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The Journal of Clinical Investigation Apr 2016Recently, 1-octanol has been shown to have efficacy in treating patients with essential tremor (ET). The primary metabolite of 1-octanol is octanoic acid (OA), which is... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
Recently, 1-octanol has been shown to have efficacy in treating patients with essential tremor (ET). The primary metabolite of 1-octanol is octanoic acid (OA), which is now thought to be the active substance that mediates tremor suppression. Our aim was to describe the maximum tolerated dose (MTD) of oral OA in patients with ET and assess the pharmacokinetics (PK) and pharmacodynamics (PD) profile of OA.
METHODS
The MTD was studied using an open-label, single-ascending 3 + 3 dose-escalation design. Predefined single doses ranged from 8 to 128 mg/kg, with grade 2 adverse events (AEs) defined as dose-limiting toxicity. Tremor was assessed using accelerometry, digital spiral analysis, and a standard clinical rating scale at baseline and up to 600 minutes after intake. Safety assessments and PK sampling were also performed.
RESULTS
Dose-limiting toxicity was not reached. The most frequent AE was mild abdominal discomfort. Exposure (AUC) increased linearly with the dose. Secondary efficacy measures suggested a dose-dependent reduction of tremor. Accordingly, a single unified PK/PD model with an effect compartment and sigmoid maximum effect (Emax) response could be built that accounted well for the time profiles of plasma concentrations as well as effects on tremor severity across the 5 dose levels.
CONCLUSION
Although our trial did not reach an MTD, a dose-dependent effect was demonstrated in the PK/PD model as well as in secondary efficacy outcomes. Future studies are needed to explore the safety in higher dose ranges and to confirm dose-dependent efficacy in a placebo-controlled design.
TRIAL REGISTRATION
Clinicaltrials.gov NCT01468948FUNDING. NINDS Intramural Research Program; TG Therapeutics Inc.
Topics: Caprylates; Dose-Response Relationship, Drug; Essential Tremor; Female; Humans; Male
PubMed: 26927672
DOI: 10.1172/JCI83621 -
Journal of Chromatography. A Sep 2023Poly(ethyleneimine) (PEI) modified silica spheres were used to graft butyric acid and octanoic acid onto their surfaces, forming two stationary phases named Sil-PEI-BAD... (Comparative Study)
Comparative Study
Poly(ethyleneimine) (PEI) modified silica spheres were used to graft butyric acid and octanoic acid onto their surfaces, forming two stationary phases named Sil-PEI-BAD and Sil-PEI-CAD, respectively. Characterized methods including fourier transform infrared spectroscopy (FT-IR), elemental analysis (EA) and thermogravimetric analysis (TGA) were utilized to determine the successful synthesis of these two stationary phase materials. The chromatographic performance of these two stationary phases was analyzed with hydrophobic and hydrophilic compounds as analytes. Compared with Sil-PEI-CAD column, Sil-PEI-BAD column was more effective in separating hydrophilic compounds including nucleosides, alkaloids and vitamins. Hydrophobic substances including polycyclic aromatic hydrocarbons (PAHs) and alkylbenzenes obtained excellent separation results on Sil-PEI-CAD column than Sil-PEI-BAD column. Additionally, according to the separation of phenols, Sil-PEI-CAD column can be used in HILIC/RPLC mixed-mode. The results showed that the properties and retention mechanisms of the prepared stationary phases depended on the length of the alkyl chains bonded on the silica surface.
Topics: Chromatography, Reverse-Phase; Hydrophobic and Hydrophilic Interactions; Nucleosides; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared
PubMed: 37544237
DOI: 10.1016/j.chroma.2023.464268 -
Shock (Augusta, Ga.) Mar 2024Background: Treatment of acute compartment syndrome (ACS)-induced skeletal muscle injury remains a challenge. Previous studies have shown that octanoic acid is a...
