Structural Changes in the Liver Parenchyma and Granulomas of Mice with Chronic BCG Granulomatosis during Therapy with Composition of Isoniazid and Dialdehyde Dextran

Male BALB/c mice were intraperitoneally infected with BCG vaccine. The therapy with isoniazid or composition of isoniazid with dialdehyde dextran (intraperitoneally, twice a week for 5 months) was started 1 month after infection. The retention time of the isoniazid-dialdehyde dextran composition in hepatocytes was much longer compared to that of isoniazid. The mice receiving the composition of isoniazid and dialdehyde dextran were characterized by a more significant decrease in the number and size of BCG granulomas, lower severity of destructive changes in the liver parenchyma, and more pronounced reparative regeneration (compared to animals of the isoniazid group). Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 116–119, 2008     

Morphological Study of the Efficiency of Isoniazid and Dialdehyde Dextran Composition in the Treatment of Mice with BCG Granulomatosis

Male BALB/c mice were intraperitoneally injected with BCG vaccine. After 1 month therapy was started: isoniazid or composition of isoniazid with dialdehyde dextran (CID) obtained by chemical and radiochemical methods. The therapeutic efficiency evaluated by the number granulomas in the liver and lungs and granuloma size was higher in mice treated with CID obtained by the radiochemical method in comparison with mice treated with isoniazid and with CID obtained by the chemical method. Hepatotoxicity evaluated by volume density of degenerative hepatocytes and necrotic zones was higher in mice treated with CID obtained by the radiochemical method than in animals treated with isoniazid, because CID contained free isoniazid and isoniazid bound to dialdehyde dextran. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 105–108, 2008     

Effect of Dialdehyde Dextran on Structural Changes in the Liver and Lungs during Chronic BCG Granulomatosis

Male BALB/c mice were intraperitoneally infected with BCG vaccine. Cytomorphological changes in BCG granulomas of the liver and lungs were compared during spontaneous tuberculous inflammation and after intraperitoneal injection of dialdehyde dextran for 5 months. Administration of dialdehyde dextran to mice infected with mycobacteria of BCG vaccine was followed by a decrease in the number and size of BCG granulomas in organs, contributed to the increase in the count of fibroblasts in hepatic and pulmonary granulomas, decreased the severity of destructive changes in the liver parenchyma, promoted reparative processes in hepatocytes, and reduced the degree of fibrosis in the liver and lungs due to a decrease in fibroplastic activity of fibroblasts in BCG granulomas. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 113–115, 2008     

Granulomatous Inflammation in the Lungs of Mice with Systemic Candidiasis Receiving a Composition of Amphotericin B and Dialdehyde Dextran

A composition of amphotericin B and dialdehyde dextran was used for the therapy of male C57Bl/6 mice with systemic candidiasis. The composition was more effective than free amphotericin B. A decrease in the number and size of candidal granulomas in the lungs was more significant after therapy with the study composition (compared to free amphotericin B). Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 80–82, 2008     

Therapeutic Efficacy of a Composition of Amphotericin B and Dialdehyde Dextran in Kidney Damage in Mice of Various Strains with Systemic Candidiasis

The therapeutic efficacy of a composition of amphotericin B and dialdehyde dextran was much higher than that of amphotericin B in the therapy for systemic candidiasis. This conclusion was derived from the earlier and progressive decrease in the numberand size of candidal granulomas in the kidneys. The composition of amphotericin B and dialdehyde dextran was more potent than amphotericin B in decreasing the nephrotoxiceffect of C. albicans. The opposite strains of CBA and C57Bl/6 mice differed in morphologicalsigns of granulomatosis in the kidneys, but not in the nephrotoxic effect of C. albicans metabolites. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 149, No. 12, Suppl. 1, pp. 76–79, December, 2008     

Structural Changes in the Liver and Content of Steroid Hormones in the Blood and Adrenal Glands of Mice with Systemic Candidiasis Treated with A Composition of Amphotericin B and Dialdehyde Dextran

In CBA mice infected with C. albicans, phasic pattern of granulomatosis development was observed. In all groups, the number of granulomas in the liver was minimum on day 56 after infection. Treatment with free amphotericin B and its composition with dialdehyde dextran (CA) reduced the number of infiltrations and granulomas in the liver, the changes were more pronounced in animals receiving CA. A different pattern of cyclic fluctuations of cortisol content in the blood and adrenal glands and progesterone content in the adrenal gland was observed. By the end of observation (day 84), cortisol content in the blood and adrenals of mice treated with CA was considerably lower than in untreated mice and animals receiving amphotericin B. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 16–19, 2008     

