TY - JOUR. T1 - Dose-response characteristics for effects of insulin on production and utilization of glucose in man.. AU - Rizza, R. A.. AU - Mandarino, L. J.. AU - Gerich, J. E.. PY - 1981/6/1. Y1 - 1981/6/1. N2 - To determine the dose-response characteristics for the effects of insulin on glucose production, glucose utilization, and overall glucose metabolism in normal man, 15 healthy subjects were infused with insulin for 8 h at sequential rates ranging from 0.2 to 5.0 mU.kg-1.min-1; each rate was used for 2 h. Glucose production and utilization were measured isotopically ([3-3H]glucose). Tissue insulin receptor occupancy was estimated from erythrocyte insulin binding. Glucose production was completely suppressed at plasma insulin concentrations of approximately 60 microunits/ml. Maximal glucose utilization (10-11 mg.kg-1.min-1) occurred at insulin concentrations of 200-700 microunits/ml. The concentration of insulin causing half-maximal glucose utilization (55 + 7 microunits/ml) was ...
Chromosome aberrations induced in vivo were studied in nine children 5-12 years old treated with total-body high-energy photon irradiation (pulsed exposure from a LINAC) for different types of malignant diseases. Dose-effect relationships were obtained for each child by taking blood at different times during exposure. In vitro dose-effect relationships for chromosome aberrations in children and adults were obtained by exposing blood under the same conditions as the children. Exposure in vivo and in vitro yielded similar linear-quadratic dose-effect relationships for dicentric aberrations. The response in vitro was slightly greater than in vivo, but the difference was not very large. It is concluded that the dose-effect relationship for dicentric chromosome aberrations obtained in vitro for adults can be used for biological dosimetry in irradiated children. Some of the children displayed a high number of "rogue cells" before exposure; this may be due to the malignant disease as it was not found ...
Dose-Related Adverse Reactions Schizophrenia Dose response relationships for the incidence of treatment-emergent adverse events were evaluated from four trials in adult patients with schizophrenia comparing various fixed doses (2, 5, 10, 15, 20, and 30 mg/day) of oral aripiprazole to placebo. This analysis, stratified by study, indicated that the only adverse reaction to have a possible dose response relationship, and then most prominent only with 30 mg, was somnolence [including sedation]; (incidences were placebo, 7.1%; 10 mg, 8.5%; 15 mg, 8.7%; 20 mg, 7.5%; 30 mg, 12.6%). In the study of pediatric patients (13 to 17 years of age) with schizophrenia, three common adverse reactions appeared to have a possible dose response relationship: extrapyramidal disorder (incidences were placebo, 5.0%; 10 mg, 13.0%; 30 mg, 21.6%); somnolence (incidences were placebo, 6.0%; 10 mg, 11.0%; 30 mg, 21.6%); and tremor (incidences were placebo, 2.0%; 10 mg, 2.0%; 30 mg, 11.8%). Extrapyramidal Symptoms ...
This Phase Ib Trial is Dose Finding Study of ABT-199 (A-1195425.0) Plus Ibrutinib (PCI-32765) and Rituximab in Patients With Relapsed/Refractory Diffuse Large
BioAssay record AID 189219 submitted by ChEMBL: Percent reduction of neutrophil accumulatiom with an minimum effective dose of 1 mg/kg when administered orally twice daily for two days before induction of acetic acid-induced colitis in the rat.
BioAssay record AID 167575 submitted by ChEMBL: In vitro functional antagonistic testing by obtaining ET-1 concentration response curves in rabbit carotid artery rings in the presence or absence of antagonist..
Corticotropin Releasing Hormone (CRH) is a hypothalamic hormone made up of 41 amino acids. Amino acids are proteins that when combined make up different substances, like hormones. The order of amino acids in CRH, has been determined, meaning that the hormone can now be synthetically reproduced in a laboratory setting.. When CRH is released from the hypothalamus it stimulates the pituitary gland to secrete another hormone, ACTH. ACTH then causes the adrenal glands to make a third hormone, cortisol. This process is known as the hypothalamic-pituitary-adrenal axis. Problems can occur in any of the steps of this process and result in a variety of diseases (Cushings Syndrome and adrenal insufficiency).. Researchers hope that CRH created in a laboratory setting, ovine CRH (oCRH) can be used to help diagnose and treat conditions of the HPA axis. This study will test the relationship for single doses of oCRH in normal volunteers and patients with disorders of the HPA axis. The oCRH will be injected ...
A Phase II, Randomized, Double-Blind, Placebo and Active Controlled, Parallel Group, Multi-Center, Dose Ranging Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Resistant Hypertension ...
A shallow slope of the exposure response relationship in the observable range in a laboratory bioassay predicts a higher low dose risk; a steep slope a lower low dose risk and thus allows a higher and less protective exposure limit. Increased variability in biological response of the host predicts a shallower exposure response relationship. BrooklynDodger hypothesizes that genetically diverse free living humans show greater variability than genetically homogeneous inbred laboratory housed animals. Therefore, a reference dose established with a dose response relationship in a laboratory study will be underestimate risk in people ...
May or may not have been receiving an approved PDE-5 inhibitor OR an approved ERA.. Subjects receiving an approved ERA or an approved PDE-5 inhibitor must have been on a stable dose for 30 days prior to Baseline, and were willing to remain on a PDE-5 inhibitor or an ERA and at the same dose for the duration of the 12-week Treatment Phase. If a subject chose to discontinue their PDE-5 or ERA prior to entering this study, they must have had a ≥30 day washout period between the last dose of the PDE-5 or ERA and start of the screening phase.. ...
