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The article provides an overview of the available literature on problems of infant nutrition, and shows the historical development of the principles of infant feeding. It discusses in greater detail the use of goat milk as a basis for infant nutrition. It notes the need for a comparative analysis of breast milk substitutes, and for clinical studies evaluating the value of goat milk in infant nutrition.

This paper reports results of international multicentre non-interventional clinical study of the effectiveness and safety of ascoril expectorant for the treatment of cough in Kazakhstan and Uzbekistan. The study included 16312 patients examined in different cities during 2011-2012. It showed that ascoril expectorant (Glenmark) at a standard dose is an effective agent for the treatment of cough in children above 3 years and adults aged up to 78 years with ARVI and acute bronchitis, exacerbation of these conditions or grade I-II chronic obstructire pulmonary disease. Most patients reported good therapeutic effect within 1 day after intake. Ascoril expectorant caused no adverse reactions and was well tolerated by the patients. 91% of the attending physicians describe the drug as highly effective.

A new method for determining the cumulation factor is proposed, which quantitatively describes the cumulative effect and allows the dosage regimes for repeated drug administration to be planned.

Pharmacokinetics of the sesquiterpene lactone leucomisin in the blood serum was studied after single intraperitoneal injection and enteral introduction. Analysis of the main pharmacokinetic prameters shows that the drug circulates in the organism for a relatively long time and can be accumulated in the cells, probably, due to the ability of penetrating through the histohematic barriers.

Association of rifampicin with polybutylcyanoacrylate nanoparticles provided considerable enhancement of drug antibacterial activity. In vitro nanoparticle-loaded rifampicin was more active against Staphylococcus aureus and Mycobacterium avium, localized in isolated alveolar macrophages. Level of rifampicin in macrophages increased 2-3-fold after incubation with rifampicinloaded nanoparticles comparing to the free drug. High therapeutic efficacy of colloidal rifampicin was demonstrated in vivo. Use of nanoparticles provided 2-fold increase in rifampicin efficacy, comparing with the free drug at treatment of staphylococcus sepsis in mice. Single administration of nanoparticulate rifampicin in the dose 25 mg/kg resulted in 80% survival of mice with salmonellosis, while 50 mg/kg of free rifampicin could provide only 10% survival. It may be considered that high antibacterial efficacy of rifampicin bound to nanoparticles is due to its effective delivery to macrophages.

The present study is dedicated to investigation of pharmacokinetics of the colloidal delivery system based on polybutylcyanoacrylate nanoparticles for the II generation photosensitizer Photosense. Free or nanoparticle-bound Photosense was injected intravenously in healthy rats in the dose 15 mg/kg. It was shown that pharmacokinetic curve of the free drug was characterized by peak concentration while plasma concentrations of nanoparticulate Photosense were relatively steady. Elimination of nanoparticulate Photosense was more rapid comparing to the free drug. It is noteworthy that nanoparticles did not enhance liver uptake of the drug. Lung level of nanoparticulate drug was found to be lower and spleen uptake was enhanced. More important is the fact that nanoparticles provided two-fold decrease of Photosense skin concentration which is potentially important for decrease of drug-related skin phototoxicity. The above data provide evidence that optimization of Photosense pharmacokinetic parameters could be achieved by the use of nanoparticles.

The indices of binding of 21 currently used antibiotics to human peripheral leukocytes (the ratio of the cellular and extracellular concentrations) were determined experimentally in regard to various age periods, i.e. at the birth, from 1 to 3 years and from 5 to 9 years of the age. It was shown that during the period up to 5 years of the age the binding lowered, especially to the polymorphonuclear leukocytes and not so much to the lymphocytes. The different parameters of the cell pharmacokinetics in children should be taken into account in chemotherapy of bacterial infections with intracellular localization of the pathogen.

The pharmacokinetics of kanamycin in patients with peritonitis was studied after its intramuscular, endolymphatic and lymphotropic administration. Endolymphatic administration of kanamycin provided an increase in its activity in the inflamed tissues of the peritoneum and omentum and markedly prolonged its halflife as compared to those after the routine intramuscular administration of the drug. Lymphotropic administration of kanamycin failed to provide the same effect. Endolymphatic therapy of the patients during the postoperative period provided a decrease in the lethality, development of complications and the terms of the treatment in the hospital. The therapeutic effect of the endolymphatic administration of kanamycin to the patients with peritonitis proved to be high. The more efficient antibiotic therapy of the cases was likely due to favourable shifts in the pharmacokinetics of kanamycin after its endolymphatic administration.

