Strains Of Female Mice Research Articles

Pengendalian Folikulogenesis Ovarium dengan Pemberian Ekstrak Biji Kapas

Gosipol is a substances contained in extracted cotton seed which is thought to have the antifertility ability therefore it is often used as a herbal contraceptive. The aim of this study were to assess the folliculogenesis in mice after administrated with cottonseed extract. 60 female mice strain DDY which was 14-15 weeks old and 30-35 g body weight were divided into five groups and given cottonseed extract each 0; 1,5; 2,1 and 2,7 g/kg BW for 5, 10, 15, 24, and 24 + 10 days (without cottonseed treatment). At the end of the treatment period, mice was euthanasia to observe follicular development histomorphology (each three mice of each treatment). Mice estrous status were evaluated based on the description of the vaginal smear cells with Giemsa staining. The results showedthat the number of developing follicles was low (P < 0.05) compared with control after 5 days cottonseed extract administration at dose 2,7 g/kg BW that were 23 ± 3,6. At dose 1,5 and 2,1 g/kg BW the number of follicles was low after 24 days that were 25 ± 10,4 and 27 ± 3,5. Recovery effects of follicle number after cottonseed extract administration for 24 days was the best at a dose of 1,5 g/kg BW. Prolonge of estrous cycle occured in mice which were administrated the cottonseed extract of at all dose treatment. In conclusion, although the decrease in the number of developing follicles and prolonge of estrous cycles occurred after cottonseed extract administration, but these effects are reversible after the administration ended.

High-Yield Superovulation in Adult Mice by Anti-Inhibin Serum Treatment Combined with Estrous Cycle Synchronization.

Producing many mature oocytes is of great importance for assisted reproductive technologies. In mice, superovulation by consecutive injections of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) has been the gold standard for oocyte collection. However, the yield of mature oocytes by this regimen can fluctuate according to the stage of the estrous cycle, strain, and age. Therefore, our objective was to develop a high-yield superovulation protocol to collect higher numbers of oocytes from adult female mice of different strains and ages. First, we aimed to synchronize the estrous cycle using C57BL/6 (B6) female mice. Most (93%) were synchronized to metestrus after two daily injections of progesterone. Second, we found that with the injection of anti-inhibin serum (AIS) instead of eCG, the mean number of ovulated oocytes almost doubled (21 vs. 41 per mouse). Third, by combining estrous cycle synchronization with two AIS injections, we obtained 62 oocytes per mouse, about three times that with the eCG-hCG protocol. Importantly, this approach increased the proportion of mice that ovulated >25 oocytes from about 40% (eCG-hCG) to 90%. The same protocol was also effective in other inbred (BALB/cA), outbred (ICR), and hybrid (B6D2F1) strains. In addition, B6 female mice aged over 1 yr ovulated 1.8-fold more oocytes by this protocol. Thus, estrous cycle synchronization followed by AIS-hCG yielded a broadly applicable, highly efficient superovulation. This protocol should promote the effective use of invaluable female mouse strains and decrease the numbers of animals euthanized.

Effects of curcumin on the social behavior, blood composition, reproductive hormones in plasma and brain acetylcholinesterase in cadmium intoxicated mice

Cadmium (Cd) exposure can induce acute lethal health-related threats in humans since it has an exceptional ability to accumulate in living organism tissues and cause toxicological effects. Curcumin (Cur) on the other hand has a wide variety of biological activities and several studies have suggested its potential therapeutic or protective effects against several ailments and infections.To study the effect of Cur on the toxicity of Cd, Swiss–Webster strain male and female mice (sixty each) were divided into 6 groups of ten each at random. Group-1 served as the naïve control and received no treatment. Group-2, 3 and 4 were the experimental controls and were administered once a day with a single oral dose of 50% dimethyl sulfoxide (DMSO), Cur (300mg/kg) or Cd (100mg/kg) respectively, for 2weeks. Group-5 and 6 received Cur and Cd in combination once a day orally for 2weeks except that Cur in a dose of 150 and 300mg/kg to group 5 and 6 respectively, was administered one hour before Cd administration to both groups.After treatment period, the male animals were subjected to social standard opponent test and females were subjected to the tube restraint tests and thereafter, their blood was collected to measure the blood composition indices and level of reproductive hormones. The animals were sacrificed to collect their brain for the estimation of acetylcholinesterase (AChE).Results indicated that Cd significantly increased nonsocial activities in males and latency to first bite in females, whereas the social activities in males and the number of bites in females were significantly decreased. All measured indices of blood composition and levels of progesterone (female) and testosterone (male) in blood and AChE in their brain tissues were significantly decreased due to Cd treatment.However, administration of Cur along with Cd had an ameliorating effect on all the behavioral and biochemical parameters studied herein and reduced the toxicity of Cd significantly and dose-dependently. Thus, Cur may be beneficial for general health and for protection from Cd intoxication.

