Peripheral Blood Concentrations of Steroids in Man Aftar Oral Administration of 17-Hydroxycorticosterone.

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

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Pharmacokinetics of the Antimalarial Drug, AQ-13, in Rats and Cynomolgus Macaques

International Journal of Toxicology ◽

10.1080/10915810490471352 ◽

2004 ◽

Vol 23 (3) ◽

pp. 179-189 ◽

Cited By ~ 15

Author(s):

Sandhya Ramanathan-Girish ◽

Paul Catz ◽

Moire R. Creek ◽

Benjamin Wu ◽

David Thomas ◽

...

Keyword(s):

Oral Dose ◽

Oral Administration ◽

Antimalarial Drug ◽

Dose Range ◽

Plasmodium Species ◽

Repeat Dose ◽

Nonlinear Kinetics ◽

Dose Administration ◽

Blood Concentrations ◽

Cynomolgus Macaques

The purpose of this study was to evaluate the bioavailability and pharmacokinetics of a new antimalarial drug, AQ-13, a structural analog of chloroquine (CQ) that is active against CQ-resistant Plasmodium species, in rats and cynomolgus macaques. Sprague-Dawley rats ( n = 4 /sex) were administered a single dose of AQ-13 intravenously (i.v.) (10 mg/kg) or orally (20 or 102 mg/kg). Blood and plasma samples were collected at several timepoints. AQ-13 achieved Cmax after oral administration at approximately 3 to 4 h and could be detected in blood for 2 to 5 days after oral administration. The ratio of area under the curve (AUC) values at the high and low dose for AQ-13 deviated from an expected ratio of 5.0, indicating nonlinear kinetics. A metabolite peak was noted in the chromatograms that was identified as monodesethyl AQ-13. Oral bioavailability of AQ-13 was good, approximately 70%. The pharmacokinetics of AQ-13 was also determined in cynomolgus macaques after single (i.v., 10 mg/kg; oral, 20 or 100 mg/kg) and multiple doses (oral loading dose of 50, 100, or 200 mg/kg on first day followed by oral maintenance dose of 25, 50, or 100 mg/kg, respectively, for 6 days). The AUC and Cmax values following single oral dose administration were not dose proportional; the Cmax value for AQ-13 was 15-fold higher following an oral dose of 100 mg/kg compared to 20 mg/kg. MonodesethylAQ-13 was a significant metabolite formed by cynomolgus macaques and the corresponding Cmax values for this metabolite increased only 3.8-fold over the dose range, suggesting that the formation of monodesethyl AQ-13 is saturable in this species. The bioavailability of AQ-13 in cynomolgus macaques following oral administration was 23.8% for the 20-mg/kg group and 47.6% for the 100-mg/kg group. Following repeat dose administration, high concentrations of monodesethyl AQ-13 were observed in the blood by day 4, exceeding the AQ-13 blood concentrations through day 22. Saturation of metabolic pathways and reduced metabolite elimination after higher doses are suggested to play a key role in AQ-13 pharmacokinetics in macaques. In summary, the pharmacokinetic profile and metabolism ofAQ-13 are very similar to that reported in the literature for chloroquine, suggesting that this new agent is a promising candidate for further development for the treatment of chloroquine-resistant malaria.

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Methadone, Buprenorphine, Oxycodone, Fentanyl, and Tramadol in Multiple Postmortem Matrices

Journal of Analytical Toxicology ◽

10.1093/jat/bkab071 ◽

2021 ◽

Author(s):

Stine Marie Havig ◽

Vigdis Vindenes ◽

Åse Marit Leere Øiestad ◽

Sidsel Rogde ◽

Cecilie Hasselø Thaulow

Keyword(s):

Peripheral Blood ◽

Vitreous Humor ◽

Pericardial Fluid ◽

Limited Information ◽

Blood Concentrations ◽

Bodily Fluids ◽

Drug Concentrations ◽

Quantitative Analyses ◽

Alternative Matrices ◽

Almost All

Abstract Peripheral blood concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid, muscle, and vitreous humor have been suggested as alternatives to blood, but only a few studies have investigated the detection of opioids in these matrices. In this study, we aimed to investigate the detection of methadone, buprenorphine, oxycodone, fentanyl, and tramadol in postmortem samples of pericardial fluid, skeletal muscle, and vitreous humor, in addition to peripheral and cardiac blood; and if drug concentrations in these alternative matrices were comparable to those in peripheral blood, and thereby useful for interpretation. In most of the 54 included cases, only one opioid was detected. Methadone, oxycodone, fentanyl, and tramadol were detected in all of the alternative matrices in almost all cases, while buprenorphine was detected less often. For methadone, the concentrations in the alternative matrices, except for in vitreous humor, were relatively similar to those in peripheral blood. Larger variations in concentrations were found for buprenorphine, oxycodone, and tramadol. Quantitative analyses appeared useful for fentanyl, in all of the alternative matrices, but only four cases were included. Toxicological analyses of opioids in these alternative postmortem matrices can be useful for detection, but interpretation of quantitative results must be performed with caution.