This is one of my favourite topics to ask in vivas. It is very easy to get yourself confused unless you have things clear in your head. Practise, practise, practise..... BT_ GS 1.3 Define and explain dose-effect relationships of drugs with reference to: · Graded and quantal response · Therapeutic index · Potency and efficacy ·…
This 2 part study will select the subcutaneous(sc) dose of Herceptin which results in comparable exposure to intravenous(iv) Herceptin in healthy male v
UCL Discovery is UCLs open access repository, showcasing and providing access to UCL research outputs from all UCL disciplines.
The identification of molecules involved in the mitogenic signaling and participating to the process of neoplastic transformation and progression has fostered the synthesis of novel agents able to selectively down-regulate such targets. PKAI seems to be one of such relevant targets suitable for therapeutic intervention, and antisense oligonucleotides against its RIα subunit have shown promising results in inhibiting human cancer cell growth in vitro and in vivo (9, 10, 11, 12 , 15) .. In the present study, we have demonstrated that HYB 165, a novel DNA/RNA hybrid MBO with improved pharmacokinetic and bioavailability properties in vivo, exhibits a dose-dependent inhibitory effect on soft agar growth of ZR-75-1 breast cancer cells.. We have also shown that HYB 165, but not its control oligo HYB 508, has a synergisitic inhibitory effect on ZR-75-1 colony formation when used in combination with docetaxel, a cytotoxic drug very active in breast cancer patients (26) . The antiproliferative activity ...
The high rate of dose interruptions and reductions in the initially approved dose of oncology drugs points out the importance and need for improvement to current dose selection strategies that are based on the MTD/3 + 3 method. For example, the FDA approved ponatinib at 45 mg once daily in December 2012 as a treatment for adult patients with chronic myeloid leukemia (CML; ref. 5). Vascular occlusions (arterial and venous thrombosis and occlusions) occurred in at least 27% of treated patients. The adverse events included fatal myocardial infarction, stroke, stenosis of large cerebral arterial vessels, and severe peripheral vascular disease, often resulting in the need for urgent revascularization procedures (5). Ponatinib, once daily at 45 mg, was determined as the MTD in a phase I dose-escalation study using the 3 + 3 design (6), and no clear understanding was reached of the dose-response relationship for these vaso-occlusive events. Eventually, the FDA revised the label to explicitly indicate ...
S78454 (also called PCI-24781) is an orally bioavailable, hydroxamate-based pan-HDACi currently being tested in clinical trials in the US and EU. Like many other HDACi, this drug induces a reversible thrombocytopenia. This thrombocytopenia, which was associated with a decrease in either GATA1 transcriptional activity or the expression of proteins of the Rho GTPase family (RhoA, Cdc42 or Rac), remains poorly understood. Given that the S78454 plasma level is above 100nM in treated patients, we performed a dose-response analysis (from 10 to 100 nM) of the drug effects on CFU-MK growth and cell proliferation. CFU-MKs were generated by ex vivo culture of CD34-positive cells and their differentiation was dose-dependently decreased after either a 24-hour treatment or a continuous exposure to S78454. This effect was associated with a dose-dependent decrease in MK proliferation. When added at day 8 of the culture, at a time-point when MK have nearly finished their endomitotic process and are entering in ...
Here, using a Tecan Sunrise™ absorbance plate reader, a pre-selected enriched SM library containing 4,182 SMs was screened at 100 µM concentration against a predominant field APEC serotype, APEC O78, grown in minimal M63 media. Of the total 4,182 SMs, 41 SMs inhibited APEC O78 growth. The majority of growth inhibitory SMs were found belonging to chemical groups; quinolines, piperidines, pyrrolidinyls, and imidazoles. Among 41 SMs, 30 SMs exhibited bacteriostatic activity, while remaining 11 SMs displayed bactericidal activity and were selected for further studies. Dose-response analysis of these selected SMs revealed their dose-dependent activity with minimal inhibitory concentration (MIC) ranging 12.5 µM to 200 µM. These selected SMs were found broadly effective against various APEC serotypes such as O1, O2, O8, O15, O18, O35, O109, and O115. Six of these SMs exhibited narrow-spectral activity affecting 1-3 tested commensal bacteria. Except SM11, other SMs were least toxic to Caco-2 ...
TY - JOUR. T1 - Studies on the mechanism of haloacetonitrile-induced gastrointestinal toxicity. T2 - interaction of dibromoacetonitrile with glutathione and glutathione-S-transferase in rats.. AU - Ahmed, A. E.. AU - Hussein, G. I.. AU - Loh, J. P.. AU - Abdel-Rahman, Sherif. PY - 1991/6. Y1 - 1991/6. N2 - The haloacetonitrile, dibromoacetonitrile (DBAN), is a direct-acting genotoxic agent that has been detected in drinking water. In a time course study, male Sprague-Dawley rats were treated with DBAN (75 mg/kg PO), and killed at 0.5, 1, 2, and 4 hr after treatment. In a dose response study, animals were treated orally with various doses of DBAN (25, 50, 75, and 100 mg/kg) and killed at one-half hour after treatment. Control animals received 1 ml/kg PO of the vehicle dimethyl sulfoxide (DMSO). In both experiments blood and organs were collected and stored at -80 degrees C until the time of analysis. At 0.5 hr after treatment, a single oral dose of DBAN caused a significant decrease of ...
Antibody vs Antigen concentration effect - posted in SDS-PAGE and Western Blotting: Someone once described to me that if there are too many non-specific bands when performing Western blot that a solution is to load more lysate? If this is true would one achieve the same effect if the lysate amount is held constant and the antibody concentration titrated? I have been trying to track down a literature article describing this. Hoping someone can shed some light. Thanks
Concerns about the present study: One Forum reviewer stated: "This appears to be a carefully designed and well executed study, but I have four concerns: (1) The study has been undertaken in high-risk individuals, more than half of whom are hypertensive, a quarter dyslipidaemic, and a quarter diabetic. It is not described what happened to the conventional risk factors during the interventions. (For example, any improvement in inflammatory markers may have come at the cost of higher blood pressure with the alcohol interventions.) (2) Was there any weight change that could have confounded any of the outcomes? (3) Both polyphenol and alcohol biomarkers were measured - did the change in these biomarkers correlate with the changes in any of the inflammatory markers; i.e., any suggestion of a dose response relationship? (4) Even though at least 30 outcome variables were assessed, the authors do not describe any correction for multiple comparisons ...
