Surface enhanced fluorescence by metallic nano-apertures associated with stair-gratings.

Metallic nano-apertures associated with stair-gratings are proposed for surface enhanced fluorescence with high excitation enhancement and narrow emission beaming effect. Fluorescence correlation spectroscopy method was utilized to analyze the fluorescence trace and fluorescence enhancement, and the angular patterns of fluorescent emission were measured with the back focal plane imaging method. The stair-grating presents a strong optical response which covering well both the excitation and the emission bands of the photoluminescence process. Such high enhancement and narrow directionality by the stair-gratings would enable the detection of single molecules with low numerical aperture objective effectively.

Post-mortem proteolysis and tenderisation are more rapid and extensive in female duck breast muscle.

The post-mortem proteolysis and tenderisation between male and female duck breast muscles were compared. The results showed that µ-calpain activity, desmin content and shear force decreased more quickly in female than in male samples stored at 5°C. It is suggested that the post-mortem proteolysis and tenderisation are more rapid and extensive in female duck breast muscle.

Targeting post-translational modifications of histones for cancer therapy.

Post-translational modifications (PTMs) on histones including acetylation, methylation, phosphorylation, citrullination, ubiquitination, ADP ribosylation, and sumoylation, play important roles in different biological events including chromatin dynamics, DNA replication, and transcriptional regulation. Aberrant histones PTMs leads to abnormal gene expression and uncontrolled cell proliferation, followed by development of cancers. Therefore, targeting the enzymes required for specific histone PTMs holds a lot of potential for cancer treatment. In this review article, we retrospect the latest studies in the regulations of acetylation, methylation, and phosphorylation of histones. We also summarize inhibitors/drugs that target these modifications for cancer treatment.

Saturated fatty acid induces cancer stem cell-like properties in human hepatoma cells.

Hepatic steatosis has been reported to be a risk factor for the development of liver cancer. The underlying mechanism for carcinogenesis remains to be elucidated. It has been postulated that cancer stem cells (CSCs) within tumor tissues are a subset of cells with stem cell properties of self-renewal and undifferentiation. The purpose of this study was to investigate the effects of a saturated fatty acid, palmitate (PA), on CSC-like properties of human hepatoma HepG2 cells. We investigated the effects of PA on HepG2 cells and primary rat hepatocytes (PRH) by exposing them to PA to induce lipid accumulation. Significant fat accumulation was observed by Oil Red O staining in cells exposed to PA, and it was accompanied by significant increase in NFκB (p65) nuclear translocation in HepG2 cells. Notably, PA significantly enhanced the sphere forming ability of HepG2 cells, but not PRH. Furthermore, PA significantly increased stemness gene expressions of Sox2 and Oct4, and sonic hedgehog (Shh) production. Notably, NFκB inhibitors, N-Acetyl-L-cysteine and pyrollidine dithiocarbamate, and a NOX inhibitor, diphenyleneiodonium, significantly attenuated PA-induced sphere forming ability of HepG2 cells. Our results suggest that lipid accumulation may not only induce pro-inflammatory responses in hepatocytes but may also activate CSC-like properties of hepatoma cells through NFκB activation.

A standard panel of microsatellites for Asian seabass (Lates calcarifer).

Microsatellites are the most popular markers for parentage assignment and population genetic studies. To meet the demand for international comparability for genetic studies of Asian seabass, a standard panel of 28 microsatellites has been selected and characterized using the DNA of 24 individuals from Thailand, Malaysia, Indonesia and Australia. The average allele number of these markers was 10.82 +/- 0.71 (range: 6-19), and the expected heterozygosity averaged 0.76 +/- 0.02 (range: 0.63-1.00). All microsatellites showed Mendelian inheritance. In addition, eight standard size controls have been developed by cloning a set of microsatellite alleles into a pGEM-T vector to calibrate allele sizes determined by different laboratories, and are available upon request. Seven multiplex PCRs, each amplifying 3-5 markers, were optimized to accurately and rapidly genotype microsatellites. Parentage assignment using 10 microsatellites in two crosses (10 x 10 and 20 x 20) demonstrated a high power of these markers for revealing parent-sibling connections. This standard set of microsatellites will standardize genetic diversity studies of Asian seabass, and the multiplex PCR sets will facilitate parentage assignment.

Appearance of a new nucleosomal protein during differentiation of human leukemia (HL-60) cells.

