[Antiviral and anti-stress activity of the gamma-L-glutamyl-histamine and its derivatives]. / Protivovirusnaia i antistressornaia aktivnost' gamma-L-glutamilgistamina i ego analogov.

Effect of gamma-L-glutamylhistamine gamma-L-Glu-HA and some of its derivatives on the state of nonspecific resistance and antiviral activity was studied using experimental models of influenza virus and herpes simplex virus infections. Activities of natural killer (NK) cells and interferon (IFN) system were measured. The model of physical-emotional stress in mice was used. It was shown that the gamma-L-Glu-HA derivative II can prevent totally or substantially a decrease in the NK activity. This agent also prevents inhibition of synthesis of alpha- and gamma-IFN during the post-stress period. The gamma-L-Glu-HA derivatives II, III, and VII increased the mice resistance to influenza virus type A/Aichi at low infection dose (10LD50). The derivative II showed its protective effect even at high dose of pathogen (100LD50). However, this gamma-L-Glu-HA derivative was virtually ineffective under harsh experimental conditions. Thus, a number of gamma-L-Glu-HA derivatives tested in this work demonstrated immunomodulation activity. These agents were able to normalize parameters of nonspecific immunity. They exerted a pronounced antiviral effect against influenza virus but were virtually ineffective against encephalitis in mice caused by herpes simplex virus, type 1. Of all tested agents, gamma-L-Glu-HA derivative II was found to be the most promising.

[Hepatoprotective effects of gamma-L-glutamylhistamine]. / Gepatoprotektornaia aktivnost' gamma-L-glutamilgistamina.

The influence of gamma-GluHA and glutarylhistamine on the lipid peroxidation, cholesterol, phospholipid and liver aminotransferase activity was investigated using carbon tetrachloride-induced model of subacute liver damage. Pretreatment of rats with gamma-GluHA and glutarylhistamine prevented liver necrosis and normalized activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood plasma, lipid peroxidation in the liver and plasma, lipid profiles and cholesterol content in the liver and plasma.

[The effect of gamma-L-glutamylhistamine analogues on the severity of experimental anaphylactic reaction, hormonal status and liver cytochrome P450 system]. / Vliianie analogov gamma-L-glutamilgistamina na izmenenie tiazhesti proiavlenii éksperimental'noi anafilakticheskoi reaktsii, gormonal'nogo statusa i sistemy tsitokhroma P450 pecheni.

The influence of gamma-L-glutamylhistamine analogues on the hexenal-induced sleeping, glucocorticoid hormone content in blood plasma and severity of experimental anaphylactic reaction was studied. It was observed that gamma-L-glutamylhistamine analogues caused decrease in the sleeping time and severity of experimental anaphylactic reaction, the elevation of glucocorticoids content in blood plasma. The present results indicate that substances have the wide spectrum of biological activity which depends on the length of the N-acyl radical.

[The effect of gamma-L-glutamyl histamine on the severity of experimental anaphylactic reaction, hormonal status and liver cytochrome p-450]. / Vliianie gamma-L-glutamilgistamina na izmenenie tiazhesti proiavlenii éksperimental;noi anafilakticheskoi reaktsii, gormonal'nogo statusa i sistemy tsitokhroma p-450 pecheni.

gamma-L-Glutamyl-histamine (gamma-GluHA) was synthesized at Department of the chemistry and technology of fine organic compounds M. V. Lomonosov Moscow state academy of fine chemical technology. It was investigated the influence of gamma-L-glutamyl-histamine on the severity of experimental anaphylactic reaction, hormonal content in blood plasma and liver cytochrome P-450. The induction of liver cytochrome P-450, the elevation of hormonal content (thyroxine and glucocorticoids) in blood plasma and decrease of the severity of experimental anaphylactic reaction are observed.

[Effect of cytochrome P450-dependent metabolites of arachidonic acid on the functional state of vessels]. / Vliianie tsitokhrom P450-zavisimykh metabolitov arakhidonovoi kisloty na funktsional'noe sostoianie sosudov.

The present paper reviews recent studies about the role of the cytochrome P-450-dependent arachidonic acid metabolites. There metabolites take part in the regulation of the vascular tone. They are the intracellular messenger and play an integral role in the relation of the vascular endothelium and smooth muscle cells. The arachidonic acid metabolites regulate the activity of the ionic channels. It is demonstrated that derivatives of arachidonic acid have the role in the pathogenesis of hypertension.