Peterson, W J., "Identification and estimation of the proportion of limiting cell types involved in the phytohemagglutinin response by limiting cell dose-response analysis." (1982). Subject Strain Bibliography 1982. 4323 ...
Dr. Mercola, who is a self proclaimed fiber guru and our featured authority, states that lower than 10% of the folks within the United States eat enough dietary fiber. A lot of wonderful info right here and as a former Health and Security Rep with particular regard to DSE (Show Screen Tools) I know your recommendation is sound and greater than value following. Heart illness, slow growth, and different points might make a dog owner suspect a genetic illness.. If asked, many aged people suffering from health points would say they wished that that they had taken better care of themselves of their earlier years. Comprehensive weight problems prevention applications function in a dose‐response relationship; the more cash thats invested within the programs, the less individuals that can become sick or die from weight problems. Your physical health is essential, taking a look at your life as a whole youll probably sustain a number of bodily injuries. Weight problems is among the the explanation why ...
Higher levels of vitamin D are associated with an increased risk of hip replacement for osteoarthritis but only in men, Australian researchers report. The study of 9135 participants from the AusDiab study found that in males a one-standard-deviation increase in 25-hydroxy-vitamin D was associated with a 25% increased incidence of hip replacement. A dose response relationship […]
Conclusions: This study has shown dose response relationships between SHS and major tobacco related mortality, and provided new evidence to support causation for COPD and ischemic stroke ...
The bioassay data displayed in this panel includes modeled AC50 values from multi-concentration data only. Single concentration data may also be available for some assay technologies. Single concentration data are included in the list of tested assays endpoints if multi-concentration data are unavailable; this can be visualized by searching for a chemical, and clicking "All Tested" in the Assay pane in the Toxcast Dashboard. Raw, normalized, and interpreted single concentration data from level 0 to level 2 are fully available from the freely downloadable MySQL database, invitrodb. Internet Explorer may enable the best functionality to view the Toxcast Dashboard. The scaled response shown on the graph below is calculated by dividing the response values by the activity cutoff thereby enabling response comparisons across assay endpoints ...
Phase I, open label, dual centre, dose finding study to evaluate the safety and tolerability of continuous twice daily oral dosing with AZD2281 when adm
The bioassay data displayed in this panel includes modeled AC50 values from multi-concentration data only. Single concentration data may also be available for some assay technologies. Single concentration data are included in the list of tested assays endpoints if multi-concentration data are unavailable; this can be visualized by searching for a chemical, and clicking "All Tested" in the Assay pane in the Toxcast Dashboard. Raw, normalized, and interpreted single concentration data from level 0 to level 2 are fully available from the freely downloadable MySQL database, invitrodb. Internet Explorer may enable the best functionality to view the Toxcast Dashboard. The scaled response shown on the graph below is calculated by dividing the response values by the activity cutoff thereby enabling response comparisons across assay endpoints ...
Drug-drug interactions associated with EE2 therapy have been primarily studied in regard to the cytochromes P450. Few studies investigating interactions with the SULTs or other major conjugating enzyme systems have been reported. The inhibition of SULT1A1 at low nanomolar concentrations of EE2 while allowing for EE2 sulfation at higher concentrations suggests a new paradigm for investigating and understanding drug-drug interactions involving SULT1A1 and possibly other isoforms. SULT1A1 is the major xenobiotic sulfating isoform in liver and is widely expressed throughout the body (Hempel et al., 2007); however, its interactions in EE2 therapy are not well studied. The potent inhibition of SULT1A1 was unexpected and indicates that more attention should be paid to sulfation of both drugs and xenobiotics during concurrent therapy with EE2-containing contraceptives. Lack of sulfation activity at the inhibitory concentrations also suggests a relatively long duration of inhibition. Combined with the ...
The inhibition of the respiration rates for all tested concentrations was in the range of -4.9 to 76 % compared to the mean control. For three lower tested concentration of 10, 32 and 100 mg/L the respiration rate of activated sludge after the incubation period of 3 hours was in the range of the control (i.e. mean values of 0.2, -2.3 and -1.4 %, respectively compared to the control). Therefore, up to and including the concentration of 100 mg/L the test item had no statistically significant inhibitory effect on the respiration rate of activated sludge after the incubation period of 3 hours (result of a Williams t-test,one-sided smaller,a = 0.05). At the higher test item concentrations of 320 and 1000 mg/L the test item had an increasing statistically significant inhibitory effect, with mean values of 56 and 75 % inhibition, respectively. A clear concentration-effect relationship on the inhibition of the respiration rate was observed. ...
A system is disclosed for dispensing an useful agent. The system comprises (1) means for storing an agent, (2) an agent stored in the means, (3) means for releasing agent from the system, (4) means for absorbing fluid into the system surrounding the storing means, and (5) means for admitting fluid into the system. In operation fluid is admitted into the system by the admitting means cooperating with the absorbing means, causing it to increase in dimensions and apply force against the storing means, which force urges the storing means to decrease its dimensions and correspondingly dispense agent through the releasing means from the system. Laminates are disclosed useful for manufacturing the system.
