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Journal Article 2014; 35(Suppl 2): 155-157 PubMed PMID: 25638380 Citation  Keywords:  Adjuvants, Immunologic:pharmacology, Animals, Cytokines:metabolism, Female, Hemocyanin:pharmacology, Mice, Mice, Inbred BALB C, Models, Animal, Oximes:pharmacology, Pyridinium Compounds:pharmacology,.   

OBJECTIVES: HI-6 or asoxime in some sources is an antidotum for nerve agents. In recent experiments, implication of HI-6 in immunity response was proved; however, the issue was not studied in details. In this experiment, role of cytokines in HI-6 impact on immunity was searched. DESIG N: BALB/c mice were exposed to saline, HI-6 in a dose 1-100 mg/kg and/or 1 keyhole limpet hemocyanin (KLH) 1 mg/kg. Mice were sacrificed 21 days after experiment beginning and interleukins (IL) 1, 2, 4, 6 were determined by Enzyme Linked Immunosorbent Assay (ELISA).

RESULTS: The animals had no pathological manifestation. From the tested cytokines, no significant alteration was found for the IL-1, IL-4 and IL-6. IL-2 was significantly increased in a dose response manner.

CONCLUSIONS: The experimental data well correlates with the previous work where HI-6 caused increase of antibodies production. HI-6 is suitable to be used as an adjuvant whenever immunity should be pharmacologically altered.

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Journal Article 2013; 34(Suppl 2): 134-137 PubMed PMID: 24362106 Citation  Keywords:  Animals, Antibodies, Bacterial:blood, Antibody Formation:drug effects, Cholinesterase Inhibitors:pharmacology, Dose-Response Relationship, Drug, Female, Francisella tularensis:drug effects, Immunity, Innate:drug effects, Mice, Mice, Inbred BALB C, Tacrine.   

OBJECTIVES: Tacrine is an inhibitor of acetylcholinestrase (AChE) formerly used to treat cognitive impairment of Alzheimer disease. In previous works, we have shown that inhibitors of AChE can modulate innate immunity responses. In the present study we focused on modulation of adaptive immunity represented by production of antibodies. It is hypothesized that the cholinergic anti-inflammatory pathway is a common mechanism how inhibitors of AChE can influence immunity. Here, tularemia is used as a model disease for experimental purposes.

DESIGN: A total of 64 BALB/c mice were divided into eight groups. The animals received a dose of tacrine 0.1-0.5 mg/kg with combination of saline or inoculum of Francisella tularensis. The doses of tacrine were derived from clinical trials. The animals were sacrificed after three days and total antibodies in plasma and bacterial burden in the liver were measured.

RESULTS: Tacrine did not alter the antibodies level in non-infected animals. Antibodies levels of infected animals administered tacrine were reduced in a dose response manner. Tacrine also caused an increase in total bacteria numbers in the liver.

CONCLUSIONS: Tacrine significantly suppressed adaptive immunity represented by the ability of the organism to produce antibodies. We infer that tacrine can modulate the cholinergic anti-inflammatory pathway by a mechanism based on inhibition of blood AChE followed by higher availability of acetylcholine. The anti-inflammatory pathway is then stimulated and the body is not able to simply resolve antigen. Application of an AChE inhibitor during infectious diseases can have detrimental consequences for the immune system....

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Journal Article 2012; 33(Suppl 3): 183-189 PubMed PMID: 23353865 Citation  Keywords:  Animals, Antioxidants:metabolism, Basal Metabolism:drug effects, Biomarkers:metabolism, Caspases:metabolism, Female, Homeostasis:drug effects, Melatonin:metabolism, Mice, Mice, Inbred BALB C, Models, Animal, Oxidative Stress:drug effects, Thiobarbituric A.   

OBJECTIVES: Melatonin is a hormone with strong antioxidant activity. It is biosynthesized in the pineal gland and serves in the biological signaling and control of the circadian rhythm. Though there is evidence of beneficial effects of melatonin, the substance was not investigated in greater details associated with specific regulation of oxidative stress in organs and tissues.

