Reactive astrogliosis in the dentate gyrus of mice exposed to active volcanic environments.

Air pollution has been associated with neuroinflammatory processes and is considered a risk factor for the development of neurodegenerative diseases. Volcanic environments are considered a natural source of air pollution. However, the effects of natural source air pollution on the central nervous system (CNS) have not been reported, despite the fact that up to 10% of the world's population lives near a historically active volcano. In order to assess the response of the CNS to such exposure, our study was conducted in the island of Sao Miguel (Azores, Portugal) in two different areas: Furnas, which is volcanically active one, and compared to Rabo de Peixe, a reference site without manifestations of active volcanism using Mus musculus as a bioindicator species. To evaluate the state of the astroglial population in the dentate gyrus in both samples, the number of astrocytes was determined using immunofluorescence methods (anti-GFAP and anti-GS). In addition, the astrocytic branches in that hippocampal area were examined. Our results showed an increase in GFAP+ astrocytes and a reduction in GS+ astrocytes in Furnas-exposed mice compared to animals from Rabo de Peixe. In addition, astrocytes in the dentate gyrus of chronically exposed animals exhibited longer branches compared to those residing at the reference site. Thus, reactive astrogliosis and astrocyte dysfunction are found in mice living in an active volcanic environment.

SUSPECTED HYPERVITAMINOSIS D IN RED-RUMPED AGOUTI ( DASYPROCTA LEPORINA) RECEIVING A COMMERCIAL RODENT DIET.

An 8 yr, intact male red-rumped agouti ( Dasyprocta leporina) was evaluated for weight loss. Examination revealed poor body condition, hypercalcemia, elevated serum 25-hydroxyvitamin D, metastatic calcification of soft tissues, and hyperechoic kidneys. The diet, formulated for laboratory rodents, contained elevated levels of vitamin D3. Histopathology from a female conspecific that died 5 mo prior identified dystrophic mineralization and nephrosclerosis, suggestive of a vitamin D3 toxicity. The male agouti responded well to a dietary reduction in vitamin D3 and calcium. Six months into therapy, progressive renal failure was identified and was further managed with enalapril, phosphorus binders, and dietary manipulation. Suspected vitamin D3 toxicity has been reported in pacas ( Cuniculus paca) and agouti and has been linked to exposure to New World primate diets. In this brief communication, an agouti developed suspected hypervitaminosis D after receiving a commercial rodent diet commonly fed to this species in captivity.

Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice.

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Ameliorate effects of resveratrol and l-carnitine on the testicular tissue and sex hormones level in busulfan induced azoospermia rats.

Busulfan (Bus), is an alkylating agent widely used in chemotherapy which has been proven to possess toxic side effects on testicles. This study was carried out to compare the probable treatment effects of resveratrol (Res) or/and l-carnitine (Lca), as strong antioxidants, on the testicular tissue as well as on the level of sex hormones in busulfan-induced azoospermic rat models. A total of 78 adult male rats, were divided into six different experimental groups including: 1) Control; 2) Lca + Res; 3) BUS; 4) Bus + Lca; 5) BUS + Res and 6) Bus + Lca + Res. Busulfan was intraperitoneally administered in a single dose (10 mg/kg b.w), while resveratrol (20 mg/kg b.w/day) and l-carnitine (200 mg/kg b.w/day) were orally administered by gavage during 48 consecutive days to the rats. At the end of the experiment in all groups the level of LH, FSH, and testosterone were biochemically analyzed by ELISA and the testicular tissue evaluated histologically using stereological technique. Results showed that Lca or/and Res, increased the body and testis weight, the volume of the testis, interstitial tissue, germinal epithelium, and seminiferous tubule, the number of the different cells of germinal epithelium and the level of testosterone. On the other hand, Lca, Res and their combination decreased the concentration of LH and FSH compared to the group treated with Bus. In conclusion, these results suggested that l-carnitine or/and resveratrol treatment significantly attenuated busulfan -induced changes of the rat reproductive system led to the recovery of both testis and sperm parameters. However, co-administration of L-ca and Res was more effective than their individual treatment. This combination may alleviate the side effects of alkylating drugs, such as busulfan and may be beneficial for spermatogenesis.

Mortality Associated with Bushfire Smoke Inhalation in a Captive Population of the Smoky Mouse (Pseudomys fumeus), a Threatened Australian Rodent.

