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1.
Brain Sci ; 14(6)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38928586

ABSTRACT

Porcine Liver Decomposition Product (PLDP) was obtained by treating pig liver homogenate with protease and filling it into capsules. We have already confirmed from three clinical trials that PLDP enhances visual memory and delays memory recall, and we believe that its activity is due to various phospholipids, including phosphatidylcholine (PC). In this study, we clinically evaluated PLDP for depressive symptoms caused by a decline in cognitive function. This clinical trial was conducted using the Revised Hasegawa Dementia Scale (HDS-R). The HDS-R (maximum score is 30 points) is a test similar to the Mini-Mental State Examination (MMSE), which is commonly used in Japan. Dementia is suspected if the score falls below 20 on the HDS-R. Additionally, in a previous clinical trial, there was no change in scores in the placebo group after three doses of the HDS-R. In order to clearly confirm the effectiveness of PLDP, this study was conducted under stricter conditions (HDS-R points of 15 to 23) than previous clinical trials (all participants had scores of 20 or higher). Therefore, from ethical considerations, a clinical trial was conducted using the scores before PLDP administration as a control. In this study, PLDP was administered orally at 4 capsules per day, and the HDS-R was confirmed 2 and 4 weeks after administration. A significant increase in HDS-R scores was observed at 2 and 4 weeks after PLDP administration. Additionally, regarding each item of the HDS-R, PLDP significantly increased 2 and 4 weeks after oral administration for the question items assessing delayed recall, and the question item assessing verbal fluency tasks was recognized. From the above results, we confirmed the reproducibility of the effect of PLDP in improving the delayed recall of verbal memories. Furthermore, increasing scores on verbal fluency tasks suggest that PLDP may enhance frontal lobe function and prevent or improve depressive symptoms. The effects observed in this study may differ from the mechanisms of action of existing antidepressants, and we believe that this may lead to the discovery of new antidepressants.

2.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 80(4): 365-373, 2024 Apr 20.
Article in Japanese | MEDLINE | ID: mdl-38382990

ABSTRACT

PURPOSE: To verify the effectiveness of optimizing the number of mask images in DSA for radiation dose reduction during cerebral angiography. METHODS: A total of 60 angiography sessions in 2 times for 30 patients performed by the same operator were included in this study. In order to compare the effects of optimization to change the injection delay time of DSA from 1 s to the shortest possible time, the number of mask images, the number of imaging frames, and radiation doses between sessions were compared and analyzed retrospectively. RESULTS: In one DSA run, the number of mask images was decreased from 6 (5-7) to 3 (2-3) frames (p<0.01)/57.1% (median [IQR]/reduction rate), the number of imaging frames was decreased from 34 (32-36) to 32 (29-34) frames (p<0.01)/7.9%, and the radiation dose was decreased from 33 (23-47) to 30 (21-40) mGy (p<0.01)/8.3%. In magnification angiography, the reductions rate was significantly increased. In one angiography session, the number of mask images was decreased from 45 (35-72) to 19 (16-34) frames (p<0.01)/54.6%, the number of imaging frames was decreased from 242 (199-385) to 211 (181-346) frames (p<0.01)/8.3%, the radiation dose of DSA was decreased from 295 (190-341) to 242 (167-305) mGy (p<0.01)/11.6%, and the total radiation dose was decreased from 369 (259-418) to 328 (248-394) mGy (p<0.01)/7.5%. CONCLUSION: Using the shortest possible injection delay time for the number of mask image optimization was an effective radiation dose reduction method.


