Webster Mice Research Articles

Analgesic and Antipyretic Activities of Ethanolic Extract of Sappan wood (Caesalpinia sappan L.) Leaves

Sappan wood (Caesalpinia sappan L.) is used as an analgesic and antipyretic by the Indonesian people, empirically. The aim of this study was to determine the analgesic and antipyretic activity of ethanolic extract of sapan wood leaves in Webster mice as experimental animals. The writhing method was used to determine the analgesic activity in acetic acid-induced mice with mefenamic acid as a positive control. The temperature reduction method was used to determine the antipyretic activity in yeast-induced mice with paracetamol as a positive control. One-way ANOVA was conducted for statistical analysis, followed by Tukey-Kramer post hoc test. Phytochemical screening showed that sappan wood contains alkaloids, flavonoids, saponins, monoterpenoids, and sesquiterpenoids. The optimum dose of analgesic and antipyretic activity was 6.3 mg and 8.4 mg/20 g BW of mice, respectively. The conclusion was ethanolic extract of sappan wood leaves has analgesic and antipyretic activities.

Plectranthus scutellarioides (L.) Reduces the Rectal Temperature of Diphteria-Pertussis-Tetanus Vaccine-Induced Mice

The pharmacological activities of Plecranthus sp include anti-oxidant, antimicrobial, inhibition on cyclooxygenase (COX) and xanthine oxidase, and cytotoxic activity. The aim of this work was to study the antipyretic activity of P. scutellarioides (L.) extract on animal model. Twenty seven Swiss Webster male mice were divided into nine groups and were pyrexia-induced by using 0.1 ml of diphteria-pertussis-tetanus (DPT) vaccine. Their body temperature was measured every 60 minutes. After 4 hours of DPT vaccine injection, the mice were treated with (I) Arabic gum suspension (PGA) 2%; (II) paracetamol 16.25 mg/kg BW; (III) paracetamol 32.5 mg/kg BW; (IV) paracetamol 65 mg/kg BW; (V) paracetamol 130 mg/kg BW; (VI) P. scutellarioides extract 70 mg/kg BW; (VII) P. scutellarioides extract 140 mg/kg BW; (VIII) P. scutellarioides extract 280 mg/kg BW; (IX) P. scutellarioides extract 560 mg/kg BW. Data were analyzed using SPSS 21. Result showed that the body temperature of the mice started to rise at 2.5 hours and reached its peak at 4 hours after vaccine induction. The P. scutellarioides extract dose 280 mg/kg of BW indicated an 80.47% decrease (α= 0.05) compared to paracetamol dose 130 mg/kg of BW which decreases 85.43% of the animals’ fever. Interestingly, higher dose of the extract indicated a decrease in the antipyretic effect. We concluded that P. scutellarioides might possess antipyretic activity which started as early as 5 hours post vaccine-induced and was maintained for 3 hours. This plant needs further scientific exploration Keywords: Diphteria-pertusis-tetanus vaccine, anti-pyretic, rectal temperature, Webster mice

Evaluation of the immunogenicity of Schistosoma mansoni egg surface.

Immunogenicity of Schistosoma mansoni egg surface was examined to determine whether intact eggshells have lower antigenicity than ruptured eggs. Swiss Webster mice were inoculated with intact or ultrasonicated S. mansoni eggs isolated from infected human feces. Mice were separated into four groups of six animals each and immunizations were performed approximately every 20 days during a 60-day period. Groups 1-4 were administered with saline solution, sonicated eggs with Freund's adjuvant, sonicated eggs without Freund's adjuvant, and intact eggs, respectively. IgG humoral immune response was assessed by ELISA using Soluble Egg Antigen produced from eggs isolated from the livers of infected mice. Sonicated eggs co-administered with adjuvant induced the highest humoral response at 58 days, which was 11.9-fold (95% CI 6.2-17.5) greater than the response induced by saline solution. Sonicated eggs without adjuvant induced a 4.3-fold stronger response (95% CI 2.4-6.2) than normal saline. Intact eggs induced humoral response that was nominally twice stronger (95% CI 0.8-3.2) than that induced by normal saline but the effect did not reach statistical significance. Soluble antigens are not abundant on the surface of S. mansoni eggs and/or are not secreted in sufficient quantities to induce a significant immune response to intact eggs. Assuming that isolation procedures had not damaged the eggs used for inoculation, our observations suggest that intact eggs either do not induce a significant immune response or, if they do, the mechanism involves insoluble antigens from the egg surface.

