Nano optical probe samarium tetracycline complex for early diagnosis of histidinemia in new born children.

A new, precise, and very selective method for increasing the impact and assessment of histidine as a biomarker for early diagnosis of histidinemia disease in new born children was developed. The method depends on the formation of the ion pair associate between histidine and the nano optical samarium tetracycline [Sm-(TC)2]+ complex doped in sol-gel matrix in a borate buffer of pH 9.2. The [Sm-(TC)2]+ complex has +I net charge which is very selective and sensitive for [histidine]- at pH 9.2 in serum and urine samples of histidinemia disease. Histidine enhances the luminescence intensity of the nano optical [Sm-(TC)2]+ complex at 645nm after excitation at 400nm, in borate buffer, pH 9.2. The remarkable enhancement of the luminescence intensity at 645nm of nano [Sm-(TC)2]+ complex doped in sol-gel matrix by various concentrations of the histidine was successfully used as an optical probe for the assessment of histidine in different serum and urine samples of new born children infected by histidinemia. The calibration plot was achieved over the concentration range 1.4×10-5 - 6.5×10-10molL-1 histidine with a correlation coefficient of (0.998) and a detection limit of (3.2×10-10molL-1). The sensitivity (98.88%) and specificity (97.41%) of histidine as a biomarker were calculated.

[Mechanism of diagnostic significance of histidase release into the blood in lymphedema]. / Mekhanizm i diagnosticheskaia zhachimost' vykhoda gistidazy v krov' pri limfedeme.

The organ-specific enzyme histidase was measured as an indicator of skin involvement in the blood of 52 patients with primary and secondary lymphedema of the upper and lower limbs. A stable type of the disease (degree I) was characterized by washing histidase off the derma into the blood. Mild and moderate histidase washing associated with skin dystrophy occurred with progression of the disease (stage II and III, respectively). In advanced lymphedema (degree 4) histidase does not enter blood from the skin. This fact is explained by total impairment of skin cell elements and their replacement for fibrous tissue. Both in primary and secondary lymphedema complicated by erysipelas histidase is washed off the dermocytes. The findings justify use of blood histidase indices for assessment of lymphedema patients' condition, formulation of indications for operation and concluding on the latter efficacy.

[The anticytolytic activity of ubiquinone-10 in a liver lesion from chlorinated hydrocarbons]. / Antitsitoliticheskaia aktivnost' ubikhinona-10 pri porazhenii pecheni khlorirovannymi uglevodorodami.

Antioxidative activity of ubiquinone-10, exceeding the level of that of vitamin E more than five times and anticytolytic activity of vitamin E and particularly of ubiquinone-10 manifested in decreasing activities of blood serum alanine aminotransferase and histidineammoniumlyase, which might be determined only during toxic liver damage, have been demonstrated. The activity of histidineammoniumlyase was considerably decreased under the effect of vitamin E and particularly in the presence of ubiquinone-10. Decreasing of activity of blood serum enzyme markers of cytolysis of hepatocytes is connected with the hepatocytes biomembrane stabilizing effect of antioxidants which was confirmed by the electron microscope investigation method. The evidence of safety of intact cellular and subcellular membranes and activation of compensative and regenerative processes in hepatocytes was also represented.

[Effect of carnosine and 4-methyluracil on the development of experimental hepatitis in rats]. / Vliianie karnozina i 4-metiluratsila na razvitie éksperimental'nogo gepatita u krys.

A comparative study of the hepatoprotective effect of carnosine and 4-methyluracil under CCl4-induced acute toxic hepatitis has been carried out. The extent of liver injury and its regeneration were established from morphological data as well as from changes in the activities of alanine aminotransferase (ALT) and histidase and the bilirubin content in blood serum. Hyperlipoperoxidation in the liver and serum was assessed by the amount of TBA-active products. It was found that by day 10 of experimental hepatitis ALT and histidase levels in blood sera of untreated animals exceeded the normal values 1.3- and 3.9-fold, whereas those in the carnosine-treated group approximated the values characteristic of intact animals. The activity of serum ALT in animals treated with vitamin B12 or 4-methyluracil exceeded normal values 1.5 and 1.6 times, whereas that of histidase was 2.5 and 2.7 times as high. Carnosine and 4-methyluracil inhibited (in approximately the same degree) the formation of TBA-active products in the liver. According to morphological dta, cessation of CCl4 injections was accompanied by rapid regeneration of liver tissues in all animal groups. Carnosine enhanced regenerative processes in parenchymatous and connective tissues in a far greater degree in comparison with other drugs. The mitotic index in the carnosine-treated group exceeded more than twofold the corresponding parameters in untreated animals. Possible mechanisms of carnosine action on liver repair are discussed.

