High resolution vessel-wall imaging for peripheral aneurysms in adult moyamoya disease: a report of three cases.

Peripheral aneurysms in patients with moyamoya disease have been reported to be hazardous owing to their rupture-prone nature. High-resolution vessel wall imaging has recently emerged as a useful modality for evaluating intracranial aneurysmal status. We present the vessel-wall imaging of peripheral aneurysms in three patients with moyamoya disease. Strong circumferential wall enhancement was observed in ruptured peripheral aneurysms. Peripheral aneurysms were located at the connection point between the single main stem and the multiple medullary tributaries of the choroidal anastomosis. Using high-resolution vessel-wall imaging, we identified the characteristics of peripheral aneurysms in patients with moyamoya disease.

Gamma knife radiosurgery for trigeminal schwannoma: a 20-year experience with long-term treatment outcome.

PURPOSE: This study evaluated the long-term tumor control rate (TCR) and symptomatic outcomes of patients treated with gamma knife radiosurgery (GKRS) for trigeminal schwannomas (TSs). METHODS: Thirty-two patients with TS who underwent GKRS between January 1994 and January 2013 with at least 2 years of follow-up were enrolled in the study. Clinical charts and surgical records were retrospectively reviewed to evaluate factors affecting TCR and symptomatic outcomes. The median patient age was 57.5 years (max = 81, interquartile range [IQR] = 51-67), and the median tumor volume was 3.55 cm3 (max = 25.2 cm3, IQR = 2.0-6.2 cm3). The median marginal and maximum doses were 13.0 Gy (max = 18.0 Gy, IQR = 12.5-15 Gy) and 23.8 Gy (max = 35 Gy, IQR = 21.7-25.0 Gy), respectively. RESULTS: At a median follow-up of 90.5 months (max = 281 months, IQR = 49-139.75 months), the actuarial 3-, 5-, and 10-year TCR were 93.8, 86.2, and 80.8%, respectively. Our data and multivariate analysis indicated that the target volume was the only significant factor determining TCR and that larger tumors (> 5 cm3) were more likely to progress (p = 0.011). Cystic tumors had a higher incidence of transient enlargement and temporary symptom change compared to those in solid tumors. An unfavorable outcome of symptoms was observed in five patients (15.6%). Complications were observed in two patients (6.25%), including hydrocephalus and radio-induced trigeminal neuropathy, respectively. CONCLUSIONS: GKRS can be a safe and effective treatment modality for TS with long-term follow-up, especially for small tumors. An extended period of follow-up observation is required to conclude the clinical response to GKRS.

Clinical outcomes and radiosurgical considerations for pediatric arteriovenous malformation: influence of clinical features on obliteration rate.

PURPOSE: Gamma knife radiosurgery (GKRS) is an established treatment modality for brain arteriovenous malformation (AVM), but there have been few published studies examining the relationship between clinical features of AVM and successful obliteration with GKRS in pediatric patients. In the current study, we investigate the outcomes of GKRS for pediatric patients with brain AVM and analyze the variables that influence obliteration. METHODS: We analyzed 68 pediatric patients (≤ 18 years) with a mean follow-up period of 61.9 months (range 6-215 months). The following parameters were analyzed to determine their influence on obliteration of AVM treated by GKRS: age, sex, target volume, irradiation dose, prior treatment, location of AVM, nidus structure, velocity of AVM, location of venous drainage, number of feeding arteries, and initial presenting symptoms. Also, we estimated clinical factors which should be considered during the follow-up period. RESULTS: Of the 68 patients, complete obliteration was confirmed in 26 (38.2%) by cerebral angiography. The response rate of AVM for GKRS was 92.6%. No significant association was observed between any of the parameters investigated and the obliteration of AVM, with the exception of number of feeding arteries, which exhibited a statistically significant difference by univariate analysis (p = 0.003). However, on multivariate analysis, nidus structure (p = 0.007), velocity of the main arterial phase (p = 0.013), velocity of the feeding artery phase (p = 0.004), and the number of feeding arteries (p = 0.018) showed statistical significance. CONCLUSION: GKRS yielded good long-term clinical outcomes in most pediatric patients. Multiple arterial feeding vessels, diffuse nidus structure, and fast flow of AVM were specific factors associated with a low rate of obliteration in pediatric AVMs.

