Finney Method Research Articles

Design, Synthesis, and Pharmacological Evaluation of Novel Tacrine Derivatives as Multi-target ANTI-Alzheimer's Agents In Rat Models.

Alzheimer's disease is a progressive neurodegenerative disorder for which no curative drugs are available and treatment available is just palliative. Current research focused on design of Tacrine-Flavone hybrids as multitargeted cholinesterase and monoamine oxidase B inhibitors. A total of 10 Tacrine- Flavone hybrids were designed, synthesized and characterized. The in vitro neurotoxicity and hepatotoxicity of the synthesized compounds determined using SHSY5Y cell line and HEPG2 cell line. One most active compound (AF1) with least toxicity in in vitro studies was chosen for in vivo studies. Acute and subacute toxicity of the novel compound AF1 conducted on Wistar rats according to OECD guideline 423 and 407. The LD50 value of the novel compound calculated according to Finney's method using Probit analysis. Anti-Alzheimer's activity studies conducted on male Wistar rats. Behavioral studies conducted and AChE and MAO-B activity determined in rat brain. All the compounds exhibited good inhibitory effect on MAO B and AChE. The neurotoxicity studies of the active compound AF1 did not show toxicity up to 100μg. The hepatotoxicity study of the most active compound AF1, showed the compound to be safe up to 200μg. The LD 50 value of the novel compound after a single oral administration was found to be 64 mg/kg bodyweight in rats. Subacute toxicity studies did not show any remarkable toxicity in the vital organs up to 40 mg/kg. Activity studies showed comparable results with standard at 20 mg/kg. The results showed that the novel Tacrine-Flavone hybrids are multitarget-directed ligands, which are safe and active compared to tacrine and can be a promising lead molecule for further study.

Comparative toxicological and hygienic assessment and combined action of modern fungicides based on azoxystrobin, pydiflumetofen, propiconazole

Annotation. The creation of combined pesticide formulations for the purpose of more effective protection of agricultural crops is a significant factor in the importance of assessing their synergistic effects. Substances that produce a similar pesticidal effect, in combination with each other, can enhance the toxic effect and, therefore, show dose additivity. The aim is toxicological and hygienic evaluation and determination of the type of combined action of pydiflumetofen, azoxystrobin and propiconazole – the active substances of the mixed formulations “Miravis Ace 275 SE” and “Miravis Neo 300 SE” according to toxicity indicators. Analytical review of scientific publications was carried out using data from EFSA, FAO, ECHA, PPDB, Internet sites. According to the literature, a comparative toxicological-hygienic evaluation of fungicidal preparations and their active substances was carried out. The general mechanism of fungicidal action was evaluated according to the classification developed by the Fungicide Resistance Action Committee (FRAC). The hazard class according to the toxic metric parameters of the substances under study was determined in accordance with the Hygienic classification of pesticides according to the degree of hazard (DSanPiN 8.8.1.002-98). The nature and type of combined action was carried out according to the Finney method with evaluation according to the criteria of acute toxicity. Systematization of data, their structuring for the purpose of further toxicological assessment of substances at the level of their inactive and threshold doses was carried out in the table editor Microsoft Excel 2019 (Microsoft Office 2019, Microsoft). As a result of the conducted research, the most toxic mixed fungicide “Miravis Neo 300 SE” based on three active substances was determined (the average lethal dose (LD50) is 550 mg/kg). It has been established that in cases of combinations of active substances to obtain a lethal effect, a dose of substances that does not exceed 100% in total is required, which indicates the strengthening (potentiation) of toxicity. It was pointed out that the share of propiconazole in the potentiation of the toxic effect in both mixed preparations is the highest compared to other active substances and is 0.87 for “Miravis Neo 300 SE” and 0.88 for “Miravis Ace 275 SE”. It was observed that the adverse effects of simultaneous exposure to several pesticides may change during the transition from acute to chronic exposure. Therefore, it is important to continue the research of the active substances of pesticides with the determination of limiting criteria for harmfulness, taking into account the remote effects of exposure. Thus, the toxicological and hygienic assessment made it possible to establish that the combined fungicides “Miravis Neo 300 SE” and “Miravis Ace 275 SE” are more toxic in the mode of single oral exposure in comparison with the single-component fungicide “Miravis 200 SC”. Increased toxicity (potentiation) can be considered as a consequence of the simultaneous exposure of several active substances. The active substance propiconazole poses the main danger of adverse effects on the body at the level of lethal doses. The obtained values of the potentiation coefficients will be taken into account in further studies of the risk assessment of complex and combined effects of pesticides on workers and their potential danger when entering the human body with food products.

