Development of a gender-relevant tobacco cessation intervention for women in Brazil-an intervention mapping approach to planning.

The purpose of this article is to describe the development of a theory-based, culturally and gender-relevant Community Health Worker (CWH)-led tobacco cessation intervention for low-income Brazilian women who augments the tobacco cessation program offered through the public health system using Intervention Mapping (IM). We began with the establishment of a network of representatives from different segments of society followed by comprehensive needs assessments. We then established a logical planning process that was guided by a theoretical framework (Social Cognitive Theory) and existing evidence-based tobacco cessation programs, taking into account socio-political context of a universal health care system. Given the gender-relevance of our intervention and the importance of social support in tobacco cessation among women, we chose an intervention that would be delivered within the public health system but augmented by CHWs that would be trained in behavior change by researchers. One of major advantages of utilizing IM was that decisions were made in a transparent and supportive manner with involvement of all stakeholders throughout the process. Despite the fact that this process is very taxing on researchers and the health care system as it takes time, resources and negotiation skills, it builds trust and promotes ownership which can assure sustainability.

Increase in Salmonella enterica serovar Paratyphi A infections in Phnom Penh, Cambodia, January 2011 to August 2013.

We report an increased number of Salmonella enterica Paratyphi A infections in adults in Cambodia. Between January 2011 and August 2013, 71 S. Paratyphi A isolates were recovered from blood cultures, representing a 44-fold increase compared to July 2007 to December 2010, while monthly numbers of cultures did not change. Infections with S. Typhi increased two-fold in the same period. Most cases came from the capital Phnom Penh. These findings warrant epidemiological investigation to support public health measures.

Multi-criteria Decision Analysis Software in Healthcare Priority Setting: A Systematic Review.

OBJECTIVE: The objectives of this systematic review were to identify studies using Multi-Criteria Decision Analysis (MCDA) software tools to support health prioritisation processes and describe the technical capabilities of the MCDA software tools identified. METHODS: First, a systematic literature review was conducted in the MEDLINE, EMBASE, Web of Science, EconLit and Cochrane databases in July 2019 to identify studies that have used MCDA software for priority setting in health-related problems. Second, the MCDA software tools found in the review were downloaded (full versions, where freely available, and trial versions otherwise) and tested to extract their key technical characteristics. RESULTS: Nine studies were included, from which seven different software tools, 1000minds®, M-MACBETH, Socio Technical Allocation of Resources (STAR), Strategic Multi-Attribute Ranking Tool (SMART), Visual PROMETHEE, EVIDEM and the Prioritisation Framework, were identified. These software tools differed in terms of the operating systems (including web interface), MCDA technique(s) available for use, visualisation features, and the capability to perform Value for Money (VfM) and sensitivity analyses. CONCLUSIONS: The use of MCDA software in prioritisation processes has a number of advantages such as inclusion of several types of stakeholders and the ability to analyse a greater number of alternatives and criteria and perform real-time sensitivity analyses. Proprietary software (i.e. software with licensing fees) seemed to have more features than freely available software. However, this field is still developing, with only a few studies where MCDA software was used to support health priority setting and opportunity costs not explicitly captured in many software tools.

Elf-1 is a transcriptional regulator of the Tie2 gene during vascular development.

Vascular development requires the tightly coordinated expression of several growth factors and their receptors. Among these are the Tie1 and Tie2 receptors, which are almost exclusively endothelial cell-specific. The critical transcriptional regulators of vascular-specific gene expression remain largely unknown. The Ets factors are a family of evolutionarily conserved transcription factors that regulate genes involved in cellular growth and differentiation. We have recently shown that the Ets factor NERF is a strong transactivator of the Tie1 and Tie2 genes. To extend these studies, we have begun to identify the Ets factors that are expressed in developing blood vessels of the chicken chorioallantoic membrane (CAM), a highly vascular embryonic network. RNA was extracted from microdissected CAM blood vessels, and reverse transcriptase-polymerase chain reaction was performed using oligonucleotides encoding conserved amino acids within the Ets domain. One of the polymerase chain reaction fragments was subcloned and identified as the chicken homologue of the Ets factor ELF-1, cELF-1. ELF-1 is most closely related to the Ets factor NERF. In situ hybridization and immunohistochemistry demonstrate that cELF-1 is enriched in developing chicken blood vessels. cELF-1 is also a strong transactivator of the Tie1 and Tie2 genes and can bind to conserved Ets sites within the promoters of these genes. A complex of similar size forms when gel shifts are performed with cellular extracts derived from the CAM blood vessels, which is recognized by an antibody against cELF-1. In summary, ELF-1 belongs to a subset of Ets factors that regulate vascular-specific gene expression during blood vessel development.

