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#38621656   2024/04/13 To Up

An intracellular VHH targeting the Luteinizing Hormone receptor modulates G protein-dependent signaling and steroidogenesis.

Luteinizing hormone (LH) is essential for reproduction, controlling ovulation and steroidogenesis. Its receptor (LHR) recruits various transducers leading to the activation of a complex signaling network. We recently identified iPRC1, the first variable fragment from heavy-chain-only antibody (VHH) interacting with intracellular loop 3 (ICL3) of the follicle-stimulating hormone receptor (FSHR). Because of the high sequence similarity of the human FSHR and LHR (LHCGR), here we examined the ability of the iPRC1 intra-VHH to modulate LHCGR activity. In this study, we demonstrated that iPRC1 binds LHCGR, to a greater extent when the receptor was stimulated by the hormone. In addition, it decreased LH-induced cAMP production, cAMP-responsive element-dependent transcription, progesterone and testosterone production. These impairments are not due to Gs nor β-arrestin recruitment to the LHCGR. Consequently, iPRC1 is the first intra-VHH to bind and modulate LHCGR biological activity, including steroidogenesis. It should help further understand signaling mechanisms elicited at this receptor and their outcomes on reproduction.
Camille Gauthier, Pauline Raynaud, Frédéric Jean-Alphonse, Amandine Vallet, Océane Vaugrente, Vinesh Jugnarain, Thomas Boulo, Christophe Gauthier, Eric Reiter, Gilles Bruneau, Pascale Crepieux

2426 related Products with: An intracellular VHH targeting the Luteinizing Hormone receptor modulates G protein-dependent signaling and steroidogenesis.

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#38610885   2024/04/05 To Up

Complete Blood Count-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Children and Adolescents with Severe Obesity.

Childhood obesity is a globally increasing pathological condition leading to long-term health issues such as cardiovascular diseases and metabolic syndrome (MetS). This study aimed to determine the clinical value of the Complete Blood Count-derived inflammation indexes Monocyte/HDL-C ratio (MHR), Lymphocyte/HDL-C ratio (LHR), Neutrophil/HDL-C ratio (NHR), and System Inflammation Response Index (SIRI) to predict the presence of metabolic syndrome and its association with cardiovascular risk markers (HOMA-IR, TG/HDL-C, and non-HDL-C) in children and adolescents with obesity. The study included a total of 552 children/adolescents with severe obesity (BMI: 36.4 [32.7-40.7] kg/m; 219 males, 333 females; age: 14.8 [12.9-16.3] years), who were further subdivided based on the presence or absence of metabolic syndrome (MetS+ and MetS respectively). The MHR, LHR, and NHR indexes ( < 0.0001), but not SIRI ( = 0.524), were significantly higher in the MetS+ compared to the MetS- subgroup, showing a positive correlation with the degree of MetS severity ( < 0.0001). Furthermore, MHR, LHR, and NHR were positively associated with cardiometabolic risk biomarkers (HOMA-IR: MHR = 0.000, LHR = 0.001, NHR < 0.0001; TG/HDL-C: MHR, LHR, NHR < 0.000; non-HDL-C: MHR, LHR < 0.0001, NHR = 0.000). Finally, the ROC curve analysis demonstrated that among the analyzed indexes, only MHR, LHR, and NHR had diagnostic value in distinguishing MetS patients among children and adolescents with obesity (MHR: AUC = 0.7045; LHR: AUC = 0.7205; NHR: AUC = 0.6934; < 0.0001). In conclusion, the MHR, LHR, and NHR indexes, but not the SIRI index, can be considered useful tools for pediatricians to assess the risk of MetS and cardiometabolic diseases in children and adolescents with obesity and to develop multidisciplinary intervention strategies to counteract the widespread disease.
Alice Marra, Adele Bondesan, Diana Caroli, Alessandro Sartorio

1164 related Products with: Complete Blood Count-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Children and Adolescents with Severe Obesity.

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#38596427   2024/04/08 To Up

Ceftriaxone Pharmacokinetics and Pharmacodynamic Target Attainment for Three Pediatric Patients Receiving Continuous Kidney Replacement Therapy.

