scholarly journals Safety of Short-Term Supplementation with Methylliberine (Dynamine®) Alone and in Combination with TeaCrine® in Young Adults

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 654 ◽  
Author(s):  
Trisha A. VanDusseldorp ◽  
Matthew T. Stratton ◽  
Alyssa R. Bailly ◽  
Alyssa J. Holmes ◽  
Michaela G. Alesi ◽  
...  
Keyword(s):  
Low Dose ◽  
Safety Data ◽  
High Density Lipoproteins ◽  
High Dose ◽  
Mean Corpuscular Hemoglobin ◽  
Blood Biomarkers ◽  
Purine Alkaloids ◽  
Clinically Significant ◽  
Continuous Use ◽  
Main Effects

Methylliberine (Dynamine®; DYM) and theacrine (Teacrine®; TCR) are purine alkaloids purported to have similar neuro-energetic effects as caffeine. There are no published human safety data on DYM, and research on TCR is limited. The purpose of this study was to examine the effect of four weeks of DYM supplementation with and without TCR on cardiovascular function and blood biomarkers. One-hundred twenty-five men and women (mean age 23.0 yrs, height 169.7 cm, body mass 72.1 kg; n = 25/group) were randomly assigned to one of five groups: low-dose DYM (100 mg), high-dose DYM (150 mg), low-dose DYM with TCR (100 mg + 50 mg), high-dose DYM with TCR (150 mg + 25 mg), and placebo. Regardless of group and sex, significant main effects for time were noted for heart rate, systolic blood pressure, and QTc (p < 0.001), high-density lipoproteins (p = 0.002), mean corpuscular hemoglobin (p = 0.018), basophils (p = 0.006), absolute eosinophils (p = 0.010), creatinine (p = 0.004), estimated glomerular filtration rate (p = 0.037), chloride (p = 0.030), carbon dioxide (p = 0.023), bilirubin (p = 0.027), and alanine aminotransferase (p = 0.043), among others. While small changes were found in some cardiovascular and blood biomarkers, no clinically significant changes occurred. This suggests that DYM alone or in combination with TCR consumed at the dosages used in this study does not appear to negatively affect markers of health over four weeks of continuous use.

scholarly journals Dose-Response Effects of Strawberries on Atherogenic Lipoproteins: A Randomized Controlled Crossover Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 75-75
Author(s):  
Ann Skulas-Ray ◽  
Chesney Richter ◽  
Trent Gaugler ◽  
Stacey Meily ◽  
Kristina Petersen ◽  
...  
Keyword(s):  
Low Dose ◽  
Optimal Dose ◽  
Serum Lipoprotein ◽  
High Dose ◽  
Funding Sources ◽  
Supplementation Period ◽  
Freeze Dried ◽  
Middle Aged Adults ◽  
Post Hoc ◽  
Main Effects

Abstract Objectives Previous research indicates that consumption of strawberries may provide benefits for reduction of atherogenic lipoproteins but has not identified an optimal dose. Our objective was to evaluate effects of 2 doses of strawberry powder, approximately equivalent to 1 and 3 servings of strawberries per day, on serum lipoprotein concentrations. Methods Middle-aged adults (n = 40, age 49 ± 1 year) with elevated LDL-C (140 ± 4 mg/dL) and elevated BMI (29.4 ± 0.4 kg/m2) consumed 0 g/d (control), 13 g/d (low-dose), and 40 g/d (high-dose) of freeze-dried strawberry powder in a randomized crossover design (4-week supplementation periods separated by a 2 week compliance break). Fasting blood samples were obtained on two separate days (and averaged) at study-entry baseline and following each supplementation period. Results There were significant main effects of treatment (P ≤ 0.05) for calculated LDL-C, nonHDL-C, and total cholesterol (TC). In post hoc tests, the low-dose resulted in 5% lower LDL-C vs. the high-dose (P = 0.01), 4% lower nonHDL-C vs. control (P = 0.04), and 3% lower TC for the low-dose vs. control and high-dose (P ≤ 0.04). Compared to baseline, low-dose strawberry supplementation also significantly reduced direct LDL-C (−6.8 mg/dL, P = 0.02), but there was not a main effect of treatment. Conclusions Our results suggest that low-dose supplementation with freeze dried strawberry powder, roughly equivalent to one serving of strawberries per day, was superior to high-dose supplementation for improving atherogenic lipoproteins in overweight adults. Funding Sources California Strawberry Commission.