Rescue bypass for the treatment of pseudoaneurysm on the distal anterior cerebral artery: a case report of vertical side-to-side anastomosis of the distal callosomarginal artery-pericallosal artery.

Pseudoaneurysm on the distal anterior cerebral artery (ACA) is rare but potentially fatal. It usually cannot be treated with typical treatment modalities. A 47-year-old female patient was diagnosed with a ruptured aneurysm on the pericallosal artery (PerA). During surgical exploration, it was found to be a pseudoaneurysm and could not be treated with clipping. We performed surgical trapping of the involved segment of the proximal PerA followed by side-to-side anastomosis between the ipsilateral PerA and the callosomarginal artery. The patient recovered without any neurologic deficit. This new method of anastomosis could be an alternative option.

Affordable self-regulating irrigation device for microsurgery using readily available malleable wire and a Silastic tube: a technical note.

BACKGROUND: A relevant irrigating and flushing maneuver during cerebral microsurgical procedures allows for a neat and optimal operative field. However, when operating on the deep region of the brain, a delicately created slim surgical corridor could unintentionally hinder the assisting surgeon from properly performing this routine maneuver. METHOD: To address this problem, the authors devised a useful and convenient irrigation system that can be used during cerebral microsurgery. RESULTS: This system only necessitates a readily available silastic feeding tube and a malleable wire. The advantages of our devised system include the convenience of free molding, good endurance of the molded contour, and easy control over the amount of irrigation. CONCLUSIONS: In this report, the authors demonstrated technical tips for using this newly devised system.

Radiosurgical considerations for cavernous sinus hemangioma: long-term clinical outcomes.

BACKGROUND: Cavernous hemangiomas are rare vascular tumors in the cavernous sinus. Cranial neuropathies induced by cavernous sinus hemangiomas (CSH) necessitate tumor reduction, but surgery is extremely difficult due to the abundant vascularization of the lesion. We studied the effectiveness and safety of Gamma Knife radiosurgery (GKRS) for CSH. METHODS: We performed a retrospective analysis of 25 patients with CSH who were treated by GKRS between March 1992 and December 2014. Age, sex, target volume, and irradiation dose were analyzed as prognostic factors for CSH treated by GKRS. RESULTS: Eleven (84.6 %) patients had tumor shrinkage within 12 months after GKRS. Two patients experienced tumor progression, but tumor size decreased over 2 years after GKRS. No patients had permanent complications, and all patients experienced symptomatic improvement. There were no significant factors that predicted the prognosis of CSH. CONCLUSIONS: The optimal treatment for CSH has been unclear; however, in this study, GKRS was an effective and safe treatment for CSH. Thus, GKRS may be a primary treatment for CSHs in high-risk surgery patients.

Unusual acute hearing loss after gamma knife surgery for a facial schwannoma.

A 34-year-old female patient suffering from right-sided facial palsy presented to our hospital. Her hearing range was within normal limits. She had undergone GKS after receiving a diagnosis of facial nerve schwannoma (FNS). On the fourth day after GKS, the patient experienced sudden onset hearing loss on the right side without aggravation of the facial palsy. Intravenous corticosteroids were administered, and her hearing function improved gradually over the course of 15 days. This is the first case report of hyperacute hearing loss after GKS for FNS.

Gamma Knife radiosurgery for brainstem cavernous malformations: should a patient wait for the rebleed?

BACKGROUND: The effectiveness of stereotactic radiosurgery (SRS) for cavernous malformation (CM) has not been fully assessed. Consequently, observation is usually recommended when a bleeding CM is initially discovered. Recurrent bleeding occurs with CMs, and these repeat hemorrhages can result in additional morbidity. METHODS: From 1992 to 2011, 49 patients with brainstem CMs were treated with Gamma Knife radiosurgery (GKS). We classified patients into two groups: Group A (n = 31), patients who underwent GKS for a CM following a single symptomatic bleed, and group B (n = 18), patients who underwent GKS for a CM following two or more symptomatic bleeds. The mean marginal dose of radiation was 13.1 Gy (range 9.0-16.8 Gy): 12.8 Gy in group A and 13.7 Gy in group B. The mean follow-up period was 64.0 months (range 1-171 months). RESULTS: In group A, the annual hemorrhage rate (AHR) following GKS was 7.06 % within the first 2 years and 2.03 % after 2 years. In group B, four patients (22.2 %) developed new or worsening neurologic deterioration as a result of repeat hemorrhages. In group B, the AHR was 38.36 % prior to GKS, 9.84 % within the first two years, and 1.50 % after two years. There was no statistically significant difference in the AHRs at each follow-up period after GKS between the two groups. Adverse radiation effects (AREs) developed in a total of four patients (8.2 %); among them, one patient (2.0 %) developed a permanent case of diplopia. No mortality occurred in this series. CONCLUSION: In this study, GKS was demonstrated to be a safe and effective alternative treatment for brain stem CMs that resulted in a reduction in the AHR. Consequently, we suggest that even CM patients who have suffered only a single bleed should not be contraindicated for SRS.