The Effects of Post-Mating Administration of Anti-IL-10 and Anti-TGFß on Conception Rates in Mice.

In fertility studies, it has been shown that transforming growth factor β (TGFβ) and interlukin 10 (IL-10) play very important roles in implantation, maternal immune tolerance, placentation and fetal development, and the release beginning of release for fetal and postnatal death. The present study aims to determine the effects of the postmating administration of neutralizing antibodies against IL-10 and TGFβ, which significantly impact pregnancy in females and the conception rates in mice via assessments of blood serum and uterine fluid concentrations of IL-2, IL-4, IL-6, IL-10, IL-17, interferon γ (IFNγ), Tumor necrosis factor α (TNFα), and TGFβ. In this experimental study, 21 BALB/c strain female mice were mated and randomly divided into three groups. The mice in the first group were selected as the control group. The second group of animals was injected with 0.5 mg of anti-IL-10 after mating, while those in the third group were intraperitoneally injected with 0.5 mg of anti-TGFβ. The animals in all groups were decapitated on the 13thday after mating and their blood samples were taken. The uteri were removed to determine pregnancy. The mice's uterine irrigation fluids were also obtained. We used the multiplex immunoassay technique to determine the cytokine concentrations in uterine fluid and blood serum of the mice. We observed no intergroup difference with respect to conception rates. A comparison of the cytokine concentrations in the uterine fluids of pregnant mice revealed higher TGFβ concentrations (p<0.01) in the second group injected with the anti-IL-10 antibody compared with the other groups. There was no difference detected in pregnant animals with regards to both uterine fluid and blood serum concentrations of the other cytokines. Post-mating administration of anti-IL-10 and anti-TGFβ antibodies in mice may not have any effect on conception rates.

Raloxifene preserves phenytoin and sodium valproate induced bone loss by modulating serum estradiol and TGF-β3 content in bone of female mice

Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. We hypothesize that estrogen deprivation following phenytoin (PHT) and sodium valproate (SVP) therapy could lead to adverse bony effects. Both PHT and SVP inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-β (TGF-β3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with calcium and vitamin D3 (CVD) supplementation, on PHT and SVP-induced alterations in bone in mice and to unravel the role of estradiol and TGF-β3 in mediation of bony effects by either AEDs or raloxifene. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of PHT and SVP was investigated. Swiss strains of female mice were treated with PHT (35mg/kg, p.o.) and SVP (300mg/kg, p.o.) for 120days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers (BTMs) in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-β3 content. Preventive and therapeutic treatment with raloxifene ameliorated bony alterations and was more effective than CVD. It also significantly restored estradiol and TGF-β3 levels. Deprived estrogen levels (that in turn reduced lumbar TGF-β3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with antiepileptic efficacy of these drugs, and hence raloxifene could be a potential therapeutic option in the management of PHT and SVP-induced bone disease if clinically approved.

Eclipta alba ameliorates carbon tetrachloride-induced structural and functional changes in liver of mice

The aim of the present investigation was to evaluate the ameliorative effect of Eclipta alba extract against carbon tetrachloride (CCl4)–induced structural and functional changes in livers of mice. Healthy adult Swiss strain female albino mice were orally administered with CCl4 (826 mg/kg body weight/day, p.o.) alone and along with Eclipta alba extract (100, 200 and 300 mg/kg body weight/day, p.o.) for 30 days. The degree of protection was determined by measuring histopathological changes and lipid peroxidation in liver as well as activities of ALT, AST, ACP, ALP, LDH, γ-GT enzymes and bilirubin contents in serum of mice. The histopathological studies revealed severe necrosis, fatty infiltration, lymphocytic infiltration and fibrosis in liver of CCl4 treated mice. In addition, biochemical studies revealed a significant increase in lipid peroxidation. The enzymes activities as well as bilirubin contents in serum were significantly (p&lt;0.05) increased in CCl4 only treated mice when compared with the control group. However, co-treatment of CCl4 along with Eclipta alba extract showed significant reductions in activities of enzymes and bilirubin content as compared with CCl4 alone treated mice. The effects were dose-dependent (r = 0.9826 to 1). Carbon tetrachloride induced lipid peroxidation was significantly (p&lt;0.05) ameliorated in a dose-dependent manner. Histopathological changes were also ameliorated on treatment with Eclipta alba extract. The ameliorative effects of Eclipta alba on CCl4–induced hepatotoxicity could be due to its antioxidative property. The extract was found to be safe as evidenced by their high LD50.