For liver disease (general), 400-1,500 milligrams of SAMe has been taken by mouth 1-2 times daily for 1-24 months in the form of Samyr . A dose of 600 milligrams of SAMe in 250 milliliters of saline has been injected in the vein for three days, followed by 400 milligrams of SAMe taken by mouth three times daily for another 30 days. The following doses of SAMe have been injected into the vein: a single dose containing 50 milligrams; 50-800 milligrams daily for 15-17; 800 milligrams, followed by 1,600 milligrams; 250 milligrams as a slow bolus drip every 12 hours for 30 days in 500 milliliters of 5 percent levulose; 500 milligrams in 250 milliliters of sugar solution daily; and 15 milligrams four times daily for 30 days. The following doses of SAMe have been injected into the muscle: 50-800 milligrams daily for up to 30 days, and 15 milligrams four times daily for 30 days. A dose of 200 milligrams of SAMe has been injected into the vein daily for 15 days, then injected into the muscle for 15 days ...
A review of the basic concept of an analytic dilution assay-one in which relative potency is defined as the ratio of the quantity of effective constituent in unit amount of test to that in the standard-indicates that such an assay is rarely achieved in practice. It is proposed that there are no invalid assays, but only invalid inferences from a set of conditions in which relative potency has been determined and found variable, to new, unknown conditions. Nonparallel log dose-response lines are then interpreted to mean that relative potency varies among other things, with response level, where relative potency is defined as the ratio of doses leading to equal responses. Formulas are given for expressing log relative potency as a function of dose or level of response (formulas 3 and 4) and for making probability statements about it (formulas 9 and 10). The methods are illustrated by reference to a non-parallel log dose-response line assay of two different corticosteroids.. ...
A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimers disease.
With aging, men and women develop a mild and progressive metabolic acidosis. This occurs as a result of declining renal function and ingestion of acid-producing...
Citation: Jacob CC, Reimschuessel R, Von Tungeln LS, Olson GR, Warbritton AR, Hattan DG, Beland FA, Gamboa da Costa G. Dose-response assessment of nephrotoxicity from a 7-day combined exposure to melamine and cyanuric acid in F344 rats. Toxicol Sci. 2011 Feb;119(2):391-7. doi: 10.1093/toxsci/kfq333. Epub 2010 Oct 28.Pubmed Abstract ...
The goal of this clinical research study is to find the best dose of the drugs dabrafenib and trametinib that can be given together or alone in patients with advanced solid cancer that has a BRAF mutation. The effects of the study drugs at different dose levels and the safety of the study drugs will also be studied
This is a multi-center, randomized, double-blind, controlled, Phase 2 study to assess the safety, tolerability, and efficacy of PB1046 at the optimally titrated dose after 16 weeks of treatment. Subjects will be randomized in a 2:1 ratio to one of two parallel dose groups: a) high-dose group where PB1046 will be up-titrated from a 0.2 mg/kg minimally effective starting dose to a target high dose level of at least 1.2 mg/kg or higher to a maximally tolerated dose (MTD), or b) a low-dose group that will start at 0.2 mg/kg and remain at this minimally effective dose (MED) level with sham up-titration. The total treatment period will be comprised of 2 phases: 1) an initial 10 week dose titration phase in which weekly doses of PB1046 will be titrated (or sham titrated) up to a target dose level of at least 1.2 mg/kg or higher to the MTD, and 2) a maintenance of treatment phase that begins when subjects reach week 11 and continues for 6 weeks during which no further up-titration should occur. Type: ...
Dose-dependent induction of HO-1 protein expression and HO-activity by curcumin. HO-1 protein expression was studied in fibroblasts treated for 24 hrs with diff
Polishing Step using CEX (SP Sepharose) - Hi experts, I would like to ask during polishing of antibody using CEX process (SP Sepharose) , does the high concentration of samples (10-20mg/ml) will give effects during loading and also elution...
Polishing Step using CEX (SP Sepharose) - Hi experts, I would like to ask during polishing of antibody using CEX process (SP Sepharose) , does the high concentration of samples (10-20mg/ml) will give effects during loading and also elution...
5 Answers - Posted in: klonopin, ritalin, withdrawal, dosage - Answer: Hi sorry I have not been on but some things came up. About this klonopin. ...
Our objective is to design, construct and evaluate an RASV delivering multiple protective pneumococcal protein antigens to be delivered orally to newborns and infants to confer protective immunity to all pneumococcal serotypes. The vaccine prototype has been demonstrated to be totally safe in newborn, pregnant, malnourished and immunodeficient mice and the collective preclinical data led to FDA approval and the granting of an IND license. Human clinical dose escalation trials with doses up to 1010 CFU have been completed with no adverse reactions, essentially no bacteremias and no shedding of viable vaccine cells in stools. Although totally safe, the RASV constructs were not as immunogenic as desired but strains with the RpoS+ phenotype gave better results than the vaccine strain that was RpoS-. A selected strain has been further improved to significantly enhance immunogenicity without compromising safety attributes. This isolate will be evaluated in human trials. The vaccine is also designed to ...
EDMONTON, Canada, July 6 (ots/PRNewswire) - Isotechnika Inc. (TSX:ISA) announced today the completion of thesingle ascending dose trial for the Companys lead...
The dose-response relationship between the quartiles (Q) of PFOS and reduced levels of TG (A) and FAs (B-E) in maternal serum samples, Sapporo, Japan, 2002
Aug 23, 2007 - CollaGenex Pharmaceuticals, Inc. (NASDAQ CGPI) today announced results of a Phase 2 dose-finding study designed to evaluate the safety and effica
An initial report into a drug trial that left one person dead and five with brain damage says a very high dose may have led to off-target effects
The next phase of treating stage 4 kidney cancer in my lungs begins tomorrow. Tomorrow I will be given a very high dose of radiation directed at the tumor mass in my right lung that refuses to shrink. This will be the third different type of treatment I will have received to battle this kidney…
Have you ever been there? Everything seems to be going perfectly with your ratios and then slowly over a matter of weeks what used to be a walk in the...