Subject(s)
Cerebral Angiography , Radiation Dosage , Humans , Cerebral Angiography/methods , Male , Female , Middle Aged , Retrospective Studies , Aged , Adult
3.
J Neuroendovasc Ther ; 17(10): 209-216, 2023.
Article in English | MEDLINE | ID: mdl-37869486

ABSTRACT

Objective: In the acute stage of ruptured cerebral aneurysms, limited devices are available, making the treatment difficult. We aimed to evaluate the outcomes of the coil embolization with stenting for the ruptured cerebral aneurysms in the acute stage. Methods: We assessed 22 cases treated with stenting among 134 of 169 consecutive patients with subarachnoid hemorrhages undergoing an endovascular treatment between April 2014 and December 2021, of which 134 underwent an embolization during the acute stage. A stent was used in the patients wherein the treatment with the balloon-assisted or double catheter technique was difficult. Stenting was performed under the loading of two or more antiplatelet agents. Results: The mean age of the patients was 68.9 years, of which five were male and 14 (63.6%) had severe grade (World Federation of Neurosurgeons grade IV, V). The aneurysm site was the anterior communicating artery in four cases, internal carotid artery in nine, middle cerebral artery in two, vertebrobasilar artery in six, and posterior cerebral artery in one. The aneurysm shape was saccular in 13 cases, dissection in seven, and fusiform in two. Stents were used for wide-neck aneurysms in 12 cases, vascular preservation in seven, and rescue in three. The mean maximum diameter was 9.6 mm. The mean neck size was 6.4 mm. Complete occlusion and neck remnant were found in eight and seven cases, respectively. The perioperative complication rate was 45.5% (thromboembolism in five cases, stent occlusion in two, re-bleeding in two, and cerebral hemorrhage in one). The outcomes included modified Rankin Scale 0-2 in seven cases, 4-5 in five, and 6 in nine. Stent-related death occurred in one case. The rate of morbidity and mortality was 18.2%. Although stents were used in the acute stage of rupture, they were used for the right reasons. However, a high rate of complications occurred: two cases of re-bleeding, in which an incomplete occlusion was a factor. Conclusion: Stent placement in patients with the acute ruptured cerebral aneurysms should be carefully determined and efforts should be made to reduce the embolic and hemorrhagic complications. However, it may be an effective treatment option when other options could be extremely difficult.

4.
J Neuroendovasc Ther ; 17(9): 196-201, 2023.
Article in English | MEDLINE | ID: mdl-37731466

ABSTRACT

Objective: Recently, the occlusion rate of transarterial embolization (TAE) for intracranial non-sinus-type dural arteriovenous fistulas (NSDAVFs) has improved after ONYX was introduced. Additionally, when TAE for NSDAVF is unsuccessful, transvenous embolization (TVE) has become available as an alternative treatment. We investigated the factor for the favorable occlusion rate of endovascular treatment for NSDAVF at our institutions. Methods: Two hundred and twenty-seven patients with intracranial dural arteriovenous fistulas (DAVFs) were treated at our institutions between September 2014 and October 2022. The patients diagnosed with NSDAVF in all DAVFs who underwent endovascular treatment were included. The clinical characteristics, angiographical outcomes, and clinical outcomes of patients who underwent endovascular treatment were evaluated. Results: Thirty-eight patients had intracranial NSDAVF (tentorial: 23 cases, parasagittal-convexity: 7, anterior cranial fossa: 6, middle cranial fossa: 2). Our participants' mean age was 64.8 ± 11.3 years, and 31 (81.6%) of them were males. Patients' symptoms were as follows: asymptomatic (24), hemorrhage (10), tinnitus (3), and trigeminal neuralgia (1). TAE and TVE were performed on 35 and 3 patients, respectively. The rate of immediate angiographical occlusion was 84.2% (32/38). The follow-up angiographical occlusion rate in 6 months was 88.5% (31/35). Complications occurred in three cases. There was no morbidity or mortality after 30 days. Conclusion: TAE using the combination of the new microcatheter and microguidewire and TVE in the case of difficult or failed TAE for NSDAVF could achieve high success rates and safety.

