Biomedical subjects

S E Weisbrode

Publications and source records attributed to S E Weisbrode.

At least 19 recordsLinked to original sources

PubMed2003

Safety evaluation of an extract from Salacia oblonga.

Plant extracts from the Salacia genus have been found to have intestinal alpha-glucosidase inhibitor activity, which may have application to the development of medical foods for people with diabetes. We evaluated the safety of a hot water extract of S. oblonga (salacinol extract) supplemented to or processed into a medical food. Thirty male Sprague-Dawley rats were assigned among one of three treatments: (1) EN-0178 (control, liquid diet), (2) EN-0178+salacinol (as 1 plus 500 mg of salacinol extract per 253 g diet, which was added to product immediately prior to feeding), (3) EN-0195 (as 1 plus 500 mg of salacinol extract per 253 g diet, which was added during product manufacture). After 14 days of free access to dietary treatments, rats were sacrificed, blood collected and organs weighed. Rats consuming salacinol extract had reduced (P <0.05) weight gain and feed intake. The relative (% of body weight) testicular weight was higher (P<0.05) for rats consuming salacinol extract, whereas, the relative liver and spleen weight was lower (P<0.05) for rats consuming salacinol extract. Of the serum chemistries analyzed, blood urea nitrogen and alkaline phosphatase was lower (P<0.05) for rats consuming salacinol extract. No differences in blood hematology were found. We conclude that salacinol extract, in a medical food consumed for 2 weeks in amounts estimated at 10-fold greater than proposed for human intake, did not result in clinical chemistry or histopathologic indications of toxic effects in male Sprague-Dawley rats.

Animals↗

PubMed2003

Left ventricular outflow tract-right atrial communication (Gerbode type defect) associated with bacterial endocarditis in a dog.

Left ventricular (LV) outflow tract-right atrial (RA) communication associated with bacterial endocarditis is described in a 6-year-old intact male Great Pyrenees dog with a 4- to 5-day history of fever, lethargy, weight loss, severe regenerative anemia, and asplenia. Typical vegetative mural endocardial lesions were observed grossly. Histologic evaluation revealed small gram-negative coccobacilli that were consistent with Bordetella avium-like organisms. These bacteria were associated with severe endocardial inflammation characterized by neutrophilic infiltration, extensive necrosis of endocardium, and fibrin deposition. LV-RA shunt (Gerbode defect) is a rare cardiac defect in humans that can be either congenital or, more rarely, secondary to septic endocarditis, valve replacement procedures, or thoracic trauma. B. avium-like organisms causing septicemia and endocarditis in immunocompromised and asplenic human patients have been described. To our knowledge, no previous descriptions of Gerbode defect associated with bacterial endocarditis in domestic animals have been reported in veterinary literature.

Animals↗

PubMed2003

Intrahepatic splenosis in a dog.

A 10-year-old castrated male Standard Poodle presented with an acute onset of lethargy and abdominal pain. The animal had a history of traumatic splenic rupture requiring splenectomy 5 years previously. Surgical exploration revealed multiple cystic red nodules involving all liver lobes, several of which were submitted for histopathology. Microscopically, the cystic nodules were dilated bile ducts and lymphatics surrounded by ectopic splenic tissue. A diagnosis of intrahepatic splenosis was made.

Animals↗

PubMed2001

Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis.

OBJECTIVE: To perform polymerase chain reaction (PCR) analysis on paraffin-embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. SAMPLE POPULATION: Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated. PROCEDURE: Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis. RESULTS: Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs.

Animals↗

PubMed2001

Effects of anti-inflammatory drugs on lipopolysaccharide-challenged and -unchallenged equine synovial explants.

