Biomedical subjects

T Whittem

Publications and source records attributed to T Whittem.

24 records · Page 2Linked to original sources

PubMed1995

The dose-related effects of phenylbutazone and a methylprednisolone acetate formulation (Depo-Medrol) on cultured explants of equine carpal articular cartilage.

The dose-related effects of phenylbutazone and Depo-Medrol on chondrocyte viability and chondrocyte-mediated synthesis and depletion of proteoglycans were investigated using cultured explants of equine middle carpal joint articular cartilage. Explants from 12 horses (941 x 3 mm diameter) were cultured for a total of 5 days, which included 3 days' exposure to either phenylbutazone (0, 2, 20, 200 or 2000 micrograms/mL) or Depo-Medrol (0, 20, 200 or 2000 micrograms/mL). For each explant, amino sugar content was used as a measure of proteoglycan content, 35S incorporation as a measure of the rate of proteoglycan synthesis and the number of pyknotic nuclei as a measure of cell death. During culture, control explants remained metabolically active and viable but suffered a net loss of proteoglycans. Proteoglycan loss was reduced by the presence of either phenylbutazone or Depo-Medrol. This effect was significant at clinically relevant concentrations of phenylbutazone (2-20 micrograms/mL), but not Depo-Medrol (20-200 micrograms/mL). Depo-Medrol caused a dose-dependent suppression of proteoglycan synthesis at all concentrations, but chondrocyte viability was affected only at the 2000 micrograms/mL dose. Phenylbutazone affected proteoglycan synthesis and cell viability only at the 2000 micrograms/mL concentration. At all concentrations, the anticatabolic effects of each drug influenced the proteoglycan content of the explants far more than did any antianabolic or cytotoxic drug effect. The results suggest that the therapeutic potential of both phenylbutazone and Depo-Medrol may not be restricted to their anti-inflammatory effects on the soft tissues of the joint.

Animals↗

PubMed1993

Kanamycin concentrations in synovial fluid after intramuscular administration in the horse.

Six adult ponies were injected in the same intramuscular site with kanamycin sulphate (10 mg/kg). Two hours later, arthrocenteses of the right metacarpophalangeal, radio-carpal, intercarpal, tibio-tarsal and metatarsophalangeal joints were performed within 3 minutes. Arthrocenteses of the same joints on the left side were conducted 5 hours later. When expressed as a percentage of plasma drug concentration, differences in synovial fluid drug concentration between the joints sampled at 2 and 5 hours after injection were not detected.

Animals↗

PubMed1992

Poly-L-aspartic acid does but triiodothyronine does not protect against gentamicin-induced cytotoxicity in the porcine kidney cell line LLC-PK1.

This study investigated the protective effect of thyroid hormone and poly-L-aspartic acid (PAA) in an in vitro model of gentamicin nephrotoxicity. LLC-PK1 porcine renal cells were grown in Medium 199 supplemented with either fetal bovine serum or thyroid hormone-depleted fetal bovine serum. After a preincubation with or without 30 nM L-triiodothyronine for 3 days, or 0.1 mM PAA for 1 hr, cells were coincubated with 1 mM gentamicin for an additional 3 days. Determinations were made of the following indicators of cell damage and/or viability: the numbers of detached dead cells, the total lactate dehydrogenase activity and its percentage release and gamma-glutamyl transpeptidase activity. Preincubation with L-triiodothyronine did not protect from gentamicin-induced cell death but did reduce cellular accumulation of gentamicin (3.2 +/- 0.8 micrograms/mg of protein vs. 5.2 +/- 1.8 micrograms/mg of protein in controls; P less than .05). In contrast, preincubation with 0.1 mM PAA decreased gentamicin-induced cell death (gentamicin: 685 +/- 416% of control dead cells and 487 +/- 48% of control lactate dehydrogenase release; PAA + gentamicin: 164 +/- 63% of control dead cells and 257 +/- 85% of control lactate dehydrogenase release; P less than .05) but failed to attenuate inhibition by gentamicin of gamma-glutamyl transpeptidase activity (gentamicin: 69 +/- 7% of control; PAA+gentamicin: 76 +/- 3% of control) and failed to alter cellular gentamicin levels. Protection against gentamicin nephrotoxicity by L-triiodothyronine was not demonstrated in LLC-PK1 cells, indicating that its protective effect in vivo is likely due to a systemic effect of the hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1990

Kinetics of triiodothyronine dissociation from bovine serum albumin: modification of the resin capture method with subsequent computer modeling.