Antibiotic binding by leukocytes from patients with chronic brucellosis was studied in vitro. The pathogens were located intracellularly. The specimens were collected during the disease aggravation prior to the treatment and at the beginning of the remission after the routine therapy. It was found that during the disease aggravation at the intoxication peak and accumulation of a large number of Brucella in the cells binding of methacycline, rifampicin and gentamicin somewhat increased. After completion of the treatment course when the number of Brucella in the leukocytes markedly lowered, up to disappearance, the antibiotic binding decreased and reached the control figures. Penetration of erythromycin into the cells infected with Brucella lowered at the disease peak and remained at that level with an insignificant tendency to normalization at the beginning of the clinical remission after the treatment. The facts suggested that intracellular localization of the bacteria would change the quantitative characteristics of interaction of the cells, i.e. human leukocytes with antibacterial chemotherapeutic agents. The direction of the shifts must depend on the particular proportion of various types of mechanisms for penetration of drugs into the intracellular medium.

Experiments on white noninbred rats were made to study the binding by isolated organoids and distribution in liver cells of etazole, norsulfazole, sulfamonomethoxine and sulfalene. The latter drug was found to be absorbed by organoids to the greatest degree. Drug complexes with organoids were discovered to be capable of dissociating with a partial release of unbound drug. Intracellular distribution of sulfanilamides is marked by their accumulation primarily by the nuclei and to a lesser degree by the mitochondria and microsomes.

Interaction of erythromycin and oleandomycin with isolated subcellular fractions of rat liver homogenates and intracellular distribution of the antibiotics were studied. It was found that the macrolides were bound by the cell organoids. The binding was partially reversible. The intracellular distribution was characterized by accumulation of erythromycin and oleandomycin in the mitochondrial fraction while erythromycin preserved higher activity in cytosol as compared to oleandomycin. Sulfalen induced redistribution of the macrolides. It decreased absorption of the macrolides by the organoids and increased the concentration of free erythromycin and especially oleandomycin in cytosol.

Binding of tetracyclines, i. e. tetracycline, oxytetracycline, morphocycline, methacycline and doxycycline by subcellular fractions of rat liver homogenates was studied on randombred albino rats. It was shown that the drugs lost their activity to a significant extent on contact with nuclei, mitochondria, microsomes and the fraction mixtures. The mitochondrial fraction bound the highest amounts of the drugs. The binding level of methacycline by the organoids was the highest, while that of morphocycline was the least. Binding of the tetracyclines with the subcellular fractions of the liver was to a certain extent reversible. Accumulation of the antibiotic in the cells may be advantageous from the viewpoint of its effect on the intracellular microbes if possible subsequent dissociation from its complex with organoids is considered. At the same time the mitochondriatropic properties of the tetracyclines may be the basis for their toxic effect on the host cells.

Interaction of gentamicin and sisomicin with isolated subcellular fractions of the rat liver and the kidney cortical layer was studied. Distribution of the antibiotics was investigated in a system with the volume ratio of the main components (organoids and cytosol-dissolved drug) simulating the natural volume ratio of the cytoplasm and organoids in the cells. It was shown that lysosomes were the most active elements in binding antibiotics. The microsomes and mitochondria were less active. By the binding capacity the subcellular structures of the kidneys were superior to the analogous structures of the liver. Dissociation of the organoid complexes with the antibiotics was possible, the mobility of the sisomicin complexes being higher than that of the gentamicin complexes. During intracellular distribution the major amount of every of the above aminoglycosides was absorbed by the organoids. Up to 20 per cent of gentamicin and up to 30 per cent of sisomicin remained in the cytoplasm in the active form. The characteristic features of the intracellular distribution of sisomicin (build up of high levels of the free antibiotic in the cytoplasm and relatively easy dissociation of the antibiotic complexes with the organoids of the kidney cortical layer) may define the higher activity of sisomicin as compared to that of gentamicin against intracellularly located microorganisms and its lower potential nephrotoxicity.

Distribution of tetracyclines, such as oxytetracycline, morphocycline, tetracycline, doxicycline and methacycline in the liver cells of rats was studied. The ratio of the subcellular structures, i. e. nuclei, mitochondria and microsomes and the liquid phase containing the drugs in the dissolved state in the system studied was close to the natural ratio of the hepatocyte organoids and cytoplasm. Distribution of tetracyclines in the subcellular fractions was not uniform. The nuclei did not absorb the drugs. The role of microsomes in drug absorption was insignificant. The mitochondria bound the highest amounts of the drugs and defined the characteristics of their intracellular distribution. The amounts of the drugs in the active form remaining in the cytoplasm after their contact with organoids were low. At the same time there was observed a a definite activating effect of the cytoplasm components on the antibiotics contained in it.

Interaction of rifampicin with isolated subcellular fractions of the rat liver (binding and dissociation of the complexes) and intracellular distribution of the antibiotic were studied in the presence of the main organoids taken in the ratio close to the natural volume ratio of the hepatocyte cell components. The nuclei and mitochondria were most active during drug binding. The microsomes were less important. Rifampicin formed mobile complexes with organoids and was easily released from the subcellular fractions recovering its activity on washing. The intracellular distribution was the following: 37.7 per cent of rifampicin in the active form was accumulated in cytosol and the remaining amount was reversibly bound in the fractions of the nuclei, mitochondria and microsomes. The characteristic features of the cell pharmacokinetics of rifampicin, i.e. significant concentration in cytosol, possible deposition in the subcellular structures and at the same time the capacity for recovery of the activity might define the antimicrobial potential of this antibiotic in respect to the intracellular microorganisms.