OBJECTIVE: To evaluate the effects of anti-inflammatory drugs on lipopolysaccharide (LPS)-challenged and -unchallenged equine synovial membrane in terms of production of prostaglandin E2 (PGE2) and hyaluronan, viability, and histomorphologic characteristics. SAMPLE POPULATION: Synovial membranes were collected from the carpal, tarsocrural, and femoropatellar joints of 6 adult horses. PROCEDURE: Synovial membranes from each horse were minced and pooled and explants were treated with one of the following: no drug (control), drug, LPS alone, or LPS and drug. Treatment drugs were phenylbutazone (PBZ), flunixin meglumine (FNX), ketoprofen (KET), carprofen (CRP), meloxicam (MEL), low-concentration methylprednisolone (METH), high-concentration METH, dimethyl sulfoxide (DMSO), or an experimental COX-2 inhibitor (dissolved in DMSO). Following 48 hours of culture, medium was assayed for PGE2 and hyaluronan concentration. Synovial explants were assessed for viability and histomorphologic characteristics. RESULTS: For the LPS-challenged explants, PBZ, FNX, KTP CRF MEL, and low-concentration METH suppressed PGE2 production, compared with LPS challenge alone. Only MEL suppressed PGE2 production from LPS-challenged explants, compared with unchallenged explants. Synovial explants maintained > 90% viability and there was no significant difference in viability or hyaluronan production among explants. Histomorphologic scores were significantly decreased for explants treated with low-concentration METH or DMSO. CONCLUSIONS AND CLINICAL RELEVANCE: PBZ, FNX, KTP, CRFP MEL, and low-concentration METH suppressed PGE2 production in LPS-challenged explants. Meloxicam appeared to have more selective suppression of COX-2 activity. Histomorphologic scores suggest detrimental effects of METH, DMSO, and the experimental COX-2 inhibitor. Commonly used nonsteroidal anti-inflammatory drugs suppress induced synovial membrane PGE2 production without detrimental effects on synovial membrane viability and function.

Animals↗

PubMed2000

Effect of long-term administration of an injectable enrofloxacin solution on physical and musculoskeletal variables in adult horses.

OBJECTIVE: To evaluate clinical safety of administration of injectable enrofloxacin. DESIGN: Randomized controlled clinical trial. ANIMALS: 24 adult horses. PROCEDURES: Healthy horses were randomly allocated into 4 equal groups that received placebo injections (control) or IV administration of enrofloxacin (5 mg/kg [2.3 mg/lb], 15 mg/kg [6.8 mg/lb], or 25 mg/kg [11.4 mg/lb] of body weight, q 24 h) for 21 days. Joint angles, cross-sectional area of superficial and deep digital flexor and calcaneal tendons, carpal or tarsal osteophytes or lucency, and midcarpal and tarsocrural articular cartilage lesions were measured. Physical and lameness examinations were performed daily. Measurements were repeated after day 21, and articular cartilage and bone biopsy specimens were examined. RESULTS: Enrofloxacin did not induce changes in most variables during administration or for 7 days after administration. One horse (dosage, 15 mg/kg) developed lameness and cellulitis around the tarsal plantar ligament during the last week of administration. One horse (dosage, 15 mg/kg) developed mild superficial digital flexor tendinitis, and 1 horse (dosage, 25 mg/kg) developed tarsal sheath effusion without lameness 3 days after the last administration. High doses of enrofloxacin (15 and 25 mg/kg) administered by bolus injection intermittently induced transient neurologic signs that completely resolved within 10 minutes without long-term effects. Slower injection and dilution of the dose ameliorated the neurologic signs. Adverse reactions were not detected with a 5 mg/kg dose administered IV as a bolus. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered IV once daily at the rate of 5 mg/kg for 3 weeks is safe in adult horses.

Animals↗

PubMed2000

Effects of phenylbutazone on bone activity and formation in horses.