Morphologic differences between ruptured and unruptured choroidal anastomosis in adult moyamoya disease: a high-resolution vessel wall imaging study.

OBJECTIVE: Choroidal anastomosis (ChA) has been implicated as the main indicator of an increased hemorrhagic risk in adult moyamoya disease. In this retrospective study, the authors aimed to identify the potential risk factors that can influence the rupture of ChA. METHODS: The authors evaluated the clinical and radiological data on brain hemispheres positive for ChA from September 2019 to March 2023. The rupture status of the ChA was determined using previously described methods. Two independent raters quantitatively investigated the lumen diameter (LD) and lumen area (LA) of the ChA using high-resolution vessel wall imaging (VWI). Multivariate logistic regression analysis was conducted to identify the risk factors for ruptured ChA. RESULTS: Ruptured and unruptured ChAs were identified in 16 and 60 hemispheres, respectively. Univariate analysis showed that the mean values of the LD (1.251 ± 0.241 vs 0.967 ± 0.214 mm, p < 0.001) and LA (1.607 ± 0.445 vs 0.945 ± 0.372 mm2, p < 0.001) of ChAs were significantly greater in the ruptured group than in the unruptured group. A periventricular anastomosis (PA) score of 1, indicating the angiographic presence of ChA alone, was more prevalent in the ruptured group than in the unruptured group (43.8% vs 11.7%, p = 0.003). Multivariate analysis demonstrated that a larger LA of the ChA (OR 37.01, 95% CI 5.787-236.7, p < 0.001) and PA score 1 (OR 6.661, 95% CI 1.260-35.21, p = 0.026) were independently associated with ruptured ChA hemispheres. Receiver operating characteristic curve analysis revealed that the optimal cutoff point for the LA was 1.285 mm2 (sensitivity 81.3%, specificity 86.7%). CONCLUSIONS: A larger LA (> 1.285 mm2) of the ChA and the angiographic presence of ChA alone are independent risk factors for a ruptured ChA. Revascularization surgery for the prevention of future hemorrhage may be indicated for hemispheres with a high-risk unruptured ChA. These characteristics may help to determine treatment strategies for patients with an unruptured ChA.

Surgical Thrombectomy for Extensive Cerebral Venous Sinus Thrombosis after COVID-19 Vaccination : A Novel Surgical Technique and Literature Review.

Surgical treatment of refractory and extensive cerebral venous sinus thrombosis (CVST) has limited applications. Here, we describe an open, direct sinus thrombectomy in the early phase of extensive CVST. A 49-year-old man with extensive CVST that occurred after the coronavirus disease 2019 (COVID-19) vaccination and affected the drainage of the Labbé vein presented with clinical deterioration and left temporal hemorrhagic infarction. Since the patient had extensive CVST, we determined that systemic anticoagulation and endovascular treatment were not suitable treatment options. Therefore, we decided on an emergency surgical treatment and performed direct surgical thrombectomy. We followed extended suboccipital approach and made multiple incisions on the sinuses, exposing the posterior superior sagittal sinus to the transverse sigmoid junction. Consequently, the clinical condition of the patient dramatically improved, resulting in a favorable outcome with a modified Rankin Scale score of 0. Performing emergency open surgical thrombectomy was a technically feasible treatment option that recanalized obstructed sinuses. Importantly, the patient recovered with a good clinical outcome. Early maximal surgical thrombectomy is an effective and lifesaving method to treat extensive CVST with hemorrhagic infarction.

