Long-term survival following elective colon cancer surgery in the aged. A population-based cohort study.

AIM: The number of colorectal cancer patients increases with age. Long-term data support personalized management due to heterogeneity within the older population. This registry- and population-based study aimed to analyse long-term survival, and causes of death, after elective colon cancer surgery in the aged, focusing on patients who survived more than 3 months postoperatively. METHODS: The data included patients ≥ 80 years who had elective surgery for Stage I-III colon cancer in four Finnish centres. The prospectively collected data included comorbidities, functional status, postoperative outcomes and long-term survival. Univariate and multivariate Cox regression analysis were conducted to determine factors associated with long-term survival. RESULTS: A total of 386 surgical patients were included, of whom 357 survived over 3 months. Survival rates for all patients at 1, 3 and 5 years were 85%, 66% and 55%, compared to 92%, 71% and 59% for patients alive 3 months postoperatively, respectively. Higher age, American Society of Anesthesiologists (ASA) score ≥ 4, Charlson Comorbidity Index ≥ 6, tumour Stage III, open compared to laparoscopic surgery and severe postoperative complications were independently associated with reduced overall survival. Higher age (hazard ratio 1.97, 1.14-3.40), diabetes (1.56, 1.07-2.27), ASA score ≥ 4 (3.27, 1.53-6.99) and tumour Stage III (2.04, 1.48-2.81) were the patient-related variables affecting survival amongst those surviving more than 3 months postoperatively. Median survival time for patients given adjuvant chemotherapy was 5.4 years, compared to 3.3 years for patients not given postoperative treatment. CONCLUSIONS: Fit aged colon cancer patients can achieve good long-term outcomes and survival with radical, minimally invasive surgical treatment, even with additional chemotherapy.

Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice.

Dopamine in prefrontal cortices is implicated in cognitive and emotional functions, and the dysfunction of prefrontal dopamine has been associated with cognitive and emotional deficits in mental illnesses. These findings have led to clinical trials of dopamine-targeting drugs and brain imaging of dopamine receptors in patients with mental illnesses. Rodent studies have suggested that dopaminergic pathway projecting to the medial prefrontal cortex (mPFC) suppresses stress susceptibility. Although various types of mPFC neurons express several dopamine receptor subtypes, previous studies neither isolated a role of dopamine receptor subtype nor identified the site of its action in mPFC. Using social defeat stress (SDS) in mice, here we identified a role of dopamine D1 receptor subtype in mPFC excitatory neurons in suppressing stress susceptibility. Repeated social defeat stress (R-SDS) reduces the expression of D1 receptor subtype in mPFC of mice susceptible to R-SDS. Knockdown of D1 receptor subtype in whole neuronal populations or excitatory neurons in mPFC facilitates the induction of social avoidance by SDS. Single social defeat stress (S-SDS) induces D1 receptor-mediated extracellular signal-regulated kinase phosphorylation and c-Fos expression in mPFC neurons. Whereas R-SDS reduces dendritic lengths of mPFC layer II/III pyramidal neurons, S-SDS increases arborization and spines of apical dendrites of these neurons in a D1 receptor-dependent manner. Collectively, our findings show that D1 receptor subtype and related signaling in mPFC excitatory neurons mediate acute stress-induced dendritic growth of these neurons and contribute to suppression of stress susceptibility. Therefore, we propose that D1 receptor-mediated dendritic growth in mPFC excitatory neurons suppresses stress susceptibility.

Abdominal diameter index is a stronger predictor of prevalent Barrett's esophagus than BMI or waist-to-hip ratio.