DESIGN: The experiment is based on exposure of BALB/c mice to doses from 10 µg to 1mg of melatonin. Mice were euthanized after one and 24 hours, respectively. Biochemical markers in plasma, ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS) and activity of caspase-3 were examined in selected organs.

RESULTS: We confirmed significant alteration in high-density lipoprotein and total cholesterols and glucose. After one day, levels of glucose and high-density lipoprotein cholesterol were decreased, while total cholesterol increased in a dose dependent manner. FRAP values increased in spleen, liver, kidney, heart, and brain indicating a growing potential of low molecular weight antioxidants 24 hours after exposure. However, TBARS values indicating oxidative stress were elevated in heart, kidney, and liver.

CONCLUSIONS: Despite the antioxidant properties of melatonin, its effect on the organism is more complicated. It influences not only the oxidative homeostasis but also the basal metabolism, as represented by, e.g., cholesterol and glucose. This substance could thus be used for therapeutical purposes such as amelioration of pathologies associated with generation of reactive species or some metabolic dysfunctions....

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Comparative Study 2009; 30(Suppl 1): 186-191 PubMed PMID: 20027169 Citation  Keywords:  Animals, Antioxidants:metabolism, Arvicolinae, Disease Susceptibility, Mice, Mice, Inbred BALB C, Molecular Weight, Tularemia:metabolism,.   

OBJECTIVES: Bacterium Francisella tularensis is the causative agent of tularemia disease. It is a zoonosis accompanied with high mortality when untreated. Small rodents and hares, in particular, are natural reservoirs of tularemia. Despite physiological similarity of common hosts, tularemia exerts different mortality rates. The pathogenesis of tularemia is still not fully understood. The main pathway is associated with proliferation in macrophages after activation by reactive oxygen species in phagosomes.

DESIGN: A fully virulent strain of F. tularensis subsb. holarctica was used for infection of laboratory BALB/c mice (Mus musculus) and common voles (Microtus arvalis) representing murine and microtine species. The total level of low-molecular- weight antioxidants (LMWA) in plasma was assayed by cyclic voltammetry.

RESULTS: It was found that common voles are more resistant to tularemia progression when compared to mice. When LMWA assayed, surprising changes in LMWA levels were found. Both mice and common voles were infected with high dose resulting in overall mortality. While there was a quick depletion of LMWA in plasma in mice, common voles were even able to increase LMWA.

CONCLUSION: It seems that LMWA play an important role in the organism s protection during tularemia. The ability to compensate the LMWA losses and increase levels of antioxidants in common voles is probably responsible for its lower susceptibility to tularemia....

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Journal Article 2007; 28(5): 585-590 PubMed PMID: 17984949 Citation  Keywords:  Adaptation, Psychological:physiology, Aggression:physiology, Animals, Corticosterone:blood, Dominance-Subordination, Hypothalamo-Hypophyseal System:physiology, Male, Mice, Mice, Inbred BALB C, Social Environment, Stress, Psychological:blood, Territorialit.   

OBJECTIVE: Social stressors modulate the hypothalamic-pituitary-adrenal axis in rodents. However, reports on the association between corticosterone level and behavioural responses to the stressor are ambivalent. This may depend on the experimental paradigm, species- and strain-differences, duration of exposure to the stressor, but also on using either the social state (dominant or subordinate) or the coping style (proactive or passive) of an animal to correlate the corticosterone level with.

DESIGN AND SETTING: We used male Balb-C mice in a resident-intruder paradigm. Adolescent intruders (aged five to eight weeks) were transferred into the cage of an adult resident (aged about four month) for five minutes. The interactions were video-taped for behavioural analysis. Ten minutes after the encounters, intruders were sacrificed and blood samples were collected.

