Clinical efficacy and tolerability of zonisamide monotherapy in dogs with newly diagnosed idiopathic epilepsy: Prospective open-label uncontrolled multicenter trial.

BACKGROUND: Zonisamide (ZNS) is a newer generation antiseizure medication (ASM) used to treat epilepsy in dogs and cats. However, scientific and clinical information, particularly regarding monotherapy, is limited. OBJECTIVES: To evaluate the antiseizure efficacy and tolerability of ZNS monotherapy in dogs with newly diagnosed idiopathic epilepsy (IE). ANIMALS: Study included 56 client-owned dogs newly diagnosed with IE. METHODS: This was a prospective multicenter, open-label, uncontrolled study. All dogs were ASM-naïve and had ≥2 seizures within 12 weeks. Dogs were administered 2.7-14.4 mg/kg ZNS PO q12h and followed up for ≥12 weeks. Data from the 12-week maintenance treatment period were compared with those from the 4- to 12-week pretreatment period for efficacy evaluation. Data from the entire ZNS administration period were used to assess tolerability. RESULTS: Fifty-six dogs were included in our study. Of the dogs, 53 were assessed for efficacy; 40 (76%) had a ≥ 50% reduction in seizure frequency, and 29 (55%) achieved seizure freedom. For 90% of the dogs with ≥50% reduction in seizure frequency, the mean ZNS dose was 4.8 (range, 2.7-8.6) mg/kg q12h and the mean trough plasma ZNS concentration was 18.9 (range, 8.0-48.0) µg/mL. In 7 of the 56 dogs (13%), reduced activity, decreased appetite, vomiting, hindlimb weakness, soft stools, or constipation was observed, albeit mild and temporary. Laboratory tests revealed no relevant changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study suggests that ZNS monotherapy is effective and well-tolerated in dogs with newly diagnosed IE.

Encapsulated gas accumulation in the spinal canal: Pneumorrhachis in two dogs.

A 17-year-old mongrel dog and 12-year-old Shiba Inu dog presented with ataxia and paresis of the pelvic limbs, respectively. Gas accumulation within the spinal canal adjacent to the herniated disc was suspected in both cases. Since the gas remained accumulated for a prolonged period, hemilaminectomy was performed to decompress the spinal cord. The bulged external lamina of the dura matter was removed and histopathologically examined. Granulomatous inflammation and hyperplasia of fibrous connective tissues was noted, suggesting that the gas was encapsulated and the fibrous nodules made reabsorption difficult. Clinical signs resolved post-surgery. This is the first report describing histopathological features of pneumorrhachis in dogs. The accumulated gas was successfully removed by surgery. Postoperative course remained uneventful in both cases.

[The current situation and agendas in the prevention and control of non-communicable diseases in Vietnam].

Objectives　In Vietnam, the number of patients with non-communicable diseases (NCDs) has been increasing in recent years in association with the country's remarkable economic growth and corresponding changes in its population's lifestyle. The purposes of this research were to identify the challenges in the prevention and control of NCDs in Vietnam and to discuss countermeasures for NCDs in Vietnam and Japan.Methods　As a 2015 Regional Public Health Overall Promotion Project, an investigation team consisting of 11 public health physicians visited Hanoi, the capital of Vietnam, and its vicinities from January 11, 2016 to January 15, 2016. In Hanoi and its vicinities, we visited local healthcare institutions, such as the World Health Organization(WHO) Representative Office in Vietnam and Ministry of Health of Vietnam, and discussed the prevention and control of NCDs in Vietnam and Japan.Results　According to a survey in 2014, 73% of people of all age groups in Vietnam died from NCDs and the number of people suffering from NCDs has been sharply increasing in recent years. Major behavioral risk factors are dietary risks, tobacco smoke, alcohol use, and physical inactivity. There are four main problems with prevention and control of NCDs: 1) low awareness among the people of NCDs, 2) regional disparity of medical services, 3) shortage of healthcare staff members with professional knowledge, and 4) poor NCD surveillance.　In Vietnam, an NCD program with screening methods and medical guidelines for respective diseases was developed in 2002. However, it only covered tertiary prevention and did not fully describe the primary and secondary prevention measures. Currently, with the technical assistance of the WHO, the implementation of countermeasures emphasizing prevention and control to reduce NCD risk factors has only just begun.Conclusion　It was considered that educating each person in Vietnam on NCD prevention measures would be necessary and that a national policy, like Healthy Japan 21 of Japan, and a nationwide screening project, such as specific medical checkups, could serve as a useful reference. We found that public health activities in Japan to penetrate a region mainly involving public health nurses had played important roles for Japanese people's health. Furthermore, Japan shares with Vietnam the challenges including the shortage of human resources, and therefore, the securement of healthcare staff members who confront health challenges and the enhancement of their abilities is required.

