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Biomedical subjects

M V Crisman

Publications and source records attributed to M V Crisman.

At least 19 recordsLinked to original sources
PubMed2005

Modulation of equine articular chondrocyte messenger RNA levels following brief exposures to recombinant equine interleukin-1beta.

The effect of recombinant equine IL-1beta (EqIL-1beta) on steady-state mRNA levels of equine articular chondrocytes in high-density monolayer culture was investigated using a customized cDNA array analysis. Total RNA samples isolated from chondrocytes cultured in media alone or with the addition of 1 ng/ml EqIL-1beta for 1-, 3-, and 6-h durations of exposure were reverse transcribed, radiolabeled, and hybridized to a customized 380-target cDNA array. Means of duplicate log base 2 transformed hybridization signals were normalized to equine glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mean signal intensities. Differentially expressed transcripts were identified using a two-stage mixed linear analysis of variance model (Statistical Analysis Software, Cary, NC). A time-dependent pattern was observed in the number of transcripts increased > or =two-fold in response to EqIL-1beta after 1, 3 and 6h (1, 2 and 109 transcripts, respectively). At 6 h of EqIL-1beta stimulation, signal intensities for 88 cDNA targets with purported function in processes related to cell cycle, intracellular signaling, transcription, translation, extracellular matrix turnover, and inflammation, as well as a number of cDNAs lacking homology to previously reported cDNA sequences, were increased >two-fold and were associated with p<0.05. Principal component analysis identified a vector component ( approximately 10% of the total variation) corresponding to a potential EqIL-1beta co-regulation of cell cycle associated gene transcription. These results support and expand our existing comprehension of the complex role of IL-1 in modulated chondrocyte gene expression and suggest the involvement of specific target gene up-regulation and activation of downstream inflammatory cascade mediators. This study adds to the current understanding of the molecular events associated with an IL-1 induced inflammation and pathobiologic processes that may be associated with the development of equine osteoarthritis.

Animals↗
PubMed2005

Detection of differentially regulated genes in ischaemic equine intestinal mucosa.

REASONS FOR PERFORMING STUDY: Colic is a serious disease syndrome in horses. Much of the mortality is associated with ischaemic-injured intestine during strangulating obstruction, yet there is limited understanding of the associated molecular events. Identification of differentially expressed genes during ischaemic injury should expand our understanding of colic and may lead to novel targeted therapeutic approaches in the future. OBJECTIVE: To isolate and identify differentially expressed genes in equine jejunum following a 2 h ischaemic event compared to normally perfused jejunum. METHODS: Suppressive subtractive hybridisation was used to clone genes that are differentially expressed in equine jejunum injured by 2 h of complete ischaemia as compared to time-matched control jejunal tissues. Expression of selected clones was further evaluated by northern blot analysis. RESULTS: Of the 384 clones selected, 157 were confirmed to possess cDNAs corresponding differentially expressed genes by dot blot analysis. Two genes, fatty acid binding protein 2 and calcium-activated chloride channel 4 were further confirmed to be differentially expressed by northern blot analysis. CONCLUSIONS: Suppressive subtractive hybridisation can be used to detect changes in expression of a broad array of genes, as confirmed by northern blot analysis of selected genes. POTENTIAL RELEVANCE: These initial results have identified a pool of equine intestinal epithelial genes that are differentially expressed following a 2 h ischaemic event. In particular, genes indicative of deranged metabolic activity and those potentially involved in early repair events were identified and may ultimately provide clues as to the nature of epithelial ischaemic injury in horses.

Animals↗
PubMed2000

Immunoglobulin isotypes in sera and nasal mucosal secretions and their neonatal transfer and distribution in horses.