6. Cytotoxic Potential of n-Hexane Extract of Calotropis gigantea L. Leaves

The present study was done to determine the cytotoxic potential of n-hexane extract of Calotropis gigantea L. leaves and its fractions. Here, dried leaves of C. gigantea L. were macerated using n-hexane to obtain crude extract of 21.16 g (1.03%). The components of n-hexane extract of C. gigantea L. leaves were separated with vacuum-liquid chromatography resulted 4 fractions which are A (0.5 g), B (0.9g), C (5.29 g), and D (6.25 g). Phytochemical screening indicated that the extract contained various secondary metabolic compounds such as steroids, terpenoids, saponins, flavonoids, coumarins, and phenolics. Cytotoxic potenital of the crude extract of C. gigantea L. and its fractions was examined using brine shrimp lethality test (BSLT). The LC50 values of C. gigantea’s n-hexane extract and its fractions that determined by Finney method were 272.27 (n-hexane extract), 31.62 (fraction A), 43.65 (fraction B), 33.89 (fraction C) and 20.98 (fraction D) ?g/mL, respectively. The most active was D fraction contained terpenoids, flavonoids, and phenolics which were assumed contribute to its cytotoxic potential. These results suggested that n-fraction of C. gigantea might possess antitumor or pesticidal activities..

Ecotoxicological studies on fish, Labeo rohita exposed to tannery industry effluent by using micronucleus test

Tannery industries are globally situated. The genotoxic effect was analyzed in erythrocytes of a freshwater fish, Labeo rohita exposed to tannery industry effluent using micronucleus test. Micronucleus test is simple, rapid and reliable method used in laboratory for monitoring genotoxic damage. The 96 h LC50 value was calculated by using Finney method and it came out to be 7.07 %. Fishes were exposed to three sub-lethal concentrations (3.53, 1.76 and 0.88 % of 96 h LC50 value) for 24, 48, 72 and 96 h. Presence of one micronucleus was predominant than two and three to five micronuclei in erythrocytes of fishes exposed to effluent. Concentration 3.53 % proved to be highly toxic and 0.88 % can act as a safe disposal concentration. The results showed concentration and time dependent response. Thus, results revealed that discharge of tannery effluent caused clastogenic effects in fish erythrocytes. This may lead to stock depletion of fishes and aquatic organisms living in rivers. Similar clastogenic effects may also occur in human population living around rivers using contaminated water and consuming contaminated fishes.

Remote sensing and GIS based assessment of soil erosion and soil loss risk around hill top surface mines situated in Saranda Forest, Jharkhand

The quantitative analysis of soil erosion changes over 7 years due to mining operations in two neighboring hilltops in West-Singhbhum District, Jharkhand, are reported. CartoSat-1, ETM+ and LISS-IV satellites' data provided spatial inputs in Universal Soil Loss Equation (USLE) and Morgan, Morgan and Finney method (MMF) models, which were used to predict the average annual soil erosion during the period of 2001–2008 in a geographic information system (GIS), in six distinct classes. In the comparative analysis of the 7-year period, the MMF model revealed a lower coefficient of variation 0.71 (2001) and 0.84 (2008) in predicted average annual soil loss, which increased by 16% (81.3–94.2 t ha−1yr−1), whereas in the case of USLE, the coefficients of variation were 3.88 (2001) and 1.94 (2008), with an increase of 61% (48.56–78.38 t ha−1yr−1). The correlation coefficient of these models was 0.1 (2001) and 0.36 (2008), which shows that both models predicted significantly differently as a result of the different factors considered. Overall, the MMF model predicted a higher soil erosion rate but less variation than USLE. Both models showed soil erosion rates were drastically increased by anthropogenic activities in the area, hence careful consideration is needed. The same sensor and imaging data could not be maintained. Correction of errors may reduce erosion, but it will still remain significant for future planning.