Modified PISAPED Criteria in Combination with Ventilation Scintigraphic Finding for Predicting Acute Pulmonary Embolism.

This prospective clinical study aimed at assessing three pulmonary scintigraphic algorithms to detect acute pulmonary embolism (PE): Lung ventilation/perfusion (V/Q) scintigraphy along with modified prospective investigation of pulmonary embolism diagnosis (PIOPED) criteria; lung perfusion scintigraphy along with prospective investigative study of acute pulmonary embolism diagnosis (PISAPED) criteria; and lung perfusion scan in combination with ventilation scan, along with modified PISAPED criteria, which were newly developed. Patients with suspicion of PE were eligible for this study if they had no abnormal chest x-ray. Their diagnostic workup included a clinical assessment, a pulmonary V/Q scintigraphy, and CT pulmonary angiography (CTPA), as well as a clinical outcome assessment over a period of 24 weeks. Referred to the final clinical diagnosis of patients, the sensitivity and specificity of each algorithm were evaluated. The diagnostic performance of each algorithm by the area under the maximum likelihood fitted receiver operating characteristic (ROC) curve was determined. With respect to the PISAPED criteria, the sensitivity was 60.8% and specificity was 87.3%. No patient was classified into nondiagnostic category. The PIOPED criteria showed that the sensitivity was 95.0% and specificity was 88.2%, while 57.4% of the patients were in nondiagnostic category. The areas under the ROC curve constructed from the PISAPED criteria results and the modified PIOPED criteria results were 0.734 and 0.859 (P < 0.01), respectively. The modified PISAPED criteria demonstrated that the sensitivity was 83.8% and specificity was 89.1%. No patient was classified into nondiagnostic category. The area under the ROC curve constructed from modified PISAPED criteria was 0.864 (P < 0.01). Perfusion scans used with ventilation scans and modified PISAPED criteria may increase the diagnostic accuracy of pulmonary scintigraphy for acute PE, compared with the two major algorithms.

Distributed strain measurement based on long-gauge FBG and delayed transmission/reflection ratiometric reflectometry for dynamic structural deformation monitoring.

In this paper, we propose a delayed transmission/reflection ratiometric reflectometry (DTR(3)) scheme using a long-gauge fiber Bragg grating (FBG), which can be used for dynamic structural deformation monitoring of structures of between a few to tens of meters in length, such as airplane wings and helicopter blades. FBG sensors used for multipoint sensing generally employ wavelength division multiplexing techniques utilizing several Bragg central wavelengths; by contrast, the DTR(3) interrogator uses a continuous pulse array based on a pseudorandom number code and a long-gauge FBG utilizing a single Bragg wavelength and composed of simple hardware devices. The DTR(3) scheme can detect distributed strain at a 50 cm spatial resolution using a long-gauge FBG with a 100 Hz sampling rate. We evaluated the strain sensing characteristics of the long-gauge FBG when attached to a 2.5 m aluminum bar and a 5.5 m helicopter blade model, determining these structure natural frequencies in free vibration tests and their distributed strain characteristics in static tests.

Vizantin inhibits endotoxin-mediated immune responses via the TLR 4/MD-2 complex.