OBJECTIVE: To determine concentrations of IgA and IgG subclasses in serum, colostrum, milk, and nasal wash samples of adult horses and foals. ANIMALS: Seven 2-year-old Welsh ponies, 27 adult mixed-breed horses, and 5 Quarter Horse mares and their foals. PROCEDURE: Serum was obtained from ponies and adult horses. Colostrum and milk were obtained from mares and serum and nasal wash samples from their foals immediately after parturition and on days 1, 7, 14, 28, 42, and 63. Nasal wash samples were also obtained from 23 adult horses. Concentrations of immunoglobulins were determined by use of inhibition ELISA. To determine transfer of maternal isotypes to foals, concentrations in colostrum and milk were compared with those in foal serum. Serum half-lives of isotypes in foals were also determined. RESULTS: IgGb was the most abundant isotype in serum and colostrum from adult horses, whereas IgA was the predominant isotype in milk. The major isotype in nasal secretions of adult horses and foals > or = 28 days old was IgA, but IgGa and IgGb were the major isotypes in nasal secretions of foals < or = 14 days old. Serum half lives of IgGa, IgGb, IgG(T), and IgA in foals were 176, 32, 21, and 3.4 days, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The early immunoglobulin repertoire of neonatal foals comprised IgGa, IgG(T), and IgA; endogenous synthesis of IgGb could not be detected until 63 days after birth. The restricted repertoire of immunoglobulins in foals may influence humoral immune responses to vaccination.

Animals↗
PubMed2000

Comparison of equine amnion and a nonadherent wound dressing material for bandaging pinch-grafted wounds in ponies.

OBJECTIVE: To evaluate healing of pinch-grafted wounds on the distal aspect of the limbs of ponies bandaged with equine amnion or a standard nonadherent wound dressing material. ANIMALS: 6 ponies. PROCEDURE: A 2.5x2.5-cm full-thickness section of skin was removed from the dorsal aspect of each limb at the midpoint of the metacarpus or metatarsus. Six days later, wounds were grafted with partial-thickness pinch grafts. Half the wounds were bandaged with amnion, and the other half were bandaged with a nonadherent dressing. Bandages were changed every 3 days until wound healing was complete. At each bandage change, numbers of grafts lost were recorded, and wounds were measured. RESULTS: Percentage of grafts lost from wounds bandaged with amnion was not significantly different from percentage lost from wounds bandaged with the nonadherent dressing. Median healing time for wounds bandaged with amnion (30 days) was significantly less than median healing time for wounds bandaged with the nonadherent dressing (39 days). All wounds were healed by day 45. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that amnion can be used for bandaging pinch-grafted wounds on the distal aspect of the limbs of ponies.

Amnion↗
PubMed1998

Neoplasia of the respiratory tract.

Tumors of the equine respiratory tract occur infrequently. An accurate diagnosis of neoplasia of the respiratory tract is critical because the prognosis is usually grave. The clinical signs and diagnostic procedures are discussed for tumors of the nasal and paranasal sinuses, nasopharynx/larynx, guttural pouch and thorax including lung, pleura, and thymus.

Animals↗
PubMed1998

Pharmacokinetics of ketoprofen in healthy foals less than twenty-four hours old.

OBJECTIVE: To determine pharmacokinetic variables that describe disposition of ketoprofen after its i.v. administration to foals < 24 hours old. ANIMALS: 6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration. PROCEDURE: Ketoprofen was administered i.v. to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at -70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis. RESULTS: Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours. CLINICAL RELEVANCE: Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity.

Aging↗
PubMed1996

In vitro cytotoxic activity of equine lymphocytes on equine herpesvirus-1 infected allogenic fibroblasts.