5.
Biochem Biophys Res Commun ; 676: 91-96, 2023 Oct 08.
Article in English | MEDLINE | ID: mdl-37499369

ABSTRACT

This study builds on our previous study, which highlighted the need for further research on the potential use of lysophospholipid (LPL) supplementation to prevent chronic and age-related diseases. We aimed to evaluate the transmembrane transport of LPL across rat and monkey blood-brain barrier (BBB) models. An in vitro monkey BBB model is required to elucidate the differences between rat and primate BBB-related data and to measure the permeability of LPLs being researched in relation to the human BBB. Based on our previous experiment, porcine liver decomposition product-derived phospholipids (PEL) strongly inhibit α-synuclein (α-Syn) aggregation. We have identified several candidates potentially relevant for the inhibition of α-Syn aggregation, such as LPC18:1, LPE18:1, and LPI18:0; however, the BBB permeability of these LPLs remains unclear. In the present study, we assessed the ability of these LPLs to pass through the in vitro rat and monkey BBB models. LPC18:1 showed high BBB permeability, LPI18:0 showed medium permeability, and the BBB permeation of LPE18:1 was negligible. Our results suggest that LPC18:1 and LPI18:0 are functional food factors that can cross the BBB.

6.
Surg Neurol Int ; 14: 8, 2023.
Article in English | MEDLINE | ID: mdl-36751444

ABSTRACT

Background: There are few reports on the treatment of carotid artery stenosis after arterial vessel replacement. We report and discuss an illustrative case of carotid artery stenting (CAS) performed for stenosis after carotid artery replacement. Case Description: A woman in her 20s experienced injury to the right carotid artery during an operation for removal of a carotid body tumor 6 years before presentation. The right common carotid artery and internal carotid artery were replaced with an artificial vessel graft at that time. Intraluminal stenosis in the graft was not identified 3 years after surgery; however, 4 years after surgery, stenosis was recognized at the non-anastomotic site inside the artificial vessel graft. Subsequently, antiplatelet therapy was initiated. The stenosis was noted to progress gradually in follow-up appointments. Therefore, we decided to intervene because of the patient's young age and the risk of long-term hemodynamic stress. Angiography revealed pseudo-occlusion in the artificial vessel. Percutaneous transluminal angioplasty was performed for stenosis with distal protection; subsequently, CAS was performed. The patient was discharged without neurological deficits 4 days after the operation, and no apparent restenosis was observed as of the 1-year follow-up. Conclusion: Stenosis after cervical artery replacement can be safely treated with CAS. Inflation pressure and stent should be selected according to the pathology of the stenosis.

7.
Biomedicines ; 10(12)2022 Dec 03.
Article in English | MEDLINE | ID: mdl-36551882

ABSTRACT

Neurodegenerative diseases (NDs) commonly present misfolded and aggregated proteins. Considerable research has been performed to unearth the molecular processes underpinning this pathological aggregation and develop therapeutic strategies targeting NDs. Fibrillary deposits of α-synuclein (α-Syn), a highly conserved and thermostable protein, are a critical feature in the development of NDs such as Alzheimer's disease (AD), Lewy body disease (LBD), Parkinson's disease (PD), and multiple system atrophy (MSA). Inhibition of α-Syn aggregation can thus serve as a potential approach for therapeutic intervention. Recently, the degradation of target proteins by small molecules has emerged as a new therapeutic modality, gaining the hotspot in pharmaceutical research. Additionally, interest is growing in the use of food-derived bioactive compounds as intervention agents against NDs via functional foods and dietary supplements. According to reports, dietary bioactive phospholipids may have cognition-enhancing and neuroprotective effects, owing to their abilities to influence cognition and mental health in vivo and in vitro. However, the mechanisms by which lipids may prevent the pathological aggregation of α-Syn warrant further clarification. Here, we review evidence for the potential mechanisms underlying this effect, with a particular focus on how porcine liver decomposition product (PLDP)-derived lysophospholipids (LPLs) may inhibit α-Syn aggregation.