OBJECTIVE: To determine the effects of phenylbutazone (PBZ) on bone activity and bone formation in horses. ANIMALS: 12 healthy 1- to 2-year-old horses. PROCEDURES: Biopsy was performed to obtain unicortical bone specimens from 1 tibia on day 0 and from the contralateral tibia on day 14. Fluorochromic markers were administered IV 2 days prior to and on days 0, 10, 15, and 25 after biopsy was performed. Six horses received PBZ (4.4 mg/kg of body weight, PO, q 12 h) and 6 horses were used as controls. All horses were euthanatized on day 30 and tissues from biopsy sites, with adjacent cortical bone, were collected. Osteonal density and activity, mineral apposition rate (MAR), and percentage of mineralized tissue filling the biopsy-induced defects in cortical bone were assessed. Serum samples from all horses were analyzed for bone-specific alkaline phosphatase activity and concentration of PBZ. RESULTS: MAR was significantly decreased in horses treated with PBZ. Regional acceleratory phenomenon was observed in cortical bone in both groups but was significantly decreased in horses treated with PBZ. Osteonal activity was similar at all time points in all horses. In control horses, percentage of mineralized tissue filling the cortical defects was significantly greater in defects present for 30 days, compared with defects present for 14 days. Differences in percentage of mineralized tissue were not detected in horses treated with PBZ. CONCLUSIONS AND CLINICAL RELEVANCE: PBZ decreased MAR in cortical bone and appeared to decrease healing rate of cortical defects in horses.

Alkaline Phosphatase↗

PubMed1999

Gallium nitrate suppresses the production of nitric oxide and liver damage in a murine model of LPS-induced septic shock.

The efficacy of gallium (Ga) nitrate was examined in a murine model of sepsis. Male Balb/c mice (6-8 weeks) were randomized into 3 groups: 1) vehicle-treated controls 2) mice with sepsis induced by treatment with 0.3 mg i.v. of Propionibacterium acnes followed one week later by 0.01 microg lipopolysaccharide (LPS) and 10 mg of D-galactosamine (GalN) 3) mice with sepsis injected with 45 mg/kg s.c. of gallium nitrate (calculated as elemental Ga) 24 hours prior to LPS/GalN. Two hours after LPS/GalN or vehicle, plasma concentrations of tumor necrosis factor (TNF-alpha) in groups 1, 2 and 3 were 54+/-31 (n=6), 21,390+/-5139 (n=4), and 21,909+/-943 (n=5) pg/ml, respectively. After 6 hours, plasma concentrations of gamma interferon (IFN-gamma) were <10 (n=8), 4771+/-1078 (n=6), and 1622+/-531 (n=15) pg/ml, respectively, and of nitrate/nitrite (products of nitric oxide) were 64+/-8 (n=7), 146+/-18 (n=8), and 57+/-8 (n=15) microM. At 18 hours, serum chemistries were; SGOT 171+/-46 (n=13), 10,986+/-3062 (n=7), and 1078+/-549 (n=8) IU/L; SGPT 165+/-59, 17,214+/-4340, and 2088+/-1097 IU/L; and total bilirubin 0.2+/-0.0, 0.9+/-0.4, and 0.2+/-0.0 mg/dl for groups 1, 2, and 3 respectively. Blinded histologic evaluation of livers at 18 hours revealed inflammatory infiltrate scores (x [range], 0=none, 1=minimal, 2=mild, 3=moderate, and 4=severe) of 0.1 [0-1] (n=8), 3.0 [2-4] (n=15), and 2.0 [0-3] (n=10), and necrosis scores of 0.0, 2.8 [0-4], and 0.9 [0-4]. Although Ga did not affect production of TNF-alpha, it ameliorated hepatocellular injury and protected against necrosis. Based on this model of sepsis, Ga may have a role in treating the human disease.

Animals↗

PubMed1999

In vitro dose-dependent effects of enrofloxacin on equine articular cartilage.