Assistência de enfermagem na terapêutica paliativa direcionada ao controle de sintomas / Nursing care in palliative therapy aimed at symptom control

Objetivo: buscar na literatura científica o que as evidências apontam sobre a assistência da enfermagem ao paciente em cuidados paliativos direcionada ao controle de sintomas. Método: Revisão integrativa da literatura realizada nas bases de dados Lilacs, Scielo, Medline e periódicos da Capes, cujo corpus da análise foi de 8 artigos. Foram incluídos artigos disponíveis nos idiomas inglês, português e espanhol, publicados nos últimos 5 anos, disponíveis na íntegra e gratuitamente. Resultados: Os artigos selecionados apresentaram características diversas, possuindo populações alvo, amostras, finalidades e métodos variados. Após análise dos dados foram encontradas informações que se complementaram acerca do tema, possibilitando apresentação dos resultados em duas categorias: Manifestações clínicas em pacientes em cuidados paliativos e Assistência de enfermagem no manejo de paciente em cuidados paliativos. Conclusão: A enfermagem tem papel de auxiliar na monitoração dos casos de câncer e intervir nos sintomas físicos e psicológicos através de tratamentos farmacológicos e não farmacológicos.(AU)

Objective: to search in the scientific literature what the evidence points about nursing care for patients in palliative care directed to symptom control. Method: Integrative literature review carried out in the Lilacs, Scielo, Medline and Capes journals databases, whose corpus of analysis was 8 articles. Articles available in English, Portuguese and Spanish, published in the last 5 years, were available in full and free of charge. Results: The selected articles had different characteristics, having target populations, samples, purposes and varied methodological means. After analyzing the data, information was found that complemented each other on the topic, made it possible to present the results in two categories: Clinical manifestations in patients in palliative care and Nursing assistance in the management of patients in palliative care. Conclusion: Nursing has the role of assisting in the monitoring of cancer cases and intervening in physical and psychological symptoms through pharmacological and non-pharmacological treatments.(AU)

Objetivo: buscar en la literatura científica qué apunta la evidencia sobre los cuidados de enfermería al paciente en cuidados paliativos dirigidos al control de síntomas. Método: Revisión integradora de la literatura realizada en las bases de datos de las revistas Lilacs, Scielo, Medline y Capes, cuyo corpus de análisis fue de 8 artículos. Los artículos disponibles en inglés, portugués y español, publicados en los últimos 5 años, estaban disponibles en su totalidad y de forma gratuita. Resultados: Los artículos seleccionados tenían características diferentes, teniendo poblaciones objetivo, muestras, propósitos y medios metodológicos variados. Luego del análisis de los datos, se encontró información que se complementaba sobre el tema, posibilitó presentar los resultados en dos categorías: Manifestaciones clínicas en pacientes en cuidados paliativos y Asistencia de enfermería en el manejo de pacientes en cuidados paliativos. Conclusión: Enfermería tiene el rol de asistir en el seguimiento de los casos de cáncer e intervenir en los síntomas físicos y psicológicos mediante tratamientos farmacológicos y no farmacológicos.(AU)

Effects of oxidized LDL on mononuclear phagocytes: inhibition of induction of four inflammatory cytokine gene RNAs, release of NO, and cytolysis of tumor cells.

A critical step in development of atherosclerosis is the interaction of oxidized low-density lipoprotein (LDL) with mononuclear phagocytes. Oxidized LDL, as well as acetyl-LDL, is rapidly taken up into macrophages via a family of scavenger receptors. We report that macrophages treated with oxidized LDL have markedly lower levels of mRNA specific for the genes MCP-1, TNF-alpha, IL-1 alpha, and KC as measured by Northern blot analyses of lipopolysaccharide (LPS)-stimulated macrophages. By contrast, acetyl-LDL does not inhibit these genes at the doses at which oxidized-LDL is effective. Similar effects are observed whether the LDL is oxidized in the presence of Cu2+ or of Fe2+. Such inhibition also occurs when maleylated bovine serum albumin (BSA), which also clears by one or more scavenger receptors on macrophages, is used as the stimulant. Fe2+ or Cu2+ oxidized LDL inhibits release of nitric oxide when triggered by LPS and direct cytolysis of tumor cells when triggered by maleylated BSA or LPS. Taken together, the data presented indicate that oxidized LDL inhibits induction of several important gene RNAs as well as functional markers that characterize the development of inflammatory and fully activated macrophages.

