scholarly journals An Absorption and Plasma Kinetics Study of Monoterpenes Present in Mastiha Oil in Humans

Foods ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1019
Author(s):  
Efstathia Papada ◽  
Aristea Gioxari ◽  
Charalampia Amerikanou ◽  
Nikolaos Galanis ◽  
Andriana C. Kaliora
Keyword(s):  
Serum Lipid ◽  
Kinetics Study ◽  
Oil Consumption ◽  
Metabolic Fate ◽  
Open Label ◽  
Alpha Pinene ◽  
Resistance To Oxidation ◽  
Before And After ◽  
Overnight Fasting ◽  
Acute Study

Monoterpenes are bioactive compounds, however studies on their metabolic fate in humans are scarce. The present work aimed to identify and quantify the bioactive monoterpenes myrcene, α- and β-pinene of the Mediterranean product Mastiha Oil, in human plasma after acute consumption of a single dose. This was an open-label, single-arm acute study. After overnight fasting, healthy males were administered with Mastiha Oil. Blood samples were collected on different time-points before and after consumption. A novel GC-MS-MS application was performed to detect and quantify terpenes in MO and in plasma. Serum lipid resistance to oxidation was also determined. Alpha-Pinene, β-pinene and myrcene were identified and quantified in plasma. Alpha-pinene concentration significantly increased after 0.5 h of Mastiha Oil consumption, remaining significantly increased at 1 h, 2 h, 4 h, 6 h and 24 h. Beta-pinene and myrcene followed similar patterns. The increase in serum lipid resistance to oxidation was significant at 1 h, reached its peak at 2 h and remained significant until 4 h. Conclusively, α-pinene, β-pinene and myrcene that are present in Mastiha Oil are absorbed by humans. (ClinicalTrials.gov Identifier: NCT04290312).

scholarly journals MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors

2021 ◽  
Author(s):  
Ying Meng ◽  
Christopher B Pople ◽  
Suganth Suppiah ◽  
Maheleth Llinas ◽  
Yuexi Huang ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Focused Ultrasound ◽  
Brain Regions ◽  
Specific Protein ◽  
Rank Test ◽  
Open Label ◽  
Isocitrate Dehydrogenase 1 ◽  
Serious Adverse Events ◽  
Before And After ◽  
Bbb Opening

Abstract Background Liquid biopsy is promising for early detection, monitoring of response and recurrence of cancer. The blood-brain barrier (BBB) limits the shedding of biomarker, such as cell-free DNA (cfDNA), into the blood, and their detection by conventional assays. Transcranial MR-guided focused ultrasound (MRgFUS) can safely and transiently open the BBB, providing an opportunity for less-invasive access to brain pathology. We hypothesized MRgFUS can enrich the signal of circulating brain-derived biomarkers to aid in liquid biopsy. Methods Nine patients were treated in a prospective single-arm, open-label trial to investigate serial MRgFUS and adjuvant temozolomide combination in patients with glioblastoma (NCT03616860). Blood samples were collected as an exploratory measure within the hours before and after sonication, with control samples from non-brain tumor patients undergoing BBB opening alone (NCT03739905). Results Brain regions averaging 7.8±6.0 cm 3 (range 0.8–23.1 cm 3) were successful treated within 111±39 minutes without any serious adverse events. We found MRgFUS acutely enhanced plasma cfDNA (2.6±1.2 fold, p<0.01, Wilcoxon signed-rank test), neuron-derived extracellular vesicles (3.2±1.9 fold, p<0.01), and brain specific protein S100b (1.4±0.2 fold, p<0.01). Further comparison of the cfDNA methylation profiles suggests a signature that is disease and post-BBB opening specific, in keeping with our hypothesis. We also found cfDNA mutant copies of isocitrate dehydrogenase 1 (IDH1) increased, although this was in only one patient known to harbour the tumor mutation. Conclusions This first-in-human proof-of concept study shows MRgFUS enriches the signal of circulating brain-derived biomarkers, demonstrating the potential of the technology to support liquid biopsy for the brain.