Low doses of mercuric chloride cause the main features of anti-nucleolar autoimmunity in female outbred CFW mice.

The growth of the influence of anthropogenic factors aimed on the improvement of human life has its side effect, for example, living organisms receive increasing exposure to toxic mercuric compounds. Experimental data show that mercury (Hg) salts are able to induce systemic autoimmunity in rodents. This Hg-induced autoimmune process (HgIA) is characterized by T cell-dependent polyclonal activation of B lymphocytes, increased level of serum immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), production of antinucleolar autoantibodies (ANoA), and immune complex deposition in multiple organs. HgIA in mice is used as a model of human systemic autoimmune disorders. However, the dose of mercuric chloride (HgCl2) usually used in laboratory mice to induce HgIA is above the allowable limit for everyday levels of Hg exposure in humans. So, we decided to determine the lowest dose of HgCl2 that is able to trigger autoimmunity in outbred Carworth Farms Swiss Webster (CFW) mice not genetically prone to HgIA development. The lowest dose (50 µg/kg body weight (b.w.)/week) was chosen to match the World Health Organization provisional weekly tolerable intake of total Hg for humans. We also tested HgCl2 at 500 and 1500 µg/kg b.w./week (6.5- and 2-fold less than usually used for induction of HgIA in mice). We found that even the lowest dose of Hg resulted in a statistically significant increase in serum level of IgG1 after 8 weeks of treatment. HgCl2 in doses 500 and 1500 µg/kg b.w./week resulted in a significant increase in serum level of IgG1 after 4 weeks of treatment, followed by ANoA production. Sera of HgCl2-treated mice stained the regions in which the major autoantigen in HgIA, fibrillarin, was revealed. These results suggest that low doses of Hg are able to induce the main features of HgIA in genetically heterozygous mice, and that humans chronically exposed to low doses of Hg may be at risk of autoimmunity induction regardless of their genetic background.

Modified dextromethorphan displays antidepressant‐like effects in the forced swim test

Dextromethorphan (DM) may serve as a safer alternative to ketamine as a fast acting antidepressant due to overlapping pharmacology. Our lab has previously shown DM produces antidepressant‐like effects through sigma‐1 (σ1) receptors in the forced swim test (FST) in male Swiss, Webster mice. However DM's rapid metabolism poses a challenge in its use as a routine clinical drug. Two approaches to inhibit its metabolism are 1) addition of the CYP2D6 inhibitor, quinidine, and 2) chemically modifying DM. The present study aimed to determine if modified DM (MDM) by itself and in the presence of quinidine elicits antidepressant‐like effects and if σ1 receptors are involved. Our results showed MDM (3‐30 mg/kg, i.p.) produces a dose‐dependent decrease in immobility time in the FST, indicative of antidepressant‐like effects. MDM also had stimulatory effects, but they cannot account for its antidepressant‐like effects because there was no correlation between the two measures. Pretreatment with BD1063 (σ1 receptor antagonist) to examine the potential role of σ1 receptors failed to block MDM's antidepressant‐like effects. Co‐administration of quinidine to slow the metabolism of MDM produced a similar dose‐dependent decrease in immobility time in the FST compared to MDM alone. Quinidine with MDM, however, had no stimulatory effects. In conclusion, MDM has antidepressant‐like effects independent of σ1 receptors in the FST. Addition of quinidine does not alter the antidepressant‐like effects of MDM, but reduces its stimulant effects, suggesting a possible way to reduce the abuse potential and increase the safety of MDM.