Massive Hyperostotic Meningioma En Plaque Mimicking Fibrous Dysplasia.

The authors report an extremely rare case of a massive hyperostotic meningioma en plaque, which had characteristics of unique bony growth. A 34-year-old man presented with a palpable solid mass in the left cranial region that had gradually grown in size with a broad base on the calvarium for 8 years. Radiologically, the area involved by the mass ranged from the sphenoid bone to the frontal, parietal, temporal, and occipital bones. Three-dimensional CT revealed multiple growing spiculate features on the inner and outer cranial surface. Even though the radiologic features resembled fibrous dysplasia, it was histologically found to be a type of meningioma.

Short-term nanostructural effects of high radiofrequency treatment on the skin tissues of rabbits.

The aim of this study is to quantitatively investigate the short-term effects of RF tissue-tightening treatment in in vivo rabbit dermal collagen fibrils. These effects were measured at different energy levels and at varying pass procedures on the nanostructural response level using histology and AFM analysis. Each rabbit was divided into one of seven experimental groups, which included the following: control group, and six RF group according to RF energy (20 W and 40 W) and three RF pass procedures. The progressive changes in the diameter and D-periodicity of rabbit dermal collagen fibrils were investigated in detail over a 7-day post-treatment period. The dermal tissues treated with the RF tissue-tightening device showed more prominent inflammatory responses with inflammatory cell ingrowth compared to the control. This effect showed more prominent with the passage of day after treatment. Although an increase in the diameter and D-periodicity of dermal collagen fibrils was identified immediately after the RF treatment, a decrease in the morphology of dermal collagen fibrils continued until post-operative day 7. Furthermore, RF treatment led to the loss of distinct borders. Increases in RF energy with the same pass procedure, as well as an increase in the number of RF passes, increased the occurrence of irreversible collagen fibril injury. A multiple-pass treatment at low energy rather than a single-pass treatment at high energy showed a large amount of collagen fibrils contraction at the nanostructural level.

Diagnostic Performance of High-Resolution Vessel Wall Magnetic Resonance Imaging and Digital Subtraction Angiography in Intracranial Vertebral Artery Dissection.

PURPOSE: Intracranial vertebral artery dissection (VAD) is being increasingly recognized as a leading cause of Wallenberg syndrome and subarachnoid hemorrhage. Conventional angiography is considered the standard diagnostic modality, but the diagnosis of VAD remains challenging. This study aimed to compare the diagnostic performance of high-resolution vessel wall imaging (HR-VWI) with digital subtraction angiography (DSA) for intracranial VAD. MATERIALS AND METHODS: Twenty-four patients with 27 VADs, who underwent both HR-VWI and DSA within 2 weeks, were consecutively enrolled in the study from March 2016 to September 2020. HR-VWI and DSA were performed to diagnose VAD and to categorize its angiographic features as either definite dissection or suspicious dissection. Features of HR-VWI were used to evaluate direct arterial wall imaging. The reference standard was set from the clinicoradiologic diagnosis. Two independent raters evaluated the angiographic features, dissection signs, and interrater agreement. Each subject was also dichotomized into two groups (suspicious or definite VAD) in each modality, and diagnosis from HR-VWI and DSA was compared with the final diagnosis by consensus. RESULTS: HR-VWI had higher agreement (90.6% vs. 53.1%) with the final diagnosis and better interrater reliability (kappa value (κ) = 0.91; 95% confidence interval (CI) = 0.64-1.00) compared with DSA (κ = 0.58; 95% CI = 0.35-1.00). HR-VWI provided a more detailed identification of dissection signs (77.7% vs. 22.2%) and better reliability (κ = 0.88; 95% CI = 0.58-1.00 vs. κ = 0.75; 95% CI = 0.36-1.00), compared to DSA. HR-VWI was comparable to DSA for the depiction of angiographic features for VAD. CONCLUSIONS: HR-VWI may be useful to evaluate VAD, with better diagnostic confidence compared to DSA.

Clinical significance of "periventricular collateral enhancement sign" in symptomatic moyamoya disease: A vessel wall imaging study.