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“The Effect of Obstructive Sleep Apnea on Peripheral Blood Amino Acid and Biogenic Amine Metabolome at Multiple Time Points Overnight“

10.21203/rs.3.rs-119577/v1 ◽

2020 ◽

Author(s):

Ott Kiens ◽

Egon Taalberg ◽

Viktoria Ivanova ◽

Ketlin Veeväli ◽

Triin Laurits ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Amino Acid ◽

Sleep Apnea ◽

Biogenic Amines ◽

Peripheral Blood ◽

Apnea Hypopnea Index ◽

Multiple Time ◽

Blood Concentrations ◽

Time Points ◽

Obstructive Sleep

Abstract There are no clinical studies that have investigated the differences in blood serum metabolome between obstructive sleep apnea (OSA) patients and controls. In a single-center prospective observational study, we compared metabolomic profiles in the peripheral blood of OSA patients with apnea-hypopnea index (AHI) > 15/h and control individuals. Blood was obtained at 3 different time points overnight: 21:00 p.m.; 5:00 a.m. and 7:00 a.m. We used a targeted approach for detecting amino acids and biogenic amines and analyzed the data with ranked general linear model for repeated measures. We recruited 31 patients with moderate-to-severe OSA and 32 controls. Significant elevations in median concentrations of alanine, proline and kynurenine in OSA patients compared to controls were detected. Significant changes in the overnight dynamics of peripheral blood concentrations occurred in OSA: glutamine, serine, threonine, tryptophan, kynurenine and glycine levels increased, whereas a fall occurred in the same biomarker levels in controls. Phenylalanine and proline levels decreased slightly, compared to a steeper fall in controls. The study indicates that serum profiles of amino acid and biogenic amines are significantly altered in patients with OSA referring to vast pathophysiologic shifts reflected in the systemic metabolism.

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Effect of plasma concentrations of ovarian steroids on their passage into uterine lumen in rabbits

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.6.e654 ◽

1986 ◽

Vol 251 (6) ◽

pp. E654-E659

Author(s):

H. Eiler

Keyword(s):

Transfer Process ◽

Peripheral Blood ◽

Plasma Concentrations ◽

Selective Inhibition ◽

Blood Concentrations ◽

Ovarian Steroids ◽

Uterine Lumen ◽

Uterine Flushing ◽

Significant Increment

Significant increment of blood-borne ovarian steroids are found in the uterine lumen 1 h after mating. Is the transfer of ovarian steroids into the uterus determined by the peripheral blood concentrations of the ovarian steroids? To answer this question, rabbits, ovariectomized 24 h earlier, were infused over a 1-h period with either estradiol (E2; 0.7 and 7.0 micrograms/h), progesterone (P4; 74 and 740 micrograms/h), or testosterone (T; 0.45 and 4.5 micrograms/h). E2, P4, and T were determined in the tissue and flushings of the uterus and tissue and flushings of the esophagus and plasma. A different group of rabbits was infused with E2 (0.7 micrograms), P4 (74 micrograms), and T (0.45 microgram/h) combined. The increase in plasma steroid concentration after infusion of either E2, P4, or T was reflected in an elevation of these steroids in the uterine lumen, albeit not in the same ratios as found in plasma. The simultaneous infusion of E2, P4, and T blocked completely the passage of T and decreased (P less than 0.05) the passage of E2 into the lumen of the uterus. Treatments did not affect the steroid concentration in the wall of the uterus. It was concluded that the content of E2, P4, or T in the uterine flushing increased when E2, P4, or T was infused individually. However, when these steroids were infused together, there was selective inhibition of the transfer process.

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P. falciparum gametocyte density and infectivity in peripheral blood and skin tissue of naturally infected parasite carriers

10.1101/803296 ◽

2019 ◽

Cited By ~ 1

Author(s):

Elamaran Meibalan ◽

Aissata Barry ◽

Matthew P. Gibbins ◽

Shehu Awandu ◽

Lisette Meerstein-Kessel ◽

...

