This article deals with the process of obtaining quality raw milk by analyzing its lipid composition. The lipid composition of raw milk depends on many factors, among which, first of all, is the species, the composition of the diet and the physiological state of the breast. In recent years, a large amount of data has accumulated on the fluctuations of certain lipid parameters of milk depending on the type, age, lactation, diet, time of year, exercise, animal husbandry technology, physiological state of the lactating organism in general and breast status in particular. Factors of regulation of fatty acid composition of raw milk: genetically determined parameters of quality and safety; fatty acid composition of the diet; synthesis of fatty acids by microorganisms of the digestive tract; synthesis of fatty acids in the breast; physiological state of the breast. The milk of each species of productive animals has its own specific lipid profile and is used in the formulation of certain dairy products to obtain the planned technological and nutritional parameters. Diagnosis of productive animals for subclinical mastitis involves the use of auxiliary (thermometry, thermography, electrical conductivity) and laboratory research methods: counting the number of somatic cells; use of specialized tests; microbiological studies of milk; biochemical studies of milk. The biochemical component in the diagnosis of subclinical forms of mastitis is underestimated. An increase in body temperature implies an increase in the intensity of heat release during the oxidation of substrates, sometimes due to a decrease in the intensity of synthesis of energy-intensive compounds. There are simply no other sources of energy in the body. The situation is the same with certain parts of the metabolism, which are aimed at the development of protective reactions to the etiological factor aimed at the defeat of the breast. That is why the biochemical composition of breast secretions in the absence of clinical signs of mastitis undergoes biochemical changes and the task of scientists is to develop mechanisms for clear tracking of such changes, identification of animals with subclinical forms of mastitis and effective treatment.
A vital problem of the contemporary pharmacology lies in creation of safer and more efficient medicinal products. Regulation of sodium balance and water being one of the important homeostatic functions is essential for developing the methods of rational therapy through means of diuretics of renal function of kidneys.This work is aimed to study the dependence of acute toxicity and diuretic activity on chemical structure of the newly synthesized 7-substituted-8-amino-3-methylxanthines in experiments on rats.The acute toxicity of 7-(2-hydroxy-3-p-methoxyphenoxy) propyl-8-substituted theophylline has been studied on the intact white nonlinear mice weighing 20-24 LD50 and has been calculated according to the method of Körber. The study of the diuretic activity of the above-mentioned compounds has been carried out on white rats of Wistar line weighing 180-195g according to the method of Y.B. Berkhina.The gained outcome of research into the acute toxicity of 7-substituted-8-amino-3methylxanthines (compounds 1-11) has shown that LD50 of the synthesized compounds is in the range from 290 to 835 mg/kg. The most toxic (LD50=290 mg/kg) compound is the 6 th one: 3-methyl-7-(2-hydroxy-3-p-methoxyphenoxy-) propyl-8-n-butylaminoethyl. Substitution in the 8 th position of the molecule of 7-substituted-8-amino-3-methylxanthines n-butylamine (compound 6) of radical with 4-benzylpiperazine-1-ilne (compound 11), p-ethoxyphenylamic (compound 10) N,N-diethylaminoethylamine (compound 4), 4-methylpiperazine-1-ilne (compound 1), N,N-diethylaminoethylamine (compound 3), N-methyl-N-benzylamine (compound 2), (pyrrolidine-1-ilne (compound 7), m-tolylamine (compound 9), βhydroxyethylepiperazine-1-ilne (compound 8), (furil-2)methylamine (compound 5) causes a reduction of the acute toxicity of the aforesaid substances.Analysis of the diuretic activity research shows that derivatives of 7-substituted-8amino-3-methylxanthines (compounds 1-11) increases excretion of urine in the range from 25.1% to 201.4% (p<0.05).The most signifying diuretic activity has been shown by the compound 5: 3-methyl-7-(2-hydroxy-3-p-methoxyphenoxy-) propyl-8-(furil-2)methylaminoxanthine, which in the dose of 41.8 mg/kg enhances the water diuresis for 201. 4% (p<0.01).Introduction to the 8 th position of the molecule of 7-substituted-8-amino-3metylxanthines instead of furil-2-methylamine (compound 5) radical of m-tolylamine (compound 9), n-butylamine (compound 6) and p-ethoxyphenylamine (compound 10) fragments leads to a reduction in renal excretory function for 143.5%; 131.8% and 111%, accordingly. Hydrochlorothiazide in the dose of 25 mg/kg enhances the water diuresis for 90.1%.Thus, the most signifying diuretic effect is observed in the compound 5, which exceeds the effect of the hydrochlorothiazide for 111.3% (p<0.05) and has been selected for further study of the specific activity.
In accordance with the principles of "me-too" technique, the preparative method for obtaining has been proposed, and the synthesis of a large series of new -(arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1-pyrrolo[3,2,1-]quinoline-5-carboxamides as structurally close analogs of tricyclic pyrrolo- and pyridoquinoline diuretics has been carried out. All target compounds were obtained with high yields and purity by amidation of ethyl ester of the corresponding 2-methyl-pyrroloquinoline-5-carboxylic acid with arylalkylamines in boiling ethanol. Their structure was confirmed by the data of elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and polarimetry. Moreover, interpretations of their ¹H and C-NMR spectra, their mass spectrometric behavior, as well as peculiarities of the polarimetric studies were discussed. The effect of-(arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1-pyrrolo[3,2,1-]quinoline-5-carboxamides on the urinary function of the kidneys was studied in white rats by the standard method of oral administration in the dose of 10 mg/kg compared to hydrochlorothiazide. According to the results of the primary pharmacological screening, the structural and biological regularities that were unexpected, but interesting for further studies were revealed. Among the substances studied, the samples, which by their diuretic effect are not inferior and even superior to both the known hydrochlorothiazide and the lead structure of the pyrroloquinoline group, have been found. On this basis, it can be argued that the introduction of the methyl group made by us in position 2 of pyrrolo[3,2,1-]quinoline nucleus can be considered as a successful and promising implementation of the "me-too" cloning of tricyclic 4-hydroxyquinoline-2-one diuretics.
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