Editorial for “Short‐Term Repeatability of In Vivo Cardiac Intravoxel Incoherent Motion ( IVIM ) Tensor Imaging in Healthy Human Volunteers”

2021 ◽  
Author(s):  
Yuxiang Zhou ◽  
Clinton E. Jokerst ◽  
Anshuman Panda
Keyword(s):  
Intravoxel Incoherent Motion ◽  
Short Term ◽  
Healthy Human ◽  
Human Volunteers

Short‐Term Repeatability of in Vivo Cardiac Intravoxel Incoherent Motion Tensor Imaging in Healthy Human Volunteers

2021 ◽  
Author(s):  
Xiu‐Shi Zhang ◽  
En‐Hui Liu ◽  
Xin‐Yu Wang ◽  
Xin‐Xiang Zhou ◽  
Hong‐Xia Zhang ◽  
...  
Keyword(s):  
Intravoxel Incoherent Motion ◽  
Short Term ◽  
Healthy Human ◽  
Human Volunteers

scholarly journals Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Duuamene Nyimanu ◽  
Richard G. Kay ◽  
Petra Sulentic ◽  
Rhoda E. Kuc ◽  
Philip Ambery ◽  
...  
Keyword(s):  
Guanidine Hydrochloride ◽  
Healthy Human ◽  
Highly Sensitive ◽  
Human Volunteers ◽  
Reproducible Method ◽  
Human Cardiovascular System ◽  
Cardiovascular Therapeutics ◽  
Development And Validation ◽  
Detection And Quantification

Abstract[Pyr1]apelin-13 is the predominant apelin peptide isoform in the human cardiovascular system and plasma. To date, few studies have investigated [Pyr1]apelin-13 metabolism in vivo in rats with no studies examining its stability in humans. We therefore aimed to develop an LC-MS/MS method for detection and quantification of intact [Pyr1]apelin-13 and have used this method to identify the metabolites generated in vivo in humans. [Pyr1]apelin-13 (135 nmol/min) was infused into six healthy human volunteers for 120 minutes and blood collected at time 0 and 120 minutes after infusion. Plasma was extracted in the presence of guanidine hydrochloride and analysed by LC-MS/MS. Here we report a highly sensitive, robust and reproducible method for quantification of intact [Pyr1]apelin-13 and its metabolites in human plasma. Using this method, we showed that the circulating concentration of intact peptide was 58.3 ± 10.5 ng/ml after 120 minutes infusion. We demonstrated for the first time that in humans, [Pyr1]apelin-13 was cleaved from both termini but the C-terminal was more susceptible to cleavage. Consequently, of the metabolites identified, [Pyr1]apelin-13(1–12), [Pyr1]apelin-13(1–10) and [Pyr1]apelin-13(1–6) were the most abundant. These data suggest that apelin peptides designed for use as cardiovascular therapeutics, should include modifications that minimise C-terminal cleavage.

scholarly journals ABT-378, a Highly Potent Inhibitor of the Human Immunodeficiency Virus Protease

1998 ◽  
Vol 42 (12) ◽  
pp. 3218-3224 ◽  
Author(s):  
Hing L. Sham ◽  
Dale J. Kempf ◽  
Akhteruzammen Molla ◽  
Kennan C. Marsh ◽  
Gondi N. Kumar ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Response To Therapy ◽  
Hiv Protease ◽  
Healthy Human ◽  
Human Volunteers ◽  
Immunodeficiency Virus ◽  
Potent Protease Inhibitor

ABSTRACT The valine at position 82 (Val 82) in the active site of the human immunodeficiency virus (HIV) protease mutates in response to therapy with the protease inhibitor ritonavir. By using the X-ray crystal structure of the complex of HIV protease and ritonavir, the potent protease inhibitor ABT-378, which has a diminished interaction with Val 82, was designed. ABT-378 potently inhibited wild-type and mutant HIV protease (Ki = 1.3 to 3.6 pM), blocked the replication of laboratory and clinical strains of HIV type 1 (50% effective concentration [EC50], 0.006 to 0.017 μM), and maintained high potency against mutant HIV selected by ritonavir in vivo (EC50, ≤0.06 μM). The metabolism of ABT-378 was strongly inhibited by ritonavir in vitro. Consequently, following concomitant oral administration of ABT-378 and ritonavir, the concentrations of ABT-378 in rat, dog, and monkey plasma exceeded the in vitro antiviral EC50 in the presence of human serum by >50-fold after 8 h. In healthy human volunteers, coadministration of a single 400-mg dose of ABT-378 with 50 mg of ritonavir enhanced the area under the concentration curve of ABT-378 in plasma by 77-fold over that observed after dosing with ABT-378 alone, and mean concentrations of ABT-378 exceeded the EC50 for >24 h. These results demonstrate the potential utility of ABT-378 as a therapeutic intervention against AIDS.

scholarly journals Comparative Bioavailabilitv Studv of Two Brands of Terbutaline Sulphate Tablets in Healthy Human Volunteers

2004 ◽  
Vol 72 (3) ◽  
pp. 227-237
Author(s):  
Nahla S. Barakat ◽  
Nawal M. Khalafallah ◽  
Said A. Khalil
Keyword(s):  
Single Dose ◽  
Reference Product ◽  
Hplc Method ◽  
Fasting State ◽  
Unchanged Drug ◽  
Healthy Human ◽  
Terbutaline Sulphate ◽  
Human Volunteers

The purpose of this study was to evaluate the bioavailability of locally produced 2.5 mg terbutaline sulphate tablets (brand A ) relative to a reference product, Bricanyl 2.5 mg tablets (brand 6). The study was a single dose 5 mg randomized crossover one in 15 healthy volunteers in the fasting state. Urine was collected at intervals of 24 h. Total terbutaline excreted in urine as unchanged drug and as conjugates (sulphate and glucuronide) was determined by a developed and validated HPLC method. In-vitro characteristics of both brands were similar. Based on percent of the dose excreted in urine, the oral bioavailability ranged from 33.5% to 75.8% for both brands. Statistics were applied to judge bioequivalence according to USP 24 in-vivo bioequivalence guidance. Results indicated that brand A and B were bioequivalent and hence interchangeable in medical practice.

