Control and Measurement Systems Supporting the Production of Haylage in Baler-Wrapper Machines.

Baler-wrappers are machines designed to produce high-quality forage, in accordance with the requirements of sustainable agriculture. Their complicated structure, and significant loads occurring during operation, prompted the creation of systems for controlling the machines' processes and measuring the most important work parameters, in this work. The compaction control system is based on a signal from the force sensors. It allows for detection differences in the compression of the bale and additionally protects against overload. The method of measuring the swath size, with the use of a 3D camera, was presented. Scanning the surface and travelled distance allows for estimating the volume of the collected material-making it possible to create yield maps (precision farming). It is also used to vary the dosage of ensilage agents, that control the fodder formation process, in relation to the moisture and temperature of the material. The paper also deals with the issue of measuring the weight of the bales-securing the machine against overload and collecting data for planning the bales' transport. The machine, equipped with the above-mentioned systems, allows for safer and more efficient work, and provides information about the state of the crop in relation to a geographical position, which allows for further inferences.

Late Aortic Remodeling after Endovascular Repair of Complicated Type B Aortic Dissection-TEVAR Protects Only the Covered Segment of Thoracic Aorta.

BACKGROUND: TEVAR is the preferred way of treatment of complicated type B aortic dissection. The purpose of the study was to assess the impact of TEVAR on aortic remodeling in the thoracic and abdominal segment in long-term follow-up. METHODS: Twenty-three patients with complicated type B aortic dissection were treated by TEVAR in years 2004-2012 in our department. Aortic remodeling was rated based on preoperative and final follow-up computed tomography angiography. Aorta was measured at the level of left bronchus, the diaphragm, celiac trunk, and the aorta below the renal arteries. Diameter of the aorta (da), total aortic area (taa), true lumen area (tla), and false lumen area (fla) were measured. RESULTS: Primary technical success was obtained in 100%. Primary clinical success rate was 82.6%. Early mortality was 13% (3 patients). Mean follow-up was 57.9 months (26-123; standard deviation, ±30.5). All patients remain in the follow-up. Diameter of the aorta increased significantly only at the B level-from baseline 35,6 mm to 40,5 mm in the follow-up (P = 0.005). Total aortic area (taa) was stable only at the A level but increased significantly at the B, C, and D levels. Area of the true lumen (tla) increased significantly at A, B, C, and D levels; area of false lumen (fla) decreased significantly at A and B levels, but the area of false lumen (fla) did not change at C and D levels. CONCLUSIONS: TEVAR for complicated acute aortic type B dissection is a safe and effective method of protecting thoracic aorta. The procedure was effective in majority of patients, and in 80% of the cases, there was no need for additional distal aortic coverage. The abdominal aorta is relatively stable over a long period of observation in complicated type B aortic dissection.

Traumatic aortic injury: does the anatomy of the aortic arch influence aortic trauma severity?

PURPOSE: Traumatic aortic injury (TAI) is a rare but life-threatening type of injury. We investigate whether the anatomy of the aortic arch influences the severity of aortic injury. METHODS: This is a retrospective study of twenty-two cases treated with TEVAR for TAI in our department from 2009 to 2014. Aortic injury was assessed in accordance with the recommendations of the Society of Vascular Surgery. We measured the aortic arch angle and the aortic arch index, based on the initial angio-CT scan, in each of the analyzed cases. RESULTS: The mean aortic arch index and mean aortic arch angle were 6.8 cm and 58.3°, respectively, in the type I injury group; 4.4 cm and 45.9° in the type III group; 3.3 cm and 37° in the type IV group. There were substantial differences in both the aortic arch index and the aortic arch angle of the type III and IV groups. A multivariate analysis confirmed that the aortic arch angle was significantly associated with the occurrence of type III damage (OR 1.5; 95% CI 1.03-2.2). CONCLUSIONS: The severity of TAI is influenced by the sharpness of the aortic arch. There is an inverse relationship between the severity of aortic injury and the aortic arch index.

G0/G1 Switch Gene 2 Regulates Cardiac Lipolysis.