[The effect of fatty compounds with different ratios of the polyunsaturated fatty acids of the omega-3 and omega-6 families on the expression of food-related anaphylaxis, on the liver cytochrome P-450 system and on 17-hydroxycorticosteroid metabolism in guinea pigs]. / Vliianie zhirovykh kompozitsii s razlichnym sootnosheniem polinenasyshchennykh zhirnykh kislot semeistv omega-3 i omega-6 na vyrazhennost' pishchevoi anafilaksii, sistemu tsitokhroma P-450 pecheni i metabolizm 17-oksikortikosteroidov u morskikh svinok.

The effect of fat composition with a different ratio of polyunsaturated fatty acids of families omega 3 and omega 6 on expression of experimental dietary anaphylaxis, liver monooxygenase system and metabolism of 17-oxycorticosteroides (17-OCS) in guinea-pig have been investigated. Fat components in experimental diets were presented by sunflower, ichthyene oils and mix of these oils in the ratio 1:1. A ratio of PUFA of a family omega 6 to omega 3 in diets were 64,0; 0,13 and 2,64. It was shown that a burden of dietary anaphylaxis were reduced significantly at the introduction in diets of sunflower oil.ulakcuu is authentically reduced. Simultaneously a marked increase of a ratios P-450B to P-450L and b5 to P-450 and reduction of a hexenal sleep duration were determined. The amount of excreted polar 17-OCS was also decreased in animals fed sunflower oil. Probable mechanisms of hypoallergenic action of dietary sunflower oil were conditioned by reorganization of liver cytochrome P-450 system and respective alterations of 17-OCS metabolism are discussed.

[Changes of anaphylactic sensitivity to some food proteins and aflatoxin B1 in guinea pigs]. / Izmenenie anafilakticheskoi chuvstvitelnosti morskikh svinok k nekotorym pishchevym belkam pod vliianiem aflatoksina B1.

The study was made of aflatoxin B1 effect on guinea pig alimentary anaphylaxis to chicken ovalbumin (CO) and pasteurized cow milk (PCM), of CO-specific IgG antibody levels, some serum indices, sensitivity of the animals to LD50 histamine. In response to aflatoxin B1 alimentary anaphylaxis both to CO and PCM became more severe, lethality of the anaphylaxis to CO being in logarithmic relation to aflatoxin B1 dose (p < 0.05); specific IgG-antibodies to CO grew in number; serum total protein increased against unchanged levels of albumins; the activity of gamma-glutamyltransferase inhibited; histamine shock gained severity, its lethality being logarithmically related to the aflatoxin B1 dose. The discussion covers mechanisms underlying the animal allergic reactivity responses to aflatoxin B1.

[Effects of dietary fat composition on food anaphylaxis and formaldehyde sensitization in guinea pigs]. / Vlianiie zhirovykh kompozitsii ratsiona na pishchevuiu anafilaksiiu i sensibilizatsiu formal'degidom u morskikh svinok.

Adult guinea pigs were fed for 10-14 days with synthetic diets, fat constituting 11% of its total energy. Dietary fat was composed of coconut, corn, dairy and soybean oils mixtures with ratio of polyunsaturated fatty acids (PUFA) omega-6 to PUFA omega-3 equal to 24.2 (K1) or 5.53 (K2). The animals were sensitized orally by pasteurized cow milk (PCM) or epicutaneously by formaldehyde (F) during these diets feeding. The degree of the sensitization was assessed in the reaction of active anaphylactic shock (AAS) in PCM-sensitized animals and in the reaction of leukocytes specific lysis (LSL) in F-sensitized guinea pigs. In the latter pigs the concentration of serum antibodies (Ab) against dietary soya protein was measured by ELISA. Animals fed by K1 and K2 were also tested for histamine mean lethal dose resistance. The lowest lethality in AAS, number of convulsions, of positive LSL cases and Ab level were found in animals fed by K1 compared to both K2 and to animals fed by common animal chew. Resistance to histamine was similar in K1 and K2 groups, but was significantly higher compared to control (chew) group. In convulsion, the changes in PUFA omega-6/PUFA omega-3 ratio have marked effect on different indices of allergic sensitivity.

[Characteristics of anaphylaxis in fasting rats]. / Osobennost proiavleniia anafilaksii u krys pri golodanii.

The effect of 4-day fasting was studied in male Wistar rats (200-150 g) sensitized by ovalbumin on anaphylaxis manifestations in vivo, antigen-dependent histamine secretion by mast cells in vitro, concentration of serum specific IgG antibodies. The fasting ended by a shocking allergen dose. It is shown that in the condition of food deprivation anaphylactic severity significantly lowered as well as antigen-dependent histamine secretion by mast cells. No changes were seen in the levels of specific antibodies in the serum.

