Pre-ovulatory temperature gradients within mammalian ovaries: a review

The existence of a temperature gradient between the testis and deep body temperature has been accepted for many years. It is based on two simultaneous principles: cooling of the testis through the scrotal wall and transfer of heat between the testicular blood vessels. The ovary is positioned in the abdomen; a temperature difference parallel to the male system therefore seems less likely. However, the temperature of large follicles has been found to be 0.5 to 1.5 degrees C cooler than the ovarian stroma in rabbits, pigs and, probably, women. The temperature difference seems to be based on a heat-consuming process in the expanding follicullar fluid, and a local transfer of heat between intra-ovarian blood vessels. The reason for the temperature gradient is not yet known; one may speculate of a common reason for the cooling of the gamete in male and female.     

Pharmacokinetics and i.m. bioavailability of ceftiofur in Asian elephants (Elephas maximus)

Captive elephants are prone to infections of the feet, lungs, and skin. Often treatment regimens are established with no pharmacokinetic data on the agents being used for treatment in these species. A pharmacokinetic study using ceftiofur (1.1 mg/kg) was conducted in four adult female captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Elephants were given both i.v. and i.m. administrations in a complete crossover design with a 3-week washout period between treatments. Blood samples were collected prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 h postadministration. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometric (LC/MS) assay. Plasma concentrations for the i.m. samples were lower than expected. The mean C(max) following i.m. administration was 1.63 microg/mL with a corresponding T(max) of 0.55 h. Following i.v. administration, the median V(d(ss)) was 0.51 L/kg and a median Cl(p) of 0.069 L/kg/h. Mean i.m. bioavailability was 19%. The results indicate that ceftiofur used at 1.1 mg/kg i.m. could be useful in elephants when given two to three times a day or alternatively, 1.1 mg/kg i.v. once daily, depending upon the MIC of the pathogen.     

Multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine in the cat

The purpose of this study was to evaluate the multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine alone and in combination in cats. Seven healthy cats were included in this randomized-crossover study. The cats were assigned to groups designated to receive cimetidine alone (15 mg/kg, p.o., q12 h), piroxicam alone (0.3 mg/kg, p.o., q24 h), and piroxicam combined with cimetidine (both at aforementioned doses). The cats were dosed for 10 days followed by at least a 2-week washout period between trials. Serial blood samples were collected following the first and last doses and analyzed utilizing a high-performance liquid chromatography with mass spectrometry detection (LC/MS) assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Endoscopic evaluation of the gastric mucosa was performed and serum urea nitrogen (SUN), creatinine, alkaline phosphatase (ALP), and alanine transaminase (ALT) activities were evaluated. There were not a clinically relevant difference between the pharmacokinetic parameters of piroxicam administered alone or in combination with cimetidine after either the first or last dose. Gastric ulcers were not observed in any cats although gastric erosions were. The SUN, creatinine, ALP, and ALT activities remained within reference ranges for all cats. It appears that once daily, short-term use of piroxicam alone and in combination with cimetidine in cats is relatively safe based on the parameters evaluated in this study. However, further studies are necessary to determine the long-term gastrointestinal safety of piroxicam.     

Effects of CD28 blockade on subsets of naïve T cells in cats

OBJECTIVE: To determine whether human CTLA4-Ig ([hu]CTLA4-Ig) inhibits costimulation-dependent lymphocyte proliferation in vitro, compare the effects of (hu)CTLA4-Ig with cyclosporine and steroids on CD4+ and CD8+ T-cell lymphocyte proliferation, and determine whether memory T-cell function remains intact in the presence of (hu)CTLA4-Ig. ANIMALS: 29 cats. PROCEDURE: Peripheral blood mononuclear cells (PBMCs) were stimulated with concanavalin A (costimulation-dependent mitogen) or phorbol 12-myristate 13-acetate and ionomycin (costimulation independent mitogens) alone or in the presence of (hu)CTLA4-Ig, cyclosporine, or dexamethasone; effects of these treatments on lymphocyte proliferation were assessed by incorporation of thymidine labeled with tritium or flow cytometry. Antigen-specific proliferation was determined by stimulating PBMCs from 2 healthy cats seropositive for Toxoplasma gondii with soluble Toxoplasma antigen alone or in the presence of (hu)CTLA4-Ig or cyclosporine. RESULTS: (hu)CTLA4-Ig inhibited costimulation-dependent lymphocyte proliferation in vitro but had no effect on costimulation-independent lymphocyte proliferation. Compared with mitogen alone, (hu)CTLA4-Ig caused a significant decrease in responder frequency and proliferative capacity of CD4+ T cells; however, the effect on CD8+ T cells was not significant. Cyclosporine alone or with dexamethasone had a significantly greater suppressive effect on responder frequency and proliferative capacity of CD4+ and CD8+ T cells, compared with (hu)CTLA4-Ig. Compared with cyclosporine, (hu)CTLA4-Ig appeared to have a sparing effect on antigen-specific proliferation of memory CD4+ and CD8+ T cells. CONCLUSIONS AND CLINICAL RELEVANCE: (hu)CTLA4-Ig selectively inhibited costimulation-dependent proliferation of lymphocytes in vitro and had a sparing effect on antigen-specific proliferation of memory cells. The specificity of its mechanism of action suggests that (hu)CTLA4-Ig may prevent allograft rejection but leave memory responses to previously encountered antigens intact.