Pharmacokinetics of clomipramine in dogs following single-dose intravenous and oral administration

OBJECTIVE: To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose. ANIMALS: 6 male and 6 female Beagles. PROCEDURES: Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. RESULTS: Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.     

"Coulomb Staircase" at Room Temperature in a Self-Assembled Molecular Nanostructure

Double-ended aryl dithiols [alpha,alpha'-xylyldithiol (XYL) and 4,4'-biphenyldithiol] formed self-assembled monolayers (SAMs) on gold(111) substrates and were used to tether nanometer-sized gold clusters deposited from a cluster beam. An ultrahigh-vacuum scanning tunneling microscope was used to image these nanostructures and to measure their current-voltage characteristics as a function of the separation between the probe tip and the metal cluster. At room temperature, when the tip was positioned over a cluster bonded to the XYL SAM, the current-voltage data showed "Coulomb staircase" behavior. These data are in good agreement with semiclassical predictions for correlated single-electron tunneling and permit estimation of the electrical resistance of a single XYL molecule (approximately18 ± 12 megohms).     

Assessment of home-based processing methods to reduce the phytate content and phytate/zinc molar ratio of white maize (Zea mays)

Various methods of processing maize suitable for household use in rural Malawi, Central Africa, were investigated for their ability to reduce its phytate content and phytate/zinc molar ratio. These methods included fermentation, germination, and soaking. Penta- and hexainositol phosphates were measured by HPLC, and zinc was measured by atomic absorption spectrophotometry. Natural lactic fermentation of maize flour slurries resulted in 88% phytate retention compared to unprocessed, unrefined maize flour porridges, whereas lower phytate retention was observed when a starter culture (61%) or germinated flour (71%) was also used. Fermentation of cooked maize flour porridges with germinated flour added resulted in 54-85% retention of phytate compared to controls. Soaking maize flour or pounded maize and decanting excess water resulted in 43 and 49% retention of phytate, respectively. The latter soaking procedures were simple and effective and were suitable for household use in rural Malawian communities.     

EFFICACY AND TOXICITY OF AN ACCELERATED HYPOFRACTIONATED RADIATION THERAPY PROTOCOL IN CATS WITH ORAL SQUAMOUS CELL CARCINOMA

Squamous cell carcinoma (SCC) is the most common feline oral tumor. Standard radiation protocols have been reported to achieve tumor control durations of 1.5–5.5 months (45–165 days). The purpose of this study was to describe the efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral SCC. Twenty‐one cats with histologically confirmed oral SCC and T1‐3N0M0 were treated with 10 once‐daily fractions (Monday–Friday) of 4.8 Gy. Seventeen cats had macroscopic disease and four were microscopic after incomplete excision. Acute toxicity consisted of grade 2 mucositis in all cats and this was effectively managed using esophageal or gastric tube feeding, pain medication, and antibiotics. Late toxicity effects for cats with available follow‐up data included alopecia (4 cats), leukotricia (6), tongue ulceration (1), and oronasal fistula (1). Response could be assessed in 17 cats (seven complete response and five partial response). Four cats (19%) developed metastatic disease without evidence of local progression. The median progression‐free survival (PFS) was 105 days (1 year PFS of 23%), median local progression‐free survival (LPFS) was 219 days (1 year LPFS of 41%), and median overall survival (OS) was 174 days (1 year OS of 29%). Only tumor stage was prognostic, with T1 having a median PFS of 590 days. Findings indicated that this accelerated hypofractionated radiation therapy protocol was well tolerated in cats with oral SCC, with manageable adverse events. Tumor response was observed in most cats and long tumor control durations were achieved in some cats.     

Longevity of Mycobacterium bovis in brushtail possum (Trichosurus vulpecula) carcasses,and contact rates between possums and carcasses

Abstract

AIM: To determine, for a variety of environmental conditions, how long Mycobacterium bovis might remain viable inside the carcass of a brushtail possum (Trichosurus vulpecula) that died of bovine tuberculosis (Tb), and to measure the rate of contact between free-ranging possums and possum carcasses.

METHODS: Lesions of M. bovis were simulated by inoculating excised spleens weighing 0.5–1 g with 0.2 mL liquid culture containing approximately 5 x 10⁷ cfu M. bovis/mL. Simulated lesions were inserted into possum carcasses (n=48) at the peripheral lymph nodes. Carcasses were placed in the field at two sites (a tussock grassland and a podocarp-broadleaved forest site) and in two seasons (summer and winter) for up to 62 days. Survival rates of M. bovis were estimated by sampling the simulated lesions over time, and culturing the recovered lesion to determine if any viable M. bovis bacteria were present.