An enriched environment improves cognitive performance in mice from the senescence-accelerated prone mouse 8 strain: Role of upregulated neurotrophic factor expression in the hippocampus.

In this study, we examined 3-month-old female mice from the senescence-accelerated prone mouse 8 strain and age-matched homologous normal aging female mice from the senescence accelerated- resistant mouse 1 strain. Mice from each strain were housed in an enriched environment (including a platform, running wheels, tunnel, and some toys) or a standard environment for 3 months. The mice housed in the enriched environment exhibited shorter escape latencies and a greater percentage of time in the target quadrant in the Morris water maze test, and they exhibited reduced errors and longer latencies in step-down avoidance experiments compared with mice housed in the standard environment. Correspondently, brain-derived neurotrophic factor mRNA and protein expression in the hippocampus was significantly higher in mice housed in the enriched environment compared with those housed in the standard environment, and the level of hippocampal brain-derived neurotrophic factor protein was positively correlated with the learning and memory abilities of mice from the senescence-accelerated prone mouse 8 strain. These results suggest that an enriched environment improved cognitive performance in mice form the senescence-accelerated prone mouse 8 strain by increasing brain-derived neurotrophic factor expression in the hippocampus.

Strain-dependent Damage in Mouse Lung After Carbon Ion Irradiation

To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung. Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with ¹³⁷Cs γ-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining. In addition, we performed immunohistochemical staining for hyaluronic acid (HA), CD44, and Mac3 and assayed for gene expression. The survival data in mice showed a between-strain variance after C-ion irradiation with 10 Gy. The median survival time of C3H/He was significantly shortened after C-ion irradiation at the higher dose of 12.5 Gy. Histologic examination revealed early-phase hemorrhagic pneumonitis in C3H/He and late-phase focal fibrotic lesions in C57BL/6J after C-ion irradiation with 10 Gy. Pleural effusion was apparent in C57BL/6J and A/J mice, 168 days after C-ion irradiation with 10 Gy. Microarray analysis of irradiated lung tissue in the three mouse strains identified differential expression changes in growth differentiation factor 15 (Gdf15), which regulates macrophage function, and hyaluronan synthase 1 (Has1), which plays a role in HA metabolism. Immunohistochemistry showed that the number of CD44-positive cells, a surrogate marker for HA accumulation, and Mac3-positive cells, a marker for macrophage infiltration in irradiated lung, varied significantly among the three mouse strains during the early phase. This study demonstrated a strain-dependent differential response in mice to C-ion thoracic irradiation. Our findings identified candidate molecules that could be implicated in the between-strain variance to early hemorrhagic pneumonitis after C-ion irradiation.

Distribution of mercury in metallothionein-null mice after exposure to mercury vapor: amount of metallothionein isoform does not affect accumulation of mercury in the brain

To examine the contribution of metallothionein (MT) to mercury accumulation in mouse tissues, 129 strain female mice and MT null mice were exposed to metallic mercury vapor at a sub-toxic level, and Hg levels in the brain, kidney and liver were determined on 1, 3 and 7 days after the exposure. After exposure to mercury vapor, significant Hg accumulation was observed in the brains of wild-type and MT-I/II null and MT-III null mice, as well as in the liver and kidneys. No strain difference was observed in the tissue Hg accumulations 24 hr after the exposure except for the kidneys, where the highest accumulation was found in MT-III null mice. Although the brains of MT-III null mice showed slightly higher Hg accumulation than the other two strains, no significant difference was observed except in the cerebrum on Day 7. Gel chromatograms of cerebrum soluble fractions revealed that a significant amount of Hg existed as an MT-bound form in all the mouse strains. On the other hand, MT-bound Hg was found as a minor fraction in soluble fractions of the kidneys and livers in wild-type and MT-III null mice. Despite a significant strain difference in total MT levels in the cerebrum, there was no difference among the three strains in the amount of Hg accumulated in the cerebrum and its distribution rates in MT fractions. The present study demonstrated that brain uptake of Hg(0) and its accumulation as Hg(2+) did not depend on the amount of MT isoform in the tissue, at least in the early phase.

