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Biomedical subjects

R Boyce

Publications and source records attributed to R Boyce.

At least 19 recordsLinked to original sources
PubMed2001

In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.

BACKGROUND: Diabetes is associated with increased risk of mortality as a consequence of acute myocardial infarction. This study determined whether rosiglitazone (ROSI) could reduce myocardial infarction after ischemia/reperfusion injury. METHODS AND RESULTS: Male Lewis rats were anesthetized, and the left anterior descending coronary artery was ligated for 30 minutes. After reperfusion for 24 hours, the ischemic and infarct sizes were determined. ROSI at 1 and 3 mg/kg IV reduced infarct size by 30% and 37%, respectively (P<0.01 versus vehicle). Pretreatment with ROSI (3 mg. kg(-1). d(-1) PO) for 7 days also reduced infarct size by 24% (P<0.01). ROSI also improved ischemia/reperfusion-induced myocardial contractile dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in ROSI-treated rats. ROSI reduced the accumulation of neutrophils and macrophages in the ischemic heart by 40% and 43%, respectively (P<0.01). Ischemia/reperfusion induced upregulation of CD11b/CD18 and downregulation of L-selectin on neutrophils and monocytes; these effects were significantly attenuated in ROSI-treated animals. Likewise, intercellular adhesion molecule-1 expression in ischemic hearts was markedly diminished by ROSI, as was the ischemia/reperfusion-stimulated upregulation of monocyte chemoattractant protein-1. CONCLUSIONS: ROSI reduced myocardial infarction and improved contractile dysfunction caused by ischemia/reperfusion injury. The cardioprotective effect of ROSI was most likely due to inhibition of the inflammatory response.

Animals↗
PubMed2001

Cloning, expression, and pharmacological characterization of a novel human histamine receptor.

Using a genomics-based reverse pharmacological approach for screening orphan G-protein coupled receptors, we have identified and cloned a novel high-affinity histamine receptor. This receptor, termed AXOR35, is most closely related to the H3 histamine receptor, sharing 37% protein sequence identity. A multiple responsive element/cyclic AMP-responsive element-luciferase reporter assay was used to identify histamine as a ligand for AXOR35. When transfected into human embryonic kidney 293 cells, the AXOR35 receptor showed a strong, dose-dependent calcium mobilization response to histamine and H3 receptor agonists including imetit and immepip. Radioligand binding confirmed that the AXOR35 receptor was a high-affinity histamine receptor. The pharmacology of the AXOR35 receptor was found to closely resemble that of the H3 receptor; the major difference was that (R)-alpha-methylhistamine was a low potency agonist of the AXOR35 receptor. Thioperamide is an antagonist at AXOR 35. Expression of AXOR35 mRNA in human tissues is highest in peripheral blood mononuclear cells and in tissues likely to contain high concentrations of blood cells, such as bone marrow and lung. In situ hybridization analysis of a wide survey of mouse tissues showed that mouse AXOR35 mRNA is selectively expressed in hippocampus. The identification and localization of this new histamine receptor will expand our understanding of the physiological and pathological roles of histamine and may provide additional opportunities for pharmacological modification of these actions.

Amino Acid Sequence↗
PubMed1999

Systemic administration of acidic fibroblast growth factor (FGF-1) prevents bone loss and increases new bone formation in ovariectomized rats.

There are no universally accepted agents that will substantially increase bone mass in osteoporotic patients. A number of peptides important in normal bone formation, such as members of the transforming growth factor-beta superfamily, are not satisfactory for this purpose either because their beneficial effects are predominantly local or there is systemic toxicity associated with their administration. We have examined the effects of exogenous fibroblast growth factor-1 and -2 (FGF-1 and FGF-2) on bone in vivo, since FGFs have been shown recently to be essential for normal skeletal development. FGF-1 was injected daily (0.2 mg/kg intravenously) for 28 days into the tail vein of adult female rats immediately following and 6 months after sham operation or ovariectomy (OVX). In rats treated immediately post-OVX, OVX produced more than a 30% decrease in tibial bone density, which was prevented by FGF-1 and estrogen. However, FGF-1 also had an anabolic effect. In sham-operated rats, FGF-1 increased bone density to 2-fold, whereas estrogen had no effect. In rats 6 months post-OVX, severe bone loss and disruption of trabecular microarchitecture occurred similar to that seen in patients with severe osteoporosis. In these rats, administration of FGF-1 induced extensive new woven bone formation with new trabecular-like structures filling much of the marrow spaces, and bone density in the tibial metaphysis increased 3-fold. FGF-1 and FGF-2 were also administered subcutaneously over the calvaria of mice in doses of 2-2000 microg/day for 3 days and shown to produce substantial increases in bone formation when examined morphologically. Thus, we conclude that both local and systemic FGF-1 increases new bone formation and bone density, and systemic FGF-1 also appears to restore bone microarchitecture and prevent bone loss associated with estrogen-withdrawal.

