Proposal to Eliminate Urethane-Treated Positive Control Dose Groups in 26-Week Tg.rasH2 Carcinogenicity Studies

2021 ◽  
pp. 109158182110033
Author(s):  
Madhav G. Paranjpe ◽  
Daniel Rudmann ◽  
Aaron Sargeant ◽  
Mark Morse ◽  
Rossalin Yonpiam ◽  
...  
Keyword(s):  
Alternative Model ◽  
Positive Control ◽  
Short Term ◽  
Control Material ◽  
Pilot Studies ◽  
Cumulative Experience ◽  
Observation Period

Short-term (26 weeks) Tg.rasH2 mouse carcinogenicity studies have been conducted as an alternative model to the conventional 2-year mouse carcinogenicity studies, using urethane as a positive control material. In these studies, urethane was used at a dose of 1,000 mg/kg/dose, administered intraperitoneally on days 1, 3, and 5. Urethane consistently produces lung adenomas and carcinomas and hemangiosarcomas of the spleen, proving validity of the assay. We conducted 3 pilot studies at 3 different sites of Charles River Laboratories using a lower dose of urethane (500 mg/kg/dose), administered on days 1, 3, and 5, followed by a 12-week observation period. Our results demonstrate that a lower dose can be used successfully with fewer number of animals per sex to prove the validity of the assay. However, based on our cumulative experience with this model, we propose to eliminate positive control dose groups in future Tg.rasH2 carcinogenicity studies.

scholarly journals COMPARISON EFFECT OF CV 12, ST 36 AND ST 40 EA ON SHORT TERM ENERGY BALANCE REGULATION IN HIGH FAT DIET RAT

2017 ◽  
Vol 52 (3) ◽  
pp. 174
Author(s):  
Purwo Sri Rejeki ◽  
Harjanto Harjanto ◽  
Raden Argarini ◽  
Imam Subadi
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Energy Balance ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Continuous Wave ◽  
Positive Control ◽  
Control Group ◽  
High Fat ◽  
Short Term

The aim of this study was to determine the comparative effects of EA (EA) on the CV12, ST36 and ST40 to weight gain prevention over the short-term regulation of energy balance. The study was conducted with a completely randomized design. Rats were divided into five groups: negative control group (no treatment, n=5), positive control (sham EA/back, n=5), EA CV 12 (n=6), EA ST 36 (n=6) and EA ST 40 (n=7). Rats were exposed to high-fat diet for two weeks and EA was simultaneously performed once daily, five days a week for two weeks with 2 Hz, for 10 minutes with continuous wave. Body weight, BMI, front limb circumference and rear were measured during study. Levels of blood glucose, cholesterol, triglycerides, LDL and HDL were measured at the end of the study; which reflects the short-term regulation of energy homeostasis. For weight loss, EA CV12, ST36 and ST40 group have lost weight significantly compared to the negative and positive control group. The ST40 group has a significant decrease than ST36 and CV12. The most significant decrease in BMI found in the ST40 group. EA did not affect blood glucose levels, but modulated blood lipid profile. In ST 40 group there was a significant decrease in cholesterol, LDL and triglycerides. EA at point ST 40 is potential in preventing increased body weight and BMI in rats exposed to high-fat diet compared to the CV 12 and ST 36. ST 40 is a point with a potential of lowering LDL and triglycerides serum so that it can play a role in the short term regulation of energy homeostasis but also in the prevention of dyslipidemia.

scholarly journals Reduction in the Number of Animals and the Evaluation Period for the Positive Control Group in Tg.rasH2 Short-Term Carcinogenicity Studies

2012 ◽  
Vol 31 (5) ◽  
pp. 423-429 ◽  
Author(s):  
Sudhir A. Shah ◽  
Madhav. G. Paranjpe ◽  
Philip I. Atkins ◽  
Eias A. Zahalka
Keyword(s):  
Positive Control ◽  
Lung Tumors ◽  
Control Group ◽  
Short Term ◽  
Evaluation Period ◽  
Target Organs ◽  
The Us ◽  
Assessment Committee ◽  
Robust Response ◽  
Positive Controls

