scholarly journals Efficacy of Divinylbenzenic Resin in Removing Indoxyl Sulfate and P-cresol Sulfate in Hemodialysis Patients: Results from an In Vitro Study and an In Vivo Pilot Trial (xuanro4-Nature 3.2)

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 170
Author(s):  
Maria Teresa Rocchetti ◽  
Carmela Cosola ◽  
Ighli di Bari ◽  
Stefania Magnani ◽  
Vanessa Galleggiante ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Pilot Trial ◽  
In Vitro Study ◽  
Serum Levels ◽  
Cardiovascular Complications ◽  
High Serum ◽  
Uremic Toxins ◽  
Indoxyl Sulfate

High serum levels of microbiota-derived uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with chronic kidney disease (CKD) progression and cardiovascular complications. IS and PCS cannot be efficiently removed by conventional hemodialysis (HD), due to their high binding affinity for albumin. This study evaluates the efficacy of a divinylbenzene-polyvinylpyrrolidone (DVB-PVP) cartridge and a synbiotic to reduce uremic toxins in HD patients. First, the in vitro efficacy of DVB-PVP in adsorbing IS and PCS was evaluated. Second, a randomized, placebo-controlled pilot study in HD patients was carried out to establish whether the administration of a synbiotic, either individually and in association with DVB-PVP-HD, could reduce the production of uremic toxins. In vitro data showed that DVB-PVP resin removed a mean of 56% PCS and around 54% IS, after 6 h of perfusion. While, in the in vivo study, the DVB-PVP cartridge showed its adsorbing efficacy only for IS plasma levels. The combination of synbiotic treatment with DVB-PVP HD decreased IS and PCS both at pre- and post-dialysis levels. In conclusion, this study provides the first line of evidence on the synergistic action of gut microbiota modulation and an innovative absorption-based approach in HD patients, aimed at reducing plasma levels of IS and PCS.

scholarly journals SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs

2021 ◽  
Vol 12 ◽  
Author(s):  
Qun Xiang ◽  
Zeqing Feng ◽  
Bo Diao ◽  
Chao Tu ◽  
Qinghua Qiao ◽  
...  
Keyword(s):  
Serum Levels ◽  
High Serum ◽  
Human Spleen ◽  
Angiotensin Converting Enzyme 2 ◽  
Reactive Protein ◽  
Secondary Lymphoid Organs ◽  
Severe Tissue

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6, Il8 and Il1b genes in infected primary macrophages and DCs in vitro, and SARS-CoV-2-NP+ macrophages and DCs also manifested high levels of IL-6 and IL-1β, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.

scholarly journals Osteogenic growth peptide increases blood and bone marrow cellularity and enhances engraftment of bone marrow transplants in mice

Blood ◽  
1996 ◽  
Vol 88 (12) ◽  
pp. 4719-4724 ◽  
Author(s):  
O Gurevitch ◽  
S Slavin ◽  
A Muhlrad ◽  
A Shteyer ◽  
D Gazit ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Feedback Loop ◽  
Serum Levels ◽  
High Serum ◽  
Normal Serum ◽  
Host Cells ◽  
Stromal Microenvironment ◽  
Marrow Cellularity

The osteogenic growth peptide (OGP) was characterized recently in regenerating bone marrow (BM) and normal serum. In vitro, the OGP regulates stromal-cell proliferation and differentiated functions. In vivo, an increase in serum OGP accompanies the osteogenic phase of postablation BM regeneration. The present results in normal mice show that OGP induces a balanced increase in WBC counts and overall BM cellularity. In mice receiving myeloablative irradiation and syngeneic or semiallogeneic BM transplants, OGP stimulates hematopoietic reconstruction and doubles the survival rate; these effects are dependent on initiating the OGP administration before irradiation. Chimerism measurements in semiallogeneic graft recipients suggest no preferential effect of OGP on residual host cells. The data implicate OGP in the acceleration of hematopoiesis secondary to expansion of the stromal microenvironment and/or enhancement of stroma-derived signals to stem cells. The low-dose effectiveness of OGP is explained by the demonstration of an autocrine positive feedback loop that together with the OGP-binding protein sustains high serum levels of the peptide. A potential OGP-based treatment in combination with chemoradiotherapy is attractive because of the OGP-induced balanced multi-lineage enhancement of hematopoiesis and possible replacement of expensive recombinant cytokines by a readily synthesized peptide.

scholarly journals Endothelial dysfunction in insulin-resistant rats is associated with oxidative stress and COX pathway dysregulation

2009 ◽  
pp. 499-509
Author(s):  
A Oudot ◽  
D Behr-Roussel ◽  
S Compagnie ◽  
S Caisey ◽  
O Le Coz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Vascular Dysfunction ◽  
Pressor Response ◽  
In Vitro Study ◽  
Cardiovascular Complications ◽  
Insulin Resistant ◽  
Pathway Dysregulation

Because insulin resistance is inevitably associated with cardiovascular complications, there is a need to further investigate the potential involvement of oxidative stress and the cyclo-oxygenase (COX) pathway in the vascular modifications associated to this pathological context. Endothelial function was evaluated in control and fructose-fed rats (FFR) by i) in vitro study of endothelium-dependent and -independent relaxations of aortic rings, and ii) in vivo telemetric evaluation of pressor response to norepinephrine. After 9 weeks of diet, FFR displayed hypertriglyceridemia, hyperinsulinemia and exaggerated response to glucose overload. Aortic rings from control rats and FFR exhibited comparable endothelium-dependent relaxations to Ach. In the presence of indomethacin, relaxations were significantly reduced. FFR showed exaggerated pressor responses to norepinephrine that were abolished with indomethacin. Urinary nitrites/nitrates, 8-isoprostanes and thromboxane B2 excretion levels were markedly enhanced in FFR, whereas the plasma levels of 6-keto prostaglandin F1α were unchanged. In conclusion, fructose overload in rats induced hypertriglyceridemia and insulin resistance associated with an enhanced oxidative stress. This was associated with COX pathway dysregulation which could be one of the contributors to subsequent vascular dysfunction. Consequently, reduction of oxidative stress and regulation of the COX pathway could represent new potential therapeutic strategies to limit vascular dysfunction and subsequent cardiovascular complications associated with insulin resistance.

