Childhood liver tumors in Argentina: Incidence trend and survival by treatment center. A report from the national pediatric cancer registry, ROHA network 2000-2015.

BACKGROUND: Information on the epidemiology of pediatric liver tumors in Latin America is limited. PURPOSE: To describe the incidence of liver tumors in a pediatric registry in Argentina according to geographic region, national trends over 16 years, and survival related to stage, age, sex, and care center. METHODS: Newly diagnosed liver tumors cases are registered in the Argentine Pediatric Oncology Hospital Registry (ROHA) with an estimated coverage of 91% of national cases. Age-standardized incidence rate per millon (ASR) was calculated based on the National Vital Statistics Reports. Five-year overall survival (OS) was estimated using the Kaplan-Meier method. The log-rank test was used to compare subgroup survival. RESULTS: Two hundred seven cases of hepatoblastoma (HB) and 73 of hepatocellular carcinoma (HCC) were identified. ASR of liver tumors was 1.8/million (95% confidence Interval [CI], 1.6-2.0) per year. ASR was 1.4 (1.2-1.6) for HB and 0.4 (0.3-0.5) for HCC. For HB, the highest incidence was found in the northwest region including the Altiplano. OS was 60.4% (53.4-66.8) for HB and 36.1% (25.2-47.2) for HCC. Five-year survival rate of children with metastatic HB treated at liver transplant hospitals (LTH) was 54.2% (30.3-73.0) compared to 13.3% (2.2-34.6) for those seen at other hospitals (OH) (P = .02), while for HCC this rate was 46.3% (30.7-60.6) at LTH compared to 17.5% (3.1-41.9) at OH (P = .01). CONCLUSIONS: The incidence rate of pediatric liver tumors was stable over the 16-year study period. Patients may benefit if at treatment initiation they are evaluated jointly with LTH specialists to define treatment strategies.

Advanced glycation end products alter steroidogenic gene expression by granulosa cells: an effect partially reversible by vitamin D.

STUDY QUESTION: Does vitamin D attenuate the adverse effects of advanced glycation end products (AGEs) on steroidogenesis by human granulosa cells (GCs)? SUMMARY ANSWER: AGEs alter the expression of genes important in steroidogenesis while 1,25-dihydroxyvitamin D3 (vit D3) in vitro attenuates some of the actions of AGEs on steroidogenic gene expression, possibly by downregulating the expression of the pro-inflammatory cell membrane receptor for AGEs (RAGE). WHAT IS KNOWN ALREADY: Vitamin D attenuates the pro-inflammatory effects of AGEs in non-ovarian tissues. STUDY DESIGN, SIZE, DURATION: Women who were undergoing IVF were enrolled. Follicular fluid samples (n = 71) were collected and cumulus GCs (n = 12) were treated in culture. PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid levels of the anti-inflammatory soluble RAGE (sRAGE), AGEs and 25-hydroxyvitamin D (25-OHD) were quantified for possible correlations. GCs of each participant were split equally and treated with either media alone (control) or with human glycated albumin (HGA as a precursor for AGEs) with or without vit D3 after which RT-PCR and immunofluorescence were performed and cell culture media estradiol (E2) levels were compared. MAIN RESULTS AND THE ROLE OF CHANCE: In follicular fluid, sRAGE levels were positively correlated with 25-OHD levels. HGA treatment (i) increased CYP11A1 (by 48%), 3ß-HSD (by 38%), StAR (by 42%), CYP17A1 (by 30%) and LHR (by 37%) mRNA expression levels (P < 0.05 for all) but did not alter CYP19A1 or FSHR mRNA expression levels; and (ii) increased E2 release in cell culture media (P = 0.02). Vit D3 treatment (i) downregulated RAGE mRNA expression by 33% and RAGE protein levels by 44% (P < 0.05); (ii) inhibited the HGA-induced increase in CYP11A1, StAR, CYP17A1 and LHR mRNA levels, but not the increase in 3ß-HSD mRNA levels; and (iii) did not inhibit the HGA-induced E2 release in cell culture media. LIMITATIONS REASONS FOR CAUTION: This study used luteinized GCs that were collected from women who received gonadotropins thus the results obtained may not fully extrapolate to non-luteinized GCs in vivo. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that there is a relationship between AGEs and their receptors (RAGE and sRAGE) with vitamin D. Understanding the interaction between AGEs and vitamin D in ovarian physiology could lead to a more targeted therapy for the treatment of ovarian dysfunction. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from NIH (R01 NS045940), American Society for Reproductive Medicine, Ferring Pharmaceuticals Inc., and University of Vermont College of Medicine Bridge Funds. All authors have nothing to disclose.