There has been much debate about the mechanism by which thyroid hormone leaves the circulation and enters cells. Critical to the development of theoretical models of thyroid hormone uptake are precise estimates of the kinetic constants describing the reversible binding of the hormone to its binding proteins. A resin capture method was modified to permit the collection of dissociation data at intervals of 0.12 sec. Columns (30 X 0.6 cm) of Amberlite IRA 400 anion exchange resin were perfused at 30 ml/min with 3.5% dextran in modified Krebs Henseleit bicarbonate buffer at pH 7.4 and 37 C. Injection of [125I]triiodothyronine (T3) tracer in BSA-free medium established the rate constant for resin capture of free T3 in this system: kRes = 0.89 +/- 0.04 sec-1 (mean +/- SD, n = 4). [125I]T3 preequilibrated with BSA was infused to achieve final BSA concentrations of 2.3, 48, 120, 290, 507, and 725 microM, yielding apparent uptake rate constants (kapp) of 0.77 +/- 0.12 (n = 6), 0.23 +/- 0.01 (n = 4), 0.17 +/- 0.04 (n = 4), 0.057 +/- 0.005 (n = 4), 0.039 +/- 0.003 (n = 4), 0.020 +/- 0.002 (n = 4) sec-1 (SSE less than 9.4 X 10(-2), respectively, when fitted by nonlinear methods. Solving the equation kapp = kRes/(1 + [BSA]/KD') gave KD' = 1.80 +/- 0.07 X 10(-5) M (r2 = 0.96, P less than 0.001, n = 26) where KD' is the apparent or flow equilibrium constant. In a further experiment T3:BSA reassociation was eliminated by BSA dilution. This resulted in determination of the dissociation rate constant kdissoc = 0.63 +/- 0.16 sec-1 (n = 8) and therefore, the association rate constant kassoc = 3.5 X 10(4) M-1 sec-1. Mathematical modeling predicted that 14.4 microM BSA would decrease the rate of T3 uptake by the resin system by 65%. The free fraction of T3 during a single pass extraction was predicted to be greater than that measured by equilibrium dialysis, suggesting that dissociation of T3 from BSA is favored in the flux model relative to that measured at equilibrium in vitro.

Animals↗

PubMedDate not supplied

Inflammatory response to intramuscular implantation of polyacrylonitrile ultrafiltration probes in sheep.

Polyacrylonitrile is used in the manufacture of dialysis membranes. These membranes are fundamental to the functioning of implantable probes for microdialysis and ultrafiltration sampling of tissue fluids. Although in vivo experimentation using polyacrylonitrile has been reported to cause little inflammatory response when implanted subcutaneously, such information is not available for intramuscular implantation in sheep. The procaine and benzathine salts of penicillin are formulated for intramuscular injection. These salts of penicillin or the formulation excipients may cause inflammatory reactions. Use of polyacrylonitrile probes to draw samples from sites at which these formulations have been injected may be compromised by inflammation or direct interaction between formulation excipients and the dialysis membrane. The aim of this project was to describe tissue responses to intramuscular implantation of polyacrylonitrile in the presence and absence of either procaine or procaine plus benzathine salts of penicillin G. Each of 20 normal sheep was implanted with two ultrafiltration probes, one at the site of an injection of procaine or benzathine plus procaine penicillin G. Similar injections were also made at remote intramuscular sites. After 8, 9, and 11 days of the experiment, sheep were killed and the injection and implantation site muscle were excised and prepared for histopathological examination. The implantation of the probe alone caused greater inflammatory response than the injection of procaine or procaine plus benzathine penicillin G at remote intramuscular sites. The histopathological lesions were greatest where the implantation site was coupled with the injection of either formulation of penicillin G. Polyacrylonitrile may not be a suitable dialysis membrane material for intramuscular implantation in sheep.

Acrylic Resins↗

PubMedDate not supplied

Gastric emptying and intestinal transit times of radiopaque markers in cats fed a high-fiber diet with and without low-dose intravenous diazepam.

Reference ranges for gastric emptying time (GET), small intestinal transit time (SITT), and colonic transit time of 1.5-mm and 5-mm radiopaque markers in healthy cats fed a high-fiber meal were determined, and the influence of low-dose diazepam intravenous injection on the gastrointestinal transit of the markers was examined. The mean GETs and SITTs, and the mean residence times (MRTs) and geometric centers (GCs) of markers in the colon were determined. The effect of intravenous diazepam injection and marker size on these parameters was examined. Diazepam injection had no significant influence on gastrointestinal transit. The GETs of the 1.5-mm markers were significantly more rapid than those of the 5.0-mm markers. There were no significant differences between the SITTs or GCs of the 1.5-mm and 5.0-mm markers. Reference values were developed for GET, SITT, and colonic transit of radiopaque markers for cats fed a high-fiber meal. Diazepam injection had no effect on these parameters.

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