A mortality event of nine threatened smoky mice (Pseudomys fumeus) occurred in January 2020 at a captive breeding facility in southeastern Australia that was affected at the time by hazardous levels of bushfire smoke, despite being more than 20 km from the nearest fire. Pathologic and clinical observations indicated smoke inhalation was the cause of death. All animals had significant pulmonary lesions, notably pulmonary edema and congestion, and moderate amounts of dark brown to black pigmented intracellular and extracellular particles from <0.5-2.5 µm in diameter were observed in the central or hilar region of the lungs of four of six animals examined histologically. Deaths occurred between three and 30 d after exposure to smoke and, for seven animals in outdoor acclimatization enclosures, were associated with very high ambient temperature (>40 C). Similar mortalities did not occur in co-located parrots, suggesting differing species sensitivity to smoke inhalation. Our findings highlight the potential for smoke to be an underdiagnosed cause of mortality in free-ranging wildlife during bushfires and for bushfires to affect wildlife populations outside of burnt areas, including in unburnt refugia. Conservation interventions for wildlife after bushfires should consider and, where possible, mitigate the risk of animals dying due to increased respiratory demand following smoke inhalation injury.

Injection Reactions after Administration of Sustained-release Meloxicam to BALB/cJ, C57BL/6J, and Crl:CD1(ICR) Mice.

The sustained-release formulation of meloxicam (MSR) is a compounded NSAID that may provide pain relief for as long as 72 h after administration. MSR injection-site skin reactions have occurred in several species but have not previously been observed in mice. We investigated the development and progression of localized skin reactions after a single injection of MSR in Crl:CD1(ICR), C57BL/6J, and BALB/cJ mice. Each mouse received a subcutaneous injection of MSR (n = 60), standard-formulation meloxicam (MEL; n = 24) or saline (control; SC; n = 24) and was scored daily according to a 5-point system for erythema and mass characteristics. Mice were euthanized at either 7 or 14 d after injection and underwent postmortem analysis. MSR-treated mice had more erythematous and mass reactions than did MEL and SC mice. Mass lesions developed in 49 MSR mice (82%; 95% CI, 70% to 90%), 5 MEL animals (21%; 95% CI, 7% to 42%), and 1 SC mouse. MSR-treated BALB/cJ developed erythematous lesions less frequently than similarly treated Crl:CD1(ICR) or C57BL/6J. Lesions often were ventrolateral to the injection site. The median times to the appearance of mass and erythematous lesions were 2 d and 3 d, respectively. Histologically, the erythematous and mass reactions correlated with necrotizing to pyogranulomatous injection-site panniculitis. Inflammation severity scores at 7 and 14 d after injection were greater in the MSR-treated group than the other 2 groups. No strain- or sex-associated differences emerged except that inflammation severity scores at day 14 were higher in Crl:CD1(ICR) females than males. The character of the inflammatory response in MSR-treated mice did not differ between 7 and 14 d after injection, indicating that MSR-induced inflammation is slow to resolve. The ventral migration and delayed onset of MSR injection-site reactions could result in their being attributed to another cause or not being identified. Researchers and clinicians should be aware of the potential for slowly resolving injection-site reactions with MSR.

Surveillance for diseases, pathogens, and toxicants of muskrat (Ondatra zibethicus) in Pennsylvania and surrounding regions.

Using diagnostic data and contemporary sampling efforts, we conducted surveillance for a diversity of pathogens, toxicants, and diseases of muskrats (Ondatra zibethicus). Between 1977 and 2019, 26 diagnostic cases were examined from Kansas and throughout the Southeast and Mid-Atlantic, USA. We identified multiple causes of mortality in muskrats, but trauma (8/26), Tyzzer's disease (5/6), and cysticercosis (5/26) were the most common. We also conducted necropsies, during November 2018-January 2019 Pennsylvania muskrat trapping season, on 380 trapper-harvested muskrat carcasses after the pelt was removed. Tissue samples and exudate were tested for presence of or exposure to a suite of pathogens and contaminants. Gastrointestinal tracts were examined for helminths. Intestinal helminths were present in 39.2% of necropsied muskrats, with Hymenolepis spp. (62%) and echinostome spp. (44%) being the most common Molecular testing identified a low prevalence of infection with Clostridium piliforme in the feces and Sarcocystis spp. in the heart. We detected a low seroprevalence to Toxoplasma gondii (1/380). No muskrats were positive for Francisella tularensis or Babesia spp. Cysticercosis was detected in 20% (5/26) of diagnostic cases and 15% (57/380) of our trapper-harvested muskrats. Toxic concentrations of arsenic, cadmium, lead, or mercury were not detected in tested liver samples. Copper, molybdenum, and zinc concentrations were detected at acceptable levels comparative to previous studies. Parasite intensity and abundance were typical of historic reports; however, younger muskrats had higher intensity of infection than older muskrats which is contradictory to what has been previously reported. A diversity of pathogens and contaminants have been reported from muskrats, but the associated disease impacts are poorly understood. Our data are consistent with historic reports and highlight the wide range of parasites, pathogens and contaminants harbored by muskrats in Pennsylvania. The data collected are a critical component in assessing overall muskrat health and serve as a basis for understanding the impacts of disease on recent muskrat population declines.