Childhood osteosarcoma: Incidence and survival in Argentina. Report from the National Pediatric Cancer Registry, ROHA Network 2000-2013.

BACKGROUND: Differences in incidence and survival in osteosarcoma reports are considerable worldwide. PURPOSE: This study describes the incidence and survival of patients with osteosarcoma in Argentina with data from the National Pediatric Cancer Registry (ROHA), and the impact of age, gender, stage, regional, and socioeconomic indicators on outcome. METHODS: Pediatric patients with osteosarcoma reported to ROHA from 2000 through 2013 were analyzed, the annual age-standardized incidence rate (ASR) was calculated using the National Vital Statistics, and survival was estimated. The extended human development index (EHDI) for each reporting region was used as an indicator of socioeconomic status. RESULTS: There were 515 cases of osteosarcoma identified, yielding an ASR of 3.2/1,000,000 children (0-14 years old). The ASR did not vary significantly by year of diagnosis but ranged from 4.0/1,000,000 in the Cuyo/Western Central region to 2.7/1,000,000 in the northeast region (P < 0.000). The estimated 5-year survival rate was 45% (95% confidence interval [CI] 44-51%), with no difference by sex, diagnosis year, region, or EHDI score (P > 0.1 in all cases). Survival rate for localized disease was 52% (95% CI 45-57%) and for metastatic 22% (95% CI 15-30%). CONCLUSIONS: In Argentina, ASR of osteosarcoma is similar to that in high-income countries, but survival is lower in all regions. Future work will focus on identification and reduction of causes of preventable treatment failure.

Influence of alkoxy chain envelopes on the interfacial photoinduced processes in tetraarylporphyrin-sensitized solar cells.

The introduction of alkoxy chains in the molecular architecture of meso push-pull porphyrins is of paramount importance aiming at high performing dye-sensitized solar cells (DSSCs) based on these specific sensitizers. Recently, we have demonstrated that the same approach is fruitful even if it is applied to tetraarylporphyrins with an acceptor/anchoring substituent in the ß-pyrrolic position. In particular, among the ortho-ortho, the ortho-para and the ortho-functionalization of the aryl rings with an octyloxy chain, we identified the latter as the most performing in the series, showing a good balance between the dye loading and the reduction of π-π aggregation. Herein, focusing our attention on the mono-ortho-functionalized molecular structure, we have investigated the effect of the alkoxy chain length and nature on the reduction of dye-to-dye aggregation as well as on the enhancement of light harvesting capabilities, finding an almost linear relationship between the device photon conversion efficiency (PCE) and the alkoxy chain length both in the presence and in the absence of a co-disaggregating agent.

Which are important targets in development of S. aureus mastitis vaccine?

Staphylococcus aureus represents one of the leading causes of mastitis in dairy cows worldwide. S. aureus IMI have variable outcomes due to virulence of the strain involved, immune defenses of the host, and by antibiotic resistance. The difficulty in eradication and the increasing concerns on antibiotics usages underscore the interest in developing new tools to control S. aureus mastitis. Vaccination represents one of the most studied of these tools but, so far, no vaccine seems to provide reliable protection. This review summarizes current knowledge on the major vaccine targets, including surface proteins, capsular polysaccharides, biofilm, and toxins. Finally, the present status of vaccination against S. aureus and the future of vaccine design were discussed, including how differences among in vivo models may influence vaccines development.

