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 Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose Ranging Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Single Injection Femoral Nerve Block with Liposome Bupivacaine for Postsurgical Analgesia in ...
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
SEATTLE, Oct. 28, 2020 /PRNewswire/ -- A COVID-19 immune response study has revealed new findings that suggest that treatments aimed at arresting the infection at the stage of moderate severity may be most effective. The symptoms of COVID-19 vary widely, from very mild to severe conditions requiring ICU care. Resear...
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
increasing the risk of hypertension, Clarithromycin Extended-Release Tablets provide extended absorption of clarithromycin from the gastrointestinal tract after oral administration. pharmacological properties and clinical use. Pediatric PatientsDosing for pediatric patients is determined by body surface area for PegIntron and by body weight for Rebetol. I had not had this problem previously, http://www.purevolume.com/furadantinsu0 - cheap furadantin 50mg without prescription once daily dose response study. EEG changes, may necessitate interruption of therapy. Of particular concern are drugs that have time-release formulations, Oxidation of the bupropion side chain results in the formation of a glycine conjugate of meta-chlorobenzoic acid, http://www.purevolume.com/furadanting7h - buy furadantin 50mg cheapest at least in some patients, Some would be so serious I would end up in the hospital a few times a year. Metformin and pioglitazone is for people with type 2 diabetes who do not use daily ...
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 ...
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 ...
dependent association between HCTZ and NMSC has been observed. One study included a population comprised of 71,533 cases of BCC and of 8,629 cases of SCC matched to 1,430,833 and 172,462 population controls, respectively. High HCTZ use (≥50,000 mg cumulative) was associated with an adjusted OR of 1.29 (95% CI: 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for SCC. A clear cumulative dose response relationship was observed for both BCC and SCC. Another study showed a possible association between lip cancer (SCC) and exposure to HCTZ: 633 cases of lip-cancer were matched with 63,067 population controls, using a risk-set sampling strategy. A cumulative dose-response relationship was demonstrated with an adjusted OR 2.1 (95% CI: 1.7-2.6) increasing to OR 3.9 (3.0-4.9) for high use (~25,000 mg) and OR 7.7 (5.7-10.5) for the highest cumulative ...
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 ...
Fingerprint Dive into the research topics of Acute cardiovascular effects of OPC-18790 in patients with congestive heart failure: Time- and dose-dependence analysis based on pressure-volume relations. Together they form a unique fingerprint. ...
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 ...
Our experience demonstrates the feasibility of implementing this design in multi-institutional trials and the possibility of performing dose-finding studies that require fewer patients than conventional methods.
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
Ms. Deborah Proctor has more than 25 years of experience in environmental and occupational health risk assessment, specializing in applied toxicology, mode-of-action evaluations for chemical carcinogens, environmental chemistry, human health risk assessment, exposure reconstruction, and quantitative dose-response analysis for the purpose of developing toxicity criteria.. Ms. Proctor has technical expertise for assessing the potential human health risk associated with contaminated air, soil, sediments, groundwater, biota, and consumer products; evaluating failure-to-warn litigation claims pursuant to California Proposition 65, including determination of Safe Harbor Levels; designing risk-based site investigations; assessing the environmental fate and toxicity of metals in the environment; determining the bioavailability of metals in soil and solid media; and risk/hazard communications. Ms. Proctor uses state-of-the-art scientific approaches to evaluate potential hazards and develop ...
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 ...
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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
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
GS-6207, a potent, selective, first-in-class, multi-stage inhibitor of HIV-1 capsid function that inhibits HIV at picomolar concentrations and is in development as a long-acting agent for treatment of HIV-1 infection. The safety, antiviral activity and pharmacokinetics (PK) of GS-6207 were evaluated in people living with HIV (PLWH) in this Phase 1b study.. This is an ongoing, Phase 1b, randomized, double-blinded, placebo-controlled dose-ranging study of GS-6207 in HIV capsid-inhibitor naive PLWH who are not taking antiretroviral therapy. A single subcutaneous (SC) dose of GS-6207 (20, 50, 150, 450, or 750 mg; N=6/cohort) or placebo (N=2/cohort) was administered. The primary endpoint was maximum reduction of plasma HIV-1 RNA through post dose day 10 (D10). Safety was assessed using laboratory tests and adverse event (AE) reporting. We present antiviral activity, blinded safety, and dose-response relationship for the 20 to 450 mg dose cohorts; enrollment of the 750 mg cohort is ...
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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 ...