Carvedilol Induces Endogenous Hydrogen Sulfide Tissue Concentration Changes in Various Mouse Organs

Carvedilol, a third generation non-selective adrenoreceptor blocker, is widely used in cardiology. Its action has been proven to reach beyond adrenergic antagonism and involves multiple biological mechanisms. The interaction between carvedilol and endogenous 'gasotransmitter' hydrogen sulfide (H2S) is unknown. The aim of the study is to assess the influence of carvedilol on the H2S tissue level in mouse brain, liver, heart and kidney. Twenty eight SJL strain female mice were administered intraperitoneal injections of 2.5 mg/kg b.w./d (group D1, n=7), 5 mg/kg b.w./d (group D2, n=7) or 10 mg/kg b.w./d of carvedilol (group D3, n=7). The control group (n=7) received physiological saline in portions of the same volume (0.2 ml). Measurements of the free tissue H2S concentrations were performed according to the modified method of Siegel. A progressive decline in H2S tissue concentration along with an increase in carvedilol dose was observed in the brain (12.5%, 13.7% and 19.6%, respectively). Only the highest carvedilol dose induced a change in H2S tissue level in the heart - an increase by 75.5%. In the liver medium and high doses of carvedilol increased the H2S level by 48.1% and 11.8%, respectively. In the kidney, group D2 showed a significant decrease of H2S tissue level (22.5%), while in the D3 group the H2S concentration increased by 12.9%. Our study has proven that carvedilol affects H2S tissue concentration in different mouse organs.

Interferon-Inducible p200-Family Proteins as Novel Sensors of Cytoplasmic DNA: Role in Inflammation and Autoimmunity

Deregulated innate immune responses that result in increased levels of type I interferons (IFNs) and stimulation of IFN-inducible genes are thought to contribute to chronic inflammation and autoimmunity. One family of IFN-inducible genes is the Ifi200 family, which includes the murine (eg, Ifi202a, Ifi202b, Ifi203, Ifi204, Mndal, and Aim2) and human (eg, IFI16, MNDA, IFIX, and AIM2) genes. Genes in the family encode structurally related proteins (the p200-family proteins), which share at least one partially conserved repeat of 200-amino acid (200-AA) residues. Consistent with the presence of 2 consecutive oligonucleotide/oligosaccharide-binding folds in the repeat, the p200-family proteins can bind to DNA. Additionally, these proteins (except the p202 proteins) also contain a pyrin (PYD) domain in the N-terminus. Increased expression of p202 proteins in certain strains of female mice is associated with lupus-like disease. Interestingly, only the Aim2 protein is conserved between the mouse and humans. Several recent studies have provided evidence that the Aim2 and p202 proteins can recognize DNA in cytoplasm and the Aim2 protein upon sensing DNA can form a caspase-1-activating inflammasome. In this review, we discuss how the ability of p200-family proteins to sense cytoplasmic DNA may contribute to the development of chronic inflammation and associated diseases.

Female and Male Sex Hormones Differentially Regulate Expression ofIfi202, an Interferon-Inducible Lupus Susceptibility Gene within theNba2Interval

Increased expression of IFN-inducible Ifi202 gene in certain strains of female mice is associated with susceptibility to systemic lupus erythematosus (SLE). Although, the development of SLE is known to have a strong sex bias, the molecular mechanisms remain unknown. Here we report that in vivo treatment of orchiectomized (NZB x NZW)F(1) male mice with the female sex hormone 17beta-estradiol significantly increased steady-state levels of Ifi202 mRNA in splenic cells, whereas treatment with the male hormone dihydrotestosterone decreased the levels. Moreover, increased expression of Ifi202 in B6.Nba2 B cells and reduced expression in T cells were associated with increased levels of estrogen receptor-alpha (ERalpha) and androgen receptor, respectively. Furthermore, the steady-state levels of Ifi202 mRNA were higher in splenic cells from C57BL/6, B6.Nba2, NZB, and (NZB x NZW)F(1) female mice as compared with males. 17beta-estradiol treatment of B cells and WT276 cells increased Ifi202 mRNA levels, whereas treatment with dihydrotestosterone decreased the levels. Interestingly, overexpression of ERalpha in WT276 cells increased the expression of Ifi202 and stimulated the activity of the 202-luc-reporter through the c-Jun/AP-1 DNA-binding site. Accordingly, ERalpha preferentially associated with the regulatory region of the Ifi202 gene in female B6.Nba2 B cells than in males. Furthermore, Ifi202 mRNA levels were detectable in splenic cells of wild-type (Esr1(+/+)), but not null (Esr1(-/-)), (NZB x NZW)F(1) female mice. Collectively, our observations demonstrate that the female and male sex hormones differentially regulate the expression of Ifi202, thus providing support for the role of Ifi202 in sex bias in SLE.

