Biomedical subjects

Jeffrey Lakritz

Publications and source records attributed to Jeffrey Lakritz.

9 recordsLinked to original sources

PubMed2006

Pharmacokinetics of intravenously administered caffeine in healthy alpacas (Lama pacos) and llamas (Lama glama).

OBJECTIVE: To determine the pharmacokinetic disposition of IV administered caffeine in healthy Lama spp camelids. ANIMALS: 4 adult male alpacas and 4 adult female llamas. PROCEDURES: Caffeine (3 mg/kg) was administered as an IV bolus. Plasma caffeine concentrations were determined by use of high-performance liquid chromatography in 6 animals and by use of liquid chromatography-mass spectrometry in 2 llamas. RESULTS: Median elimination half-life was 11 hours (range, 9.3 to 29.8 hours) in alpacas and 16 hours (range, 5.4 to 17 hours) in llamas. The volume of distribution at steady state was 0.60 L/kg (range, 0.45 to 0.93 L/kg) in alpacas and 0.75 L/kg (range, 0.68 to 1.15 L/kg) in llamas. Total plasma clearance was 44 mL/h/kg (range, 24 to 56 mL/h/kg) in alpacas and 42 mL/h/kg (range, 30 to 109 mL/h/kg) in llamas. CONCLUSIONS AND CLINICAL RELEVANCE: High-performance liquid chromatography and liquid chromatography-mass spectrometry were suitable methods for determination of plasma caffeine concentrations in alpacas and llamas. Plasma caffeine concentration-time curves were best described by a 2-compartment model. Elimination half-lives, plasma clearance, volume of distribution at steady state, and mean residence time were not significantly different between alpacas and llamas. Intravenous administration of caffeine at a dose of 3 mg/kg did not induce clinical signs of excitement.

Animals↗

PubMed2005

Effect of prepartum intramammary treatment with pirlimycin hydrochloride on prevalence of early first-lactation mastitis in dairy heifers.

OBJECTIVE: To determine whether prepartum intramammary treatment of dairy heifers with pirlimycin hydrochloride would reduce the prevalence of intramammary infection (IMI) and lower the somatic cell count (SCC) during early lactation or improve 305-day mature equivalent milk production. DESIGN: Prospective clinical trial. ANIMALS: 183 Holstein-Friesian heifers (663 quarters) from 2 dairy farms. PROCEDURE: Heifers were assigned to treatment and control groups. Treated heifers received a single 50-mg dose of pirlimycin in each mammary quarter approximately 10 to 14 days prior to parturition. Prepartum mammary gland secretions and postpartum milk samples were collected for bacterial culture. Postpartum milk samples were also collected for determination of SCC or California mastitis testing and were tested for pirlimycin residues. Mature equivalent 305-day milk production data were recorded. RESULTS: Treated heifers in herd A had a higher overall cure rate, higher cure rates for IMI caused by coagulase-negative staphylococci (CNS) and Staphylococcus aureus, lower SCC, and lower prevalence of chronic IMI, compared with control heifers. Treated heifers in herd B had a higher overall cure rate and cure rate for IMI caused by CNS, compared with control heifers, but postpartum California mastitis test scores and prevalence of chronic IMI did not differ between groups. Mature equivalent 305-day milk production did not differ between herds or treatment groups. No pirlimycin residues were detected in postpartum milk samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that prepartum treatment of dairy heifers with pirlimycin may reduce the prevalence of early lactation IMI, particularly IMI caused by CNS, without causing pirlimycin residues in milk.

Animals↗

PubMed2004

Correlation of helical and incremental high-resolution thin-section computed tomographic and histomorphometric quantitative evaluation of an acute inflammatory response of lungs in dogs.

OBJECTIVE: To compare quantitative densitometric computed tomography (CT), morphometric, and histologic data of normal lungs in dogs with similar parameters obtained after induction of an acute inflammatory response and determine whether CT densitometry correlated with histopathologic changes. ANIMALS: 6 healthy adult dogs. PROCEDURE: After initial CT, 1 mL of 0.1 M hydrochloric acid (HCI) and 3 mL of autologous blood were instilled into the right middle (RM) and caudal segment of the left cranial (LCCd) lung lobes, respectively. Immediately and 24 hours after instillation, CT was repeated. At 24 hours, dogs were euthanatized and lungs were fixed and sampled for morphometric and histologic evaluation. The CT data were compared with lung morphology and morphometry by use of unpaired t tests. Comparison with lungs from control dogs was performed using Spearman rank correlation coefficients. RESULT: Mean Hounsfield units (HU) from control and baseline HU from experimental dogs were identical. Immediately after instillation of HCI or blood, there was increased attenuation in both lobes. Autologous blood initially induced severe changes that almost completely resolved at 24 hours; HCI induced severe changes at 24 hours. Significant increases in percentage of parenchymal airspace and alveolar diameter resulted in decreased surface area-to-volume ratio in lobes receiving HCl. Histologic scores were significantly higher in the RM lobe, compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: Computed tomography attenuation correlated well with histomorphometry and histologic findings in this model. Lung lesions after autologous blood were transient and of limited severity. Lesions induced by HCl were severe; alterations in morphometric and histologic parameters were reflected in CT attenuation measurements.