The objectives of this study were to: (1) develop a technique to analyze the in vitro cytotoxic activity of lymphocytes from adult horses against equine herpesvirus-1 (EHV-1) infected allogenic equine dermal fibroblasts (EDF); (2) evaluate the ability of a 72-h in vitro incubation with interleukin-2 (IL-2) to enhance the lymphocytic cytolytic activity against EHV-1 infected EDF; (3) compare the cytotoxic activity of lymphocytes isolated from pregnant mares and non-pregnant mares against EHV-1 infected EDF; (4) ascertain if any correlations existed between the percent cytotoxicity and percentage of lymphocytes phenotypically identified by five different mouse-anti-equine monoclonal antibodies; and (5) determine if any correlation existed between virus-neutralizing antibody titers and the percent cytotoxicity. Results of the study indicate that in vitro cytotoxic activity of equine lymphocytes against EHV-1 infected allogenic fibroblasts can be measured with a standard 4-h 51Cr release assay. This activity was enhanced by an in vitro incubation with IL-2. The cytolytic activity of freshly isolated lymphocytes was greater for non-pregnant than pregnant mares. However, after IL-2 stimulation the cytolytic activity was greater for lymphocytes from pregnant mares. A positive correlation was not detected between the percentage of phenotypically identified cells and the percent cytotoxicity, although several negative correlations were present. This suggests that the cytotoxic activity was either not mediated by any of the phenotypically identified cell populations or that the activity was

Animals↗
PubMed1996

Pharmacokinetics of flunixin meglumine in healthy foals less than twenty-four hours old.

OBJECTIVE: To determine pharmacokinetic variables that describe the disposition of flunixin after i.v. administration of flunixin meglumine to foals < 24 hours old. ANIMALS: 6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours). PROCEDURE: Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined intervals over a 48-hour period. Samples were centrifuged, and plasma was frozen at -70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by Akaike's information criterion analysis. RESULTS: Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance was significantly lower than that determined for older foals and adult horses. Volume of distribution was larger than that determined for adults. Mean plasma half-life for healthy foals < 24 hours old was 8.5 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals < 24 hours old, compared with adults. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to induce comparable therapeutic concentrations; longer dose intervals, on the basis of clinical response, would be necessary to avoid drug toxicity.

Aging↗
PubMed1993

Pharmacokinetic disposition of intravenous and oral pentoxifylline in horses.

The pharmacokinetics of pentoxifylline (P) and its alcohol metabolite I (MI) were determined after administration of intravenous pentoxifylline, sustained release pentoxifylline tablets (Trental), and crushed pentoxifylline tablets in corn syrup, to five healthy adult horses. Pharmacokinetics were evaluated in a model-independent manner. After intravenous administration, pentoxifylline was rapidly eliminated (mean residence time 1.09 +/- 0.67 h), had a large steady-state volume of distribution (2.81 +/- 1.16 l/kg), and high clearance (3.06 +/- 1.05 l/kg/h). Oral absorption of pentoxifylline from both dose forms varied considerably between individuals. Times to peak concentration ranged from 1-10 h for either dose form. There was no difference in relative bioavailability (F') between whole (0.98 +/- 0.30) and crushed Trental tablets. Ratios between areas under the curve (AUC) for pentoxifylline and MI were different following administration of oral versus intravenous doses. This finding suggests that route of administration may affect the metabolic profile of pentoxifylline. Given the extreme differences in absorption characteristics between individuals in this study, recommendations are not made as to appropriate dose, dose interval, or dose form for administration of pentoxifylline to horses.

Absorption↗
PubMed1993

Pharmacokinetics of phenylbutazone in neonatal foals.

Single doses (2.2 mg/kg of body weight) of phenylbutazone (PBZ) were administered IV to 6 neonatal horses (5 to 17 hours old at time of dosing). Plasma concentrations of PBZ and its metabolite oxyphenbutazone were monitored serially for 120 hours after drug administration. Pharmacokinetic variables were calculated, using 1- and 2-compartment open models. Descriptive equations from the best model for each foal were then used to derive model-independent variables describing PBZ disposition. Median volume of distribution at steady-state was 0.274 L/kg (range, 0.190 to 0.401 L/kg). Median terminal half-life was 7.4 (6.4 to 22.1) hours, and median total plasma clearance of PBZ for foals in this study was 0.018 L/kg/h (range, 0.013 to 0.038 L/kg/h). Volume of distribution was larger, half-life was longer, and total clearance was lower, compared with similar values reported for administration of PBZ to adult horses.

Aging↗
PubMed1992

Immunodeficiency associated with lymphosarcoma in a horse.