A 60-kilodalton protein was identified in chromatin digested by micrococcal nuclease during retinoic acid-induced differentiation of human leukemia (HL-60) cells to mature-like granulocytes. The protein was not detected in a retinoic acid-resistant variant of the HL-60 cell line treated with retinoic acid, in HL-60 cells induced with dimethyl sulfoxide, or in normal human granulocytes. This protein may have an important role in the regulation of retinoic acid-induced leukemic cell differentiation.

Demonstration of a mitochondrial DNA-compatible workflow for genetically variant peptide identification from human hair samples.

Hair is an evidentiary sample that typically does not provide sufficient nuclear DNA for forensic analysis. Therefore, state-of-the-art forensic examination for hair samples include subjective microscopic evaluation, mitochondrial DNA (mtDNA) analysis, and more recently, proteomic genotyping that uses protein variation in the form of genetically variant peptides (GVPs) to infer single nucleotide polymorphism (SNP) alleles. Since many cases involve limited sample amounts (approximately 2 cm or less), any additional destructive testing (besides mtDNA) would be excluded. If a mtDNA-compatible protein extraction workflow could be developed, GVPs would provide additional forensic value without sacrificing any portion of the original hair sample. Here, we demonstrate an optimized method that can be used to obtain both whole genome mtDNA and putative GVP profiles from a single limited hair sample. The method involves urea-based extraction of proteins from hair, followed by buffer exchange and protease digestion. Peptides are eluted through a 30 kDa membrane and analyzed using traditional proteomic techniques. DNA is subsequently extracted from the filter and analyzed using whole mt-genome analysis. The method was verified with a range of hair sample types (head, pubic, and arm hair) from a diverse cohort of 22 individuals. Specifically, putative GVP profiles and mtDNA haplotypes concordant with buccal swab samples from the same donor were obtained from 22 individuals. Further, the utility of the method was verified across two different laboratories. The method is applicable for proteomic-based GVP analysis and mt-genome analysis for forensic research applications.

Pegylated interferons for chronic hepatitis C virus infection: an indirect analysis of randomized trials.

Dual therapy with pegylated interferon and ribavirin is recommended for patients with chronic hepatitis C virus infection who meet criteria for treatment, but it is unclear whether pegylated interferon alfa-2a or pegylated interferon alfa-2b is more effective or associated with fewer adverse events. Because data from head-to-head trials of pegylated interferon regimens are sparse, we performed adjusted indirect analysis using trials comparing dual therapy with pegylated interferon alfa-2a or pegylated interferon alfa-2b vs dual therapy with non-pegylated interferon. We searched for potentially relevant randomized controlled trials using electronic databases and reference lists. A total of 16 trials met inclusion criteria. Adjusted indirect comparisons found no statistically significant differences between dual therapy with pegylated interferon alfa-2a and dual therapy with pegylated interferon alfa-2b on the outcomes sustained virologic response [relative risk (RR) = 1.59, 95% CI: 0.56-4.46], withdrawal due to adverse events (RR = 0.86, 95% CI: 0.29-2.55), anaemia (RR = 1.67, 95% CI: 0.32-8.84), depression (RR = 1.09, 95% CI: 0.41-2.90) or flu-like symptoms (RR = 1.10, 95% CI: 0.53-2.29). Adjusting for potential publication bias and stratifying analyses by indicators of methodological quality, human immunodeficiency virus infection status, hepatitis C virus genotype, dose of ribavirin or dose of pegylated interferon did not change conclusions. There is insufficient evidence to support conclusions that dual therapy with one pegylated interferon is superior to the other. However, because estimates are imprecise, our results also do not rule out a clinically significant difference. Head-to-head trials are needed to verify the results of indirect analyses and provide additional guidance on optimal treatment choices.

The complete mitochondrial genome sequence and characterization of single-nucleotide polymorphisms in the control region of the Asian seabass (Lates calcarifer).

We determined the complete mtDNA nucleotide sequence of Lates calcarifer using the shotgun sequencing method. The mitochondrial DNA (mtDNA) was 16,535 base pairs (bp) in length, and contained 13 protein coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and one major noncoding control region (CR). The CR was unusually short at only 768 bp. A striking feature of the mitochondrial genome was the high G+C content (46.1%), which is among the highest in fish. The gene order was identical to that of a typical vertebrate. Phylogenetic analyses using concatenated amino acid sequences of 12 protein-coding genes of 30 fish species representing 14 suborders clearly showed Lates calcarifer was located in the cluster of fish species from the order Perciformes, supporting the traditional systematic classification. We characterized single-nucleotide polymorphisms (SNPs) in the CR by sequencing the complete CR of 25 individuals obtained from Australia and Singapore. A total of 68 SNPs were detected. Eighteen SNPs were fixed with alternative nucleotides in Australian and Singapore seabass, and these SNPs could be used for differentiating fish from the two countries.