The possibility that pharmacological response might help to refine psychiatric nosology has been the subject of recurrent speculation, but few clear-cut results have been obtained. Only bipolar depressives and several other minor patient subgroups manifest consistent drug responses in a...read more ...
Has anyone gotten brain zaps when theyve gone to a higher dose? I did 5mg Lexapro for 3 weeks, then 10 days at 10mg, 4 days at 15mg and today I went to 20mg of Lexapro, per doctors instructions. When I started and at the other dose changes I just had headaches and felt dizzy till I adjusted. I have, on occasion, had brain zaps. But today its been going on all day ...
Hello everyone, I am new to this forum but have been reading for a while. You guys are awesome & are so helpful! Thanks to many GREAT posts! :clap I have a 9 day old little boy & we have been EBF since day one. He is the second that I BF. My first son only received it for 6 months- I had to introduce a bottle to him pretty early on & had many issues. After I delivered my first son, I was given very high doses of steroids and had to pump and dump for a few days. There were many
23-year-old Hayley Steinfeld says she has renewed her musical career from the ashes of a failed relationship with 26-year-old Niall Horan, a member of ...
Sometimes a treatment may be started at a lower dose or the dose needs to be changed during treatment. There may also be times when your treatment is delayed. This can happen if your doctor thinks you are likely to have severe side effects, if you get severe side effects, if your blood counts are affected and causing delays in treatment, or if you are finding it hard to cope with the treatment. This is called a dose reduction, dose change or treatment delay. Your doctor will explain if you need any changes or delays to your treatment and the reason why. ...
This study will consist of 2 sequential parts: the first part (VLA009A)is a study of intravenous CVA21 as a single agent for the treatment of 4 different advanced solid tumours; the second part (VLA009B) is a study of intravenous CVA21 in combination with cytotoxic therapy appropriate for the solid tumour selected in the first part. Both parts will be open-label, multi-centre, ascending dose escalation (3+3 design) dose-finding and signal seeking studies.
Clinical Trials - clinicaltrials.gov An open-label study designed to evaluate the safety, tolerability, and pharmacokinetics of ALA-1000 in opioid-dependent sub...
Most GLP-1 receptor agonists are injectable; semaglutide will be one of the first oral GLP-1s. A new study compares oral semaglutide to injectable.
The dosage of Vincristine had been raised from 50% to 75%, and its an indication of how powerful this drug is that an additional 0.19 mg. should make such a massive difference in terms of side effects.Our experience with the lower dosage had made us feel pretty confident about chemotherapy - "We can handle this!" - but this cycle put us back on the defensive again ...
No DDDs have been established because of highly individualised use and wide dosage ranges. The doses used vary substantially because of various types and severity of neoplastic diseases, and also because of the extensive use of combination therapy ...
One day i take my pressure and it is ok, next time it is high. should i worry or call the dr? I just started for - Answered by a verified Health Professional
Feeling DRUG DOSE OMISSION while using Ativan? DRUG DOSE OMISSION Causes, Patient Concerns and Latest Treatments and Ativan Reports and Side Effects.
For about at least 6 times now, every time I know I am coming down with the flu or at the start of the flu, I take the Azithromycin 5-Day pak and m...
As with many antidepressants, Zoloft has been linked with numerous adverse side effects, some of which are potentially life-threatening.
... is a treatment for the side effects of Parkinsons disease. Learn more about how it works, dosage information and adverse side effects.
Maximum effects of ThioGel - L is available from Ethical Alternative Products, for high quality dietary suppliments that are known to work.
What is Isomalto-Oligosaccharide (IMO)? Where does it come from? What are its benefits? What is the preferred dosage? Does it have any adverse side effects?
23 yrs old Female asked about Stimach problem, 1 doctor answered this and 48 people found it useful. Get your query answered 24*7 only on | Practo Consult
During the period and end of the period i had sex with my boy friend. Next day i took postinor 1. After 6 days i have bleeding in brown color. Can you explain this situation?
19 yrs old Male asked about Mastrubate, 1 doctor answered this and 362 people found it useful. Get your query answered 24*7 only on | Practo Consult
Cobicistat reduces the action of enzymes in your liver that break down certain antiviral medicines. This allows the antiviral medicines to be used more safely and effectively at lower doses.
I dont know if this is relatable to the general population, but for me as a person who struggles with disabled conditions, to experience and live a good day, is one of the rarest but most satisfying feelings in the world. The days included among my happiest was such as the day I sat in…
Heres a bit more of the progress... [mention]Sadie[/mention] wrote:It seems to be progressing really well now-in a few days I think it may come to life Maybe
I have been so depressed the last 3 days I dont even want to get out of bed. I have to force myself to do anything. I cry a lot.I feel so worthless. Why cant I go on with my life and do the things I need to do? My DH has Alzheimers and I.... ...
My husband says in the 42 days I have not smoked, I have been having many conniptions :o...I thought I was very sweet..Like he has never had any ...ha! Any one...
How is micrograms per liter abbreviated? µg/L stands for micrograms per liter. µg/L is defined as micrograms per liter very frequently.
The treatment is not a cure for excessive sweating. It needs to be repeated every three to six months for maximum effect. Call 020 7565 0333.