Keyword(s):

Malaria Elimination ◽

Peripheral Blood ◽

Venous Blood ◽

Asexual Parasite ◽

Gametocyte Density ◽

Blood Concentrations ◽

Transmission Potential ◽

Finger Prick ◽

Skin Biopsies ◽

Two Populations

ABSTRACTTransmission of Plasmodium falciparum depends on the presence of mature gametocytes that can be ingested by mosquitoes taking a bloodmeal when feeding on human skin. It has long been hypothesised that skin sequestration contributes to efficient transmission. Although skin sequestration would have major implications for our understanding of transmission biology and the suitability of mosquito feeding methodologies to measure the human infectious reservoir, it has never been formally tested. In two populations of naturally infected gametocyte carriers from Burkina Faso, we assessed transmission potential to mosquitoes and directly quantified male and female gametocytes and asexual parasites in: i) finger prick blood, ii) venous blood, iii) skin biopsies, and in pools of mosquitoes that fed iv) on venous blood or, v) directly on the skin. Whilst more mosquitoes became infected when feeding directly on the skin compared to venous blood, concentrations of gametocytes in the subdermal skin vasculature were identical to that in other blood compartments. Asexual parasite densities, gametocyte densities and sex ratios were identical in the mosquito blood meals taken directly from the skin of parasite carriers and their venous blood.We also observed sparse gametocytes in skin biopsies from legs and arms of gametocyte carriers by microscopy. Taken together, we provide conclusive evidence for the absence of significant skin sequestration of P. falciparum gametocytes. Gametocyte densities in peripheral blood are thus informative for predicting onward transmission potential to mosquitoes. Quantifying this human malaria transmission potential is of pivotal importance for the deployment and monitoring of malaria elimination initiatives.IMPORTANCEOur observations settle a long-standing question in the malaria field and close a major knowledge gap in the parasite cycle. By deploying mosquito feeding experiments and stage-specific molecular and immunofluorescence parasite detection methodologies in two populations of naturally infected parasite carriers, we conclusively reject the hypothesis of gametocyte skin sequestration. Our findings provide novel insights in parasite stage composition in human blood compartments, mosquito bloodmeals and their implications for transmission potential. We demonstrate that gametocyte levels in venous or finger prick blood can be used to predict onward transmission potential to mosquitoes. Our findings thus pave the way for methodologies to quantify the human infectious reservoir based on conventional blood sampling approaches to support the deployment and monitoring of malaria elimination efforts for maximum public health impact.

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EFFECT OF OIL CONTAINING n-3 POLYUNSATURATED FATTY ACIDS (PUFA) ON THE IMMUNE RESPONSE AND GROWTH FACTORS IN PIGLETS

Acta Veterinaria Hungarica ◽

10.1556/avet.47.1999.3.6 ◽

1999 ◽

Vol 47 (3) ◽

pp. 325-334 ◽

Cited By ~ 4

Author(s):

Viera Revajová ◽

D. Magic ◽

M. Levkut ◽

Ĺ. Bindas ◽

M. Horváth ◽

...

Keyword(s):

Fatty Acids ◽

Immune Response ◽

Growth Factors ◽

Oral Administration ◽

Polyunsaturated Fatty Acids ◽

Metabolic Activity ◽

Peripheral Blood ◽

Inflammatory Processes ◽

The Individual ◽

Experimental Group

Oral administration of n-3 polyunsaturated fatty acids (PUFA) to piglets slightly enhances the immune response. As compared to the control, in the experimental piglets the absolute values of monocytes in the peripheral blood were significantly increased (P < 0.05), while the metabolic activity of phagocytes and the number of lymphocytes within the individual subpopulations were slightly higher. The level of growth factors, determined on the basis of somatomedin in the blood serum, was significantly higher in the experimental group (P < 0.05). n-3 PUFA interfere with the synthesis of prostaglandins and influence the metabolism of fatty acids. This finding may contribute to the therapy of inflammatory processes influencing immune and growth factors in piglets.

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Pediatric Xylose Absorption Test: Measurements in Blood Preferable to Measurements in Urine

Clinical Chemistry ◽

10.1093/clinchem/16.9.749 ◽

1970 ◽

Vol 16 (9) ◽

pp. 749-752 ◽

Cited By ~ 27

Author(s):

K I Hawkins

Keyword(s):

Celiac Disease ◽

Oral Administration ◽

Urinary Excretion ◽

Diagnostic Tool ◽

Older Patients ◽

Pediatric Patients ◽

Age Difference ◽

Absorption Test ◽

Blood Concentrations ◽

Lower Limits

Abstract Data from 129 pediatric patients given oral xylose tolerance tests were reviewed and statistically analyzed to determine if blood concentrations are a more acceptable diagnostic tool than urinary excretion. After oral administration of D-(+)-xylose, blood xylose concentrations were measured at 0.5, 1, 2, 3, and 4 h, and a 5-h urine sample was analyzed. Urinary xylose excretion was more variable than blood concentration. The best criterion of celiac disease through blood sampling is a failure of blood xylose to increase during the first hour of the test. An age difference was observed but appears to be critical only if the patient is less than six months old: the lower limits of normal as determined at 0.5, 1, and 2 h are 10, 15, and 15 mg/100 ml, respectively, for patients less than six months old; and 15, 20, and 20 mg/100 ml, respectively, for older patients.

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