Identification of a nuclear matrix-associated region of the c-myc protooncogene and its recognition by a nuclear protein in the human leukemia HL-60 cell line.

A nuclear matrix (NM)-associated region (MAR) of the protooncogene c-myc is identified in a human leukemia cell line (HL-60). A binding assay between isolated NM and 32P-end-labeled c-myc fragments in the presence of unlabeled competitors was used, and a 3'-end DraI/DraI fragment of 172 base pairs containing the first of the two polyadenylation [poly(A)] signals was identified as an in vitro MAR. Direct detection of endogenous c-myc fragments remaining NM bound after restriction digestion was used, and an in vivo MAR has been identified as the ClaI/EcoRI 1.4-kilobase pair fragment containing the 172-base pair in vitro MAR fragment. In addition, a nuclear protein (Mr = 25,000, p25) demonstrating preferential binding to the 172-base pair c-myc MAR has been identified and partially purified. This protein is diminished in the nuclei of the cells induced by phorbol ester to undergo macrophage differentiation. Footprint analysis shows that p25 binds to two regions of the 172-base pair fragment. One contains the first of two poly(A) addition signals and a topo II box-like sequence, and the other (AATTTCAATCCTAGTA) is 17 base pairs downstream of the first poly(A) signal.

Absolute quantitation of coronary steal induced by intravenous dipyridamole.

OBJECTIVE: The study was done to determine whether coronary steal (defined as an absolute decrease in perfusion from resting blood flow) is induced by intravenous (IV) dipyridamole in patients with severe coronary artery disease (CAD). BACKGROUND: Myocardial ischemia during coronary vasodilation is usually attributed to coronary steal. However, there is limited data on the absolute magnitude of coronary steal in humans. METHODS: Eighteen patients with multivessel CAD underwent dynamic positron emission tomography (PET) imaging with 13NH3 at rest and after infusion of IV dipyridamole. Eight myocardial sectors were analyzed per short axis slice and myocardial blood flow calculated with a two-compartment model in absolute terms. RESULTS: Coronary steal occurred in 8 of the 18 patients. In the 8 patients with coronary steal, myocardial blood flow decreased from 90 +/- 18 ml/100 g/min at rest to 68 +/- 27 ml/100 g/min following dipyridamole in the segments with steal, and increased from 87 +/- 19 to 138 +/- 16 ml/100 g/min following dipyridamole in the segments without steal. Significant clinical correlates of coronary steal were either ST elevation or the combination of ST depression and angina. CONCLUSIONS: Coronary vasodilation with IV dipyridamole is associated with significant reductions in blood flow to collateral-dependent myocardium consistent with coronary steal in about 45% of patients with severe CAD.

Changes in hospitality workers' exposure to secondhand smoke following the implementation of New York's smoke-free law.

OBJECTIVE: To assess the impact on hospitality workers' exposure to secondhand smoke of New York's smoke-free law that prohibits smoking in all places of employment, including restaurants, bars, and bowling facilities. DESIGN: Pre-post longitudinal follow up design. SETTINGS: Restaurants, bars, and bowling facilities in New York State. SUBJECTS: At baseline, 104 non-smoking workers in restaurants, bars, and bowling facilities were recruited with newspaper ads, flyers, and radio announcements. Of these, 68 completed a telephone survey and provided at least one saliva cotinine specimen at baseline. At three, six, and 12 month follow up studies, 47, 38, and 32 workers from the baseline sample of 68 completed a telephone survey and provided at least one saliva cotinine specimen. INTERVENTION: The smoke-free law went into effect 24 July 2003. MAIN OUTCOME MEASURES: Self reported sensory and respiratory symptoms and exposure to secondhand smoke; self administered saliva cotinine specimens. Analyses were limited to subjects in all four study periods who completed a telephone survey and provided at least one saliva cotinine specimen. RESULTS: All analyses were limited to participants who completed both an interview and a saliva specimen for all waves of data collection (n = 30) and who had cotinine concentrations < or = 15 ng/ml (n = 24). Hours of exposure to secondhand smoke in hospitality jobs decreased from 12.1 hours (95% confidence interval (CI) 8.0 to 16.3 hours) to 0.2 hours (95% CI -0.1 to 0.5 hours) (p < 0.01) and saliva cotinine concentration decreased from 3.6 ng/ml (95% CI 2.6 to 4.7 ng/ml) to 0.8 ng/ml (95% CI 0.4 to 1.2 ng/ml) (p < 0.01) from baseline to the 12 month follow up. The prevalence of workers reporting sensory symptoms declined from 88% (95% CI 66% to 96%) to 38% (95% CI 20% to 59%) (p < 0.01); there was no change in the overall prevalence of upper respiratory symptoms (p < 0.16). CONCLUSION: New York's smoke-free law had its intended effect of protecting hospitality workers from exposure to secondhand smoke within three months of implementation. One year after implementation, the results suggest continued compliance with the law.