OBJECTIVE: To determine whether enrofloxacin has detrimental, dose-dependent effects on equine articular cartilage in vitro. ANIMALS: Cartilage explants were developed from 6 healthy horses between 0 and 96 months old. PROCEDURE: Patellar cartilage explants were incubated in 5 concentrations of enrofloxacin (2 microg/ml, 10 microg/ml, 1,000 microg/ml, 10,000 microg/ml, and 50,000 microg/ml) for 72 hours. Proteoglycan synthesis (Na35SO4 incorporation for 24 hours), proteoglycan degradation (Na35SO4 release for 72 hours), endogenous proteoglycan content (dimethylmethlene blue assay), and total protein content were determined. Cartilage explants were evaluated by use of histomorphologic and histomorphometric techniques (toluidine blue stain) for cytologic and matrix characteristics. Quantitative data were analyzed with a one-way ANOVA to compare results among various enrofloxacin concentration groups and the control group. A general linear model was used to determine whether age had an effect. RESULT: Proteoglycan synthesis was excellent in control specimens and in specimens incubated in low concentrations of enrofloxacin (2 microg/ml and 10 microg/ml). High concentrations of enrofloxacin (> 1,000 microg/ml) effectively eliminated proteoglycan synthesis regardless of horse age. Proteoglycan degradation at low concentrations (2 microg/ml and 10 microg/ml) was not different than control. High concentrations of enrofloxacin (> 1,000 microg/ml) caused significant degradation. Different concentrations of enrofloxacin did not affect endogenous proteoglycan. High concentrations of enrofloxacin were associated with a significant increase in number of pyknotic nuclei. CONCLUSION: Concentrations of enrofloxacin that might be achieved following systemic administration did not suppress chondrocyte metabolism in vitro. High concentrations of enrofloxacin (> 1,000 microg/ml) were toxic to chondrocytes.

Analysis of Variance↗

PubMed1999

Nitric oxide synthase activity in healthy and interleukin 1beta-exposed equine synovial membrane.

OBJECTIVE: To quantitate nitric oxide synthase (NOS) activity in healthy and interleukin 1beta (IL-1beta)-exposed equine synovial membrane. ANIMALS: 6 healthy horses, 2 to 8 years old. PROCEDURE: Recombinant human IL-1beta (0.35 ng/kg of body weight) was injected intra-articularly into 1 metacarpophalangeal joint of each horse. The contralateral joint served as an unexposed control. All horses were euthanatized 6 hours after injection of IL-1beta, and synovial membrane specimens were assayed for NOS activity by measuring conversion of arginine to citrulline. Severity of inflammation was semiquantitated by analysis of synovial fluids and histologic examination of synovial membrane. RESULTS: Equine synovial membrane had minimal NOS activity. A significant difference was not detected in NOS activity between control and IL-1beta-exposed specimens. Histologic examination revealed a neutrophilic infiltrate in synovial membrane exposed to IL-1beta. Synovial fluid from IL-1beta-exposed joints had a moderate inflammatory response and significantly greater concentrations of IL-1beta and interleukin-6 than fluid from healthy joints. CONCLUSION: Healthy equine synovial membrane had low NOS activity that was not affected by exposure to IL-1beta.

Animals↗

PubMed1999

Instability-induced osteoarthritis in the metacarpophalangeal joint of horses.

OBJECTIVE: To establish an instability model of osteoarthritis (OA) that mimics the early changes of naturally acquired OA. ANIMALS: 6 mature radiographically normal horses. Procedure-The collateral and lateral collateral sesamoidean ligaments were transected in a metacarpophalangeal (MCP) joint in each horse. Lameness examinations were performed every 7 days after surgery for 8 weeks. Radiographs were taken immediately before and after desmotomy and 8 weeks after surgery. Eight weeks after surgery, bilateral MCP joints were grossly evaluated, specimens of articular cartilage were harvested for histologic examination and tissue culture, and synovial membrane was harvested for histologic examination. RESULTS: Lameness scores significantly increased over time (mean score of 1.6 for the 8-week study period). Joint circumference was significantly greater and range of motion significantly less in OA joints, compared with contralateral joints. Number and size of osteophytes were significantly greater in OA joints. Amount of newly synthesized proteoglycan (PG) was significantly greater at 18 and 72 hours of cartilage explant culture for OA joints, compared with contralateral joints. Total PG content and PG degradation did not differ between OA and contralateral joints. IMPLICATIONS FOR HUMAN MEDICINE: This instability model in horses may be useful in the study of OA in humans. CONCLUSION: Desmotomy of the lateral collateral and lateral collateral sesamoidean ligaments induced instability similar to that of naturally acquired OA in horses, as documented by lameness, clinical signs of OA, osteophyte formation, and erosions of articular cartilage surfaces and score lines in OA joints.