Abdominal obesity is associated with gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE). Increased body mass index (BMI) and waist-to-hip ratio (WHR) have been associated with BE. Abdominal diameter index (ADI, sagittal abdominal diameter divided by thigh circumference) was previously shown to be a more accurate predictor of incident cardiovascular disease compared to other measurements. Our aim is to examine whether abdominal diameter index was a more accurate predictor of prevalent BE compared to other anthropometric measurements. We conducted a case-control study of patients presenting to our institution. Our study population was consecutive Caucasian men with a known history of BE, and we recruited control patients who had GERD without BE. Both groups completed a questionnaire about demographics, smoking, and medications and underwent a series of anthropometric body measurements using standardized measuring tools. BMI, waist-to-hip ratio, and abdominal diameter index were calculated. Thirty-one BE patients and 27 control patients were recruited. The BE cohort were older and had a higher rate of hiatal hernia. The mean abdominal diameter index for patients with BE was 0.65 ± 0.07 and without BE was 0.60 ± 0.07 (p = 0.01). The predictive value of abdominal diameter index was analyzed using a receiver-operator characteristic (ROC) curve and was a more powerful predictor of BE than waist-to-hip ratio or BMI (AUROC = 0.70 vs. 0.60 vs. 0.52, respectively). Using a cut-point abdominal diameter index value of 0.60, abdominal diameter index had a sensitivity of 77.4% and a specificity of 63.0% for the presence of BE. When controlling for age, smoking status, and BMI, an abdominal diameter index ≥0.60 was a significant independent risk factor for BE (OR = 5.7, 95% CI = 1.29-25.4). In this pilot study, the abdominal diameter index appears to be a more powerful predictor of the presence of BE than BMI and waist-to-hip ratio and remained the only significant predictor of BE in multivariate analysis. We propose further validation of abdominal diameter index before inclusion in future prediction tools for BE.

Spontaneous immortalization of chicken fibroblasts generates stable, high-yield cell lines for serum-free production of cultured meat.

Cellular agriculture could meet growing demand for animal products, but yields are typically low and regulatory bodies restrict genetic modification for cultured meat production. Here we demonstrate the spontaneous immortalization and genetic stability of fibroblasts derived from several chicken breeds. Cell lines were adapted to grow as single-cell suspensions using serum-free culture medium, reaching densities of 108 × 106 cells per ml in continuous culture, corresponding to yields of 36% w/v. We show that lecithin activates peroxisome proliferator-activated receptor gamma (PPARγ), inducing adipogenesis in immortalized fibroblasts. Blending cultured adipocyte-like cells with extruded soy protein, formed chicken strips in which texture was supported by animal and plant proteins while aroma and flavour were driven by cultured animal fat. Visual and sensory analysis graded the product 4.5/5.0, with 85% of participants extremely likely to replace their food choice with this cultured meat product. Immortalization without genetic modification and high-yield manufacturing are critical for the market realization of cultured meat.

Abdominal diameter index and 12-year cardiovascular disease incidence in male bridge and tunnel workers.

BACKGROUND: A recent study has suggested that abdominal diameter index (ADI), that is, the supine sagittal abdominal diameter divided by thigh circumference, may be a better measure of the increased risk of abdominal adiposity for prevalent ischemic cardiovascular disease (CVD) than body mass index or waist circumference. The risk associated with all of these measures is believed to arise from the link between visceral obesity and insulin resistance. METHODS: Male bridge and tunnel workers in New York City without ischemic CVD in the highest and lowest quartiles of ADI (n=218) in a 1993-1994 cross-sectional study of risk factors and prevalent coronary heart disease were administered telephone follow-up questionnaires after 12 years (2005-2006) to assess incident ischemic CVD (new-onset angina, coronary revascularization, myocardial infarction, stroke, peripheral vascular disease and cardiovascular death). RESULTS: In the univariate analysis of 111 participants able to be contacted, study members in the highest quartile vs the lowest quartile of ADI had a significantly increased cumulative incidence of ischemic CVD (Relative risk (RR)=7.9, P=0.002). In a logistic regression analysis controlling for other cardiovascular risk factors including age, smoking, total cholesterol, high-density lipoprotein cholesterol, triglycerides, blood pressure and glucose, ADI lost statistical significance (RR=4.37, P=0.063), suggesting that ADI may be an anthropometric surrogate for these cardiovascular risk factors. CONCLUSIONS: ADI is a powerful anthropometric index for 12-year cumulative incidence of ischemic CVD in working men in New York City.

Psoriasis and non-alcoholic fatty liver disease.

Several recent studies have found an increased prevalence of non-alcoholic fatty liver disease within psoriasis patients. The exact pathophysiological mechanisms behind these observations are unclear, but are likely related to the high prevalence of obesity and metabolic syndrome within this patient population. Chronic inflammation, mediated by either proinflammatory adipokines or skin-derived cytokines, may contribute to fatty liver disease development by increasing insulin resistance which in turn promotes hepatic lipid accumulation. These same adipokines in addition to hepatic cytokines may act on the skin to influence psoriasis disease severity.