[Dynamics of glutathione metabolizing enzyme activity in experimental acute cholecystitis]. / Dinamika aktivnosti fermentov obmena glutationa pri éksperimental'nom ostrom kholetsistite.

Dynamics of glutathione-related enzymes activity was studied in erythrocytes of 22 dogs with destructive form of cholecystitis. As clinical symptoms of intoxication developed the enzymatic activity was decreased. In the animals with purulent-inflammatory complications distinct decrease was detected in activity of glutathione reductase (by 54.3%), glutathione-S-transferase--by 46.94% and glutathione peroxidase--by 42.1% (P less than 0.05). These data suggest that specific methods should be chosen for correction of impairments in the enzymatic activity in order to improve the treatment course efficiency as well as for prophylaxis of complications. The procedure developed for cholecystitis treatment, which involved channelled transport of antibiotics by means of autologous erythrocyte ghosts, proved to be more effective as compared with routine methods as shown by evaluation of the animals clinical state as well as by dynamics of hepato-specific enzymes activity and the glutathione-related enzymes activity. This procedure may be used in clinical practice; the laboratory tests described may serve for evaluation of the treatment course efficiency.

[Glutathione levels and the activity of the enzymes of glutathione metabolism in erythrocytes of patients with acute cholecystitis]. / Dinamika urovnia glutationa i aktivnosti fermentov obmena glutationa v éritrotsitakh bol'nykh ostrym kholetsistitom.

It is shown that in acute cholecystitis patients versus chronic cholecystitis ones and donors, the total glutathione in blood is lower while the activity of glutathione metabolism enzymes in red blood cells inhibited. Enzymological findings correlate with clinical symptoms of intoxication. Surgery aggravates disturbed activity of the enzymes. Conventional conservative therapy is not effective in normalizing the enzymes activity either. A good therapeutic response can be achieved by a directed transport of antibiotics in autologous blood ghosts which promotes recovery of normal activity of glutathione metabolism enzymes, routine glutathione level, early stabilization of hepatocytic membranes beneficial for surgical patients.

[Experimental study of the hepatoprotective effect of transcranial transcutaneous electrostimulation and the synthetic analog of leu-enkephalin dalargin]. / Izuchenie v éksperimente gepatoprotektornogo deistviia transkranial'noi chreskozhnoi élektrostimuliatsii i sinteticheskogoanaloga lei-enkefalina dalargina.

Results obtained from the study of mechanisms of hepatoprotective effect of transcranial transcutaneous electrostimulation are cited (TTES). In experiments on cholestase and pancreatitis models in rats we studied hepatospecific enzymes i.e. histidase and urokininanse in blood and liver and membrane-linked enzyme 5'-nucleotidase in the liver tissue. We made three series of experiments: 1 - TTES + valium, 2 - synthetis hexapeptide (SH) - leuenkephaline analog; 3 - TTES + valium + SH. Results obtained from experiments showed that mechanisms of TTES hepatoprotective action are in part conditioned by endogenous opiopeptides mobilization which produced membranestabilizing effect on the hepatocyte. We concluded that in patients with hepatic pathology it was reasonable to combine the electroanesthesia with SH.

[Effect of the components of electro-drug anesthesia and ataralgesia on the appearance of hepato-specific enzymes in the blood]. / Izuchenie vliianiia komponentov élektromedikamentoznoi anestezii i ataralgezii na poiavlenie v krovi gepatospetsificheskikh fermentov.

The influence of diazepam, droperidol, fentanyl and central transcutaneous electrical stimulation (ES) on hepatocytes was studied in experiments on healthy rats (group I). Organospecific enzymes (histidase and urokinase) were chosen for the evaluation of side effects of drugs and their combination with ES on physiological functions of the liver. Drugs and their combinations with ES used in the clinical practice caused no marked damage of hepatocytes in healthy animals. A pronounced decrease in the above enzyme activity (3-fold, as compared to the control group) was revealed in rats with acute cholestasis and pancreatitis 72 h after ES. This fact shows hepatoprotective effects of ES. The most marked unfavourable effect on hepatocytes was registered in group II, where fentanyl was used.

[The role of changes in the antioxidative activity and phospholipid composition of the rat liver in the mechanism of phenazepam action on the liver and the protective effect of talamonal]. / O roli izmenenii antiokislitel'noi aktivnosti i sostava fosfolipidov pecheni krys v mekhanizme deistviia fenazepama na pechen' i zashchitnom éffekte talamonala.

