[The correlation between plasma heat shock proteins 90α levels and white matter hyperintensity in patients with cerebral small vessel disease].

Objective: To investigate the relationship between plasma heat shock proteins 90α(Hsp90α) levels and the white matter hyperintensity(WMH) in patients with cerebral small vessel disease(SVD). Methods: Patients admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from March to August 2021 and diagnosed with WMH by magnetic resonance examination (MRI) were selected as the case group, matched with physical examination patients who visited the Department of Medical Examination during the same period and showed no WMH on MRI and no history of neurological diseases as the control group, and the level of plasma Hsp90α was quantitatively detected by enzyme-linked immunosorbent assay. Mann-Whitney U test was used to compare whether there was a difference in plasma Hsp90α levels between the control group and the case group.Multivariate logistic regression analysis was used to explore the related factors of WMH in patients with SVD. Results: Of the 183 subjects, the control group (n=73) consisted of 28 males and 45 females, aged (54±10) years, while the case group (n=110) consisted of 71 males and 39 females, aged (64±10) years old. Plasma Hsp90α level was higher in the case group than that of the control group [53.33(35.33, 70.09) ng/ml vs 35.02(18.51, 54.95) ng/ml, P<0.001]. After adjusting for confounding factors by multivariate analysis, the results showed that plasma Hsp90α levels greater than 58.34 ng/ml was associated with WMH (P=0.002, OR=5.931, 95%CI:1.955-17.995). Conclusion: Higher level of plasma Hsp90α is associated with WMH in patients with SVD.

Supplementation with nutrients modulating insulin-like growth factor-1 negatively correlated with changes in the levels of pro-inflammatory cytokines in community-dwelling elderly people at risk of undernutrition.

BACKGROUND: Suboptimal nutrition accompanied by chronic low-grade increases in circulating cytokine levels is more common in elderly people. We explored the improvement in nutritional status, especially in the level of insulin-like growth factor-1 (IGF-1) and its relationship with changes in circulating cytokine levels, after providing extra protein and energy content to community-dwelling older adults at risk of undernutrition. METHODS: Sixty nondiabetic subjects, aged ≥65 years and living independently in a community for elderly people, with a serum pre-albumin level ≤30 mg dL-1 and a body mass index <25 kg m-2 , were recruited. The subjects were followed for a 2-week pre-intervention period, during which they maintained routine dietary habits. This was followed by an intervention period, during which they received oral nutritional supplementation for 2 weeks. RESULTS: Following 2 weeks of intervention, there were significant increases in total lymphocyte count (TLC) and insulin-like growth factor (IGF)-1, pre-albumin and transferrin compared to baseline. Body weight and mid-arm circumference significantly increased without alteration of tricep skinfold thickness at the end of the intervention. There was a significant reduction in interleukin (IL)-6 levels and a trend toward a decrease in the tumor necrosis factor (TNF)-α levels. At baseline, age was negatively correlated with IGF-1 levels and positively correlated with IL-6 and TNF-α levels. The change (▵, from baseline) in IGF-1 level was positively correlated with age and negatively correlated with ▵IL-6 and ▵TNF-α. CONCLUSIONS: A 2-week intervention with oral nutritional supplementation improved nutritional status and decreased circulating cytokine levels. Specifically, ▵IGF-1 was negatively correlated with changes in pro-inflammatory cytokine levels in community-dwelling elderly people at risk of undernutrition. (Clinicaltrials.gov: NCT02656186).

Cataract surgery is associated with a reduced risk of dementia: a nationwide population-based cohort study.

BACKGROUND AND PURPOSE: Our purpose was to determine the association of cataract surgery with subsequent development of dementia in older adults with newly diagnosed cataract. METHODS: By using data from Taiwan National Health Insurance Research Database (NHIRD), a population-based cohort study including 491 226 subjects aged 70 or older with first-time diagnosis of cataract coded from 2000 to 2009 was conducted. After matching cataract patients receiving cataract surgery with cataract patients without receiving cataract surgery for age, sex, index date, Charlson Comorbidity Index score, interval between first coding of cataract diagnosis and index date, hypertension and diabetes mellitus, 113 123 patients in each cohort were enrolled. The main outcome measure was newly diagnosed dementia coded by neurologists or psychiatrists more than 365 days after cataract surgery. Incidence rate and hazard ratio of dementia were compared between the cataract surgery and cataract diagnosis cohorts. RESULTS: The incidence rate of dementia was 22.40 per 1000 person-years in the cataract surgery cohort and 28.87 per 1000 person-years in the cataract diagnosis cohort. The rate of dementia was significantly lower in the cataract surgery group (hazard ratio 0.77, 95% confidence interval 0.75-0.79, P < 0.001). Female gender (P < 0.001) and a shorter interval between the date of first coding of a cataract diagnosis and the date of cataract surgery (P = 0.009) were significantly associated with a lower incidence rate of dementia. CONCLUSION: In an NHIRD cohort of Taiwanese aged 70 years and older with a diagnosis of cataract, patients undergoing cataract surgery were associated with a reduced risk of subsequent dementia compared with those without cataract surgery.