scholarly journals Subchronic Toxicological Assessment of Dr Iguedo Goko Cleanser® on Lipid Profile and Serum Antioxidant Enzymes in Exposed Wistar Rats

2020 ◽  
pp. 16-25
Author(s):  
Godswill J. Udom ◽  
Jude E. Okokon ◽  
John A. Udobang ◽  
Daniel N. Obot ◽  
Nkechi J. Onyeukwu
Keyword(s):  
Oxidative Stress ◽  
Lipid Profile ◽  
Wistar Rats ◽  
Low Dose ◽  
Herbal Remedy ◽  
Female Rats ◽  
Male Rats ◽  
High Density Lipoproteins ◽  
High Dose ◽  
Low Density

Dr Iguedo Goko Cleanser® is a polyherbal mixture promoted as an effective herbal remedy for numerous diseases. Study aimed to evaluate the toxicity concern of the polyherbal mixture (PHM) on lipid profile and oxidative status in Wistar rats of both gender. Acute toxicity study was conducted using modified method of Lorke. Thirty Wistar rats of bother gender were randomly divided into six groups (5/group) and exposed to the polyherbal mixture for 60 days via oral gavage. Control groups (1 and 4) received 10 mL/kg distilled water, while groups 2-3 and 5-6 received 476.24 and 158.75 mg/kg body weight of Dr Iguedo Goko Cleanser® respectively. On 62nd day, animals were sacrificed under diethyl ether anaesthesia; blood samples were collected by cardiac puncture for biochemical analysis. PHM significantly (p < 0.05) increased high density lipoproteins (HDL) levels in male rats as well as high dose female rats relative to control. However, low dose female rats recorded low HDL levels relative to control. Total cholesterol, triglycerides, low density and very low density lipoprotein levels were significantly reduced in all test groups relative to controls. The low dose males (LDM) had reduced serum glutathione peroxidase (GPX) activity; while increased and decreased GPX and glutathione (GSH) activities were respectively recorded for female rats. Male rats had dose-dependent increase in malondialdehyde. The recorded reductions in serum lipids suggest that the polyherbal mixture may have hypolipidemic potentials. While the increased malondialdehyde as well as decreased GPX and GSH indicate lipid peroxidation and oxidative stress inducing potentials of the PHM. Despite the positive modulation on lipid profile, findings suggest utmost caution on chronic use as its oxidative stress inducing potentials is considerable.

scholarly journals Steady-State Pharmacokinetic and Safety Profiles of Voriconazole and Ritonavir in Healthy Male Subjects

2007 ◽  
Vol 51 (10) ◽  
pp. 3617-3626 ◽  
Author(s):  
Ping Liu ◽  
Grover Foster ◽  
Kuan Gandelman ◽  
Robert R. LaBadie ◽  
Mark J. Allison ◽  
...  
Keyword(s):  
Steady State ◽  
Low Dose ◽  
Safety Data ◽  
Fold Increase ◽  
High Dose ◽  
Time Curve ◽  
Period 2 ◽  
Parallel Group ◽  
Male Subjects ◽  
Parallel Group Trial

ABSTRACT Since there is a likelihood of coadministration of voriconazole and ritonavir, two studies were conducted to evaluate the potential of drug interaction. Study A was a randomized, placebo-controlled, two-period, parallel-group trial (n = 34). Study B had the same design without the placebo group (n = 17). In period 1, subjects received 200 mg voriconazole or placebo twice daily (BID) for 3 days (400 mg BID on day 1). In period 2, following a 7-day washout, subjects received ritonavir alone at 400 mg BID (study A) or 100 mg BID (study B) for 10 days (days 11 to 20), and then ritonavir was coadministered with 200 mg BID voriconazole or placebo for the next 10 days (days 21 to 30). Serial plasma samples were collected on days 3, 20, and 30, and safety data were collected throughout the study. High-dose (400 mg BID) ritonavir substantially reduced the steady-state mean voriconazole exposure (area under the concentration-time curve from 0 to 12 h [AUC0-12], −82%; maximum concentration [C max], −66%). However, the effect of low-dose (100 mg BID) ritonavir was less pronounced (AUC0-12, −39%; C max, −24%). The decrease in voriconazole exposure was probably due to the induction of CYP2C19 and CYP2C9 by ritonavir. It is interesting that one subject in each study exhibited the opposite effect of ritonavir on voriconazole exposure (a 2.5- to 3-fold increase), probably due to lack of CYP2C19. Voriconazole had no apparent effect on the exposure of high-dose ritonavir but slightly decreased the exposure of low-dose ritonavir (AUC0-12, −14%; C max, −24%). The safety profile of combination therapy was not notably different from that of voriconazole or ritonavir alone. Due to the significant effect of ritonavir on voriconazole exposure, coadministration of voriconazole with 400 mg BID ritonavir is contraindicated; coadministration with 100 mg BID ritonavir should be avoided, unless an assessment of the benefit/risk to the patient justifies the use.