The lack of a clear guidance on the adequate number of animals used for positive controls in the short-term (26-weeks) transgenic mouse carcinogenicity studies has resulted in the use of high number of animals. In our earlier Tg.rasH2 studies, 25 mice/sex were used in the urethane-positive control dose groups that were sacrificed by 18 weeks. Based on a robust response, several of our protocols for Tg.rasH2 studies with 15 mice/sex and terminal sacrifice at 17 ± 1 weeks were submitted and accepted by the Carcinogenicity Assessment Committee of the US Food and Drug Administration since we demonstrated close to 100% response for the development of lung and splenic tumors (target organs) in 500 mice/sex. These 500 mice/sex included 17 groups of 25 mice/sex and 5 groups of 15 mice/sex.  The objective of this investigation was to determine whether the number of animals can be further reduced along with the shortened duration of exposure to urethane. Accordingly, 10 Tg.rasH2 mice/sex/group were administered a total of 3 intraperitoneal (IP) injections of urethane (1000 mg/kg per day) on study days 1, 3, and 5, and the presence of tumors in the lungs and spleen was evaluated after 8, 10, 12, 14, or 16 weeks. Our results demonstrate that 100% of the mice at 8 weeks had developed lung tumors, whereas close to 100% of the mice at 14 weeks had developed splenic tumors. Based on the development of lung tumors alone in 100% of the mice, we recommend that 10 mice/sex are sufficient and that these mice can also be sacrificed as early as 10 ± 1 weeks following the administration of urethane.

scholarly journals Radial Retinotomies with Endodiathermy for Severe Proliferative Vitreoretinopathy: Short-Term Results

2016 ◽  
Vol 2016 ◽  
pp. 1-9
Author(s):  
Zhaoxin Jiang ◽  
Suo Qiu ◽  
Bingsheng Lou ◽  
Miaoli Lin ◽  
Junlian Tan ◽  
...  
Keyword(s):  
Silicone Oil ◽  
Fundus Photography ◽  
Oil Removal ◽  
Efficacy And Safety ◽  
Slit Lamp ◽  
Less Invasive Surgery ◽  
Short Term ◽  
Noncomparative Trial ◽  
Slit Lamp Microscopy ◽  
Observation Period

Purpose.Retinal redetachment of silicone oil-filled eyes continues to be a frustrating condition that typically requires retinectomy. We proposed radial retinotomy as a potentially less invasive surgery. Here, we preliminarily explored its feasibility, efficacy, and safety.Methods.Totally 9 eyes of 9 consecutive patients were included in a prospective noncomparative trial. A series of retinotomies were created by endodiathermy in a radial pattern to relax the foreshortened retina. The eye was refilled with fresh silicone oil. The treated eyes were examined via visual acuity (VA) tests, tonometry, slit-lamp microscopy, and fundus photography during a 6-month observation period.Results.The procedure was completed in an average of 28 minutes from silicone oil removal to fresh silicone oil placement. Fundus photography demonstrated that 7 of the 9 eyes (78%) exhibited retinal reattachment. On average, VA was significantly improved within the first 2 weeks (P=0.02) and remained stable for the following 6 months. The change in intraocular pressure was not significant (P=0.76), and no adverse event was observed (0%).Conclusion.Radial retinotomies with endodiathermy were shown to be feasible, effective, and safe in selected cases of inferior contracted retina without vitreous base fibrosis over a 6-month observation period. This trial is registered withNCT02201706.

scholarly journals Biological Safety and Biodistribution of Chitosan Nanoparticles

Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 810 ◽  
Author(s):  
Dmitry Sonin ◽  
Evgeniia Pochkaeva ◽  
Sergei Zhuravskii ◽  
Viktor Postnov ◽  
Dmitry Korolev ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Dose Range ◽  
Chitosan Nanoparticles ◽  
Hemodynamic Changes ◽  
Short Term ◽  
Good Tolerance ◽  
Dose Dependent ◽  
Cultured Cardiomyocytes ◽  
Single Intravenous Administration ◽  
Observation Period