Mechanical and oral antibiotic bowel preparation versus no bowel preparation in right and left colectomy: subgroup analysis of MOBILE trial.

BACKGROUND: In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared with no bowel preparation (NBP). METHOD: This was a subgroup analysis of a multicentre randomized trial that included patients scheduled for elective colectomy. The MOABP group underwent mechanical bowel preparation, and took 2 g neomycin and 2 g metronidazole orally during the day before surgery. The NBP group did not undergo bowel preparation. Patients were categorized according to the side of resection (right versus left colectomy), and these subgroups compared for postoperative outcomes. RESULTS: Among 217 patients undergoing right colectomy (106 in MOABP and 111 in NBP group), SSI was detected in seven (7 per cent) and 10 (9 per cent) patients (odds ratio (OR) 0.71, 95 per cent c.i. 0.26 to 1.95; P = 0.510), anastomotic dehiscence in two (2 per cent) and two (2 per cent) patients (OR 1.05, 0.15 to 7.58; P = 1.000), and the mean(s.d.) Comprehensive Complication Index (CCI) score was 9.4(12.9) and 10.5(18.0) (mean difference -1.09; 95 per cent c.i. -5.29 to 3.11; P = 0.608) in the MOABP and NBP groups respectively. Among 164 patients undergoing left colectomy (84 in MOABP and 80 in NBP group), SSI was detected in five (6 per cent) and eight (10 per cent) patients (OR 0.57, 0.18 to 1.82; P = 0.338), anastomotic dehiscence in four (5 per cent) and five (6 per cent) patients (OR 0.75, 0.19 to 2.90; P = 0.742), and the CCI score was 10.2(13.1) and 6.5(11.0) (mean difference 3.68, -0.06 to 7.42; P = 0.053) in the MOABP and NBP groups respectively. CONCLUSIONS: MOABP did not decrease the rate of SSI or complications in patients undergoing either right or left colectomy compared with NBP.

Mu opioid receptors in the medial habenula contribute to naloxone aversion.

The medial habenula (MHb) is considered a brain center regulating aversive states. The mu opioid receptor (MOR) has been traditionally studied at the level of nociceptive and mesolimbic circuits, for key roles in pain relief and reward processing. MOR is also densely expressed in MHb, however, MOR function at this brain site is virtually unknown. Here we tested the hypothesis that MOR in the MHb (MHb-MOR) also regulates aversion processing. We used chnrb4-Cre driver mice to delete the Oprm1 gene in chnrb4-neurons, predominantly expressed in the MHb. Conditional mutant (B4MOR) mice showed habenula-specific reduction of MOR expression, restricted to chnrb4-neurons (50% MHb-MORs). We tested B4MOR mice in behavioral assays to evaluate effects of MOR activation by morphine, and MOR blockade by naloxone. Locomotor, analgesic, rewarding, and motivational effects of morphine were preserved in conditional mutants. In contrast, conditioned place aversion (CPA) elicited by naloxone was reduced in both naïve (high dose) and morphine-dependent (low dose) B4MOR mice. Further, physical signs of withdrawal precipitated by either MOR (naloxone) or nicotinic receptor (mecamylamine) blockade were attenuated. These data suggest that MORs expressed in MHb B4-neurons contribute to aversive effects of naloxone, including negative effect and aversive effects of opioid withdrawal. MORs are inhibitory receptors, therefore we propose that endogenous MOR signaling normally inhibits chnrb4-neurons of the MHb and moderates their known aversive activity, which is unmasked upon receptor blockade. Thus, in addition to facilitating reward at several brain sites, tonic MOR activity may also limit aversion within the MHb circuitry.

Long-term biological consequences of nuclear war.

Subfreezing temperatures, low light levels, and high doses of ionizing and ultraviolet radiation extending for many months after a large-scale nuclear war could destroy the biological support systems of civilization, at least in the Northern Hemisphere. Productivity in natural and agricultural ecosystems could be severely restricted for a year or more. Postwar survivors would face starvation as well as freezing conditions in the dark and be exposed to near-lethal doses of radiation. If, as now seems possible, the Southern Hemisphere were affected also, global disruption of the biosphere could ensue. In any event, there would be severe consequences, even in the areas not affected directly, because of the interdependence of the world economy. In either case the extinction of a large fraction of the Earth's animals, plants, and microorganisms seems possible. The population size of Homo sapiens conceivably could be reduced to prehistoric levels or below, and extinction of the human species itself cannot be excluded.

