The Incorporation of [4-14C] δ-Aminolaevulic Acid into Urinary Porphyrins in Symptomatic Porphyria

1970 ◽  
Vol 39 (2) ◽  
pp. 159-168 ◽  
Author(s):  
P. Goldswain ◽  
E. Dowdle ◽  
Norma Spong ◽  
L. Eales
Keyword(s):  
Oral Dose ◽  
Control Subject ◽  
Single Oral Dose ◽  
Metabolic Pathways ◽  
Specific Activity ◽  
Specific Activities ◽  
Urinary Porphyrins

1. The specific activities of urinary uroporphyrin and coproporphyrin were measured as functions of time following the administration of a single oral dose of [4-14C] δ-aminolaevulic acid (ALA) to six patients with symptomatic porphyria and one control subject. 2. The peak specific activity of coproporphyrin preceded that of uroporphyrin in all subjects studied and exceeded that of uroporphyrin in the patients with symptomatic porphyria. 3. These results are interpreted as indicating the existence of two distinct metabolic pathways in the liver for the disposal of ALA, rather than as contradicting the generally accepted role of uroporphyrinogen as a precursor of coproporphyrinogen.

scholarly journals Role of Phosphodiesterase Inhibitors in Improving Urodynamic Parameters in Patients with Spinal Cord Injury: A Preliminary Report

2020 ◽  
Vol 09 (01) ◽  
pp. 30-34
Author(s):  
Muzzain Iqbal ◽  
Sarbjit Singh Chhiber ◽  
Baldev Singh Wazir ◽  
Altaf Umar Ramzan ◽  
Mohammad Saleem Wani
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Bladder Capacity ◽  
Final Conclusion ◽  
Bladder Compliance ◽  
Cord Injury ◽  
Urodynamic Parameters

Abstract Objective To analyze role of phosphodiesterase 5 (PDE5) inhibitors on urodynamic parameters in patients with suprasacral spinal cord injury. Materials and Methods This was a prospective observational hospital-based study conducted on a cohort of patients, aged between 18 and 65 years with suprasacral spinal cord injury, who were registered in Department of Neurosurgery/Urology. Cutoff period since injury was 2 years. After taking consent, baseline urodynamic study was performed, which was repeated 2 hours after taking single oral dose of 20 mg tadalafil. Urodynamic parameters such as maximum detrusor filling/voiding pressures, maximum bladder capacity, and bladder compliance before and after taking drug were compared for final results and conclusion. Results Following administration of 20 mg of tadalafil, maximum bladder capacity in mL showed statistically significant improvement from 268.39 ± 130.0 to 298.55 ± 112.0.(p < 0.05). Bladder compliance improved from 18.68 ± 6.4 to 20.25 ± 7.5 mL/cm H2O (p > 0.05). Maximum detrusor filling pressure improved from 36.03 ± 20.54 to 32.90 ± 16.47 cm H2O (p > 0.05). Maximum detrusor voiding pressure improved from 64.65 ± 33.19 to 58.13 ± 20.7 cm H2O (0 > 0.05). In patients with injury above D6 spinal cord level, statistically significant improvement was seen in maximum bladder capacity and bladder compliance after 2 hours of single oral dose of tadalafil (p < 0.05). Conclusion Our study suggests a positive role of PDE inhibitors in improving urodynamic parameters in patients with suprasacral spinal cord injury with improvement in parameters such as bladder capacity, detrusor pressures, and bladder compliance. Because this is a small study group, more studies such as this are required to reach to final conclusion.

Unequal Absorption of Radiolabeled and Nonradiolabeled Drug from the Oral Dose Leads to Incorrect Estimates of Drug Absorption and Circulating Metabolites in a Mass Balance Study

2019 ◽  
Vol 13 (1) ◽  
pp. 37-44
Author(s):  
Ryan H. Takahashi ◽  
Jae H. Chang ◽  
Jodie Pang ◽  
Xiaorong Liang ◽  
Shuguang Ma
Keyword(s):  
Oral Dose ◽  
Mass Balance ◽  
Specific Activity ◽  
The Body ◽  
Total Drug ◽  
Beagle Dogs ◽  
Balance Study ◽  
Drug Concentrations ◽  
Specific Activities ◽  
Mass Balance Study

Background: Mass balance studies conducted using radiolabeled material (14C or 3H) definitively characterize the Absorption, Metabolism, and Excretion (AME) of a drug. A critical aspect of these studies is that the radiotracer maintains its proportion to total drug from its administration to its complete elimination from the body. In the study of GDC-0276 in beagle dogs, we observed that the 14C radiotracer proportion (specific activity) varied through the study. Method: High resolution-accurate mass spectrometric measurements of 12C and 14C isotopes of GDC- 0276 and its metabolites in plasma and excreta samples were used to determine the apparent specific activities, which were higher than the specific activity of the dosing formulation. Drug concentrations were adjusted to the observed specific activities to correct the readouts for GDC-0276 AME and PK. Results: The enrichment of 14C, which resulted in higher specific activities, was consistent with faster and more extensive absorption of the radiotracer from the dosing formulation. This resulted in overestimating the dose absorbed, the extent of elimination in urine and bile, and the exposures to circulating metabolites. These biases were corrected by the specific activities determined for study samples by mass spectrometry. Conclusion: Assuming that the radiotracer was proportional to total drug throughout a radiolabeled study was not valid in a 14C study in beagle dogs. This presumably resulted from unequal absorption of the radiotracer and nonradiolabeled test articles from the oral dose due to inequivalent solid forms. We were able to provide a more accurate description of the AME of GDC-0276 in dogs by characterizing the differential absorption of the radiotracer.