Effects of Intracage Ammonia on Markers of Pulmonary Endothelial Integrity in Mice Housed in Static Microisolation Cages.

Time-weighted exposure limits to ammonia are established for humans; however similar guidelines have not been defined for laboratory rodents. The Guide recommends maintaining air pollutants at concentrations below levels irritating to mucous membranes but does not provide specific values. Numerous studies have examined ammonia and its effects on animal health, yet none have assessed the effects of naturally occurring intracage ammonia on the lower pulmonary tree and pulmonary endothelial and epithelial integrity in mice. We performed several assays commonly used in mouse acute lung-injury studies (bronchoalveolar lavage fluid [BAL] cell counts and protein concentration, excess lung water content [ELW], Evans blue permeability assay [EBA], lung tissue myeloperoxidase assay [MPO], and lung histopathology) to evaluate the effects of exposure to cyclical, naturally occurring ammonia levels on pulmonary integrity and inflammation. C57BL/6 mice were maintained in static microisolation or open-top cages. Cages were changed weekly, and ammonia levels were measured for 6 wk on days 0, 1, 3, 5, and 7 of each cage-change cycle. Ammonia levels in static microisolation cages began to increase on day 3 and peaked at a mean of 141.3 ppm on day 7. Ammonia levels in open-top cages never exceeded 5 ppm. Neither BAL cell counts, protein concentration, ELW, EBA, nor MPO differed significantly between groups. Lung histopathology showed minimal, incidental changes in all mice. Our findings indicate that the ammonia concentrations in the static microisolation cages we used did not alter the integrity of the lower pulmonary tract nor influence key indicators used to assess acute lung injury.

Dose-dependant hypothyroidism in mice induced by commercial trimethoprim-sulfamethoxazole rodent feed.

Trimethoprim-sulfamethoxazole (TMP-SMX) medication in the feed or water is commonly administered to immunocompro mised mice to prevent the occurrence of Pneumocystis murina (formerly P. carinii) pneumonia. Therapeutic doses of SMX can cause decreased total and free thyroxine (T4) levels in dogs and thyroid hypertrophy and hyperplasia in mice, rats, and dogs. Our primary objective was to determine whether SMX at doses present in commercially available rodent TMP-SMX feed would pro duce hypothyroidism in mice. Plasma T4 levels were determined prior to and after placement of Brand A TMP-SMX feed (daily SMX dose, 240 mg/kg), Brand B TMP-SMX feed (daily SMX dose, 2400 mg/kg), and their respective controls (doses calculated for a 25-g mouse according to vendor's information). T4 levels in the mice fed Brand B TMP-SMX feed were significantly decreased by 2 wk after feed placement. Levels of thyroid stimulating hormone in male and female mice given Brand B TMP-SMX feed were significantly elevated compared with those of control groups at 6 wk after feed placement, when only these mice showed evidence of thyroid hypertrophy and hyperplasia. No significant change in T4 levels occurred over the course of 11 wk in mice given the Brand A TMP-SMX chow or either control feed. In light of the significant clinical hypothyroidism that occurred in our mice while receiving Brand B TMP-SMX diet, we recommend SMX levels more similar to that of Brand A to avoid such unwanted effects which could confound research data.

Interstrain Differences in CO2-Induced Pulmonary Hemorrhage in Mice.

