A Case of Acute In-Stent Mobile Plaque after Carotid Artery Stenting Aspirated with a Distal Access Catheter.

Objective: Carotid artery stenting (CAS) is common procedure for carotid stenosis, but sometimes acute in-stent thrombosis or plaque protrusion after CAS leads to postoperative stroke. There are few reports of aspiration of in-stent plaque protrusion. This paper reports a case of acute in-stent mobile plaque aspirated with a distal access catheter. Case Presentation: A 74-year-old male underwent CAS for symptomatic internal carotid artery stenosis and postoperative course was thought to be good, but in-stent mobile plaque was detected by carotid duplex at postoperative day 6. As mobile plaque is a high risk for stroke, we performed plaque aspiration with a distal access catheter, without neurological deficit or a new cerebral lesion in magnetic resonance imaging. We present a case report, including a literature review, of acute thrombosis or in-stent plaque protrusion. Conclusion: Aspiration removal may be effective for in-stent mobile plaque, which is expected to be fragile, avoiding the disadvantages of increasing stents.

A Case of Primary Leptomeningeal Lymphoma Presenting with Hydrocephalus Characterized by Disproportionately Large Fourth Ventricle.

Primary leptomeningeal malignant lymphoma (PLML) is a rare variant of primary central nerve system malignant lymphoma (PCNSL) which is restricted to leptomeninges. The lesions of PLML can often be detected as abnormal enhancement on the surface of central nervous system or the ventricular wall on magnetic resonance imaging (MRIs). Cerebrospinal fluid (CSF) evaluation together with such MRI findings provides the definitive diagnosis of PLML. Here, we present a 45-year-old female case of PLML in which hydrocephalus with disproportionately large fourth ventricle was observed at presentation with gait instability. Head MRI revealed no abnormal enhancement and CSF cytology was negative, leaving the cause of hydrocephalus undetermined. Endoscopic third ventriculostomy (ETV) was effectively performed for hydrocephalus and her symptoms disappeared. Nearly 2 years later, she was brought to emergent room due to unconsciousness with the recurrence of hydrocephalus. MRI showed expanded fourth ventricle and abnormal enhancement on the ventricular wall. The endoscopic surgery for improving CSF flow was successful and inflammatory change was endoscopically observed on the ventricular wall involving aqueduct. Pathological diagnosis of the specimen from the ventricular wall proved B-cell lymphoma. Because neither brain parenchymal masses nor systemic tumors were identified, she was diagnosed with PLML and treated by high-dose methotrexate. She was in a stable state 2 years after the diagnosis of PLML. We report and discuss the characteristics of this case.

Atmospheric sea-salt and halogen cycles in the Antarctic.

Atmospheric sea-salt and halogen cycles play important roles in atmospheric science and chemistry including cloud processes and oxidation capacity in the Antarctic troposphere. This paper presents a review and summarizes current knowledge related to sea-salt and halogen chemistry in the Antarctic. First, presented are the seasonal variations and size distribution of sea-salt aerosols (SSAs). Second, SSA origins and sea-salt fractionation on sea-ice and ice sheets on the Antarctic continent are presented and discussed. Third, we discuss SSA release from the cryosphere. Fourth, we present SSA dispersion in the Antarctic troposphere and transport into inland areas. Fifth, heterogeneous reactions on SSAs as a source of reactive halogen species and their relationship with atmospheric chemistry are shown and discussed. Finally, we attempt to propose an outlook for obtaining better knowledge related to sea-salt and halogen chemistry and their effects on the Antarctic and the Arctic.

Malignant Glioma in the Cerebellum Presenting as Multiple Small Lesions.

Malignant glioma, the most common malignant primary brain tumor in adults, usually occurs in supratentorial space as a single mass lesion, and cerebellar location and multiple appearance are uncommon. We report a case of a 69-year-old female with three lesions simultaneously found in the cerebellum on magnetic resonance images (MRIs) after suffering from gait disturbance. Two lesions were around 15 mm in size and the other one was observed as a spotty enhancement. Although MRI findings suggested brain metastases, whole body examinations denied any primary malignancies. Biopsy for one lesion in the cerebellum was performed, which resulted in pathological diagnosis of malignant astrocytoma. The lesions were considered multicentric glioma based on MRI definition. The treatment with temozolomide and whole brain radiation was completed. Although the patient was discharged in an independent state with the shrinkage of the tumors, she unexpectedly died following sudden loss of consciousness from an unknown cause one month after discharge. The coincidence of cerebellar location and multicentricity characterized by smallness is quite rare in glioma patients, and such MRI findings might be misleading for the diagnosis. We describe the details of the case and discuss the pathogenesis of this unique presentation of malignant glioma with the literatures.