scholarly journals An open-label study to evaluate biomarkers and safety in systemic sclerosis patients treated with paquinimod

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Roger Hesselstrand ◽  
Jörg H. W. Distler ◽  
Gabriela Riemekasten ◽  
Dirk M. Wuttge ◽  
Marie Törngren ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Type I ◽  
Type I Ifn ◽  
Open Label ◽  
Reactive Protein ◽  
Before And After ◽  
Modified Rodnan Skin Score ◽  
Skin Biopsies ◽  
Rank 2

Abstract Objectives To evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc). Methods In this open-label, single-arm, multicenter study, SSc patients with a rapidly progressive disease received paquinimod for 8 weeks. Blood and skin biopsies were collected at baseline, during treatment, and at follow-up for the analyses of type I interferon (IFN) activity, chemokine (C-C motif) ligand 2 (CCL2), and the number of myofibroblasts. The safety of paquinimod was evaluated throughout the study. Results Nine SSc patients were enrolled and completed the study treatment with paquinimod at 3 mg/day for 8 weeks. After the treatment, a reduction of type I IFN activity in the plasma from one patient with elevated baseline IFN activity was recorded. A trend towards reduced IFN activity in the skin after treatment was also observed in patients. The serum level of CCL2 was reduced in 7 of 9 patients after paquinimod treatment. There was a median reduction of 10% of the number of myofibroblasts in skin biopsies at week 8 compared to baseline. No change in modified Rodnan skin score and quality of life was detected in the study. Reported adverse events (AEs) were mild to moderate and expected with the most common being arthralgia (n = 3) and headache (n = 3), and C-reactive protein (CRP) increase. Conclusions Analysis of biomarkers before and after treatment suggest reduced type I IFN activity and reduced number of myofibroblasts in lesional skin. Paquinimod was overall well tolerated with mild to moderate and expected AEs. Trial registration ClinicalTrials.gov, NCT01487551. Registered on 7 September 2011

scholarly journals Are Three Weeks of Oral Anticoagulation Sufficient for Safe Cardioversion in Atrial Fibrillation?

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 554
Author(s):  
Stefan Naydenov ◽  
Nikolay Runev ◽  
Emil Manov
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Oral Anticoagulation ◽  
Left Atrial ◽  
Left Atrial Volume ◽  
Open Label ◽  
Before And After ◽  
Individualized Approach ◽  
Baseline Factors ◽  
And Function

Background and Objectives: Patients with atrial fibrillation (AF), lasting >48 h, considered for cardioversion, are recommended ≥3 weeks of oral anticoagulation before sinus rhythm restoration because of high risk of development of left atrial thrombosis (LAT) and stroke. However, the optimal duration of anticoagulation in the presence of overt LAT is unknown. Materials and Methods: An open-label study aimed to investigate the prevalence of spontaneous echo contrast (SEC) and LAT before and after 3 weeks of direct oral anticoagulant (DOAC) treatment. We included 51 consecutive patients (50.9% males), mean age 69.3 ± 7.4 years with paroxysmal/unknown duration of AF, considered for cardioversion, who agreed to have transesophageal echocardiography at enrollment and 3 weeks later. Results: At baseline SEC was present in 26 (50.9%) and LAT in 10 (19.6%) of 51 patients. After 3 weeks on DOAC, SEC persisted in 12 (25.0%) and LAT in 7 (14.5%) of 48 patients, p < 0.05 vs. baseline. Factors, associated most strongly with persistence of SEC/LAT, were left atrial appendage (LAA) emptying velocity <20 cm/s (OR = 2.82), LAA lobes >2 (OR = 1.84), and indexed left atrial volume ≥34 mL/m2 (OR = 1.37). Conclusions: In our study the incidence of SEC/LAT, particularly in AF with unknown duration, was not as low as we expected. The prevalence of SEC/LAT seemed to be dependent on factors not routinely evaluated in AF patients planned for cardioversion (indexed LA volume, LAA morphology and number of lobules, LAA emptying velocity, etc.). Our data suggested an individualized approach for DOAC duration in AF patients before an attempt for restoration of sinus rhythm is made, taking into consideration the LAA morphology and function.