The anabolism and catabolism of myocardial triacylglycerol (TAG) stores are important processes for normal cardiac function. TAG synthesis detoxifies and stockpiles fatty acids to prevent lipotoxicity, whereas TAG hydrolysis (lipolysis) remobilizes fatty acids from endogenous storage pools as energy substrates, signaling molecules, or precursors for complex lipids. This study focused on the role of G0/G1 switch 2 (G0S2) protein, which was previously shown to inhibit the principal TAG hydrolase adipose triglyceride lipase (ATGL), in the regulation of cardiac lipolysis. Using wild-type and mutant mice, we show the following: (i) G0S2 is expressed in the heart and regulated by the nutritional status with highest expression levels after re-feeding. (ii) Cardiac-specific overexpression of G0S2 inhibits cardiac lipolysis by direct protein-protein interaction with ATGL. This leads to severe cardiac steatosis. The steatotic hearts caused by G0S2 overexpression are less prone to fibrotic remodeling or cardiac dysfunction than hearts with a lipolytic defect due to ATGL deficiency. (iii) Conversely to the phenotype of transgenic mice, G0S2 deficiency results in a de-repression of cardiac lipolysis and decreased cardiac TAG content. We conclude that G0S2 acts as a potent ATGL inhibitor in the heart modulating cardiac substrate utilization by regulating cardiac lipolysis.

A downstream CpG island controls transcript initiation and elongation and the methylation state of the imprinted Airn macro ncRNA promoter.

A CpG island (CGI) lies at the 5' end of the Airn macro non-protein-coding (nc) RNA that represses the flanking Igf2r promoter in cis on paternally inherited chromosomes. In addition to being modified on maternally inherited chromosomes by a DNA methylation imprint, the Airn CGI shows two unusual organization features: its position immediately downstream of the Airn promoter and transcription start site and a series of tandem direct repeats (TDRs) occupying its second half. The physical separation of the Airn promoter from the CGI provides a model to investigate if the CGI plays distinct transcriptional and epigenetic roles. We used homologous recombination to generate embryonic stem cells carrying deletions at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn alleles were analyzed by using an ES cell imprinting model that recapitulates the onset of Igf2r imprinted expression in embryonic development or by using knock-out mice. The results show that the CGI is required for efficient Airn initiation and to maintain the unmethylated state of the Airn promoter, which are both necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the second half of the CGI play a minor role in Airn transcriptional elongation or processivity, but are essential for methylation on the maternal Airn promoter that is necessary for Igf2r to be expressed from this chromosome. Together the data indicate the existence of a class of regulatory CGIs in the mammalian genome that act downstream of the promoter and transcription start.

Early and Mid-Term Results of Native and Abdominal Aortic Graft Infection Treatment via Surgeon-Constructed Porcine Pericardial Aortic Tubes.

The search for optimal material for aortic infection reconstruction is ongoing. Our study presents the early and mid-term results of surgeon-constructed porcine pericardial tubes in the in-situ reconstruction of abdominal aortic infections, focusing on the safety as well as the durability of surgeon-created tubes. We performed a retrospective analysis of 8 patients treated for native aortic (n = 3) and aortic graft infections (n = 5) with surgeon-created tubes made of porcine pericardium patch (8 × 14 cm NO-REACT Ⓡ, BioIntegral Surgical Inc., Mississauga, ON, Canada). There were 7 males and 1 female, aged 68.5 (±4.8 years). Three patients had an aorto-enteric fistula. Technical success was obtained in all patients. Thirty-day mortality was 12.5% (n = 1). Mid-term follow-up was 12 months (2-63 months). One-year mortality was 37.5% (n = 3). Reintervention rate was 28.5% (n = 2). False aneurysm rate in the follow-up was 14.2% (n = 1). Surgeon-constructed porcine pericardial tubes seem to be a promising alternative as a replacement for native as well as graft-related abdominal aortic infections. The mid-term durability is encouraging, once the infection is controlled in cases with successful fistula repair and in native aortic infections patients. Further observations on larger groups, in longer follow-ups are necessary to confirm these preliminary observations.

Surgical repair of a symptomatic celiac artery aneurysm with resection and end-to-end anastomosis.

A true aneurysm of the celiac artery is a rare form of a visceral aneurysm, constituting ∼4% of visceral aneurysms. Mortality in ruptured cases is high; thus, early recognition and treatment are crucial. Recent guidelines suggest endovascular therapy; however, numerous complications are associated with endoluminal treatment. Open repair in select cases, using an individualized strategy fit for the patient's anatomy still provides excellent early and long-term results. Our patient was treated with open surgical resection and end-to-end anastomosis of the celiac and common hepatic arteries. A 43-month follow-up computed tomography angiogram revealed excellent hepatic artery patency and no pseudoaneurysm formation.

Monoglyceride lipase deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance.