8.
Biomed Pharmacother ; 156: 113891, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36265307

ABSTRACT

Accumulation and aggregation of α-Synuclein (α-Syn) are the hallmarks of the incidence of α-Synucleinopathies, which comprises dementia with Lewy bodies (LBs). Aggregation inhibitors are anticipated to reduce α-Syn toxicity and serve as therapeutic agents. As a result, α-Syn is regarded as the potential and priority target for drug development. Here, we report inhibition of α-Syn aggregation by a certain lysophospholipids (LPLs) species. LPLs are small bioactive lipid molecules characterized by a single carbon chain and polar head group. The LPLs used here were extracted from porcine liver decomposition product (PLDP), which was previously reported to enhance cognitive function in healthy older adults. In this study, we found that PLDP-extracted lipids (PEL) reduced α-Syn aggregation in a cellular model. In particular, lysophosphatidylcholine (LPC) 16:0, LPC18:0, LPC18:1, and lysophosphatidylethanolamine (LPE) 16:0, which are known to be contained in PEL, were found to strongly inhibit α-Syn aggregation. Furthermore, when α-Syn was co-incubated with LPLs, the fluorescence emission of Thioflavin-T (ThT) declined remarkably, indicating a lower fibril formation. Interestingly, differences were observed in the degrees of effect on the reduction of insoluble α-Syn among each LPL. In this context, LPC18:1 and LPE18:1 appeared to interact with α-Syn below 1 nM in vitro. Taken together, these studies indicated the potential of PLDP-derived LPLs as effective therapeutic agents against α-Synucleinopathies.


Subject(s)
Synucleinopathies , alpha-Synuclein , Animals , Swine , alpha-Synuclein/metabolism , Neurons , Brain/metabolism , Lysophospholipids/pharmacology
9.
Foods ; 11(14)2022 Jul 08.
Article in English | MEDLINE | ID: mdl-35885275

ABSTRACT

Previously, we have reported that the intake of oyster extract (OE), prepared from Pacific oysters (Crassostrea gigas), can attenuate symptoms of dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. Herein, we aimed to evaluate whether OE intake ameliorates chronic experimental colitis induced by repeated DSS administration in mice. Male C57BL/6J (4-week-old) mice were fed either the standard diet AIN93G (control diet) or the control diet containing 5.0% (w/w) OE (OE diet). After 21 days of diet feeding, chronic experimental colitis was induced by three cycles of 2.0% (w/w) DSS solution administration (5 days), followed by distilled water (5 days). Mice fed OE alleviated the shortened colonic length, increased the relative weight of the spleen, colonic histopathological score (regeneration), and blood in the stool score compared with mice fed control diet. A tendency to improve the α-diversity of fecal microbiota, which was exacerbated by colitis, was observed in mice fed OE. Correlation analysis suggested that the anti-colitis effect of OE intake could be related to the valeric acid content and relative abundances of Ruminococcus and Enterococcus in the feces. In conclusion, OE could ameliorate DSS-induced chronic experimental colitis by improving the gut environment, including the microbiota community and SCFA composition.

10.
Yakugaku Zasshi ; 142(3): 289-293, 2022.
Article in Japanese | MEDLINE | ID: mdl-35228381

ABSTRACT

In recent years, lifestyle-related diseases such as hypertension and diabetes have been on the rise. These conditions can cause serious conditions such as myocardial and cerebral infarctions. Therefore, proper control of blood pressure and blood glucose levels is important issues in preventive medicine. Traditional fermented foods have been shown to have various functions, and their effects on lifestyle-related diseases have attracted particular attention. In this study, we investigated the effects of fermented soybeans and rice bran (OE-1) and supplements containing OE-1 on blood glucose levels and weight changes. We identified an inhibitory effect on elevated blood glucose levels upon administration of OE-1, and this effect was thought to be due to digestive enzyme inhibition. These effects of foods containing OE-1 are expected to have a positive effect on the prevention and improvement of lifestyle-related diseases as health foods.