Effect of Denileukin Diftitox on Pruritus and Other Skin-Related Symptoms Vs Placebo In Patients with Cutaneous T-Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4922-4922
Author(s):  
Lauren Pinter-Brown ◽  
Anna Kozlovski
Keyword(s):  
Placebo Group ◽  
T Cell ◽  
Dose Group ◽  
Low Dose ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Dose ◽  
Cutaneous T Cell Lymphoma ◽  
Score Improvement ◽  
Clinically Significant

Abstract Abstract 4922 Introduction. Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin's lymphomas (NHLs) that develop primarily in the skin but may progress to involve lymph nodes, blood, and visceral organs. CTCL is characterized by skin patches, plaques, tumors, and erythroderma. Pruritus is frequently associated with skin lesions in CTCL and may be severe. Some treatments have been noted to produce improvements in pruritus that appears to be independent of the response rate. Denileukin diftitox (DD, Ontak), a recombinant fusion protein targeting IL-2-receptor-expressing T lymphocytes, has demonstrated a significant effect on overall response rate with minimal immunosuppression in patients with CD25 assay-positive CTCL. For this post-hoc analysis, we used data from a randomized, double-blind, placebo-controlled, phase III clinical trial to assess the effect of DD on pruritus and overall skin condition in patients with CTCL. Patients and methods. Patients with CD25 assay-positive, stage Ia to III CTCL were randomized to receive 9 μg/kg/d DD (n=45), 18 μg/kg/d DD (n=55), or placebo (n=45). Study medications were administered on the first 5 days of a 21-day cycle for up to 8 cycles. Four grading scales were used to assess clinical signs and symptoms (Table 1). Results. Higher percentages of DD-treated patients experienced clinically significant improvements in skin-related symptoms than did patients on placebo during treatment and follow-up (Table 2). The differences between the proportions of patients in the placebo group experiencing clinically significant improvement and the proportions of those in the 18 μg/kg/d and combined DD dose groups were statistically significant for all 4 assessments. Substantially more DD-treated patients had ≥20% and ≥50% improvement in pruritus (relative to baseline) at any time than those receiving placebo; improvements were maintained for ≥6 weeks. The global skin score improvement and pruritus score improvement in both high dose and low dose groups were significantly correlated, with higher correlation in high dose group compared to low dose group (p=0.0004 vs p=0.0381). There is no correlation in placebo group for the two scores (p=0.3798). Improvement in pruritis was to some extent independent of response, as demonstrated by the proportion of agreement between tumor response and significant pruritus improvement (27% and 19% for high dose and low dose, respectively, in DD groups), based on Kappa concordance coefficient. Conclusion. Patients treated with DD, particularly at the 18-μg/kg/d dose, were more likely to experience clinically significant improvements in pruritus and other skin-related symptoms than were patients receiving placebo. DD was observed to improve pruritus independent of response. Disclosures: Kozlovski: Eisai Inc.: Employment.