Background: Treatment of acute compartment syndrome (ACS)-induced skeletal muscle injury remains a challenge. Previous studies have shown that octanoic acid is a promising treatment for ACS owing to its potential ability to regulate metabolic/epigenetic pathways in ischemic injury. The present study was designed to investigate the efficacy and underlying mechanism of octanoic acid in ACS-induced skeletal muscle injury. Methods: In this study, we established a saline infusion ACS rat model. Subsequently, we assessed the protective effects of sodium octanoate (NaO, sodium salt of octanoic acid) on ACS-induced skeletal muscle injury. Afterward, the level of acetyl-coenzyme A and histone acetylation in the skeletal muscle tissue were quantified. Moreover, we investigated the activation of the AMP-activated protein kinas pathway and the occurrence of mitophagy in the skeletal muscle tissue. Lastly, we scrutinized the expression of proteins associated with mitochondrial dynamics in the skeletal muscle tissue. Results: The administration of NaO attenuated muscle inflammation, alleviating oxidative stress and muscle edema. Moreover, NaO treatment enhanced muscle blood perfusion, leading to the inhibition of apoptosis-related skeletal muscle cell death after ACS. In addition, NaO demonstrated the ability to halt skeletal muscle fibrosis and enhance the functional recovery of muscle post-ACS. Further analysis indicates that NaO treatment increases the acetyl-CoA level in muscle and the process of histone acetylation by acetyl-CoA. Lastly, we found NaO treatment exerts a stimulatory impact on the activation of the AMPK pathway, thus promoting mitophagy and improving mitochondrial dynamics. Conclusion: Our findings indicate that octanoic acid may ameliorate skeletal muscle injury induced by ACS. Its protective effects may be attributed to the promotion of acetyl-CoA synthesis and histone acetylation within the muscular tissue, as well as its activation of the AMPK-related mitophagy pathway.
Topics: Rats; Animals; Acetyl Coenzyme A; AMP-Activated Protein Kinases; Histones; Mitophagy; Muscle, Skeletal; Compartment Syndromes; Caprylates
PubMed: 38300834
DOI: 10.1097/SHK.0000000000002304 -
Food Research International (Ottawa,... Nov 2019We investigated the antimicrobial efficacy of octanoic acid (OA) against Escherichia coli O157:H7 inoculated on the surface of baby spinach and grape tomatoes during...
We investigated the antimicrobial efficacy of octanoic acid (OA) against Escherichia coli O157:H7 inoculated on the surface of baby spinach and grape tomatoes during simulated washing processes. 3 mM OA at 45 °C achieved >6 log CFU/g reduction from the surface of tomatoes within 2 min. However, washing baby spinach with 6 mM OA at 5 °C resulted in <1 log CFU/g reduction, highlighting the role of surface properties in inactivation efficacy. OA significantly (p < 0.05) reduced the risk of cross-contamination during washing of spinach as well as tomatoes. Also, total mold and yeast population on surface of spinach was significantly reduced immediately after OA wash and inhibited during following 14 days. Baby spinach and grape tomatoes washed with OA did not cause significant (p > 0.05) difference in color compared to the control and no residual OA was detected in most cases following rinsing of produce in water. OA at the concentrations above 2 mM and temperature higher than 25 °C induced severe membrane damage along with release of ATP and other intracellular constituents resulting in bacterial death. OA can be an attractive natural decontamination agent for washing fresh produce.
Topics: Anti-Bacterial Agents; Caprylates; Escherichia coli O157; Food Microbiology; Solanum lycopersicum; Spinacia oleracea
PubMed: 31554067
DOI: 10.1016/j.foodres.2019.108523 -
Analytical Sciences : the International... Jun 2023In this study, octanoic acid (OA) was used as an extraction solvent for the pre-concentration and determination of three antibiotic drugs (levofloxacin, metronidazole,...
A new application of continuous sample drop flow microextraction using octanoic acid as a green extraction solvent for the determination of antibiotic drugs in urine samples.
In this study, octanoic acid (OA) was used as an extraction solvent for the pre-concentration and determination of three antibiotic drugs (levofloxacin, metronidazole, and tinidazole) in urine samples. To extract the antibiotic drugs, a green solvent was used as the extraction solvent in the continuous sample drop flow microextraction method, followed by a high-performance liquid chromatography photodiode array detector. According to the findings, the present study offers an environmentally friendly analytical method with a high capacity for the microextraction of the antibiotic drugs at very low concentrations. The calculated detection limits were 6.0-10.0 µg/L and the linear range was found between 20 and 780 µg/L. The proposed method showed excellent repeatability with the RSD values ranging from 2.8 to 5.5%. The relative recoveries were between 79.0 and 92.0% in the urine samples with spiked levels of 40.0-100.0 µg/L for metronidazole and tinidazole, and 100.0-200.0 μg/L for levofloxacin.