Subject(s)
Blood Glucose/metabolism , Body Weight/drug effects , Diabetes Mellitus/prevention & control , Dietary Supplements , Fermentation , Glycine max/chemistry , Hypertension/prevention & control , Oryza/chemistry , Plant Extracts/pharmacology , Adult , Animals , Diabetes Mellitus/etiology , Humans , Hypertension/etiology , Life Style , Male , Mice, Inbred ICR , Middle Aged , Plant Extracts/administration & dosage
11.
Radiol Case Rep ; 17(5): 1487-1490, 2022 May.
Article in English | MEDLINE | ID: mdl-35265246

ABSTRACT

The pathogenesis of new visual symptoms after flow diverter stent placement in the ophthalmic artery for internal carotid artery aneurysms remains unclear. We report two cases of patients who developed visual field disturbance and decreased visual acuity following flow diverter placement. The "doughnut sign" was found around the optic nerve on magnetic resonance imaging. The patients had progressive visual field defects and impairment on the side where the flow diverter was placed. Short tau inversion recovery coronal images showed a doughnut-shaped high-signal around the optic nerve on the affected side. Both patients were treated with steroid pulse therapy, and 1 received endovascular therapy. Their symptoms gradually improved, and the "doughnut sign" disappeared. The "doughnut sign" observed around the optic nerve on magnetic resonance imaging may be found alongside visual disturbance symptoms after paraclinoid aneurysm treatment. It is recommended that short tau inversion recovery sequences be performed preoperatively in patients presenting with visual impairment and in whom the possibility of postoperative exacerbation is suspected.

12.
Foods ; 11(3)2022 Jan 27.
Article in English | MEDLINE | ID: mdl-35159523

ABSTRACT

Drugs for inflammatory bowel diseases can be associated with serious side effects, and the development of alternative candidate resources derived from natural products has attracted considerable attention. Oyster extract (OE) derived from Crassostrea gigas contains glycogen, taurine, and amino acids, and has been assigned diverse health-promoting properties. This study investigated the anti-colitis effect of OE intake on fecal microbiota and its metabolites of acute experimental colitis mouse model induced by dextran sulfate sodium (DSS). C57BL/6J mice (male) were divided into three groups: (1) American Institute of Nutrition (AIN) 93G diet + DSS-untreated, (2) AIN93G diet + DSS-treated, and (3) 5% OE diet + DSS-treated. Mice were fed each diet for 21 days, and then administered 2.5% DSS solution to induce acute colitis for 7 days. In DSS-induced colitis mice, OE decreased body weight loss and increased disease activity index during the DSS-induced period. In addition, OE tended to decrease the colon length shortening and the relative spleen weight and alleviated colonic tissue damage. Moreover, OE improved fecal short-chain fatty acids compositions and altered the structure of fecal microbiota. These results provide insight into the health-promoting property of OE in alleviating DSS-induced acute colitis, providing a basis for the development and use of functional foods.

13.
J Neuroendovasc Ther ; 16(1): 56-62, 2022.
Article in English | MEDLINE | ID: mdl-37502025

ABSTRACT

Objective: We treated a case of scalp arteriovenous malformation (sAVM) by transvenous embolization using Onyx. Case Presentation: We describe the case of a 17-year-old woman with a pulsatile mass at the right temporal area. DSA identified sAVM with the venous pouch between the right occipital artery (OA) and the right two occipital veins (OVs), which was also fed by multiple branches of the right posterior auricular artery (PAA) and superficial temporal artery (STA). The shunts were completely occluded by the reverse pressure cooker technique (RPCT), which involves navigating the balloon catheters just distal to the shunt point in the OVs approaching from the right external jugular vein (EJV) and injecting Onyx to each feeder retrogradely with balloons inflated. Conclusion: This technique may be useful for treating sAVM with venous angioarchitecture enabling a transvenous approach.