Ultrastructural characteristics of type A epithelioid cells during BCG-granulomatosis and treatment with lysosomotropic isoniazid

We studied BCG-granulomas, their cellular composition, and ultrastructure of type A epithelioid cells in the liver of male BALB/c mice with spontaneous granulomatous inflammation. The animals received free isoniazid or isoniazid conjugated with lysosomotropic intracellularly prolonged matrix (dialdehyde dextran, molecular weight 65–75 kDa). Lysosomotropic isoniazid was accumulated in the vacuolar apparatus of epithelioid cells and produced a stimulatory effect on plastic processes in these cells. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 474–477, April, 2006     

Effects of modified amphotericin in experimental systemic candidiasis

Lysosomotropic composition of dialdehyde dextran and amphotericin B had a greater therapeutic effect in mice with systemic candidiasis compared to free amphotericin B. This composition normalized glucocorticoid function of the adrenal glands and decreased the severity of liver destruction at late terms of granulomatous inflammation. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 4, pp. 367–369, April, 2007     

Effect of complex isoniazid on mononuclear cells in a tuberculous granuloma

Light and electron microscopy shows that the use of dextran matrix in a complex with isoniazid ensures its lysosomotropism, prolonged action, and the capacity to stimulate plastic processes and accelerate the differentiation of cells — monocyte derivatives — in epithelioid cells in tuberculous granulomas. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 559–561, May, 1996     

Morphological Changes in the Liver of Pregnant C57Bl/6 Mice with BCG Granulomatosis

Morphological changes in the liver of pregnant C57Bl/6 mice infected with BCG vaccine before pregnancy and on day 13 of gestation were studied by means of light microscopy and morphometry. The formation of BCG granulomas in mice of both groups was followed by a decrease in the numerical density and diameter of granulomas, increase in the volume density of hepatocyte degeneration and necrosis, and rise in the numerical density of binucleate hepatocytes (compared to nonpregnant mice infected with BCG vaccine). Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 83–85, 2008     

BCG Granulomatosis in Adult Mice of Different Strains with a History of Intrauterine Hypoxia

Specific features of the formation and spontaneous regression of BCG granulomas, depending on mouse genotype and history of intrauterine hypoxia, were detected in 2-month-old male CBA and C57Bl/6 mice. The numerical density of granulomas, their size and (partially) cell composition varied. There are good grounds to assume that the number of BCG granulomas in the liver, irrespective of the experimental conditions and animal strains, decreases after elimination of M. tuberculosis persisting in granuloma phagocytes and subsequent migration of cells constituting the granuloma. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 93–96, 2008     

Prevalence of <Emphasis Type="Italic">Toxocara</Emphasis>-induced liver granulomas,detected by immunohistochemistry,in a series of autopsies at a Children’s Reference Hospital in Vitoria,ES, Brazil

The aim of this investigation was to study the frequency of visceral larva migrans (VLM) granulomas in autopsies at a Children’s Reference Hospital in Vitoria, ES Brazil, where anti-Toxocara antibodies are frequently detected in the serum of children admitted at the hospital. Two liver fragments from 310 autopsies of children aged between 1 and 15 years were paraffin embedded, and sections were stained with hematoxylin and eosin and submitted to detection of Toxocara antigens using a rabbit anti-Toxocara serum. Among the 24 cases with granulomatous lesions, ten had eosinophil-rich granulomas positively stained with the anti-Toxocara serum. Some were typical epithelioid granulomas, with a positive reaction in multinucleated giant cells, epithelioid cells, or necrotic debris. The results showed that VLM granulomas are the most frequent granulomatous hepatitis in children in our county. This agrees with the high prevalence of anti-Toxocara antibodies in the serum of children admitted to the Children’s Reference Hospital. The 3.2% frequency of liver VLM granulomas in autopsies is less than the 30–39% frequency of positive serology in these children, probably reflecting the low larval burden in infected children.     

Mononuclear phagocyte system in mice with intrauterine Candida albicans infection and postnatal experimental tuberculosis

Intrauterine Candida albicans infection in mouse fetuses affected the type of granulomatous inflammation induced by BCG vaccine during the postnatal period. It manifested in increased formation of granulomas and variations in their cellular composition. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 1, pp. 103–106, January, 2006     

Lipid peroxidation in the brain and liver of rats during acute stress and melatonin treatment