Anti-inflammatory effect of Lippia origanoides

Introduction: Lippia origanoides Kunth is an aromatic shrub known as “salva-do-marajo”. Aerial parts are used to treat gastrointestinal and respiratory problems and by Oriximina (PA, Brazil) midwife to treat postpartum bleeding (“to clean woman inside”) or to woman inflammation [1]. Although there are ethnobotanical data, there is no scientific evidence of information obtained. In this regard this work aimed to evaluate the effects of ethanol extract from leaves of L. origanoides in models of inflammation. Methods: L. origanoides was collected at Embrapa Amazonia Ocidental. Voucher (CESJ39532) is deposited at herbarium of Federal University of Juiz de Fora, Brazil. Leaves were dried, triturated and extracted by maceration with ethanol (EE). Webster mice (20 – 25 g, n = 6 – 8) were orally treated with EE (10, 30,100 mg/kg). Anti-inflammatory effect was evaluated by formalin [2] or subcutaneous air pouch (SAP) [3]. Results are presented as medium ± DP. Statistics was done by ANOVA/Bonferroni (*p < 0.05). Protocols for animal use number is #ICBDFBC-015 (COBEA/UFRJ/Brazil). Results: Conclusion: Ethanol extract from leaves of L. origanoides has a significant anti-inflammatory effect confirming the traditional use. Acknowledgements: Alan Minho (technical support), Instituto Vital Brazil (donation of animals), CAPES, CNPq and FAPERJ (financial support). Keywords: Lippia origanoides, anti-inflammatory effect

Immunization against a merozoite sheddase promotes multiple invasion of red blood cells and attenuates Plasmodium infection in mice.

BackgroundSubtilisin-like protease 2 (SUB2) is a conserved serine protease utilized by Plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. To determine if SUB2 is a suitable vaccine target to interfere with malaria parasite development, the effects of SUB2-immunization on the Plasmodium life cycle were examined in its vertebrate and invertebrate hosts.MethodsSwiss Webster mice were immunized with SUB2 peptides conjugated to Keyhole limpet hemocyanin (KLH) or KLH alone, and then challenged with Plasmodium berghei. To determine the effects of immunization on parasite development, infected mice were evaluated by blood film and Giemsa staining. In addition, collected immune sera were used to perform passive immunization experiments in non-immunized, P. berghei-infected mice to determine the potential role of SUB2 in parasite development in the mosquito.ResultsFollowing P. berghei challenge, SUB2-immunized mice develop a lower parasitaemia and show improved survival when compared to control immunized mice. Moreover, SUB2 immunization results in an increase in the number of multiply invaded red blood cells, suggesting that SUB2 antibodies interfere with merozoite invasion. Passive immunization experiments imply that SUB2 may not have a major role in ookinete invasion, but this requires further investigation.ConclusionBy interfering with red blood cell invasion, immunization against SUB2 limits malaria parasite development and confers protection from severe malaria. Together, these results provide proof-of-principle evidence for future investigation into the use of SUB2 as a vaccine or drug target to interrupt parasite development in more relevant human malaria models.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-313) contains supplementary material, which is available to authorized users.

Immunohistochemical comparison of whisker pad cutaneous innervation in Swiss Webster and hairless mice

To establish the mouse mutant, hairless (Hr), as a useful model for future analyses of target–ending interactions, we assessed the cutaneous innervation in the whisker pad after loss of primary hair targets. Postnatal (P) development of fur in Hr begins similarly to that of “normal” Swiss Webster (SW) mice. Around P10, hairs are shed and the follicles rendered permanently incompetent. Hair loss progresses rostrocaudally until the entire skin is denuded. Substantial alterations in the distribution and density of sensory and autonomic endings in the mystacial pad vibrissal and intervibrissal fur innervation were discovered. Pilo-neural complexes innervating fur hairs were dismantled in Hr. Epidermal innervation in SW was rich; only a few endings expressed growth-associated protein-43 kdal (GAP), suggesting limited changes in axonal elongation. Innervation in Hr formed a dense layer passing upward through the thickened epidermis, with substantial increases among all types of endings. Vibrissal follicle–sinus complexes were also hyperinnervated. Endings in Hr vibrissae and fur were strongly GAP-positive, suggesting reorganization of innervation. Dermal and vascular autonomic innervation in both strains co-localized tyrosine hydroxylase and neuropeptide Y, but only in Hr did neuropeptide Y co-localize calcitonin gene-related peptide (CGRP) and express GAP immunolabeling. Stereological quantitation of trigeminal ganglia revealed no differences in neuron number between Hr and SW, although there were small increases in cell volume in Hr trigeminal ganglion cells. These results suggested that a form of collateral sprouting was active in Hr mystacial pads, not in response to local injury, but as a result of loss of primary target tissues.

