[Breast milk proteins as a focus for the improvement of recipes for infant adapted milk formulae].

After a long evolutionary development starting at the appearance of the first mammals about 200 million years ago, breast milk (BM) was formed into a unique functional nutrition system with an individual composition that promotes normal growth and development of the newborn, and determines the prospects for health throughout life. The review describes the properties and functions of BM in order to objectify the physiological effects of breastfeeding and justify the composition of formulae for artificial feeding (AF). It discusses modern ideas about the protein composition of BM and its significance for the growth and development of the infant, the problems of adapting the protein component of AF formulae, and the prospects for their optimization on the basis of modern production technologies. The conclusion is that BM is a complex dynamic matrix, and therefore extensive research, including on the main protein components and their interrelationships, is needed to fully understand and scientifically substantiate approaches to its adaptation.

[Development of the infant formula industry].

The creation of the first prototypes of modern breastmilk substitutes at the end of the nineteen century brought in a new era in feeding infants in the first year of life. Currently, artificial feeding of newborns consists of adapted milk formulae made with the latest production technologies. This review briefly discusses the history of the development and classification of breastmilk substitutes, the main local and international documents regulating their composition, as well as the basic principles of approximation (adaptation) of formulae to breast milk. Obviously, these issues are key in understanding the specifics and correct definition of the prospects and directions for the development of the breastmilk substitute industry.

Cholesterol - an essential component of infant milk formulae?

It is recognized that breast milk is the ideal food for newborns. Indeed breast milk can provide basic guidelines to improve the composition of ingredients in adapted infant formulae. One of the main parts of breast milk is milk fat. Although the exact functionality of the entire spectrum of fat is not yet fully understood, it is known that various lipids present in breast milk, can modulate functions of the gastrointestinal tract, the lipoprotein metabolism, the structure and function of cell membranes, as well as many signal pathways in the infant's organism. In this paper we tried to present evidence that dietary cholesterol (CHOL) is a very important component of the infant's nutrition. Meanwhile, almost all infant formulae, both cow and goat milk based, use nearly only vegetable oils as their fat component providing phytosterols, rather than CHOL as in breast milk. It is known that breast milk is a rich source of CHOL and phytosterols cannot perform the functions of CHOL. One can imagine that when the infant is transferred to artificial feeding with such formulae, and denied the opportunity to receive dietary CHOL in any useful amounts, this may affect outcomes like optimal child development, and may have a major long-term 'programming' effect on the metabolism of CHOL. We propose to discuss the thesis of the great importance of the presence of CHOL in infant formulae. The applied value of this thesis is the need to optimize the fat component of breast milk substitutes by introducing CHOL, for example, in the composition of milk fat. Although it is clear that compelling evidence of the potential benefits of adding various sources of CHOL infant formula is insufficient, at this stage, there is cause for a critical discussion and review of the composition of functional components of breast milk substitutes.

[Modern trends in study of polymorphism of genes encoding goat's milk proteins].

This review emphasises the genotypical heterogeneity of the population of goats, which at the molecular level is manifested in the form of gene polymorphism in the milk proteins. Polymorphic genes, represented in the population of heterogeneous alleles, cause a wide variance in the chemical composition and processing properties of goat milk. We summarized the literature about the main features of genes encoding proteins of goat milk. It is stressed that goat's milk, due to genetic polymorphism has a great value when creating a new functional food product for children.

[Milk fat globules, as determinants of the nutritional and biological value of goat milk].

This review summarizes the most complete information on such fundamentally important quality parameters of goat milk as the cellular composition of somatic cells and the structure of cytoplasmic debris in milk. It also focuses on the characterization of an essential component of the energetic value and nutritional content of milk--milk fat globules and milk fat globule membranes. The survey also clarifies some of the terms and meanings of physiological processes associated with the formation of the milk of various ruminants and breast milk.

[Historical journey to infant feeding].

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.

[Enhanced activity of rifampicin loaded with polybutyl cyanoacrylate nanoparticles in relation to intracellularly localized bacteria]. / Povyshenie aktivnosti rifampitsina, assotsiirovannogo s nanochastitsami iz polibutiltsianoakrilata, v otnoshenii bakterii, lokalizovannykh vnutri kletok.

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.

Toxicological studies of doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles in healthy rats and rats with intracranial glioblastoma.

Polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (NP) were shown to enable the transport of a number of drugs including the anti-tumour antibiotic doxorubicin (DOX) across the blood-brain barrier (BBB) to the brain after intravenous administration and to considerably reduce the growth of brain tumours in rats. The objective of the present study was to evaluate the acute toxicity of DOX associated with polysorbate 80-coated NP in healthy rats and to establish a therapeutic dose range for this formulation in rats with intracranially implanted 101/8 glioblastoma. Single intravenous administration of empty poly(butyl cyanoacrylate) NP in the dose range 100-400 mg/kg did not cause mortality within the period of observation. NP also did not affect body weight or weight of internal organs. Association of DOX with poly(butyl cyanoacrylate) NP did not produce significant changes of quantitative parameters of acute toxicity of the anti-tumour agent. Likewise, the presence of polysorbate 80 in the formulations was not associated with changes in toxicity compared with free or nanoparticulate drug. Dose regimen of 3x1.5 mg/kg on days 2, 5, 8 after tumour implantation did not cause drug-induced mortality. The results in tumour-bearing rats were similar to those in healthy rats. These results demonstrate that the toxicity of DOX bound to NP was similar or even lower than that of free DOX.

[Optimization of "Photosens" pharmakokinetics by biodegradable nanospheres]. / Optimizatsiia farmakokinetiki preparata "Fotosens" s pomoshch'iu biodegradiruemykh nanochastits.

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.

Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles.

PURPOSE: To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles). METHODS: Rats obtained 5 mg/kg of doxorubicin by i.v. injection in form of 4 preparations: 1. a simple solution in saline, 2. a simple solution in polysorbate 80 1% in saline, 3. bound to poly(butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1% polysorbate 80 (Tween 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC. RESULTS: No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (>6 microg/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection limit (< 0.1 microg/g). CONCLUSIONS: The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.