The effect of unmodified chitosan nanoparticles with a size of ~100 nm and a weakly positive charge on blood coagulation, metabolic activity of cultured cardiomyocytes, general toxicity, biodistribution, and reactive changes in rat organs in response to their single intravenous administration at doses of 1, 2, and 4 mg/kg was studied. Chitosan nanoparticles (CNPs) have a small cytotoxic effect and have a weak antiplatelet and anticoagulant effect. Intravenous administration of CNPs does not cause significant hemodynamic changes, and 30 min after the CNPs administration, they mainly accumulate in the liver and lungs, without causing hemolysis and leukocytosis. The toxicity of chitosan nanoparticles was manifested in a dose-dependent short-term delay in weight gain with subsequent recovery, while in the 2-week observation period no signs of pain and distress were observed in rats. Granulomas found in the lungs and liver indicate slow biodegradation of chitosan nanoparticles. In general, the obtained results indicate a good tolerance of intravenous administration of an unmodified chitosan suspension in the studied dose range.

scholarly journals Synthesis, Spectroscopic Characterization, Antibacterial and Short Term in vitro Cytotoxicity Studies of Copper(II) Complexes of Novel Tridentate N,N,S Donor Ligand 2-Benzoylpyridine-N(4),N(4)-(N,N-diethyl-N-methylamine-2,2'-diyl)thiosemicarbazone

2019 ◽  
Vol 31 (10) ◽  
pp. 2269-2274
Author(s):  
Janey Mary Mathew ◽  
Varughese Philip ◽  
Jesty Thomas
Keyword(s):  
Spectroscopic Characterization ◽  
Positive Control ◽  
In Vitro Cytotoxicity ◽  
Planar Geometry ◽  
Blue Dye ◽  
Short Term ◽  
Donor Ligand ◽  
Cytotoxicity Studies ◽  
Uv Visible

A tridentate N,N,S-donor ligand, 2-benzoylpyridine-N(4),N(4)-(N,N-diethyl-N-methylamine-2,2'-diyl)thiosemicarbazone (Hbptsc) has been synthesized and characterized by elemental CHN analysis, UV-visible, FT-IR and 1H NMR spectroscopy. Copper(II) complexes of the ligand, Hbptsc synthesized have been characterized by elemental analysis, UV-visible spectra, FTIR spectra and EPR spectroscopic simulation. The complexes hold the stoichiometry of the type [CuLX] where X= Cl (1), NO3 (2), SO4 (3), N3 (4), SCN (5) confirmed by the molar conductivity studies of 10-3 M solutions in DMF at room temperature. The EPR spectra of the complexes recorded in DMF at 77 K shows an axial type spectra with two distinct g-values, g|| and g⊥ indicating a four coordinated planar geometry. The antimicrobial studies of the copper(II) complexes shows an appreciable activity against both gram positive and gram negative bacteria using streptomycin as positive control. The short term in vitro cytotoxicity studies following trypan blue dye exclusion method exhibits pronounced activity against the Dalton’s Lymphoma Ascites tumour cells extruded from the peritoneal cavity of mice.

Influence of silver-containing filler on antibacterial properties of experimental resin composites against Enterococcus faecalis

2021 ◽  
Vol 109 (2) ◽  
pp. 59-67
Author(s):  
Sanadra Adeeb ◽  
Saja Adeeb ◽  
G. Chladek ◽  
W. Pakieła ◽  
A. Mertas
Keyword(s):  
Enterococcus Faecalis ◽  
Test Performance ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Positive Control ◽  
Control Material ◽  
In Vivo Test ◽  
Laboratory Test Results ◽  
The Impact

