Synthesis of 5b-Androsta-17b-(1'-oxocyclohex-2'-en-3'-yl)-3b,14b,diol-3-b-D-glucopyranoside, a Potent Cardiac Glucoside with High Safety Margin

Heterocycles ◽  
1989 ◽  
Vol 29 (7) ◽  
pp. 1275 ◽  
Author(s):  
Uttam K. Pati ◽  
Karel Wiesner
Keyword(s):  
Safety Margin ◽  
Cardiac Glucoside

The limits of human performance

2008 ◽  
Vol 44 ◽  
pp. 11-26 ◽  
Author(s):  
Ralph Beneke ◽  
Dieter Böning
Keyword(s):  
Human Performance ◽  
Safety Margin ◽  
Afferent Input ◽  
Metabolic Energy ◽  
Human Organism ◽  
Mechanical Resistance ◽  
As Doping ◽  
Gene And Protein Expression ◽  
Underlying Mechanisms ◽  
Biochemical Research

Human performance, defined by mechanical resistance and distance per time, includes human, task and environmental factors, all interrelated. It requires metabolic energy provided by anaerobic and aerobic metabolic energy sources. These sources have specific limitations in the capacity and rate to provide re-phosphorylation energy, which determines individual ratios of aerobic and anaerobic metabolic power and their sustainability. In healthy athletes, limits to provide and utilize metabolic energy are multifactorial, carefully matched and include a safety margin imposed in order to protect the integrity of the human organism under maximal effort. Perception of afferent input associated with effort leads to conscious or unconscious decisions to modulate or terminate performance; however, the underlying mechanisms of cerebral control are not fully understood. The idea to move borders of performance with the help of biochemicals is two millennia old. Biochemical findings resulted in highly effective substances widely used to increase performance in daily life, during preparation for sport events and during competition, but many of them must be considered as doping and therefore illegal. Supplements and food have ergogenic potential; however, numerous concepts are controversially discussed with respect to legality and particularly evidence in terms of usefulness and risks. The effect of evidence-based nutritional strategies on adaptations in terms of gene and protein expression that occur in skeletal muscle during and after exercise training sessions is widely unknown. Biochemical research is essential for better understanding of the basic mechanisms causing fatigue and the regulation of the dynamic adaptation to physical and mental training.

Social Recourses of the Population under Conditions of Losing Economic Stability

2015 ◽  
pp. 86-99 ◽  
Author(s):  
E. Avraamova ◽  
T. Maleva
Keyword(s):  
Economic Development ◽  
Social Policy ◽  
Social Development ◽  
Safety Margin ◽  
Economic Stability ◽  
Socio Economic Development ◽  
Development Stability ◽  
Made In

The loss of country’s socio-economic development stability puts on the agenda the problem of finding solutions contributing to the maintenance of Russian households’ welfare. The authors believe that these solutions lie in the broader area than applying various instruments of monetary support. The most effective solutions are related to the actualization of own resources of households that can act as a safety margin as well as a source of social development. The attempt to evaluate the households’ resource provision and highlight the significance of each resource enabling or creating barriers to the growth of households’ welfare is made in this article. On the basis of received conclusions social policy areas directed at preserving or enhancing the welfare are defined.

Surgical treatment of alveolar echinococcosis: a single centre experience and systematic review of the literature

2019 ◽  
Vol 98 (4) ◽  
pp. 167-173
Keyword(s):  
Case Report ◽  
Echinococcus Multilocularis ◽  
Alveolar Echinococcosis ◽  
Lymphatic System ◽  
Surgical Intervention ◽  
Clinical Symptoms ◽  
Safety Margin ◽  
Surgical Removal ◽  
Single Centre Experience ◽  
Therapeutic Procedures

Introduction: Alveolar echinococcosis (AE) is a zoonosis caused by Echinococcus multilocularis. AE is primarily localised in the liver. Echinococcus multilocularis imitates tumour-like behaviour. It can metastasise through blood or lymphatic system to distant organs. Echinococcosis often remains asymptomatic due to its long incubation period and indistinct symptoms. Clinical symptoms are determined by the parasite’s location. Diagnosis of echinococcosis is based on medical history, clinical symptoms, laboratory tests, serology results, imaging methods and final histology findings. Surgical removal of the cyst with a safety margin, followed by chemotherapy is the therapeutic method of choice. Case report: We present a case report of alveolar echinococcosis in a thirty-year-old female patient in whom we surgically removed multiple liver foci of alveolar echinococcosis. The disease recurred after two years and required another surgical intervention. Conclusions: Alveolar echinococcosis is a disease with a high potential for a complete cure provided that it is diagnosed early and that the recommended therapeutic procedures are strictly adhered to.