Toxicities of total-body irradiation for pediatric bone marrow transplantation.

PURPOSE: To determine the acute and late effects, including cognitive function, of total body irradiation (TBI) and chemotherapy for bone transplant (BMT) in children with immunodeficiency or hematologic disorders. METHODS AND MATERIALS: At UCSF, 15 children with immunodeficiency disorders and 58 children with leukemia received chemoradiotherapy between July 1982 and November 1993 and were evaluated for toxicity. Patients with severe combined immunodeficiency disorder (SCID) received 7 Gy TBI while leukemia patients received 12 Gy TBI. RESULTS: Eight immunodeficient patients (53%) are alive at 4 months to 11 years posttransplant. Acute toxicity was limited and treatment well tolerated. Most patients developed mild nausea and vomiting, skin rash, or erythema. Transient fever/chills, oral mucositis, and alopecia were noted in approximately 50% of patients. Seventy-three percent of all patients demonstrated acute liver dysfunction, but only four (27%) developed veno-occlusive disease. All children had decreased growth velocity but normal growth hormone levels. Other endocrinologic evaluations including adrenocorticotropic hormone (ACTH), cortisol, and thyroid hormones were normal. Only one evaluable girl had delayed puberty with late onset of secondary sexual characteristics. Neuropsychological testing demonstrated an intelligence quotient (IQ) reduction between the baseline and 1 year post-BMT, with some recovery at 3 years. Only one patient developed a clinically significant cataract. Thirteen percent of patients had chronic interstitial lung disease. Four children developed exostosis. Only 1 of the 15 children developed a second malignancy (acute myelogenous leukemia) at age 5, 51 months posttransplant for SCID. For patients with leukemia, similar toxicities were observed. Twenty-nine percent disease-free survival was noted with a mean follow-up of 4.7 years. Twenty-two percent had chronic interstitial lung disease and two patients were diagnosed with cataracts. Graft-vs.-host-disease (GVHD), pubertal development arrest, and delayed puberty were seen. One child developed papillary thyroid carcinoma, 49 months post-BMT. Similar neuropsychological testing decrements were also observed. CONCLUSION: Our experience suggests that intensive chemoradiotherapy, even at a young age, does not cause severe, acute, or late toxicities but does result in a small IQ decrement and the risk of secondary malignancy in children with long-term follow-up.

Acute toxicity of three-dimensional conformal radiotherapy in prostate cancer patients eligible for implant monotherapy.

PURPOSE: To assess the acute toxicity of three-dimensional conformal radiotherapy (3D-CRT) in prostate cancer patients eligible for implant monotherapy. METHODS AND MATERIALS: Between December 1991 and June 1998, 198 prostate cancer patients were treated with 3D-CRT at the University of California Davis Medical Center. Fifty-two of these patients had a prostate-specific antigen (PSA) level /= Grade 3, e.g., hourly nocturia, gross hematuria, diarrhea requiring parenteral support, narcotics for pain control, or catheterization for acute urinary retention, was observed. CONCLUSION: Although relatively high doses of radiation are delivered to prostate cancers with 3D-CRT compared with conventional radiotherapy, 3D-CRT is surprisingly well-tolerated. No patients in the cohort eligible for implant monotherapy experienced acute toxicity >/= Grade 3.

Acute urinary toxicity following transperineal prostate brachytherapy using a modified Quimby loading method.

