present study investigates cardiovascular risk and kidney damage in patients with solitary kidneys.
METHODS
Included in the study were 40 children with a unilateral functioning kidney and 60 healthy controls, all of whom were evaluated for carotid intima-media thickness, ischemia-modified albumin and oxidative stress parameters, and 24-h ambulatory blood pressure monitoring.
RESULTS
Serum creatinine and urine microalbumin levels were higher and creatinine clearance was lower in the patient group than in the control group, and serum ischemia-modified albumin, carotid intima-media thickness, aldosterone, plasma renin activity and blood pressure were all higher in the patient group than in the control group. In addition, the patient group was showed a non-dipper pattern.
CONCLUSION
Children with a normal functioning solitary kidney are likely at higher risk of developing cardiovascular disease and such patients should be followed closely before marked kidney impairment occurs.
Topics: Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Carotid Intima-Media Thickness; Child; Female; Heart Disease Risk Factors; Humans; Hypertension; Male; Risk Factors; Serum Albumin; Solitary Kidney
PubMed: 35037126
DOI: 10.1007/s10157-021-02169-7 -
Angewandte Chemie (International Ed. in... Dec 2021Analytical tests/devices that are used outside laboratory settings are required to have a very simple analytical protocol to get clearance by regulatory authorities....
Analytical tests/devices that are used outside laboratory settings are required to have a very simple analytical protocol to get clearance by regulatory authorities. This study describes sink/float magnetic immunoassays, a new type of rapid, mix-and-observe, instrument-free tests for the detection of biomarkers in untreated biological samples that are very simple and might meet the simple-to-use criterion of authorities to be used in the field. These tests can tell whether an analyte is above or below a predetermined level within 25-45 minutes based on the sinking or floating of a mm-sized sphere on the surface of which an immunoassay that uses reporter antibodies conjugated to superparamagnetic nanoparticles is performed. This manuscript describes the theory and proof-of-concept applications of sink/float magnetic immunoassays for the detection of C-Reactive Protein, anti-Treponema pallidum antibodies and E. coli bacteria.
Topics: Animals; Antibodies, Bacterial; Antibodies, Immobilized; C-Reactive Protein; Escherichia coli; Humans; Immunoassay; Magnetic Iron Oxide Nanoparticles; Magnetic Phenomena; Proof of Concept Study; Rabbits; Treponema pallidum
PubMed: 34647402
DOI: 10.1002/anie.202108714 -
Journal of Clinical Pharmacology Apr 2024Ozoralizumab is a bispecific NANOBODY compound that binds tumor necrosis factor alpha (TNFα) and human serum albumin. Ozoralizumab inhibits the TNFα physiological...
Ozoralizumab is a bispecific NANOBODY compound that binds tumor necrosis factor alpha (TNFα) and human serum albumin. Ozoralizumab inhibits the TNFα physiological activity while maintaining long-term plasma retention owing to its human serum albumin-binding ability. A population pharmacokinetic (PK) model was developed using data from 494 Japanese patients with rheumatoid arthritis in Phase II/III and Phase III trials to assess the effects of potential PK covariates. The ozoralizumab PK after subcutaneous administration was described using a 1-compartment model with first-order absorption and first-order elimination processes. A proportional error model was used for inter- and intra-individual variabilities, with covariance set between inter-individual variabilities of the apparent clearance and apparent distribution volume. Body weight, sex, antidrug antibody status, estimated glomerular filtration rate, and concomitant methotrexate use were identified as covariates for apparent clearance, while body weight and sex were covariates for apparent distribution volume in the final model. Body weight had the greatest effect on the PK of ozoralizumab, while the other covariates had minor effects. When administered at 30 mg every 4 weeks, the predicted steady-state plasma trough concentration in a patient weighing 83.2 kg exceeded the trough concentration required to maintain efficacy of ozoralizumab, and the estimated exposure in a patient weighing 42.5 kg did not exceed the mean exposure at 80 mg, a well-tolerated dose, throughout 52 weeks. We developed a population PK model that adequately described the ozoralizumab PK in Japanese patients with rheumatoid arthritis, and none of the evaluated covariates showed clinically relevant effects on the PK of ozoralizumab.