Topics: Solvents; Levofloxacin; Metronidazole; Tinidazole; Anti-Bacterial Agents
PubMed: 36807896
DOI: 10.1007/s44211-023-00292-x -
Journal of Food Science Apr 2012This study evaluated the effects of peroxyacetic acid (PAA), malic acid (MA), octanoic acid (OA), and potassium lactate (KL) followed by mixing with trisodium phosphate... (Comparative Study)
Comparative Study
UNLABELLED
This study evaluated the effects of peroxyacetic acid (PAA), malic acid (MA), octanoic acid (OA), and potassium lactate (KL) followed by mixing with trisodium phosphate (TSP) and an ultra-chilled CO₂ snow shower on microbial counts of Escherichia coli (EC), coliform (CF), aerobic plate count (APC), and Salmonella Typhimurium (ST) on inoculated beef trimmings and the instrumental color attributes of the resultant ground beef. Beef trimmings inoculated with EC and ST were treated with either 0.02% PAA; 2% MA; 0.04% OA; or 2% KL, followed by mixing with 10% TSP and rapid chilling with CO₂ snow shower. Treated trimmings were then ground, packaged, displayed under simulated retail conditions, and sampled on days 1, 2, 3, 5, and 7 for microbial counts and instrumental color characteristics. PAA, MA, OA, and KL reduced (P < 0.05) the microbial counts of EC, CF, APC, and ST during display. Among treatments, OA was most effective on EC, CF, ST, and APC during retail display. Chilling beef trimmings with CO₂ improved instrumental color characteristics of the produced ground beef but made little difference in reducing microbial counts during display. During retail display, ground beef produced from beef trimmings treated with antimicrobials tended to maintain redness, myoglobin redox form stability (630 nm/580 nm), and overall instrumental color characteristics.
PRACTICAL APPLICATION
This research provides a practical and cost-effective decontamination technology for beef processors that can be immediately implemented in the ground beef production chain. Using antimicrobial intervention coupled with rapid chilling could benefit the meat industry by preserving the quality attributes of ground beef during retail display under aerobic packaging environment.
Topics: Animals; Anti-Bacterial Agents; Antioxidants; Caprylates; Cattle; Cold Temperature; Colony Count, Microbial; Food Preservation; Food Storage; Gram-Negative Bacteria; Lactates; Malates; Meat; Microbial Viability; Myoglobin; Peracetic Acid; Phosphates; Pigmentation; Protein Stability; Quality Control
PubMed: 22352902
DOI: 10.1111/j.1750-3841.2011.02600.x -
G3 (Bethesda, Md.) Dec 2017The dietary specialist fruit fly has evolved to specialize on the toxic fruit of its host plant Toxicity of fruit is primarily due to high levels of octanoic acid...
The dietary specialist fruit fly has evolved to specialize on the toxic fruit of its host plant Toxicity of fruit is primarily due to high levels of octanoic acid (OA). Using RNA interference (RNAi), prior work found that knockdown of family genes (), , and led to increased susceptibility to OA in adult flies, likely representing genes underlying a Quantitative Trait Locus (QTL) for OA resistance in While genes in this major effect locus are beginning to be revealed, prior work has shown at least five regions of the genome contribute to OA resistance. Here, we identify new candidate OA resistance genes by performing differential gene expression analysis using RNA-sequencing (RNA-seq) on control and OA-exposed flies. We found 104 significantly differentially expressed genes with annotated orthologs in , including six gene family members, consistent with previous functional studies and gene expression analyses. Gene ontology (GO) term enrichment showed significant enrichment for cuticle development in upregulated genes and significant enrichment of immune and defense responses in downregulated genes, suggesting important aspects of the physiology of that may play a role in OA resistance. In addition, we identified five candidate OA resistance genes that potentially underlie QTL peaks outside of the major effect region, representing promising new candidate genes for future functional studies.
