A single dose of lithium carbonate acutely elevates intact parathyroid hormone levels in humans

1989 ◽  
Vol 121 (2) ◽  
pp. 174-176 ◽  
Author(s):  
Ellen W. Seely ◽  
Thomas J. Moore ◽  
Meryl S. LeBoff ◽  
Edward M. Brown
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Human Subjects ◽  
Lithium Carbonate ◽  
Serum Levels ◽  
Ionized Calcium ◽  
Intact Parathyroid Hormone ◽  
Intact Pth

Abstract. Hyperparathyroidism has been reported in patients receiving lithium therapy, and lithium alters calcium-regulated PTH release in vitro. Previous studies in vivo have used assays which measure fragments of PTH as well as the intact hormone. To determine if lithium acutely elevates intact PTH levels, we studied 9 subjects who received a single oral dose of lithium carbonate (600 mg). Serum levels of intact PTH, ionized calcium, and lithium were measured before, 2 and 14 h after the dose of lithium. PTH levels rose significantly 2 h following the dose of lithium (before 22 ± 5.0, post 32 ± 7.3 ng/l, p < 0.02). PTH levels had returned to baseline at 14 h (22 ± 3.8 ng/l). There were no significant changes in ionized calcium levels. Therefore, a single oral dose of lithium carbonate acutely elevates intact PTH values in human subjects.

Morphological Distinction Unravels Mechanisms Of Platelet Biogenesis From Bone Marrow Megakaryocytes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2428-2428
Author(s):  
Satoshi Nishimura ◽  
Koji Eto ◽  
Ryozo Nagai
Keyword(s):  
Bone Marrow ◽  
Fluorescent Protein ◽  
Conflicts Of Interest ◽  
Human Subjects ◽  
Blood Platelets ◽  
Serum Levels ◽  
Cytokine Balance ◽  
Green Fluorescent

Abstract Blood platelets are generated in the bone marrow (BM) from their precursors, megakaryocytes (MK). Although we know that MKs produce platelets throughout life, precisely how platelets are produced in vivo remains uncertain, largely because of the rarity of MKs in the BM and the lack an adequate visualization technique. In the present study, we were able to visualize MK dynamics leading to platelet release in living animals at high resolution. To clearly understand the nature of thrombopoiesis in BM MKs, we optimized an in vivo imaging technique based on two-photon microscopy that enabled us to visualize living BM in CAG- enhanced green fluorescent protein (eGFP) mice. By visualizing living bone marrow in vivo, we observed that two modes (fragmentation and proplatelet formation) can be ongoing simultaneously in the same mouse. We observed that these two modes detectable by different morphological behavior can be ongoing simultaneously in the same BM of mouse, and are regulated by specific cytokines. Short proplatelets from megakaryocytes predominated at steady state, and more elongated proplatelets were accelerated by thrombopoietin (TPO) with responding to chronic platelet needs including recovery form BM transplantations. In contrast, acute platelet needs by blood loss, 5-FU administration or pritoneal acute inflammation increased cytoplasmic fragmentation following rapid ‘rupture’. Observed two modes are both dependent on tubulin reorganization on platelet biogenesis. In addition, platelet increase at acute phase is independent of proliferation by MK progenitors and this factor might exert apoptosis machinery on already reserved mature type of MKs. This humoral factor was identified by combination of in vitro screening systems and in vivo MK visualization analysis. Factor serum levels were reduced independently of the thrombopoietin level in human subjects with low platelet counts. It thus appears the cytokine balance dynamically regulates the mode of thrombopoiesis and the cellular programming of MKs. Thus, these novel factor may be a novel therapeutic target in thrombocytopenic situations, especially when associated with acute loss of platelets or when platelet transfusion is limited or unsuccessful. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jackelyn Murray ◽  
Robert J. Hogan ◽  
David E. Martin ◽  
Kathy Blahunka ◽  
Fred D. Sancilio ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Virus Replication ◽  
Mammalian Cells ◽  
Clinical Utility ◽  
Plasma Concentrations ◽  
Hamster Model ◽  
Potential Clinical Utility

AbstractEffective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC90 value are achievable for 24 h following a single oral dose. These data support the potential clinical utility of probenecid to control SARS-CoV-2 infection in humans.

scholarly journals Glycyrrhetinic acid might increase the nephrotoxicity of bakuchiol by inhibiting cytochrome P450 isoenzymes

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2723 ◽  
Author(s):  
Aifang Li ◽  
Nana Ma ◽  
Zijing Zhao ◽  
Mei Yuan ◽  
Hua Li ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Liver Microsomes ◽  
Glycyrrhetinic Acid ◽  
Internal Exposure ◽  
Functional Markers ◽  
Dependent Manner ◽  
Cyp Isoforms