Maleylated-BSA induces hydrolysis of PIP2, fluxes of Ca2+, NF-kappaB binding, and transcription of the TNF-alpha gene in murine macrophages.

The interaction of altered lipids or proteins with the several scavenger receptors (SR) on macrophages can lead to disparate results in both gene expression and cell function. However, the molecular bases of signaling induced by SR ligation have remained obscure. Here we report that maleylated-bovine serum albumin (maleyl-BSA) binds a low-affinity SR, initiating PIP2 hydrolysis, [Ca2+]i spikes, phospholipase A2 (PLA2) activation, nuclear factor-kappa(B) (NF-kappa(B)) binding to its cognate nucleotide and tumor necrosis factor alpha (TNF-alpha) gene transcription. We recently reported that oxidized low-density lipoprotein (ox-LDL), which binds another macrophage SR, induced pertussis-toxin-sensitive hydrolysis of PIP2 and elevations in [Ca2+]i [J. Biol. Chem. 270, 3475-3478, 1995]. By contrast, maleyl-BSA-initiated events were not pertussis toxin-sensitive and produced less [Ca2+]i spiking than ox-LDL. Furthermore, maleyl-BSA led to binding of NF-kappa(B) to its cognate nucleotide and TNF-alpha gene transcription, whereas ox-LDL suppressed these events. Collectively, this data suggests that maleyl-BSA and ox-LDL bind to distinct SR on murine macrophages, initiate distinct signal transduction pathways, and produce different functional effects.

Systematic screening for drug-resistant tuberculosis with Xpert(®) MTB/RIF in a referral hospital in Cambodia.

SETTING: Limited access to drug susceptibility testing (DST) in referral hospitals contributes to delayed detection of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To document the impact of identifying rifampicin (RMP) resistance using Xpert(®) MTB/RIF on time to diagnosis and time to treatment, and evaluate its performance under programmatic conditions. METHODS: Using a prospective observational study, we screened presumptive MDR-TB cases with Xpert and solid culture/conventional DST. RMP resistance was confirmed using a line-probe assay (LPA). We recorded diagnostic and treatment delays. We performed rpoB gene sequencing post hoc to resolve discordant RMP susceptibilities. RESULTS: We screened 299 of 345 presumptive MDR-TB individuals, and identified 44 Xpert RMP-resistant cases: 16/165 (10%) were new and 28/136 (20%) retreated. The median time to diagnosis was 2 days (Xpert) vs. an additional 6 with LPA; the median time to treatment was 14 days. Confirmatory LPA on 39/44 revealed 27 concordant, 6 discordant and 6 invalid results. Xpert RMP resistance was confirmed in respectively 24/30 (80%) and 21/23 (91%) by phenotypic DST and rpoB sequencing. CONCLUSION: Screening presumptive MDR-TB patients with Xpert enabled rapid diagnosis and treatment of MDR-TB. Xpert performed well, provided appropriate risk assessment was done. Rapid confirmatory testing added little to clinical decision making. Our findings support the latest World Health Organization guidelines to abandon confirmatory LPA in favour of repeat Xpert when in clinical doubt, pending phenotypic DST.

Is frontloaded sputum microscopy an option in active tuberculosis case finding?