Topics: Humans; Tumor Necrosis Factor-alpha; Arthritis, Rheumatoid; Antibodies, Monoclonal; Body Weight; Serum Albumin, Human; Models, Biological
PubMed: 37909264
DOI: 10.1002/jcph.2380 -
Revista Espanola de Quimioterapia :... Sep 2022Cefiderocol is a new cephalosporin with a catechol in its chemical structure faciliting its access to the interior of bacteria through iron channels. In addition, it is... (Review)
Review
Cefiderocol is a new cephalosporin with a catechol in its chemical structure faciliting its access to the interior of bacteria through iron channels. In addition, it is broadly stable to beta-lactamases. The pharmacokinetic profile is a beta-lactam one: no oral absorption, and with a wide distribution within the vascular space and the interstitial fluid of well vascularized tissues, reaching therapeutic concentrations in the alveolar lavage fluid and within the macrophage. The binding of cefiderocol to human plasma proteins, primarily albumin, is moderate (range 40-60%). The terminal elimination half-life in healthy adult subjects was 2 to 3 hours. Cefiderocol is mainly renally eliminated, so dose adjustments are recommended in subjects with moderate / severe renal impairment, in case of dialysis, and probably in patients with external clearance. Like other beta-lactams, the PK / PD parameter that has been shown to best correlate with efficacy is the efficacy time of unbound plasma concentrations (%fT>MIC), which must be close to 100% to achieve a bactericidal effect. This is possible with 2 g in a 3-hour infusion every 8 hours. In controlled trials appears to be well tolerated, similar to comparators: meropenem or imipenem-cilastatin. Cefiderocol has no apparent clinically significant effect on ECG parameters nor on plasma iron values.
Topics: Adult; Albumins; Anti-Bacterial Agents; Blood Proteins; Catechols; Cephalosporins; Cilastatin, Imipenem Drug Combination; Humans; Iron; Meropenem; beta-Lactamases; beta-Lactams; Cefiderocol
PubMed: 36193982
DOI: 10.37201/req/s02.04.2022 -
Journal of Diabetes and Metabolic... Jun 2021To investigate the protective effect of vanillic acid (VA) in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats.
PURPOSE
To investigate the protective effect of vanillic acid (VA) in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats.
METHODS
Experimental diabetes mellitus in rats was induced by intraperitoneally administration of single dose of STZ (55 mg/kg). The animals were divided into 5 groups viz., normal control, diabetic control, glimepiride (0.5 mg/kg, orally) and VA treatment (50 and 100 mg/kg, orally) groups. The treatment was started after the confirmation of hyperglycemia (> 250 mg/dl) and continued for 6 weeks. Serum glucose level, and body weight were measured weekly. At the end of study, HbA1c in whole blood, insulin, lipid profile, urea, creatinine and albumin in serum. Creatinine and albumin were measured in urine along with creatinine clearance. In addition, kidney weight and histopathology were assessed.
RESULTS
Treatment with VA markedly attenuated STZ-induced body weight loss and hyperglycemia, along with improved lipid profile and HbA1c, without significant alteration of serum insulin levels. It also decreased urea, creatinine and increased albumin in serum. Moreover, VA, significantly reduced urine volume, urinary albumin along with marked improvement in creatinine clearance. Further, the VA treatment significantly reverse the raised levels of oxidative stress markers, pro-inflammatory and fibrotic markers viz. TNF-α, IL-1β, IL-6, TGF-β1 and NFκB activity in kidney tissue. These effects are associated with amelioration of histopathological alterations compared to diabetic control rats. While glimepiride produced similar antihyperglycemic effect but the effect on albuminuria, oxidative stress markers and cytokine levels were less significant as compared to VA (100 mg/kg).
