Search results for: Unconjugated
#33626869 2021/02/24 To Up
Quantum Dot Nanomedicine Formulations Dramatically Improve Pharmacological Properties and Alter Uptake Pathways of Metformin and Nicotinamide Mononucleotide in Aging Mice.Orally administered AgS quantum dots (QDs) rapidly cross the small intestine and are taken up by the liver. Metformin and nicotinamide mononucleotide (NMN) target metabolic and aging processes within the liver. This study examined the pharmacology and toxicology of QD-based nanomedicines as carriers of metformin and NMN in young and old mice, determining if their therapeutic potency and reduced effects associated with aging could be improved. Pharmacokinetic studies demonstrated that QD-conjugated metformin and NMN have greater bioavailability, with selective accumulation in the liver following oral administration compared to unconjugated formulations. Pharmacodynamic data showed that the QD-conjugated medicines had increased physiological, metabolic, and cellular potency compared to unconjugated formulations (25× metformin; 100× NMN) and highlighted a shift in the peak induction of, and greater metabolic response to, glucose tolerance testing. Two weeks of treatment with low-dose QD-NMN (0.8 mg/kg/day) improved glucose tolerance tests in young (3 months) mice, whereas old (18 and 24 months) mice demonstrated improved fasting and fed insulin levels and insulin resistance. High-dose unconjugated NMN (80 mg/kg/day) demonstrated improvements in young mice but not in old mice. After 100 days of QD (320 μg/kg/day) treatment, there was no evidence of cellular necrosis, fibrosis, inflammation, or accumulation. AgS QD nanomedicines improved the pharmacokinetic and pharmacodynamic properties of metformin and NMN by increasing their therapeutic potency, bypassing classical cellular uptake pathways, and demonstrated efficacy when drug alone was ineffective in aging mice.
Nicholas J Hunt, Glen P Lockwood, Sun W S Kang, Lara J Westwood, Christina Limantoro, Wojciech Chrzanowski, Peter A G McCourt, Zdenka Kuncic, David G Le Couteur, Victoria C Cogger
1068 related Products with: Quantum Dot Nanomedicine Formulations Dramatically Improve Pharmacological Properties and Alter Uptake Pathways of Metformin and Nicotinamide Mononucleotide in Aging Mice.1000 tests100ug200ul0.1 mg25 mg10 mg100ug10 mg100 mg1,000 tests200ug
#33626278 2021/02/24 To Up
Glucagon Like Peptide 1 Receptor Agonists for Targeted Delivery of Antisense Oligonucleotides to Pancreatic Beta Cell.The extra hepatic delivery of antisense oligonucleotides (ASOs) remains a challenge and hampers the widespread application of this powerful class of therapeutic agents. In that regard, pancreatic beta cells are a particularly attractive but challenging cell type because of their pivotal role in diabetes and the fact that they are refractory to uptake of unconjugated ASOs. To circumvent this, we have expanded our understanding of the structure activity relationship of ASOs conjugated to Glucagon Like Peptide 1 Receptor (GLP1R) agonist peptide ligands. We demonstrate the key role of the linker chemistry and its optimization to design maleimide based conjugates with improved efficacy. In addition, truncation studies and scoping of a diverse set of GLP1R agonists proved fruitful to identify additional targeting ligands efficacious including native hGLP1(7-36)NH. Variation of the carrier peptide also shed some light on the dramatic impact of subtle sequence differences on the corresponding ASO conjugate performance , an area which clearly warrant further investigations. We have confirmed the remarkable potential of GLP1R agonist conjugation for the delivery of ASOs to pancreatic beta cell by effectively knocking down islet amyloid polypeptide (IAPP) mRNA, a potential proapoptotic target, in mice.