Long-Lasting Symptomatic Cerebral Hyperperfusion Syndrome following Superficial Temporal Artery-Middle Cerebral Artery Bypass in a Patient with Stenosis of Middle Cerebral Artery.

Cerebral hyperperfusion syndrome (CHPS) is a complication that can occur after cerebral revascularization surgeries such as superficial temporal artery- (STA-) middle cerebral artery (MCA) anastomosis, and it can lead to neurological deteriorations. CHPS is usually temporary and disappears within two weeks. The authors present a case in which speech disturbance due to CHPS lasted unexpectedly long and three months was taken for full recovery. A 40-year-old woman, with a history of medication of quetiapine, dopamine 2 receptor antagonist as an antipsychotics for depression, underwent STA-MCA anastomosis for symptomatic left MCA stenosis. On the second day after surgery, the patient exhibited mild speech disturbance which deteriorated into complete motor aphasia and persisted for one month. SPECT showed the increase of cerebral blood flow (CBF) in left cerebrum, verifying the diagnosis of CHPS. Although CBF increase disappeared one month after surgery, speech disturbance continued for additionally two months with a slow improvement. This case represents a rare clinical course of CHPS. The presumable mechanisms of the prolongation of CHPS are discussed, and the medication of quetiapine might be one possible cause by its effect on cerebral vessels as dopamine 2 receptor antagonist, posing the caution against antipsychotics in cerebrovascular surgeries.

Important contributions of sea-salt aerosols to atmospheric bromine cycle in the Antarctic coasts.

Polar sunrise activates reactive bromine (BrOx) cycle on the Antarctic coasts. BrOx chemistry relates to depletion of O3 and Hg in polar regions. Earlier studies have indicated "blowing snow" as a source of atmospheric BrOx. However, surface O3 depletion and BrO enhancement occurs rarely under blowing snow conditions at Syowa Station, Antarctica. Therefore, trigger processes for BrOx activation other than the heterogeneous reactions on blowing snow particles must be considered. Results of this study show that enhancement of sea-salt aerosols (SSA) and heterogeneous reactions on SSA are the main key processes for atmospheric BrOx cycle activation. Blowing snow had Br- enrichment, in contrast to strong Br- depletion in SSA. In-situ aerosol measurements and satellite BrO measurements demonstrated clearly that a BrO plume appeared simultaneously in SSA enhancement near the surface. Results show that surface O3 depletion at Syowa Station occurred in aerosol enhancement because of SSA dispersion during the polar sunrise. Amounts of depleted Br- from SSA were matched well to the tropospheric vertical column density of BrO and BrOx concentrations found in earlier work. Our results indicate that SSA enhancement by strong winds engenders activation of atmospheric BrOx cycles via heterogeneous reactions on SSA.

Endovascular Intervention in Basilar Artery Entrapment within the Longitudinal Clivus Fracture: A Case Report.

Although vascular complications after head trauma is well recognized, basilar artery entrapment within the longitudinal clivus fracture is rare. A 69-year-old man presented with progressive disturbance of consciousness and right hemiplegia after trauma. Computed tomography scan showed a right-sided acute subdural hematoma and multiple skull fractures, including a longitudinal clivus fracture. Magnetic resonance imaging revealed basilar artery occlusion and a small infarction at the ventral part of the pons. On the assumption of acute arterial occlusion caused by thrombus, endovascular thrombectomy was attempted, but resulted in perforation. After the procedure, basilar artery entrapment within the longitudinal clivus fracture turned out to be the cause of the occlusion. The present case suggests that basilar artery entrapment within the longitudinal clivus fracture is a possible cause of neurological deficits after trauma. In this subset, endovascular intervention without a correct diagnosis of this phenomenon is high risk.

Independent Anomalous Origin of the Right Vertebral Artery from the Right Common Carotid Artery.

An anomalous origin of the right vertebral artery is rare. The left vertebral artery from the aortic arch is where most of the anomalies occur. The next is an origin of the right vertebral artery from the right common carotid artery in association with the aberrant right subclavian artery. However, independent anomalous origin of the right vertebral artery from the right common carotid artery has not been well known in the previous literature. We present this anomaly, and able to understand the mechanism of the occurrence by embryological knowledge. Failure of involution of the fourth segmental artery and the ductus caroticus remaining are associated with this anomaly. To understand this, an aberrant may be helpful to avoid injury of the vertebral artery when performing the surgical procedures and catheterization.