Integration of seawater and grey water reuse to maximize alternative water resource for coastal areas: the case of the Hong Kong International Airport.

Development, population growth and climate change have pressurized water stress in the world. Being an urbanized coastal city, Hong Kong has adopted a dual water supply system since the 1950s for seawater toilet flushing for 80% of its 7 million inhabitants. Despite its success in saving 750,000 m(3)/day of freshwater, the saline sewage (consisting of about 20-30% of seawater) appears to have sacrificed the urban water cycle in terms of wastewater reuse and recycling. Can seawater toilet flushing be applied without affecting the urban water cycle with respect to sustainable water resource management? To address this issue, we examined the entire urban water cycle and developed an innovative water resource management system by integrating freshwater, seawater and reclaimed grey water into a sustainable, low-freshwater demand, low-energy consumption, and low-cost triple water supply (TWS) system. The applicability of this novel system has been demonstrated at the Hong Kong International Airport which reduced 52% of its freshwater demand.

Prenatal ethanol exposure alters the effects of gonadectomy on hypothalamic-pituitary-adrenal activity in male rats.

Prenatal ethanol exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. In adulthood, ethanol-treated rats show altered gonadal hormone responses and reproductive function, and increased HPA responsiveness to stressors. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that the gonadal hormones play a role in mediating prenatal ethanol effects on HPA function. To examine a possible testicular influence on HPA activity in males, we compared the effects of gonadectomy on HPA stress responses of adult male offspring from ethanol, pair-fed (PF) and ad libitum-fed control dams. Intact ethanol-treated rats showed increased adrenocorticotrophic hormone (ACTH) but blunted testosterone and luteinising hormone (LH) responses to restraint stress, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels compared to those observed in PF and/or control rats. Gonadectomy: (i) significantly increased ACTH responses to stress in control but not ethanol-treated and PF males; (ii) eliminated differences among groups in plasma ACTH and AVP mRNA levels; and (iii) altered LH and gonadotrophin-releasing hormone responses in ethanol-treated males. Taken together, these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure, with normal testicular influences on HPA function markedly reduced in ethanol-treated animals. A decreased sensitivity to inhibitory effects of androgens could contribute to the HPA hyperresponsiveness typically observed in ethanol-treated males.

Anterior debridement may not be necessary in the treatment of tuberculous spondylitis of the thoracic and lumbar spine in adults: a retrospective study.

AIM: Many aspects of the surgical treatment of patients with tuberculosis (TB) of the spine, including the use of instrumentation and the types of graft, remain controversial. Our aim was to report the outcome of a single-stage posterior procedure, with or without posterior decompression, in this group of patients. PATIENTS AND METHODS: Between 2001 and 2010, 51 patients with a mean age of 62.5 years (39 to 86) underwent long posterior instrumentation and short posterior or posterolateral fusion for TB of the thoracic and lumbar spines, followed by anti-TB chemotherapy for 12 months. No anterior debridement of the necrotic tissue was undertaken. Posterior decompression with laminectomy was carried out for the 30 patients with a neurological deficit. RESULTS: The mean kyphotic angle improved from 26.1° (- 1.8° to 62°) to 15.2° (-25° to 51°) immediately after the operation. At a mean follow-up of 68.8 months (30 to 144) the mean kyphotic angle was 16.9° (-22° to 54°), with a mean loss of correction of 1.6° (0° to 10°). There was a mean improvement in neurological status of 1.2 Frankel grades in those with a neurological deficit. Bony union was achieved in all patients, without recurrent infection. CONCLUSIONS: Long posterior instrumentation with short posterior or posterolateral fusion is effective in the treatment of TB spine. It controls infection, corrects the kyphosis, and maintains correction and neurological improvement over time. TAKE HOME MESSAGE: With effective anti-TB chemotherapy, a posterior only procedure without debridement of anterior lesion is effective in the treatment of TB spondylitis, and an anterior procedure can be reserved for those patients who have not improved after posterior surgery. Cite this article: Bone Joint J 2016;98-B:834-9.