Purpose: The aim of the presented work was to investigate the impact of the S-P introduction into resin-based composites on their effectiveness against Enterococcus faecalis (E. faecalis). Design/methodology/approach: Seven experimental composites based on typical matrix were developed. Six of them contained a filler with antimicrobial properties (silver sodium hydrogen zirconium phosphate, S-P), while the control material contained only common reinforcement fillers. The materials were characterized in terms of the dispersion of the extender in the matrix and then subjected to microbiological tests. The efficiency in the reduction of E. faecalis in the microenvironment was tested. Findings: The composites show a satisfactory distribution of fillers and a high initial reduction of bacteria colonies for the tested strain of E. faecalis. The reduction in bacteria colonies achieved for S-P concentrations from 7% to 13% was similar (median value from 99.8 to 99.9%, when for control material and compound with 1% S-P the number of colonies increased compared to positive control. Research limitations/implications: Laboratory test results may differ from in vivo test performance. In addition, there are many models for conducting laboratory antimicrobial efficacy studies, the results of which are also varied. The cytotoxic tests, long-term investigations and in vivo experiments need to be performed in future experiments. Practical implications: E. faecalis is a Gram-positive bacterium that is commonly detected in persistent endodontic infections and may enter the root canal through the coronal part. Development of composites with antimicrobial properties against this bacterium is as important as obtaining efficacy against cariogenic bacteria. Originality/value: The antimicrobial effectiveness against E. faecalis of experimental composites with submicrometer-sized particles of S-P was not investigated until now.

Short-term Effects of Feed Composition on Sleeping and Crying in Newborns

PEDIATRICS ◽  
1992 ◽  
Vol 90 (5) ◽  
pp. 733-740
Author(s):  
Tim F. Oberlander ◽  
Ronald G. Barr ◽  
Simon N. Young ◽  
Jessica A. Brian
Keyword(s):  
Caloric Intake ◽  
Early Morning ◽  
Short Term ◽  
Feed Composition ◽  
Postprandial Period ◽  
Adult Humans ◽  
Formula Group ◽  
Single Meal ◽  
To Receive ◽  
Observation Period

To determine whether the composition of feedings would affect newborn behavior independently of the act of feeding itself, 53 two- to three-day-old normal newborns were randomly assigned to receive an extra feeding of water, carbohydrate (lactose), or balanced formula 3 hours after their usual early morning feeding. Previous studies in adult humans and animals, and a single study in human newborns, have indicated that more sleep might be expected following the carbohydrate feed compared with the water and balanced-formula feeds because of recruitment of centrally mediated serotonergic systems. Behavioral effects were assessed for 40 minutes postfeeding by direct observation of the newborn's states (quiet, active, and indeterminate sleep; drowsiness; non-cry wakefulness; and fret/cry). Feed composition did affect behavior, and the effects were fairly specific to particular newborn states. Non-cry wakefulness and drowsiness were unrelated to the presence or type of nutrients, but they tended to occur soon after the meal in all groups. Crying was increased in water-fed newborns relative to both carbohydrate- and formula-fed newborns. Sleeping showed specific patterns of change in all three groups. Sleep duration was increased in the balanced-formula group compared with the water group throughout the observation period. Contrary to the prediction, sleeping duration in carbohydrate-fed newborns never exceeded that of formula-fed newborns; rather, it resembled that of water-fed newborns early in the postprandial period, but formula-fed newborns later. These effects could not easily be explained by potential confounding factors such as handling, volume ingested, caloric intake, or plasma glucose concentration. The results confirm that variations in the composition of a single meal can affect newborn behavior in the postprandial period and that these effects vary over time. Predictions of more sleep in the carbohydrate vs balanced-formula groups were not confirmed, implying that serotonergic systems are less important than other putative mechanisms. The results suggest that typical variations in feeding composition have implications for the understanding of early newborn behavior, mother-infant interaction, and clinical disturbances in newborn state.

scholarly journals PP030 Socioeconomics Of Cardiac Rehabilitation: A Meta-Analysis

2017 ◽  
Vol 33 (S1) ◽  
pp. 83-84
Author(s):  
Yin Ge ◽  
Tomoyuki Takura ◽  
Ebata Nozomi
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Health Economic ◽  
Cost Effectiveness ◽  
Cardiac Rehabilitation ◽  
Meta Analysis ◽  
Medical Costs ◽  
Short Term ◽  
Life Years ◽  
Observation Period