PURPOSE: To examine the acute urinary toxicity following transperineal prostate implant using a modified Quimby loading method with regard to time course, severity, and factors that may be associated with a higher incidence of morbidity. METHODS AND MATERIALS: One hundred thirty-nine patients with prostate adenocarcinoma treated with brachytherapy from 1997 through 1999 had follow-up records available for review. Patients considered for definitive brachytherapy alone included those with prostate specific antigen (PSA) < or = 6, Gleason score (GS) < or = 6, clinical stage < T2b, and prostate volumes generally less than 40 cc. Patients with larger prostate volumes were given neoadjuvant antiandrogen therapy. Those with GS > 6, PSA > 6, or Stage > T2a were treated with external beam radiation therapy followed by brachytherapy boost. Sources were loaded according to a modified Quimby method. At each follow-up, toxicity was graded based on a modified RTOG urinary toxicity scale. RESULTS: Acute urinary toxicity occurred in 88%. Grade I toxicity was reported in 23%, grade II in 45%, and grade III in 20%, with 14% requiring prolonged (greater than 1 week) intermittent or indwelling catheterization. Overall median duration of symptoms was 12 months. There was no difference in duration of symptoms between patients treated with I-125 or Pd-103 sources (p = 0.71). After adjusting for GS and PSA, multivariate logistic regression analysis showed higher incidence of grade 3 toxicity in patients with larger prostate volumes (p = 0.002), and those with more seeds implanted (p < 0.001). Higher incidence of prolonged catheterization was found in patients receiving brachytherapy alone (p = 0.01), with larger prostate volumes (p = 0.01), and those with more seeds implanted (p < 0.001). CONCLUSION: Interstitial brachytherapy for prostate cancer leads to a high incidence of acute urinary toxicity, most of which is mild to moderate in severity. A prolonged need for catheterization can occur in some patients. Patients receiving brachytherapy alone, those with prostate volumes greater than 30 cc, and those implanted with a greater number of seeds have the highest incidence of significant toxicity.

Changes in noradrenergic sensitivity to tumor necrosis factor-alpha in brains of rats administered clonidine.

Tumor necrosis factor-alpha (TNF alpha) and the imidazoline clonidine modulate norepinephrine (NE) release from noradrenergic nerve terminals in the central nervous system. The present study demonstrates an intrinsic association between presynaptic alpha 2-adrenergic receptor sensitivity and TNF alpha responsiveness in governing this NE release. Superfusion and electrical field stimulation were applied to a series of rat hippocampal brain slices in order to study the regulation of [3H]-NE release. The alpha 2-adrenergic agonist clonidine and the cytokine TNF alpha concentration-dependently inhibit [3H]-NE release; whereas, the alpha 2-adrenergic antagonist idazoxan potentiates [3H]-NE release. The fractional release of [3H]-NE during field stimulation of control hippocampal slices was decreased by the addition of TNF alpha in a concentration-dependent manner, an effect which was potentiated by the alpha 2-adrenergic antagonist idazoxan; whereas, TNF alpha attenuated the concentration-dependent potentiating effect of idazoxan. Furthermore, constitutive TNF alpha, demonstrated to be present in several brain areas, was significantly decreased following administration of the alpha 2-adrenergic agonist clonidine (0.6 mg/kg, i.p., twice daily) to rats for either 1 or 14 days, without a change in TNF alpha mRNA accumulation. We next investigated whether the presynaptic sensitivity to TNF alpha was changed after clonidine administration to rats. TNF alpha enhanced, rather than inhibited, [3H]-NE release after 1 day of clonidine administration, while a suppressed sensitivity to TNF alpha was observed in the hippocampus after 14 days of clonidine administration. In addition, in the presence of idazoxan, TNF alpha potentiation of [3H]-NE release after 1 day clonidine administration was reversed to a decreased inhibition as compared to control slices exposed to idazoxan. Therefore, the temporary reversal in the presynaptic TNF alpha response after 1 day of clonidine administration illustrates a mechanism of action for its persistent antihypertensive effect, its transient sedative and antihyperpathic effects, and its acute ability to promote antidepressants. These results demonstrate a novel role for an immune mediator in the central nervous system, and demonstrates that presynaptic TNF alpha responsiveness is intimately associated with adrenergic receptor sensitivity.

Beta-adrenergic receptor regulation of macrophage-derived tumor necrosis factor-alpha production from rats with experimental arthritis.