Formerly eclamptic women have lower nonpregnant blood pressure compared with formerly pre-eclamptic women: a retrospective cohort study.

OBJECTIVE: To compare nonpregnant blood pressure and circulating metabolic factors between formerly pre-eclamptic women who did and did not deteriorate to eclampsia. DESIGN: Retrospective observational cohort study. SETTING: Tertiary referral centre. POPULATION: Formerly pre-eclamptic women with (n = 88) and without (n = 698) superimposed eclampsia. METHODS: Women who experienced pre-eclampsia with or without superimposed eclampsia during their pregnancy or puerperium were tested for possible underlying cardiovascular risk factors at least 6 months postpartum. We measured blood pressure and determined cardiovascular and metabolic risk markers in a fasting blood sample. Groups were compared using Mann-Whitney U test, Spearman's Rho test or Fisher's Exact test (odds ratios). MAIN OUTCOME MEASURES: Differences in postpartum blood pressures and features of the metabolic syndrome between formerly pre-eclamptic and formerly eclamptic women. RESULTS: Formerly pre-eclamptic women who developed eclampsia differed from their counterparts without eclampsia by a lower blood pressure (P < 0.01) with blood pressure correlating inversely with the likelihood of having experienced eclampsia (P < 0.001). In addition, formerly eclamptic women had higher circulating C-reactive protein levels than formerly pre-eclamptic women (P < 0.05). All other circulating metabolic factors were comparable. Finally, 40% of all eclamptic cases occurred in the puerperium. CONCLUSIONS: Formerly pre-eclamptic women with superimposed eclampsia have lower nonpregnant blood pressure compared with their counterparts without neurological sequelae with blood pressure negatively correlated to the occurrence of eclampsia. As about 40% of all eclamptic cases occur postpartum, routine blood pressure monitoring postpartum should be intensified.

Short communication: study on veterinarian communication skills preferred and perceived by dairy farmers.

Effective communication in dairy farms improves management and herd health, and it is also pivotal for public health in a "from farm to fork" perspective. This paper reports the results of a descriptive study on dairy farmers' perception of veterinarian and other consultants' communication skills. Perceived communication skills showed to be significantly lower than desired ones for all the professional figures considered. Despite these unsatisfactory results, veterinarian were the most appreciated and skilled consultants. The observed farmers' dissatisfaction increases farmers' difficulties in identifying proper targets and proper consultant. An increase in the skill of veterinarian to deliver effective and tailored messages could help to overcome the problem.

Indoor pollution and burning practices in wood stove management.

This study evaluates effects of good burning practice and correct installation and management of wood heaters on indoor air pollution in an Italian rural area. The same study attests the role of education in mitigating wood smoke pollution. In August 2007 and winters of 2007 and 2008, in a little mountain village of Liguria Apennines (Italy), indoor and outdoor benzene, toluene, ethylbenzene, and xylene (BTEX) concentrations were measured in nine wood-heated houses. During the first sampling, several mistakes in heating plant installations and management were found in all houses. Indoor BTEX concentrations increased during use of wood burning. Low toluene/benzene ratios were in agreement with wood smoke as main indoor and outdoor pollution source. Other BTEX sources were identified as the indoor use ofsolvents andpaints and incense burning. Results obtained during 2007 were presented and discussed with homeowners. Following this preventive intervention, in the second winter sampling all indoor BTEX concentrations decreased, in spite of the colder outdoor air temperatures. Information provided to families has induced the adoption of effective good practices in stoves and fire management. These results highlight the importance ofeducation, supported by reliable data on air pollution, as an effective method to reduce wood smoke exposures.

Iodopropyl-branched polysiloxane gel electrolytes with improved ionic conductivity upon cross-linking.