Dietary glutamine supplementation affects macrophage function, hematopoiesis and nutritional status in early weaned mice

To investigate the effect that early weaning associated with the ingestion of either a glutamine-free or supplemented diet has on the functioning of peritoneal macrophages, hematopoiesis and nutritional status of mice. Swiss Webster mice were early weaned on their 14th day of life and distributed to two groups, being fed either a glutamine-free diet (-GLN) or a glutamine-supplemented diet (+GLN). Animals belonging to a control group (CON) were weaned on their 21st day of life. The -GLN and +GLN groups had a lower lean body mass, carcass protein and ash content, plasma glutamine concentration and lymphocyte counts both in the peripheral blood and bone marrow when compared to the CON group (P<0.05). Dietary supplementation with glutamine reversed both the lower concentrations of protein and DNA in the muscle and liver, as well as the reduced capacity of spreading and synthesizing nitric oxide, hydrogen peroxide, TNF-alpha, IL-1 beta and IL-6 in cultures of peritoneal macrophages obtained from the -GLN group (P<0.05). These data indicate that the ingestion of glutamine modulates the function of peritoneal macrophages in early weaned mice. However, a glutamine-supplemented diet cannot substitute maternal milk in respect to immunological and metabolic parameters.

Reflection and penetration depth of millimeter waves in murine skin

Millimeter (mm) wave reflectivity was used to determine murine skin permittivity. Reflection was measured in anesthetized Swiss Webster and SKH1-hairless mice in the 37-74 GHz frequency range. Two skin models were tested. Model 1 was a single homogeneous skin layer. Model 2 included four skin layers: (1) the stratum corneum, (2) the viable epidermis plus dermis, (3) fat layer, and (4) muscle which had infinite thickness. We accepted that the permittivity of skin in the mm wave frequency range results from the permittivity of cutaneous free water which is described by the Debye equation. Using Fresnel equations for reflection we determined the skin parameters best fitting to the reflection data and derived the permittivity of skin layers. The permittivity data were further used to calculate the power density and specific absorption rate profiles, and the penetration depth of mm waves in the skin. In both murine models, mm waves penetrate deep enough into tissue to reach muscle. In human skin, mm waves are mostly absorbed within the skin. Therefore, when extrapolating the effects of mm waves found in animals to humans, it is important to take into account the possible involvement of muscle in animal effects.

Cytogenetic Effects of 1,1-Dichloroethane in Mice Bone Marrow Cells

The major concern for the halogenated compounds is their widespread distribution, in addition to occupational exposures. Several chlorinated alkanes and alkenes were found to induce toxic effects. In this study, we investigated the genotoxic potential of 1,1-dichloroethane in the bone marrow cells obtained from Swiss-Webster mice, using chromosomal aberrations (CA), mitotic index (MI), and micronuclei (MN) formation as toxicological endpoints. Five groups of three male mice each, weighing an average of 24 +/- 2 g, were injected intraperitoneally, once with doses of 100, 200, 300, 400, 500 mg/kg body weight (BW) of 1,1-dichloroethane dissolved in ethanol. A control group was also made of three animals injected with ethanol (1%) without the chemical. All animals were sacrificed 24 hours after the treatment. Chromosome and micronuclei preparations were obtained from bone marrow cells following standard protocols. Chromatid and chromosome aberrations were investigated in 100 metaphase cells per animal and percent micronuclei frequencies were investigated in 1,000 metaphase cells per animal. 1,1-dichloroethane exposures significantly increased the number of chromosomal aberrations and the frequency of micronucleated cells in the bone marrow cells of Swiss-Webster mice. Percent chromosomal aberrations of 2.67 +/- 0.577, 7.66 +/- 2.89, 8.33 +/- 2.08, 14.67 +/- 2.51, 20.3 +/- 3.21, 28 +/- 3.61; mitotic index of 9.4%, 7.9%, 6.2%, 4.3%, 3.0%, 2.6% and micronuclei frequencies of 3.33 +/- 0.7, 7.33 +/- 0.9, 8.00 +/- 1.0, 11.67 +/- 1.2, 15.33 +/- 0.7, 18.00 +/- 1.7 were recorded for the control, 100, 200, 300, 400, and 500 mg/kg BW respectively; indicating a gradual increase in number of chromosomal aberrations and micronuclei formation, with increasing dose of 1,1,-dichloroethane. Our results indicate that 1,1-dichloroethane has a genotoxic potential as measured by the bone marrow CA and MN tests in Swiss-Webster mice.