[Effect of milk proteins and their enzymatic hydrolyzates on non-specific resistance of some systems to food allergens]. / Vliianie belkov moloka i poluchennykh na ikh osnove fermentativnykh gidrolizatov na sostoianie nekotorykh sistem, obespechivaiushchikh nespetsificheskuiu rezistentnost k pishchevym allergiziruiushchim vozdeistviiam.

Noninbred male guinea-pigs (b. mass 250-300 g) were kept for 35 days on diets in which 50% of standard proteins were replaced for cow milk protein (CMP) 20/80 and its enzymatic hydrolyzate (EH) 20/80 obtained by ultrafiltration. CMP 20/80 and EH 20/80 have been examined for the effect on proteolytic activity of gastric mucosa, small intestinal activity of trypsin and chymotrypsin, hepatic cytochrome P-450 and metabolism of excreted 17-OCS. The animals given EH 20/80 exhibited enhanced total proteolytic activity of trypsin and chymotrypsin, higher total levels of cytochromes P-450 and P-450B in the liver, increased urine excretion of 17-OCS, reduced amount of polar forms in all the glucocorticoid fractions. Potential mechanisms securing the action of enzymatic hydrolyzates on the systems responsible for nonspecific resistance to food allergens are suggested for discussion.

[The effect of starvation on mast cell functional activity and on the content of microsomal cytochromes in the liver]. / Vliianie golodaniia na funktsional'nuiu aktivnost' tuchnykh kletok i soderzhanie mikrosomal'nykh tsitokhromov v pecheni.

Histamine secretion and ATP levels were measured in mast cells from the abdominal and pleural cavities of Wistar rat males (250-300 g) which had been starving for 2-4 days. Food deprivation had no effect on histamine levels and secretion in exposure to substance 48/80. ATP concentration got reduced from starvation day 2. Food deprivation for 2 days led to decline in the content of cytochromes P-450, P-450B, in the ratio P-450B/P-450L, but had no effect on rat liver cytochrome B5. 4-day starvation did not entail further changes.

[Experimental evaluation of the allergen activity of a peptide preparation produced from an enzymatic hydrolysate of milk proteins using ultrafiltration]. / Eksperimental'naia otsenka allergennogo deistviia peptidnogo preparata, poluchennogo iz fermentativnogo gidrolizata belkov moloka s ispol'zovaniem ul'trafil'tratsii.

Noninbred guinea-pig experiments were performed to investigate specific potential allergenicity of cow milk proteins (CMP) consisting of casein (80%) and serum proteins (20%), of low-molecular peptides (LMP 20/80) produced from CMP 20/80 by enzymatic hydrolysis and ultrafiltration; to evaluate nonspecific effect of test diet CMP 20/80 and LMP 20/80 on anaphylactic response of the animals to ovalbumin and histamine LD50. LMP 20/80 versus CMP 20/80 had a hypoallergenic effect. Potential mechanisms of low anaphylactic sensitivity induced by LMP 20/80 are discussed.

[The function of mono-oxygenase system in exposure to tricresol (experimental research)]. / Sosotianie monooksigenaznoi sistemy pri vozdeistvii trikrezola (éksperimental'noe issledovanie).

Studies of monoxygenase system in rat liver exposed to tricresol showed, that the microsomal enzymes status depends on the route of tricresol administration and on the exposure intensity. Monoxygenase system status compared with the serum enzymes activity characterizing the function of the liver showed that changes in microsomal system are more marked, appear earlier and after lower levels of exposure. Changes of cytochrome P-450 enzyme system are the main principle of tricresol harmful action.

[Characteristics of food anaphylactic reactions to proteins and protein preparations in guinea pigs with different duration of hexenal-induced sleep]. / Osobennosti reaktsii pishchevoi anafilaksii na belki i belkovye preparaty u morskikh svinok s razlichnoi prodol-zhitel'nost'iu geksenalovogo sna.

The state of guinea pig sensitization was studied in the direct test in vivo by induction of active food anaphylaxis (FA). The animals were orally sensitized with food allergens: chick ovalbumin (OVA), bovine serum albumin, and protein preparations N 1 and N 2 (PP N 1 and N 2). In guinea pigs with null hexenal-induced sleep (NHS) and long hexenal-induced sleep (LHS), 40 min, the duration of HS is reliably reproduced in repeated testing. The intensity of FA reactions in guinea pigs with NHS was less manifested than in the animals with LHS with both food allergens. Significantly higher allergenic properties of PP N 2 were expressed in the animals with LHS. It was shown that varying anaphylactic sensitivity of guinea pigs in the above groups was not related with different permeability of the gastrointestinal tract of these animals for OVA macromolecules. Possibilities of metabolic validation of increasing anaphylactic sensitivity of guinea pigs with LHS have been considered.