[A Case of Dural Arteriovenous Fistula that Developed 21 Months after Cerebral Venous Sinus Thrombosis].

A 56-year-old man experienced a sudden onset of left hemiparesis. The computed tomography(CT)scan revealed a lobar hemorrhage in the right fronto-parietal lobe. After his admission, deep vein thrombosis was detected in his left lower limb, and angiograms taken on the 36th day of hospitalization revealed cerebral venous sinus thrombosis. Anticoagulant treatment was induced. After 21 months, he experienced a sudden onset of left hemiparesis again. The CT scan revealed a new lobar hemorrhage in the right frontal lobe, and angiograms revealed that two dural arteriovenous fistulas(dAVF)developed in the superior sagittal sinus(SSS)and the left transverse-sigmoid sinus. The one in the SSS had retrograde drainage from the bilateral middle meningeal artery, and we performed transarterial embolization with 50% n-butyl-cyanoacrylate. Postoperative course was uneventful and no further stroke occurred. Intracranial dAVF is known to be an acquired disease caused by venous hypertension, but we rarely find new development of dAVFs after venous diseases. This patient's case will help to elucidate the pathophysiology of dAVF.

Evaluation of the characteristics of various types of finishing coils for the embolization of intracranial aneurysms in an experimental model with radiolucent coils.

In endovascular coil embolization of intracranial aneurysms, very soft coils, often called "finishing coils," are usually selected in the final stage of coil embolization. The authors developed a radiolucent coil made of thin nylon thread to evaluate the performance of coils under a situation simulating the course of embolization. The characteristics of various types of finishing coils were investigated using radiolucent coils. Experimental embolization was performed with a silicone aneurysm filled with radiolucent coils simulating the final stage of embolization. Three indices, i.e. area, perimeter, and circularity of the inserted coils, were investigated on the X-ray images after coil insertion. The coils used were as follows: Target Ultra Helical, MicroPlex Hypersoft, Axium Helix, ED Coil Extrasoft, and DeltaPlush. In the analysis of area and perimeter, there were significant differences in multiple comparisons. There was no significant difference in circularity, although it was generally ranked in order by coil brand. Target Ultra and MicroPlex Hypersoft had higher scores for area and perimeter and lower scores for circularity, in contrast to DeltaPlush, which had lower scores for area and perimeter and a higher score for circularity. Based on these results, the finishing coils were divided into three groups: Target Ultra Helical and MicroPlex Hypersoft; Axium Helix and ED Coil Extrasoft; DeltaPlush. They are better for use in early, midst, and end of finishing, respectively. The characteristics of various finishing coils were evaluated, and the results obtained reflected actual clinical experience and provide useful information to appropriately select finishing coils.

Relationship between low response to clopidogrel and periprocedural ischemic events with coil embolization for intracranial aneurysms.

OBJECTIVES: Low response to antiplatelet drugs is one of the risk factors for ischemic events. We examined the influence of low response to clopidogrel on symptomatic ischemic events and new ischemic MRI lesions with endovascular intracranial aneurysmal coil embolization. MATERIALS AND METHODS: Between August 2010 and July 2013, 189 procedures in 181 consecutive patients who underwent endovascular coiling and received clopidogrel before treatment were investigated retrospectively. Platelet aggregation activity was examined by VerifyNow analysis. Low response to clopidogrel was defined as P2Y12 reaction units ≥230 in this study. Symptomatic ischemic complications within 30 days and postoperative new ischemic lesions on MRI-diffusion weighted imaging were evaluated. RESULTS: 66 of 189 (34.9%) cases were low responders to clopidogrel. Ischemic complications occurred in 2 of 66 (3.0%) low responders compared with 6 of 123 (4.9%) responders (p=0.72). A new high intensity spot larger than 5 mm was significantly more frequent in low responders (26 of 66; 39.4%) than in responders (26 of 121; 21.2%; p=0.01). On multivariate analysis, independent risk factors for larger new ischemic lesions were low response to clopidogrel, smokers, posterior location, and aneurysms with a larger neck. CONCLUSIONS: Low response to clopidogrel had little effect on clinical outcome although it increased asymptomatic large ischemic lesions in this cohort.

Results and current trends of multimodality treatment for infectious intracranial aneurysms.

