Carprofen-induced oxidative stress in mitochondria of the colonic mucosa of the dog

The purpose of the study was to compare the conductance and mannitol permeability of canine colonic mucosa in response to carprofen or 2,4-dinitrophenol (DNP) with or without tempol pretreatment. Ten colonic mucosa sections per dog were mounted in Ussing chambers. Treatments were done in duplicate. Mucosa was exposed to carprofen (200 μg/mL) or DNP (0.25 mM), both with and without tempol (1 mM) pretreatment. Conductance was calculated every 15 min for 240 min. Mannitol flux was calculated over 3 consecutive 60-minute periods. Histology or electron microscopy was done after exposure. Conductance over time, mannitol flux, frequency of histologic categories, and electron microscopic changes were analyzed for treatment effects. The mean ± standard deviation (SD) conductance over time for carprofen or DNP-treated colons was not significantly different from control regardless of tempol pretreatment. Period 3 mannitol fluxes for carprofen and DNP-treated colon were not significantly different, but were greater than control. Period 3 mannitol flux for tempol + carprofen was significantly less than tempol + DNP-treated colon. Sloughing of cells and erosions were seen in the mucosa of carprofen-treated colon. Mitochondrial damage was seen more often in carprofen-treated than DNP-treated or control colon. Tempol pretreatment resulted in more ruptured mitochondria in the carprofen-treated colon; however, other mitochondrial changes were not significantly affected by tempol pretreatment in either carprofen or DNP treated colon. Treatment with carprofen or DNP increased the mannitol flux, but pretreatment with tempol mitigated the carprofen effect. It is apparent that structural mitochondrial damage occurs in the canine colonic mucosa after carprofen and DNP exposure.     

Efficacy of Medroxyprogesterone Acetate in Suppression of Estrus in Cycling Mares

The effects of compounded medroxyprogesterone acetate (MPA) on follicular activity and estrous behavior were evaluated. Eighteen cycling mares were assigned to one of three treatment groups. Mares in the MPA group (n = 6) were injected intramuscularly with 1,600 mg MPA (week 1), then 400 mg weekly for the next 5 weeks. Saline mares (n = 6) were injected intramuscularly weekly for 6 weeks. Altrenogest mares (n = 6) received 10 mL orally daily for 7 weeks. Mares were teased daily for 60 days and categorized as displaying estrous, diestrous, or neutral behavior. Transrectal ultrasound examinations were performed three times weekly, or daily when a 30-mm follicle was identified, until ovulation. Blood samples were harvested weekly for analysis of progesterone concentration and daily from days 14 to 23 for analysis of luteinizing hormone (LH) concentration. Mares treated with saline or MPA showed normal intervals of diestrus and estrus during the study. All altrenogest mares showed behavioral diestrus during treatment. All mares in the saline and MPA groups showed normal follicular development and ovulations. No altrenogest mares ovulated during treatment; four mares returned to estrus and resumed normal follicular development after treatment ceased. Progesterone analyses agreed with transrectal ultrasonographic ovarian activity for all mares. LH levels were lower for altrenogest-treated mares compared with MPA-treated and saline-treated mares during the treatment period. In conclusion, compounded MPA at dose rates and intervals used in this study was not effective in suppression of estrus, follicular development, or LH secretion in mares.     

PCR-AGE, automated and manual methods to identify Candida strains from veterinary sources: A comparative approach

The increasing incidence of candidiasis has drawn the attention of scientists and clinicians attempting to improve methods of studying Candida yeasts. PCR amplification followed by agarose gel electrophoresis (PCR-AGE) and the manual method (morphological characteristics, biochemical profiles and culturing on CHROMagar-Candida) and VITEK 2 automated method were used to test a total of 30 fungal strains from dog sources. The strains were obtained from cases of dermatitis, otitis externa and from the ears, oral mucosa, vaginal mucosa, prepuce and perianal region of clinically normal dogs. After identification as Candida yeasts by the manual method, the strains were analyzed using both VITEK and PCR-AGE methods. Isolates of C. parapsilosis ATCC 22019, C. krusei ATCC 6258 and C. albicans ATCC 10231 were included as controls. The universal primers ITS1, ITS3 and ITS4 were used in two independent PCR reactions. Of 30 yeast isolates, 3 isolates (Saccharomyces cerevisiae, C. rugosa and C. parapsilosis) that were incompletely identified by the manual method were identified with the PCR-AGE and VITEK methods. The results revealed a 96.7% and 86.7% concurrent identification between the PCR-AGE and VITEK methods versus the manual method, respectively. PCR-AGE showed a greater level of concordance with the manual method, besides being faster and more sensitive than the other methods examined, and is therefore indicated for routine diagnostic testing of Candida spp. strains from veterinary sources.     

Long-term monitoring of tropical bats for anthropogenic impact assessment: Gauging the statistical power to detect population change

Bats are ecologically important mammals in tropical ecosystems; however, their populations face numerous environmental threats related to climate change, habitat loss, fragmentation, hunting, and emerging diseases. Thus, there is a pressing need to develop and implement large-scale networks to monitor trends in bat populations over extended time periods. Using data from a range of Neotropical and Paleotropical bat assemblages, we assessed the ability for long-term monitoring programs to reliably detect temporal trends in species abundance. We explored the magnitude of within-site temporal variation in abundance and evaluated the statistical power of a suite of different sampling designs for several different bat species and ensembles. Despite pronounced temporal variation in abundance of most tropical bat species, power simulations suggest that long-term monitoring programs (?20 years) can detect population trends of 5% per year or more with adequate statistical power (?0.9). However, shorter monitoring programs (?10 years) have insufficient power for trend detection. Overall, our analyses demonstrate that a monitoring program extending over 20 years with four surveys conducted biennially on five plots per monitoring site would have the potential for detecting a 5% annual change in abundance for a suite of bat species from different ensembles. The likelihood of reaching adequate statistical power was sensitive to initial species abundance and the magnitude of count variation, stressing that only the most abundant species in an assemblage and those with generally low variation in abundance should be considered for detailed population monitoring.     

Cardiac myosin activation: a potential therapeutic approach for systolic heart failure

Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase cardiac contractility indirectly through signaling cascades but are limited by their mechanism-related adverse effects. To avoid these limitations, we previously developed omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin. Here, we show that it binds to the myosin catalytic domain and operates by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. Paradoxically, it inhibits adenosine 5'-triphosphate turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of contraction. Cardiac myosin activation may provide a new therapeutic approach for systolic heart failure.