scholarly journals Effects of Open-Label Placebos on State Anxiety and Glucocorticoid Stress Responses

2021 ◽  
Vol 11 (4) ◽  
pp. 508
Author(s):  
Michael Schaefer ◽  
Julian Hellmann-Regen ◽  
Sören Enge
Keyword(s):  
Stress Responses ◽  
Acute Stress ◽  
Stress Test ◽  
Self Report ◽  
Control Group ◽  
Relaxation Techniques ◽  
Open Label ◽  
Before And After ◽  
Cortisol Responses ◽  
Negative Feelings

Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held that placebos require deception to provoke a response, recent studies demonstrate intriguing evidence that placebos may work even without concealment (e.g., against anxiety or pain). Most of these studies are based on self-report questionnaires and do not include physiological measures. Here we report results of a study examining whether placebos without deception reduce acute stress. A total of 53 healthy individuals received either placebos without deception or no pills before participating in a laboratory stress test (Maastricht Acute Stress Test, MAST). We recorded self-report stress measures and cortisol responses before and after the MAST. Results showed no significant differences between the placebo and the control group, but when comparing participants with high relative to low beliefs in the power of placebos we found significant lower anxiety and cortisol responses for the placebo believers. These results show that non-deceptive placebos may successfully reduce acute anxiety and stress, but only in participants who had a strong belief in placebos. We discuss the results by suggesting that open-label placebos might be a possible treatment to reduce stress at least for some individuals.

Evaluation of Ship Performance Using Operation Records

2018 ◽  
Author(s):  
Kenichi Fukuda ◽  
Yoshihisa Okada ◽  
Akinori Okazaki ◽  
Hiroyuki Adachi ◽  
Yuichiro Hisamuara ◽  
...  
Keyword(s):  
Big Data ◽  
Fuel Oil ◽  
Time Dependent ◽  
Oil Consumption ◽  
Sea Trial ◽  
Before And After ◽  
Report Data ◽  
Unique Approach ◽  
Performance Conditions ◽  
Ship Performance

Recently, the big data can be employed as the economical ship operating or evaluation of ship performance conditions. However, such data cannot be easily obtained and analyzed for every ship. In this case, for example, an evaluation of ship performance during operation is usually dependent on ship owner’s experience. The time-dependent ship performance is an essential topic for ship owners because if they realize their current ship performance, they can implement something such as hull or propeller cleaning for their economical operation. This study is focused on the usage of noon report data rather than the big data due to their obtainability. Usually, such data are considered as references because different ship operational condition and environmental condition obscure current ship performance. However, our unique approach, which is used integrally the noon report data such as BHP, propeller revolution and fuel oil consumption, ship sea trial data and propeller performance, can be evaluated ship performance during ship in service. The analyzed output data can be produced as increasing of ship resistance (delta Rw) versus ship performance efficiency, fuel oil consumption (ton per day) or sea margin. Under this output conditions, it can be comparable at same conditions even though the conditions of operations are different. Therefore, this analyzed data has a potential ability to have a look at ship performance conditions during ship in service. The purpose of this paper is to introduce our unique approach using noon data for time-dependent ship performance and then discuss the verification of this approach. As the case study, the noon report data for Japanese domestic bulker was chosen and the ship performance was evaluated in terms of different points of views. It was done comparing the conditions of before and after dry dock to evaluate our approach. In addition, the potential application of this approach will be discussed in this paper.