The authors retrospectively reviewed their cases of infectious intracranial aneurysms and discuss results and trends of current treatment modalities including medical, neurosurgical, and endovascular. Twenty patients (10 males and 10 females; mean age 46 years) with 23 infectious aneurysms were treated by various treatment modalities during a 15-year period. Fifteen cases (75.0%) were caused by infective endocarditis. Eleven aneurysms (47.8%) were ruptured. Two aneurysms (8.7%) presented a mass effect and 7 (30.4%) were unruptured and asymptomatic. The average aneurysm size was 6.5 ± 4.8 mm (range 1-22 mm). The aneurysms were located in proximal cerebral circulation in 7 (30.4%) and distal in 16 (69.6%). Six (26.1%) aneurysms were treated surgically (5: trapping, 1: neck clipping), 10 (43.5%) endovascularly (7: trapping, 2: proximal occlusion, 1: saccular coiling), and the remaining 7 (30.4%) medically. Endovascular treatment was gradually increased with time. Medical and surgical treatments were continuously performed during the study period. Surgery was preferred for the patient with intraparenchymal hematoma or treated by bypass surgery. Three periprocedural minor complications occurred in endovascular treatment. There was one postoperative infarction with permanent deficit developed from surgical treatment. During the follow-up period (mean 28.8 months), none of the aneurysms presented a recurrence or rebleeding. Thirteen patients (65.0%) had favorable clinical outcomes (modified Rankin Scale: 0-2), although four (20.0%) had poor outcomes (modified Rankin Score: 5-6). A multimodal approach for the management of infectious aneurysms achieved satisfactory results. Endovascular intervention is a feasible and efficacious treatment option and surgical intervention is still an indispensable procedure.

The 'one and a half round microcatheterization technique' for stent-assisted coil embolization of intracranial aneurysm: technical case series.

BACKGROUND: Stent-assisted coil embolization is useful for wide-necked, large and giant aneurysms, and is effective for avoiding coil herniation. However, the mobility of the microcatheter is often restricted, resulting in deviated or unbalanced coiling. In order to prevent this insufficient coiling, the authors devised a method for microcatheterization, the 'one and a half round microcatheterization technique'. This technique is based on the formation of a one and a half round loop by the microcatheter along the aneurysmal wall. Furthermore, this technique can be supplemented with the double-catheter technique. METHODS: From July 2010 to July 2012, the authors used this technique for 20 aneurysms in 20 patients (6 men and 14 women; mean age 61.7 years). The one and a half round microcatheterization technique was used alone in 12 cases and was supplemented with the double-catheter technique in eight. The clinical and angiographic results were retrospectively evaluated. RESULTS: The average aneurysm size was 16.7 mm; 12 aneurysms (60%) were located at the internal carotid artery, 5 (25%) at the basilar artery and 3 (15%) at the vertebral artery. Immediate angiographic results showed complete obliteration in 6 aneurysms (30%) and residual neck in 10 (50%), leaving 4 residual aneurysms (20%). This technique was useful and acceptably safe for packing the aneurysmal sac entirely. During an average follow-up of 20.5 months, 13 of the 18 aneurysms (72%) were stable or had improved, although 3 (16%) required retreatment. CONCLUSIONS: The one and a half round microcatheterization technique provides dense coil packing for stent-assisted embolization of large or giant aneurysms.

Spinal cord infarction is an unusual complication of intracranial neuroendovascular intervention.

Spinal cord infarction is an unusual complication of intracranial neuroendovascular intervention. The authors report on two cases involving spinal cord infarction after endovascular coil embolization for large basilar-tip aneurysms. Each aneurysm was sufficiently embolized by the stent/balloon combination-assisted technique or double catheter technique. However, postoperatively, patients presented neurological symptoms without cranial nerve manifestation. MRI revealed multiple infarctions at the cervical spinal cord. In both cases, larger-sized guiding catheters were used for an adjunctive technique. Therefore, guiding catheters had been wedged in the vertebral artery (VA). The wedge of the VA and flow restriction may have caused thromboemboli and/or hemodynamic insufficiency of the spinal branches from the VA (radiculomedullary artery), resulting in spinal cord infarction. Spinal cord infarction should be taken into consideration as a complication of endovascular intervention for lesions of the posterior circulation.

Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.