We here report the implementation of poly[(3-N-methylimidazoliumpropyl)methylsiloxane-co-dimethylsiloxane]iodides as suitable polymeric hosts for a novel class of in situ cross-linkable iodine/iodide-based gel-electrolytes for dye-sensitized solar cells. The polymers are first partially quaternized and then subjected to a thermal cross-linking which allows the formation of a 3D polymeric network which is accompanied by a dramatic enhancement of the ionic conductivity.

Maturation is associated with changes in rat cerebral artery structure, biomechanical properties and tone.

AIM: This study evaluated the hypothesis that physiological maturation affects cerebral artery smooth muscle-endothelial interactions involved in pressure-induced tone and alters the dimensional and biomechanical properties of small posterior cerebral arteries (PCA). METHODS: Secondary branches of PCA from young (4-5 weeks old, n=11), adult (14-16 weeks old, n=11) and mature (44-47 weeks old, n=11) male Sprague-Dawley rats were isolated, cannulated, pressurized and subjected to a range of intraluminal pressures (10-110 mmHg) to determine tone with and without pharmacologic nitric oxide synthase (NOS) inhibition. Measurements of passive lumen diameter and wall thickness as a function of pressure were used to determine changes in structure, distensibility and wall stress; histological analysis was performed on vessel cross-sections to assess collagen and elastin contents. RESULTS: Although pressure-dependent tone decreased significantly during ageing, differences between groups were abolished by NOS inhibition. Vessel diameters increased in adult vs. young rats (at 90 mmHg, 233 ± 6.0 µm vs. 192 ± 4.5 µm; P<0.05), possibly secondary to somatic growth. Further ageing was associated with reductions in lumen diameter (207 ± 6.5 µm; P<0.05), increased wall and media thickness (and wall/lumen ratio) and cross-sectional area. Distensibility and wall collagen were unchanged, although elastin content was significantly reduced. CONCLUSIONS: Maturation is associated with differences in PCA dimensional properties that indicate a pattern of initial outward eutrophic, followed by inward hypertrophic remodelling. Functionally, the contribution of basal NO increases with age in a way that reduces pressure-dependent tone and diminishes vasodilator reserve.

Prenatal exposure to thalidomide, altered vasculogenesis, and CNS malformations.

Malformations of cortical development (MCD) result from abnormal neuronal positioning during corticogenesis. MCD are believed to be the morphological and perhaps physiological bases of several neurological diseases, spanning from mental retardation to autism and epilepsy. In view of the fact that during development, an appropriate blood supply is necessary to drive organogenesis in other organs, we hypothesized that vasculogenesis plays an important role in brain development and that E15 exposure in rats to the angiogenesis inhibitor thalidomide would cause postnatal MCD. Our results demonstrate that thalidomide inhibits angiogenesis in vitro at concentrations that result in significant morphological alterations in cortical and hippocampal regions of rats prenatally exposed to this vasculotoxin. Abnormal neuronal development was associated with vascular malformations and a leaky blood-brain barrier. Protein extravasation and uptake of fluorescent albumin by neurons, but not glia, was commonly associated with abnormal cortical development. Neuronal hyperexcitability was also a hallmark of these abnormal cortical regions. Our results suggest that prenatal vasculogenesis is required to support normal neuronal migration and maturation. Altering this process leads to failure of normal cerebrovascular development and may have a profound implication for CNS maturation.

[Open wedge osteotomy of the distal femur in the valgus knee]. / Offnende Keilosteotomie des distalen Femurs beim Valgusknie.

This review presents a novel technique for open-wedge varus osteotomies of the distal femur in lateral compartment osteoarthritis in valgus knees. Indications and contraindications are discussed. The technique, its potential pitfalls, and postoperative management are presented. The authors' results with this technique are compared to the data of the literature.

Impact of perioperative haemodynamic monitoring on cardiac morbidity after major vascular surgery in low risk patients. A randomised pilot trial.