Phenylalanine metabolism in control subjects, mental patients, and phenylketonurics

1962 ◽  
Vol 17 (6) ◽  
pp. 985-992 ◽  
Author(s):  
William Sacks
Keyword(s):  
Control Subject ◽  
Whole Blood ◽  
Specific Activity ◽  
Normal Subjects ◽  
Activity Ratios ◽  
Normal Humans ◽  
Phenylalanine Metabolism ◽  
Specific Activities ◽  
A Minor ◽  
Carboxyl Carbon

After injection of dl-phenylalanine-1-C14 or l-phenylalanine-1-C14, C14O2 specific activities in whole blood were frac15–frac13 as high as those after injection of dl-tyrosine-1-C14 or l-tyrosine-1-C14 in normal subjects and chronic psychotic patients. In phenylalanine-C14 studies, tyrosine specific activities were 1/16–1/10 of corresponding phenylalanine specific activities. After injection of l-phenylalanine-1-C14 into two phenylketonuric (PKU) patients, C14O2 activities in one, a child, approximated those in other experiments, whereas they were lower in the adult PKU-patient. Maximal tyrosine specific activity (adult PKU patient) was frac16 the corresponding phenylalanine specific activity. Ratios of specific activities of maximal C14O2 to phenylalanine were similar in the control subject and PKU patient, suggesting that catabolism of phenylalanine proceeds at the same rate in phenylketonuria. Results with l-phenylalanine-U-C14 indicated that more than the carboxyl carbon contributed to blood 14O2. The data suggest that hydroxylation of phenylalanine to form tyrosine may be a minor pathway in intermediary metabolism of phenylalanine in normal humans and in chronic psychotic and phenylketonuric patients. Submitted on April 11, 1962

Glucose metabolism in the lactating beagle dog

1962 ◽  
Vol 202 (2) ◽  
pp. 329-333 ◽  
Author(s):  
Jack R. Luick ◽  
Arthur L. Black ◽  
Harold R. Parker ◽  
Mogens G. Simesen
Keyword(s):  
Plasma Glucose ◽  
Metabolic Pathways ◽  
Milk Fat ◽  
Specific Activity ◽  
Energy Requirement ◽  
Similar Data ◽  
Lactating Cows ◽  
Diabetic Dog ◽  
Oxidation Of Glucose

A study was made of the role of glucose as an oxidizable substrate and as a source of C for the synthesis of milk using lactating beagle dogs. Uniformly C14-labeled glucose was used as a tracer of these metabolic pathways. Our data indicate that the labeled glucose was completely eliminated from the dog's body within 24 hr after injection. Sixty percent of the injected dose appeared in the expired CO2, 40% in the various milk products. Comparison of the integrated specific activity of plasma glucose with that of expired CO2 indicates that 36% of the dog's energy requirement is met by the oxidation of glucose. This presumably means that the catabolism of noncarbohydrate substances must be of considerable importance to the energy metabolism of not only the fasted dog and the diabetic dog, as has been demonstrated earlier, but also of the fed dog. We have also shown that 68–100% of the C required for the synthesis of lactose is derived from plasma glucose. In addition, plasma glucose contributes 7.2–12% of milk protein C and 5.1–8.7% of milk fat C. These results are compared with similar data obtained earlier in our laboratory using lactating cows and sows.

Detection of protein disulphide-isomerase in sheep pancreas fractions

1982 ◽  
Vol 2 (5) ◽  
pp. 343-349 ◽  
Author(s):  
David A. Hillson ◽  
Jacqueline Anderson
Keyword(s):  
Specific Activity ◽  
Protein Biosynthesis ◽  
Major Site ◽  
General Role ◽  
Protein Disulphide Isomerase ◽  
Isomerase Activity ◽  
Liver Homogenates ◽  
Specific Activities

Conclusions The use of diethylpyrocarbonate to inhibit endogenous ribonuclease in sheep pancreas allows the detection of protein-disulphide-isomerase activity in homogenates, at specific activities of up to 4 units/g. This is higher than the specific activity in sheep liver homogenates (about 2 units/g) or in homogenates of other sheep tissues (16). It is thus evident that high levels of protein-disulphide-isomerase activity are present in sheep pancreas. This is consistent both with the postulated general role of protein disulphide-isomerase in protein biosynthesis (10,11) and with the in vitro action of the enzyme on its conventional substrate scrambled ribonuclease, since pancreas is the major site of ribonuclease synthesis.

scholarly journals Oxidative Metabolism in ‘Valencia’ Sweet Orange (Citrus sinensis Osbeck) Abscission Zone Tissue Treated with the Abscission Agent 5-Chloro-3-Methyl-4-Nitro-1H-Pyrazole