Actinic keratosis: an occupational and environmental disorder.

Solar ultraviolet light electromagnetic waves are a known environmental carcinogenic agent closely associated with the development of skin cancer in light-complexioned individuals. Outdoor workers have higher annual exposure to ultraviolet light. We will review the topic of actinic keratoses among these individuals as this common rudimentary form of superficial cutaneous squamous cell carcinoma is explored in greater detail.

Clinical user evaluation of field dental equipment under military deployment conditions.

The purpose of this work was to evaluate the clinical performance of a number of types of field (i.e., portable) dental equipment used under actual military deployment conditions. This equipment is often used under demanding field conditions where temperature, humidity, and air quality are not controlled. This article presents the results of a project conducted by the Naval Institute for Dental and Biomedical Research and the Air Force Dental Evaluation and Consultation Service to evaluate commercially available field dental equipment through laboratory testing and clinical user evaluations at military deployment sites. The purpose of the study was to identify the best-performing and most cost-effective field dental equipment for possible operational use by the U.S. Navy. Initial laboratory testing was performed at the Naval Institute for Dental and Biomedical Research and the equipment was then shipped to Okinawa, Japan, where it was tested by military dentists and assistants under deployment conditions. The testing provided beneficial results by identifying equipment that performed properly and equipment that exhibited shortcomings serious enough to render it inappropriate for field use.

Current update on portable dental equipment.

The dental care needs of the elderly are increasing as their population grows. For some of the elderly (eg, the nonambulatory, homebound, institutionalized), accessing dental care is a problem because they are unable to visit a traditional dental clinic. In the past, dental care has been taken to the homebound or institutionalized elderly by dentists using portable dental equipment. However, the perception that such equipment is difficult or impossible to obtain has limited the availability of on-site care. The purpose of this article is to describe various types of portable dental equipment and their features so that dentists interested in providing care to this group of patients are aware of them.

Vertical expandable prosthetic titanium ribs (VEPTR) in early-onset scoliosis: impact on thoracic compliance and sagittal balance.

BACKGROUND: Theoretically, dynamic thoracic compliance (DTC) should be reduced by vertical expandable prosthetic titanium ribs (VEPTR) since titanium rods, scar tissue and ossifications increase stiffness of the rib cage. The effect of VEPTR on thoracic compliance has not yet been elucidated. The impact of VEPTR on the development of sagittal balance has not been fully investigated. PATIENTS AND METHODS: In a retrospective study, we investigated 21 consecutive children who were treated by VEPTR from 2004 to 2011 and three control groups. We compared the development of thoracic compliance during growth to Nr1. Development of sagittal balance during growth was compared to Nr2 and to Nr3 (which has been instrumented from ileum to rib). Mean follow-up was 60.67 months (standard error of the mean (SE 4.77). RESULTS: The difference of change of DTC during growth of VEPTR group versus a control group was not significant (p < 0.05). However, initial DTC and DTC at last follow-up of VEPTR group were lower than DTC of the control group. The difference was significant (p < 0.05). Mean correction of Cobb angle after the first operation was 16.41° (SE 3.01). Until last follow-up, we saw a loss of correction of 8.23° (SE 3.22). The differences between the development of parameters of sagittal balance during growth between the VEPTR group, control group 2 and control group 3 were not significant (p > 0.05). CONCLUSIONS: VEPTR treatment should start as early as possible since VEPTR seems to lead to an increased rate of DTC that is similar to healthy controls. Sagittal balance showed a similar development as in healthy children.

Evaluation of field dental equipment in a deployment environment.

Dental officers and technicians must have reliable, durable, well-performing field dental equipment to enable them to provide dental care to deployed troops in operational environments. Unfortunately, no organized program exists to test such equipment before its purchase and use in the field. This article presents the results of a project conducted by the Naval Institute for Dental and Biomedical Research and the Air Force Dental Evaluation and Consultation Service to evaluate commercially available field dental equipment through laboratory testing and clinical-user evaluations in theater. The purpose of this 2-year project was to identify the best-performing and most cost-effective field dental equipment for possible future procurement. Initial laboratory testing was performed at the Naval Institute for Dental and Biomedical Research, and the equipment was then shipped to Kuwait for in-theater environmental and clinical-user testing. A seven-member scientific team of military dental officers and technicians was deployed for 1 month to perform in-theater testing under regional environmental conditions and to coordinate clinical-user evaluations. The testing provided beneficial results by identifying equipment that performed properly and equipment that exhibited shortcomings serious enough to render it inadequate for operational use. It is recommended that the project serve as a model for future testing and evaluation of medical/dental equipment by all of the military services.

