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Pegylation of phenothiazine – A synthetic route towards potent anticancer drugs
No full textIntroduction
Cancer is a big challenge of the 21 century, whose defeat requires efficient antitumor drugs.
Objectives
The paper aims to investigate the synergistic effect of two structural building blocks, phenothiazine and poly(ethylene glycol), towards efficient antitumor drugs.
Methods
Two PEGylated phenothiazine derivatives were synthetized by attaching poly(ethylene glycol) of 550 Da to the nitrogen atom of phenothiazine by ether or ester linkage. Their antitumor activity has been investigated on five human tumour lines and a mouse tumor line as well, by determination of IC50. The in vivo toxicity was determined by measuring the LD50 in BALB/c mice by the sequential method and the in vivo antitumor potential was measured by the tumours growth test. The antitumor mechanism was investigated by complexation studies of zinc and magnesium ions characteristic to the farnesyltransferase enzyme, by studies of self-aggregation in the cells proximity and by investigation of the antitumor properties of the acid species resulted by enzymatic cleavage of the PEGylated derivatives.
Results
The two compounds showed antitumor activity, with IC50 against mouse colon carcinoma cell line comparable with that of the traditional antitumor drugs 5-Fluorouracil and doxorubicin. The phenothiazine PEGylation resulted in a significant toxicity diminishing, the LD50 in BALB/c mice increasing from 952.38 up to 1450 mg/kg, in phenothiazine equivalents. Both compounds inflicted a 92% inhibition of the tumour growth for doses much smaller than LD50. The investigation of the possible tumour inhibition mechanism suggested the nanoaggregate formation and the cleavage of ester bonds as key factors for the inhibition of cancer cell proliferation and biocompatibility improvement.
Conclusion
Phenothiazine and PEG building blocks have a synergetic effect working for both tumour growth inhibition and biocompatibility improvement. All these findings recommend the PEGylated phenothiazine derivatives as a valuable workbench for a next generation of antitumor drugs
Etiopathogenetic aspects in tumoral diseases
Get PDFThe tumoral disease is a pathology encountered more and more often, especially in pets. Whatever the type of tumor
that appears in an animal, the general etiology is often the same, being represented by a combination of genetic and
environmental factors that by association cause the transformation of normal cells into cells with aberrant behavior,
unlimited mitotic capacity and potential for metastasis and invasiveness. Knowing these general etiological factors, as
well as identifying the specific ones, can help us prevent the appearance of tumors, control the evolution of the disease
and even formulate an effective treatment. The present study aims to illustrate what are the potential causes of tumors in
general and how they can lead to their formation. Among the main factors to be considered are the environmental or
infectious factors that can either induce point mutations or epigenetic changes in various genes or that stimulate the
expression of already existing changes that have been passed down through generations in a dormant state. Even so, for
a tumour to be formed these events are not enough and it requires a cascade of phenomena that will ensure the
preservation, propagation and expansion of the nuclear and cellular changes that occurred during this first induction
moment
Operational research – strategic tool in environment–agribusiness interaction
No full textAlthough it is a science in its own right operational research is not so well known in the field of economics and
agribusiness but it possesses methods and relationships that could help ensure the natural-agribusiness environmental
balance. Operational research is not a strictly mathematical science; it uses mathematical techniques but has a much
wider application spectrum representing a systematized approach to solving problems that uses analytical methods in
the process of finding the appropriate solution. In the environment-agribusiness interaction, operational research can
represent a tool that can contribute to more effective planning, generating scientifically based solutions to current
problems and therefore gaining a competitive advantage in relation to similar enterprises. By means of the specific
methodology (modeling, simulation, optimization through linear programming, etc.) it can determine the optimization
of production flows, establish the most efficient way of determining feed in the livestock sector and realize the
optimization of transport networks (e.g. the shortest path problem). The decision-making process under conditions of
risk and uncertainty is one of the essential elements in the management of a company that can provide the necessary
data for a viable strategic approach, providing optimal solutions to the problems encountered. The work aims to
highlight the importance of operational research as a science, to provide an image of how to use specific techniques and
methods, indicating the favorability of using it as a strategic tool both in agricultural business and for environmentally
friendly policy
Morphological characteristics of the facial muscles in wild boar (Sus scrofa)
Get PDFThe observations of the study were focused on the facial musculature in wild boar in order to describe and observe their
peculiarities. The study was realized by dissection on a head of a wild boar, 1,5-2 years old, in two layers, a superficial and
a deep one. There were analyzed the muscles of the mouth, of the nose and of the eye, and the masseter muscle. It was
noticed a large cutaneous muscle of the face, especially the ventral part (risorius muscle), that inserts on the commissure of
the lips. The main particular aspects were remarked for the muscles of the upper lip and nostrils. In this way it was found
that the levator muscle of the upper lip is very developed, occupying the dorsal half of the canine fossa and has a very
strong tendon inserted in the dorsal part of the upper lip. The depressor muscle of the upper lip is also developed, but less
than the levator one, placed in the ventral part of the canine fossa. Its tendon ramifies before insertion in the ventral part of
the upper lip. The canine muscle is also massive, placed dorsally to the depressor muscle of the upper lip, in the ventral