scholarly journals In vitro and in vivo protective effect of Lotus seedpod extract against acetaminophen-induced liver injury

2020 ◽  
Author(s):  
Hsien-Chun Tseng ◽  
Jen ying Hsu ◽  
Xiao-Yin Huang ◽  
Hui-Hsuan Lin ◽  
Jing-Hsien Chen
Keyword(s):  
Liver Injury ◽  
In Vitro Study ◽  
Serum Levels ◽  
Molecular Data ◽  
In Vivo Study ◽  
Main Compound ◽  
Enzyme Markers ◽  
Lotus Seedpod

Abstract Background Acetaminophen (APAP) is one of the most widely used analgesic agents while overdose APAP will lead to severe hepatotoxicity. Lotus seedpod, a traditional herbal, is rich in polyphenol and has been shown to possess antioxidant, radioprotective and anti-cancer activities. This study examined the hepatoprotective role of lotus seedpod extracts (LSE) in vitro and in vivo. Methods Firstly, LSE or its main compound epigallocatechin (EGC) dose-dependently improved the survival of human hepatocyte HepG2 cells from APAP-induced loss of viability. In vivo study, the BALB/c mice were supplemented with or without LSE (1% and 2%) during the 9-week treatment period in the presence or absence of APAP (i.p.; 400 mg/kg) twice per week. Results In vitro study revealed that LSE or EGC showed potential in reducing APAP-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the distribution of hypodiploid phase, apoptotic bodies formation, and caspases activation. Molecular data showed that antiapoptotic effects of LSE or EGC mediated via intrinsic, extrinsic and ASK 1/JNK apoptotic signaling pathways. Further data showed that LSE inhibited the APAP-induced the protein expression of iNOS to decrease inflammation. In vivo study showed that LSE treatments significantly decreased the serum levels of the hepatic enzyme markers GOT and GPT induced by APAP. LSE also inhibited the serum levels of inflammatory cytokines (IL-6 and IL-1β) during APAP treatment. LSE at 1% significantly restored the decrease in glutathione (GSH) content and elevated the levels of antioxidant enzymes, including catalase and glutathione reductase (GRd), in the liver. Western blotting data demonstrated that LSE inhibited the expression of caspase − 3, -8, -9 in APAP-induced liver injury. Conclusions LSE protected APAP-induced hepatotoxicity which could be a novo strategy for treatment.

Effects of TSH and calcitriol on bone metabolism: in vivo and in vitro study

2014 ◽  
Author(s):  
Ivo Dumic-Cule ◽  
Dunja Rogic ◽  
Damir Jezek ◽  
Lovorka Grgurevic ◽  
Slobodan Vukicevic
Keyword(s):  
Bone Metabolism ◽  
In Vitro Study ◽  
Vitro Study

Pilot Study of Probiotic Supplementation on Uremic Toxicity and Inflammatory Cytokines in Chronic Kidney Patients

2020 ◽  
Vol 16 (4) ◽  
pp. 470-480
Author(s):  
Cristina T. Roth-Stefanski ◽  
Carla Dolenga ◽  
Lia S. Nakao ◽  
Roberto Pecoits-Filho ◽  
Thyago P. de Moraes ◽  
...  
Keyword(s):  
Pilot Study ◽  
Inflammatory Cytokines ◽  
Lactobacillus Acidophilus ◽  
Serum Levels ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Bacterial Metabolism ◽  
Probiotic Supplementation ◽  
Primary Endpoints ◽  
Inflammatory Profile

Background: Bacterial metabolism contributes to the generation of uremic toxins in patients with chronic kidney disease (CKD). It has been investigated the use of probiotics in the reduction of uremic toxins intestinal production. Objective: The aim of this pilot study was to evaluate the effect of probiotic supplementation on reducing the production of uremic toxins and the inflammatory profile of CKD patients. Methods: We performed a randomized, blind, placebo-controlled, crossover study on patients with CKD stages 3 and 4. The intervention was a probiotic formulation composed of Lactobacillus acidophilus strains given orally three times a day for 3 months. Changes in uremic toxins (p-Cresylsulfate and Indoxyl Sulfate) and serum inflammatory cytokines were the primary endpoints. Results: Of the 44 patients randomized, 25 completed the study (mean age 51 ± 9.34, 64% female, mean eGFR 36 ± 14.26 mL/min/1.73m², mean BMI 28.5 ± 5.75 kg/m²). At 3 months, there were no significant changes in any of the studied biomarkers including p-cresylsulfate (p = 0.57), Indoxyl sulfate (p = 0.08) and interleukin-6 (p = 0.55). Conclusion: Lactobacillus acidophilus strains given as probiotic were not able to reduce serum levels of uremic toxins and biomarkers of inflammation in CKD patients in stage 3 and 4.

scholarly journals In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michele Dei Cas ◽  
Jessica Rizzo ◽  
Mariangela Scavone ◽  
Eti Femia ◽  
Gian Marco Podda ◽  
...  
Keyword(s):  
Oral Administration ◽  
Whole Blood ◽  
Serum Levels ◽  
Reversed Phase ◽  
Weekly Treatment ◽  
Low Dose Aspirin ◽  
Liquid Chromatography Tandem Mass ◽  
Enteric Coated

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.

scholarly journals Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

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