Laparoscopic Wide Mesocolic Excision and Central Vascular Ligation for Carcinoma of the Colon.

BACKGROUND AND AIMS: The principle of complete mesocolic excision for colon cancer has been introduced to improve oncologic outcome. However, this approach is scantily discussed for laparoscopic surgery and there is a lack of randomized trials. This study examined oncologic and clinical outcome after laparoscopic wide mesocolic excision and central vascular ligation for colon cancer. MATERIAL AND METHODS: This is a review of prospectively gathered data from a single-institution colorectal cancer database. This study was conducted in the Central Hospital of Central Finland. From January 2003 to December 2011, 222 patients underwent laparoscopic colonic resections with wide mesocolic excision and central vascular ligation in the multimodal setting. The main measures of outcome were cancer recurrence and survival, with early recovery, 30d-mortality and morbidity, reoperation, readmission, and late complications as secondary outcomes. RESULTS: The median follow-up was 5.5 (interquartile range (IQR) = 3.7-8.0) years. The 5-year overall survival for all 222 patients was 80.2% and disease-specific survival was 87.5%, and for those 210 R0-patients with stage I-III disease, 83.9% and 91.3%, respectively. The 5-year disease-free survival was 85.8%: stage I was 94.7%, stage II was 90.8%, and stage III was 75.6% ( p = 0.004). Increasing lymph node ratio significantly decreased the 5-year disease-free survival. Conversion rate to open surgery was 12.2%. Thirty-day mortality was 1.3% and morbidity, 19.7%. Median postoperative hospital stay was 5 (IQR = 3-7) days. CONCLUSION: Laparoscopic wide mesocolic excision and central vascular ligation for colon cancer resulted in good long-term oncologic outcome. Randomized trials are needed to show that laparoscopic complete mesocolic excision technique would become the standard of care for the carcinoma of the colon.

The site and stoichiometry of the N-phenylmaleimide reaction with myosin when weakly-binding crossbridges are formed in skinned rabbit psoas fibers.

Treatment of relaxed skinned rabbit psoas muscle fibers with 0.1 mM N-phenylmaleimide (NPM) for 1 h locks all of the crossbridges in a weakly-binding state resembling that of the myosin.ATP crossbridge. Under these conditions, NPM reacts mainly with myosin heavy chain (Barnett et al. (1992) Biophys. J. 61, 358-367). Here the specific sites for that reaction are explored. Small bundles of rabbit psoas muscle fibers were treated with Triton X-100 to make the fiber sarcolemmas permeable. The bundles were treated with 0.1 mM [14C]NPM for 1 h, and homogenized for SDS-PAGE. 43 +/- 2.2% of the muscle fiber protein ran in the myosin heavy chain band, the same as for untreated fibers. An alkylating stoichiometry of 2.2 +/- 0.33 moles NPM per mole myosin heavy chain was determined. Exhaustive trypsin digestion followed by two-dimensional thin-layer chromatography and reverse-phase HPLC revealed two major sites on myosin heavy chain for NPM binding. The sites contained about the same amount of linked NPM, suggesting that the reaction stoichiometry of each site under the conditions studied is approx. 1 mol NPM/mol myosin heavy chain. Comparison of the labeled tryptic peptides with NPM-reacted synthetic SH1 and SH2 tryptic peptides and analysis of the treated fiber bundles' ATPase activity suggested that the sites for NPM reaction on myosin heavy chain when it locks crossbridges in a weakly-binding state are Cys-697 (SH2) and Cys-707 (SH1).

Comparison of laparoscopic and open colonic resection within fast-track and traditional perioperative care pathways: Clinical outcomes and in-hospital costs.