Gender- and age-specific cytotoxic susceptibility to benzene metabolites in vitro.

Benzene, a widely used compound, is a known carcinogen and hematopoietic toxicant. Several studies have shown gender and age differences in the responses to benzene-induced hematotoxicity. It is not known if these differences in response are due to age- or gender-associated metabolic differences or to age- or gender-associated differences in the susceptibilities of the target cells. In order to address this issue, mouse colony-forming units-erythroid (CFU-e, an erythroid precursor cell particularly susceptible to benzene toxicity) were cultured in the presence of either individual benzene metabolites or binary mixtures of these metabolites. CFU-e were obtained from unexposed age-matched adult male and female (both virgin and pregnant) Swiss Webster (SW) mice and from SW male and female 16-day fetuses. The metabolites used were phenol, hydroquinone, catechol, benzoquinone, and trans, trans-muconic acid. The concentrations of the individual metabolites used were 10, 20, and 40 microM. Binary mixtures of metabolites were prepared using the lowest concentrations of the individual metabolites that caused cytotoxicity. These concentrations were 10 microM for hydroquinone, catechol, and benzoquinone, and 40 microM for phenol and muconic acid. In general, the CFU-e from adult females (both virgin and pregnant) were more resistant to the toxic effects of the individual metabolites than CFU-e from other subjects. CFU-e from adult males were more susceptible to the cytotoxic effects of hydroquinone and benzoquinone than CFU-e from other subjects and CFU-e from both male and female fetuses were highly sensitive to the toxic effects of catechol. On the other hand, CFU-e from adult males were less susceptible to the cytotoxic effects of catechol than CFU-e from other subjects. Similar results were observed with binary mixtures of metabolites. CFU-e from adult males were more susceptible to the binary mixtures than CFU-e from virgin females and CFU-e from fetal males were more susceptible than CFU-e from fetal females. In addition, CFU-e from fetuses were more 'resistant than CFU-e from adults to the cytotoxic effects of those binary mixtures that did not contain catechol. In contrast, binary mixtures containing catechol were more toxic to fetal cells than to adult cells. These results suggest that differences in benzene hematotoxicity associated with gender and age may be due, at least in part, to intrinsic factors at the level of the target cell rather than solely to age- or gender-related differences in the metabolism of benzene.

Gastritis in urease-immunized mice after Helicobacter felis challenge may be due to residual bacteria

BACKGROUND & AIMS: Oral immunization with recombinant Helicobacter pylori urease (rUre) coadministered with a mucosal adjuvant protects mice against challenge with Helicobacter felis. In this study, the duration of protection and gastritis after challenge were characterized at sequential time intervals up to 1 year.METHODS: Outbred Swiss- Webster mice were orally immunized with rUre plus adjuvant and examined for the presence of H. felis infection and leukocyte infiltration into the gastric mucosa.RESULTS: When defined by gastric urease activity, 70%-95% of rUre-immunized mice were protected for between 2 and 57 weeks. Challenge with H. felis increased the inflammatory response in the gastric mucosa of rUre-immunized mice, which also had elevated CD4+ and CD8+ T cells. The CD8+ cells represented a population of gastric intraepithelial cells, which expressed the mucosal alpha E-integrin. Epithelial changes consisting of parietal cell loss and hyperplasia of the epithelium occurred in approximately 20% of the mice. Antimicrobial triple therapy significantly decreased the degree of gastritis and epithelial alteration in the stomach.CONCLUSIONS: These results indicate that oral immunization of mice with rUre produces a long- lasting inhibition of H. felis infection but that residual bacteria may produce a persistent lymphocytic infiltration under these experimental conditions.(Gastroenterology 1997 Oct;113(4):1118-28)

Sensory irritation response in mice to sulfur dust.