14.
Neuroradiology ; 64(4): 837-841, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34839378

ABSTRACT

Endovascular treatment for partially thrombosed giant basilar tip aneurysms has not been established because of its low cure rate and numerous associated comorbidities. Although some authors reported the growth mechanism of partially thrombosed aneurysm, there is no report for the process of its shrinkage after treatment. We describe a case of a partially thrombosed giant basilar tip aneurysm presenting with disturbance of consciousness because of a mass effect and brain edema. The patient underwent stent-assisted coiling using a low-profile visualized intraluminal support stent (Terumo). Although pre-operative magnetic resonance imaging (MRI) and angiography revealed prominent neovascularization of the inner aneurysmal layer, this vessel was absent on follow-up angiography 1 month after treatment. Repeat angiography demonstrated the gradual recanalization of the aneurysm. However, repeat MRI examinations showed remarkable shrinkage of the thrombosed aneurysm, and the complete disappearance of the thrombosed component was noted 6 months after treatment. The disappearance of neovascularization 1 month after the treatment may have contributed to the shrinkage of the thrombosed aneurysm. Stent-assisted coiling combined with alteration caused a hemodynamic change in this aneurysm, and the flow-diverting effect might have controlled this partially thrombosed giant aneurysm.


Subject(s)
Brain Edema , Embolization, Therapeutic , Intracranial Aneurysm , Brain Edema/complications , Cerebral Angiography/methods , Embolization, Therapeutic/methods , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Magnetic Resonance Imaging , Stents , Treatment Outcome
15.
Medicina (Kaunas) ; 57(11)2021 Nov 18.
Article in English | MEDLINE | ID: mdl-34833482

ABSTRACT

Valve vegetation is one of the most fearful findings for physicians. The first diagnosis that comes to their mind is infective endocarditis (IE), but it can also be noninfective; nonbacterial thrombotic endocarditis (NBTE). NBTE can be even more challenging than IE for physicians because of the wide range of differential diagnoses such as malignancies, autoimmune disorders and human immunodeficiency virus. A 45-year-old woman presented at the emergency room with a sudden onset of dysarthria and right-sided hemiplegia. Laboratory data showed her blood counts and coagulation test were mostly normal and the magnetic resonance imaging detected a high-signal-intensity change in her left brain. An echocardiogram found a vegetation-like structure on her atrial valve. We highly suspected IE leading to cerebral embolism. The clot was successfully removed by our neurosurgeons and anticoagulation therapy was started concurrently. Her state of consciousness improved, but then she suffered a brain hemorrhage and died. The autopsy revealed that the cause of her vegetation was acute promyelocytic leukemia (APL). Based on these findings, it is important to remember that APL can be the cause of NBTE even if the blood count and coagulation tests are almost normal.


Subject(s)
Endocarditis , Leukemia, Promyelocytic, Acute , Thrombosis , Autopsy , Echocardiography , Endocarditis/diagnosis , Endocarditis/diagnostic imaging , Female , Humans , Leukemia, Promyelocytic, Acute/complications , Middle Aged , Thrombosis/etiology
16.
Ther Drug Monit ; 43(4): 519-526, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34250964

ABSTRACT

BACKGROUND: Plasma teicoplanin concentrations do not reach the therapeutic range in several patients with hematological malignancies. Nevertheless, the characteristics of the population pharmacokinetic (PPK) models have not been clarified for malignancy. The decrease in the teicoplanin concentration in patients with cancer has been attributed to augmented renal clearance (ARC). It is essential to identify the causative factors of ARC to construct a PPK model to optimize the administration method. The authors aimed to establish a PPK model and develop an appropriate dosing regimen for teicoplanin in patients with hematological malignancies. METHODS: PPK analysis was performed using therapeutic drug monitoring (TDM) data from 119 patients with hematological malignancies. The developed model was verified by predictive performance. RESULTS: The covariates affecting systemic clearance were serum creatinine, presence or absence of neutropenia (<500/µL), and body size descriptor. Patients with hematologic malignancies and neutropenia showed a 25% increase in clearance compared with those with a normal neutrophil count. The PPK model was constructed based on the presence or absence of neutropenia. This model allowed the selection of the most appropriate dosage regimen out of those recommended by the TDM guidelines for patients with eGFR of >60 mL/min/1.73 m2. The PPK model predicted a dosing regimen for achieving a 10% improvement in the coverage probability of the target concentration range during the loading and maintenance phases. CONCLUSIONS: The PPK model may help optimize dose regimens and evaluate dosing methods, using comparative simulations, in patients with hematological malignancies.