RESULTS: Dominant intruders showed offensive behaviours (attack, chase, tail tracking) and won most of the fights, whereas subordinate intrudes showed mainly submissive behaviours (flight, freezing) and were further classified into active and passive subordinates. Active subordinates displayed significantly more flight-behaviour than passive subordinates. Dominant intruders showed significantly higher post-stress levels of corticosterone than subordinates, which did not differ from control mice, which experienced five minutes of novel-cage exposure. Comparing all three behavioural phenotypes we found the lowest corticosterone levels in active subordinates.

CONCLUSION: Social state significantly affects the HPA-axis response to acute social stressors....

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Journal Article 2003; 24(6): 459-462 PubMed PMID: 15073576 Citation  Keywords:  Agenesis of Corpus Callosum, Animals, Brain Diseases:blood, Corpus Callosum:pathology, Incidence, Male, Mice, Mice, Inbred BALB C, Mice, Mutant Strains, Testosterone:blood, Thyroxine:blood,.   

OBJECTIVES: Approximately 20% of BALB/cCF mice are born with partial or total absence of the corpus callosum. Here, we analyzed testosterone and free thyroxin blood levels in adult male mice of this strain in order to see if these hormones are related to the incidence of callosal defects.

METHODS: Blood collected from the axillary blood vessels of 12 normal and 10 acallosal deeply anesthetized adult male mice was used in order to determine testosterone and free thyroxin levels through chemiluminescence (IMMULITE, Diagnostics Products Corporation, USA).

RESULTS: No significant difference (one-way ANOVA: F = 0.11, df = 1, p > 0.10) was found between normal ((-)X= 1.95, SD = 0.62) and acallosal ((-)X= 1.86, SD = 0.62) mice for free thyroxin level. On the other hand, in those mice that had detectable testosterone levels (above 0.2 ng/ml), a significant difference was found (t = 2.8, df = 6.06, p = 0.03): normal mice (n = 7, (-)X= 8.73, SD = 7.64) had a higher level than acallosal mice (n = 4, (-)X= 0.62, SD = 0.41).

CONCLUSIONS: The present results indicate that the incidence of callosal agenesis is not related to free thyroxin levels in the blood of adult BALB/cCF mice. On the other hand, in spite of the fact that low testosterone levels seems to be frequent in male mice of this strain, acallosal mice tend to have lower levels of this hormone than normal mice....

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Journal Article 2001; 22(5): 337-341 PubMed PMID: 11600875 Citation  Keywords:  Aging, Animals, Apoptosis, Cell Count, Cell Division, Duodenum, Epithelial Cells, Gastric Mucosa:cytology, Histocytochemistry, Immunohistochemistry, Intestinal Mucosa:cytology, Male, Melatonin:biosynthesis, Mice, Mice, Inbred BALB C, Mice, Nude, Neurosecr.   

OBJECTIVES: Diffuse neuroendocrine system (DNES) cells regulate homeostasis via neurocrine, endocrine and paracrine mechanisms. Extensive effects of peptide hormones and biogenic amines necessitate studying of DNES cell biology in aging. In this connection, the functional morphology of gut neuroendocrine cells (NEC), proliferative activity and apoptosis of mucous epithelial cells in aging have been studied.

MATERIAL AND METHODS: The study was performed on BALB/c-nu mice of 4, 21 and 34 months of age. NEC, proliferative activity and apoptosis of mucous epitheliocytes in stomach and duodenum have been studied by histochemical, immunohistochemical and morphometrical methods.

RESULTS: The total number of NEC shows an increasing trend with advancing age. However, the different types of NEC elicit differential patterns. The total number of epithelial cell nuclei does not show any statistically significant difference during aging. The proliferative activity of mucous epitheliocytes also shows no difference among the three animal groups studied. On the contrary, the apoptotic index increases with advancing age.

CONCLUSIONS: The results demonstrate that various gut NEC show differential behavior with age and their time-courses are dependent on the site of location (stomach or duodenum). The picture seems quite complex to allow a comprehensive interpretation, nonetheless it gives us some useful indications for further investigation. In fact, since the gut does not show evident gross age-related physiological changes, modifications with age in specific biological parameters can suggest the key mechanisms of compensative regulatory processes possibly acting during aging....

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