CONCLUSIONS
In conclusion, VA exhibited nephroprotective effect through amelioration of kidney dysfunction and damage in diabetic rats. The observed nephroprotective effect of VA may be ascribed to inhibition of hyperglycemia induced oxido-inflammatory stress and necroptosis of renal tissue possibly due to its antihyperglycemic, antioxidant and anti-inflammatory actions.
PubMed: 34222078
DOI: 10.1007/s40200-021-00782-7 -
Stroke Apr 2023Recent evidence suggests that higher CRP (C-reactive protein) levels are associated with lower risk of Alzheimer disease, speculating that CRP might be involved in Aβ...
BACKGROUND
Recent evidence suggests that higher CRP (C-reactive protein) levels are associated with lower risk of Alzheimer disease, speculating that CRP might be involved in Aβ clearance mechanisms. Testing this hypothesis, we explored whether genetically proxied CRP levels are also associated with lobar intracerebral hemorrhage (ICH), commonly caused by cerebral amyloid angiopathy.
METHODS
We used 4 genetic variants within the gene that explain up to 64% of the variance of circulating CRP levels and explored in 2-sample Mendelian randomization analyses associations with risk of any, lobar, and deep ICH (1545 cases and 1481 controls).
RESULTS
Higher genetically proxied CRP levels were associated with lower odds of lobar ICH (odds ratio per SD increment in CRP, 0.45 [95% CI, 0.25-0.73]) but not deep ICH (odds ratio, 0.72 [95% CI, 0.45-1.14]). There was evidence of colocalization (posterior probability of association, 72.4%) in the signals for CRP and lobar ICH.
CONCLUSIONS
Our results provide supportive evidence that high CRP levels may have a protective role in amyloid-related pathology.
Topics: Humans; C-Reactive Protein; Cerebral Hemorrhage; Cerebral Amyloid Angiopathy; Magnetic Resonance Imaging
PubMed: 36891905
DOI: 10.1161/STROKEAHA.122.041889 -
International Journal of Molecular... Jan 2024Hepatitis C virus (HCV) infection alters lysophosphatidylcholine (LPC) metabolism, enhancing viral infectivity and replication. Direct-acting antivirals (DAAs)...
Hepatitis C virus (HCV) infection alters lysophosphatidylcholine (LPC) metabolism, enhancing viral infectivity and replication. Direct-acting antivirals (DAAs) effectively treat HCV and rapidly normalize serum cholesterol. In serum, LPC species are primarily albumin-bound but are also present in lipoprotein particles. This study aims to assess the impact of HCV eradication on serum LPC species levels in patients infected with HCV. Therefore, 12 different LPC species were measured by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the sera of 178 patients with chronic HCV infections at baseline, and in 176 of these patients after therapy with DAAs. All LPC species increased at 4 and 12 weeks post-initiation of DAA therapy. The serum profiles of the LPC species were similar before and after the viral cure. Patients with HCV and liver cirrhosis exhibited lower serum levels of all LPC species, except LPC 16:1, both before and after DAA treatment. Percentages of LPC 18:1 (relative to the total LPC level) were higher, and % LPC 22:5 and 22:6 were lower in cirrhotic compared to non-cirrhotic patients at baseline and at the end of therapy. LPC species levels inversely correlated with the model of end-stage liver disease score and directly with baseline and post-therapy albumin levels. Receiver operating characteristic curve analysis indicated an area under the curve of 0.773 and 0.720 for % LPC 18:1 (relative to total LPC levels) for classifying fibrosis at baseline and post-therapy, respectively. In summary, HCV elimination was found to increase all LPC species and elevated LPC 18:1 relative to total LPC levels may have pathological significance in HCV-related liver cirrhosis.
Topics: Humans; Hepacivirus; Antiviral Agents; Lysophosphatidylcholines; Tandem Mass Spectrometry; Hepatitis C, Chronic; Hepatitis C; Albumins; Liver Cirrhosis
PubMed: 38256273
DOI: 10.3390/ijms25021198