Attentional Engagement for Pain-Related Information among Individuals with Chronic Pain: The Role of Pain Catastrophizing.

Although the evidence of the attentional bias of chronic pain individuals toward pain-related information is established in the literature, few studies examined the time course of attention toward pain stimuli and the role of pain catastrophizing on attentional engagement toward pain-related information. This study examined the time course of attention to pain-related information and the role of pain catastrophizing on attentional engagement for pain-related information. Participants were fifty young adult participants with chronic pain (35% male, 65% female; M = 21.8 years) who completed self-report questionnaires assessing pain catastrophizing levels (Pain Catastrophizing Scale (PCS)), depression (the Center for Epidemiologic Studies Depression Scale (CES-D)), anxiety (State-Trait Anxiety Inventory (STAI)), and pain disability (the Pain Disability Index: (PDI)). Attentional engagements to pain- and anger-related information were measured by the eye tracker. Significant interaction effects were found between (1) time and stimulus type for pain-related information (F (5, 245) = 11.55, p < 0.001) and (2) bias scores and pain catastrophizing (F (1, 48) = 6.736, p < 0.05). These results indicated that the degree of increase for pain bias scores were significantly greater than anger bias scores as levels of pain catastrophizing increased. Results of the present study provided the evidence for the attentional bias and information processing model which has clinical implications; high levels of pain catastrophizing may impair individuals' ability to cope with chronic pain by increasing attentional engagement toward pain-related information. The present study can add knowledge to attentional bias and pain research as this study investigated the time course of attention and the role of pain catastrophizing on attentional engagement toward pain-related information for adults with chronic pain conditions.

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

BACKGROUND: The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. METHODS: To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. RESULTS: Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. CONCLUSIONS: Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic disorders.

Self-expandable metal stents for malignant esophageal obstruction: a comparative study between extrinsic and intrinsic compression.

Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic.

Esophageal mucosal mast cell infiltration and changes in segmental smooth muscle contraction in noncardiac chest pain.

Mast cells release potent mediators that alter enteric nerve and smooth muscle functions and may contribute to the pathogenesis of functional gastrointestinal disorders. The goal of this study was to determine if mucosal mast cell infiltration was associated with smooth muscle segmental changes in esophageal contraction. All patients with noncardiac chest pain (NCCP) were divided into two groups consisting of patients with non-erosive reflux disease or functional chest pain (FCP) according to the results of ambulatory 24 hours esophageal pH monitoring and high-resolution manometry. Pressure-volume (PV) was calculated by multiplying the length of the esophageal segment, duration of the contraction, and mean pressure over the entire space-time box (P mean). Quantification of mast cells was performed in five consecutive nonoverlapping immunostained sections. Spearman correlation analysis showed that the distal segment PV correlated with the mast cell count in all of the patients combined and in patients with FCP with correlation coefficients of 0.509 and 0.436, respectively (P = 0.004 and P = 0.042). Similar findings were observed for the segmental ratio of distal to proximal smooth muscle PV in all patients and in patients with FCP (correlation coefficients 0.566; P = 0.001 and correlation coefficients 0.525; P = 0.012, respectively). Mucosal mast cell infiltration was associated with distal esophageal contraction as a key pathophysiologic factor of NCCP.

Heterogeneity of mucosal mast cell infiltration in subgroups of patients with esophageal chest pain.

BACKGROUND: Although there is growing evidence that an increase in mucosal mast cells (MMCs) in the small and large intestine is associated with visceral hypersensitivity, few studies have evaluated MMCs in humans with esophageal symptoms. The aim of this study was to investigate esophageal MMC distribution in patients with non-cardiac chest pain (NCCP) and to examine the association between the number of gut MMCs and other functional gastrointestinal disorders. METHODS: Forty-two consecutive NCCP patients and 10 healthy controls completed a questionnaire for bowel symptoms, chest pain intensity score, and psychologic depression. Esophageal, duodenal, and rectal MMCs were identified immunohistochemically and quantified by image analysis. KEY RESULTS: Numbers of MMCs were significantly higher in NCCP patients vs healthy controls (11.8 ± 5.6 vs 7.6 ± 3.7 MMCs/high-power field, p = 0.026). In comparison of subgroups classified by 24-h impedance-pH monitoring, esophageal MMC counts were highest in the hypersensitive esophagus group (p < 0.01) and were also significantly increased in the functional chest pain group (p < 0.05). A positive correlation between esophageal and duodenal MMC counts was observed in patients with functional dyspepsia (FD; Spearman ρ = 0.604, p = 0.037). In particular, patients with clinical overlap with irritable bowel syndrome showed a strong positive correlation between esophageal and rectal MMC numbers (Spearman ρ = 0.857, p = 0.010). CONCLUSIONS & INFERENCES: Among NCCP patients, increased MMC infiltration occurs in subgroups with hypersensitive esophagus and functional chest pain. In subpopulations with overlap with FD or irritable bowel syndrome, esophageal MMC counts demonstrated significant positive correlations with duodenal or rectal MMC counts.