ನಿಕೋಟಿನ್‌ನ ಎಲ್‌ಡಿ50 ಪ್ರಮಾಣ ಇಲಿಗಳಿಗೆ 50 ಮಿಗ್ರಾ/ಕಿಗ್ರಾ ಮತ್ತು ಮೂಗಿಲಿಗಳಿಗೆ 3 ಮಿಗ್ರಾ/ಕಿಗ್ರಾ. 40-60 ಮಿಗ್ರಾಂ. (0.5-1.0 mg/kg) ಇದು ವಯಸ್ಕ ಮನುಷ್ಯರಿಗೆ ಘಾತಕ ಪ್ರಮಾಣವಾಗಿರುತ್ತದೆ.[೪೩][೪೪] ಆದ್ದರಿಂದ, ಕೊಕೈನ್‌ನಂತಹ ಇತರ ಕ್ಷಾರಗಳಿಗೆ ತುಲನೆ ಮಾಡಿ ನೋಡಿದಾದ ನಿಕೋಟಿನ್ ಹೆಚ್ಚಿನ ವಿಷತ್ವವನ್ನು ಹೊಂದಿದೆ, ಅದು ಮೈಸ್‌ಗೆ ನಿರ್ವಹಣೆ ಮಾಡಿ ನೋಡಿದಾಗ 95.1 ಮಿಗ್ರಾಂ/ಕಿಗ್ರಾಂ ನ LD50 ಪ್ರಮಾಣವನ್ನು ಹೊಂದಿದೆ. ಆದಾಗ್ಯೂ, ಕೇವಲ ಧೂಮಪಾನದ ಮೂಲಕ ನಿಕೋಟಿನ್ ಅನ್ನು ಅತಿ ...
خاک نقش مهمی را در چرخه بیوژئوشیمیایی به عنوان یک منبع مهم ذخیره عناصر ایفا می-کند. از عوامل مهمی که در کشاورزی حائز اهمیت است نوع ویژگی-های خاک، پراکنش و میزان تغییرات آن می-باشد. در این مطالعه 600 نمونه خاک با فواصل تقریبی 100 متر در 100 متر از عمق 30-0 سانتی-متری در 800 هکتار از اراضی شرکت کشت و صنعت شریف آباد قزوین جمع-آوری شد. آنالیز آمار توصیفی و زمین آماری داده-های جمع-آوری شده، انجام شد. نتایج نشان داد دامنه تغییرات نیتروژن کل خاک در محدوده 82/0- 02/0% با میانگین 26/0 درصد، فسفر قابل استخراج با اولسن در محدودهmg/kg 07/93-58/9 با میانگین 21/36 میلی-گرم بر کیلوگرم، پتاسیم قابل
Резюме: Оценката на качеството на храните е ключов въпрос и загриженост за всички правителства. Правила и наблюдение на храните в хранителната верига са приети във всички страни. Няма съмнение, че храната е тясно свързана с човешкото здраве. Един от най-често срещаните замърсители са нитрати и нитрити, които имат положително не само отрицателно влияние. В статията са представени резултати от оценка съдържанието на NO3- в различни продукти на пазара на хранителни вериги в България. Открито е по-голямо количество NO3- до 900 mg / kg в пресни картофи, със ...
And things get even murkier or perhaps more clear when Dr. H. Kamel discusses challenges to the notion that the risk of stroke in afib is in fact solely due to thrombi in the left atrium and proposes that things are much more complicated including the notion that at least sometimes a stroke can cause an atrial thrombus. It is well known that stroke can precede the onset of afib.He and coauthors discuss a new model for stroke and afib in which both afib and emboli are downstream effect of abnormal atria substrate (an atrial myopathy).This model might explain why stroke risk is not eliminated by rhythm control strategies and why stroke can predate afib and generally the poor temporal relationship that exist between afib onset and stroke and why some reports do not show a dose response relationship between afib duration and stroke(.However, other reports such as the TRENDS data do show dose response relationship ...
BACKGROUND: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). METHODS: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. RESULTS: We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. CONCLUSIONS: There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs.
Assessment of the efficacy of CN-100 a non-Steroidal antiphlogistic on the pain after the extraction of the impacted mandibular wisdom tooth. An optimal dose finding study by a multi-centered double blind study.:-An optimal dose finding study by a multi-centered double blind study- (1991 ...
Half maximal effective concentration (EC50) refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time.[1] It is commonly used as a measure of a drugs potency. EC50 is expressed in molar units (M), where 1 M is equivalent to 1 mol/L. The EC50 of a graded dose response curve therefore represents the concentration of a compound where 50% of its maximal effect is observed.[2] The EC50 of a quantal dose response curve represents the concentration of a compound where 50% of the population exhibit a response,[3] after a specified exposure duration. It is also related to IC50 which is a measure of a compounds inhibition (50% inhibition). For competition binding assays and functional antagonist assays IC50 is the most common summary measure of the dose-response curve. For agonist/stimulator assays the most common summary measure is the EC50.[4] The half maximal effective concentration is sometimes also ...
I am a 60-year-old female with osteoporosis. I took Fosamax 70 mg once weekly for seven months until I could no longer endure the side effects. For the following month, I took no medication. Since January 21, 2008, I have been on 680 mg strontium citrate once daily. I intend to relate my progress. My first DEXA scan was done May 8, 2007. My T-score at the lumbar spine was -3.0 (-2.0 at L1, -2.7 at L2, -3.4 at L3 and -3.8 at L4). My T-score at the left hip was -2.2 (-2.8 at neck, -2.0 at troch, -1.9 at inter). My BMD results in g/cm2 were 0.712 at the spine (L1-L4), 0.53 at the left hip (neck), and 0.670 at the left hip (total). A followup scan is planned for July 6, 2009. For these results, see: http://strontiumforbones.blogspot.com/2009/07/improved-t-scores-after-treatment. ...
Information relevant for assessing potential adverse health effects from occupational exposure to chlorobenzene (108907) was reviewed and summarized. Topics included physical properties, chemical properties, production levels, industrial uses, occupational exposure levels, toxicokinetics, acute and chronic toxicity, organ system toxicity, immunotoxicity, allergy, genotoxicity, carcinogenicity, teratogenicity, reproductive toxicity, dose/response relationships, and research needs. Studies have indicated that chlorobenzene is absorbed via respiratory and dermal routes and has resulted in headaches, dizziness, somnolence, and dyspeptic disorders in humans chronically exposed. There were no case reports or epidemiological studies available concerned with the potential carcinogenicity of chlorobenzene in humans. There was some limited evidence indicating that the compound is genotoxic and that it may induce hematopoietic toxicity at relatively moderate doses. Chlorobenzene was not classifiable as a ...