BackgroundLicorice, a popular traditional Chinese medicine (TCM), is widely used to moderate the effects (detoxification) of other herbs in TCM and often combined withFructus Psoraleae. However, the classical TCM book states thatFructus Psoraleaeis incompatible with licorice; the mechanism underlying this incompatibility has not been identified. Glycyrrhetinic acid (GA), the active metabolite of licorice, may increase the toxicity of bakuchiol (BAK), the main chemical ingredient inPsoralea corylifolia, by inhibiting its detoxification enzymes CYP450s.MethodsThe effect of concomitant GA administration on BAK-induced nephrotoxicity was investigated, and the metabolic interaction between BAK and GA was further studied in vitro and in vivo. The cytotoxicity was assessed using an MTT assay in a co-culture model of HK-2 cell and human liver microsomes (HLMs). The effect of GA on the metabolism of BAK, and on the activities of CYP isoforms were investigated in HLMs. The toxicokinetics and tissue exposure of BAK as well as the renal and hepatic functional markers were measured after the administration of a single oral dose in rats.ResultsIn vitrostudies showed that the metabolic detoxification of BAK was significantly reduced by GA, and BAK was toxic to HK-2 cells, as indicated by 25∼40% decreases in viability when combined with GA. Further investigation revealed that GA significantly inhibited the metabolism of BAK in HLMs in a dose-dependent manner. GA strongly inhibits CYP3A4 and weakly inhibits CYP2C9 and CYP1A2; these CYP isoforms are involved in the metabolism of BAK.In vivoexperiment found that a single oral dose of BAK combined with GA or in the presence of 1-aminobenzotriazole (ABT), altered the toxicokinetics of BAK in rats, increased the internal exposure, suppressed the elimination of BAK prototype, and therefore may have enhanced the renal toxicity.ConclusionThe present study demonstrated that GA inhibits CYP isoforms and subsequently may increase the nephrotoxicity of BAK, which underlie one of the possible mechanisms responsible for the incompatibility of Licorice withFructus Psoraleae.

Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives

1983 ◽  
Vol 98 (3) ◽  
pp. 385-389 ◽  
Author(s):  
Francesco Di Carlo ◽  
Elena Gallo ◽  
Giuseppe Conti ◽  
Silvia Racca
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Medroxyprogesterone Acetate ◽  
The Other ◽  
Receptor Interaction ◽  
Oestrogen Receptors ◽  
Rat Uterus ◽  
The Hours

The effects of two progesterone derivatives, namely medroxyprogesterone acetate (MPA) and chlormadinone, and two 19-nor-testosterone derivatives, namely norgestrel and norethisterone, on the binding of oestradiol to its cytoplasmic receptors in the rat uterus were compared. In experiments performed in vivo, the rats were given a single oral dose (15 mg/kg) of one of the four progestins and killed 1, 6, 24 and 48 h later. Norgestrel, norethisterone and MPA induced a prompt and remarkable decrease in oestradiol–receptor interaction 1 h after treatment. This reduction lasted almost unchanged for 24 h in rats treated with MPA or norgestrel, but was much lower in animals given norethisterone. In the hours that followed, the effect of MPA and norgestrel began to decrease, but was still detectable after 48 h, whereas the effect of norethisterone had disappeared by this time. The effect of chlormadinone was much less than that induced by both MPA and norgestrel 1, 6 and 24 h after treatment. On the other hand, this effect was less than that caused by norethisterone 1 h after administration, equal after 6 h and much greater after 24 and 48 h. In experiments performed in vitro, the different ability of the four progestins to interfere with the capacity of oestradiol to bind to its receptors was confirmed. In conclusion, all the synthetic progestins used were able to reduce the binding of oestradiol to its cytoplasmic receptors, although there was a clear difference between the progestins in the intensity and duration of this effect. This could be one of the mechanisms by which progestins modulate the activity of oestrogens in target tissues.

scholarly journals Probenecid Inhibits SARS-CoV-2 Replication In Vivo and In Vitro

2021 ◽  
Author(s):  
Jackelyn Murray ◽  
Robert J. Hogan ◽  
David E. Martin ◽  
Kathy Blahunka ◽  
Fred Sancillo ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Virus Replication ◽  
Mammalian Cells ◽  
Clinical Utility ◽  
Plasma Concentrations ◽  
Hamster Model ◽  
Potential Clinical Utility

Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC90 value are achievable for 24h following a single oral dose. These data support the potential clinical utility of probenecid to control SARS-CoV-2 infection in humans.