The effects of statins on the clinical outcomes of Clostridium difficile infection in hospitalised patients.

BACKGROUND: An association between exposure to statin drugs and favourable treatment outcomes for various types of infections has been established. AIM: To determine the clinical characteristics and treatment outcomes of Clostridium difficile infection (CDI) among hospitalised patients taking statin drugs. METHODS: The medical records were reviewed for consecutive in-patients with CDI confirmed by positive toxin assay (A or B), C. difficile culture, or the presence of pseudomembrane on endoscopy. Treatment success was defined as the resolution of diarrhoea within 6 days of therapy. The primary end points were assessed by average symptom recovery time and treatment response (success or failure). RESULTS: Among 949 patients, the overall response to metronidazole was 91.9%. The baseline characteristics showed some differences between statin users and statin non-users with respect to mean disease severity score. In the multivariate analysis, successful treatment response was significantly associated with the absence of exposure to proton pump inhibitors (PPIs) (OR = 0.690, 95% CI = 0.513-0.929, P = 0.014) and with exposure to statins (OR = 1.449, 95% CI = 1.015-2.070, P = 0.041). Contrary to the treatment response, univariate and multivariate analyses failed to show that exposure to PPIs or statins affected symptom recovery times. Sixty-day CDI recurrence rates for those patients with statin exposure were significantly lower compared with those patients without statin exposure (3% vs. 7.3%, respectively; RR = 0.393, 95% CI = 0.167-0.926, P = 0.033). CONCLUSION: Prior statin exposure in patients with C. difficile infection is associated with a successful response to treatment.

Time-course microarrays reveal modulation of developmental, lipid metabolism and immune gene networks in intrascapular brown adipose tissue during the development of diet-induced obesity.

OBJECTIVE: The aim of this study was to establish the time-course of molecular events in intrascapular brown adipose tissue (iBAT) during the development of diet-induced obesity using microarrays and molecular network analysis. DESIGN: C57BL/6J male inbred mice were fed a high-fat diet (HFD) or normal diet (ND) and killed at multiple time-points over 24 weeks. METHODS: Global transcriptional changes in iBAT were determined by time-course microarrays of pooled RNA (n=6, pools per time-point) at 2, 4, 8, 20 and 24 weeks using Illumina MouseWG-6 v2.0 Beadchips. Molecular networks were constructed using the Ingenuity knowledgebase based on differentially expressed genes at each time-point. RESULTS: Body weight and subcutaneous adipose were progressively increased over 24 weeks, whereas iBAT was significantly increased between 6 and 12 weeks in HFD-fed C57BL/6J mice compared with controls. Blood glucose and insulin levels were increased between 16 and 24 weeks. Time-course microarrays, revealed 155 differentially expressed genes at one or more time-points over 24 weeks in the iBAT of HFD-fed mice compared with controls. Time-course network analysis revealed a network of skeletal muscle development genes that was activated between 2 and 4 weeks, subsequently a network of immune trafficking genes was activated at 8 weeks. After 20 and 24 weeks, multiple lipid metabolism and immune response networks were activated. Several target genes identified by time-course microarrays were independently validated using RT-qPCR. Tnnc1 was upregulated early between 2 and 4 weeks, later Cd68 and Col1a1 were upregulated between 20 and 24 weeks, whereas 11ß-hydroxysteroid dehydrogenase (Hsd11b1) was consistently downregulated during the development of diet-induced obesity. CONCLUSION: Molecular networks in iBAT are modulated in a time-dependent manner in response to a HFD. A broad range of gene targets exists to alter molecular changes within iBAT during the development of diet-induced obesity.

Restriction fragment mass polymorphism (RFMP) analysis based on MALDI-TOF mass spectrometry for detecting antiretroviral resistance in HIV-1 infected patients.