SETTING: Active tuberculosis (TB) case finding (ACF) in Phnom Penh, Cambodia using light-emitting diode fluorescence microscopy (FM). OBJECTIVE: To evaluate the smear-positive yield of frontloaded (same-day) smear microscopy in ACF. DESIGN: All presumptive TB cases screened through ACF were asked to provide three sputum specimens: two spot specimens on Day 1 and a morning specimen on Day 2 (spot-spot-morning, SSM). Laboratory technicians blinded to previous results read the smears using FM. We considered only SSM series with at least one positive smear to calculate the proportion of TB cases missed and to determine the difference between the spot-spot (SS) and spot-morning (SM) approach. RESULTS: Of 4616 presumptive TB patients enrolled, 3306 provided three sputum samples. Of 2957 (89.4%) who followed the SSM approach, 188 (6.4%) were smear-positive: 177 on SM and 160 on SS. The incremental yield of the second sputum sample was 18.1% for SM vs. 9.4% for SS. Relative to any smear-positive case detected by SSM, 28/188 (14.9%, 95%CI 10.1-20.8) TB cases would be missed by SS vs. 11/188 (5.9%, 95%CI 3.0-10.2) by SM. The difference in the proportion of missed TB patients was 9.0% (P = 0.006). CONCLUSION: ACF frontloaded sputum microscopy is inferior in terms of smear-positive yield: the SS approach would have missed a significant proportion of smear-positive TB.

Deletion of cysteine 369 in lysyl hydroxylase 1 eliminates enzyme activity and causes Ehlers-Danlos syndrome type VI.

This study describes the relative contribution of the 10 cysteine residues in lysyl hydroxylase 1 (LH1) to enzyme activity. We have identified a novel mutation of a 15-bp deletion in exon 11 in one LH1 allele, that codes for amino acids 367-371 (DLCRQ), in two unrelated compound heterozygous patients with Ehlers-Danlos type VI. The mutations in their other alleles were a C1119T change (exon 10) and a predicted Q49X (exon 2). We confirmed that the loss of cysteine 369 in the deleted sequence contributed to the diminished enzyme activity by structure/function analysis of mutant LH1 constructs, in which C369 and the nine other cysteines were individually mutated to serine by site-directed mutagenesis of a normal pAcGP67/LH1cDNA construct. Following their expression in an Sf9 insect cell/baculovirus system, SDS-PAGE and Western analysis showed that equivalent levels of correctly-sized (85-kDa) products were secreted. The mutation of residues C369 and also C375, C552 and C687 virtually eliminated LH activity, whereas mutations of C267, C270, and C680 had an intermediate effect. In contrast, the C204S, C484S and C566S constructs had normal activity. Although disulfide bond formation may affect the relative contribution of each cysteine to LH activity, catalytic activity does not appear to be directly related to dimerization of the enzyme.

Lovastatin induces a pronounced differentiation response in acute myeloid leukemias.

We recently identified HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, as a potential therapeutic target of various retinoic acid responsive cancers. Lovastatin, a competitive inhibitor of HMG-CoA reductase, induced a retinoic acid-like differentiation response followed by extensive apoptosis in neuroblastoma cell lines at relatively low concentrations (<20 microM) of this agent. More recently, we demonstrated that acute myeloid leukemias but not acute lymphocytic leukemias also displayed increased sensitivity to lovastatin-induced apoptosis. In this study, we examined the ability of lovastatin to induce differentiation of acute myeloid leukemic cells and to evaluate the role differentiation may hold in the anti-leukemic properties of this agent. Increased expression of the leukocyte integrins CD11b and CD18 as well as down-regulation of the anti-apoptotic gene bcl-2 are associated with late stage differentiation of the myeloid lineage and retinoic acid induced maturation of acute myeloid leukemic cells. Lovastatin exposure induced increased expression of CD11b and CD18 markers similar to retinoic acid treatment. Following 24 hrs exposure to 20 microM lovastatin, all 7 acute myeloid leukemia cell lines tested showed a decrease in bcl-2 mRNA expression while only 1/5 acute lymphocytic leukemia cell lines showed a similar response. A role for bcl-2 in the apoptotic response of acute myeloid leukemia cells to lovastatin was demonstrated as exogenous constitutive expression of bcl-2 in the AML-5 cell line inhibited apoptosis in a time and dose dependent manner. Thus, lovastatin exposure of acute myeloid leukemia cells induced a differentiation response that may contribute to the therapeutic potential of this agent in the treatment of this disease.

An improved titration model reducing over estimation of total volatile fatty acids in anaerobic digestion of energy crop, animal slurry and food waste.