Ceftriaxone is used commonly for sepsis, including in children requiring continuous kidney replacement therapy (CKRT). No reports exist of pharmacokinetic (PK) parameters for children receiving ceftriaxone on CKRT. We enrolled children admitted to our pediatric intensive care unit (PICU) who received CKRT for >24 hours and received >1 dose of ceftriaxone while on and off CKRT. We measured free ceftriaxone -concentrations from residual blood samples then used Bayesian estimation with PK modeling software to generate concentration-time profiles and determine PK parameters and the percentage of time free ceftriaxone concentrations were above 1× or 4× MIC (% T >MIC). Three patients aged 2 to 17 years were included; all were anuric at CKRT initiation and received 50 mg/kg (max 2000 mg) ceftriaxone every 12 to 24 hours. Total ceftriaxone clearance (CL) was 0.50 to 3.67 L/hr while receiving CKRT and 0.29 to 2.71 L/hr while off, indicating CKRT provided 25% to 42% of total ceftriaxone CL. All achieved 100% T >1× and 4× MIC using an estimated MIC (1 mg/L) for patients 1 to 2 (no culture data) and a measured MIC (0.016 mg/L) for patient 3. Therefore, CKRT contributed significantly to total ceftriaxone clearance in 3 children though the dosing strategies used in each patient attained PD targets.
H Rhodes Hambrick, Francisco Cervantes, Min Dong, Peter Tang, Trent Arbough, Alexander A Vinks, Tomoyuki Mizuno, Stuart L Goldstein, Jennifer Kaplan, Sonya Tang Girdwood

1006 related Products with: Ceftriaxone Pharmacokinetics and Pharmacodynamic Target Attainment for Three Pediatric Patients Receiving Continuous Kidney Replacement Therapy.

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#38592161   2024/02/27 To Up

Complete Blood Count (CBC)-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Adults with Severe Obesity.

Metabolic syndrome (MetS) is a globally increasing pathological condition. Recent research highlighted the utility of complete blood count-derived (CBC) inflammation indexes to predict MetS in adults with obesity. This study examined CBC-derived inflammation indexes (NHR, LHR, MHR, PHR, SIRI, AISI, and SII) in 231 adults with severe obesity (88 males, 143 females; age: 52.3 [36.4-63.3] years), divided based on the presence (MetS+) or absence (MetS-) of MetS. The relationships between the indexes and the cardiometabolic risk biomarkers HOMA-IR, TG/HDL-C, and non-HDL-C were also evaluated. Individuals with metabolic syndrome (MetS+) had significantly higher values of MHR, LHR, NHR, PHR, and SIRI than those without (MetS-) (MHR and NHR: < 0.0001; LHR: = 0.001; PHR: = 0.011; SIRI: = 0.021). These values were positively correlated with the degree of MetS severity. Logistic regression (MHR and NHR: = 0.000; LHR: = 0.002; PHR: = 0.022; SIRI: = 0.040) and ROC analysis (MHR: AUC = 0.6604; LHR: AUC = 0.6343; NHR: AUC = 0.6741; PHR: AUC = 0.6054; SIRI: AUC = 0.5955) confirmed the predictive potential of CBC-derived inflammation indexes for MetS in individuals with severe obesity. CBC-derived inflammation indexes also correlated with HOMA-IR (MHR, LHR, and NHR: < 0.0001; PHR: < 0.001; SIRI: = 0.000) and TG/HDL-C (MHR, LHR, NHR and PHR: < 0.0001; SIRI: = 0.006). In conclusion, this study validates CBC-derived inflammation indexes for predicting MetS in individuals with severe obesity. The relationships between these indexes and cardiometabolic risk factors can enable clinicians to better grade MetS associated with obesity.
Alice Marra, Adele Bondesan, Diana Caroli, Alessandro Sartorio

1053 related Products with: Complete Blood Count (CBC)-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Adults with Severe Obesity.

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#38590230   // To Up

Association of Three Novel Inflammatory Markers: Lymphocyte to HDL-C Ratio, High-Sensitivity C-Reactive Protein to HDL-C Ratio and High-Sensitivity C-Reactive Protein to Lymphocyte Ratio With Metabolic Syndrome.

We aimed to compare the association of three novel inflammatory indicators with metabolic syndrome (MetS) among Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort participants.
Rana Kolahi Ahari, Nazanin Akbari, Negin Babaeepoor, Zahra Fallahi, Sara Saffar Soflaei, Gordon Ferns, Mahmoud Ebrahimi, Mohsen Moohebati, Habibollah Esmaily, Majid Ghayour-Mobarhan

1164 related Products with: Association of Three Novel Inflammatory Markers: Lymphocyte to HDL-C Ratio, High-Sensitivity C-Reactive Protein to HDL-C Ratio and High-Sensitivity C-Reactive Protein to Lymphocyte Ratio With Metabolic Syndrome.

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#38581619   2024/04/06 To Up

Lung-derived soluble factors support stemness/plasticity and metastatic behaviour of breast cancer cells via the FGF2-DACH1 axis.