Carbon dioxide is the most commonly used gas for euthanasia of rodents. The current AVMA Guidelines recommend slowly filling the container with CO2 (SF) and now indicate that the practice of placing conscious animals in containers prefilled with CO2 (PF) is unacceptable. An investigator noted pulmonary hemorrhage (PH) in BALB/c mice euthanized by SF that was not observed after PF. Here we evaluated whether the air-displacement rate (SF compared with PF) influenced the development of PH or nasal hemorrhage (NH) in 2 commonly used mouse strains. In addition, we investigated the prevalence of PH and NH in mice euthanized by isoflurane overdose (IO). Male and female (age groups, 6 wk and 6 mo) BALB/c and C57BL/6 mice were euthanized by SF or PF. In addition, 6-mo-old BALB/c male mice were euthanized by IO. Lung, nasal turbinates, brain, and reproductive organs were collected for gross and histologic evaluation and scored for degree of hemorrhage (score, 0 to 3). Severity of hemorrhage did not differ according to mouse age or sex. PH in BALB/c mice was more severe after SF than PF, and SF and PF induced more severe PH in BALB/c than in C57BL/6 mice. PH in 6-mo-old male BALB/c mice was more severe after SF than IO. Neither SF, PF, nor IO influenced the prevalence of NH in any group. This study demonstrates that the method of euthanasia may need to be altered depending on the mouse strain used.

Chronic noise exposure and testosterone deficiency -- meta-analysis and meta-regression of experimental studies in rodents.

INTRODUCTION: Chronic psychological distress can cause suppression of the hypothalamic-pituitary-testicular axis and thus lead to male hypogonadism, which is associated with psycho-social dysfunction, chronic diseases, and as a result, considerable economic costs. Conversely, noise is a prototypal environmental stressor of growing importance, already linked to birth outcomes and diabetes. However, its effects on male testosterone levels have been paid little attention. MATERIAL AND METHODS: This paper reports a systematic review and meta-analysis of experimental studies in rodents, which have examined the effect of chronic noise stress on serum testosterone levels. A systematic search in MEDLINE, EMBASE and the Internet yielded seven studies. A quality effects meta-analytical model was applied to compute pooled Hedges's g. Quality effects meta-regression was carried out as well. RESULTS: We found pooled Hedges's g of -2.41 (95% CI: -3.28, -1.54), indicating a very large effect of noise exposure on testosterone. Metaregression confirmed that the overall duration of exposure explained a significant proportion of the variance across individual effect sizes (Q (1) = 3.95, p = 0.047). However, there was considerable inter-study heterogeneity (I2 = 82%) and publication bias (p = 0.016). After inputting two studies previously thought to be missing, the pooled effect dropped to g = -1.53 (95% CI: -3.01, -0.05). CONCLUSIONS: Chronic noise exposure of ≈ 100 dB leads to a significant reduction of serum testosterone in male rodents. Research on humans is highly warranted, especially given the steady trend in Western societies for increasing the burden of both male hypogonadism and noise pollution.

[Background data of spontaneous tumors in F344/DuCrlCrlj rats].

INTRODUCTION: We investigated the 2-year survival rate and incidence of spontaneous tumors in F344/DuCrlCrlj rats used in carcinogenicity studies of chemical substances. Records for animals used in the control groups of carcinogenicity studies which were conducted during the last 10 years were obtained from the database of the Japan Bioassay Research Center (JBRC). Six hundred ninety-nine males and 550 females were used in 14 and 11 inhalation studies, respectively, and 500 animals of each sex were used in 10 male and 10 female oral studies. METHODS: In each study, SPF (specific pathogen free) animals were housed for 2 years (104 weeks) as control groups in the carcinogenicity studies. All animals underwent necropsy and histopathological examination. Each study was conducted in accordance with the Good Laboratory Practice. RESULTS: The incidence of interstitial cell tumors was highest in both inhalation studies and oral studies (inhalation studies 86.1%, oral studies 68.6%). Tumors which had an incidence of 6% or higher were adenoma of the pituitary, C-cell adenoma of the thyroid, and mononuclear cell leukemia (LGL leukemia) of the spleen in male and female rats; fibroma of the subcutaneous tissue, adrenal pheochromocytoma, and islet cell adenoma of the pancreas in male rats; and endometrial stromal polyps and fibroadenoma of the mammary gland in female rats. Tumors other than the above had rare incidence rates. A clear difference in the incidence of spontaneous tumors was not observed between the inhalation and oral studies. The incidences of spontaneous tumors in control groups of previous oral studies are similar to our findings. There are no other reports of the spontaneous tumor incidence in the control groups of inhalation studies using F344/DuCrlCrlj rats. The 2-year survival rate was about 77% in both the inhalation and oral studies, and a gender difference was not observed. The F344/DuCrlCrlj rats used at JBRC had a higher 2-year survival rate than F344/N rats. This difference is possibly due to the low incidence of LGL leukemia in the F344/DuCrlCrlj rat. CONCLUSIONS: The incidences of spontaneous tumors in F344/DuCrlCrlj rats used in control groups of both inhalation and oral studies during the last 10 years at JBRC are similar to each other and similar to those reported in other studies. This is the first report on the incidence of spontaneous tumors in inhalation studies and contributes to the toxicological evaluation of studies using F344/DuCrlCrlj rats.