INTRODUCTION:The Guidelines for Rehabilitation in Patients with Cardiovascular Disease recommends convalescent cardiac rehabilitation (CR) as the standard treatment for patients with ST elevation myocardial infarction (STEMI) (class I, evidence level B) (1). However, health economic evaluation of cardiac rehabilitation (CR) is limited.METHODS:This systematic review, meta-analysis study elucidated the cost-effectiveness of CR in the short term. The target population in this study included convalescent and comprehensive CR patients with coronary artery disease (CAD), most with myocardial infarction (MI). We used mortality, life years (LY, expected life years), medical costs, and cost-effectiveness as the evaluation parameters in this analysis. We set medical costs in the analysis associated with testing, diagnosis, and treatment during the observation period related to CR. For cost-effectiveness analysis, we analyzed medical cost per LY. We examined the differences in effects for two comparisons (CR versus Usual Care, UC) using the Risk Ratio (RR) and Standardized Mean Difference (SMD). We assumed the standard deviation (SD) of cost effectiveness in this study by applying the error propagation.RESULTS:We reviewed fifty-nine studies and identified three that matched our selection criteria. The studies had the following characteristics: two randomized clinical trials and one systematic review/meta-analysis; a control that does not include exercise in patients with CAD; an observation period longer than 1 year; adapting medical costs, LY, cost/LY, and mortality as the evaluation index. In total, 129,272 patients were included. Meta-analysis results revealed that the CR arm significantly improved LY (SMD: -.78, 95 percent Confidence Interval (CI): -1.37, -.19) compared with UC. Similar to LY, the CR arm significantly improved the mortality (SMD: .57, 95 percent CI: .22, 1.47) compared with UC arm. Since medical costs showed a high tendency (SMD:.02, 95 percent CI: -.08, .13), cost/LY demonstrated no improvement (SMD: .00; 95 percent CI: -.17, .18). Substantial statistical heterogeneity was observed between the studies with respect to LY and cost/LY.CONCLUSIONS:While sufficient evidence to conclude health economic efficiency is not available at present, these results suggest that CR is not potentially cost-effective in the short term.

Studies of the Toxicological Potential of Tripeptides (L-Valyl-L-prolyl-L-proline and L-lsoleucyl-L-prolyl-L-proline): VIII. Assessment of Cytotoxicity and Clastogenicity of Tripeptides-Containing Casein Hydrolysate and Lactobacillus helveticus-fermented Milk Powders in Chinese Hamster Lung Cells

2005 ◽  
Vol 24 (4_suppl) ◽  
pp. 97-105 ◽  
Author(s):  
Masafumi Maeno ◽  
Seiichi Mizuno ◽  
John H. Mennear ◽  
Bruce K. Bernard
Keyword(s):  
Mitomycin C ◽  
Chromosomal Aberrations ◽  
Chinese Hamster ◽  
Casein Hydrolysate ◽  
Fermented Milk ◽  
Positive Control ◽  
Lactobacillus Helveticus ◽  
Continuous Exposure ◽  
Short Term ◽  
Mutagenic Potential

The objective of this chromosomal aberration test was to assess the mutagenic potential of tripeptides by determining their ability to induce chromosomal aberrations in cultured Chinese hamster lung (CHL) cells. The test agents used in these experiments were (1) powdered casein hydrolysate (CH) and (2) powdered Lactobacillus helveticus-fermented milk (FM). Both test agents contain two tripeptides, L-valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline (IPP). CHL cells were cultured and exposed in the presence or absence of a rat hepatic metabolizing system (S9); CH or FM (1250, 2500, 5000 /μg/ml of incubation medium); or positive-control agents, mitomycin C (0.1 or 0.05 /ig/ml) or benzo(a)pyrene (20 /μg/ml). In experiments with CH, cells were incubated for 6 h (either in the presence or absence of S9) or for 24 h (without S9). In experiments with FM, the cells were incubated for 6 h (either in the presence or absence of S9) or for 24 or 48 h (without S9). Neither short-term nor continuous exposure to either CH or FM caused the induction of significant changes in cell growth indices, incidences of chromosomal aberrations or the incidence of polyploids. Exposures of cells to mitomycin C and benzo(a)pyrene consistently resulted in the induction of the anticipated aberrant cells after either short-term or continuous exposures. The results of these assays support the conclusions that, under the conditions of these experiments, neither CH nor FM possesses demonstrable potential for the induction of cytotoxicity or clastogenesis.

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