Is removal of the implants needed after fixation of burst fractures of the thoracolumbar and lumbar spine without fusion? a retrospective evaluation of radiological and functional outcomes.

METHODS: In this study of patients who underwent internal fixation without fusion for a burst thoracolumbar or lumbar fracture, we compared the serial changes in the injured disc height (DH), and the fractured vertebral body height (VBH) and kyphotic angle between patients in whom the implants were removed and those in whom they were not. Radiological parameters such as injured DH, fractured VBH and kyphotic angle were measured. Functional outcomes were evaluated using the Greenough low back outcome scale and a VAS scale for pain. RESULTS: Between June 1996 and May 2012, 69 patients were analysed retrospectively; 47 were included in the implant removal group and 22 in the implant retention group. After a mean follow-up of 66 months (48 to 107), eight patients (36.3%) in the implant retention group had screw breakage. There was no screw breakage in the implant removal group. All radiological and functional outcomes were similar between these two groups. Although solid union of the fractured vertebrae was achieved, the kyphotic angle and the anterior third of the injured DH changed significantly with time (p < 0.05). DISCUSSION: The radiological and functional outcomes of both implant removal and retention were similar. Although screw breakage may occur, the implants may not need to be removed. TAKE HOME MESSAGE: Implant removal may not be needed for patients with burst fractures of the thoracolumbar and lumbar spine after fixation without fusion. However, information should be provided beforehand regarding the possibility of screw breakage.

The systematic assessment of variations in medical practices and their outcomes.

The Health Care Financing Administration of the Department of Health and Human Services has carried out for several years the systematic assessment of variations over time and among geographic locales in patterns of care and patterns of outcomes experienced by Medicare beneficiaries. This routine monitoring focuses principally on hospitalizations and their outcomes (death and readmission) and is based on the Medicare enrollment file and the claims file for inpatient care. The period 1985-88 has been marked by declining adjusted post-admission risks for mortality (down 4 percent) and readmission (down 6 percent) for Medicare beneficiaries. The downward trend in mortality risks is most evident following hospitalizations for acute myocardial infarction (down 8 percent) and stroke (down 12 percent). Hospital admission and population mortality rates, adjusted for differences in demographic and socioeconomic characteristics of the populations, vary substantially among areas as large as States and Metropolitan Statistical Areas, as do risk-adjusted post admission probabilities of death among those areas and among hospitals. Thus, if overall admission and mortality rates in the upper three quartiles of Metropolitan Statistical Areas were brought down to the average of the lowest quartile, there would be 20 percent fewer admissions and 12 percent fewer deaths within 180 days of admission for hospitalized patients. Although favorable trends in the effectiveness of the hospital care received by Medicare beneficiaries appear discernible, the existence of substantial variations suggests that further improvement may be possible.

A non-invasive isotope dilution technique for quantifying hepatic blood flow using radiolabelled red blood cells.

Clinically significant changes in hepatic haemodynamics accompany the development of portal hypertension, hepatocellular carcinoma, liver metastases and liver cirrhoses, and after major liver resection. Hepatic blood flow parameters, such as hepatic arterial flow (HAF), hepatic portal flow (HPF), total hepatic blood flow (THBF) and hepatic perfusion index (HPI), are useful adjuncts to the diagnosis of liver pathology, the evaluation of disease progress and prognostication. Here, we describe a non-invasive method that combines the measurement of these parameters in a single study in real time. Red blood cells from eight pigs were labelled with 99Tc(m) using an in-vitro method and re-injected into the pigs. Data acquisition over the heart, lungs, liver and kidneys was started immediately and a blood sample was obtained 15 min post-injection. Hepatic arterial flow was determined from the ratio of the maximum gradients between the integrated time-activity curve of the left ventricle and the first-pass time-activity curve of the liver before the peak of the kidneys time-activity curve. The hepatic perfusion index was determined by comparing the slope of the liver time-activity curve before and after the kidney peak. Hepatic portal flow was determined from the hepatic arterial flow and the hepatic perfusion index, and total hepatic blood flow was determined as the sum of arterial and portal flow. The results were compared against those obtained from a clearance method using 99Tc(m)-DISIDA. The average hepatic perfusion index was 0.38, and the average hepatic arterial flow and hepatic portal flow were 168.3 +/- 52.9 and 274.6 +/- 60.1 ml x min(-1) respectively. The average total hepatic blood flow was 442.8 +/- 53.5 ml x min(-1), while the total hepatic flow determined by 99Tc(m)-DISIDA clearance was 419.7 +/- 62.6 ml x min(-1). No significant difference in total hepatic blood flow was found between the two methods. The results of this study show that it is possible to obtain all hepatic haemodynamics data in a single study using a non-invasive method.