Prostaglandin E2 (PGE2) and beta-adrenergic agonists can suppress lipopolysaccharide-induced tumor necrosis factor-alpha (TNF) production from elicited macrophages. We assessed the responsiveness of rat peritoneal macrophages to PGE2 and the beta-adrenergic agonist isoproterenol during immunologically-mediated arthritis. We assessed macrophage sensitivity to these mediators from resident macrophages and macrophages elicited with either streptococcal cell wall or complete Freund's adjuvant. Peritoneal macrophages were obtained from female Lewis rats that were (1) injected with complete Freund's adjuvant and non-arthritic (CFA); (2) injected with streptococcal cell wall and arthritic (ART); (3) injected with streptococcal cell wall and non-reactive (NON) and (4) non-elicited resident macrophages (RES). When challenged with graded concentrations of lipopolysaccharide (0.1 to 10,000 ng/ml), macrophages obtained from each group of rats released TNF in a concentration-dependent manner, with macrophages from arthritic rats (ART) producing the greatest amount of TNF (p < 0.001). While PGE2 suppressed lipopolysaccharide (100 ng/ml) stimulated TNF production in a concentration-dependent manner in all groups, the greatest sensitivity to PGE2 was observed with macrophages obtained from rats which received streptococcal cell wall when compared to both complete Freund's adjuvant-elicited and resident macrophages (p < 0.05). The beta-adrenergic agonist isoproterenol also inhibited lipopolysaccharide-stimulated TNF production from macrophages in all groups. In addition, the specific beta 2-adrenergic antagonist, ICI 118.551, shifted isoproterenol concentration-effect curves to the right (p < 0.01). Minimal responsiveness to isoproterenol was observed with resident peritoneal macrophages. Maximum isoproterenol-induced inhibition of TNF production was observed with complete Freund's adjuvant-elicited macrophages, and significantly less in macrophages of streptococcal cell wall-injected rats. Of particular interest, macrophages obtained from streptococcal cell wall-injected rats, which became arthritic, were significantly less sensitive to isoproterenol than those which did not develop arthritis (p < 0.02). In addition, these changes in sensitivity were not reflected by changes in the sensitivity of both CFA and ART groups to dibutyryl cAMP. The present study demonstrates a shift in the balance between inhibitory mediator responses in rats inoculated with one of two different adjuvants. These investigations support the role of PGE2 and a neurotransmitter as immunomodulating compounds which may effectively maintain an inflammatory lesion such as arthritis.

Adrenergic regulation of macrophage-derived tumor necrosis factor-alpha generation during a chronic polyarthritis pain model.

Increases in the levels of proinflammatory cytokines, such as TNF alpha, have been intricately linked with arthritis and the pathogenesis of several models of neuropathic pain. In addition, arthritis (as well as other types of persistent pain) is associated with increased sympathetic activity and alterations of other responses in autonomic nervous activity. Adrenergic regulation of LPS-stimulated TNF production by M phi isolated from rats with streptococcal-cell-wall (SCW)-induced arthritis has been examined. Serum TNF levels and the cellular composition of peritoneal exudates have also been assessed. M phi were obtained from: (1) normal control rats, (2) animals injected with complete Freund's adjuvant (CFA), 3 rats injected with SCW and arthritic, and (4) those injected with SCW, which failed to develop arthritis. Serum levels of TNF alpha in rats that develop arthritis are significantly greater (2.4 fold) than levels from the other groups. The proportion of OX19-positive T cell subpopulations are the same in peritoneal exudates from all groups. Immunocytochemical staining also reveals differences between M phi subgroups in the degree of activation. Peritoneal exudates from rats that develop arthritis contain a greater proportion of the high TNF producing subclass of M phi, as identified by positive ED3 staining (p < 0.001). In contrast, Ia antigen presenting M phi (OX6-positive) in the peritoneal exudate cells are only elevated in rats administered CFA. The selective blockade of adrenergic receptors by idazoxan or propranolol demonstrates that the constitutive involvement of either alpha 2 or beta-adrenergic regulation of M phi-derived TNF production is pronounced in rats with arthritis (p < 0.001). These investigations demonstrate a distinctive pattern of peripheral M phi populations in rats that develop chronic polyarthritic pain. We believe that identification of interactions between the adrenergic responses and proinflammatory cytokines will lead to the development of improved strategies to treat patients with chronic pain.