Brief intravenous infusions of oblimersen (Genasense; Bcl-2 antisense) alone and in combination with multiple agents are highly effective in human tumor xenografts

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14061-14061
Author(s):  
B. D. Brown ◽  
G. D. Paine-Murietta ◽  
T. N. Julian ◽  
R. P. Warrell
Keyword(s):  
Low Dose ◽  
Safety Data ◽  
Human Tumor ◽  
Lymphocytic Leukemia ◽  
Antisense Oligodeoxynucleotide ◽  
High Dose ◽  
Human Tumor Xenografts ◽  
Tumor Xenografts ◽  
Intravenous Infusions ◽  
Response To Chemotherapy

14061 Background: Oblimersen (OBL; Genasense®) is a phosphorothioate-modified antisense oligodeoxynucleotide (ODN) that down-regulates Bcl-2 and may enhance the response to chemotherapy in patients with melanoma and chronic lymphocytic leukemia (CLL). Extensive safety data for Genasense and other systemically administered ODNs have been obtained using low-dose continuous intravenous infusions (CIVI). However, this method is inconvenient and unsuitable for drug combinations that employ frequent or discontinuous dosing. We have now established that OBL can be effectively administered by high-dose, short IV infusions. Methods: We tested multiple treatment schedules of OBL, alone and in combination with paclitaxel, paclitaxel albumin nanoparticles, imatinib, sorafenib, sunitinib, and erlotinib against human tumor xenografts (melanoma A375, NSCLC A549 and H460, colon HT29 and SW620) grown in C.B-17/SCID mice. Results: Periodic OBL monotherapy (high dose IV Q2–3d) yielded consistently superior antitumor efficacy when compared with low- dose daily IV injections. These results have been obtained against all tumor models evaluated to date. This increased efficacy was also observed when OBL was combined with any other therapeutic agent. For combination treatments that included taxanes, efficacy was shown to be schedule dependent. Conclusions: These results, and recent clinical observations, suggest that brief high-dose IV infusions of OBL may significantly increase antitumor activity, and may obviate the need for CIVI. Brief high-dose IV infusions are being incorporated into ongoing clinical trials to evaluate the safety and efficacy of OBL in combination with other agents. No significant financial relationships to disclose.

Evaluation of QTc Interval Prolongation Among Patients With Cancer Using Enteral Methadone

2018 ◽  
Vol 36 (3) ◽  
pp. 177-184 ◽  
Author(s):  
Amanda G. Lovell ◽  
Bridget McCrate Protus ◽  
Maureen L. Saphire ◽  
Sachin S. Kale ◽  
Amy Lehman ◽  
...  
Keyword(s):  
Low Dose ◽  
Torsades De Pointes ◽  
High Dose ◽  
Qtc Interval ◽  
Moderate Dose ◽  
Qtc Prolongation ◽  
Patients With Cancer ◽  
Qtc Interval Prolongation ◽  
High Incidence ◽  
Clinically Significant

Context: The effect of methadone on corrected QT interval (QTc) in patients with cancer pain is not well-known. Objectives: To describe and characterize the effect of low-, moderate-, and high-dose enteral methadone on QTc interval in patients with cancer. Methods: Retrospective cohort study including patients prescribed enteral methadone during the 27-month study period. Participants were divided into 3 methadone daily dose groups: <30 (low dose), 30 to 59 (moderate dose), ≥60 (high dose) mg. The primary outcome was the incidence of QTc prolongation (>450 ms for females and >430 ms for males). Secondary outcomes included the magnitude of change in QTc after starting methadone, the incidence of clinically significant QTc prolongation (>500 ms) and the prevalence of torsades de pointes and syncope. Results: Two hundred three patients met study inclusion criteria: 91 (45%) low dose, 52 (26%) moderate dose, and 60 (29%) high dose. Incidence of QTc prolongation for low-, moderate-, and high-dose groups was 50 (55%), 37 (71%), and 43 (72%), respectively ( P = .039, low vs high dose). Incidence of clinically significant QTc prolongation was 10 (11%), 4 (8%), and 7 (12%) for low-, moderate-, and high-dose groups. For patients without QTc prolongation prior to initiating methadone, 62% of moderate-dose patients and 67% of high-dose patients had QTc prolongation, while taking methadone. Conclusion: This study found a notably high incidence of QTc prolongation in patients with cancer using enteral methadone. Future studies should aim to determine the risk of adverse cardiac effects in the cancer population and determine appropriate monitoring of methadone for pain management.

scholarly journals 142 Effects of antibiotics on blood profiles in weanling pigs experimentally infected with a pathogenic E. coli