Prevalence of Helicobacter pylori in gastric cancer in a South-East Asian population by 14C-urea breath test.

BACKGROUND: Helicobacter pylori is believed to play an important role in the aetiology of gastric cancer. There is a great variability in seropositivity and histological frequency of H. pylori in gastric cancer. The present prospective study investigates the prevalence of H. pylori infection in gastric cancer patients using 14C-urea breath testing. METHODS: Patients with endoscopic biopsy-proven gastric cancer were fasted for 6 h prior to ingesting 18.5 x 104 Bq of 14C-urea cocktail orally. Breath samples were collected after 20 min by asking them to blow into a hyamine solution and measurements were read in a scintillation counter. RESULTS: Fifty out of 51 patients (98%) with gastric cancer were positive on the 14C-urea breath test compared to 29 patients (61%) who were positive on histology. There was no association between sex, age or tumour site, stage, differentiation, Lauren type and H. pylori status. The test was negative in one patient with cardial tumour in which histology of the resected specimen was also negative for the bacteria. CONCLUSIONS: Active H. pylori infection is highly prevalent in gastric cancer in a South-East Asian population. The 14C-urea breath test is a highly sensitive method for detecting the presence of H. pylori even in gastric adenocarcinoma irrespective of the stage.

Delayed cholestatic hepatitis due to methimazole.

We report on a 71-year-old man who presented to the medical department of Our Lady of Maryknoll Hospital with progressive cholestatic hepatitis. Tests for hepatitis viral markers gave negative results and ultrasonography revealed no dilated bile ducts. Endoscopic retrograde cholangiopancreatography showed a normal biliary tree. The patient had completed a 5-month course of methimazole to treat thyrotoxicosis a few weeks before the onset of the jaundice. Methimazole was suspected to be the cause of the cholestatic hepatitis; this diagnosis was supported by the results from a liver biopsy. The presentation of the patient was unusual by virtue of the delayed onset and prolonged course of cholestasis.

iTRAQ-based proteomic profiling of the marine medaka (Oryzias melastigma) gonad exposed to BDE-47.

A recent study demonstrated that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) may have an adverse effect on the reproduction in marine medaka (Oryzias melastigma), but the molecular mechanisms remain largely unknown. In this study, we investigated the protein expression profiles of male and female gonads of O. melastigma exposed to dietary BDE-47 at two dosages (0.65 and 1.30 µg/g/day, respectively) for 21 days. Extracted proteins were labeled with iTRAQ and analyzed on a MALDI TOF/TOF analyzer, as results, 133 and 144 unique proteins were identified in testis and ovary, respective, and they exerted dose- and sex-dependent expression patterns. In testis, among the 42 differentially expressed proteins; down-regulation of histone variants and parvalbumins implicated BDE-47 may disrupt the spermatogenesis and induce sterility in fishes. In ovary, 38 proteins were differentially expressed; the elevation of vitellogenins and apolipoprotein A-I expression indicated BDE-47 acts as an estrogen-mimicking compound and led to reproductive impairment in O. melastigma.

Gender-specific transcriptional profiling of marine medaka (Oryzias melastigma) liver upon BDE-47 exposure.