Monoglyceride lipase (MGL) influences energy metabolism by at least two mechanisms. First, it hydrolyzes monoacylglycerols (MG) into fatty acids and glycerol. These products can be used for energy production or synthetic reactions. Second, MGL degrades 2-arachidonoyl glycerol (2-AG), the most abundant endogenous ligand of cannabinoid receptors (CBR). Activation of CBR affects energy homeostasis by central orexigenic stimuli, by promoting lipid storage, and by reducing energy expenditure. To characterize the metabolic role of MGL in vivo, we generated an MGL-deficient mouse model (MGL-ko). These mice exhibit a reduction in MG hydrolase activity and a concomitant increase in MG levels in adipose tissue, brain, and liver. In adipose tissue, the lack of MGL activity is partially compensated by hormone-sensitive lipase. Nonetheless, fasted MGL-ko mice exhibit reduced plasma glycerol and triacylglycerol, as well as liver triacylglycerol levels indicative for impaired lipolysis. Despite a strong elevation of 2-AG levels, MGL-ko mice exhibit normal food intake, fat mass, and energy expenditure. Yet mice lacking MGL show a pharmacological tolerance to the CBR agonist CP 55,940 suggesting that the elevated 2-AG levels are functionally antagonized by desensitization of CBR. Interestingly, however, MGL-ko mice receiving a high fat diet exhibit significantly improved glucose tolerance and insulin sensitivity in comparison with wild-type controls despite equal weight gain. In conclusion, our observations implicate that MGL deficiency impairs lipolysis and attenuates diet-induced insulin resistance. Defective degradation of 2-AG does not provoke cannabinoid-like effects on feeding behavior, lipid storage, and energy expenditure, which may be explained by desensitization of CBR.

Prediction of chemical-protein binding activity using contrast graph patterns.

The problem of classifying chemical compounds is studied in this chapter. Compounds are represented as two-dimensional topological graphs of atoms (corresponding to nodes) and bonds (corresponding to edges). We use a method called contrast common pattern classifier (CCPC) to predict chemical-protein binding activity. This approach is strongly associated with the classical emerging patterns techniques known from decision tables. It uses two different types of structural patterns (subgraphs): contrast and common. Results show that the considered algorithm outperforms all other existing methods in terms of classification accuracy.

Iliac artery injury during lumbar microdiscectomy.

BACKGROUND: Accidental laceration of major abdominal vessels during lumbar disc surgery is a relatively rare complication that requires rapid diagnosis and management. CASE REPORT: A 25-yr-old woman, operated on for an L4-L5 disc hernia, developed cardiovascular collapse after disc removal. This was treated with volume replacement and ephedrine, and a postoperative CT scan revealed a large retroperitoneal haematoma. During an immediate laparotomy, a 10 cm laceration of the left iliac artery was repaired and massive blood loss replaced (to lowest haemoglobin concentration during the surgery was 2.1 mmol L(-1)).The patient made a full recovery. CONCLUSION: In any case of unexpected hypotension during lumbar disc herniation surgery, accidental vascular damage should be suspected and a CT scan performed immediately.

Effects of thoracic epidural anaesthesia on cardiac repolarization.

1. Prolongation of the QT interval is associated with a risk of life-threatening cardiac arrhythmias. In the present study, we examined whether reversible blockade of preganglionic sympathetic fibres of the heart, achieved by thoracic epidural anaesthesia, affects cardiac repolarization and thus confers an anti-arrhythmic effect. 2. Fifty-two men, aged between 28 and 65 years, were included in the study: 28 were patients scheduled for thoracic epidural anaesthesia (Group T) and 24 were patients scheduled for lumbar epidural anaesthesia (Group L). Epidural blockade was achieved with 0.5% isobaric bupivacaine solution. Measurements were taken from electrocardiogram fragments obtained before epidural anaesthesia and after detection of blockade (T1 or T8 segment sensory block in Groups T and L, respectively). Correction of the QT interval was calculated using Bazett's formula (QTcb), Fridericia's correction (QTcf) and the Framingham formula (QTcF). Transmural dispersion of repolarization (TDR) was determined using the Tpeak--Tend time, where Tpeak is the peak of the T wave and Tend is the end of the T wave. 3. Significant shortening of the QTcb interval and TDR was detected after blockade in Group T. However, there were no changes in the ECG parameters in Group L. 4. In conclusion, reversible blockade of preganglionic sympathetic fibres to the heart, achieved by thoracic epidural anaesthesia, results in a reduction in QTcb, as well as the TDR. These changes may explain the anti-arrhythmic action seen with central blockade.