Laurent Knerr, Thazha P Prakash, Richard Lee, William J Drury Iii, Mehran Nikan, Wuxia Fu, Elaine Pirie, Leonardo De Maria, Eric Valeur, Ahlke Hayen, Maria Ölwegård-Halvarsson, Johan Broddefalk, Carina Ämmälä, Michael E Østergaard, Johan Meuller, Linda Sundström, Patrik Andersson, David Janzén, Rasmus Jansson-Löfmark, Punit P Seth, Shalini Andersson
2472 related Products with: Glucagon Like Peptide 1 Receptor Agonists for Targeted Delivery of Antisense Oligonucleotides to Pancreatic Beta Cell.100ul100ug200ul100ug100ug Lyophilized100ug0.1ml (1mg/ml)50 ug250ul100ug 100ul100ug Lyophilized
#33614980 2021/02/10 To Up
Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis.Bile acids are known to contribute to hepatic glucose and lipid metabolism regulation. Although glucose homeostasis sustains well-characterized modifications during uncomplicated pregnancies, changes in bile acids concentrations and relative proportions throughout pregnancy remain unknown. Furthermore, literature shows strong associations between bile acids profiles and glucose homeostasis under normal metabolic conditions. We seek, first, to characterize bile acids' metabolic changes across trimesters and, second, to evaluate associations between changes in bile acids and glucose homeostasis indexes in the first and second trimesters.
Marianne Gagnon, Jocelyn Trottier, S John Weisnagel, Claudia Gagnon, Anne-Marie Carreau, Olivier Barbier, Anne-Sophie Morisset
1648 related Products with: Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis.600 Tests / Kit430 Tests / Kit430 tests10 mg100 mg96T200ug1000 TESTS/0.65ml250ul50 mg100 assays1g
#33610570 2021/02/18 To Up
Fabrication and Characterization of Surface Engineered Rifampicin Loaded Lipid Nanoparticulate Systems for the potential treatment of Tuberculosis: An In vitro and In vivo Evaluation.The main aim of the present investigation highlights the development of mannose appended rifampicin containing solid lipid nanoparticles (Mn-RIF-SLNs) for the management of pulmonary TB. The developed Mn-RIF-SLNs showed particle size of Mn-RIF-SLNs (479 ± 13 nm) which was found to be greater than that of unconjugated SLNs (456 ± 11 nm), with marginal reduction in percentage entrapment efficiency (79.41 ± 2.42 %). The in vitro dissolution studies depicted an initial burst release followed by sustained release profile indicating biphasic release pattern, close-fitting Weibull model having least F-value. The cytotoxicity studies using J774A.1 cell line represented that the developed SLNs were non-toxic and safe as compared to free drug. Fluorescence imaging and flow cytometric (FACS) analysis depicted significant (1.79-folds) intracellular uptake of coumarin-6 (fluorescent marker) loaded Mn-C6-SLNs. The in vivo pharmacokinetic studies in sprague-dawley rats were performed and Mn-RIF-SLNs showed remarkable enhancement in terms of relative bioavailability (∼17-folds) as compared to its drug solution via oral administration. The biodistribution studies revealed higher lung accumulation (1.8-folds) of Mn-RIF-SLNs as compared to the Un-RIF-SLNs. In conclusion, the developed Mn-RIF-SLNs could serve as a promising tool for delivering the drug cargo to the site of infection (lungs) in the treatment of TB.