Viral genotype assessment is important for effective clinical management of HIV-1 infected patients, especially when access and/or adherence to antiretroviral treatment is reduced. In this study, we describe development of a matrix-assisted laser desorption/ionization-time of flight mass spectrometry-based viral genotyping assay, termed restriction fragment mass polymorphism (RFMP). This assay is suitable for sensitive, specific and high-throughput detection of multiple drug-resistant HIV-1 variants. One hundred serum samples from 60 HIV-1-infected patients previously exposed to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were analysed for the presence of drug-resistant viruses using the RFMP and direct sequencing assays. Probit analysis predicted a detection limit of 223.02 copies/mL for the RFMP assay and 1268.11 copies/mL for the direct sequencing assays using HIV-1 RNA Positive Quality Control Series. The concordance rates between the RFMP and direct sequencing assays for the examined codons were 97% (K65R), 97% (T69Ins/D), 97% (L74VI), 97% (K103N), 96% (V106AM), 97% (Q151M), 97% (Y181C), 97% (M184VI) and 94% (T215YF) in the reverse transcriptase coding region, and 100% (D30N), 100% (M46I), 100% (G48V), 100% (I50V), 100% (I54LS), 99% (V82A), 99% (I84V) and 100% (L90M) in the protease coding region. Defined mixtures were consistently and accurately identified by RFMP at 5% relative concentration of mutant to wild-type virus while at 20% or greater by direct sequencing. The RFMP assay based on mass spectrometry proved to be sensitive, accurate and reliable for monitoring the emergence and early detection of HIV-1 genotypic variants that lead to drug resistance.

Efficacy of leukotriene receptor antagonist for erosive esophagitis: a preliminary retrospective comparative study.

While diagnostic overlap exists between gastroesophageal reflux disease and eosinophilic esophagitis especially on histological findings, therapeutic approaches for the two disease entities are very different. Recently, anti-inflammatory treatment, in addition to acid suppressants, has been investigated for gastroesophageal reflux disease. This study investigated whether the incidence of endoscopic erosive esophagitis was lower in recipients of long-term leukotriene receptor antagonist (LTRA) treatment. This retrospective comparative study included 207 recipients of an LTRA and an equal number of controls who underwent screening upper endoscopic examination. Twenty-two (10.6%) and 51 (24.6%) cases of erosive esophagitis were detected in the LTRA and control groups, respectively (P < 0.001). A significantly higher incidence of minimal change esophagitis was also found in the controls compared with the LTRA group (14.5% vs. 2.4%, P < 0.001). On multivariate analysis, LTRA treatment was significantly and inversely associated with erosive esophagitis (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.13 to 0.46). Within the LTRA treatment group, an increased risk of erosive esophagitis was strongly associated with the presence of hiatal hernia (OR, 5.89; 95% CI, 2.20-15.73, P < 0.001) and short duration of LTRA treatment (OR, 0.64; 95% CI, 0.37-0.89, P= 0.022). In conclusion, this preliminary retrospective analysis demonstrated that patients who underwent long-term treatment with a LTRA had low incidence of endoscopic minimal change esophagitis.

Differences in post-operative functional disability and patient satisfaction between patients with long (three levels or more) and short (less than three) lumbar fusions.

We examined the differences in post-operative functional disability and patient satisfaction between 56 patients who underwent a lumbar fusion at three or more levels for degenerative disease (group I) and 69 patients, matched by age and gender, who had undergone a one or two level fusion (group II). Their mean age was 66 years (49 to 84) and the mean follow-up was 43 months (24 to 65). The mean pre-operative Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg pain, and the mean post-operative VAS were similar in both groups (p > 0.05), but post-operatively the improvement in ODI was significantly less in group I (40.6%) than in group II (49.5%) (p < 0.001). Of the ten ODI items, patients in group I showed significant problems with lifting, sitting, standing, and travelling (p < 0.05). The most significant differences in the post-operative ODI were observed between patients who had undergone fusion at four or more levels and those who had undergone fusion at less than four levels (p = 0.005). The proportion of patients who were satisfied with their operations was similar in groups I and II (72.7% and 77.0%, respectively) (p = 0.668). The mean number of fused levels was associated with the post-operative ODI (r = 0.266, p = 0.003), but not with the post-operative VAS or satisfaction grade (p > 0.05). Post-operative functional disability was more severe in those with a long-level lumbar fusion, particularly at four or more levels, but patient satisfaction remained similar for those with both long- and short-level fusions.

Histologic diagnosis based on forceps biopsy is not adequate for determining endoscopic treatment of gastric adenomatous lesions.