Acute-Phase Reaction↗

PubMed2004

Characterization of gelatinases in bronchoalveolar lavage fluid and gelatinases produced by alveolar macrophages isolated from healthy calves.

OBJECTIVE: To characterize gelatinases in bronchoalveolar lavage fluid (BALF) and gelatinases produced by alveolar macrophages of healthy calves. SAMPLE POPULATION: Samples of BALF and alveolar macrophages obtained from 20 healthy 2-month-old calves. PROCEDURE: BALF was examined by use of gelatin zymography and immunoblotting to detect gelatinases and tissue inhibitor of metalloproteinase (TIMP)-1 and -2. Cultured alveolar macrophages were stimulated with lipopolysaccharide (LPS), and conditioned medium was subjected to zymography. Alveolar macrophage RNA was used for reverse transcriptase-polymerase chain reaction assay of matrix metalloproteinases (MMPs), cyclooxygenase-2, and inducible nitric oxide synthase. RESULTS: Gelatinolytic activity in BALF was evident at 92 kd (14/20 calves; latent MMP-9) and 72 kd (18/20; latent MMP-2). Gelatinolytic activity was evident at 82 kd (10/20 calves; active MMP-9) and 62 kd (17/20; active MMP-2). Gelatinases were inhibited by metal chelators but not serine protease inhibitors. Immunoblotting of BALF protein and conditioned medium confirmed the MMP-2 and -9 proteins. Endogenous inhibitors (ie, TIMPs) were detected in BALF from all calves (TIMP-1) or BALF from only 4 calves (TIMP-2). Cultured alveolar macrophages expressed detectable amounts of MMP-9 mRNA but not MMP-2 mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: Healthy calves have detectable amounts of the gelatinases MMP-2 and -9 in BALF Endogenous inhibitors of MMPs were detected in BALF (ie, TIMP-1, all calves; TIMP-2, 4 calves). Lipopolysaccharide-stimulated alveolar macrophages express MMP-9 but not MMP-2 mRNA. The role of proteases in the pathogenesis of lung injury associated with pneumonia has yet to be determined.

Animals↗

PubMed2004

Evaluation of immune responses in horses immunized using a killed Sarcocystis neurona vaccine.

Clinically normal horses developed cellular immunity to Sarcocystis neurona following IM vaccination with a commercial killed S. neurona vaccine, as indicated by the development of measurable anti-S. neurona IgG antibodies and additional intradermal skin testing. Large-scale independent assessments of the vaccine's performance and safety are in progress under field conditions. The next step in the evaluation of this vaccine would be to attempt experimental challenge after a reproducible reliable equine model of S. neurona encephalitis has been established that allows for reisolation of the pathogen after challenge.

Animals↗

PubMed2003

Correlation of helical and incremental high-resolution thin-section computed tomographic imaging with histomorphometric quantitative evaluation of lungs in dogs.

OBJECTIVE: To develop protocols for helical computed tomography (CT) and axial high-resolution CT (HRCT) of lungs and correlate densitometric CT values with morphometric and histologic data for normal pulmonary tissue in dogs. ANIMALS: 8 healthy adult dogs. PROCEDURE: 2 dogs were used to establish a protocol for helical CT and HRCT of lungs. Six dogs were used to acquire densitometric CT data regarding normal lungs. After the dogs were euthanatized, their lungs were fixed and sampled for morphometric and histologic evaluation. Four CT acquisitions were compared by means of paired t tests. RESULTS: For normal lung tissue of dogs, mean densitometric CT value obtained during helical CT scans reconstructed in a sharp algorithm was -846 Hounsfield units. Values obtained via helical CT or HRCT acquisitions and reconstructed with sharp or standard algorithms did not differ significantly. Morphometric analysis was used to determine the proportion of lung parenchymal (82%) and non-parenchymal tissue (18%). Alveolar size, estimated by mean linear intercept, was approximately 172 microm, and alveolar surface area-to-volume ratio was 0.024 to 0.026 microm(-1). Histologic evaluation confirmed the presence of normal lung tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Correlation of densitometric CT data with morphometric and histologic findings and the establishment of helical CT and HRCT protocols were attained; clinical use of this information may facilitate investigation of pulmonary disease in dogs. Sharp helical CT acquisitions were preferred because of better lung parenchyma detail and rapid image acquisitions, compared with HRCT.

Animals↗

PubMed2002

Whole-blood concentrations of glutathione in cattle exposed to heat stress or a combination of heat stress and endophyte-infected tall fescue toxins in controlled environmental conditions.