Dexmedetomidine sedation for carotid endarterectomy.

BACKGROUND: General anaesthesia and deep sedation during endarterectomy exclude direct contact with the patient, required for safe performance of the surgery. The aim of the study was to assess sedation with dexmedetomidine and its cardiovascular effects. METHODS: Sixty-four adult patients, scheduled on internal carotid artery surgery under infiltration analgesia, were randomly divided to receive dexmedetomidine in the loading dose of 1 microg kg(-1) over 10 min, followed by 0.2 microg kg(-1) h(-1) continuous infusion (group D) or placebo (group P).The BIS score, heart rate (HR) and mean arterial pressure (MAP) were noted. RESULTS: In the group D, during carotid artery clamping (CAC) mean BIS scores were lower, compared to the baseline and to the values recorded in the group P. The BIS scores in the group P did not differ from baseline. In the group D, we did not observe cardiovascular reactions that could be attributed to CAC; in the group P, MAP and HR increased during CAC, and returned to normal 10 min after clamp release. Significant decrease of HR was observed after 12 min of dexmedetomidine infusion, at 10 and 15 min after CAC in group D. Urapidil and fentanyl were administered more often in the placebo group. CONCLUSIONS: The 0.2 microg kg(-1) h(-1) dexmedetomidine infusion, administered during carotid endarterectomy, secured cardiovascular stability and reduced the need for additional analgesia.

REBOA - new era of bleeding control, literature review.

It is extremely difficult to provide non-compressible torso hemorrhage control particularly in trauma setting. A vast majority of cases present inability of successful exsanguination arrest, leading to cardiovascular collapse, myocardial and cerebral hypoperfusion and death eventually. The only possible treatment for these patients is prompt bleeding control, either open or endovascular. Aortic occlusion seems to be the most rapid and convenient way to restrain blood loss and possibly increase survival. However, it is not proven yet. Traditional aortic occlusion for trauma consisted of supradiaphragmatic thoracic aorta cross-clamping through resuscitative thoracotomy (RT). This complicated and devastating procedure triggered the necessity to work on a simpler, less invasive resuscitation bridge which can be implemented in emergency departments or even in prehospital setting. Resuscitative balloon occlusion of the aorta (REBOA) provides a novel method of hemorrhagic shock stabilization in bleeding below the diaphragm. The mechanism lies in improving myocardial and cerebral perfusion and ceasing major bleeding itself. This method together with invasive endovascular and surgical procedures creates a new approach of choice for trauma patients. It is called Endovascular Hybrid Trauma and Resuscitation Management (EVTM) and introduces this concept to modern clinical practice. Through a detailed review, this article aims to introduce REBOA procedure to a broader recipient and present REBOA details, benefits and limitations.

Action of a novel anticancer agent, CHS 828, on mouse fibroblasts: increased sensitivity of cells lacking poly (ADP-Ribose) polymerase-1.

We observed stronger cytotoxic effect of CHS 828 on poly(ADP-ribose) polymerase-1(PARP-1) knock-out cells as compared with the normal counterpart. The proliferation of PARP-1 -/- cells was inhibited by a drug concentration approximately 3-fold lower than that in the normal cells. The monitoring of p53 levels revealed that CHS 828 induced p53 response in a dose-dependent manner in only normal cells. The drug, however, failed to activate the p53 protein in PARP-1-deficient cells even after combined treatment with multidrug-resistant modulators. These results show that the PARP-1 inactivation sensitizes cells to the novel anticancer drug CHS 828 and that the drug is able to activate different cellular pathways depending on PARP-1 status.