The paraneoplastic retinopathies (PRs) are a group of eye diseases characterized by a sudden and progressive dysfunction of the retina caused by an antibody against a protein in a neoplasm. Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1) protein was one of the antigens for the autoantibody against the ON bipolar cells in PR patients. However, it has not been determined how the autoantibody causes the dysfunction of the ON bipolar cells. We hypothesized that the antibody against TRPM1 in the serum of patients with PR causes a degeneration of retinal ON bipolar cells. To test this hypothesis, we injected the serum from the PR patient, previously shown to contain anti-TRPM1 antibodies by westerblot, intravitreally into mice and examined the effects on the retina. We found that the electroretinograms (ERGs) of the mice were altered acutely after the injection, and the shape of the ERGs resembled that of the patient with PR. Immunohistochemical analysis of the eyes injected with the serum showed immunoreactivity against bipolar cells only in wild-type animals and not in TRPM1 knockout mice,consistent with the serum containing anti-TRPM1 antibodies. Histology also showed that some of the bipolar cells were apoptotic by 5 hours after the injection in wild type mice, but no bipolar cell death was found in TRPM1 knockout mice, . At 3 months, the inner nuclear layer was thinner and the amplitudes of the ERGs were still reduced. These results indicate that the serum of a patient with PR contained an antibody against TRPM1 caused an acute death of retinal ON bipolar cells of mice.

Stent/balloon combination assist technique for wide-necked basilar terminal aneurysms.

We describe an enhanced endovascular procedure for the coiling of broad-necked basilar terminal aneurysms with a combined balloon/stent assist technique. A balloon-assisted catheter is inserted in the origin of one posterior cerebral artery (PCA) and an assisted stent is deployed from the opposite PCA to the basilar artery. A microcatheter for coiling is inserted through the stent strut (trans-cell approach), and the aneurysm is coiled under stent support and assisted balloon inflation to keep the patency of both PCAs. This technique is more beneficial for reducing the risk of stent deformity than Y-stenting, and it provides a simpler procedure than other advanced stent techniques. Additionally, it enables an easy approach when retreatment is necessary for aneurysm recurrence. This technique may be one of the useful procedures for embolizing broad-necked basilar terminal aneurysms safely and effectively.

[Systematic review of complications for proper informed consent (9) periprocedural complications of carotid artery stenting: a review article].

BACKGROUND: Carotid artery stenting(CAS)is a common procedure for the treatment of high surgical risk patients with carotid artery stenosis. Recent clinical study failed to show the non-inferiority of CAS to carotid endarterectomy(CEA)because of higher complication rates of CAS. However the result of a multicenter case study in Japan with tailored application of adequate devices including stents and protection devices revealed the safety of CAS in Japan. In this article the overall review in the previous reports of CAS are reviewed focusing on the complications and clinical outcome. METHOD: Five randomized controlled trials concerning CAS versus CEA and 14 case series of CAS were reviewed, and the rates of periprocedural complications of CAS including death, stroke, myocardial infarction, hypotension and bradycardia, cranial nerve palsy, major vascular injury, cholesterol crystal embolization and hyperperfusion syndrome were summarized. RESULT: Mortality within 30 days of procedures was 0.9%. The rate of any stroke was 6.0% from the five RCT results, but a recent 14-case series reported any stroke rate at 3-4% and severe stroke rate at 1-2% respectively. The rates of acute myocardial infarction, hypotension, and bradycardia were 1%, 4%, and 4-12% respectively. The rate of bleeding complication of the access root was about 2% and non-bleeding was 1-2%. Cholesterol crystal embolization occurred in 0.2%. Incidence of hyperperfusion syndrome occurred in 1.5%, and intracranial hemorrhage in 0.8%. CONCLUSION: Historically, the rapid improvement of devices and technical skills have contributed to the better clinical results. Also the lessons from complication cases have led to more appropriate indication and perfect protection to avoid adverse events. Therefore the rate of complication is always improving and those written in this article may not reflect the present real number. This article should be quoted with the previous reference as well as the newest data according to the operator's own experiences on taking informed consent.

Endovascular intervention for acute cervical carotid artery occlusion.