CTIM-22. NIVOLUMAB AND BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA; T-CELL REACTIVITY AGAINST AUTOLOGOUS TUMOR CELLS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi54-vi55
Author(s):  
Simone Maarup ◽  
Signe Skadborg ◽  
Annie Borch ◽  
Arianna Draghi ◽  
Benedikte Hasselbalch ◽  
...  
Keyword(s):  
Intracellular Cytokine Staining ◽  
Tumor Infiltrating Lymphocytes ◽  
Recurrent Glioblastoma ◽  
Autologous Tumor ◽  
Open Label ◽  
Cell Reactivity ◽  
Translational Study ◽  
Novel Treatments ◽  
Before And After

Abstract INTRODUCTION Glioblastoma is an aggressive brain tumor with a median survival of 14.6 months. We have no standard treatment for relapse and known options have limited effect. Novel treatments are necessary to improve survival and quality of life. METHODS We present our trial; phase II open label, two-armed translational study of Nivolumab and Bevacizumab for recurrent GBM, who have failed Stupp’s regimen. Patients are included in two arms depending on the possibility of salvage neurosurgical resection. Both arms receive Nivolumab and Bevacizumab administrated every second weekend, and the surgical arm also receive Nivolumab 7 days prior surgery. Forty-four patients were included by January 2021; 20 in each arm (four screen-failures). In the surgical arm, 20 fresh tumor samples as well as paired tissue from primary tumor were available. Tumor infiltrating lymphocytes (TILs) and tumor digest were produced in vitro from recurrent settings. Young TILs were expanded from fresh tumor fragments after minimal-culture, whereas rapidly expanded TILs (REP TILs) were obtained after massive expansion. By intracellular cytokine staining, we investigated the TIL reactivity after exposure to autologous tumor digest in order to evaluate whether the TILs were tumor-reactive, non-reactive or bystanders. RNA and whole exome sequencing were available before and after treatment. RESULTS Material from 19 patients was analyzed (one out of the 20 collected biopsies was limited in size, therefore no tumor digest could be produced). Four out of 19 TIL samples showed tumor reactivity after exposure to the autologous tumor digest. Tumor reactivity was ranged between 1,2 to 13,6 tox% in CD8+ TILs and between 2,8 to 10,9 tox% in CD4+ TILs. By flowcytometry we found, IgG4+ CD3+ TILS from tumor biopsies, meaning that Nivolumab were found in the brain. Currently controls are included to evaluate these results. CONCLUSIONS Updated results will be presented at SNO.

scholarly journals Body composition and serum lipid profile of Royal Navy submariners before and after a three month deployment

2017 ◽  
Vol 76 (OCE1) ◽  
Author(s):  
F. Gunner ◽  
M. Lindsay ◽  
P.E.H. Brown ◽  
A.M. Shaw ◽  
S.E. Britland ◽  
...  
Keyword(s):  
Body Composition ◽  
Lipid Profile ◽  
Serum Lipid ◽  
Serum Lipid Profile ◽  
Royal Navy ◽  
Before And After

scholarly journals Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas

2011 ◽  
Vol 55 (4) ◽  
pp. 266-271 ◽  
Author(s):  
Rogerio Silicani Ribeiro ◽  
Julio Abucham
Keyword(s):  
Pituitary Adenomas ◽  
Erectile Function ◽  
Prospective Trial ◽  
Open Label ◽  
Dopaminergic Therapy ◽  
Testosterone Levels ◽  
Nonfunctioning Pituitary Adenomas ◽  
Before And After ◽  
Previously Treated ◽  
Male Patients

OBJETIVE: To evaluate the effect of clomiphene in men with hypogonadism and conventionally treated nonfunctioning pituitary adenomas (NFPA). PATIENTS AND METHODS: Open label, single-arm, prospective trial. Nine hypogonadal men (testosterone < 300 ng/dL and low/normal LH) with previously treated NFPA. Clomiphene (50 mg/day orally) for 12 weeks. Testosterone, estradiol, LH, FSH, prolactin and erectile function were evaluated before and after 10 days, 4, 8 and 12 weeks of clomiphene treatment. RESULTS: After clomiphene treatment, testosterone and erectile function improved in only one patient. In the remaining eight patients, testosterone levels decreased whereas LH, FSH, and estradiol remained unchanged. Insulin sensitivity increased in unresponsive patients. CONCLUSIONS: Compared with hypogonadal men with prolactinomas under dopaminergic therapy, clomiphene treatment failed to restore normal testosterone levels in most patients with conventionally treated NFPA.

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