Warfarin is widely used oral anticoagulant and its pharrnacokinetic (PK) and pharrnacodynamic (PD) properties have been extensively studied. It has a narrow therapeutic index and displays poor quality of treatment due to its complex pharmacology and wide inter and intraindividual variability in the dose-response relationship. This study developed an integrated PK-PD model using STELLA® to describe the dose concentration- effect relationship for warfarin. This model used previously reported\ population PK and PD models and parameter values to generate dose-response data. A one compartment stereo-specific semi-physiological PK model with zero-order drug input was linked to an indirect PD model describing the anticoagulant effect. The indirect PD model consisted of two components: (i) the plasma concentration of S-enantiomer of warfarin (Cs) was related to synthesis of prothrombin complex activity (PCA) described by sigmoid Imax model (ii) conversion of PCA to prothrombin time ratio (PTR), which is
The experimental investigations used skin fibroblasts cultures at a density of 50,000 cells/100ml of media (5% fetal calf serum 3% antibiotics) exposed to UVB doses (0-5.6 J/cm2) with damage levels assessed by two cytotoxicity assays (Figure 1).. The MTS results in Figure 2 showed a dose response relationship between exposure and cellular mitochondrial dehydrogenase activity as measured by the MTS assay. A decrease in the mitochondrial activity was directly associated with increased UVB dose. The cell exposure to a dose of 2.1 J/cm2 of UVB reduced the mitochondrial activity by more than 50%, while at 5.6 J/cm2 of UVB we witnessed a reduction in activity by 80%.. The relationship between UVB exposure and cellular viability was further investigated using the NR assay. The damage caused by UVB was assessed by determining the reduction in NR dye uptake by the lysosomes because cells with damaged cellular membranes leak and cannot retain the dye [10]. The leakage results in reducing the NR dye uptake ...
Phencyclidine (PCP), a noncompetitive N-methyl d-aspartate (NMDA) receptor antagonist, provides the most complete pharmacologic model of schizophrenia in humans and animals. Acute PCP causes hyperlocomotion, disrupts prepulse inhibition (PPI), and increases social avoidance in rats. We have previously shown that repeated treatment with the dopamine (DA) D2-like receptor agonists, quinpirole or ropinirole, prevents agonist-induced PPI disruption. In the present study, we examined whether repeated ropinirole treatment similarly attenuates the effects of PCP in a more complete model of schizophrenia symptoms and examined the effect of repeated D2-like agonist treatment on locomotion, PPI, and social interaction after acute PCP challenge. The acute effect of PCP (3.0 or 6.0 mg/kg) on locomotor activity was examined to establish a minimum effective dose. Thereafter, the effect of PCP challenge (3.0 mg/kg) on locomotor activity, PPI, and social interaction was assessed in adult male rats before or ...
We observed a moderate positive association between smoking and risk of testicular cancer. Although smoking to any degree was suggestive of an increased risk, the strongest-large effect size and statistically significant-results were observed, independent of smoking status, among those who smoked between 12 and 24 pack-years [OR = 1.96 (95% CI: 1.04-3.69)] or more [,24 pack-years, OR = 2.31 (95% CI 1.12-4.77)] and among those who smoked about ≥21 years [OR = 3.18 (95% CI: 1.32-7.64; Table 2⇓ )]. Although levels of smoking less than this were not statistically significant, examination of the effect estimates and CIs, particularly for pack-years, suggests a dose response relationship.. Modest but suggestive associations between testicular cancer and smoking have been noted in two large population based studies. The United Kingdom Testicular Cancer Group (4) reported a slight elevation in risk among ever smokers relative to never smokers [OR = 1.18 (95% CI: 0.96-1.46)]. No meaningful ...
How does concentration effect on results of particle size distribution test?,Industry News,News,Jinan Winner Particle Instruments Joint Stock Co. Ltd.,Generally, the particle size distribution measurement is performed by the system to identify and re
Increased time outdoors can help prevent myopia onset and lower the myopic shift in refractive error, reported Shuyu Xiong, and coauthors, in a recent study. However, spending time outdoors did not slow myopic progression in eyes that already had myopia. The investigators meta-analysis and review included 25 articles, 23 of which involved children. They found a significant protective effect from outdoor time for incident myopia and prevalent myopia. "With dose-response analysis, an inverse nonlinear relationship was found with increased time outdoors reducing the risk of incident myopia," they wrote. "Also, pooled results from clinical trials indicated that when outdoor time was used as an intervention, there was a reduced myopic shift of -0.30 D (in both myopes and nonmyopes) compared with the control group after 3 years of follow-up." Still, when only myopes were considered, a relationship was not found between time outdoors and myopic progression. Future studies can focus on evaluating the ...
TY - JOUR. T1 - A phase 1, open label, dose escalation study to investigate the safety, tolerability, and pharmacokinetics of MG1102 (apolipoprotein(a) Kringle V) in patients with solid tumors. AU - Kim, Gun Min. AU - Reid, Tony. AU - Shin, Sang Joon. AU - Rha, Sun Young. AU - Ahn, Joong Bae. AU - Lee, Sung Sil. AU - Chung, Hyun Cheol. PY - 2017/12/1. Y1 - 2017/12/1. N2 - Purpose MG1102 is a potent inhibitor of angiogenesis in both in vitro and in vivo models. The purpose of the study was to investigate the safety and tolerability, pharmacokinetic (PK) profile, and preliminary antitumor efficacy of MG1102. Methods Patients with refractory solid tumors were eligible. Each patient received 1 dose of MG1102 followed by a 6-day rest period, during which they underwent PK assessments and safety monitoring. If the initial dose was tolerated, the patient continued with the 21-day treatment of MG1102 (5 days on, 2 days off for 3 weeks). Dose escalation was planned in 6 cohorts (6, 12, 24, 48, 96, and ...