The effect of the rat age on the binding of tetracyclines to the subcellular fractions of liver homogenates was studied. The tetracyclines significantly lost their activity after the contact with the cell organoids. The level of the binding was lower in the newborn and old rats, the complex of tetracycline with mitochondria being less stable. The greater part of the antibiotic reduced its activity after washing of the organoids. The deposition of the antibiotics in the cells was the most pronounced in the pubertal animals.

In vitro binding of tetracycline, gentamicin, erythromycin and rifampicin by the liver organoids and intracellular distribution of the antibiotics in the hepatocytes of rats with acute irradiation disease were studied. Total gamma-irradiation of the animals with 60Co in a dose of 750 R resulted in the development of a typical radiation disease and induced pronounced changes in binding of tetracycline, gentamicin and erythromycin by isolated subcellular fractions. Simultaneous impairment of the antibiotic intracellular distribution was observed. Rifampicin interaction with the cell structures was unchanged. It is suggested that there is a relation between the level of the impairment of the antibiotic cell pharmacokinetics in acute radiation disease and the mechanism of the drug intracellular binding in health.

Penetration of carbenicillin, cefotaxime, gentamicin and sisomicin into leukocytes of peripheral blood in man and their intracellular distribution were studied. By its capacity for penetration into leukocytes cefotaxime was superior to the other antibiotics. The levels of sisomicin and carbenicillin absorption by the cells were equal. The level of gentamicin penetration into the cells was the lowest. After penetration into the cells the main part of carbenicillin was preserved in its active form in the cytoplasm. Absorption of the antibiotic by the nuclei, granules, mitochondria and microsomes was insignificant. Cefotaxime was bound to the organoids and not more than 20 per cent of the antibiotic were preserved in its active form. The aminoglycosides were mainly absorbed by the cell granule fraction and the level of the active form of sisomicin in the cytoplasm was twice as higher as that of gentamicin. On the basis of the data on the cell pharmacokinetics of the above antibiotics, their mean therapeutic serum levels and mean geometric values of their MICs for P. aeruginosa it was suggested that in case of intracellular localization of P. aeruginosa the increase in the antibiotic efficacy was of the following order: gentamicin less than cefotaxime less than or equal to sisomicin less than carbenicillin.

The studies showed that the tetracyclines tested (morphocycline, tetracycline and methacycline) penetrated into leucocytes of the human peripheral blood. Agranulocyte absorbed the drugs more actively than granulocytes. Pinocytosis was suggested to be involved in the penetration. On interaction with intracellular structures the tetracyclines reversibly bound to the organoid cells lost their biological activity to a significant degree. Progressive dissociation of organoid-drug complexes and the egress of tetracyclines from the cells were likely to occur as their contents in the extracellular environment decreased. The penetration capacity and subcellular structure affinity of methacycline were the highest among the drugs tested. It is suggested that penetration of the tetracyclines through the cytoplasmic membranes and their distribution inside the cells are reciprocal.

Binding of the tetracyclines by the cell components of various organs of rats was studied comparatively. It was shown that binding of the tetracyclines by the subcellular fractions was decreasing as follows: the liver, the heart, the kidneys. The mitochondria were the fraction most actively binding the antibiotics. For determination of the features of this process the characteristics of tetracycline binding by the liver organoids of the rats and rabbits were compared. The quantitative indices of binding of the tetracyclines by the cell components of the rats and rabbits were rather similar.

Interaction of rabbit alveolar macrophages with morphocycline, tetracycline and methacycline was studied. The use of the membrane microfiltration technique in investigation of the antibiotic absorption by the macrophages provided description of the time course of the drug interaction with the cells at its early stages. It was shown that the macrophages mainly absorbed the tetracyclines within the first 20 seconds (1 minute incubation). Later, within the period of 1-5 minutes no significant time course was observed. The medium temperature within 4-37 degrees C and the number of the cells in the system (0.1-5 minutes no significant time course was observed. The medium temperature within 4-37 degrees C and the number of the cells in the system (0.5-1 million/ml) had no effect on the parameters of the tetracyclines sorption by the macrophages. The percentage of the decrease of the morphocycline level in the extracellular medium was stable at the drug concentration in the cells ranging within 10-50 micrograms/ml. The respective figures for tetracycline and methacycline were 10-100 and 10-5000 micrograms/ml. Further increasing of the concentration of the antibiotics in the incubation medium resulted in a significant lowering of the percentage of their binding. It was suggested that absorption of the tetracyclines by the cells was associated with their intracellular binding.