Vizantin has immunostimulating properties and anticancer activity. In this study, we investigated the molecular mechanism of immune activation by vizantin. THP-1 cells treated with small interfering RNA for TLR-4 abolished vizantin-induced macrophage activation processes such as chemokine release. In addition, compared with wild-type mice, the release of MIP-1ß induced by vizantin in vivo was significantly decreased in TLR-4 knockout mice, but not in TLR-2 knockout mice. Vizantin induced the release of IL-8 when HEK293T cells were transiently cotransfected with TLR-4 and MD-2, but not when they were transfected with TLR-4 or MD-2 alone or with TLR-2 or TLR-2/MD-2. A dipyrromethene boron difluoride-conjugated vizantin colocalized with TLR-4/MD-2, but not with TLR-4 or MD-2 alone. A pull-down assay with vizantin-coated magnetic beads showed that vizantin bound to TLR-4/MD-2 in extracts from HEK293T cells expressing both TLR-4 and MD-2. Furthermore, vizantin blocked the LPS-induced release of TNF-α and IL-1ß and inhibited death in mice. We also performed in silico docking simulation analysis of vizantin and MD-2 based on the structure of MD-2 complexed with the LPS antagonist E5564; the results suggested that vizantin could bind to the active pocket of MD-2. Our observations show that vizantin specifically binds to the TLR-4/MD-2 complex and that the vizantin receptor is identical to the LPS receptor. We conclude that vizantin could be an effective adjuvant and a therapeutic agent in the treatment of infectious diseases and the endotoxin shock caused by LPS.

Potential requirement of positron emission tomography apparatuses in Asia and latin america including Mexico.

The number of positron emission tomography (PET) machines has been increasing in regions of East-, Southeast-, and South-Asia as well as in Latin America including Mexico. This study was performed to assess the potential requirement of PET machines in 19 countries which already use PET in the aforementioned regions. Data on the number of PET machines and internationally available characteristics of the restrictive countries such as the land area, the total population, the gross national income (GNI), and the average life span of inhabitants were obtained from IAEA, UN, WB, and WHO. Correlation between the number of PET machines and the characteristics of each country was evaluated. The potentially required number of PET machines, which was obtained by adjusting the number of PET machines with statistically significant, correlative characteristics of each country, standardized on the state of Japan, were compared. The number of PET machines could be significantly correlated to the GNI of a country and the average life span of its inhabitants (P < 0.05). Based on Japan, most of the countries in the regions would require considerably more PET machines. With installation of the potentially required number of PET machines in each of the countries, the number of PET machine per 10(6) population would increase by 1.1- to 12-fold, in comparison with the current situation. With regards to the potentially required number of PET machines, most of the countries in these regions may require a considerable increase of PET machines. Nevertheless, some countries in the Asia seem to require outside assistance such as international support in order to introduce PET and enhance the efficacy of their health services.

Development of vizantin, a safe immunostimulant, based on the structure-activity relationship of trehalose-6,6'-dicorynomycolate.

Vizantin, 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose, was developed as a safe immunostimulator on the basis of a structure-activity relationship (SAR) study with trehalose 6,6'-dicorynomycolate (TDCM). It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells. Because vizantin stimulated human macrophages, it is a promising candidate for clinical application.

[Utilization of radionuclide therapy facility and assembly-temporary type therapeutic facility for medical treatment of radioactivity contaminated patients in nuclear emergency].

Medical management of patients internally contaminated in nuclear emergency needs, in addition to general medical treatment, to evaluate doses due to intakes of radioactive materials, to conduct effective treatment with stable isotopes and chelating agents and to keep public away from radioactive materials in and excreted from patients. The idea of medical treatment for internal contamination is demonstrated in the general principles on medical management of victims in nuclear emergency issued by the Cabinet Office in Japan. However, if impressive number patients with internal contamination are generated, the current medical management scheme in nuclear emergency is not able to admit them. The utilization of radionuclide therapy facilities where patients with thyroid diseases are treated with radioisotope and assembly-temporary housing type treatment facilities dedicated for internal contaminated patients may be expected to complement the medical management scheme in nuclear emergency. The effect or more medical management system for patients internally contaminated may become one of the safety nets in the contemporary society that inclines to use nuclear energy on account of accessibility.

[Medical management of patients internally contaminated with radionuclides in radionuclide therapy facility and assembly-temporary type therapeutic facility in nuclear emergency].

The utilization of radionuclide therapy facility and temporary therapeutic facility has been proposed for securing the effectiveness of the higher medical management of patients internally contaminated in nuclear emergency. However it is not then practical to conduct all of the medical management. The purpose of the medical management of contaminated patients in the facilities is to continue the medical treatment of the patients who already undergo medication in order to decrease the amount of radionuclides inside of the bodies and reduce possible cancer risks and, from the view point of radiation protection, to prevent the proliferation of radionuclides from the patients and the expansion of secondary radiation exposure from them to the general public. It is here described a basic idea for medical management for contaminated patients in the radionuclide therapy facility and temporary therapeutic facility to complement the current medical management scheme in nuclear emergency.

