Circadian rhythm of core body temperature in two laboratory mouse lines.

The circadian rhythm of core body temperature (Tb) was examined in two mouse lines bidirectionally selected for nest-building behavior (small (SNB) and big nest-builders (BNB)). This selection also resulted in more robust circadian organization of wheel-running activity in the SNB compared to the BNB mice. Tb was measured by an e-mitter implanted in the abdominal cavity. The circadian Tb rhythm of the SNB was more robust compared to the BNB regardless of whether the animals had access to a running wheel or not and regardless of the lighting conditions, i.e., 12 h:12 h light:dark (LD) cycle or constant dark (DD). Wheel-running activity rhythms of SNB were more robust in LD and DD compared to BNB. The amplitude of the circadian Tb rhythm increased significantly in response to wheel access in both mouse lines, but was not significantly different between the BNB and SNB. However, BNB tended to have lower amplitudes of circadian Tb rhythm in the absence of running wheels and a larger increase in the amplitude upon access to a running wheel compared to SNB. No differences were found in LD and DD between the lines in mean Tb and wheel-running activity levels. In addition, no differences between the two mouse lines were found in the free-running period of the Tb or wheel-running activity rhythms in DD. Overall, our findings reveal a more robust circadian phenotype of the SNB compared to the BNB.

Cryptosporidium inactivation by low-pressure UV in a water disinfection device.

Using animal infectivity tests, the authors evaluated a water disinfection device, UV Waterworks (UVW), for its ability to inactivate Cryptosporidium parvum oocysts. The UVW employs low-pressure, germicidal ultraviolet (UV) light, delivering a dose of approximately 120 millijoules per square centimeter (mJ/cm2) under ideal water conditions at a flow rate of 4 gallons per minute (gpm). Dechlorinated tap water containing live oocysts was passed through the UVW at 4 gpm. The oocysts were captured on a filter, separated from the filter, and concentrated into inocula--10 microliters (microL) each, containing between 10(3) and 10(7) oocysts--which were administered orally into 60 neonatal mice. After one week, the mice were killed, and sections of their terminal ilea were analyzed microscopically for signs of Cryptosporidium infection. In spite of the high dose of oocysts, none of the mice showed signs of infection. A process control run with the UV lamp off resulted in 95 percent infection at a dose of 10(3) oocysts per inoculum. The calculated reduction in oocyst infectivity from passage through UV Waterworks was at least 5.4 orders of magnitude. The authors conclude that exposure to low-pressure UV at 120 mJ/cm2 effectively disables Cryptosporidium.

Effects of dihydrotestosterone and estradiol on experimental IgA nephropathy induced by vomitoxin.

Ingestion of the trichothecene vomitoxin (VT) by mice induces effects that mimic the common human glomerulonephritis, IgA nephropathy (IgAN). These include elevation of serum IgA, IgA immune complexes, and mesangial IgA deposition. Based on previous observations that male mice are more prone to VT-induced IgAN, the effects of castration of male and female B6C3F1 mice and sex hormone supplementation on several immunopathologic indicators of the disease were compared. In the first study, castrated and intact male and female mice were fed control AIN-76A diet or the same diet containing 10 ppm VT for 12 weeks. At Week 12, all but the intact female group fed VT exhibited increased serum IgA, with castrated female mice having greater levels than intact females. When microscopic hematuria was used as an indicator of disease severity in intact VT-fed mice, erythrocyte counts for males exceeded those for females at weeks 4 and 12. VT-fed, castrated females exhibited greater hematuria than intact counterparts, whereas VT-fed, castrated males had lower urinary erythrocyte counts than intact counterparts. In a second study, castrated male and female mice were implanted with controlled release pellets of placebo, 5 alpha-dihydrotestosterone (DHT), or 17 beta-estradiol (E2) and then were fed either control diet or a 10 ppm VT diet for 8 weeks. Castrated male and female mice treated with VT and DHT pellet exhibited more severe hematuria, higher IgA levels, and greater mesangial IgA deposition than mice exposed to the same diet with placebo or E2 pellet at Week 8. While VT-fed animals with an E2 pellet exhibited greater hematuria and mesangial IgA deposition at Week 8 than the placebo groups, their IgA levels were not significantly elevated over those for VT-fed mice with a placebo pellet. Relative to two other pathologic markers for IgAN, the aforementioned effects in both studies were generally consistent with mesangial deposition of complement component C3 but not IgG. The results suggest that (1) enhanced male susceptibility to VT-induced IgAN may be related to modulation by the biologically active androgen DHT and (2) while castration of females increased severity of VT-induced IgAN, supplementation of castrated male or female mice with E2 did not reverse this effect but rather increased disease severity.