The potential of sulfur dust to produce sensory irritation was evaluated in mice. Male Swiss--Webster mice were exposed by head-only inhalation to 106, 263, or 451 mg/m3 sulfur dust aerosol at room temperature. Breathing frequency and patterns were monitored before, during, and after exposure to evaluate the animal's sensory irritation response to the test atmosphere. Group average breathing rates were decreased 7 and 17% below pretest values in mice exposed to 106 and 263 mg/m3, respectively; however, breathing patterns appeared normal, indicating that there was no sensory irritation. Mice exposed to 451 mg/m3 showed an increase in breathing frequency of 7%, with 1/4 mice displaying very slight signs of pulmonary (deep lung) irritation. Some of the mice in the low- and high-dose groups exhibited signs of slight eye irritation immediately after exposure, but all mice were normal 1 day later. On the basis of these findings, exposure to sulfur dust up to 451 mg/m3 did not produce any sensory or upper airway irritation in mice.

Inhibition of macrophage-activating cytokines is beneficial in the acute septic response.

Interferon-gamma and other cytokines enhance macrophage (M phi) antimicrobial function and have been considered for therapeutic use in sepsis. Systemic sequelae of macrophage activation, however, are unclear. This study examined the effects of M phi activating cytokines (interferon-gamma [IFN-gamma] and interleukin-4 [IL-4]) and monoclonal antibodies directed against these cytokines in modulating the acute septic response. CFW/Swiss Webster mice (n = 345) received endotoxin (lipopolysaccharide [LPS]: 60 mg/kg body weight intraperitoneally) and were randomized to five treatment groups: IFN-gamma (10(4) units), IL-4 (10(4) units), IgG1 isotype antibody (TRFK5: 200 micrograms), anti-IFN-gamma (200 micrograms), or anti-IL-4 (200 micrograms) monoclonal antibodies (MAbs) given simultaneously or 2 hours after LPS. Animals were divided into two groups and studied for mortality or measurement of peritoneal M phi superoxide anion release (O2-), tumor necrosis factor (TNF), and IL-6 production 6 hours after administration of LPS +/- experimental regimens. Serum TNF and IL-6 also were assessed at 2 and 4 hours after LPS, respectively. Administration of LPS resulted in a 27% survival compared with 10% in the IFN-gamma and 13% in the IL-4 groups. Treatment with anti-IFN-gamma offered protection against LPS lethality (93%-100% survival, p less than 0.001 vs. other groups) when given either simultaneously or 2 hours after LPS. Anti-IFN-gamma also significantly decreased PM phi O-2 and TNF release. Thus anti-IFN-gamma may have an important role in the modulation of the acute septic response.

Quantitative and cytoarchitectural studies of the entorhinal region and the hippocampus of New Zealand Black mice

New Zealand Black (NZB) mice were suggested as an animal model for human dementia. We performed quantitative and cytoarchitectural studies of the entorhinal region and the hippocampus of 10 NZB mice and compared the results with those for a control group of 10 Carworth Farm Webster (CFW) mice. No cytoarchitectural disturbances were observed in the entorhinal cortex and hippocampus of the NZB mice. We, however, found a reduced density of nerve cells in the entorhinal region as well as in the CA1 and CA3 regions of the Ammon's horn in NZB mice. Since the entorhinal region is an important link between sensory and association cortices and the limbic system which seems to play an important role in learning and memory, the present findings may be a cause of learning and/or memory deficits in the NZB mice. The undisturbed cytoachitecture of the entorhinal cortex suggests that the reduced cell sensity in NZB mice is rather an acquired lesion than a developmental malformation and, therefore, indicates therapeutic studies on memory and learning deficits in NZB mice.

Assessment of carbamate pesticide immunotoxicity.

Adult female Swiss Webster and B6C3F1 mice received distilled water only or water containing 0.1, 1.0, 10, 100 or 1000 ppb of aldicarb daily for 34 days. The target concentration of aldicarb present in the 10 ppb dosing solution was analytically verified on a daily basis as was its stability over a 48-hr period. To develop an immune profile of this compound, functional parameters measured after exposure included resistance to infectious viral challenge; quantitation of splenic antibody-forming cells to sheep erythrocytes; splenic lymphocyte blastogenesis to B-cell mitogens; and T-cell mixed lymphocyte culture response. In addition, gross and histopathologic examinations of tissues relevant to the immune system were performed. The absence of significant effects on any of these parameters suggests that aldicarb at environmentally relevant exposure concentrations is not immunotoxic in rodents.