Role of prebiotics and probiotics in oral health

2018 ◽  
Vol 48 (1) ◽  
pp. 16-29 ◽  
Author(s):  
Richard Frank Tester ◽  
Farage H. Al-Ghazzewi
Keyword(s):  
Oral Care ◽  
The Body ◽  
In Vivo Studies ◽  
Gut Health ◽  
Healthy Human ◽  
Content Type ◽  
Human Volunteers ◽  
Health Related

Purpose This paper aims to focus on the utilisation of pre- and probiotics for oral care and the state of knowledge at this time. Design/methodology/approach Pre- and probiotics describe beneficial carbohydrates and microbiota, respectively, for optimal gut health. Carbohydrates provide energy selectively for the gut-friendly bacteria. The use of both carbohydrates and bacteria is, however, being expanded into other areas of the body – including the skin, vagina and oral cavity – for health-related applications. Findings There is increased interest in both pre- and probiotics for oral care products. The importance of oral microflora and their selective substrates is discussed against a background of contemporary oral care approaches. The issues and benefits are discussed in this review. Originality/value It is clear that consumption of prebiotics and probiotics may play a role as potential prophylactic or therapeutic agents for reducing the presence of organisms in the mouth associated with tooth decay. To confirm a beneficial effect of pre- and probiotics further in vivo studies involving healthy human volunteers should be considered.

In vivo generation of human dendritic cell subsets by Flt3 ligand

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 878-884 ◽  
Author(s):  
Eugene Maraskovsky ◽  
Elizabeth Daro ◽  
Eileen Roux ◽  
Mark Teepe ◽  
Charlie R. Maliszewski ◽  
...  
Keyword(s):  
T Cell Immunity ◽  
Human Dendritic Cell ◽  
Flt3 Ligand ◽  
Healthy Human ◽  
Cell Immunity ◽  
Human Volunteers ◽  
Immune Response Regulation ◽  
Dendritic Cell Subsets

Abstract Dendritic cells (DCs) represent a family of ontogenically distinct leukocytes involved in immune response regulation. The ability of DCs to stimulate T-cell immunity has led to their use as vectors for immunotherapy vaccines. However, it is unclear whether and to what degree in vitro–generated DCs are representative of DCs that develop in vivo. Treatment of mice with human Flt3 ligand (FL) dramatically increases the number of DCs. We report here that administration of FL to healthy human volunteers increased the number of circulating CD11c+ IL-3Rlow DC (mean 44-fold) and CD11c− IL-3Rhigh DC precursors (mean 12-fold). Moreover, the CD11c+ DCs were efficient stimulators of T cells in vitro. Thus, FL can expand the number of circulating, functionally competent human DCs in vivo.

scholarly journals The in vivo use of the stable isotope-labelled biomarkers lactose-[15N]ureide and [2H4]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers

2004 ◽  
Vol 92 (3) ◽  
pp. 439-446 ◽  
Author(s):  
V. De Preter ◽  
K. Geboes ◽  
K. Verbrugghe ◽  
L. De Vuyst ◽  
T. Vanhoutte ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Lactobacillus Casei ◽  
Functional Foods ◽  
Direct Evidence ◽  
Intestinal Flora ◽  
Healthy Human ◽  
Beneficial Effects ◽  
Potential Biomarker ◽  
Human Volunteers

Amongst the various claimed beneficial effects of pro- and prebiotics for the human host, it has been hypothesised that functional foods are able to suppress the generation and accumulation of toxic fermentation metabolites (NH3, p-cresol). Direct evidence supporting this hypothesis is lacking mainly because of the unavailability of reliable biomarkers. Preliminary data indicate that lactose-[15N]ureide and [2H4]tyrosine may be potential biomarker candidates. The aim of the present study was to evaluate the effect of pro- and prebiotics on the colonic fate of these biomarkers in a randomised, placebo-controlled, cross-over study with nineteen healthy volunteers. At the start of the study and at the end of each 2-week study period, during which they were administered either a probiotic (n 10; 6·5×109Lactobacillus casei Shirota cells twice daily) or a prebiotic (n 9; lactulose 10 g twice daily), the volunteers consumed a test meal containing the two biomarkers. Urine was collected during 48 h. Results were expressed as percentage of the administered dose. As compared with the placebo, the decrease in the percentage dose of p-[2H4]cresol in the 24–48 h urine fraction was significantly higher after probiotic intake (P=0·042). Similar changes were observed for the 15N tracer (P=0·016). After prebiotic intake, a significantly higher decrease in the percentage dose of p-[2H4]cresol (P=0·005) and 15N tracer (P=0·029) was found in the 0–24 h urine collection. The present results demonstrate that suppression of the generation and accumulation of potentially toxic fermentation metabolites by pro- and prebiotics can reliably be monitored in vivo by the use of stable isotope-labelled biomarkers.

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