A review on the clinical uses of SPECT/CT.

In the era when positron emission tomography (PET) seems to constitute the most advanced application of nuclear medicine imaging, still the conventional procedure of single photon emission computed tomography (SPECT) is far from being obsolete, especially if combined with computed tomography (CT). In fact, this dual modality imaging technique (SPECT/CT) lends itself to a wide variety of useful diagnostic applications whose clinical impact is in most instances already well established, while the evidence is growing for newer applications. The increasing availability of new hybrid SPECT/CT devices with advanced technology offers the opportunity to shorten acquisition time and to provide accurate attenuation correction and fusion imaging. In this review we analyse and discuss the capabilities of SPECT/CT for improving sensitivity and specificity in the imaging of both oncological and non-oncological diseases. The main advantages of SPECT/CT are represented by better attenuation correction, increased specificity, and accurate depiction of the localization of disease and of possible involvement of adjacent tissues. Endocrine and neuroendocrine tumours are accurately localized and characterized by SPECT/CT, as also are solitary pulmonary nodules and lung cancers, brain tumours, lymphoma, prostate cancer, malignant and benign bone lesions, and infection. Furthermore, hybrid SPECT/CT imaging is especially suited to support the increasing applications of minimally invasive surgery, as well as to precisely define the diagnostic and prognostic profile of cardiovascular patients. Finally, the applications of SPECT/CT to other clinical disorders or malignant tumours is currently under extensive investigation, with encouraging results in terms of diagnostic accuracy.

Clinical implication of main pulmonary artery Windkessel size after banding operation.

BACKGROUND: The Windkessel model, proposed in 1895 by O. Frank, successfully explained systemic and abnormal pulmonary hemodynamics of congenital cardiac defects. The model is essentially a functional one and describes only hemodynamics, not anatomical or geographic structures. Because pulmonary arterial banding (PAB) adds a substantial resistance proximal to arterioles, it provides an ideal anatomical structure of the Windkessel model, namely, an elastic reservoir of much dilated main pulmonary artery (mPA) followed by a substantial artificial resistance of banding. METHODS: The pulmonary artery (PA) Windkessel size (WS) of 10 patients, several months to years after PAB, were estimated both in peak systole (WSs) and minimum diastole (WSd), as the product of Windkessel compliance and proximal to distal pulmonary arterial pressure difference at each cardiac phase. They were compared to cineangiogram-determined corresponding volumes (Vs, Vd) of PA proximal to the band or mPA. RESULT: WSs and WSd correlated well with Vs and Vd, respectively, with the correlation coefficient of 0.91 and 0.62, indicating that the Windkessel in these patients corresponds to mPA. Among five patients whose resistance at the band comprised more than half of the whole PA resistance, the coefficients proved even better. CONCLUSION: Much bigger secondarily developed Windkessel, as placed proximal to the band on top of a substantial resistance at PAB, contributed much to alleviate the stress downstream at the periphery caused by greatly increased systolic stroke volume into mPA in these cardiac defects.

Is the lung scan alive and well? Facts and controversies in defining the role of lung scintigraphy for the diagnosis of pulmonary embolism in the era of MDCT.

PURPOSE: The last decade has seen a changing pattern of utilization of multidetector CT (MDCT) versus lung perfusion scintigraphy in the investigation of pulmonary venous thromboembolism (VTE). In response to this the International Atomic Energy Agency (IAEA) determined that the subject required an overview. METHOD: The IAEA has invited a group of five specialists in the relevant fields to review the current status and optimum role of scintigraphy, to explore some of the facts and controversies surrounding the use of both modalities and to make recommendations about the continued role of nuclear medicine for the investigation of pulmonary embolism. This paper identifies the relative merits of each technique, highlights benefits, focuses on complementary roles and seeks a nonadversarial symbiosis. CONCLUSION: The consultants reached a consensus that the continued use of scintigraphy for diagnosis of thromboembolic disease is recommended, particularly in scenarios where scintigraphy confers specific benefits and is complementary to MDCT.