Bacterial endotoxin (LPS)–induced DNA damage in preimplanting embryonic and uterine cells inhibits implantation

To investigate lipopolysaccharide (LPS)-induced DNA damage in preimplanting embryonic and uterine cells during preimplantation period of pregnancy that may ultimately inhibit the process of implantation in mouse. Animal study. Academic research environment. Sixty four Park strain female mice. The "minimum dose" (MD) of LPS was injected intraperitoneally in the pregnant females on day 0.5 of pregnancy, and individual embryos and uterine cells were assessed by comet assay on days 1.5, 2.5, 3.5, and 4.375 of the preimplantation period of pregnancy. Percentage of embryos and uterine cells with tail, mean comet tail length, percentage of fragmented DNA in tail. Significantly higher numbers of embryos with higher mean comet tail length and percentage of fragmented DNA in tail were observed in the LPS-treated compared with control animals as the period of pregnancy approaches the stage of implantation. At the same time, DNA damage was also significantly higher in the uterine cells of LPS-treated compared with control animals. The MD of LPS can induce DNA damage in the preimplantation-stage embryos and uterine cells, which causes poor embryonic development and improper preparation of uterine horns during the preimplantation period of pregnancy, which may ultimately inhibit the process of implantation in mouse.

Strain differences regarding susceptibility to ursolic acid-induced interleukin-1β release in murine macrophages

Interleukin (IL)-1β is a proinflammatory cytokine responsible for the onset of a broad range of diseases, such as inflammatory bowel disease and rheumatoid arthritis. We have recently found that aggregated ursolic acid (UA), a triterpene carboxylic acid, is recognized by CD36 for generating reactive oxygen species (ROS) via NADPH oxidase (NOX) activation, thereby releasing IL-1β protein from murine peritoneal macrophages (pMϕ) in female ICR mice. In the present study, we investigated the ability of UA for inducing IL-1β production in pMϕ from 4 different strains of female mice (C57BL/6J, C3H/He, DDY, and ICR), as well as an established macrophage line (RAW264.7 cells). The levels of IL-1β released from UA-treated pMϕ of C57BL/6J and DDY mice were significantly lower than from those of ICR mice, whereas IL-1β was not released from the pMϕ of C3H/He mice or RAW264.7 cells. Of paramount importance, CD36 as well as the NOX components gp91 phox and p47 phox (C3H/He mice) and gp91 phox (RAW264.7 cells) were scarcely detected. In addition, the different susceptibilities to UA-induced IL-1β release were suggested to be correlated with the amount of superoxide anion (O 2 −) generated from the 5 different types of Mϕ. Notably, intracellular, but not extracellular, O 2 − generation was indicated to play a major role in UA-induced IL-1β release. Together, our results indicate that the UA-induced IL-1β release was strain-dependent, and the expression status of CD36 and gp91 phox is strongly associated with inducibility.

Differences in gene expression and benzo[a]pyrene‐induced DNA adduct formation in the liver of three strains of female mice with identical AhRb2 genotype treated with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin and/or benzo[a]pyrene