Subject(s)
Hematologic Neoplasms , Neutropenia , Teicoplanin , Creatinine , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Humans , Neutropenia/drug therapy , Teicoplanin/administration & dosage , Teicoplanin/pharmacokinetics
17.
J Oleo Sci ; 70(7): 947-954, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-34121036

ABSTRACT

Lysophospholipids (LPLs) are small bioactive lipid molecules characterized by a single carbon chain and a polar head group. LPLs have recently shown to be involved in many physiological and pathological processes such as nervous system regulation. In our previous studies, a porcine liver decomposition product (PLDP) has been identified as a substance that improves cognitive function at old ages. This PLDP is a rich source of LPLs, including lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). This study was designed to evaluate the anti-inflammatory effect of these LPLs on lipopolysaccharide (LPS)-stimulated SIM-A9 microglial cells in terms of cytokine expression and oxidative stress and to investigate the potential mechanisms underlying these effects. SIM-A9 cells were pretreated with LPLs prior to LPS stimulation, and the anti-inflammatory potential of the LPLs in LPS-induced SIM-A9 cells was examined. Pretreatment with LPLs significantly inhibited the LPS-induced expression of IL-6 in SIM-A9 cells. Furthermore, oxidative-related protein, NADPH oxidase 2 (Nox2) levels were markedly increased in the LPS-treated cells, and pretreatment with LPC and LPE significantly reduced to basal levels. In addition, LPS-induced ROS production was eliminated in apocynin-treated cells, indicating that ROS production was dependent on Nox2. Our findings revealed that pretreatment with LPC and LPE decreased LPS-stimulated ROS production. These results indicated that LPC and LPE exerted significant protective effects against LPS-induced inflammation and oxidative stress in SIM-A9 cell.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Inflammation/drug therapy , Lysophosphatidylcholines/pharmacology , Lysophospholipids/pharmacology , Microglia/drug effects , Oxidative Stress/drug effects , Animals , Cell Line , Cell Survival/drug effects , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-6/metabolism , Lipopolysaccharides , Mice , NADPH Oxidase 2/metabolism , Reactive Oxygen Species/metabolism
18.
J Biochem ; 170(3): 327-336, 2021 Oct 12.
Article in English | MEDLINE | ID: mdl-33822960

ABSTRACT

Lysophosphatidylethanolamines (LPEs) are bioactive lysophospholipids that have been suggested to play important roles in several biological processes. We performed a quantitative analysis of LPE species and showed their composition in mouse brain. We examined the roles of oleoyl-LPE (18:1 LPE), which is one of the abundant LPE species in brain. In cultured cortical neurons, application of 18:1 LPE-stimulated neurite outgrowth. The effect of 18:1 LPE on neurite outgrowth was inhibited by Gq/11 inhibitor YM-254890, phospholipase C (PLC) inhibitor U73122, protein kinase C (PKC) inhibitor Go6983 or mitogen-activated protein kinase (MAPK) inhibitor U0126. Additionally, 18:1 LPE increased the phosphorylation of MAPK/extracellular signal-regulated kinase 1/2. These results suggest that the action of 18:1 LPE on neurite outgrowth is mediated by the Gq/11/PLC/PKC/MAPK pathway. Moreover, we found that application of 18:1 LPE protects neurons from glutamate-induced excitotoxicity. This effect of 18:1 LPE was suppressed by PKC inhibitor Go6983. These results suggest that 18:1 LPE protects neurons from glutamate toxicity via PKC inhibitor Go6983-sensitive PKC subtype. Collectively, our results demonstrated that 18:1 LPE stimulates neurite outgrowth and protects against glutamate toxicity in cultured cortical neurons. Our findings provide insights into the physiological or pathological roles of 18:1 LPE in the brain.