Animals↗

PubMed1998

Phenotypic changes in T cell populations during the reactivation of tuberculosis in mice.

The phenotypic changes of T lymphocytes during the reactivation of latent Mycobacterium tuberculosis infection by activation of the hypothalamic-pituitary-adrenal (HPA) axis was monitored using flow cytometric analysis. Subsets of CD4+ and CD8+ lymphocyte populations from the lung, spleen and draining lymph nodes of infected mice were identified based on their differential expression of the cell surface antigens CD44 and CD45RB. Latent infection was characterized by an accumulation of both naive, activated and memory CD4 and CD8 T lymphocytes in the lung and mediastinal lymph nodes. No changes were observed in the spleen of mice with latent infection when compared with uninfected mice. Immediately following the activation of the HPA axis, a reduction in all CD4+ and CD8+ T cells in the lung and mediastinal lymph nodes was observed. This correlated with the reactivation of mycobacterial growth. The decrease was transient for memory and naive CD4 and CD8 T lymphocyte populations in the lung. However, the number of naive CD4 and CD8 T lymphocyte populations in the mediastinal lymph node following reactivation was less than that found in mice with latent infection. These data provide the first characterization of T lymphocyte populations which may be functionally involved in the immunological response to HPA axis-induced reactivation of M. tuberculosis infection.

Animals↗

PubMed1998

Cell trafficking, mediator release, and articular metabolism in acute inflammation of innervated or denervated isolated equine joints.

OBJECTIVES: To describe the acute cellular response, inflammatory mediator release, and effect on chondrocyte metabolism of interleukin 1 beta (IL-1 beta) in isolated innervated or denervated equine metacarpophalangeal joints. ANIMALS: One metacarpophalangeal joint of 24 adult horses. PROCEDURES: The metacarpophalangeal joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated metacarpophalangeal joint preparation. Isolated joints were assigned to 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular injection of IL-1 beta. Synovial fluid was collected for cytologic examination and determination of IL (IL)-1 beta, (IL-6), prostaglandin E2 (PGE2), and substance P (SP) values. Synovial membrane was immunostained with SP and nerve-specific enolase (NSE) antibodies. Cartilage was collected for determination of proteoglycan (PG) synthesis and degradation. RESULTS: IL-1 beta induced significant neutrophilic leukocytosis in synovial and synovial membrane. IL-1 beta concentration and returned to baseline by 5.5 hours, but IL-6 concentration significantly increased throughout the study. Total SP content was significantly higher in inflamed joints. There was a significant increase in 24- and 48-hour PG degradation in inflamed innervated joints. CONCLUSION: Cellular response to IL-1 beta was rapid and sustained; joint clearance of IL-1 beta was rapid, and endogenous production of IL-1 beta did not follow. The IL-6 and PGE2 concentrations significantly increased, and SP content was increased in association with inflammation but not denervation. A degradative response of cartilage of IL-1 beta was observed, and was enhanced by innervation. This model was useful for investigation of the articular response to acute inflammation and the influence of denervation in modulating this response.

Animals↗

PubMed1997

Gallium nitrate suppresses lupus in MRL/lpr mice.