[Characteristics of peptide preparations obtained during enzymatic hydrolysis and ultrafiltration of milk proteins for use in specialized nutrition products]. / Kharakteristika peptidnykh preparatov, poluchennykh pri fermentativnom gidrolize i ul'trafil'tratsii belkov moloka, prednaznachennykh dlia ispol'zovaniia v spetsializirovannykh produktakh pitaniia.

+Ultrafiltrated bovine milk proteins with whey protein/casein ratios 20/80, 60/40 and 97/3 were subjected to pancreatin hydrolysis, and the hydrolysates obtained were fractionated to high- and low-molecular weight (LMW) fractions by means of ultrafiltration. The preparations obtained were characterized according to routine physico-chemical indices, amino-nitrogen content, amino acids score, molecular weight distribution, and concentration of precipitating milk antigens. The capacity of LMW fractions for inducing oral anaphylactic sensitization in guinea pig and for changing its susceptibility to histamine LD50 was studied. The conclusion has been made that LMW preparations with whey/casein ratios 20/80 and 60/40 could be effectively used in specialized formulae intended for nutrition of allergic children and adults, nursing women, and also for enteral nutrition.

[Changes in the immunochemical properties of beta-lactoglobulin during proteolysis and exposure to various physico-chemical factors]. / Izmenenie immunokhimicheskikh svoistv beta-laktoglobulina pri proteolize i nekotorykh fiziko-khimicheskikh vozdeistviiakh.

Heating of cow milk beta-lactoglobulin at 96 degrees, pH 8.0 led to the protein aggregation because of intermolecular disulfide exchange as shown by agarose gel immunoelectrophoresis, where additional precipitation strips were detected. At the same time, there was not observed dissociation of beta-lactoglobulin into separate fractions after proteolysis or denaturation in 8 M urea. beta-Lactoglobulin, its thermoaggregated and S-carboxymethyl denaturated forms exhibited similar anaphylactic effect on sensitized guinea pigs. Allergenic properties of beta-lactoglobulin appears to be unaltered in food hydrolyzates after thermal treatment and limited proteolysis.

[Turnover of microsomal hemeproteins in the guinea pig liver during food sensitization]. / Osobennosti obnovleniia mikrosomal'nykh gemoproteinov pecheni morskikh svinok v dinamike pishchevoi sensibilizatsii.

A phase-dependent type of microsomal hemoproteins turnover in liver tissue, estimated by incorporation of 14C-amino-levulinic acid, was detected in guinea pig males in dynamics of alimentary sensitization (1, 7, 14 and 21 days) with ovalbumin and bovine blood serum albumin (BSA). The first phase was expressed as elevated catabolism of microsomal cytochromes simultaneously with a decrease in their turnover; the second phase involved an increase in the hemoproteins biosynthesis. Less distinct sensitization with BSA exhibited the shortened period of the first phase, while activation of aminopyrine N-demethylase and aniline p-hydroxylase as well as considerably increased rate of microsomal cytochromes turnover were found during the second phase in liver tissue.

[A comparative experimental evaluation of the potential allergenicity of milk proteins and their hydrolysates obtained by different technological means]. / Sravnitel'naia éksperimental'naia otsenka potentsial'noi allergennosti nekotorykh molochnykh belkov i ikh gidrolizatov, poluchennykh razlichnymi tekhnologicheskimi sposobami.

Some samples of cow milk proteins and enzymatic hydrolysates prepared on their basis were investigated in experiments on male guinea pigs to elucidate their sensitizing properties and influence on sensitivity to histamine LD50. The data obtained are discussed with respect to a possible modulation of allergic reactions by the products of incomplete enzymatic proteolysis.

[An experimental evaluation of the hypoallergenic action of fat constituents for specialized therapeutic products]. / Eksperimental'naia otsenka gipoallergennogo deistviia nekotorykh zhirovykh kompozitsii dlia spetsializirovannykh lechebnykh produktov.

The influence of fatty compositions with varying proportions of polyunsaturated fatty acids (PUFA) omega-6 and omega-3 on the manifestation severity of anaphylaxis to ovalbumin (OVA), whole pasteurized cow milk (WPCM), and sensitivity to histamine LD50 were investigated in male guinea pigs. Hypoallergenic effect to OVA and WPCM, decreased sensitivity to to histamine LD50 were manifested in the animals which received the fatty composition with a high ratio of omega-6 and omega-3 PUFA (24, 20). A correlation was established between the hypoallergenic action of the fatty composition and the content of medium- and long-chain saturated fatty acids in this composition. The results obtained have been considered with respect to the characteristics of the immunomodulatory effects of PUFA omega-6, omega-3 and saturated fatty acids.