To search for genes whose products modify aryl hydrocarbon receptor (AhR)-dependent toxicity caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), gene expression profiles in the liver were surveyed using microarrays 24 h after the administration of TCDD to three strains of female mice, BALB/cAnN (BALB), C3H/HeN (C3H) and CBA/JN (CBA) all of identical AhR genotype. The BALB/cAnN strain had a more marked induction of a number of glutathione S-transferase (GST) sub-families, particularly the GSTmicro gene family, compared with the other two strains. To assess the effects of GSTs induction to metabolize carcinogens, TCDD (40 microg kg(-1)) was administered to BALB and CBA strains, followed 24 h later by an i.p. injection of low or high dose of benzo[a]pyrene (B[a]P, 50 or 200 mg kg(-1)). The 32P-postlabelling analysis showed that administration of TCDD alone failed to induce DNA adduct formation in both BALB and CBA strain mouse livers. The low dose of B[a]P alone produced DNA adduct in the liver of both strains to a similar extent. Treatment with TCDD 24 h before the low dose of B[a]P suppressed the formation of B[a]P-induced DNA-adduct more markedly in the BALB strain compared with the CBA strain. Taken together, these findings show that TCDD treatment causes strain-specific alterations in gene expression and B[a]P-induced DNA adduct formation in the liver of female mice of the same AhRb2 genotype. Furthermore, it suggests that TCDD-treated female mice of the BALB strain may have genes whose products modify the toxicity of B[a]P as evidenced by TCDD-induced alterations in B[a]P-DNA adduct formation.

The development of IgY(ΔFc) antibody based neuro toxin antivenoms and the study on their neutralization efficacies

Introduction. Immunotherapy for treatment of snake bites has been based on mammalian IgG. Recently, polyvalent ovine Fab has become available. However, papain, used in the Fab fragmentation process, is a human allergen. Avian eggs are a source of antibodies and a truncated version of IgY, IgY(ΔFc), is found in ducks. In this study, we induced duck antibodies by using detoxified cobra and krait venoms and then purified IgY(ΔFc) antibodies from the hyperimmune duck egg yolk. Methods. Ducks were used for immunization and their eggs were collected for antibody production. ICR strain female mice were used in the in vivo neutralization test. Monovalent antivenoms to Formosan cobra venom and Formosan multi-banded krait venom were raised and purified from hyper-immune duck egg yolk individually. The LD50 of venoms were determined by subcutaneous injection of different venom doses into the mice. The survival/death ratios were recorded after 24 hours. Results. The antibody purified from egg yolk showed high titer response to its immunogen (cobra or krait venom) by an ELISA. Overall, the antibodies from duck eggs efficiently protected mice from envenomations. Discussion. The antivenoms purified from the egg yolk of ducks immunized with cobra venom and krait venom neutralized the lethal effects of these venoms with good efficacy in a mouse model. The antivenoms were effective in neutralizing lethality in mice injected at 4×LD50 of venoms. Conclusions. These results indicate that antibodies derived from ducks can serve as a new source for the generation of antivenoms.

Effect of the estrus cycle stage on sensitivity to pheromone 2,5-dimethylpyrazine in the house mouse Mus musculus

Frequency of cytogenetic disturbances was estimated in mitotically dividing bone marrow cells of CBA strain female mice after the 24-h long action of pheromone 2,5-dimethylpyrazine (2,5-DMP). The stage of the estrous cycle of each animal was taken into account at the moment of the end of the pheromone action. The analysis was performed using the anatelophase method that allows evaluating frequencies of various types of disturbances--bridges, fragments, delayed chromosomes. The spontaneous level of the mitotic disturbances revealed by the anatelophase method in animals of the control group amounts to 5.4 %. Action of pheromone 2,5-dimethylpyrasine induced the mitosis disturbances detected in the dividing bone marrow cells at the anaphase-telophase stage in the females at the di- + postestrus stage. The corresponding frequency of disturbances after the pheromone action was equal to 9.2%. In the female in estrus, the mitotic disturbance level amounted 6.7%, which did not differ statistically significantly from control. It is suggested that differences in the female mouse hormonal state at different estrous cycle stages affect sensitivity to olfactory signals. Mechanisms of the revealed effect and significance of the differences in sensitivity to pheromone for reproductive processes are discussed.

Helicobacter and Gastric Malignancies

Over the past year Helicobacter pylori has been confirmed as the most important risk factor for non-cardia gastric adenocarcinomas and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Eradication therapy has been proven to be beneficial when given prior to the development of intestinal metaplasia, but is less efficacious when administered later. However, the best data from clinical trials indicate that H. pylori eradication alone will have only a moderate effect on gastric cancer incidence worldwide. The mechanisms responsible for H. pylori-associated gastric carcinogenesis continue to be dissected. Accumulating evidence suggests that some H. pylori may be able to invade through the gastric epithelial barrier, though pro-carcinogenic effects may also be related to the complex and evolving pathways of altering signal transduction pathways within gastric epithelial cells that are stimulated by adherence and translocation of H. pylori products through its type IV secretory system. Determinants of the host response to H. pylori infection continue to focus on polymorphisms in genes related to the innate and acquired immune responses, including NOD2, COX-2, and TLR-4. H. pylori eradication is indicated for low-grade gastric B-cell MALT lymphoma and may even provide "cure" in some apparently H. pylori-negative cases. How and why does H. pylori promote lymphomagenesis? Some evidence from human and murine models points to specific chromosomal translocations and host genetic polymorphisms as relating to the outcome of infection. Finally, Helicobacter hepaticus infection has been linked to both intestinal and breast tumorigenesis in susceptible strains of female mice - a provocative and novel finding warranting further investigation.