Phenazepame exhibited properties of prooxidant in a model system of oleic acid methyl ester oxidation. After single intraperitoneal administration of phenazepame (5 mg/kg) the antioxidative activity (AOA) of rat liver lipids was decreased, correlating with level of histidase and urokinase activity in blood plasma indicating the liver tissue injury. Distinct alterations in the relative content of liver phospholipids were also noted. A phase type of alterations was observed in the content of these phospholipids as well as in the ratio phosphatidyl choline/phosphatidyl ethanolamine; at the same time, the phospholipid ratio was altered simultaneously with the alterations of the enzymatic activities in blood. After administration of the antioxidant, which normalized the AOA level and the phospholipid composition, activities of histidase and urokinase were markedly decreased in blood. The neuroleptanalgetic drug thalamonale, protecting liver tissue against the impairments, normalized the AOA level and the phospholipid composition. Thus, alterations in AOA and in the phospholipid composition reflected distinctly the unfavourable effect of phenazepame as well as the protecting action of thalamonale on liver tissue.

[Evaluation of the hepatotoxic activity of several chlor-nitro derivatives of benzoic acid]. / Otsenka gepatotoksicheskogo deistviia nekotorykh khlor- nitroproizvodnykh benzoinoi kisloty.

Hepatotoxic effects of 4-chloro-3-nitrobenzoic acid (x-NBA), 3-nitrobenzoic acid (NBA) and 4-chlorobenzoic acid (CBA) were studied at the doses corresponding to LD50, 1/10 LD50 and 1/50 LD50. The toxic effects were estimated by monitoring alterations in activity of protein-synthesizing system in liver tissue and by the analyses for the presence in blood serum of two tissue-specific cytoplasmic enzymes of liver cells--urokaninase (EC 4.2.1.49) and histidase (EC 4.3.1.3). Single peroral administration of the toxic substances at a dose equal to LD50 led to dissimilar alterations in synthesis of liver proteins: activation within 0.5-5 hrs, distinct increase up to the maximal value within 60 hrs, with a gradual decrease approaching the control values within 8 days. Urokaninase and histidase activities were found in blood serum within 8 hrs after the intoxication, reaching the maximum within 15 hrs and exhibited the constant level during 25 hrs. Then the enzymatic activity was gradually decreased but it did not reach the control values within 70 hrs. After daily peroral administration of these toxic substances at the doses corresponding to 1/10 LD50 and 1/50 LD50, only the first dose inhibited the protein synthesis within 2 weeks. Within this period the enzymes studied were not found in blood serum. Distinct inhibition of the protein synthesis was observed within 4 weeks after administration of both these doses. In this case enzymatic activity was present in blood serum (up to 3 mumole/I L blood serum). Within 2 months after administration of these preparations the alterations studied were the most distinct.

[Effect of phenazepam and seduxen on the presence of histidase and urokinase in the blood]. / Vliianie fenazepama i seduksena na poiavlenie v krovi gistidazy i urokaninazy.

Liver tissue specific enzymes histidase and urokinase were found in blood of 160 rats after intraperitoneal administration of phenazepam at the doses of 1.0 and 2.5 mg/200 g of body weight as well as of diazepam at the dose of 2.0 mg/200 g. Administration of products of diazepam enzymatic degradation caused also the liberation of these enzymes from liver tissue into blood.

[Structural and enzymatic disorganization of biological membranes in rat liver cells in thermal burns]. / K voprosu o strukturnoi i fermentnoi dezorganizatsii biologicheskikh membran v kletkakh pecheni krys pri termicheskikh ozhogakh.

Permeability of hepatocyte cell membrane was studied from the release into blood of hepatospecific enzymes and from 5'-nucleotidase activity in plasma membranes. A study was also made of membrane permeability of mitochondria, lysosomes and microsomes in liver cells of burnt rats from the level of non-sedimented activity and activity of malate dehydrogenase, succinate dehydrogenase, cathepsin D and glucose-6-phosphatase in appropriate organelles. Permeability of cell and lysosomal membranes was demonstrated to be disordered within the first hours after burn. One day after burn generalized disturbance of membrane permeability in the cell was observed, followed by the release into cytosol of organelles template enzymes and a decrease in the activity of membrane-bound enzymes in these organelles. The alterations persisted during 7 days of observation.

[Thin layer chromatographic test for the indirect and direct detection of the enzyme defect in histidinemia]. / Indirekter und direkter dünnschichtchromatographischer Nachweis des Enzymdefektes bei der Histidinämie.

A thin layer chromatographic method for the direct and indirect detection of the enzyme defect in histidineemia is described. Histidin and urocanic acid are analyzed in 0,2-1 mg stratum corneum for specific screening. 5-10 mg skin biopsy material is needed for the direct measurement of the enzyme activity. This simple metabolic test is convenient even in normal hospital laboratories.