half of the canine fossa, being partially covered by the levator muscle of the upper lip. It has a large area of insertion, in the
lateral wing of the nostril, by a lot on tendinous branches, the main one being the most dorsally placed. The three muscles
from canine fossa are partially covered by the nasolabial levator muscle, which is large oro-aborally, and short dorsoventrally,
being thin and having the fibers oblique disposed. The buccal muscle and depressor muscle of the lower lip are
short due to the deep commissure of the lips. The buccal muscle is covered dorsally by the zygomatic muscle which is
relatively short. The orbicular muscle of the mouth is large and thin. The orbicular muscle of the eye is also thin, as the
malar muscle is. For the masseter muscle it was remarked a superficial and a deep layer, reversely disposed. The
superficial layer includes many tendinous fibers. The study revealed a large development especially for the muscles that act
on the snout, respectively on the upper lip. The aspect is similar with that of domestic pig, but more evident
Inducing ovulation with human chorionic gonadotrophin improves cumulative pregnancy rates of dairy cows during the warm season
Get PDFThis study was designed to assess the effects of the GnRH agonist gonadorelin and human chorionic gonadotrophin,
during a timed artificial insemination program, on the fertility of lactating dairy cows during the warm and cold seasons
of the year. Cows were treated intramuscularly with GnRH-agonist (Day 0) and PGF2α (Day 7), followed by either
GnRH-agonist (GPG treatment; 38 animals) or hCG (GPH treatment; 26 animals) on Day 9. All cows were fixed-time
inseminated (TAI) 16–22 h after the end of treatment. In this study, replacing the Day 9 dose of GnRH with a dose of
hCG may result in an increase in the cumulative pregnancy rate (46.6% vs. 25%, P ≤ 0.05) but not the pregnancy rate
(26.6% vs. 18.8%, P > 0.05) in heat-stressed cows (THI > 70). However, in cold season, no effects were observed in the
pregnancy rates or cumulative pregnancy rates of the examined cows. This finding indicates that hCG therapy in TAI
programs may mitigate the negative effects of heat stress on dairy cows reproduction. This tendency can be explained
also by some studies that have shown that hCG can significantly reduce the number of small luteal cells while
increasing the number of large luteal cells as the corpus luteum gets bigger in diameter, area, and volume
Comportarea unor soiuri pentru struguri de masă obținute prin hibridare interspecifică în condițiile climatice ale centrului viticol Copou - Iasi
Get PDFThe adaptation of the new created genotypes to the eco-pedo-climatic conditions of various geographical areas is an important characteristic in order to expand and promote them into the vineyards. The purpose of this work was to study the behavior in the climatic conditions of the Copou-Iași viticultural center, of two new grapevine varieties for table grapes (Codreanca and Argessis), obtained by interspecific hybridization. The two genotypes stood out for their earliness and high yields (4-6 kg/vine stock), similar to the control variety Moldova, as common genitor. Sugar accumulations occurred according to the biological potential of each variety, varying between 165 and 195 g/L, ensuring, along with total acidity (4.9-6.0 g/L), a harmonious taste balance. The analyzed interspecific varieties efficiently capitalized the climatic resources of the ecosystem, showing good resistance to stress factors, ensuring high and quality productions, being well adapted to the climatic area of cultivation (N-E of Romania)
Parameters analysis of the Ostrinia nubilalis Hbn. attack at maize crops in the conditions of central Moldova
Get PDFMaize is cultivated on 2,678.5 thousand ha in Romania, and its cultivation on large areas attracts a number of pests that attack various parts of the plant in different developmental phases. One of these dangerous pests is Ostrinia nubilalis Hbn., a species that occurs during the growing season of maize and causes production losses by the attack on the stem and cob. The larvae produce various attacks, influenced by climatic conditions, the frequency of attacked plants being between 15.7 and 67.9% in the south-west of the country, in the south-east of the country varies between 43.3-79.4%, in the Transylvanian Plain has values between 60.00% and 81.88%, in the west of the country the attack is around 41%, and in the east of the country by 30.20%. The importance of attacks by Ostrinia nubilalis Hbn. at maize led to the initiation of studies in 2019 at the A.R.D.S. Secuieni to determine the influence of technological factors on the parameters of attack (frequency of attack, average number of holes, galleries and larvae and average length of gallery) produced by larvae. For the maize sown in epochs, the optimal epoch, the IIIrd, recorded the lowest values of the parameters: the frequency of the attack was 18.65%, were identified 0.60 holes/plant, 0.39 galleries/plant and 0.38 larvae/plant, and the average length of the galleries was 8.39 cm. The behavior of genotypes at the attack produced by larvae varied within very wide limits, the frequency of the attack was between 36.56% at the early genotype Vibrion and reached 48.50% at the late genotype Olt
Biochar a promising strategy for pesticide-contaminated soils
No full textSoil pesticide contamination induced by modern agriculture has become a serious global
issue. Its uncontrolled and inefficient application is among the main reasons for their enrichment in
plants and animals subsequently transferred to humans and providing a public health risk. Biochar
as a renewable and economical carbonaceous material provides a natural solution for immobilizing
pesticides and improving soil health. The biochar impact in agricultural contaminated soil is governed
by various factors such as the physico-chemical properties of biochar, pyrolysis, soil conditions, and
the application method, which can lead to significant gaps in the removal or mitigation of toxic
substances. The current study summarizes the negative effects of pesticide use and the advantages
of biochar according to other remediation techniques, succeeded by the mechanism and controlling
factors on minimizing pesticide leaching and bioavailability in soil. In addition, the role of biochar
on fundamental processes of adsorption, desorption, biodegradation, and leaching is discussed.