scholarly journals 731. Pharmacokinetics of Gepotidacin (GSK2140944) in Subjects with Hepatic Impairment

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S327-S327
Author(s):  
Jonathan T Hands ◽  
Yu Tao ◽  
Courtney Tiffany ◽  
Caroline R Perry ◽  
Etienne Dumont ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Hepatic Impairment ◽  
Geometric Mean ◽  
Hepatic Clearance ◽  
Hepatic Function ◽  
Major Route ◽  
Bacterial Replication

Abstract Background Gepotidacin (GEP), a first in class novel triazaacenaphthylene bacterial topoisomerase inhibitor, inhibits bacterial replication and has in vitro and in vivo efficacy activity against key pathogens, including drug-resistant strains, associated with a range of infections. In a previous absorption, distribution, metabolism, and excretion study for GEP, the mean recovery of radioactivity in urine and feces accounted for approximately 31.2% and 52.5%, respectively, of [14C]-GEP administered as a single oral dose. GEP was eliminated mainly as parent in urine, accounting for approximately 20% of the administered dose. Elimination via metabolism accounted for a total of 13% to 19% of the dose. Average total intravenous clearance of approximately 43 L/hour and renal clearance (CLr) of approximately 16 L/hour provides a hepatic clearance of 27 L/hour, suggesting that hepatic clearance is a major route of elimination of GEP. Methods Participants with normal and varying degrees of hepatic impairment (HI) received a single oral dose of GEP 1,500 mg. PK collections of blood, urine and saliva were performed. Results Relative to normal hepatic function, GEP Cmax and AUC(0-∞) in plasma were increased by 1.2-fold in subjects with moderate, and between 1.7-fold to 1.9-fold in severe HI. The fraction of dose excreted in urine increased with an increase in hepatic impairment. GEP urine concentrations remained high over a 12-hour period. Saliva concentrations displayed a linear relationship with plasma (both total and unbound) concentrations (R2 = 0.76). The geometric mean ratio of saliva AUC to unbound plasma AUC values ranged from 0.746 to 0.839 across all groups. Administration of 1,500 mg oral GEP was generally tolerated. Conclusion An increase in the dosing interval or dose reduction may be required in patients with severe hepatic impairment. Disclosures All authors: No reported disclosures.

Effects of alcoholic extract from Ma-Klua (Diospyros mollis) on adults and larvae of the dwarf tapeworm, Hymenolepis nana in mice and on the infectivity of the eggs

Parasitology ◽  
1983 ◽  
Vol 87 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Jun Maki ◽  
Asami Kondo ◽  
Toshio Yanagisawa
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Drug Administration ◽  
Post Infection ◽  
Alcoholic Extract ◽  
Severe Damage ◽  
Hymenolepis Nana ◽  
Anthelmintic Effect

SUMMARYThe anthelmintic effect of an alcoholic extract from a shrub, Diospyros mollis, popularly known as Ma-Klua in Thailand, on the adults and larvae of the dwarf tapeworm, Hymenolepis nana, in mice was studied in comparison with that of flubendazole. The experimentally infected mice were given a single oral dose of 10–1000 mg of Ma-Klua extract or flu-bendazole/kg body wt 1, 2, 3, 4, or 12 days post-infection and autopsied 14 days post-infection. Ma-Klua extract was effective in the elimination of adults (ED50 = 79 mg/kg) but not larvae. Drastic effects of Ma-Klua extract on the motility and structure of adults were observed and the number of the adults in mice decreased with time after administration of the drug 12 days post-infection. The small numbers of adults remaining in the host intestine 2 days after the drug administration showed severe damage in the gravid segments. These facts were thought to be responsible for the significant reduction in egg output observed 1 and 2 days after medication. Fresh eggs exposed to Ma-Klua extract in vitro and in vivo, or in vivo alone showed reduced infectivity. The effect of flubendazole on adults and larvae was minimal.

Effect of Aspirin on the Thrombelastogram of Human Blood

1973 ◽  
Vol 30 (03) ◽  
pp. 494-498 ◽  
Author(s):  
G de Gaetano ◽  
J Vermylen
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Platelet Function ◽  
Human Blood ◽  
Platelet Rich Plasma ◽  
Plasma Samples ◽  
Release Reaction ◽  
Platelet Release

SummaryThrombelastograms of both native blood and re-calcified platelet-rich plasma samples taken from subjects given a single oral dose of aspirin (1 gram) were not significantly different from the pretreatment recordings. Aspirin also did not modify the thrombelastogram when preincubated in vitro with platelet-rich plasma at concentrations inhibiting the platelet “release reaction” by collagen. Thrombelastography therefore cannot evaluate the effect of aspirin on platelet function.

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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