Marine medaka (Oryzias melastigma) were exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) to investigate the gender-specific transcriptional profiles of liver tissue in response to this flame retardant. A cDNA library of O. melastigma was constructed, and 2304 clones were amplified from the library to fabricate a cDNA microarray. Sequences of these genes were assembled into 1800 sequences using Geneious, a bioinformatics software. Corresponding expressed sequence tags were blasted against the National Centre for Biotechnology Information non-redundant database and further classified into various biological categories according to the Gene Ontology project. Male and female three-month-old were fed a diet of BDE-47 contaminated Artemia at low dosage (290.3±172.3ng BDE-47/day) and high dosage (580.5±344.6ng BDE-47/day) for 5 and 21 days, respectively. The transcriptional profiles of O. melastigma liver were then generated by the species-specific cDNA microrarray. The results from microarray analysis suggested very different gene expression patterns between males and females for both BDE-47 exposure-dose and exposure-time, with male livers having stronger gene regulatory responses than female livers. Importantly, our results revealed that in male O. melastigma only, BDE-47 exposure may activate phosphoinositide-3-kinase and mitogen-activated protein kinase, proteins that play importance roles in cell growth, proliferation and survival.

Evidence for lipoxygenase-catalyzed bioactivation of phenytoin to a teratogenic reactive intermediate: in vitro studies using linoleic acid-dependent soybean lipoxygenase, and in vivo studies using pregnant CD-1 mice.

Teratogenicity of the anticonvulsant drug phenytoin and structurally related compounds has been postulated to result in part from its cooxidative bioactivation to an embryotoxic reactive intermediate by the hydroperoxidase component of arachidonic acid-dependent prostaglandin H synthase (PHS). However, lipoxygenases (LPOs) could constitute a competing, arachidonate-dependent bioactivating system. The teratologic importance of LPO alone and together with PHS was evaluated in vitro and in vivo. To evaluate directly the potential role of LPO in phenytoin bioactivation, in vitro incubation conditions measuring the linoleic acid-dependent, soybean LPO-catalyzed covalent binding of phenytoin to protein, believed to constitute teratologic initiation, were optimized for substrate concentration, enzyme activity, incubation time, inhibitor vehicle, and inhibitor concentration. Under optimal conditions, 4.24 nM [3H]phenytoin, 100,000 units of soybean LPO (Type 1B, Sigma Chemical Co.), and 5 mg bovine serum albumin, with or without 5 mM linoleic acid, were adjusted with 100 mM Tris-HCl buffer (pH 9) to a 1-ml final volume and incubated at 37 degrees C for 60 min. Addition of linoleic acid substrate to the incubation medium enhanced the covalent binding of phenytoin by over threefold (p < 0.05). Linoleic acid-dependent covalent binding of phenytoin was inhibited in a concentration-dependent fashion by the selective and nonselective LPO/PHS inhibitors indomethacin, nordihydroguaiaretic acid, quercetin, BW755C, and 5,8,11,14-eicosatetraynoic acid (ETYA) and by the hydroperoxidase inhibitor methimazole (p < 0.05). In vivo, on Gestational Days 12 and 13, pregnant CD-1 mice were treated with the irreversible dual PHS/LPO inhibitor ETYA (0, 0.5, 5, 50, 100, and 125 mg/kg ip) or its vehicle, 2 hr before a teratogenic dose of phenytoin (65 mg/kg ip). Dams were killed on Day 19 and the fetuses were delivered by Caesarian section. ETYA pretreatment produced a dose-related decrease in phenytoin teratogenicity, with maximal reductions by 50 mg/kg of ETYA in the incidence of phenytoin-induced fetal cleft palates (1.8 +/- 1.8% vs 26.8 +/- 3%) (% +/- SE; p < 0.00001) and resorptions (22.5 +/- 5% vs 60 +/- 2%) (p < 0.05). Higher ETYA doses were embryotoxic. The reduction in phenytoin teratogenicity by the dual PHS/LPO inhibitor ETYA was considerably greater than that previously reported for acetylsalicylic acid, which inhibits only PHS.(ABSTRACT TRUNCATED AT 250 WORDS)

Economics and extended longevity: a case study.

Preventive and therapeutic advances have brought life expectancy in the United States to well over 70 years and have shifted mortality causes from acute to chronic diseases, the determinants of which are genetics, lifestyle, the environment, and aging itself. Plausible approaches to chronic disease prevention are likely to increase longevity further, with some foreseeable effects on demographic and economic projections. Primarily, longevity advances would swell forecasts of population size, and would thus have to be met by production advances in order to maintain or improve living standards. This study, a restricted example, considers the probable demographic and economic consequences of a limited prevention program in the context of the Ford Motor Company, based on actual experience and certain expectations up to the year 2000. According to the results, prevention would reduce outlays for life insurance, disability, and health care, but would also generate the higher costs of extending pension plans. Undoubtedly, prevention will continue to be highly ranked in society's pursuit of happiness, and society must prepare to meet its effects with appropriate social and economic policies.