OBJECTIVE: to evaluate whether perioperative haemodynamic optimisation influences outcome from infrarenal abdominal aortic aneurysm repair. METHODS: a consecutive series of 100 eligible patients were randomised to either haemodynamic optimisation through the use of a pulmonary artery catheter (CI > 3.0 l/min/sqm, PWP > 10 and <18 mmHg, SVR <1450 dyne/sec/cm(-5), DO(2)> 600 ml/min/sqm) or conventional treatment. RESULTS: there were no differences in terms of in-hospital mortality, cardiovascular morbidity, postoperative renal failure or duration of hospital stay between the groups. CONCLUSIONS: in this study perioperative haemodynamic optimisation was not beneficial.

Mechanical signaling through connective tissue: a mechanism for the therapeutic effect of acupuncture.

The mechanism of action of acupuncture remains largely unknown. The reaction to acupuncture needling known as 'de qi', widely viewed as essential to the therapeutic effect of acupuncture, may be a key to understanding its mechanism of action. De qi includes a characteristic needling sensation, perceived by the patient, and 'needle grasp' perceived by the acupuncturist. During needle grasp, the acupuncturist feels pulling and increased resistance to further movement of the inserted needle. We hypothesize that 1) needle grasp is due to mechanical coupling between the needle and connective tissue with winding of tissue around the needle during needle rotation and 2) needle manipulation transmits a mechanical signal to connective tissue cells via mechanotransduction. Such a mechanism may explain local and remote, as well as long-term effects of acupuncture.

Threshold duration of ischemia for myogenic tone in middle cerebral arteries: effect on vascular smooth muscle actin.

BACKGROUND AND PURPOSE: We investigated the effect of different periods of ischemia on the myogenic tone of middle cerebral arteries (MCAs) and tested the hypothesis that ischemia disrupts the actin cytoskeleton in vascular smooth muscle. METHODS: The MCA occlusion model was used in male Wistar rats (n=27) to induce different periods of ischemia (15, 30, and 120 minutes) with 24 hours of reperfusion. Successful occlusion was determined by laser-Doppler flowmetry. MCAs were then studied in vitro with a specialized arteriograph system that allowed control of transmural pressure and measurement of lumen diameter. After equilibration for 1 hour at transmural pressure of 75 mm Hg, lumen diameter was measured, and the amount of spontaneous myogenic tone was determined. Arteries were then fixed with 10% formalin while still pressurized in the arteriograph bath and stained for filamentous (F-) actin with fluorescently labeled phalloidin, a specific probe for F-actin. The amount of F-actin was quantified by confocal microscopy. RESULTS: The amount of tone was similar between control and 15 minutes of ischemia (27.0+/-2.0% and 25.3+/-1.7%, respectively; P>0.05) but was significantly diminished after 30 and 120 minutes (11.7+/-2.0% and 8.5+/-2.0%, respectively; P<0.01 versus control). F-actin content also decreased at the longer ischemic periods and correlated significantly with vascular tone (P=0.04) such that the lesser the tone, the lesser was the F-actin content. Fluorescence intensity for control and 15, 30, and 120 minutes of ischemia was (x10(7)) 3.21+/-0.25, 2.54+/-0.32 (P>0.05), 2.32+/-0.15 (P<0.01), and 2.22+/-0.16 (P<0.01), respectively. CONCLUSIONS: These results demonstrate that ischemia disrupts the actin cytoskeleton in smooth muscle and diminishes vascular tone of MCAs in a threshold-dependent manner. This effect likely exacerbates brain tissue damage during stroke, including infarction and edema formation.

Efficacy of antioxidant therapies in transient focal ischemia in mice.