We studied the effects of acute stress and exogenous melatonin in various doses on the intensity of lipid peroxidation in emotiogenic structures of the brain and liver of rats with different activity in the open field. Stress had no effect on the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and liver of active and passive rats receiving physiological saline. The influence of melatonin on malonic dialdehyde content depended on the dose of this substance. The amount of malonic dialdehyde in brain structures (active and passive rats) and liver (active rats) increased after administration of exogenous melatonin in doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content in the liver of passive rats. The effects of melatonin are partly related to modulation of lipid peroxidation in central and peripheral tissues of the organism. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 19–23, July, 2004     

In Vitro Effect of Oxidized Dextrans on Peritoneal Cells

We studied the dependence of in vitro dextran biocompatibility on the method of oxidation of 35-kDa dextran. The biocompatibility of dextran oxidized with potassium permanganate was higher compared to that obtained by radiochemical oxidation. It was related to the formation of peroxide compounds during radiochemical oxidation. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 120–122, 2008     

Pro-oxidant effects of Mebendazole in albino rats experimentally infected with <Emphasis Type="Italic">Trichinella spiralis</Emphasis>

Trichinellosis treated with Mebendazole often leads to complications in the course of the disease in humans and animals as a result of intoxication and hyper-sensitization of an organism due to the massive destruction of parasites. This study was conducted to research Mebendazole incidence on lipid peroxidation processes (LPP) in rats’ blood in Trichinella spiralis-infected and parasite-free albino rats. The research was conducted to evaluate erythrocyte superoxide dismutase (SOD) activity and malonic dialdehyde (MDA) concentration in blood serum. The parameters of the SOD–MDA system in infected albino rats, which were treated or untreated with Mebendazole were analyzed. It was concluded that Mebendazole amplifies the LPP in the blood of both infected and parasite-free animals: in a dose of 150 mg/kg anthelmintic causes disturbances of biochemical homeostasis in the SOD–MDA system, thus working as a pro-oxidant.     

Comparative Study of the In Vitro Effect of Nanoliposomes with Oxidized Dextrans on Peritoneal Cells

We studied the in vitro effect of hybrid molecular-nanosomal biocompatible compositions on cultured peritoneal cells. The compositions consisted of oxidized dextrans with a mean molecular weight of 35 and 60 kDa, which were obtained by chemical and radiochemical oxidation of dextran. Hybrid nanoliposomal compositions of chemically oxidized dextran (permanganate method) had greater biocompatibility and tropic activity to macrophages compared to nanoliposomes of radiochemically oxidized dextran. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Suppl. 1, pp. 123–126, 2008     

Effect of endotoxemia on skin antioxidant enzymes under experimental conditions

Intraperitoneal injection of bacterial lipopolysaccharide in a dose of 1 mg/kg was followed by prestimulation of whole blood leukocytes in rats. Activities of peroxide-and lipoperoxide-utilizing antioxidant enzymes glutathione peroxidase, glutathione S-transferase, and catalase increased 1 day after lipopolysaccharide administration, while the content of malonic dialdehyde in the skin remained unchanged. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 10, pp. 393–395, October, 2006     

Extracellular DNA in Culture of Primary and Transformed Cells,Infected and Not Infected with Mycoplasma

The composition and kinetics of accumulation of extracellular DNA in cultures of primary human endotheliocytes, cervical adenocarcinoma, and mycoplasma-infected cervical adenocarcinoma cells were studied. The content of DNA bound to cell surface did not change during culturing. The concentration of extracellular DNA in culture medium increased during the lag phase and at the beginning of the exponential growth phase, which probably attests to active secretion of DNA by cells. Spontaneous extracellular DNA synthesis was observed only in cell culture infected with mycoplasma. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 67-70, January, 2009     

The effects of T cell deficiency on the development of worms and granuloma formation in mice infected with <Emphasis Type="Italic">Schistosoma japonicum</Emphasis>

It is widely accepted that the immune response of the host attacks the parasite and the parasite appears to develop strategies to evade the assault. However, there is increasing evidence that the development of a parasite may be also positively influenced by the immune response of host. In this paper, we explore the effects of T cell deficiency on the development of the worms and granuloma formation in mice infected with cercariae of Schistosoma japonicum. T cell-deficient (nude) mice supported normal parasite survival and fecundity, but compared to normal mice delayed the worms’ development (length and female fecundity) until 28 days after infection. However, these differences equaled out at 35 and 42 days. The nude mice apparently suppressed the size of granuloma in the livers around the eggs of S. japonicum. The granulomas were composed predominantly of neutrophils but with significantly fewer eosinophils in nude compared to normal mice. In addition, hepatocyte necrosis occurred in the vicinity of granulomas in nude but not normal mice. This is consistent with egg-granuloma formation in the host being dependent on T-lymphocyte functions and shows that the effect of T cell deficiency on the development of the worms is transitory in S. japonicum.