A cumulative dose study of levalbuterol and racemic albuterol administered by hydrofluoroalkane-134a metered-dose inhaler in asthmatic subjects

The short-acting beta(2)-agonists levalbuterol and racemic albuterol are available for administration through a hydrofluoroalkane-134a (HFA) metered-dose inhaler (MDI). This study compared the short-term safety and efficacy of cumulative doses of levalbuterol HFA MDI and racemic albuterol HFA MDI in asthmatic subjects. This was a randomized, modified-blind, active-controlled, multicenter, 2-way crossover study. Subjects (n = 49) were randomized to 16 cumulative doses (1x, 2x, 4x, 8x, and 16x) of levalbuterol (45 microg per dose) or racemic albuterol (90 microg per dose) administered over a 2-hour period. After a 7-day washout period, subjects were crossed over to the other treatment. After each dose, safety outcomes and pulmonary function were assessed. Heart rate and (R)-albuterol exposure increased for both racemic albuterol HFA and levalbuterol HFA. For cumulative doses of 8x or greater, racemic albuterol HFA treatment had greater increases in mean heart rate than levalbuterol HFA (least-squares mean [+/- SD] difference at the 8x dose was 2.8 beats/min [95% CI, 0.3-5.3] and at the 16x dose was 3.5 beats/min [95% CI, 0.6-6.4]). (R)-albuterol plasma levels ranged from 10% to 18% higher after racemic albuterol HFA MDI dosing versus after levalbuterol HFA MDI. FEV(1) improvements were similar for both treatments. The relative potencies of the 2 therapies, based on FEV(1), were similar (ratio, 1.1 [90% CI, 0.9-1.2]; Finney method). In this study single-day cumulative dosing of asthmatic subjects with levalbuterol HFA MDI or racemic albuterol HFA MDI resulted in similar improvements in FEV(1) and tolerability. Plasma (R)-albuterol levels and mean heart rate were less with levalbuterol HFA MDI.

Perencanaan Jangka Pendek DAS dengan Metode Perhitungan Erosi Kuantitatif dengan Penginderaan Jauh dan Sistem Informasi Geografis

Short-term Planning of Watershed Using Calculation of Quantitative Erosion Method Based on Remote Sensing and Geographic Information SystemPriority determination of some sub watersheds experienced difficulties based on the fact that data collection of the related sub watersheds takes time and quite costly. Whereas to comprehensively manage sub watershed, some prioritizet sub watersheds have to be chosen to manage holistically and integrally with good coordination between some related agencies. The study was carried out in India in two Nawagaon Maskara Raoi watersheds, Saharanpur city, located 250 km to the east of New Delhi. The study appointed a sub watershed to be the prioritu among the other 10 available using quantitative calculation method (MMF: Morgan, Morgan, and Finney method). The research aimed to measure the quantitative erosion based on MMF model and calculate the value index to determine the priority in sub watershed.The erosion calculation by MMF model produced five erosion levels i.e. very low (vl=0-5t/ha/yr), low (l=5-10 t/ha/yr), medium (m=10-25 t/ha/yr), high (h=25-50 t/ha/yr), and very high (vh 50 t/ha/yr). At the highest erosion level (vh) location with the most extensive land damage to the narrowest respectively was Sarbar Rao (SB) = 116.84 ha, Galr Rao (GR), Sahansra Thakur (ST), Shakumbari Rao (SH), Khawonwala Rao (KH) Kahan Rao (KR), Nawagaon Rao (NW), Chamarla Rao (CH), Track Fallows (TF), Barkala Rao (BR), and Maskara Rao (MR) = 0.34 ha. Of 11 sub watershed, priority value index was calculated, and the highest value (main priority) to the lowest one (least priority) is respectively as follows: GR (Galr Rao) = 33,5, KR (Kahan Rao), ST (Sahansra Thakur), TF (Track Fallows), BR (Barkala Rao), SB (Sarbar Rao), SH (Shakumbari Rao), CH (Chamarla Rao), KH (Kharonwala Rao), MR (Maskara Rao), and NW (Nawagaon Rao) = 18,2. Therefore the main priority fell for sub watershed Galr Rao (997.32) and the least priority for watershed Nawagaon Rao (7646.78 ha).