BACKGROUND AND PURPOSE: Ginkgo biloba extract (EGb) and alpha-lipoic acid (LA) are commercially available "antioxidant supplements" with a variety of actions that may be beneficial during acute stroke. These actions include inhibiting platelet and leukocyte activation and adhesion, reducing free radical generation, and increasing cerebral blood flow. Both EGb and LA have been shown to be neuroprotective in cell culture and global central nervous system ischemia models. In this study we investigated the neuroprotective efficacy of EGb and LA in a clinically relevant, transient focal central nervous system ischemic model. METHODS: In the EGb study, 60 adult C57blk mice were randomized to treatment with EGb given orally (via gavage) for 7 days: low dose, 50 EGb mg/kg daily; high dose, 100 mg/kg daily; matched placebo. On day 7, reversible middle cerebral artery occlusion was produced by advancing a silicone-coated 8-0 filament into the internal carotid artery for 45 minutes followed by reperfusion. At 24 hours, the animals were evaluated on a 28-point clinical scale, and infarct volume was determined with the use of triphenyltetrazolium chloride. In the LA study, 24 C57blk mice were treated with 100 mg/kg SC of LA or placebo 1.5 hours before transient MCAO, as in the EGb study. RESULTS: In the EGb study, values for infarct volume at 24 hours were as follows (mean+/-SD): low dose (n=18), 13+/-5 mm(3); high dose (n=22), 22+/-12 mm(3); placebo (n=20), 20+/-10 mm(3) (P:=0.03 overall; P=0.02, low dose versus placebo). Infarct percentage of hemisphere values were as follows: low dose, 14+/-5%; high dose, 21+/-11%; placebo, 20+/-9% (P=0.03 overall; P=0.02, low dose versus placebo). Ten percent of the high-dose group showed significant intracerebral hemorrhage (ICH) within the infarct, while no ICH was seen in the other groups. Neurological function scores were as follows: low dose, 11.8+/-1.5; high dose, 11.4+/-1.7; placebo, 11.3+/-1.8 (P=NS). In the LA study, infarct volume was as follows: 100 mg/kg LA (n=12), 16.8+/-8.3 mm(3); placebo (n=12), 27.2+/-14.6 mm(3) (P<0.05). LA also produced a significant improvement in neurological function at 24 hours: LA, 9.5+/-1.2; placebo, 11.2+/-1.8 (P=0.02). There was no evidence of ICH in any of the animals. CONCLUSIONS: Both oral EGb and LA therapies produced significant reductions in stroke infarct volume. However, for EGb this beneficial effect appears to be dose related, with higher doses potentially increasing the risk of ICH.

Diabetes and endothelial dysfunction: a clinical perspective.

The main etiology for mortality and a great percent of morbidity in patients with diabetes mellitus is atherosclerosis. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction, defined pragmatically as changes in the concentration of the chemical messengers produced by the endothelial cell and/or by blunting of the nitric oxide-dependent vasodilatory response to acetylcholine or hyperemia. Endothelial dysfunction has been documented in patients with diabetes and in individuals with insulin resistance or at high risk for developing type 2 diabetes. Factors associated with endothelial dysfunction in diabetes include activation of protein kinase C, overexpression of growth factors and/or cytokines, and oxidative stress. Several therapeutic interventions have been tested in clinical trials aimed at improving endothelial function in patients with diabetes. Insulin sensitizers may have a beneficial effect in the short term, but the virtual absence of trials with cardiovascular end-points preclude any definitive conclusion. Two trials offer optimism that treatment with ACE inhibitors may have a positive impact on the progression of atherosclerosis. Although widely used, the effect of hypolipidemic agents on endothelial function in diabetes is not clear. The role of antioxidant therapy is controversial. No data have been published regarding the effects of hormonal replacement therapy on endothelial dysfunction in postmenopausal women with type 2 diabetes.

An uncommon cause of pericardial actinomycosis.