Animals↗
PubMed1995

Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice.

Human breast cancer frequently metastasizes to the skeleton to cause osteolysis and subsequent pain, pathological fracture, and hypercalcemia. Because bone continuously releases growth factors stored in bone matrix by bone resorption during physiological remodeling and, thus, possibly provides a favorable microenvironment for metastatic breast cancer cells to proliferate, inhibitors of bone resorption used either prophylactically or in patients with established disease, therefore, would seem likely to be useful adjuvant therapy in patients with breast cancer. However, the parameters for monitoring progressive osteolytic bone disease in humans are imprecise. We examined the effects of the third generation bisphosphonate, risedronate, which is a specific inhibitor of osteoclastic bone resorption, in a bone metastasis model in nude mice in which intracardiac injection of the human breast cancer cell line MDA-231 leads to osteolytic bone metastases. Risedronate (4 micrograms/animal/day) was given s.c. to animals (a) after radiologically small but defined osteolytic metastases were observed; (b) simultaneously with MDA-231 cell inoculation through the entire experimental period; or (c) by short-term prophylactic administration before inoculation of MDA-231 cells. In all experiments, risedronate either slowed progression or inhibited the development of bone metastases assessed radiographically. Furthermore, mice treated continuously with risedronate showed significantly longer survival than did control mice. Histomorphometrical analysis revealed that osteoclast numbers were diminished at metastatic tumor sites. Unexpectedly, there was also a marked decrease in tumor burden in bone in risedronate-treated animals. In contrast, the growth of metastatic breast cancer in soft tissues surrounding bones was not affected by risedronate. Moreover, risedronate had no effects on the local growth of s.c. implanted MDA-231 breast cancers in nude mice or on MDA-231 cell proliferation in culture. These data demonstrate that risedronate decreases metastatic MDA-231 breast cancer burden selectively in bone, as well as suppresses progression of established osteolytic lesions and prevents the development of new osteolytic lesions; thus, the data suggest that inhibition of osteoclastic bone resorption may be a useful adjunctive therapy for the treatment of cancers that have colonized in bone.

Animals↗
PubMed1995

Validation of wall thickness estimates obtained with polarized light microscopy using multiple fluorochrome labels: correlation with erosion depth estimates obtained by lamellar counting.

Numerous methods are currently being employed to estimate completed wall thickness and final erosion depth. Conflicting estimates of calculated bone balance have been obtained from the estimates of wall thickness and erosion depth using these various methods. To assess the utility of two specific methods to estimate wall thickness (polarized microscopy) and erosion depth (lamellar counts), we conducted a study in normal young adult beagle dogs, a model where bone balance should approximate 0. Dogs were administered multiple fluorochrome labels in vivo to label activity forming bone pockets. These labels were used to confirm the position of the cement line of the bone structural unit (BSU) in fluorescent light. Parallel measurements of wall thickness were then collected in polarized light. These estimates were compared to estimates of erosion depth obtained by lamellar counting and bone balance was calculated. Estimates of wall thickness correlated well with estimates of erosion depth with bone balance not differing significantly from 0. These data suggest that the combination of these two methods is a reasonable approach to obtaining estimates of bone balance at the level of the remodeling unit.

Animals↗
PubMed1994

Inhibition of IL-1 release from human monocytes and suppression of streptococcal cell wall and adjuvant-induced arthritis in rats by an extract of Tripterygium wilfordii Hook.

1. It was investigated whether an extract of Tripterygium wilfordii Hook f (TW) inhibits IL-1 production by monocytes and suppresses the development of IL-1-dependent arthritis induced in rats with streptococcal cell wall and adjuvant. 2. TW preferentially inhibited IL-1 alpha and IL-1 beta production by bacterial lipopolysaccharide (LPS)-stimulated human monocytes with IC50 of approximately 1 microgram/ml. 3. Oral administration of TW dose-dependently suppressed joint swelling and structural damage in streptococcal cell wall-induced arthritis (ED50 = 20 mg/kg/day) and in adjuvant-induced arthritis (ED50 = 46 mg/kg/day for developing and 8 mg/kg/day for established arthritis).

Animals↗
PubMed1994

Why aren't more pharmacists counseling?