BACKGROUND AND STUDY AIMS: Controversy persists around the treatment of gastric low-grade dysplasia (LGD). The aim of this study was to investigate possible indications for the endoscopic resection of gastric LGD through analysis of the histologic discrepancies between specimens of gastric LGD obtained by forceps biopsy and by endoscopic mucosal resection (EMR), and of their clinicopathologic characteristics. PATIENTS AND METHODS: The study involved 293 gastric LGD that were histologically proven on the basis of forceps biopsy in Severance Hospital between January 2004 and December 2007. Twenty cases were regularly followed up, and the remaining 273 were resected by EMR. We performed univariate and multivariate analyses of clinical and endoscopic characteristics including lesion size, number of biopsy fragments, and endoscopic appearance, in order to analyze the factors affecting histologic discrepancies. RESULTS: Of the 273 lesions resected by EMR, 207 (75.8 %) showed concordant histology, whereas for 51 (18.7 %) the histology was upgraded after endoscopic resection. Lesion size, absence of whitish discoloration, and the presence of spontaneous bleeding were found by univariate analysis to be statistically significant factors predicting an upgraded histology after EMR ( P = 0.026, P < 0.001, and P = 0.025, respectively). Multivariate analysis also showed absence of whitish discoloration to be a statistically significant factor influencing histologic discrepancies ( P = 0.001, odds ratio 5.29, 95 % confidence interval 1.95 - 14.37). Perforation and bleeding rates associated with EMR for LGD were 0.7 % and 6.2 %, respectively. Twenty patients who did not undergo EMR were followed up for a mean of 22 months, and 3 were revealed to have adenocarcinoma and 1 high-grade dysplasia on the latest histologic exam. CONCLUSIONS: We should consider endoscopic resection for gastric LGD that are 2 cm or more in size and do not have whitish discoloration.

Survey of PCDDs and PCDFs in air and soil around various incinerators in Korea, 2003-2007.

To investigate the levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) pollution in soils and air around incinerators, a total of 574 soil and 48 air samples were collected around 22 incineration facilities in Korea from 2003 to 2007. The concentrations of PCDD/Fs in the flue gases and air ranged from 0.01 to 21.50 ng I-TEQ Sm(-3) and 0.0002 to 9.95 pg I-TEQ Sm(-3), respectively whereas concentrations in soils ranged from n.d. to 153.23 pg I-TEQ g(-1) dw. The average value was 8.14 pg I-TEQ g(-1) dw in soil samples.

Caudal midazolam does not affect sevoflurane requirements and recovery in pediatric day-case hernioplasty.

BACKGROUND: This prospective, randomized, double-blind study aimed to determine whether caudal midazolam combined with ropivacaine affects anesthetic requirements, recovery profiles, and post-operative analgesia compared with ropivacaine alone in pediatric day-case hernioplasty. METHODS: Sixty boys (2-5 years old) received caudal injections of 0.2% ropivacaine 1 ml/kg and epinephrine 1 : 200,000 with (RM group) or without (R group) 50 microg/kg of midazolam under sevoflurane anesthesia. The sevoflurane requirement was determined by adjusting to a bispectral index score=50. RESULTS: Concentrations of end-tidal sevoflurane (ETsevo%) after induction were similar in both groups. After caudal block, ETsevo% before and after surgical stimuli did not show significant intra- or intergroup differences. Recovery characteristics, including post-operative sedations, were similar in both groups. Post-operative pain scores were significantly lower in the RM group than the R group. CONCLUSIONS: Caudal midazolam (50 microg/kg) added to 2% ropivacaine did not influence sevoflurane requirement or recovery but improved post-operative analgesia compared with ropivacaine alone in pediatric day-case hernioplasty.

The effect of pneumoperitoneum and Trendelenburg position on acute cerebral blood flow-carbon dioxide reactivity under sevoflurane anaesthesia.

This study compared cerebral blood flow-carbon dioxide (CBF-CO2) reactivities in the supine and modest Trendelenburg position under pnemoperitoneum during sevoflurane anaesthesia. After induction of anaesthesia in 25 patients, mechanical ventilation was adjusted to increase Paco2 from 4.7 (T1) to 6.0 kPa (T2) in the supine position, and the change in jugular bulb oxygen saturation was measured as an index of CBF. Then, after establishment of pneumoperitoneum and 30 degrees Trendelenburg position, the CO(2) step and measurement of CBF were repeated. The CBF-CO2 reactivity was 7.5 (3.3) %xkPa(-1) (% change in jugular bulb oxygen saturation per unit change in Paco2) in the supine position and 6.8 (2.3) %xkPa(-1) in the 30 degrees Trendelenburg-pneumoperitoneum condition (p = 0.086). We conclude that CBF-CO2 reactivity is unchanged by the modest Trendelenburg position under pneumoperitoneum during sevoflurane anaesthesia.