The time taken for a free-ranging possum to first encounter a dead possum in its home range was estimated by live-trapping possums and fitting them with proximity loggers (n=13). A ‘contact’ was recorded if these possums came within 40–50 cm of proximity loggers fitted to possum carcasses.

RESULTS: There were strong seasonal and site effects in the survival rate of M. bovis in possum carcasses. In the grassland habitat, no viable bacilli were cultured from any carcass after 3 days in summer, whereas in winter all samples were culture-positive for the first 20 days, and some were still positive after 27 days. The survival rates for forest habitat were intermediate between the results for grassland, and there were no culture-positive carcasses after 9 days in summer or 27 days in winter.

In summer, infected carcasses (n=6) were first encountered by possums a mean 1.9 (range 0.4–6.7) days after placement.

CONCLUSIONS: Possum carcasses were contacted by free-ranging possums within the period that viable M. bovis were shown to survive in a carcass. The risk of such infection is likely to be most significant in winter or in areas with microhabitats where the survival of M. bovis is high. However, the generally low survival rate of M. bovis in possum carcasses and the low frequency of possum-to-carcass contacts indicate this route of transmission alone could not maintain Tb in a possum population.     

A Case of Successful Pregnancy in a Ewe with Uterus Didelphys

Uterus didelphys is a rare congenital abnormality of the reproductive tract. Although it occurs in various species, there are no published reports describing pregnancy outcome in association with this abnormality. Herein we describe a case of successful unilateral singleton pregnancy in a ewe incidentally found to have uterus didelphys during the course of a biomedical research study. The pregnancy was established using assisted reproductive techniques and interrupted in late gestation, at which point the abnormality was identified. Serial ultrasound assessment of foetal biometry revealed a normal foetal growth trajectory. Despite a 45% reduction in placentome number, total placentome weight was near normal secondary to compensatory placentome growth and development. To our knowledge, this is the first detailed report of normal foetal growth in an animal with uterus didelphys and illustrates the ability of the ovine placenta to adapt to a reduced number of placentomes and maintain foetal nutrient supply.     

Pleistocene collapse of the west antarctic ice sheet

Some glacial sediment samples recovered from beneath the West Antarctic ice sheet at ice stream B contain Quaternary diatoms and up to 10(8) atoms of beryllium-10 per gram. Other samples contain no Quaternary diatoms and only background levels of beryllium-10 (less than 10(6) atoms per gram). The occurrence of young diatoms and high concentrations of beryllium-10 beneath grounded ice indicates that the Ross Embayment was an open marine environment after a late Pleistocene collapse of the marine ice sheet.     

A retrospective analysis of radiation therapy for the treatment of feline vaccine‐associated sarcoma*

We retrospectively evaluated predictive prognostic factors in 73 cats with vaccine‐associated sarcoma given postsurgical curative (n = 46, most with clean margins) or coarse fractionated radiotherapy (n = 27, most with either macroscopic disease or dirty margins). The former animals displayed a median survival of 43 months and a median progression free interval (PFI) of 37 months, the latter reached a median survival of 24 months and a median PFI of 10 months. In cats undergoing coarse fractionated therapy, factors predictive of a better outcome included lack of visible mass (n = 10) as opposed to macroscopic disease (n = 17, survival: 30 versus 7 months, P = 0.025; PFI: 20 versus 4 months, P = 0.01), adjuvant chemotherapy for gross disease (n = 5/17, survival: 29 versus 5 months, P = 0.04) and a smaller number of surgeries preceding radiation therapy (coeff = 0.41, P = 0.03). The Ki67 index was not predictive for survival. We concluded that postsurgical curative and coarse fractionated radiotherapy are effective legitimate options for managing vaccine‐associated sarcomas.     

Effects of organic manure and chemical fertilizer on soil fertility and productivity of plant and ratoon crops of sugarcane

A long-term field experiment was initiated in November, 1967 at Research Area of Department of Soil Science to study the response of nitrogen to pearl millet-wheat cropping system at various doses and modes of farmyard manure application. The soil organic carbon increased with farmyard manure application and ranged from 0.68% in control to 1.82% in the plot receiving the highest annual dose (90 Mg ha^?1) of farmyard manure. To study the contribution of farmyard manure on the productivity of pearl millet and wheat crops, the constants (intercept and slope) were determined between the grain yield of pearl millet and wheat crops with increasing dose of fertilizer nitrogen. Another linear regression was fitted between the intercept of the linear model and the soil organic carbon content. It has been observed that with each unit increase in the soil organic carbon, the productivity of pearl millet increased by 273 kg ha^?1 and that of wheat by 1591 kg ha^?1. The regression between the slope and soil organic carbon was linear in case of pearl millet (R² 0.49) but in case of wheat there was no relationship.