Titration methodologies have been used for the many years for low cost routine monitoring of full scale anaerobic digestion plants. These methodologies have been correlated to indicate the carbonate alkalinity and the volatile fatty acids (VFA) content within digesters. Two commonly used two end-point titration methods were compared using a dataset of 154 samples from energy crop and animal slurry digestates and were shown to be inaccurate in the estimation of tVFA. Using this dataset correlated with HPLC VFA analysis, two empirical bivariate linear regression equations were derived, where the validation dataset showed an absolute tVFA mean error improvement from ±3386 and ±3324 mg kg(-1) tVFA to ±410 and ±286 mg kg(-1) tVFA, respectively. The same equation was then applied to a food waste dataset where an absolute tVFA mean error was improved from ±3828 to ±576 mg kg(-1) tVFA. The newly derived titration equations can provide greater confidence in digester performance monitoring and are tools that can improve digester management.

The utility of stool cultures for diagnosing tuberculosis in people living with the human immunodeficiency virus.

BACKGROUND: Delayed diagnosis of tuberculosis (TB) increases mortality. OBJECTIVE: To evaluate whether stool culture improves the diagnosis of TB in people living with the human immunodeficiency virus (PLHIV). DESIGN: We analysed cross-sectional data of TB diagnosis in PLHIV in Cambodia, Thailand and Viet Nam. Logistic regression was used to assess the association between positive stool culture and TB, and to calculate the incremental yield of stool culture. RESULTS: A total of 1693 PLHIV were enrolled with a stool culture result. Of 228 PLHIV with culture-confirmed TB from any site, 101 (44%) had a positive stool culture; of these, 91 (90%) had pulmonary TB (PTB). After adjusting for confounding factors, a positive stool culture was associated with smear-negative (odds ratio [OR] 26, 95% confidence interval [CI] 12-58), moderately smear-positive (OR 60, 95%CI 23-159) and highly smear-positive (OR 179, 95%CI 59-546) PTB compared with no PTB. No statistically significant association existed with extra-pulmonary TB compared with no extra-pulmonary TB (OR 2, 95%CI 1-5). The incremental yield of one stool culture above two sputum cultures (5%, 95%CI 3-8) was comparable to an additional sputum culture (7%, 95%CI 4-11). CONCLUSION: Nearly half of the PLHIV with TB had a positive stool culture that was strongly associated with PTB. Stool cultures may be used to diagnose TB in PLHIV.

First National Workshop on Antibiotic Resistance in Cambodia: Phnom Penh, Cambodia, 16-18 November 2011.

The First National Workshop on Antibiotic Resistance in Cambodia was organised by the Cambodian Ministry of Health with support from several national and international partner institutions. It brought together policy-makers, clinicians, pharmacists, laboratory technicians and other professionals dealing with the problems of bacterial infection and antibiotic resistance across the country. Antibiotic resistance data from starting up and experienced laboratories were presented, showing high rates of resistance in key pathogens to most antibiotics currently available in Cambodia, e.g. 70-90% multidrug resistance and 70-80% decreased ciprofloxacin susceptibility in Salmonella enterica serovar Typhi, 20-40% meticillin resistance rates in Staphylococcus aureus and 30-50% extended-spectrum ß-lactamase production in Escherichia coli. A five-point plan was discussed, which included initiatives from government and non-governmental partners, focusing on rational prescribing, clinical practice guidelines, improved laboratory services, infection prevention and enhanced education at all levels. Implementation, however challenging, is a priority given the high levels of resistance seen in key pathogens and the overall health needs in the country.

Induction of cytochrome P450 enzymes in rat liver by two conazoles, myclobutanil and triadimefon.