BACKGROUND: Periventricular collaterals are associated with high risk of hemorrhagic stroke in adult moyamoya disease (MMD). However, the clinical significance of the periventricular collateral enhancement sign (PCES), which indicates wall enhancement of periventricular collaterals on contrast-enhanced vessel wall imaging (VWI), has yet to be determined. METHODS: Thirty-seven patients with MMD with acute neurological symptoms were consecutively recruited. Periventricular collaterals including lenticulostriatal artery, thalamic artery, and choroidal artery collaterals were evaluated on digital subtraction angiography, and then PCES was detected on pre- and postcontrast VWI. First, the association between PCES and hemorrhagic presentation was evaluated using multivariate analyses. Second, two raters investigated the culprit vessels responsible for bleeding in hemorrhagic MMD using the Cohen kappa statistic. RESULTS: Fifteen sites of PCES on postcontrast VWI were observed in 15 patients. Multivariate analysis revealed that hemorrhagic presentation was the only independent factor for PCES (OR = 37.3, 95%CI = 3.9-113, p =.002). In patients with hemorrhagic presentation (n = 20), the identification rate of the ruptured vessel was 80% by rater 1, with excellent agreement. (inter-rater, κ = 0.86, 95%CI = 0.59-1.00; intra-rater, κ = 0.83, 95%CI = 0.50-1.00). Choroidal (50%) and thalamic artery collaterals (15%) were the most common and the second most common types of culprit vessels. Inter-rater and intra-rater reliabilities for the classification of culprit vessels were also excellent (intra-rater, κ = 0.86, 95%CI = 0.67-1.00; inter-rater, κ = 0.93, 95%CI = 0.79-1). CONCLUSION: Acute hemorrhagic stroke in MMD is independently associated with PCES on postcontrast VWI. PCES can help to detect the culprit vessels that are responsible for hemorrhage in patients with MMD.

Cerebellopontine angle tumors causing hemifacial spasm: types, incidence, and mechanism in nine reported cases and literature review.

OBJECTIVE: Although hemifacial spasm is usually caused by vascular compression around the root exit zone of the facial nerve, it is sometimes brought on by a cerebellopontine angle tumor. We reviewed and analyzed data from past experience with hemifacial spasm induced by cerebellopontine angle tumors. METHODS: Nine patients of a total 2,050, who had presented with hemifacial spasms associated with cerebellopontine angle tumors between 1986 and 2009, were reviewed. RESULTS: Two vestibular schwannomas, five meningiomas, and two epidermoid tumors were included in this study. Hemifacial spasm occurred on the same side of the lesion in eight patients whereas it occurred on the opposite side of the lesion in one patient. With respect to the pathogenesis of hemifacial spasms, offending vessels were found in six patients, tumor encasement of the facial nerve in one patient, hypervascular tumor compression of the facial nerve without offending vessels in one patient, and a huge tumor compressing the brain stem and, thus, contralateral facial nerve compression in one patient. Hemifacial spasm was resolved in seven patients, whereas in two patients with a vestibular schwannoma and an epidermoid tumor, it improved transiently and then recurred in a month. CONCLUSIONS: Each type of tumor had different characteristics with respect to the induction of hemifacial spasm; therefore, it is suggested that neurosurgeons, who are planning surgeries both for the purposes of relieving hemifacial spasm and removal of cerebellopontine angle tumor, should thoroughly prepare appropriate approaches and specific dissecting strategies according to each causative lesion.

Geometric Classification of Paraclinoid Aneurysms for Microcatheter Superselection in Coil Embolization.

AIM: To suggest a geometric classification of paraclinoid aneurysms for microcatheter superselection. MATERIAL AND METHODS: Clinical data from 76 patients (80 paraclinoid aneurysms) who underwent endovascular treatments were retrospectively reviewed. Paraclinoid aneurysms were classified according to the six directions where the aneurysm neck lies and simplified into three groups as follows: superior, medial, and lateral groups. The medial group was further divided into proximal, mid, and distal subgroups according to the location of the aneurysm neck on lateral angiography. Furthermore, we assessed the superselection success rate with the first-selected pre-shaped microcatheter per group. RESULTS: According to the aneurysm direction, the medial group showed relatively lower superselection success rates (66.1%) than the superior (81.8%) and lateral groups (85.7%). The S-shaped microcatheter was the most frequently used in the superior (69.2%) and lateral groups (62.5%). Acute-angled J- and C-shaped microcatheters (88.5%) were preferred for proximal aneurysms; and obtuse-angled 45°- and 90°-angled microcatheters (75%), for distal aneurysms. The mid-portion group showed the lowest success rate (45.8%) and more difficulties in pre-shaped microcatheter superselection. CONCLUSION: Medially directed mid-portion aneurysms were difficult to access using pre-shaped microcatheters; thus, tailored steam-shaping techniques may be considered. Superiorly and laterally directed aneurysms could be accessed using pre-S-shaped microcatheters. Acute-angled microcatheters may be considered for proximal aneurysms; and obtuse-angled microcatheters, for distal aneurysms.