Patients with triple-negative breast cancer (TNBC) have an increased propensity to develop lung metastasis. Our previous studies demonstrated that stem-like ALDHCD44 breast cancer cells interact with lung-derived soluble factors, resulting in enhanced migration and lung metastasis particularly in TNBC models. We have also observed that the presence of a primary TNBC tumor can 'prime' the lung microenvironment in preparation for metastasis. In this study, we hypothesized that soluble lung-derived factors secreted in the presence of a primary TNBC tumor can influence stemness/plasticity of breast cancer cells. Using an ex vivo pulmonary metastasis assay (PuMA), we observed that the lung microenvironment supports colonization and growth of ALDHCD44 TNBC cells, potentially via interactions with lung-derived FGF2. Exposure of TNBC cells to lung-conditioned media (LCM) generated from mice bearing TNBC primary tumors (tbLCM) significantly enhanced the proportion of ALDHCD44 cells compared to control or LCM from tumor-naïve mice (tnLCM). Further analysis using a human cancer stem cell qPCR array revealed that, relative to tnLCM or control, exposure of TNBC cells to tbLCM leads to downregulation of the transcription factor and putative tumor suppressor Dachshund homolog 1 (DACH1), a downstream regulator of FGF2. In addition, inhibition of DACH1 using siRNA or treatment with recombinant FGF2 enhanced the ALDHCD44 phenotype. Taken together, our findings suggest that the FGF2-DACH1 signaling axis supports stemness/plasticity of TNBC cells in the lung microenvironment and lays the foundation for future evaluation of FGF2 as a potential novel therapeutic target for treatment or prevention of breast cancer metastasis to the lung.
Vasudeva Bhat, Matthew Piaseczny, David Goodale, Urvi Patel, Ashkan Sadri, Alison L Allan

2149 related Products with: Lung-derived soluble factors support stemness/plasticity and metastatic behaviour of breast cancer cells via the FGF2-DACH1 axis.



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#38553691   2024/03/29 To Up

Evaluation of heroin-assisted treatment in Norway: protocol for a mixed methods study.

Opioid agonist treatment (OAT) for patients with opioid use disorder (OUD) has a convincing evidence base, although variable retention rates suggest that it may not be beneficial for all. One of the options to include more patients is the introduction of heroin-assisted treatment (HAT), which involves the prescribing of pharmaceutical heroin in a clinical supervised setting. Clinical trials suggest that HAT positively affects illicit drug use, criminal behavior, quality of life, and health. The results are less clear for longer-term outcomes such as mortality, level of function and social integration. This protocol describes a longitudinal evaluation of the introduction of HAT into the OAT services in Norway over a 5-year period. The main aim of the project is to study the individual, organizational and societal effects of implementing HAT in the specialized healthcare services for OUD.
Lars Henrik Myklebust, Desiree Eide, Espen A Arnevik, Omid Dadras, Silvana De Pirro, Rune Ellefsen, Lars T Fadnes, Morten Hesse, Timo L Kvamme, Francesca Melis, Ann Oldervoll, Birgitte Thylstrup, Linda E C Wusthoff, Thomas Clausen

1660 related Products with: Evaluation of heroin-assisted treatment in Norway: protocol for a mixed methods study.

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#38546250   2023/04/10 To Up

Antenatally Detected Thoracic Lesions: Prognosis, Management and Outcome.

Foetal thoracic lesions are uncommon, with the incidence of 1 in 15,000 live births. Antenatal monitoring of these lesions is required to prognosticate the parents about the postnatal outcome of the lesions and about the well-being of the baby. Foetal ultrasound and magnetic resonance imaging (MRI) are the modalities to detect these lesions and follow-up during pregnancy and postnatally. Congenital pulmonary adenomatoid malformations (CPAM), congenital diaphragmatic hernia (CDH) and bronchopulmonary sequestrations (BPS) are the commonly detected foetal thoracic lesions. Parameters such as congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) and lung-to-head ratio (LHR) determine the prognosis of these lesions. With this background, we planned to study the prognosis and outcome of antenatally detected thoracic lesions.
Md Mokarram Ali, Nilesh Tank, Monika Bawa

1234 related Products with: Antenatally Detected Thoracic Lesions: Prognosis, Management and Outcome.

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#38533293   2024/03/22 To Up

A New Dosing Frontier: Retrospective Assessment of Effluent Flow Rates and Residual Renal Function Among Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

In 2020, cefiderocol became the first Food and Drug Administration-approved medication with continuous renal replacement therapy (CRRT) dosing recommendations based on effluent flow rates (). We aimed to evaluate the magnitude and frequency of factors that may influence these recommendations, that is, intrapatient variability and residual renal function.
Damini Lakshmipathy, Xiaoyi Ye, Joseph L Kuti, David P Nicolau, Tomefa E Asempa

2248 related Products with: A New Dosing Frontier: Retrospective Assessment of Effluent Flow Rates and Residual Renal Function Among Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

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