Simultaneous monitoring technique for ASE and MPI noises in distributed Raman Amplified Systems.

We develop a new technique for simultaneously monitoring the amplified spontaneous emission (ASE) and multi-path interference (MPI) noises in distributed Raman amplified (DRA) systems. This technique utilizes the facts that the degree-of polarization (DOP) of the MPI noise is 1/9, while the ASE noise is unpolarized. The results show that the proposed technique can accurately monitor both of these noises regardless of the bit rates, modulation formats, and optical signal-to-noise ratio (OSNR) levels of the signals.

An evaluation of a six-week intervention designed to facilitate coping with psychological stress.

Community dwelling Korean adults (N = 40) coping with the stress of severe mental illness were randomly assigned to a six-week differentiation furthering intervention (experimental) or a directed problem-solving treatment program (control) and administered pre- and posttreatment measures including the Morey Personality Assessment Screener (PAS) and Group Embedded Figures Test (GEFT). As predicted, the experimental group showed greater improvement on 6 out of 10 mental health subscales (PAS) and on the GEFT than the controls. For the entire sample, differentiation gainers showed more improvement on three PAS subscales compared with the no change or loss in differentiation groups. A three-month follow-up showed greater attendance at mental health appointments for the experimental group over controls and for total sample differentiation gainers over nongainers. Implications are discussed of this empirically tested model of a community intervention to facilitate coping with stress and enhancing competence.

Impact of a targeted asthma intervention program on treatment costs in patients with asthma.

OBJECTIVE: To evaluate the impact of a targeted asthma intervention on treatment costs, utilization of medical services, number of prescription drugs filled, and trends of medication use from a third-party perspective. STUDY DESIGN: Longitudinal population-based study. METHODS: Study asthmatic patients were classified into intermittent and persistent asthma groups according to the Health Plan Employer Data and Information Set (HEDIS) 2000 asthma measurement. The intervention instituted appropriate asthma drug therapy according to National Heart, Lung, and Blood Institute guidelines. A paired t test and analysis of covariance were used to compare treatment costs and the number of prescriptions dispensed in the 9 months before and the 9 months after the intervention. RESULTS: The study patients (n = 1616) included 566 with intermittent asthma and 1050 with persistent asthma. After the intervention, treatment costs per patient increased significantly by $122 in the intermittent asthma group (P = .001) but decreased significantly by $247 in the persistent asthma group (P < .001). Costs incurred by patients with persistent asthma decreased by $149 for hospitalization (P = .003), $16 for emergency room visits (P < .001), $82 for physician visits (P < .001), and increased by $1 for asthma medications (P = .938). The number of asthma medication prescriptions per patient increased by 0.72 prescriptions in the intermittent asthma group (P < .001), whereas the persistent asthma group had a per patient reduction of 0.99 prescriptions (P < .001). CONCLUSION: A targeted asthma intervention resulted in decreased hospitalization, emergency room, and physician visit costs in patients with persistent asthma.

Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells.

The mechanisms of the antineoplastic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) still are unknown, but the induction of apoptosis is one of the possible mechanisms. We attempted to demonstrate the role of mitogen-activated protein (MAP) kinases, generally considered to be important mediators of proliferative and apoptotic signals, in NSAID-induced colon cancer cell apoptosis. Apoptosis was detected by demonstration of DNA fragmentation in agarose gel electrophoresis. Cell death was assessed by trypan blue dye exclusion method. MAP kinase activation was assessed by Western blot using phosphospecific antibodies to MAP kinases. Kinase assay using activating transcription factor-2 (ATF-2) fusion protein as a substrate was also performed for measuring p38 MAP kinase activity. For the inhibition of p38 MAP kinase, pyridinylimidazole compound (SB203580) was utilized. Caspase-3 activity was measured using the tetrapeptide fluorogenic substrate Ac-DEVD-AMC. Treatment of HT-29 cells with NSAIDs results in time- and dose-dependent induction of apoptosis, accompanied by sustained activation of all three MAP kinase subfamilies. The SB203580, a p38 MAP kinase inhibitor, reduced indomethacin-induced cell death by 43%, while PD098059, a MAPK/ERK kinase (MEK)1 inhibitor, did not affect cell death. p38 MAP kinase and caspase-3 activation were not significantly interlinked in indomethacin-induced apoptosis. From these results, we conclude that NSAIDs can induce prolonged activation of MAP kinases in colon cancer cells and that, of these, p38 MAP kinase may play a partial but significant role in indomethacin-induced apoptosis.