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 78-78
Author(s):  
Kwangwook Kim ◽  
Yijie He ◽  
Cynthia Jinno ◽  
Seijoo Yang ◽  
Minho Song ◽  
...  
Keyword(s):  
Blood Cell ◽  
Low Dose ◽  
Control Diet ◽  
Hemoglobin Concentration ◽  
High Dose ◽  
Mean Corpuscular Hemoglobin ◽  
Post Inoculation ◽  
E Coli ◽  
Cell Counts ◽  
Blood Profiles

Abstract The experiment was conducted to investigate the effects of antibiotics on blood profiles and serum inflammatory mediators of weaned pigs experimentally infected with F18 Escherichia coli (E. coli). Twenty-six pigs (6.88 ± 1.03 kg BW) were individually housed in disease containment rooms and randomly allotted to one of three treatments with 8–12 replicate pigs per treatment. The three dietary treatments were control diet and 2 additional diets supplemented with 0.5 or 50 mg/kg carbadox, respectively. The experiment lasted 18 d (7 d before and 11 d after first inoculation [d 0]). F18 E. coli inoculum was daily and orally as 1010 cfu/3 mL for 3 d. Blood samples were collected before E. coli inoculation and on d 2, 5, 8, and 11 post-inoculation (PI). Total and differential blood cell count were analyzed by CBC test. All data were analyzed by ANOVA using PROC MIXED of SAS. Supplementation of low-dose antibiotics had greatest (P < 0.05) neutrophils but lowest (P < 0.05) monocytes on d 2 PI, compared with control and high-dose antibiotics groups. Pigs in the low-dose antibiotics group still had higher (P < 0.05) white blood cell counts and lymphocytes than pigs in the other groups on d 11 PI. In consistent with CBC results, pigs supplemented with low-dose antibiotics had greatest (P < 0.05) serum C-reactive protein on d 2 and 5 PI and serum TNF-α on d 5 PI, compared with pigs in the control and high-dose antibiotics groups. No differences were observed in the red blood cell profiles between pigs in control and low-dose antibiotics groups, whereas supplementation of high-dose antibiotics had lowest (P < 0.05) packed cell volume but highest (P < 0.05) mean corpuscular hemoglobin concentration among three treatments. In conclusion, low-dose antibiotic supplementation may exacerbate systemic inflammation caused by F18 E. coli infection.

scholarly journals Valproic acid disables the Nrf2 anti-oxidant response in acute myeloid leukaemia cells enhancing reactive oxygen species-mediated killing

2021 ◽  
Author(s):  
Yao Jiang ◽  
Andrew D. Southam ◽  
Sandro Trova ◽  
Flavio Beke ◽  
Bader Alhazmi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Valproic Acid ◽  
Low Dose ◽  
De Novo ◽  
Safety Data ◽  
Reactive Oxygen ◽  
Lipid Lowering ◽  
High Dose ◽  
Oxygen Species ◽  
Refractory Aml

Abstract Background We previously demonstrated the in vitro killing of AML cells by the combination of the lipid-lowering agent bezafibrate (BEZ) and the contraceptive hormone medroxyprogesterone acetate (MPA). A phase II trial demonstrated in vivo safety and efficacy of BEZ and MPA (BaP) in elderly, relapsed/refractory AML and high-risk myelodysplastic syndrome (MDS) patients. However, we observed dose-limiting toxicities in a second trial that attempted to improve outcomes via escalation of BaP doses. Thus we sought to identify a third repurposed drug that potentiates activity of low dose BaP (BaP 0.1 mM). Methods and Results We demonstrate that addition of a commonly used anti-epileptic, valproic acid (VAL) to low dose BaP (BaP 0.1 mM)(VBaP) enhanced killing of AML cell lines/primary AML cells to levels similar to high dose BaP (BaP 0.5 mM). Similarly, addition of VAL to BaP 0.1 mM enhanced reactive oxygen species (ROS), lipid peroxidation and inhibition of de novo fatty acid synthesis. Overexpression of Nrf2 in K562 and KG1a completely inhibited ROS production and rescued cells from VAL/BaP 0.1 mM/VBaP killing. Conclusions Given the good safety data of low-dose BaP in elderly/relapsed/refractory AML patients, and that VAL alone is well-tolerated, we propose VBaP as a novel therapeutic combination for AML.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

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