The influence of epidural blockade on gut permeability in patients undergoing open surgical repair of abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic clamping during aneurysm repair may cause a decrease in splanchnic blood flow and deterioration of gut barrier integrity. Epidural blocks have beneficial effects on vital organs during abdominal surgery, but sparse data are available on the influence on gut permeability during open aortic surgery. The aim of this study was to verify the hypothesis that epidural blocks may have beneficial effects on intestine permeability changes. METHODS: Seventy individuals undergoing elective open abdominal aortic aneurysm repair were randomly assigned to receive either balanced anaesthesia (continuous epidural and general anaesthesia, group E&G) or only general anaesthesia (group G). For group E&G, an epidural catheter was inserted into the epidural space before the induction of general anaesthesia. Ropivacaine was used for intraoperative and postoperative blocks. For both groups general anaesthesia was maintained with sevoflurane. For group G, analgesia was provided with remifentanil. The assessments of gut function were based on measurements of the absorption and percentages of urinary excretion of four sugars (m 3-O-methyl-D-glucose, D-xylose, L-rhamnose and lactulose) and the lactulose/rhamnose (L/R) ratio. RESULTS: No intergroup differences were observed for sugar recovery or L/R ratio. Significant decreases in 3-O-methyl-D-glucose, D-xylose, and L-rhamnose recoveries were revealed in both examined groups when comparing the results obtained at 12 and 24 hours following the administration of anaesthesia. The rate of blood pressure decrease was significantly higher in group E&G. CONCLUSIONS: Aortic clamping during open abdominal aortic repair led to unfavorable changes in intestinal permeability. Epidural block did not attenuate this deterioration.

Advantage of a baculovirus expression system for protein-protein interaction studies. Involvement of posttranslational phosphorylation in the interaction between wt p53 protein and poly(ADP-ribose) polymerase-1.

We recently observed an interaction between poly(ADP-ribose) polymerase-1 (PARP-1) and the tumor suppressor p53 protein. However, more extensive studies on both proteins, especially those on characterization of their domains involved in the interaction were difficult due to very low expression levels of p53 in mammalian cells. Therefore, we generated recombinant proteins for such studies. To clarify which domains of human PARP-1 and of human wild-type (wt) p53 were involved in this protein-protein interaction, we generated baculoviral constructs encoding full length or distinct functional domains of both proteins. Full length PARP-1 was simultaneously coexpressed in insect cells with full length wt p53 protein or its distinct truncated fragments and vice versa. Reciprocal immunoprecipitation of Sf9 cell lysates revealed that the central and carboxy-terminal fragments of p53 each were sufficient to confer binding to PARP-1, whereas the amino-terminal part harbouring the transactivation functional domain was dispensable. On the other hand, the amino-terminal and central fragments of PARP-1 were both necessary for complex formation with p53 protein. Since the most important features of p53 protein are regulated by phosphorylation, we addressed the question whether its phosphorylation is essential for the binding between the two proteins. Baculovirally expressed wt p53 was post-translationally modified. At least six distinct p53 isomers were resolved by immunoblotting following two-dimensional separation of baculovirally expressed wt p53 protein. Using specific phospho-serine antibodies, we identified phosphorylation of baculovirally expressed p53 protein at five distinct sites. To define the role of p53 phosphorylation, pull-down assays using untreated and dephosphorylated p53 protein were performed. Dephosphorylated p53 failed to bind PARP-1, indicating that complex formation between the two proteins was regulated by phosphorylation of p53. The marked phosphorylation of p53 at Ser392 observed in unstressed cells suggests that the phosphorylated carboxy-terminal part of p53 undergoes complex formation with PARP-1 resulting in masking of the NES and thereby preventing its export.

Does epidural anaesthesia reduce the incidence of postoperative oxygen desaturation episodes in patients undergoing open abdominal aortic aneurysm repair?

BACKGROUND: Postoperative desaturation can lead to severe hypoxaemia and even tissue hypoxia, followed by cardiological and neurological complications. Opioid usage is the one of the most important risk factors of postoperative desaturation and hypoxemia. Epidural anaesthesia is recommended for vascular surgery for many reasons; the reduction or elimination of opioid doses is one reason. The aims of the study were to evaluate the incidence of desaturation episodes in patients after surgical procedures with abdominal aortic clamping, to determine whether the episodes in question lead to clinical symptoms of hypoxia and to determine whether epidural anaesthesia decreases the incidence of desaturation episodes. METHODS: After abdominal aortic repair, 58 patients who did not have any respiratory disease, were classified as ASA II-III, and were aged from 46 to 80 years were observed in the ICU during spontaneous breathing with oxygen supplementation. Non-invasive O2 saturation measurements were taken continuously, and all desaturation incidents (defined as O2 saturation ≤ 93% for 4 min) were noted. Patients were divided into two equal groups: A - epidural blockade used after the operation for pain relief and B - intravenous opioids administered during the postoperative period. We evaluated and compared the desaturation frequency during the postoperative period. RESULTS: Desaturation was observed among 26 (89%) patients in group A and 27 (93%) patients in group B. There were no statistical differences among the groups (P = 1.0). Severe hypoxemia (O2 saturation ≤ 84%) was observed among 7 (24.1%) patients in group A and 10 patients in group B (34.5%) (P = 0.38). Clinical symptoms of hypoxia were similar in both groups (P = 1.0). CONCLUSIONS: Epidural anaesthesia did not protect against postoperative desaturation. Though oxygen therapy was used, desaturation was observed in approximately 90% of patients.