Proto-oncogene activation during chemically induced hepatocarcinogenesis in rodents.

The liver is a frequent site for the development of chemically induced cancer in rodents. This is primarily owing to the capability of the liver to activate a large variety of exogenous chemicals metabolically to reactive electrophilic species that can covalently interact with cellular DNA and other macromolecules (Miller and Miller, 1966; Miller, 1978). It is the potential alteration of the hepatocellular genome by mutational events that forms the theoretical basis for the heritable nature of cancer as well as, at least in part, the altered phenotype of neoplastic cells; however, our understanding of the exact nature of these heritable genetic alterations remains fragmentary. Within the last decade the delineation of the molecular basis of viral oncogenesis, especially by retroviruses, has revealed potential targets in the cell genome for the reactive forms of chemical agents in relation to their carcinogenic action (Bishop, 1987). Primary among such potential targets are proto-oncogenes, homologous to the transforming genes of oncogenic retroviruses from which they have evolved (Temin, 1974). The objective of this brief review is to consider the evidence that induced alterations in the structure and/or regulation of expression of proto-oncogenes may play one or more roles in rodent hepatocarcinogenesis, especially in relation to the stages of initiation, promotion, and progression (Pitot et al., 1988).

Ecotoxicological risks associated with land treatment of petrochemical wastes. III. Immune function and hematology of cotton rats.

Landfarming is a widely used method of treating petrochemical waste through microbial bio-degradation. The effects of residual petrochemical contamination on wildlife, especially terrestrial mammals, are poorly understood. The effects of contaminants on the immune system and hematology of cotton rats (Sigmodon hispidus) living on five abandoned petrochemical landfarms (units 1-5) in Oklahoma were studied. Cotton rats were sampled seasonally (summer and winter) from each landfarm and from five ecologically matched reference sites for 2 yr (1998-2000) and returned to the laboratory for immunological and hematological assays. Overall analysis indicated that rats inhabiting landfarms exhibited decreased relative spleen size compared to rats collected from reference sites, with the landfarm at unit 1 showing the greatest reduction. Cotton rats collected from landfarms also had increased hemoglobin, hematocrit, and platelet levels and decreased blood leukocytes during summer. During winter, an increase in the number of popliteal node white blood cells was observed from rats collected on landfarms. No marked difference was detected for lymphocyte proliferation in response to concanavalin A, pokeweed, or interleukin-2. Lymphokine-activated killer cell lytic ability showed a seasonal pattern, but no treatment differences. No differences between landfarm and reference sites were detected in the hypersensitivity reaction of rats given an intradermal injection of phytohemagluttinin (PHA-P). Comparisons within individual sites indicated that two sites (units 1 and 3) had the greatest effects on immune function and hematology of cotton rats. The results of this study suggest that residual petrochemical waste affects the immune system and hematology of cotton rats living on abandoned landfarms during summer and is complicated by variation in the contaminants found on individual petroleum sites.

A comparison of central nervous lesions directly induced by Escherichia coli lipopolysaccharide in piglets, calves, rabbits and mice.

To evaluate the role of endotoxin during Gram-negative bacterial meningitis, the nervous lesions of piglets, calves, rabbits and mice were compared by direct inoculation of Escherichia coli lipopolysaccharide into the central nervous system. Suppurative leptomeningitis was induced in piglets by small doses of lipopolysaccharide. Mice also had a mild suppurative inflammation in the leptomeninges. In contrast, calves showed suppurative pachymeningitis, but no lesions in the leptomeninges. Leptomeningeal inflammation was not induced in rabbits. Induction of the leptomeningitis by endotoxin was compared with sensitivity to intravenous or intraperitoneal endotoxin in these species.

Calcification of the urinary bladder in the wild cotton rat (Sigmodon hispidus).

Calcification of the urinary bladder epithelium was observed in 19 of 30 and 18 of 30 wild cotton rats from control and petrochemical-contaminated sites, respectively. The rats in the two sites did not differ significantly in respect of serum calcium and phosphorus concentrations. The calcification was considered to be dystrophic in nature. An unidentified factor common to both control and petrochemical-contaminated sites was considered to be responsible for this syndrome.