Bone Quality and Bone Strength in BXH Recombinant Inbred Mice

The relationship between bone quality and strength was studied in 11 BXH recombinant inbred (RI) strains of mice. The bone quality parameters studied were bone mineralization, microhardness, architecture, and connectivity. Previous studies have demonstrated considerable variability in bone density, biomechanical properties, and microstructure among inbred strains of mice. In particular, C3H/HeJ (C3H) mice exhibit thicker femoral and vertebral cortices and fewer trabeculae in the vertebral body compared with C57BL/6J (B6) mice, despite having similar vertebral bone strength. A set of RI mouse strains has been generated from B6 and C3H (denoted BXH) in an attempt to isolate genetic regulation of numerous traits, including bone. The objective of this study was to investigate relationships among bone quality and bone strength in femurs and vertebrae among BXH RI mice. The study involved 11 BXH RI strains of female mice (n = 5-7) as well as the B6 and C3H progenitor strains. Parameters contributing to bone quality were evaluated, including BMD, bone mineralization, microhardness, architecture, and connectivity. There was a strong correlation between femoral and vertebral BMD in all strains (P < 0.001) except in BXH-9 and -10 (P < 0.001). Within the vertebrae, cortical bone was more mineralized than trabecular bone, and a strong correlation existed between the two (P < 0.001). However, cortical microhardness did not differ from trabecular microhardness. Cortical bone was more mineralized in the femur than in the vertebrae and significantly harder, by 30%. There was a wide range in trabecular connectivity, architecture, and femur geometry among BXH RI strains. BMD explained 43% of vertebral bone strength but only 11% of femoral bone strength. Trabecular connectivity explained an additional 8% of vertebral strength, while mineralization and femur geometry explained 7% and 50% of femoral strength, respectively. Different bone quality parameters had varying influences on bone mechanical properties, depending on bone site. BMD may play a larger role in explaining bone strength in the vertebrae than in the femur. Moreover, cortical bone in the femur is harder than in vertebrae. The control of cortical bone material properties may be site-dependent.

Alcohol Metabolism-mediated Oxidative Stress Down-regulates Hepcidin Transcription and Leads to Increased Duodenal Iron Transporter Expression

Patients with alcoholic liver disease frequently exhibit iron overload in association with increased hepatic fibrosis. Even moderate alcohol consumption elevates body iron stores; however, the underlying molecular mechanisms are unknown. Hepcidin, a circulatory peptide synthesized in the liver, is a key mediator of iron metabolism. Ethanol metabolism significantly down-regulated both in vitro and in vivo hepcidin mRNA and protein expression. 4-Methylpyrazole, a specific inhibitor of the alcohol-metabolizing enzymes, abolished the effects of ethanol on hepcidin. However, ethanol did not alter the expression of transferrin receptor1 and ferritin or the activation of iron regulatory RNA-binding proteins, IRP1 and IRP2. Mice maintained on 10-20% ethanol for 7 days displayed down-regulation of liver hepcidin expression without changes in liver triglycerides or histology. This was accompanied by elevated duodenal divalent metal transporter1 and ferroportin protein expression. Injection of hepcidin peptide negated the effect of ethanol on duodenal iron transporters. Ethanol down-regulated hepcidin promoter activity and the DNA binding activity of CCAAT/enhancer-binding protein alpha (C/EBPalpha) but not beta. Interestingly, the antioxidants vitamin E and N-acetylcysteine abolished both the alcohol-mediated down-regulation of C/EBPalpha binding activity and hepcidin expression in the liver and the up-regulation of duodenal divalent metal transporter 1. Collectively, these findings indicate that alcohol metabolism-mediated oxidative stress regulates hepcidin transcription via C/EBPalpha, which in turn leads to increased duodenal iron transport.