HortScience ◽  
2016 ◽  
Vol 51 (4) ◽  
pp. 377-382 ◽  
Author(s):  
Naveen Kumar ◽  
Robert C. Ebel
Keyword(s):  
Oxidative Metabolism ◽  
Indole Acetic Acid ◽  
Specific Activity ◽  
Sweet Orange ◽  
Malonic Dialdehyde ◽  
Citrus Fruit ◽  
Abscission Zone ◽  
Specific Activities ◽  
Orange Trees

5-Chloro-3-methyl-4-nitro-1H-pyrazole (CMNP) is an abscission agent, standardized for the mechanical harvesting of late season ‘Valencia’ sweet oranges in Florida. This work was conducted to investigate the role of CMNP to induce oxidative stress in the abscission zone (AZ) of ‘Valencia’ sweet orange. Fully mature ‘Valencia’ sweet orange trees in a commercial grove were sprayed with 2.0 mm of CMNP. The experiment was repeated three times during the Apr.–May 2013 harvest season. Fruit were harvested at 0, 1, 2, and 3 days after CMNP application. Hydrogen peroxide (H2O2) concentration and malonic dialdehyde (MDA) concentration, as well as superoxide dismutase (SOD), ascorbate peroxidase (APOD), glutathione reductase (GR), peroxidase (POD), and lipoxygenase (LOX) specific activities were measured 0, 1, 2, and 3 days after CMNP treatment (DAT). Rate of lipid peroxidation remains unchanged throughout the abscission period. However, LOX activity increased 1 DAT in AZ of treated fruit, which might produce jasmonic acid (JA), known to promote abscission in citrus. Levels of H2O2 were similar in the AZ of control and treated fruit except at 3 DAT. The specific activity of SOD declined at 2 DAT, which showed compromised SOD defense against superoxide radicals (O·−). APOD activity declined sharply at 3 DAT. Interestingly, GR activity was 1.9-fold higher in CMNP-treated fruit at 3 DAT. Higher GR and low APOD activity reflects limited functioning of the APOD/GR cycle (e.g., APOD and GR) in scavenging of H2O2 at 3 DAT. Guaiacol POD activity transiently increased at 1 DAT and then declined. POD plays an important role in cell wall lignification and indole acetic acid (IAA) oxidation. The decline in POD activity may cause a decrease in lignification while higher activity made the AZ sensitive to ethylene and thus promote abscission in citrus fruit. This work also showed that CMNP-induced abscission is a collaborative effort of oxidative metabolism in flavedo tissue (FT) and AZ.

scholarly journals Role of GLP-1 in the Hypoglycemic Effects of Wild Bitter Gourd

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ting-ni Huang ◽  
Kan-Ni Lu ◽  
Yi-Ping Pai ◽  
Chin Hsu ◽  
Ching-jang Huang
Keyword(s):  
Oral Dose ◽  
Glucose Tolerance ◽  
Single Oral Dose ◽  
Bitter Taste ◽  
Taste Receptor ◽  
Water Extract ◽  
Bitter Gourd ◽  
Oral Glucose ◽  
Insulinogenic Index

This study aimed to examine the role of GLP-1 in the hypoglycemic activity of wild bitter gourd (Momordica charantiaL., BG). In vitro, the GLP-1 secretion in STC-1, a murine enteroendocrine cell line, was dose dependently stimulated by water extract (WE), its fractions (WEL, >3 kD and WES, <3 kD), and a bitter compounds-rich fraction of BG. These stimulations were partially inhibited by probenecid, a bitter taste receptor inhibitor, and by U-73122, a phospholipase Cβ2 inhibitor. These results suggested that the stimulation might involve, at least in part, certain bitter taste receptors and/or PLCβ2-signaling pathway. Two cucurbitane triterpenoids isolated from BG, 19-nor-cucurbita-5(10),6,8,22-(E),24-pentaen-3β-ol, and 5β,19-epoxycucurbita-6,24-diene-3β,23ξ-diol (karavilagenine E,) showed relative high efficacy in the stimulation. In vivo, mice fed BG diet showed higher insulinogenic index in an oral glucose tolerance test. A single oral dose of WE or WES pretreatment significantly improved intraperitoneal glucose tolerance. A single oral dose of WES significantly decreased glucose and increased insulin and GLP-1 in serum after 30 min. This acute hypoglycemic effect of WES was abolished by pretreatment with exendin-9, a GLP-1 receptor antagonist. Our data provide evidence that BG stimulates GLP-1 secretion which contributes, at least in part, to the antidiabetic activity of BG through an incretin effect.

Role of Renal Kallikrein in Modulating the Antihypertensive Effect of a Single Oral Dose of Captopril in Normal- and Low-Renin Essential Hypertensives

1987 ◽  
Vol 5 (6) ◽  
pp. 645-648 ◽  
Author(s):  
Paolo Madeddu ◽  
Mario Oppes ◽  
Speranza Rubattu ◽  
Paolo Dessi??-Fulgheri ◽  
Nicola Glorioso ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Antihypertensive Effect ◽  
Renal Kallikrein
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