Clearly, the answers to the question "Why aren't more pharmacists counseling patients?" are complex. Factors affecting counseling vary by practice site, geographical region, and pharmacists' attitudes. Advocates of patient counseling may label many factors mentioned by workshop participants as "just excuses not to change" or may question their validity. However, our experiences have shown that these are real problems with logical explanations and relatively simple solutions. By focusing this column on the steps for overcoming these common barriers to counseling, we hope to help pharmacists expand their role in patient care.

Communication Barriers↗
PubMed1994

Finding time for counseling.

To implement patient counseling, pharmacists must integrate new services into a significantly restructured prescription dispensing process to prevent marked reductions in efficiencies. Trying to add on counseling services--without changing existing systems--will reduce efficiency and increase unnecessary frustrations. Most pharmacy restructuring will require little or no additional expense--just changes in work flow, procedures, and functions, and/or small changes in physical layout. In a few situations, increasing efficiency may require major physical and design changes.

Humans↗
PubMed1989

Resorption is not essential for the stimulation of bone growth by hPTH-(1-34) in rats in vivo.

Chronic low doses of hPTH-(1-34) stimulate bone growth in rats in vivo. The objective of these studies was to determine if the anabolic effect of hPTH-(1-34) on rat bone in vivo is dependent on an initial stimulation of resorption by blocking resorption with either salmon calcitonin (CT) or dichloromethylene diphosphonate (Cl2MDP). Male Sprague-Dawley rats, 70-100 g, were treated with daily subcutaneous (SC) injections of vehicle (V) or hPTH-(1-34), 8 micrograms per 100 g (PTH), for 12 days. In experiment 1, rats were given CT for 3 (CT3) or 12 (CT12) days, either alone or in combination with hPTH-(1-34) (CT3-PTH and CT12-PTH) or vehicle for 12 days. In experiment 2, rats were pretreated for 4 days with Cl2MDP or its vehicle before starting the daily PTH or vehicle injections. Rats were then killed. Sera, femora, tibiae, and kidneys were removed for chemical and histomorphometric analyses. PTH, PTH-CT3, and PTH-CT12 rats showed significant increases in total bone calcium (18-23%), dry weight (DW, 13-25%), and bone-forming surfaces compared with their respective controls. Eroded (resorption) surfaces were comparable between the groups. Although weight gain and serum calcium were normal in rats treated for 3 days with CT, rats treated for 12 days with CT gained 14% less weight than controls and were hypophosphatemic, with reduced serum calcium and urea nitrogen. Total bone mass increased both in Cl2MDP rats (Ca 21%, DW 2%), where resorption was presumably blocked, and in PTH rats (Ca 31%, DW 19%). The increase in bone mass was greater in PTH-Cl2MDP rats (Ca 48%, DW 29%) than in rats treated with Cl2MDP alone, suggesting that although Cl2MDP blocked resorption, the anabolic response to PTH was not altered. As neither short-term treatment with CT nor Cl2MDP blocked the anabolic response of bone to hPTH-(1-34), this response does not appear to depend on the early stimulation of resorption.

Alkaline Phosphatase↗
PubMed1989

Altered actin and immunoglobulin C mu expression in nitrogen mustard-resistant human Burkitt lymphoma cells.

Raji-HN2 is a B cell lymphoma (Burkitt lymphoma) line that was made resistant to nitrogen mustard. The drug-resistant phenotype was accompanied by changes in gene expression. The expression of four unrelated genes was examined by Northern blot analysis. Raji-HN2 cells were found to contain about twice the number of actin mRNA found in Raji cells. Both cell lines were found to contain equivalent amounts of beta 2-microglobulin, c-myc oncogene, and immunoglobulin C mu mRNAs. The C mu mRNA was, however, larger in size in Raji-HN2 cells. Alterations in actin and C mu mRNAs in Raji-HN2 cells were not due to gene amplification or rearrangement because Southern blot analysis revealed no changes in the genomic organization of these genes. The increased actin mRNA content was correlated with an increased actin content of Raji-HN2 cells. The F-actin (stained with 7-nitrobenz-2-oxa-1,3-diazolylphallacidin) content of single cells was quantitated in a meridian interactive laser cytometer. Raji-HN2 cells contained about twice the amount of F-actin present in the parental Raji cells. Similar results were obtained when large populations, 10(6) cells each, were examined in a flow cytometer.

Actins↗
PubMed1984

Transitional cell carcinoma of the urethra metastatic to the eyes in a dog.

Hyphema and secondary glaucoma were ocular manifestations of disseminated neoplasia in a 4-year-old dog. The dog was euthanatized following enucleation after disseminated intravascular coagulopathy had developed. The histopathologic diagnosis was transitional cell carcinoma of the urethra, with metastasis to the lungs, heart, adrenal gland, and eyes.

Animals↗