Nimitt V Chokshi, Shruti Rawal, Dhruvi Solanki, Saumitra Gajjar, Vivek Bora, Bhoomika M Patel, Mayur M Patel
2628 related Products with: Fabrication and Characterization of Surface Engineered Rifampicin Loaded Lipid Nanoparticulate Systems for the potential treatment of Tuberculosis: An In vitro and In vivo Evaluation.48 samples96 tests1 mL0.1 mg50 mg
#33609622 2021/02/18 To Up
Generation of αCD11b-CpG antibody conjugates for the targeted stimulation of myeloid cells.CpG oligonucleotides are short single-stranded synthetic DNA molecules. Upon binding to Toll-like receptor 9 (TLR9), CpG activates immune cells in humans and mice. This results in robust Th1 type immunity potentially resulting in clearance of pathogens, reduction of allergy and anti-tumor immunity. However, the effectiveness of CpG as an adjuvant depends on its administration route, with only strong effects seen when CpG is administered locally. As local administration is not always feasible, we generated conjugates to specifically deliver CpG to myeloid cells often abundantly present in tumors. For this we coupled CpG (3'-Thiol-modified phosphorothioate (PTO) CpG-ODN1826 type B (5'-tccatgacgttcctgacgtt-3')) to monoclonal antibodies (mAbs) directed against the myeloid cell marker CD11b using maleimide-thiol coupling. The CD11b-CpG mAb (αCD11b-CpG) conjugates contained about four CpG molecules/conjugate and displayed binding and internalization characteristics similar to unconjugated CD11b mAbs (αCD11b). The αCD11b-CpG conjugates readily induced maturation of murine dendritic cells (DCs) in a TLR9-dependent manner in vitro. Following intravenous injection, αCD11b-CpG conjugates efficiently targeted CD11b immune cells in the blood, lymph nodes and spleen. Finally, injection of αCD11b-CpG conjugates, but not untargeted conjugates, induced maturation of CD11b cell subsets in vivo. In conclusion, conjugating CpG to αCD11b enabled specific targeting and activation of myeloid cells in vivo.
N Balneger, M Kroesen, D Lindau, M Wassink, L Boon, M H den Brok, C Büll, G J Adema
1476 related Products with: Generation of αCD11b-CpG antibody conjugates for the targeted stimulation of myeloid cells.25 µg100.00 ug1mg0.25 mg 100ul100ul100ug100μg 100ul
#33604208 2021/01/12 To Up
A Rare Case Report of Crigler Najjar Syndrome Type II.Crigler-Najjar syndrome is an inborn error of metabolism caused by a point mutation in one of the five exons of UGT1A1 gene, the product of which is responsible for elimination of bilirubin via bile. A number of hyperbilirubinemia disorders similar to Crigler-Najjar syndrome are reported, but they differ in their level of unconjugated bilirubin and responses to the treatment. Here we report a 14-year-old male patient admitted to hospital with the complaint of vomiting and frequent tonsillitis. Further examination revealed that he was jaundiced since birth and had a family history of similar disorder. This report is about an extremely rare case of Crigler-Najjar syndrome type II and also management of the condition to provide the patient with a healthy lifestyle.
Eusha Abdul Raffay, Ayesha Liaqat, Maria Khan, Ali I Awan, Bakhat Mand
#33588585 2021/02/15 To Up
EXPRESS: Effects of bilirubin configurational photoisomers on the measurement of direct bilirubin by the vanadate oxidation method.Direct bilirubin (DB) levels measured using vanadate chemical oxidation method do not exactly match the conjugated bilirubin concentration. One of the causes is the effect of bilirubin photoisomers. However, the quantitative evaluation of the effects of these photoisomers has not been sufficiently conducted. In particular, the influence of bilirubin configurational isomers (BCI) on DB is the most critical factor.
Shohei Kawamoto, Kosuke Koyano, Miyo Ozaki, Takeshi Arai, Takashi Iwase, Hitoshi Okada, Susumu Itoh, Koji Murao, Takashi Kusaka
1536 related Products with: EXPRESS: Effects of bilirubin configurational photoisomers on the measurement of direct bilirubin by the vanadate oxidation method.480/kit480/kit500 Units100 μg1mg 1 G480/kit1 100 G100.00 ul
#33587317 2021/02/15 To Up
Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin.Silymarin is an extract from the seeds (fruits) of Silybum marianum that contains flavonolignans and flavonoids. Although it is frequently used as a hepatoprotective agent, its application remains somewhat debatable, in particular, due to the low oral bioavailability of flavonolignans. Moreover, there are claims of its potential interactions with concomitantly used drugs. This review aims at a systematic summary and critical assessment of known information on the pharmacokinetics of particular silymarin flavonolignans. There are two known major reasons for poor systemic oral bioavailability of flavonolignans: (1) rapid conjugation in intestinal cells or the liver and (2) efflux of parent flavonolignans or formed conjugates back to the lumen of the gastrointestinal tract by intestinal cells and rapid excretion by the liver into the bile. The metabolism of phase I appears to play a minor role, in contrast to extensive conjugation and indeed the unconjugated flavonolignans reach low plasma levels after common doses. Only about 1%-5% of the administered dose is eliminated by the kidneys. Many in vitro studies tested the inhibitory potential of silymarin and its components toward different enzymes and transporters involved in the absorption, metabolism, and excretion of xenobiotics. In most cases, effective concentrations are too high to be relevant under real biological conditions. Most human studies showed no silymarin-drug interactions explainable by these suggested interferences. More interactions were found in animal studies, likely due to the much higher doses administered.