Immune system dysfunction and immunoglobulin deficiency was diagnosed in a 2-year-old horse with disseminated lymphosarcoma. Prolonged (35 days) parenteral nutrition was delivered to support the horse during a period in which immune function studies could be performed. Correction of nutritional compromise by use of parenteral nutrition did not correct the immunoglobulin deficiency, and results of lymphocyte phenotype testing did not indicate abnormal proportions of leukocytes. Lymphoblast transformation studies were suggestive of a circulating immunosuppressive factor in the horse's serum. Normal cell function was detected when the cells were stimulated in precolostral equine serum.

Animals↗
PubMed1992

Effects of transport on constituents of bronchoalveolar lavage fluid from horses.

To determine whether road transport affected pulmonary phagocyte activity, 7 healthy Thoroughbred horses were shipped 1,160 kilometers over 36 hours. Fluid collected by bronchoalveolar lavage (BAL) 12 hours, and 7 and 14 days after transport was analyzed. Results were compared to those from the same horses pre-transport, and 7 non-transported control horses that had BAL performed at the same times as the transported horses. Of cells recovered with BAL the percentage of viable pulmonary alveolar macrophages (PAMs) declined from 90.0 +/- 0.9% pre-transport to 80.0 +/- 3.7% by 2 weeks post transport. Although the ability of PAMs to inhibit the growth of Staphylococcus epidermidis had decreased by 2 weeks post-transport (19.2 +/- 3.7% vs. 8.8 +/- 2.3% inhibition) this could not be attributed to transport as a similar effect occurred in the control group. In contrast, the ability of PAMs to phagocytose sheep erythrocytes labelled with rabbit anti-erythrocyte antibodies increased from 74.0 +/- 8.1% to 92.3 +/- 1.5% by 12 hours post-transport. As all variables were unchanged or only mildly altered following transport, we conclude that this form of transport did not alter the PAM functions we assessed.

Albumins↗
PubMed1991

Inhibition of lymphocyte blastogenesis by whey.

Bovine whey samples were evaluated by use of lymphocyte-transformation tests to determine their effect on lymphocyte blastogenesis. Whey samples from mammary glands with clinical mastitis strongly inhibited DNA synthesis and blastogenesis in lymphocytes stimulated with mitogens or dividing because of bovine leukemia virus infection. Whey samples from apparently healthy glands either did not inhibit lymphocyte DNA synthesis or inhibited it to a lesser degree than did whey from mastitic glands. Degree of inhibition was dose-dependent. The molecules causing inhibition were noncytotoxic and underwent minimal binding to the lymphocytes. Inhibitory molecules were susceptible to various proteolytic and glycolytic enzymes, indicating a glycoprotein-like structure. Whey inhibited incorporation of thymidine if it was in the cell cultures during the early stages of stimulation. Incubation of lymphocytes in whey that inhibited thymidine incorporation did not affect DNA synthesis in subsequent culturing of the same cells without whey. Degree of inhibition was affected by the method of whey preparation.

Animals↗
PubMed1990

Lymphocyte blastogenesis inhibition by milk whey as an indicator of mastitis.

Sixty milk whey samples prepared from quarters of five cows with a history of mastitis were tested for their ability to inhibit DNA synthesis in mitogen-stimulated lymphocytes. The inhibitory activity was compared with milk SCC, electrical conductivity, pH, and the number of colony-forming bacteria in the milk. Milk whey contained factors that inhibited DNA synthesis in cultured lymphocytes. Inhibition of mitogen-induced DNA synthesis increased with the clinical severity of mastitis and with increased values of indirect indicators of mastitis. The increases in inhibition and electrical conductivity were delayed past the increases in SCC. Milk whey (10 microliters) from quarters with clinical mastitis and from quarters with SCC greater than 900,000 inhibited 96 to 100%, 84 to 100%, and 69 to 100% of DNA synthesis in 3-d cultures of lymphocytes stimulated with Concanavalin A, phytohemagglutinin P, and pokeweed mitogen, respectively. The numbers of colony-forming bacteria correlated least with the inhibitory activity.

Animals↗