Subject(s)
Brain/drug effects , Glutamic Acid/toxicity , Lysophospholipids/pharmacology , Neuronal Outgrowth/drug effects , Neurons/metabolism , Animals , Brain/metabolism , Cells, Cultured , Chromatography, Liquid/methods , Extracellular Signal-Regulated MAP Kinases/metabolism , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , Male , Mice , Mice, Inbred C57BL , Neurites/metabolism , Phosphorylation , Protein Kinase C/metabolism , Signal Transduction/drug effects , Spectrometry, Mass, Electrospray Ionization/methods , Type C Phospholipases/metabolism
19.
J Neuroendovasc Ther ; 15(9): 555-564, 2021.
Article in English | MEDLINE | ID: mdl-37501745

ABSTRACT

We introduce our technique to treat dural arteriovenous fistulae (dAVFe) under sinus balloon protection. The Kaneka Shoryu 7 × 7 mm balloon was used for sinus occlusion. Initially, the balloon was inflated slowly using 1.5-2.0 mL of saline on the table. A 6F guiding catheter was navigated into the proximal portion of the lesion from the jugular vein of the affected side. The balloon catheter was introduced to the point occluding the shunt. The balloon was temporarily inflated to determine the occlusion point without occluding the outlet of the vein of Labbe. ONYX injection was started from the microcatheter located at just proximal to the shunt point under sinus balloon occlusion. ONYX penetrated the feeding arteries in an antegrade and retrograde manner. After the penetration of ONYX into each feeding artery, the inflated balloon was temporarily deflated to examine the residual shunt. If a small shunt remained, the balloon was inflated again and ONYX injection was continued. To cure dAVF, the location of the balloon is important. The guiding catheter should be placed just proximal to the shunt and the balloon catheter should be gently pulled to stabilize the balloon position.

20.
Biochem Biophys Res Commun ; 534: 179-185, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33298313

ABSTRACT

Neurite outgrowth is important in neuronal circuit formation and functions, and for regeneration of neuronal networks following trauma and disease in the brain. Thus, identification and characterization of the molecules that regulate neurite outgrowth are essential for understanding how brain circuits form and function and for the development of treatment of neurological disorders. In this study, we found that structurally different lysophosphatidylethanolamine (LPE) species, palmitoyl-LPE (16:0 LPE) and stearoyl-LPE (18:0 LPE), stimulate neurite growth in cultured cortical neurons. Interestingly, YM-254890, an inhibitor of Gq/11 protein, inhibited 16:0 LPE-stimulated neurite outgrowth but not 18:0 LPE-stimulated neurite outgrowth. In contrast, pertussis toxin, an inhibitor of Gi/Go proteins, inhibited 18:0 LPE-stimulated neurite outgrowth but not 16:0 LPE-stimulated neurite outgrowth. The effects of protein kinase C inhibitors on neurite outgrowth were also different. In addition, both 16:0 LPE and 18:0 LPE activate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2, but the effect of the MAPK inhibitor differed between the 16:0 LPE- and 18:0 LPE-treated cultures. Collectively, the results suggest that the structurally different LPE species, 16:0 LPE and 18:0 LPE stimulate neurite outgrowth through distinct signaling cascades in cultured cortical neurons and that distinct G protein-coupled receptors are involved in these processes.


Subject(s)
Lysophospholipids/pharmacology , Neuronal Outgrowth/drug effects , Receptors, G-Protein-Coupled/metabolism , Signal Transduction/drug effects , Animals , Axons/drug effects , Axons/ultrastructure , Brain/cytology , Butadienes/pharmacology , Cells, Cultured , Dendrites/drug effects , Dendrites/ultrastructure , Egg Yolk/chemistry , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/antagonists & inhibitors , GTP-Binding Protein alpha Subunits, Gq-G11/antagonists & inhibitors , Heterotrimeric GTP-Binding Proteins/antagonists & inhibitors , Lysophospholipids/chemistry , Mice, Inbred ICR , Neurons/drug effects , Neurons/enzymology , Nitriles/pharmacology , Peptides, Cyclic/pharmacology , Pertussis Toxin/pharmacology , Protein Kinase Inhibitors/pharmacology
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