BACKGROUND: Acute cervical carotid artery occlusion presents with a severe neurological deficit and is associated with unfavorable outcomes. In this study, the authors report their experience with patients having had acute ischemic stroke due to cervical carotid occlusion, who underwent endovascular intervention. METHOD: Sixteen acute cervical carotid occlusion patients (15 males and 1 female; mean age 67.7 years) were treated by endovascularly between January 2009 and November 2012. Clinical, procedural, and angiographic data were retrospectively evaluated. Successful intracranial recanalization was based on thrombolysis in cerebral infarction score of 2B-3. A favorable outcome was defined as a modified Rankin Scale score of 0-2 at 90 days. FINDINGS: The average score of National Institutes of Health Stroke Scale before treatment was 15.9. Ten of 16 patients (63 %) were associated with intracranial tandem occlusion. Ten (63 %) cases were caused by atherosclerotic, 4 (25 %) by atrial fibrillation (AF), and 2 (13 %) by dissection. Thirteen of 16 (81 %) achieved successful cervical recanalization and 7 of 16 (44 %) patients obtained sufficient cervical and intracranial perfusion. As a result, 5 of 16 (31 %) patients demonstrated favorable outcomes. Five of seven patients (71 %) with successful cervical and intracranial recanalization presented favorable outcomes. In contrast, none of the patients without cervical or intracranial recanalization presented favorable outcomes. Three of 6 (50 %) patients initially without intracranial occlusion showed favorable outcomes, but only 2 of 10 (20 %) patients associated with intracranial occlusion had favorable outcomes. On the aspect of etiology, in atherosclerotic cases, 4 of 10 (40 %) showed favorable outcomes. However, all four AF cases deteriorated into poor outcomes. CONCLUSIONS: This study demonstrated the feasibility of endovascular intervention for acute cervical carotid artery occlusion. Although treatment for tandem occlusion and AF cases is an issue that should be resolved, intervention must be encouraged. Successful cervical and intracranial revascularization will be essential for favorable outcomes.

[Resistance to antiplatelet agents assessed by a point-of-care platelet function test and thromboembolic adverse events in neurointervention].

OBJECTIVE: To clarify the frequency of Japanese patients who are resistant to antiplatelet agents, and then clarify correlations between resistance and thromboembolic adverse events in neurointervention. METHODS: Blood samples were collected from 163 patients who were taking antiplatelet agents and received neurointervention, with 128 samples collected just before neurointervention. Residual platelet function was measured using a point-of-care platelet function test, VerifyNow®, and then the frequency of patients resistant to drugs (low-responders), correlations between resistance and thromboembolic events, and effects of adding cilostazol to clopidogrel administration were analyzed. Cut-off values were defined as 550 Aspirin Reaction Units (ARU), 230 P2Y12 Reaction Units (PRU), and 50%inhibition of P2Y12, respectively. RESULTS: Three of 105 patients (2.9%) taking aspirin at 100 mg/day were low-responders, whereas 48 (41.0%, as measured by PRU) or 80 (68.4%, as measured by %inhibition) of 117 patients taking clopidogrel at 75 mg/day were low-responders. Among the 19 patients taking cilostazol 200 mg/day in addition to clopidogrel 75 mg/day, platelet functions were significantly more strongly inhibited compared to patients taking clopidogrel alone (p=0.02 by PRU, p=0.005 by %inhibition). Thromboembolic adverse events occurred in 7 patients. Among these 7 patients, 6 who were taking aspirin were all responders to aspirin, while 4 of the 6 patients taking clopidogrel were low-responders to clopidogrel. In 69 patients who received aneurysmal transarterial embolization, 2 thromboembolic complications occurred among low-responders (p=0.09). CONCLUSION: Aspirin resistance is rare in Japanese individuals. With aneurysmal transarterial embolization, thromboembolic events tended to occur among clopidogrel low-responders. Addition of cilostazol may offer one method of overcoming clopidogrel resistance.

Differential effects between marimastat, a TNF-alpha converting enzyme inhibitor, and anti-TNF-alpha antibody on murine models for sepsis and arthritis.

We investigated the effects of marimastat, an inhibitor of TNF-alpha converting enzyme and matrix metalloproteinases, and anti-TNF-alpha antibodies on a murine model for sepsis, and on arthritis in human TNF-alpha transgenic mice. Marimastat (25-200 mg/kg) inhibited lipopolysaccharide (LPS)-induced soluble TNF-alpha production in mice in a dose-dependent manner. At an oral dose of 200 mg/kg, marimastat almost completely inhibited LPS-induced soluble TNF-alpha production, but only slightly delayed LPS lethality. On the other hand, anti-TNF-alpha antibodies completely abolished LPS-induced morbidity. In addition, anti-TNF-alpha antibodies, but not marimastat (200 mg/kg/day), inhibited the development of arthritis in human TNF-alpha transgenic mice. These results suggest that cell surface TNF-alpha may be important in the pathogenesis of murine models for sepsis and arthritis.