Use of PET and PET/CT for radiation therapy planning: IAEA expert report 2006-2007.

Positron Emission Tomography (PET) is a significant advance in cancer imaging with great potential for optimizing radiation therapy (RT) treatment planning and thereby improving outcomes for patients. The use of PET and PET/CT in RT planning was reviewed by an international panel. The International Atomic Energy Agency (IAEA) organized two synchronized and overlapping consultants' meetings with experts from different regions of the world in Vienna in July 2006. Nine experts and three IAEA staff evaluated the available data on the use of PET in RT planning, and considered practical methods for integrating it into routine practice. For RT planning, (18)F fluorodeoxyglucose (FDG) was the most valuable pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT target volume determination in non-small cell lung cancer (NSCLC). There was also evidence for utility of PET in head and neck cancers, lymphoma and in esophageal cancers, with promising preliminary data in many other cancers. The best available approach employs integrated PET/CT images, acquired on a dual scanner in the radiotherapy treatment position after administration of tracer according to a standardized protocol, with careful optimization of images within the RT planning system and carefully considered rules for contouring tumor volumes. PET scans that are not recent or were acquired without proper patient positioning should be repeated for RT planning. PET will play an increasing valuable role in RT planning for a wide range of cancers. When requesting PET scans, physicians should be aware of their potential role in RT planning.

Effect of erythromycin on biological activities induced by clostridium perfringens alpha-toxin.

Clostridium perfringens alpha-toxin, an important agent of gas gangrene with inflammatory myopathies, possesses lethal, hemolytic, and necrotic activities. Here, we show that alpha-toxin-induced lethality in mice was inhibited by i.v. preadministration of erythromycin (ERM). Administration of ERM resulted in a drastic reduction in the release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 and systemic hemolysis induced by alpha-toxin, whereas the administration of kitasamycin did not. Furthermore, the lethality and systemic hemolysis caused by alpha-toxin were blocked by the preinjection of anti-TNF-alpha, but not the anti-IL-1beta- or anti-IL-6-antibody. In addition, TNF-alpha-deficient mice were resistant to alpha-toxin, indicating that TNF-alpha plays an important role in the lethality. ERM inhibited the toxin-induced release of TNF-alpha from neutrophils and phosphorylation of toropomyosin-related kinase receptor A (TrkA) and extracellular-regulated kinase (ERK) 1/2. Furthermore, K252a, a TrkA inhibitor, and PD98059 (2'-amino-3'-methoxyflavone), an ERK1/2 inhibitor, inhibited the toxin-induced release of TNF-alpha from neutrophils. The observation shows that the toxin-induced release of TNF-alpha is dependent on the activation of ERK/mitogen-activated protein kinase signal transduction via TrkA in neutrophils and that ERM specifically blocks the toxin-induced events through the activation of neutrophils.

Clinical significance of reduced systemic Windkessel size in severe ventricular septal defect patients.

BACKGROUND: Large-shunt ventricular septal defect (VSD) infants manifest varied serious symptoms resulting from peripheral arterial constriction to compensate for increased pulmonary blood flow (Qp) and concomitantly decreased systemic blood flow (Qs). The aim of the present paper was therefore to estimate the whole arterial space proximal to arterioles as the systemic Windkessel size (WS) in these infants and compare it with aortic volume (AV) estimated angiographically. METHOD: Subjects were divided into three groups. Group 1a consisted of the so-called balanced-pressure VSD infants; group 1b consisted of those with normal or moderately increased pulmonary artery pressure (PAP) and highly augmented Qp; and group 2 consisted of those with a history of mucocutaneous lymph node syndrome as controls for Qp and pulmonary artery pressure. WS was computed from the Windkessel model, while the AV was calculated from the angiogram. Maximal systolic (WSs), mean (WSm), and minimum diastolic (WSd) WS were defined, computed, and compared. RESULT: All WS were significantly smaller in group 1a; those of group 1b were between group 1a and group 2, with Qs-dependent reduction of WS throughout all these three groups. WSs, WSm, and WSd had negative correlations with right ventricular systolic pressure/left ventricular systolic pressure in group 1a and group 1b. WSm, or the time averaged size, proved to be larger than the corresponding AV in all patients. The ratio of WSm/AV was significantly reduced in group 1a compared to group 1b and group 2, indicating that systemic arterial Windkessel space in severe VSD infants is significantly small, especially so in terms of space distal to aortic valve and proximal to arterioles. CONCLUSION: In severe VSD infants the whole systemic arterial space proximal to arterioles (WS) is reduced in size according to severity.