Incidental Microaneurysms During Microvascular Surgery: Incidence, Treatment, and Significance.

BACKGROUND: Although new imaging tools have been developed for the detection of smaller aneurysms, angiographically negative microaneurysms are still encountered during cerebral microsurgery. Currently, only limited information regarding incidence and efficacy of treatment of these microaneurysms is available. METHODS: We investigated the incidence and treatment of incidental microaneurysms (IMAs) in the last 5 years. IMAs are unidentifiable and invisible on preoperative angiography, but are detected during microvascular surgery. The inclusion criteria were aneurysm cases treated with microsurgery via transsylvian approaches, and those undergoing preoperative digital subtraction angiography. RESULTS: This study enrolled 484 surgical cases (248 cases of subarachnoid hemorrhage and 236 cases of unruptured aneurysms) in 460 patients, and 33 tiny aneurysms were found in 31 operative cases (6.4% incidence per operation). The most typical type was located on another branching site of the middle cerebral artery found during neck clipping of the middle cerebral artery bifurcation aneurysm. A patient with multiple aneurysms presented a statistically significant risk (375/78 vs. 15/16; P < 0.001) of IMA identification. IMAs were treated by clipping and wrapping in 18 and 15 cases, respectively, without complications. CONCLUSIONS: This study revealed a 6.4% incidence of IMAs; however, this could be underestimated because of the limited range of inspection. Early detection of an IMA through careful inspection during microvascular surgery could be beneficial, especially in patients with multiple aneurysms.

Life-Threatening Hemothorax Caused by Spontaneous Extracranial Vertebral Aneurysm Rupture in Neurofibromatosis Type 1.

BACKGROUND: Although vascular abnormality is an uncommon comorbidity of neurofibromatosis type 1 (NF1), it is potentially fatal. We present spontaneous hemothorax caused by rupture of a vertebral artery (VA) aneurysm in a patient with NF1. CASE DESCRIPTION: A 36-year-old man with a history of NF1 was transferred to the emergency department with dyspnea. Chest computed tomography scan revealed hemothorax in the left lung field with mediastinal shifting and aneurysmal dilatation of the left VA at the C6 vertebra level. Immediate drainage of the hematoma by chest tube insertion was performed. Diagnostic angiogram showed a 3- to 4-cm fusiform aneurysm of the VA. After the angiogram, cardiopulmonary arrest occurred after a rebleed of the VA aneurysm. The aneurysmal segment of the VA was urgently occluded with detachable coils. Postoperatively, the patient was in intensive care for 1 month because of fulminant pneumonia. After the patient regained consciousness, he was found to have right hemiparesis from a small infarction at the pons. The patient's function improved to near normal after 1 year of recovery. CONCLUSIONS: Hemothorax caused by VA rupture in a patient with NF1 is an extremely rare condition that can be fatal. Careful examination with suspicion for early detection and treatment is required for this urgent condition. Endovascular coiling was safe even for an unstable patient with massive bleeding.

Effects of astaxanthin on the production of NO and the expression of COX-2 and iNOS in LPS-stimulated BV2 microglial cells.

Astaxanthin has shown antioxidant, antitumor, and antiinflammatory activities; however, its molecular action and mechanism in the nervous system have yet to be elucidated. We examined the in vitro effects of astaxanthin on the production of nitric oxide (NO), as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Astaxanthin inhibited the expression or formation of nitric oxide (NO), iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Astaxanthin also suppressed the protein levels of iNOS and COX-2 in LPS-stimulated BV2 microglial cells. These results suggest that astaxanthin, probably due to its antioxidant activity, inhibits the production of inflammatory mediators by blocking iNOS and COX-2 activation or by the suppression of iNOS and COX-2 degradation.