Safe Use of the Assimilative Capacity of the Marine Environment for Waste Disposal – Is It Feasible?

1986 ◽  
Vol 18 (4-5) ◽  
pp. 233-244 ◽  
Author(s):  
J. E. Portmann ◽  
R. Lloyd
Keyword(s):  
Marine Environment ◽  
Salt Marshes ◽  
Safety Margin ◽  
Assimilative Capacity ◽  
Anthropogenic Inputs ◽  
Upper Limit ◽  
Safe Limits ◽  
Control Authority ◽  
The Right ◽  
To Receive

For centuries the sea has absorbed a variety of inputs from rivers, streams, salt marshes and the atmosphere. It is generally accepted that additional limited inputs by man are unlikely to have a significant effect on the marine environment. Various control systems have been constructed to provide a framework within which the regulation of anthropogenic inputs can be achieved. These are briefly reviewed. With care, and in the light of past experience in both freshwater and marine environments, reasonable assumptions or estimations can be applied where uncertainties exist; safe limits can therefore be set for discharges. Case histories are used to illustrate the contention that it is possible to assess the assimilative capacity of a marine area to receive wastes. There is a major distinction to be drawn between contamination and pollution of the marine environment. Moreover, acknowledgement of the assimilative capacity concept in the marine environment does not automatically provide dischargers with the right to utilise that capacity either in part or to the upper limit. What it does is indicate the upper limit which must not be exceeded if pollution is to be avoided, and provide an indication to the control authority of the safety margin involved in the discharge limits they set accordingly.

Risk-Informed Safety Margin Characterization Methods Development Work

2014 ◽  
Author(s):  
Curtis L Smith ◽  
Zhegang Ma ◽  
Tom Riley ◽  
Diego Mandelli ◽  
Joseph W Nielsen ◽  
...  
Keyword(s):  
Safety Margin ◽  
Development Work ◽  
Characterization Methods ◽  
Methods Development

Cytotoxicity Studies of Curcumin Loaded-Cockle Shell-Derived Calcium Carbonate Nanoparticles

2019 ◽  
Vol 09 ◽  
Author(s):  
Maryam Muhammad Mailafiya ◽  
Mohamad Aris Mohd Moklas ◽  
Kabeer Abubakar ◽  
Abubakar Danmaigoro ◽  
Samaila Musa Chiroma ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Safety Margin ◽  
Bone Diseases ◽  
In Vivo Studies ◽  
Normal Cells ◽  
Cytotoxicity Studies ◽  
Standard Techniques ◽  
Cockle Shell

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possess wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attentions. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Method: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Result: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at higher dose of 500 µg/ml and 40 µg/ml respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone related ailments.

scholarly journals Bootstrap and Order Statistics for Quantifying Thermal-Hydraulic Code Uncertainties in the Estimation of Safety Margins

2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Enrico Zio ◽  
Francesco Di Maio
Keyword(s):  
Confidence Interval ◽  
Order Statistics ◽  
Nuclear Reactor ◽  
Safety Margin ◽  
Fuel Cladding ◽  
Complete Group ◽  
Bootstrap Technique ◽  
Safety Margins ◽  
Group Distribution

In the present work, the uncertainties affecting the safety margins estimated from thermal-hydraulic code calculations are captured quantitatively by resorting to the order statistics and the bootstrap technique. The proposed framework of analysis is applied to the estimation of the safety margin, with its confidence interval, of the maximum fuel cladding temperature reached during a complete group distribution blockage scenario in a RBMK-1500 nuclear reactor.

scholarly journals Continental vs. Global Niche-Based Modelling of Freshwater Species’ Distributions: How Big Are the Differences in the Estimated Climate Change Effects?