Ultimately, the major future research regulation and key strategies that are fundamental for pesticidecontaminated
soil remediation are proposed
Microbiological Assessment of Broiler Compound Feed Production as Part of the Food Chain—A Case Study in a Romanian Feed Mill
No full textCompound feed and the raw materials used in their production are potential vectors of microbiological contamination in the food chain. The purpose of this study was to microbiologically asses raw materials (maize, wheat, soybean meal, and sunflower meal), and broiler compound feed (starter, grower, and finisher) from a representative feed mill in Romania; the microbiological contaminants that were analyzed were yeasts and molds, Salmonella spp., Escherichia coli, and Clostridium perfringens. Our study occured during the years 2019 and 2020; in 2019, 191 samples of raw materials and 360 samples of compound feed were analyzed and in 2020, 143 samples of raw materials and 241 samples of compound feed were analzyed. Among the tested samples of raw materials, the mean values of the yeasts and molds for maize, wheat, soybean, and sunflower meal were 1.3 × 103, 9.5 × 102, 6.4 × 102, and 7.4 × 102 cfu/g in 2019 and 1.5 × 103, 1.0 × 103, 5.2 × 102, and 7.1 × 102 cfu/g in 2020. In the analyzed compound feed samples, the mean amounts for the starter, grower, and finisher were 5.9 × 102, 4.2 × 102, and 4.2 × 102 cfu/g in 2019 and 5.3 × 102, 6.5 × 102, and 5.8 × 102 cfu/g in 2020. Potentially toxigenic fungi from Aspergillus, Penicillium, and Fusarium genera have been identified as the most common in all of the samples. In the raw materials, in both years the highest numbers of Aspergillus-positive samples were recorded: 66.6% in 2019 and 100% in 2020 for the maize samples, 50% in 2019 and 75% in 2020 for the wheat samples, 76% in 2019 and 87.5% in 2020 for the soybean meal samples and 71.4% in 2019 and 100% in 2020 for the sunflower meal. In the starter compound feed, the Aspergillus genera was prevailing in 2019 (46.6%), while in 2020, the species of the Penicillium and Cladosporium genera were identified in the majority of the samples (50%); for the grower and finisher compound feed, the Aspergillus genera was predominantly identified in 2019 (60% and 72.2% of the samples, respectively) and 2020 (61.5% and 46.6%, respectively). All of the results of the bacteriological analysis for determining the contamination with Salmonella spp., E. coli, and Clostridium perfringens were negative. Based on the results obtained in this study, monitoring and analysis of microbiological hazards in a feed mill will help to control and prevent contamination and have a direct impact on food safety
Bicentenarul marelui savant - Louis Pasteur
Get PDFMoving to the East of France, Jura-land, the Pasteurian land, allowed us to get to know up close a hilly area on the border with Switzerland which is very favourable for grapes. The viticulture sector, being developed in Bourgogne since ancient times, has attracted the attention of many scholars and artists. One of them was the great Pasteur, whose Museum-House is located in the small town of Arbois, a large wine-growing center. Throughout the summer and autumn of 2022, under the auspices of the Academy of Sciences and the “Terre de Louis Pasteur” cultural team, events, symposia, festivals, and meetings with scientists are organized to commemorate the bicentennial jubilee. Admirable are the places where the future scientist lived, the local church, the house where he went to school and the laboratory of the great French microbiologist Louis Pasteur (27.12.1822–28.09.1895). Born near Dole (70 km North), his parents bought (in 1830) a four-level house right on the banks of the Cuisance river, where on the 1st and 2nd floors were his residence, the upper 3rd and 4th floors were intended for science. The article reveals the concerns of the scientist in whose laboratories they studied: microbiology, vaccines, hygiene, sanitation, immunity, the process of acquiring table salt from underground water, the biochemistry of fermentation and pasteurization