Osteopetrosis-like disease in a cat with respiratory distress.

Magnetic resonance (MR) and computed tomography (CT) were performed in an 8-year-old, spayed female cat with chronic effort respiration at the inspiration phase and stertor. Increased bone opacity in the areas of the head, neck and thorax were observed on radiography. MR images showed no signal intensity on both transverse T1WI and T2WI of the nasal cavity. CT revealed increased bone density and hypertrophy of the nasal turbinate and a narrowed nasal passage. From these results, we concluded this case had osteopetrosis-like disease, and that the respiratory distress was caused by hypertrophy of the nasal turbinate.

Molecular therapy of human neuroblastoma cells using Auger electrons of 111In-labeled N-myc antisense oligonucleotides.

UNLABELLED: Auger electrons can create breaks in nucleic acids, giving them possible therapeutic utility. We investigated the therapeutic effect of Auger electrons emitted by 111In-labeled phosphorothioate antisense oligonucleotides on human neuroblastoma cells in which N-myc was overexpressed. METHODS: Human SK-N-DZ neuroblastoma cells (5 x 10(6) cells) were treated with cationic reverse-phase evaporation vesicles (REVs) encapsulating 111In-labeled antisense (40 MBq/2 nmol of oligonucleotides/mumol of total phospholipids) that had an average diameter of 250 nm. Hybridization of the radiolabeled oligonucleotides with N-myc messenger RNA (mRNA), N-myc expression, and cell proliferation were investigated. The tumorigenicity of treated cells was analyzed in nude mice. Nonradiolabeled antisense, 111In-labeled sense, or empty cationic REVs were used as controls. RESULTS: 111In-Labeled antisense, which hybridized with N-myc mRNA, was detected in cells at 12 and 24 h after the initiation of treatment. Reduced N-myc expression and inhibited cell proliferation were shown in the same cells at 48 h after the completion of treatment. N-myc expression-suppressed cells produced intraperitoneal tumors in nude mice, but the average weight of the tumors was lower than that of tumors in control mice. CONCLUSION: Auger electrons emitted from 111In in close proximity to their target N-myc mRNA may prolong the time to cell proliferation in human neuroblastoma cells due to inhibition of the translation of N-myc. Auger electron therapy therefore has potential as an internally delivered molecular radiotherapy targeting the mRNA of a tumor cell.

Colonic blood flow responses in experimental colitis: time course and underlying mechanisms.

Human inflammatory bowel diseases (IBD) are associated with significant alterations in intestinal blood flow, the direction and magnitude of which change with disease progression. The objectives of this study were to determine the time course of changes in colonic blood perfusion that occur during the development of dextran-sodium-sulfate (DSS)-induced colonic inflammation and to address the mechanisms that may underlie these changes in blood flow. Intravital microscopy was used to quantify blood flow (from measurements of vessel diameter and red blood cell velocity) in different-sized submucosal arterioles of control and inflamed colons in wild-type (WT) mice. A significant (18-30%) reduction in blood flow was noted in the smallest arterioles (<40 microm diameter) on days 4-6 of DSS colitis. The arteriolar responses to bradykinin in control and DSS-treated WT mice revealed an impaired endothelium-dependent, but not endothelium-independent, vasodilation in the inflamed colon. However, this impaired vasodilatory response to bradykinin after DSS treatment was not evident in mutant mice that overexpress Cu,Zn-superoxide dismutase. Rescue of the bradykinin-induced vasodilation during DSS colitis was also observed in mice that are genetically deficient in the NAD(P)H oxidase subunit gp91(phox). These findings indicate that the decline in blood flow during experimental colitis may result from a diminished capacity of colonic arterioles to respond to endogenous endothelium-dependent vasodilators like bradykinin and that NAD(P)H oxidase-derived superoxide plays a major role in the induction of the inflammation-induced endothelium-dependent arteriolar dysfunction.