Topics: Animals; Caprylates; Drosophila melanogaster; Gene Expression Profiling; Gene Expression Regulation; Morinda; Quantitative Trait Loci; RNA Interference; Receptors, Odorant; Sequence Analysis, RNA; Species Specificity; Transcriptome
PubMed: 29021218
DOI: 10.1534/g3.117.300297 -
Biochimie Jan 2016Caprylic acid (octanoic acid, C8:0) belongs to the class of medium-chain saturated fatty acids (MCFAs). Dairy products and specific oils like coconut oil are natural... (Review)
Review
Caprylic acid (octanoic acid, C8:0) belongs to the class of medium-chain saturated fatty acids (MCFAs). Dairy products and specific oils like coconut oil are natural sources of dietary C8:0 but higher intakes of this fatty acid can be provided with MCT (Medium-Chain Triglycerides) oil that consists in 75% of C8:0. MCFAs have physical and metabolic properties that are distinct from those of long-chain saturated fatty acids (LCFAs ≥ 12 carbons). Beneficial physiological effects of dietary C8:0 have been studied for a long time and MCT oil has been used as a special energy source for patients suffering from pancreatic insufficiency, impaired lymphatic chylomicron transport and fat malabsorption. More recently, caprylic acid was also shown to acylate ghrelin, the only known peptide hormone with an orexigenic effect. Through its covalent binding to the ghrelin peptide, caprylic acid exhibits an emerging and specific role in modulating physiological functions themselves regulated by octanoylated ghrelin. Dietary caprylic acid is therefore now suspected to provide the ghrelin O-acyltransferase (GOAT) enzyme with octanoyl-CoA co-substrates necessary for the acyl modification of ghrelin. This review tries to highlight the discrepancy between the formerly described beneficial effects of dietary MCFAs on body weight loss and the C8:0 newly reported effect on appetite stimulation via ghrelin octanoylation. The subsequent aim of this review is to demonstrate the relevance of carrying out further studies to better understand the physiological functions of this particular fatty acid.
Topics: Acylation; Acyltransferases; Animals; Caprylates; Chylomicrons; Dietary Fats; Exocrine Pancreatic Insufficiency; Ghrelin; Humans; Lipoylation
PubMed: 26253695
DOI: 10.1016/j.biochi.2015.08.002 -
European Journal of Gastroenterology &... Jan 2000The purpose of this multicentre study was to assess the accuracy and reproducibility of the 13C-octanoic acid breath test compared to scintigraphy for measurement of... (Comparative Study)
Comparative Study
OBJECTIVES
The purpose of this multicentre study was to assess the accuracy and reproducibility of the 13C-octanoic acid breath test compared to scintigraphy for measurement of gastric emptying.
METHODS
Sixty-nine healthy subjects (40 men, 29 women; mean age 30 years, range 21-61) were studied at least once by using the 13C-octanoic breath test. In 34 healthy subjects, gastric emptying was simultaneously measured by gastric scintigraphy, and the 13C-octanoic breath test was then repeated in 18 of these cases. Fifty-four patients (30 men, 24 women; mean age 46 years, range 13-74) with dyspeptic or reflux symptoms were studied according to the same procedure.
RESULTS
The correlation between breath test and scintigraphic values was highly significant (r = 0.744, P<0.001). The concordance of results of scintigraphy and breath test (normal versus abnormal) and the reproducibility (Bland and Altman method) of the breath test were good (CVinter = 24%, CVintra = 15%). As compared to scintigraphy, breath test detected an abnormal gastric emptying with 67% sensitivity and 80% specificity (ROC analysis).
CONCLUSION
These results confirm the value of breath test as an accurate measurement of gastric emptying. Its excellent reproducibility makes it a method of choice for pharmacological studies. However, at least when scintigraphy is considered the gold standard, breath test sensitivity may be insufficient for the detection of gastroparesis in an individual patient.
Topics: Adolescent; Adult; Aged; Breath Tests; Caprylates; Carbon Isotopes; Case-Control Studies; Female; Gastric Emptying; Gastroesophageal Reflux; Humans; Male; Middle Aged; ROC Curve; Radionuclide Imaging; Reproducibility of Results; Sensitivity and Specificity
PubMed: 10656216
DOI: 10.1097/00042737-200012010-00016 -
Journal of Applied Physiology Mar 1964
Topics: Absorption; Biomedical Research; Caprylates; Carbon Dioxide; Carbon Isotopes; Fatty Acids; Glucose; Intestine, Small; Intestines; Lipid Metabolism; Oxidation-Reduction
PubMed: 14155309
DOI: 10.1152/jappl.1964.19.2.335