Some effects and properties of Duvernoy's gland secretion from Hypsiglena torquata texana (Texas night snake)

D. K. Vest. Some effects and properties of Duvernoy's gland secretion from Hypsiglena torquata texana (Texas night snake). Toxicon 26, 417 – 419, 1988. — The Texas night snake ( Hypsiglena torquata texana), a small opisthoglyphic colubrid snake, produces a Duvernoy's secretion which has a relatively low lethal toxicity for mice, but produces pain, hemorrhage, and oedema at the site of injection. The subcutaneous ld 50 of Hypsiglena torquata texana Duvernoy's secretion in Swiss - Webster mice was 26 mg/kg. Local hemorrhaging occurred at doses as low as 2.0 μg/mouse, while marked hemorrhage and oedema resulted at doses greater than 200 μg/mouse. The dry secretion contained 77% protein, and SDS - PAGE electrophoresis revealed the presence of seven major proteinaceous components.

Acetaminophen: fatty enhanced toxicity

Drug toxicity accounts for 10%-30% of all medical in-patients admissions; some of the drug induced illnesses often occur following hospitalization. 5%-6% of medical in-patients deaths are initiated or induced by drug intake (1-4); about one-third of these cases are caused by non-prescription drugs. Acetaminophen, considered among the safest of all over-the-counter analgesics, has been reported to induce fatal hepatic necrosis both in man and animals (5-8). Frequently, adverse drug reactions arise from hypersensitivity to a drug and its side effects, or to drug interactions with food and food additives. This study is undertaken to observe the effect of acetaminophen on the liver when a fatty diet is simultaneously administered.Swiss Webster mice were individually gavaged with a 286 mg/Kg dosis of acetaminophen for 4 days; control animals received saline alone. Both groups received rat feed plus 20% fat and were euthanized on the 5th day. Liver tissues were either fixed in 2% gluteraldehyde; post-fixed in 1% osmnium tetroxide in 0.1M sodium cacodylate buffer and embedded in Araldite 502 for TEM; or processed for alkaline phosphatase activity (9).Hepatocyte derived from mice exposed to acetaminophen (Fig. 1) showed increased Golgi Apparatus (GA) and secretory granules (SG) activity. These phenomena appear to be responsible for the elevated alkaline phosphatase activity (Fig. 2) in response to acetaminophen detoxification exerted by the hepatocyte. However, when a fatty diet is incorporated into the study: the hepatocyte exhibited generalized cytoplasmic lysis and increased lipid droplets (Fig. 3), localized coagulative necrosis of the hepatocyte normally found in the caudal and right lobes of the liver (Fig. 4) and increased pynotic hepatocytes (Fig. 5) are noted

Spleen changes in animals inhaling ambient levels of nitrogen dioxide.

The effects of ambient levels of NO2 on the spleens of adult and newborn Swiss Webster (S/W) mice were determined. Spleens were evaluated by the following criteria: (1) spleen weight, expressed as a percent of the body weight (% spleen weight), (2) size of the spleen lymphoid nodules as determined by computed image analysis, (3) spleen cell counts, and (4) histopathologic evaluation. Data for NO2-exposed animals were compared with data for control animals that inhaled filtered air. Totals of 217 control and 217 NO2-exposed animals were studied. After 6 wk of exposure to NO2 at ambient levels (0.35 +/- 0.05 ppm), the following significant changes were observed in the spleens of exposed mice: (1) increase in % spleen weight (p less than 0.0025), (2) increase in size of spleen lymphoid nodules (p less than 0.01), (3) smaller increase in spleen cell number per given weight increment of spleen as determined by correlation coefficients (p less than 0.0125) and linear regression analysis of spleen cell counts, and (4) an apparently greater predominance of red cells in the red pulp. It is concluded that inhalation of NO2 is associated with quantifiable spleen changes, which may prove to be useful indicators for assessing effects of inhaled NO2.