MNNG induces dramatic DNA damage and non-apoptotic changes in cervical carcinoma HeLa cells.

It has been previously reported that a short treatment of human cervix carcinoma HeLa cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced apoptosis. We examined the action of MNNG on HeLa cells and compared it with that of cisplatin. MNNG damaged the integrity of the cell membrane and killed the cells within 3 hours. During this period no changes characteristic for apoptosis, such as cell shrinkage, condensation of nuclei, chromatin fragmentation or activation of caspases, could be detected. However, the exposure of HeLa cells to 50 micro M MNNG for 1 h resulted in dramatic DNA damage. The MNNG-induced disruption of cell membrane associated with cell death indicates that HeLa cells die by necrosis.

The influence of epidural anesthesia on the electrical activity of heart atria.

INTRODUCTION: High thoracic epidural anesthesia (TEA) causes blockade of sympathetic fibers involved in innervation of the heart (segments T1-T4), which results in changes of cardiac electrophysiology. The anti-arrhythmic effects of TEA on supraventricular arrhythmias, mainly atrial fibrillation, are controversial. THE AIM OF THE STUDY: The aim of the study was to assess the influence of epidural anesthesia on the electrical function of heart atria, including proven markers of increased risk of perioperative atrial fibrillation, such as P wave dispersion and P wave maximum duration. MATERIAL AND METHODS: The study involved 50 male patients, without a history of previous heart diseases, scheduled for elective surgical procedures. Patients received thoracic epidural anesthesia (group T, n = 25) or lumbar epidural anesthesia (group L, n = 25). The measurements were obtained from a continuous recording of ECG before epidural anesthesia and after the detection of blockade (T1 or T8 segment sensory block in groups T and L, respectively). RESULTS: The statistical analysis of electrocardiographic parameters, including the maximum, minimum and mean P wave duration; P wave dispersion; the maximum, minimum and mean PR interval duration; and PR interval dispersion, did not show any inter- or intragroup differences at selected time points. CONCLUSIONS: Regardless of its location, epidural anesthesia and sympathetic blockade associated with this procedure do not significantly affect the electrical functions of the cardiac atria reflected in superficial ECG, including the electrocardiographic parameters that are considered to be markers of increased risk of perioperative atrial fibrillation, such as P wave dispersion and its maximum duration.

Nitric oxide production and endothelium-dependent vasorelaxation ameliorated by N1-methylnicotinamide in human blood vessels.

N(1)-methylnicotinamide (MNA(+)) has until recently been thought to be a biologically inactive product of nicotinamide metabolism in the pyridine nucleotides pathway. However, the latest observations imply that MNA(+) may exert antithrombotic and anti-inflammatory effects through direct action on the endothelium. We examined both in vivo and in vitro whether the compound might induce vasorelaxation in human blood vessels through the improvement of nitric oxide (NO) bioavailability and a reduction of oxidative stress mediated by endothelial NO synthase (eNOS) function. MNA(+) treatment (100 mg/m(2) orally) in healthy normocholesterolemic and hypercholesterolemic subjects increased the l-arginine (l-NMMA)-inhibitable flow-mediated dilation (FMD) of brachial artery responses that also positively correlated with MNA(+) plasma concentrations (r=0.73 for normocholesterolemics and r=0.78 for hypercholesterolemics; P<0.0001). MNA(+) increased FMD at the same concentration range at which it enhanced NO release from cultured human endothelial cells after stimulation with either the receptor-dependent (acetylcholine) or the receptor-independent endothelial NO synthase agonists (calcium ionophore A23187). MNA(+) restored the endothelial NO synthase agonist-stimulated NO release after the exposure of the cells to oxidized low-density lipoprotein. This effect was also associated with the normalization of the [NO]/[superoxide] balance in the endothelial cells. Taken together, the increased NO bioavailability in the endothelium contributes to the vasorelaxating properties of MNA(+). Targeting eNOS with MNA(+) might be therapeutically relevant for functional disorders of the endothelium, such as hypercholesterolemia and atherosclerosis.