This study was undertaken to examine the inductive effects of two triazole antifungal agents, myclobutanil and triadimefon, on the expression of hepatic cytochrome P450 (CYP) genes and on the activities of CYP enzymes in male Sprague Dawley rats. Rats were dosed with the conazoles at three dose levels by gavage for 14 days: myclobutanil (150, 75, and 10mgkg(-1) body weight day(-1); triadimefon (115, 50, and 10 mg kg(-1) body weight day-'), which included their maximum tolerated dose levels (MTD). Both myclobutanil and triadimefon significantly induced pentoxyresorufin O-depentylase activities at their MTD levels: myclobutanil, 8.1-fold at 150mgkg(-1) body weight day- ; and triadimefon, 18.5-fold at 115mgkg(-1) body weight day-'. Benzyloxyresorufin O-debenzylase activities were similarly increased: myclobutanil, 13.3-fold; triadimefon, 27.7-fold. Quantitative real-time reverse-transcription polymerase chain reaction assays were used to characterize the mRNA expression of specific CYP genes induced by these two conazoles. Myclobutanil and triadimefon treatment at their MTD levels significantly increased rat hepatic mRNA expression of CYP2B1 (14.3- and 54.6-fold), CYP3A23/3A1 (2.2- and 7.3-fold), and CYP3A2 (1.5- and 1.7-fold). Western immunoblots of rat hepatic microsomal proteins identified significantly increased levels of CYP isoforms after myclobutanil or triadimefon treatment at their MTD levels: CYP2BI/2 (4.8- and 5.3-fold), and CYP3A1 (2.2- and 2.9-fold). Triadimefon also increased CYP3A2 immunoreactive protein levels 1.8-fold. These results indicate that triadimefon and myclobutanil, like other triazole-containing conazoles, induced CYP2B and CYP3A families of cytochromes in rat liver.

Maleylated-BSA enhances production of nitric oxide from macrophages.

Maleylated-bovine serum albumin (maleyl-BSA) elicits transcription and secretion of a number of proinflammatory genes via ligation of the low-affinity scavenger receptor (SR) on macrophages. We now demonstrate that while neither maleyl-BSA, nor interferon-gamma (INF-gamma) alone induce nitric oxide (NO) production, when combined they promote release of NO from murine peritoneal macrophages. This effect was blocked by treatment with oxidized-low density lipoprotein. Maleyl-BSA activated NF-kappaB dimers capable of binding the NF-kappaBd sequence unique to the iNOS promoter, but this failed to induce significant new transcription or accumulation of iNOS mRNA. The combination of maleyl-BSA and IFN-gamma failed to demonstrate synergy at the transcriptional or mRNA levels, as these levels were comparable to those elicited by IFN-gamma alone. These studies suggest that the synergy in NO production between maleyl-BSA and IFN-gamma occurs after the accumulation of iNOS-specific mRNA, possibly at the translational or post-translational level.

Oxidized low density lipoprotein suppresses activation of NF kappa B in macrophages via a pertussis toxin-sensitive signaling mechanism.

The interaction of oxidized low density lipoprotein (ox-LDL) and macrophages is generally believed to be a significant inductive step in atherogenesis. Endocytosis of ox-LDL by scavenger receptors (SR) on macrophages is one result of this interaction, as is suppressed expression of several lipopolysaccharide (LPS)-stimulated, inflammatory genes such as tumor necrosis factor-alpha (TNF-alpha). Events subsequent to SR ligation, including intracellular signaling events if any, have not been established. We report here that ox-LDL initiates rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate 2 (PIP2) and intracellular fluxes of Ca2+ in macrophages, both of which are sensitive to pertussis toxin. ox-LDL also suppresses the LPS-induced binding of macrophage extracts to an NF kappa B sequence oligonucleotide and the LPS-initiated accumulation of RNA specific for TNF-alpha. These latter two effects are pertussis toxin-sensitive. Ligation of SR by ox-LDL thus initiates a pertussis toxin-sensitive signaling pathway in macrophages, which involves hydrolysis of PIP2 and which can suppress expression of the TNF-alpha gene by modulating activation of NF kappa B.

Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages.

Aspirin has been reported to inhibit the activation of nuclear factor-kappaB (NF-kappaB) through stabilization of inhibitor kappaB (IkappaB). This observation led us to investigate the role of aspirin in suppressing the activation of the NF-kappaB-regulated tumor necrosis factor-alpha (TNF-alpha) gene expression in primary macrophages. We now report that therapeutic doses of aspirin suppress lipopolysaccharide-inducible NF-kappaB binding to an NF-kappaB binding site in the TNF-alpha promoter, lipopolysaccharide-induced TNF-alpha mRNA accumulation, and protein secretion. IkappaB is also stabilized under these conditions. The aspirin-initiated stabilization of IkappaB, suppression of induced TNF-alpha mRNA, and NF-kappaB binding to the TNF-alpha promoter are blocked by pretreatment with pertussis toxin. These studies suggest that aspirin may exert significant anti-inflammatory effects by suppressing the production of macrophage-derived inflammatory mediators.