Avaliação da DL50 e edema pulmonar induzido pelo veneno de Tityus serrulatus (Scorpiones; Buthidae) procedente da Bahia, Brasil

O escorpião Tityus serrulatus é conhecido como a espécie mais importante, do ponto de vista médico, pois é o que causa os acidentes mais graves registrados para o território brasileiro. Este trabalho trata da caracterização do veneno do escorpião T. serrulatus, através da obtenção da DL50 e determinação da capacidade em induzir edema pulmonar, em ratos. O veneno foi obtido através de estímulo elétrico. A toxicidade foi determinada através da avaliação da DL50, pelo método de Finney (1971). Os valores demonstraram a baixa toxicidade do veneno (96,16 mg/camundongo), que corresponde a 3 - 7 vezes menos tóxico que venenos de espécimes de outras regiões do Brasil. O veneno testado também não induziu edema pulmonar, avaliado através da diferença entre o peso do pulmão de animais experimentais e controle. Estes resultados demonstram uma variação do veneno de T. serrulatus e poderia explicar a ausência de óbitos e do registro de edema pulmonar nos pacientes picados nestas regiões do Estado da Bahia, Brasil.

A test of three soil erosion models incorporated into a geographical information system

AbstractAn examination is carried out of the application of three soil erosion models, USLE/RUSLE, SLEMSA and the Morgan, Morgan and Finney method, to the Simeto catchment in Sicily, and of the differences in the results using the three models. The models are incorporated into a grid‐based geographical information system, and the results are validated qualitatively and quantitatively. The significance of the choice of method to estimate the distributed input parameters and the method to validate the quality of the models are discussed. Copyright © 2003 John Wiley & Sons, Ltd.

Nitrous oxide fluxes from grassland in the Netherlands: I. Statistical analysis of flux‐chamber measurements

SummaryAccurate estimates of total nitrous oxide (N2O) losses from grasslands derived from flux‐chamber measurements are hampered by the large spatial and temporal variability of N2O fluxes from these sites. In this study, four methods for the calculation of mean N2O fluxes (n= 6) on total N2O losses are compared, namely the arithmetic mean, the geometric mean, the lognormal mean and the mean derived from Finney's method. Mean fluxes were calculated from weekly flux measurements on grassland at four contrasting sites in the Netherlands with three management treatments each. Total losses were calculated by interpolation of the mean fluxes and integration over time. Spatial variation of N2O fluxes was large. The geometric mean was generally much smaller, up to a factor of 7, than the arithmetic mean. The lognormal mean was much larger, up to a factor of 11, than the arithmetic mean, possibly because this estimator is biased for small sample size. Arithmetic means and Finney's method were generally in reasonable agreement. The order in estimated N2O loss increased in the order geometric mean<arithmetic mean≤Finney's mean<lognormal mean. Because of the small sample size (n = 6), the uncertainty about the precise frequency distribution, the sensitivity of estimators based on logtransformed data, and the problems associated with negative fluxes, the arithmetic mean was preferred as the most appropriate estimator. Evidently, the choice of an estimator of the mean can have great effects on the estimation of total N2O losses.

Evaluation of Statistical Estimation Methods for Lognormally Distributed Variables

Distributions of many chemical, physical, and microbiological properties of soils appear to be lognormal. Several conflicting recommendations exist in the soil science and statistical literature on how to best estimate the population mean, variance, and coefficient of variation of lognormally distributed data. We chose to determine with statistical certainty which of the following three methods is best: (i) the method of moments (method 1); (ii) maximum likelihood (method 2); and (iii) Finney's method (method 3). We assessed the efficacy of these three methods for estimating the mean, variance, and coefficient of variation of lognormal data in the range of sample sizes from = 4 to 100. Three test lognormal populations were used in our evaluation with coefficients of variation that span the range seen for many soil variables (CVs of 50%, 100%, and 200%). We found Finney's method was best for estimating the mean and variance of lognormal data when the coefficient of variation of the underlying lognormal frequency distribution exceeds 100%, below this value the extra computational effort required to implement Finney's technique buys little, relative to the method of moments. Finney's method has not been previously applied by soil scientists, but its superiority over maximum likelihood suggests that the latter should not be generally recommended for estimating the mean, variance and coefficient of variation of lognormal data.

Comparison of two correction methods for the bias due to the logarithmic transformation in the estimation of biomass

Finney's method and the method of maximum likelihood for correcting the bias due to the logarithmic transformation in the estimation of biomass are presented as step-by-step procedures and are compared using empirical data and statistical theory. Based on theoretical considerations, ease of computation, and the use of empirical data, the method of maximum likelihood is recommended.