Determination of dissolution profiles for several commercially available therapeutic [131I]sodium iodide capsules.

The dissolution profiles for [131I]sodium iodide therapeutic capsules from three commercial vendors were studied. The 131I release rate in water was rapid for the capsules with 100% release attained within 35 min. There was no significant difference in dissolution profiles for the capsules from the three vendors.

Biodistribution of bis-[beta-(N,N,N-trimethylamino)ethyl]selenide-75Se diiodide, a potential articular cartilage imaging agent.

In an effort to develop a specific radiodiagnostic agent for articular cartilage imaging, we have investigated the biodistribution of bis[beta-(N,N,N-trimethylamino)ethyl]-selenide-75Se diiodide (75Se BISTAES) in rabbits. At an intravenous dose of 5 mg/kg, the greatest localization of the compound occurred in articular cartilage 15 min after injection. The compound was excreted rapidly in the urine. The results suggest that 75Se BISTAES has potential clinical use as an articular cartilage imaging agent.

Cyclic fatigue-crack propagation, stress-corrosion, and fracture-toughness behavior in pyrolytic carbon-coated graphite for prosthetic heart valve applications.

Fracture-mechanics tests were performed to characterize the cyclic fatigue, stress-corrosion cracking, and fracture-toughness behavior of a pyrolytic carbon-coated graphite composite material used in the manufacture of cardiac valve prostheses. Testing was carried out using compact tension C(T) samples containing "atomically" sharp precracks, both in room-temperature air and principally in a simulated physiological environment of 37 degrees C Ringer's lactate solution. Under sustained (monotonic) loads, the composite exhibited resistance-curve behavior, with a fracture toughness (KIc) between 1.1 and 1.9 MPa square root of m, and subcritical stress-corrosion crack velocities (da/dt) which were a function of the stress intensity K raised to the 74th power (over the range approximately 10(-9) to over 10(-5) m/s). More importantly, contrary to common perception, under cyclic loading conditions the composite was found to display true (cyclic) fatigue failure in both environments; fatigue-crack growth rates (da/dN) were seen to be a function of the 19th power of the stress-intensity range delta K (over the range approximately 10(-11) to over 10(-8) m/cycle). As subcritical crack velocities under cyclic loading were found to be many orders of magnitude faster than those measured under equivalent monotonic loads and to occur at typically 45% lower stress-intensity levels, cyclic fatigue in pyrolytic carbon-coated graphite is reasoned to be a vital consideration in the design and life-prediction procedures of prosthetic devices manufactured from this material.

Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal regulation after adrenalectomy and corticosterone replacement.

BACKGROUND: Previous studies have demonstrated that rats prenatally exposed to ethanol (E) exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness, demonstrated by increased and/or prolonged elevations of adrenocorticotropin (ACTH) and/or corticosterone (CORT) after stress. This study investigated possible mechanisms of HPA hyperresponsiveness in E rats by manipulating CORT feedback regulation of HPA activity via adrenalectomy (ADX) with or without CORT replacement. METHODS: Male Sprague-Dawley rat offspring from prenatal E, pair-fed (PF) and ad libitum-fed control (C) groups were tested at 90 to 120 days of age. Rats were either sham-operated or underwent ADX, with or without CORT replacement. CORT (25 microg/ml) was replaced via the drinking water to achieve basal plasma CORT levels and maintain a phasic CORT signal. Seven days after surgery, animals were decapitated at the diurnal peak either under basal conditions or after a 15-min restraint stress, and trunk blood was collected. RESULTS: After ADX, loss of the CORT feedback signal resulted in increased plasma ACTH in all groups compared with those in sham animals. In addition, under basal conditions, ADX E rats had significantly greater plasma ACTH levels than both PF and C rats. However, no differences were seen in ADX rats after stress. CORT replacement after ADX was partially effective in normalizing ACTH levels under both basal and stress conditions, with no differences among E, PF, and C animals. CONCLUSIONS: These results suggest that E males may exhibit enhanced stimulatory inputs to the hypothalamus, increased pituitary sensitivity to secretagogues, or both, which may be revealed after ADX. In contrast, E animals seem similar to controls in their ability to use an exogenous CORT signal to regulate HPA activity.