Role of gender and strain in vomitoxin-induced dysregulation of IgA production and IgA nephropathy in the mouse.

Prolonged dietary exposure of female B6C3F1 mice to the trichothecene vomitoxin results in hyperproduction of immunoglobulin A (IgA) with a concurrent immunopathology that mimics human IgA nephropathy. To assess the role of gender and strain in the mouse model, semipurified AIN-76A diet containing 25 ppm vomitoxin was fed to B6C3F1 male mice and to B6C3F1, BALB/c, C3H/HeN, C3H/HeJ, and C57BL/6 female mice for 8 wk, and immunopathologic indicators of IgA nephropathy were compared to mice fed clean diet. At the cessation of the experiment, all treatment groups weighed less than respective controls. Serum IgA was increased in male and female B6C3F1 mice as well as in C3H/HeJ, C57BL/6, and BALB/c female mice compared to corresponding controls. Serum IgA levels were two- to sixfold higher in B6C3F1 male treatment animals compared to female treatment groups from all strains. In contrast, at wk 8 serum IgG levels were unaffected or decreased, and serum IgM was decreased in all groups at wk 8. There was a trend toward increased IgA production by Peyer's patch (PP) lymphocytes isolated from treatment mice as compared to controls in all groups except the C3H/HeJ mice. Notably, IgA levels were 18-fold higher in B6C3F1 male treatment PP cultures than in B6C3F1 female treatment cultures. Hematuria was significantly greater in treatment mice than respective controls at both wk 4 and 8. Increased mesangial IgA deposition was also detectable in all treatment groups except the C57BL/6 mouse. The results suggested that the male B6C3F1 mouse and the five strains of female mice exhibited many of the immunopathologic effects found in IgA nephropathy and that IgA elevation was more marked in male B6C3F1 than female B6C3F1 mice.

Vomitoxin (deoxynivalenol)-induced IgA nephropathy in the B6C3F1 mouse: dose response and male predilection.

Oral exposure to the trichothecene vomitoxin (VT or deoxynivalenol) in mice induces marked elevation of total and autoreactive IgA, IgA immune complexes, and mesangial IgA deposition in a manner that is highly analogous to human IgA nephropathy. In this study, immunopathologic markers indicative of IgA nephropathy were compared in male and female B6C3F1 mice fed semipurified AIN-76A diet containing 0, 2, 10 or 25 ppm VT for 12 weeks. Males fed 10 and 25 ppm VT and females fed 25 ppm VT had increased serum IgA at 4 weeks. At week 8, male mice fed the minimal dose of 2 ppm VT and female mice fed 10 ppm also exhibited elevated serum IgA. IgA levels were consistently higher in treatment males than females with significant differences being observed in the 10-ppm dose group at 4 and 12 weeks. IgA coproantibodies were marginally increased (maximum of 2-fold) in mice of both genders fed 10 and 25 VT. At 8 and 12 weeks, serum IgM was depressed in male and female mice eating 10 and 25 ppm VT, whereas consistent effects on serum IgG or IgE were not observed. In similar fashion, male mice in the 2, 10 and 25 ppm VT groups exhibited microscopic hematuria as early as 4 weeks, whereas this occurred in females fed 10 and 25 ppm VT only at week 10 with urinary erythrocyte counts being lower than male counterparts. Mesangial deposition of IgA and C3 was significantly increased in males exposed to 2, 10 and 25 ppm VT and in females exposed to 10 and 25 ppm VT, with males exhibiting a greater deposition than corresponding females. Based on these immunological parameters, males appeared more susceptible than female mice to VT-induced IgA dysregulation and IgA nephropathy in terms of latency, threshold dose, and severity.