OBJECTIVE: To determine whether cattle exposed to heat stress alone or heat stress while consuming endophyte-infected fescue (EIF) have lower whole-blood (WB) concentrations of glutathione (GSH). ANIMALS: 10 Simmental cows. PROCEDURE: Cows were sequentially exposed to thermoneutral (TN; 2 weeks; 18 C, 50% relative humidity [RH]), heat stress (HS; 2 weeks; alternating 4-hour intervals at 26 and 33 C; 50% RH), and heat stress while consuming EIF (10 microg of ergovaline/kg/d; 2 weeks, HS + EIF). Blood samples were collected after each period and tested for GSH and oxidized glutathione (GSSG) concentrations. RESULTS: Feed consumption was similar when data were analyzed for time points at which WB concentrations of GSH or GSSG were determined. However, significant effects of treatment, cow, days exposed to heat, cow-by-treatment interaction, and treatment-by-days exposed to heat interaction were detected when data were considered simultaneously. Mean +/- SD hematocrit for TN, HS, and HS + EIF were 35.3+/-3, 33.3+/-2, and 37.1+/-3%, respectively. Mean WBGSH concentrations for TN, HS, and HS + EIF were 3.2+/-0.65, 2.7+/-0.62, and 2.4+/-0.56 mmol/L of RBC, respectively. Reduced WBGSH concentrations were associated with reduced feed intake during the later part of each heat period. CONCLUSIONS AND CLINICAL RELEVANCE: Decreased GSH and increased GSSG concentrations were evident during heat stress, especially when cattle consumed EIF These were associated with reduced feed intake during heat stress. Heat stress, reductions in feed intake, and thermoregulatory effects of EIF may induce oxidative stress in cattle.

Animals↗

PubMed2002

Tilmicosin reduces lipopolysaccharide-stimulated bovine alveolar macrophage prostaglandin E(2) production via a mechanism involving phospholipases.

Tilmicosin is a potent antimicrobial with broad-spectrum activity against the bacterial agents involved in the bovine respiratory disease complex. Recent studies indicate that in addition to being bactericidal, tilmicosin is capable of modulating inflammation in the lung. A series of experiments were designed to determine whether tilmicosin alters alveolar macrophage-prostaglandin E(2) (PGE(2)) production induced by Escherichia coli (O55:B5) lipopolysaccharide (LPS). Twenty-two healthy Holstein bull calves were used to study the effects of LPS-induced PGE(2) production of alveolar macrophages after in vivo or in vitro treatment with tilmicosin. In Experiment 1, tilmicosin was given by subcutaneous injection (15 mg/kg) twice, 48 hours apart, to four calves; four control calves received no treatment. Twenty-four hours after the second treatment, alveolar macrophages were stimulated with LPS in vitro. In Experiment 2, alveolar macrophages from five untreated calves were harvested and treated in vitro with tilmicosin, followed by LPS stimulation. In Experiment 3, the ability of in vitro tilmicosin treatment to alter the expression of LPS-induced cyclooxygenase-2 (COX-2) mRNA was evaluated. In Experiments 4 and 5, secretory phospholipase A(2) activity was examined in untreated calves. Treatment of calves with tilmicosin resulted in reduced LPS-induced alveolar macrophage PGE(2) production. Similar reductions in PGE(2) by LPS-stimulated alveolar macrophages after in vitro tilmicosin treatment were noted. This in vitro tilmicosin treatment was not associated with reduction of the expression of LPS-induced COX-2. Alveolar macrophage phospholipase A(2) activity induced by LPS was significantly reduced by prior tilmicosin treatment in vitro. Tilmicosin (in vivo and in vitro) appears to reduce the PGE(2) eicosanoid response of LPS-stimulated alveolar macrophages by reducing the in vitro substrate availability without altering in vitro COX-2 mRNA expression.

Actins↗

PubMedDate not supplied

Effects of supplemental lactoferrin on serum lactoferrin and IgG concentrations and neutrophil oxidative metabolism in Holstein calves.

Lactoferrin (LF) is an iron-binding protein present in both colostrum and secondary granules of polymorphonuclear neutrophils (PMNs). We hypothesized that supplemental LF enhances neutrophil function in neonatal calves. Newborn calves were assigned to receive colostrum (C), colostrum + LF (CLF, 1 g/kg), or milk replacer + LF (MRLF, 1 g/kg). Serum (LF and IgG) and whole blood (neutrophil isolation) samples were obtained prior to treatment (day 0) and at 24 hours and 9 days of age. Serum IgG concentrations (mean +/- SD) in C, CLF, and MRLF calves at 24 hours were 1,911 +/- 994 mg/dL, 2,181 +/- 625 mg/dL, and 0 mg/ dL, respectively. Serum LF concentrations in C, CLF, and MRLF calves on day 0 were 324 +/- 334 ng/mL (range 0-863 ng/mL), 135 +/- 158 ng/mL (range 0-429 ng/mL), and 318 +/- 337 ng/mL (range 0-964 ng/mL), respectively. LF concentrations in C, CLF, and MRLF calves at 24 hours were significantly higher (P < .05), at 1,564 +/- 1,114 ng/mL (range 335-3,628 ng/mL, 2,237 +/- 936 ng/mL (range 31-3,287 ng/mL), and 3,189 +/- 926 ng/mL (range 1,736-4,120 ng/mL), respectively. Cytochrome c reduction in opsonized zymosan-treated or phorbol ester-treated cells was not significantly affected by supplemental LF provided at birth. Oral LF is absorbed in calves but does not alter PMN superoxide production and does not alter IgG absorption.

Animal Nutritional Physiological Phenomena↗