Water ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 816
Author(s):  
Danijela Markovic ◽  
Jörg Freyhof ◽  
Oskar Kärcher
Keyword(s):  
Climate Change ◽  
Thermal Properties ◽  
Safety Margin ◽  
Thermal Response ◽  
Future Climate Change ◽  
Freshwater Species ◽  
Response Curves ◽  
Preferred Temperature ◽  
Continental Scale ◽  
Management Actions

Thermal response curves that depict the probability of occurrence along a thermal gradient are used to derive various species’ thermal properties and abilities to cope with warming. However, different thermal responses can be expected for different portions of a species range. We focus on differences in thermal response curves (TRCs) and thermal niche requirements for four freshwater fishes (Coregonus sardinella, Pungitius pungitius, Rutilus rutilus, Salvelinus alpinus) native to Europe at (1) the global and (2) European continental scale. European ranges captured only a portion of the global thermal range with major differences in the minimum (Tmin), maximum (Tmax) and average temperature (Tav) of the respective distributions. Further investigations of the model-derived preferred temperature (Tpref), warming tolerance (WT = Tmax − Tpref), safety margin (SM = Tpref − Tav) and the future climatic impact showed substantially differing results. All considered thermal properties either were under- or overestimated at the European level. Our results highlight that, although continental analyses have an impressive spatial extent, they might deliver misleading estimates of species thermal niches and future climate change impacts, if they do not cover the full species ranges. Studies and management actions should therefore favor whole global range distribution data for analyzing species responses to environmental gradients.

scholarly journals Development of Fragility Curves for Piping and Slope Stability of River Levees

Water ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 738
Author(s):  
Nicola Rossi ◽  
Mario Bačić ◽  
Meho Saša Kovačević ◽  
Lovorka Librić
Keyword(s):  
Slope Stability ◽  
Fragility Curves ◽  
Safety Margin ◽  
Water Levels ◽  
Flood Event ◽  
Soil Parameters ◽  
Design Code ◽  
A Site ◽  
Insight Into

The design code Eurocode 7 relies on semi-probabilistic calculation procedures, through utilization of the soil parameters obtained by in situ and laboratory tests, or by the means of transformation models. To reach a prescribed safety margin, the inherent soil parameter variability is accounted for through the application of partial factors to either soil parameters directly or to the resistance. However, considering several sources of geotechnical uncertainty, including the inherent soil variability, measurement error and transformation uncertainty, full probabilistic analyses should be implemented to directly consider the site-specific variability. This paper presents the procedure of developing fragility curves for levee slope stability and piping as failure mechanisms that lead to larger breaches, where a direct influence of the flood event intensity on the probability of failure is calculated. A range of fragility curve sets is presented, considering the variability of levee material properties and varying durations of the flood event, thus providing crucial insight into the vulnerability of the levee exposed to rising water levels. The procedure is applied to the River Drava levee, a site which has shown a continuous trend of increased water levels in recent years.

scholarly journals Long-term safety evaluation of Daxocox® tablets (enflicoxib) in dogs after weekly oral administrations for seven months

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Josep Homedes ◽  
Marta Salichs ◽  
Antonio Guzman
Keyword(s):  
Safety Margin ◽  
Clinical Signs ◽  
Safety Evaluation ◽  
Clinical Pathology ◽  
Occult Blood ◽  
Study Groups ◽  
Placebo Control ◽  
Relevant Dose ◽  
Mucosal Bleeding ◽  
Animal Safety

Abstract Background Daxocox® [Ecuphar/Animalcare Group] contains the selective COX-2 inhibitor enflicoxib, approved in the EU for the treatment of pain and inflammation associated with osteoarthritis in dogs. The safety of Daxocox® was evaluated in a target animal safety study: Groups of 4 dogs per sex each were treated once weekly with placebo or Daxocox tablets at 1-, 3- and 5-times (1X, 3X and 5X) the maximum recommended therapeutic dose of enflicoxib (0, 4, 12 or 20 mg/kg, respectively). After an initial loading dose, dogs in the placebo control, 1X and 3X groups were administered for 32 weeks, and those in the 5X group were administered for 13 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose observations. Body weight measurements, physical examinations, clinical pathology, urinalysis, faecal occult blood (FOB) and electrocardiographic (ECG) and blood pressure measurements, buccal mucosal bleeding time (BMBT), ophthalmology and gastroduodenal endoscopy examinations were conducted throughout the study. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on selected tissues from all animals in all groups. Results No clinical signs were noted, and no toxicologically relevant dose-associated effects were observed. Conclusions Results show that Daxocox® is well-tolerated and has a broad safety margin when administered as directed in dogs.

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