Tannic acid intoxication in sheep and mice.

Acute tannic acid intoxication was studied in mice and sheep. In mice, following oral administration of 2.0 to 4.6 g of tannic acid kg-1 bodyweight, periacinar coagulative and haemorrhagic necrosis occurred in the liver. In sheep, following oral (8 g kg-1 bodyweight) administration of tannic acid, liver necrosis was not observed either histologically or detected biochemically, although transmission electron microscopy showed focal hepatocellular necrosis, steatosis and acicular crystal cleft formation. In sheep given tannic acid intraperitoneally (0.1 g kg-1 bodyweight), liver necrosis occurred and plasma sodium and glucose levels significantly (P < 0.05) decreased while packed cell volume and plasma aspartate aminotransferase, alkaline phosphatase, creatinine and bilirubin significantly (P < 0.01) rose. The results for blood-gas and acid-base determinations, blood haemoglobin and oxygenation showed significant increases in arterial blood methaemoglobin concentration (P < 0.05) and decreases in blood pH (P < 0.01) and oxyhaemoglobin concentration (P < 0.05) in sheep by 32 hours after oral dosing with 8 g of tannic acid kg-1 bodyweight. In sheep given tannic acid intraperitoneally, methaemoglobinaemia was not detected, but metabolic acidosis with a compensatory respiratory alkalosis occurred. Thus, it would appear that although tannic acid is hepatotoxic when given orally to mice or intraperitoneally to sheep, it does not produce renal or significant hepatic injury in sheep when given orally, but rather causes metabolic acidosis and methaemoglobinaemia.

Age-related incidence of spontaneous non-neoplastic lesions in a colony of Han:AURA hamsters.

In toxicologic testing or experimental studies using animals, an adequate knowledge of spontaneously occurring lesions is required. 144 male and 184 female untreated Syrian golden hamsters (strain Han:AURA) were kept for life under standard laboratory conditions and an investigation of non-neoplastic lesions in relationship to the lifespan was performed. The average lifespan of the males was 106 weeks and that of the female hamsters 97 weeks. While cartilage degeneration of the sternum and fatty degeneration of the femoral bone marrow occurred already in the first half of life with high incidence, the majority of lesions were observed in the second half. The most frequent non-neoplastic changes in various organs were fatty change, calcification, cystic change, hyperplasia and amyloidosis. Such spontaneous lesions were discussed in connection with the same alterations which can also be induced by chemical or hormonal agents.

Analysis of the epitopes on staphylococcal enterotoxin A responsible for emetic activity.

To identify which region of staphylococcal enterotoxin A (SEA) is responsible for the emetic activity, twelve synthetic peptides corresponding to the entire SEA amino acid sequence and their respective anti-peptide antibodies were prepared and tested. The anti-peptide antibodies were tested for neutralization of SEA-induced emesis in Suncus murinus (Shrew mouse). The results indicate that SEA-induced emesis was neutralized by the mixture of three anti-peptide antibodies to A-7 (corresponding to amino acid residues 121-140), A-8 (141-160) and A-9 (160-180). These findings suggest that the regions corresponding to residues 121-180 may be the epitopes responsible for the emetic activity of SEA.

Changes in quantitative profile of extracellular matrix components in the kidneys of rats with adriamycin-induced nephropathy.

Extracellular matrix components (ECMs) in histological sections of the kidney cortex from the rats with adriamycin (ADR)-induced nephropathy (5 mg/kg, i.v.) were quantified by an immunohistochemical micromethod. Changes in kidney histopathology and urine and blood biochemistry were investigated. Enlarged kidneys were granular on the surface and pale in color in ADR-treated rats, and these rats had kidneys with glomeruli with expanded mesangial area and with capillary aneurysm. Severe albuminuria, hypoalbuminemia, hypercholesterolemia and disorders in other nephrotic parameters were observed in ADR-treated rats. Type I and IV collagens, fibronectin and laminin contents in the renal cortex of ADR-treated rats at 10 weeks were 329, 317, 263 and 295%, respectively, higher than in each vehicle control, and those at 28 weeks were 1,211, 930, 1,057 and 1,012%, respectively. The glomerular sclerotic abnormalities progressed in a time-dependent manner. Moreover, there was a strong correlation between the ECM levels and serum creatinine and blood urea nitrogen levels. In conclusion, microquantification provided useful information for accurate diagnosis and prognosis of nephrotic lesions and is a good tool to assess the advancement of renal disorders in patients with nephropathy.