Developed during the follow-up period, 700 women a type of cancer known to be related to smoking. Among the women who was never smoked beta-carotene. Inversely with the risk of developing tobacco-related cancer, with a dose - response relationship over the observed beta-carotene categories However, among women ever smoked ever smoked, the results were reversed: cancer risk was highest among women in the high-beta-carotene group. The Journal of the National… Read Article →. ...
Current excessive use and abuse of antibiotics has resulted in increasing bacterial resistance to common treatment options which is threatening to deprive us of a pillar of modern medicine. In this work methods to optimize the use of existing antibiotics and to help development of new antibiotics were developed and applied.. Semi-mechanistic pharmacokinetic-pharmacodynamic (PKPD) models were developed to describe the time course of the dynamic effect and interaction of combinations of antibiotics. The models were applied to illustrate that colistin combined with a high dose of meropenem may overcome meropenem-resistant P. aeruginosa infections.. The results from an in vivo dose finding study of meropenem was successfully predicted by the meropenem PKPD model in combination with a murine PK model, which supports model based dosage selection. However, the traditional PK/PD index based dose selection was predicted to have poor extrapolation properties from pre-clinical to clinical settings, and ...
Breast-Feeding Promotion Interventions: Good Public Health and Economic Sense. Bonuck, Karen; Arno, Peter S; Memmott, Margaret M; Freeman, Kathy; Gold, Marji; Mckee, Diane // Journal of Perinatology;Jan2002, Vol. 22 Issue 1, p78 The health benefits of breast-feeding are well documented, as are the positive effects of breast-feeding promotion interventions. There is a clear dose -- response relationship between breast-feeding and infant health in the first year of life, and beyond. Further, nearly all breast-feeding... ...
A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and Cemiplimab in Patients With Advanced Solid Tumors
In a 2-year study in Sprague-Dawley rats, albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at dietary doses of 2.0, 10, and 50 mg/kg (approximately ½, 2, and 10 times, respectively, the maximum recommended daily oral dose for adults and children, on a mg/m2 basis). In another study this effect was blocked by the coadministration of propranolol, a non-selective beta-adrenergic antagonist. In an 18-month study in CD-1 mice albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 500 mg/kg (approximately 60 times the maximum recommended daily oral dose for adults and children on a mg/m2 basis). In a 22-month study in the Golden hamster albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/kg (approximately 8 times the maximum recommended daily oral dose for adults and children on a mg/m2 basis). Albuterol sulfate was not mutagenic in the Ames test with or without metabolic ...
LA and triggered cellular and subcellular reactions are pivotal events of early atherosclerosis and restenosis. We came to 3 basic conclusions after completing the present study. First, in monocultures of HCAECs and HCMSMCs, the surface expression of ICAM-1 was reduced in a dose-dependent manner after incubation with 5 and 10 mmol/L aspirin, but no effect was detected after incubation with 1 and 2 mmol/L aspirin. Second, in the 3DLA model, 5 mmol/L aspirin significantly inhibited the adherence of monocytes and CD4+ lymphocytes and the chemotaxis of monocytes. Third, 5 mmol/L aspirin significantly reduced the reactive proliferative response of cocultured HCMSMCs after selective monocyte or CD4+ lymphocyte attack in the 3DLA model.. A dose-dependent inhibitory effect of aspirin on NF-κB-mediated signal cascades agrees with the prior reports of Weber et al14 and Amberger et al,15 who studied endothelial cells from human umbilical veins. The exact mechanism of aspirin on TNF-α-induced and ...
Tonolo, G., Fraser, R., Connell, J. and Kenyon, C. (1988) Chronic Low-Dose Infusions of Dexamethasone in Rats - Effects on Blood-Pressure, Body-Weight and Plasma Atrial Natriuretic Peptide. Journal of Hypertension, 6(1), pp. 25-31 ...
Back in February of this year a excellent Israeli study was done documenting the superior therapeutic properties of whole plant CBD-rich Cannabis extract as compared to synthetic, single-molecule cannabidiol (CBD) which is made in the lab. The notion that botanical extracts are "low grade and crude" as opposed to pure single molecule synthetic compounds made by the pharmaceutical companies is what was challenged. The study was Published in the journal Pharmacology & Pharmacy (Feb. 2015).. The study showed that administration of pure, single-molecule CBD resulted in a bell-shaped dose-response curve, that means when the amount of CBD exceeded a certain point its therapeutic impact declined dramatically. "Healing was only observed when CBD was given within a very limited dose range, whereas no beneficial effect was achieved at either lower or higher doses," the authors observed. This characteristic of single-molecule CBD-manifested as a bell-shaped dose response-imposes serious obstacles that ...
Lay summary: Many therapeutic strategies for FA aim at increasing the cellular level of FXN or alleviating the secondary pathological events which are both impairing mitochondria function and bioenergetics. However, most of the clinical trials have relied on peripheral cells (blood or buccal cells) to validate the short-term bio-availability and the biological effect of the investigational drug. In the present proposal, we aim at developing a comprehensive framework for facilitating the preclinical development and validation of therapeutic strategies for FA cardiomyopathy, with a particular focus on the cardiac gene therapy protocol that we have developed. We have previously shown the proof of concept for the prevention and the correction of FA cardiomyopathy by in vivo gene therapy [1]. More recently, we have conducted a series of dose response studies, which have defined the therapeutic thresholds (histological and molecular) conditioning the stabilization or the correction of the cardiac ...