Cardiac actinomycosis is rare; the pericardium is the most frequently involved site, but myocardial, endocardial and valvular involvement have all been documented. Most cases originate from a thoracopulmonary site of actinomycosis and spread directly to the pericardium. Widespread dissemination from extrathoracic organs is uncommon; in fact actinomycosis is prevented by anatomical barriers and hematogenous diffusion is rare. We describe an uncommon case of pericardial actinomycosis due to a draining fistula from the liver to the pericardial space across the diaphragm. The massive dissemination through the fistula could explain the peculiar echocardiographic images of macroscopic, echo-reflective, irregular masses, floating in the pericardial space, probably consistent with aggregates of sulfur granules.

High resolution imaged laser speckle strain gauge for vascular applications.

An imaged laser speckle strain gauge that yields strain rates directly is described for vascular applications. The strain gauge does not rely upon cross correlations between a reference image and subsequent strain-modulated images as most current speckle interferometric methods do. Instead, it relies upon a two-dimensional frequency transform of "stacked speckle histories" which are time series of one-dimensional views of the speckle patterns arranged into a spatio-temporal array such that space is along the abscissa and time is along the ordinate. The tilt of the stacked speckle histories is related to the time rate of speckle pattern shift. The strain gauge is sensitive only to in-plane strains. Strain rates of 30.1 +/- 3.2 and 24.83 +/- 2.1 mu epsilon/s were evaluated in vitro on a fresh human tibial artery and rat inferior vena cava, respectively. The total strains measured were 21.6 and 19.86 mu epsilon, respectively. This is at least one order of magnitude more sensitive than other current soft-tissue strain measurement techniques.

The effect of elevated homocysteine levels on adrenergic vasoconstriction of human resistance arteries: the role of the endothelium and reactive oxygen species.

PURPOSE: This study investigated the effect of elevated homocysteine levels on adrenergic contraction of human resistance arteries and tested the hypothesis that homocysteine-induced generation of reactive oxygen species contributes to vascular reactivity changes. METHODS: Small (<200 microm) subcutaneous arteries were cannulated and pressurized in an arteriograph chamber that allowed the measurement of lumen diameter. Two arteries from the same patient were obtained; one was perfused and superfused (intraluminal pressure = 50 mm Hg) with physiologic saline solution (control, n = 6), and the other was perfused and superfused with physiologic saline solution plus 200 micromol/L homocysteine (HC, n = 6); the reactivity to adrenergic stimulation was assessed. Another group of arteries was incubated in 200 micromol/L homocysteine plus 1200 U/mL superoxide dismutase and 120 U/mL catalase (HC + SC, n = 6), and the reactivity to norepinephrine was determined. The vasoreactivity of homocysteine was further assessed in intact (n = 6) and denuded (n = 6) arteries that were precontracted with an intermediate concentration of norepinephrine and homocysteine (20-200 micromol/L) added to the bath while the lumen diameter was continuously recorded. RESULTS: Sensitivity to norepinephrine was diminished in HC arteries, which increased the median effective concentration (EC(50)) from 0.24 +/- 0.06 micromol/L in control arteries to 0.65 +/- 0.10 micromol/L in HC arteries (P <.01). Homocysteine also caused concentration-dependent vasodilation of arteries contracted with an intermediate concentration of norepinephrine that was greater in intact than denuded arteries, with the half-maximum responses occurring at 61 +/- 6 micromol/L (intact) and 90 +/- 11 micromol/L (denuded; P <.05). There was no significant difference in sodium nitroprusside sensitivity between control and homocysteine arteries (EC(50) = 61 +/- 3 nmol/L vs 50 +/- 19 nmol/L; P >.05) or in sensitivity to acetylcholine (EC(50) = 19 +/- 7 nmol/L vs 12 +/- 3 nmol/L; P >.05). Arteries in the presence of superoxide dismutase and catalase had similarly impaired reactivity to norepinephrine as did homocysteine arteries (EC(50), 0.58 +/- 0.15 micromol/L; P >.05 vs HC, P <.01 vs control). CONCLUSION: An elevated homocysteine level in vitro diminishes adrenergic contraction, with a differential endothelial versus smooth muscle influence that appears unrelated to the generation of reactive oxygen species.