Gallium (Ga) nitrate, a drug which prevents a variety of experimental autoimmune diseases, was investigated in a murine model of systemic lupus erythematosus (SLE). In one experiment, female MRL/Mp lpr/lpr (MRL/lpr) mice were randomized into 2 groups of 6: 1) vehicle (trisodium citrate) and 2) Ga. Subcutaneous injections began at 3 weeks of age and continued weekly until the mice were euthanized a week after the thirteenth injection. The loading dose of Ga (calculated as elemental Ga) was 45 mg/kg, followed by 15 mg/kg/week. In another experiment (n = 18) with 3 males and 3 females per group, mice received 1) vehicle, 2) Ga x 1 (one 45 mg/kg dose), and 3) Ga x 13. In the experiment with 12 mice, axillary lymph nodes from Ga-treated mice were significantly smaller than those from vehicle-treated mice (91+/-42 and 360+/-358 mg respectively, mean+/-SD), and spleens as well as lymph nodes from the former showed significantly less lymphoid infiltrate. In the experiment with 18 mice, prescapular lymph nodes weighed 312+/-98, 217+/-52, and 42+/-34 mg, and spleens weighed 732+/-492, 409+/-164, and 192+/-93 mg in the groups which received vehicle, Ga x 1, and Ga x 13 respectively. Control mice had significantly more lymphoid infiltrates in the lungs, spleen, and lymph nodes and, unlike Ga x 13 mice, exhibited glomerulitis and renal vasculitis. Within groups, females developed more severe disease than males. The Ga x 13 group had increased percentages of CD4-bearing and CD8-bearing lymphocytes in lymph nodes and increased CD4-bearing lymphocytes in the spleen, with an increased proliferative response to mitogen stimulation in vitro in lymph nodes, although not in the spleen. The Ga x 13 group also gained less weight and developed osteosclerosis. Although preliminary, our findings suggest that clinical trials with Ga in SLE are merited.

Animals↗

PubMed1997

Endotoxin-induced ileal Vo2-Do2 alterations do not correlate with the severity of ileal injury.

PURPOSE: Altered Vo2-Do2 relationships are most often noted to occur in the setting of sepsis or endotoxin (LPS)-induced systemic organ microvascular injury and are generally thought to be causally linked to that injury. However, we have recently shown that ileal microvascular injury is not associated with altered ileal Vo2-Do2, relationships. Thus, we hypothesized that the severity of LPS-induced systemic organ microvascular injury would not correlate with the development of systemic organ Vo2-Do2 alterations. MATERIALS AND METHODS: To test this hypothesis, we used the in situ autoperfused feline ileal preparation to simultaneously examine microvascular permeability, reflected as the ileal lymph to plasma protein concentration ratio (CL/CP), and ileal Vo2-Do2 relationships 2 hours after intravenous LPS (0.75-2.0 mg/kg; n = 9) and in matching controls (n = 5). RESULTS: As expected, all LPS-treated animals were found to have extensive ileal histological damage and marked increases in the CL/CP compared with controls (0.308 +/- 0.019 v 0.097 +/- 0.009; P < .001). In addition, although the critical Do2 (Do2c) was elevated in the LPS-treated animals relative to controls (34.2 +/- 5.0 v 16.7 +/- 1.4 mL/min/kg; P < .03), there was no correlation between the Do2c and the CL/CP in the LPS-treated animals. Finally, ileal wet to dry weight ratios after LPS did not differ from controls. CONCLUSION: Taken together, these data suggest that factors other than organ injury, as assessed by morphological and permeability alterations, are important in the pathogenesis of altered systemic organ Vo2-Do2 relationships after LPS.

Animals↗

PubMed1997

Ischemia/reperfusion injury to the ileum does not account for the ileal VO2-DO2 alterations induced by endotoxin.