Václav Tvrdý, Jana Pourová, Eduard Jirkovský, Vladimír Křen, Kateřina Valentová, Přemysl Mladěnka
1662 related Products with: Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin.5 G96T100ul50 mg1 kit25 mg1 ml100ug10 mg10 plates1000 tests500 mg
#33585066 2020/04/23 To Up
Hemolysis due to Alpha-Hemolytic Enterococcus Urinary Infection: A Rare Cause of Early and Severe Unconjugated Hyperbilirubinemia in a Neonate.The reason for reporting this case is to remind that some microorganisms may cause hemolysis leading to early and severe hyperbilirubinemia by secreting hemolysin in cases; where bilirubin levels cannot be successfully decreased despite effective phototherapy, intravenous immunoglobulin, and even exchange transfusion, or in cases of increased rebound bilirubin (although urinary tract infection is associated with increased conjugated bilirubin fraction and prolonged jaundice). The most common causes of hemolysis are ABO/Rh incompatibility and enzyme deficiencies such as glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK), and galactose-1-phosphate uridyltransferase (GALT). Our patient was a male infant, weighing 3,160 g, at 38 + 4 gestational week; he was referred to our unit with total bilirubin level of 14.7 mg/dL recorded at the postnatal 20th hour and was initiated treatment with intensive phototherapy and prepared for exchange transfusion. The G6PD, PK, and GALT enzyme levels studied at the postnatal 96th hour and reducing substances in urine were detected to be normal/negative, whereas complete urinalysis revealed pyuria (7 leukocytes per each high power field). α-hemolysis-producing 105 colony-forming unit/mL grew on blood agar in the urine culture. As reported in our case, hemolysin-secreting α and β-hemolytic bacteria can lead to severe and early hemolysis and unconjugated hyperbilirubinemia, as in blood type incompatibility and enzyme deficiencies.
Birol Karabulut, Esin Alpagut Gafil
2647 related Products with: Hemolysis due to Alpha-Hemolytic Enterococcus Urinary Infection: A Rare Cause of Early and Severe Unconjugated Hyperbilirubinemia in a Neonate.100ug100ug25 100ug100 100ug100ug Lyophilized100ug100ug Lyophilized1 mg1 kit
#33574829 2021/01/26 To Up
Evaluation of Maternal Serum sHLA-G Levels for Trisomy 18 Fetuses Screening at Second Trimester.Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8-234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7-831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5-1136.4 U/ml) ( < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30-807.97, < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871-0.959, < 0.001), for AFP MoM was 0.796 (95% CI, 0.730-0.861, < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829-0.934, < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828-0.923, < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.
Danping Xu, Yiyang Zhu, Lanfang Li, Yingping Xu, Weihua Yan, Meizhen Dai, Linghong Gan
1862 related Products with: Evaluation of Maternal Serum sHLA-G Levels for Trisomy 18 Fetuses Screening at Second Trimester.2 Sample Kit100ug500 ml96T10reactions 1 mg50 ug100ug Lyophilized10reactions (20 µl each)100 ml100,000IU
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