BACKGROUND: This study examined short-term clinical outcomes and in-hospital costs of laparoscopic and open colonic resection within fast-track and traditional care pathways. MATERIAL AND METHODS: A case-control study was performed. From 2007 to 2009, 116 patients underwent laparoscopic or open colonic resection for benign or malignant disease within fast-track care pathway. The control group consisted of 116 age-, sex-, comorbidity-, type of surgery-, and diagnosis-matched patients who received a traditional perioperative care from 2000 to 2007. The main measures of outcome were postoperative hospital stay and in-hospital costs, with 30-day mortality, morbidity, reoperation, and readmission rates as secondary outcomes. RESULTS: The study groups were well balanced for baseline characteristics. Postoperative hospital stay was shorter in the fast-track than in the control group: laparoscopic resection median 3 versus 5 days (p < 0.001) and open resection 4 versus 7 days (p < 0.001). In multivariate analysis fast-track care, laparoscopic surgery and complications were independent determinants affecting the length of hospital stay. Overall, there was a trend toward lower in-hospital costs in the fast-track group compared with the traditional care group, but the difference was not statistically significant. Open surgery within fast-track care was the least costly option compared to laparoscopic or open surgery within traditional care but not significantly so when compared with laparoscopy within fast-track care. Intake of solid food and bowel function recovered 1 day earlier in the fast-track group than in the control group (p < 0.001). Complications were more frequent after open surgery than after laparoscopic surgery (23.3% vs 11.0%, p = 0.012). Reoperation and readmission rates were similar between the study groups. CONCLUSION: Laparoscopy improves the efficiency of fast-track perioperative care without significantly increasing in-hospital costs.

Kallikrein gene family expression in the rat ovary: localization to the granulosa cell.

The glandular or tissue kallikreins are a multigene family of serine proteases, of which 13 genes (rKLK1-13) have been identified in the rat and are expressed in a wide variety of tissues. Kallikrein-like enzyme activity has been detected during the periovulatory period in the gonadotropin-primed immature female rat ovary and suggested to play a role in the inflammatory-like response at ovulation. In this study, we examined whether this enzyme activity was due to local expression of a rat KLK gene family member. Ovarian RNA, prepared from gonadotropin-treated animals, was assessed for rKLK gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) with universal rKLK primers derived from highly conserved regions in the rat KLK genes. Southern blot analysis of the RT-PCR products, using oligonucleotide probes specific for the individual genes, indicated that five rKLK gene family members, rKLK1 (encoding true kallikrein), rKLK3, rKLK7, rKLK8, and rKLK9, were expressed at varying levels in the ovaries of both untreated control and gonadotropin-treated immature female rats. The identities of these five rKLK messenger RNAs were further confirmed by DNA sequence analysis of the PCR products. In situ hybridization of gonadotropin-treated ovaries localized rKLK3 and rKLK7 gene expression to the luteinizing granulosa cells of periovulatory follicles. In an enriched population of nonluteinizing granulosa cells prepared from estrogen-primed animals, we also demonstrated rKLK3, rKLK7, rKLK9, and rKLK12 (but not rKLK1 or rKLK8) expression, whereas all six genes were expressed in the ovaries of these animals. In summary, we have reported the expression of six KLK gene family members in the rat ovary and localized this expression primarily to the granulosa cell. The potential roles of these enzymes in ovulation or other aspects of ovarian, particularly granulosa cell, function are yet to be elucidated.

The impact of the nonpeptide corticotropin-releasing hormone antagonist antalarmin on behavioral and endocrine responses to stress.

The nonpeptide CRH antagonist antalarmin has been shown to block both behavioral and endocrine responses to CRH. However, it's potential activity in blunting behavioral and endocrine sequelae of stressor exposure has not been assessed. Because antagonism of central CRH by alpha-helical CRH attenuates conditioned fear responses, we sought to test antalarmin in this regard. In addition, it remains unclear as to whether this is a result of receptor blockade during conditioning or during testing. Thus, we explored whether CRH mediates the induction or expression of conditioned fear (freezing in a context previously associated with 2 footshocks; 1.0 mA, 5 sec each). Furthermore, because rats previously exposed to inescapable shock (IS; 100 shocks, 1.6 mA, 5 sec each), demonstrate enhanced fear conditioning, we investigated whether this effect would be blocked by antalarmin. Antalarmin (20 mg/kg x 2 ml i.p.) impaired both the induction and expression of conditioned fear. In addition, antalarmin blocked the enhancement of fear conditioning produced by prior exposure to IS. Despite the marked behavioral effects observed in antalarmin-treated rats, antalarmin had no effect on IS-induced rises in ACTH or corticosterone. However, antalarmin did block the ACTH response produced by exposure to 2 footshocks.