PURPOSE: Endotoxin (lipopolysaccharide [LPS])-induced systemic organ injury leads to disruption of normal systemic organ metabolic processes, which are manifest clinically by signs of accelerated anaerobic metabolism (e.g., tissue acidosis and hyperlactatemia) and altered VO2-DO2 relationships. The association of increased anaerobic metabolism with VO2-DO2 alterations has led to the notion that ischemia/ reperfusion (I/R) injury may be a prerequisite for the development of VO2-DO2 alterations during endotoxemia. However, in contrast to sepsis, in which oxygen consumption is often increased, oxygen consumption is severely decreased after I/R injury. Based on these observations, we hypothesized that I/R injury would result in systemic organ VO2-DO2 alterations, which are distinct from those that occur in sepsis. MATERIALS AND METHODS: We used the in situ autoperfused feline ileal preparation to simultaneously examine microvascular permeability, reflected as the ileal lymph to plasma protein concentration ratio (CL/CP), and ileal VO2-DO2 relationships after either intravenous LPS (2.0 mg/kg; n = 5) or I/R injury (n = 5), and in matching controls (n = 5). RESULTS: As expected, all LPS-treated and I/R-injured animals were found to have extensive ileal histological damage and marked increases in the CL/CP compared with controls (0.315 +/- 0.009 and 0.329 +/- 0.034, respectively, v 0.097 +/- 0.009; P < .001, both comparisons). In addition, the critical DO2 (DO2c) was elevated, and the critical oxygen extraction was decreased in both the I/R and LPS groups relative to controls. However, as initially hypothesized, the VO2 at the critical DO2 was markedly decreased in the I/R group compared with that of the LPS group. CONCLUSIONS: These data indicate that I/R injury is insufficient to account for the systemic organ VO2-DO2 alterations that occur with LPS injury.

Acidosis↗

PubMed1997

Effects of vigorous exercise training and beta-agonist administration on bone response to hindlimb suspension.

The effectiveness of dobutamine (Dob) in preventing bone loss during 14 days of hindlimb suspension (Sus) was tested in exercise-trained (Ex; n = 25) and sedentary (Sed; n = 22) rats (age 155 days). One-half of each group was given Dob (2 mg . kg-1 . day-1) or saline (Sal). Histomorphometric measurements at midfemur revealed a 17% smaller cortical bone area (CBA) and a 32% lower periosteal mineral apposition rate (MAR) in suspended vs. nonsuspended Sed/Sal rats. Dob abolished this decline in CBA in Sed/Sus rats, probably via an attenuation of the decrease in periosteal MAR; similar but nonsignificant effects on cross-sectional moment of inertia were observed. Nonsuspended Ex rats had no change in bone CBA when CBA is indexed to body weight. Sus appeared to uncouple the relationship between soleus weight and CBA. Dob attenuated the 43% decline in soleus weight after Sus in Ex but not in Sed rats. In summary, vigorous Ex before Sus does not affect loss of bone mass due to unloading; Dob effectively maintains CBA in Sed rats subjected to suspension.

Adrenergic beta-Agonists↗

PubMed1997

Biochemical, histochemical, and immunohistochemical characterization of distal tibial osteochondrosis in horses.

OBJECTIVE: To compare the biochemical, histochemical, and immunohistochemical profiles of articular cartilage from horses with naturally acquired distal tibial osteochondrosis (OC) with cartilage from a similar location in clinically normal horses. ANIMALS: 9 affected horses (group 1, 16 OC lesions) and 4 control horses (group 2, 8 normal osteochondral specimens). PROCEDURE: OC specimens were collected during arthroscopic removal of the fragment, and control specimens were collected by aseptic osteotomy. Uronic acid, total protein, total glycosaminoglycan (GAG), chondroitin sulfate (CS), and keratan sulfate (KS) contents were determined. Histomorphologic, histochemical, and immunohistochemical examinations were performed on specimens after snap freezing at -80 C and cryosectioning. Monoclonal antibodies (MAB) 3B3 and 5D4 were applied for location of epitopes of CS and KS, respectively. RESULTS: OC lesions had significantly lower quantity of uronic acid, total GAG, and CS, compared with normal cartilage. OC cartilage had significantly less intense staining with toluidine blue, along with irregular cellularity and tidemark characteristics, compared with normal cartilage. Monoclonal antibodies 3B3 and 5D4 stained OC cartilage, whereas MAB 5D4 did not stain control cartilage. Additionally, MAB 3B3 and 5D4 stained the fibrous tissue that was found firmly attached to the OC lesion located between the parent distal portion of the tibia and OC fragment. CONCLUSION: OC cartilage lesions of the distal intermediate ridge of the tibia in horses are biochemically, histochemically, and immunohistochemically distinct from normal cartilage from the same location. Results may reflect the inability of the chondrocyte of the developing joint to alter matrix components that would allow proper maturation and differentiation into bone.

Animals↗