Cacao Procyanidins-Induced Lifespan Extension in Caenorhabditis elegans in a Nervous System and CaMKII-Dependent Manner.

Procyanidins are gaining attention due to their potential health benefits. We found that cacao liquor procyanidin (CLPr) from Theobroma cacao seeds increased the lifespan of Caenorhabditis elegans, a representative model organism for aging studies. The genetic dependence of the lifespan-extending effect of CLPr was consistent with that of blueberry procyanidin, which is dependent on unc-43, osr-1, sek-1, and mev-1, but not on daf-16, sir-2.1, or skn-1. The lifespan-extending effect of CLPr was inhibited by neuron-specific RNA interference (RNAi) targeting unc-43 and pmk-1, and in worms with loss-of-function mutations in the odr-3, odr-1, or tax-4 genes, which are essential in sensory neurons, including AWC neurons. It was also inhibited in worms in which AWC neurons or AIB interneurons had been eliminated, and in worms with loss-of-function mutations in eat-4 or glr-1, which are responsible for glutamatergic synaptic transmission. These results suggest that the lifespan-extending effect of CLPr is dependent on the nervous system. In addition, it also requires unc-43 and pmk-1 expression in nonneuronal cells, as demonstrated by the experiments with RNAi in wild-type worms, the neuronal cells of which are not affected by systemic RNAi. The osr-1 gene is expressed in hypodermal and intestinal cells and regulates the response to osmotic stress along with unc-43/calcium/calmodulin-dependent protein kinase II and the p38 mitogen-activated protein kinase pathway. Consistent with this, CLPr improved osmotic stress tolerance in an unc-43- and pmk-1-dependent manner, and it was also dependent on AWC neurons. The lifespan-extending and osmotic-tolerance-improving activities were attributed to procyanidins with a tetrameric or higher-order oligomeric structure.

Nutritional Value of Yogurt as a Protein Source: Digestibility/Absorbability and Effects on Skeletal Muscle.

Yogurt is a traditional fermented food that is accepted worldwide for its high palatability and various health values. The milk protein contained in yogurt exhibits different physical and biological properties from those of non-fermented milk protein due to the fermentation and manufacturing processes. These differences are suggested to affect the time it takes to digest and absorb milk protein, which in turn will influence the blood levels of amino acids and/or hormones, such as insulin, and thereby, the rate of skeletal muscle protein synthesis via the activation of intracellular signaling, such as the mTORC1 pathway. In addition, based on the relationship between gut microbiota and skeletal muscle conditions, yogurt, including lactic acid bacteria and its metabolites, has been evaluated for its role as a protein source. However, the substantial value of yogurt as a protein source and the additional health benefits on skeletal muscle are not fully understood. The purpose of this review is to summarize the research to date on the digestion and absorption characteristics of yogurt protein, its effect on skeletal muscle, and the contribution of lactic acid bacterial fermentation to these effects.

[Intraoperative Neurophysiological Monitoring in Pediatric Patients].

Because of technological advancements in preserving neurological function during surgery, intraoperative neurophysiological monitoring has become mandatory and increasingly common. Few studies have reported on the safety, feasibility, and reliability of intraoperative neurophysiological monitoring in children, especially infants. The maturation of nerve pathways is not fully achieved until 2 years of age. Moreover, it is often difficult to maintain stable anesthetic depth and hemodynamic status when operating on children. The interpretation of neurophysiological recordings in children is different from that in adults and requires further consideration.

Application of elemental analysis-coupled isotope ratio mass spectrometry for protein turnover analysis using deuterium labeling: Purification and analysis of hydrogen isotope ratio of non-derivatized protein-bound alanine.

RATIONALE: Heavy water can be used as a tracer for the evaluation of protein turnover. By adding heavy water (D2 O) to the precursor pool, nonessential amino acids, including alanine, can be isotopically labeled in vivo. Protein turnover can then be quantified by measuring the hydrogen isotope ratio of protein-bound alanine. METHODS: In this study, we constructed a novel method to apply deuterium labeling of alanine to the evaluation of protein turnover using elemental analysis-coupled isotope ratio mass spectrometry (EA-IRMS). We established a preparative high-performance liquid chromatography method to isolate alanine from protein hydrolysates. EA-IRMS was then used to determine the hydrogen isotope ratio of alanine isolated from hydrolysates of protein from mouse myoblast C2C12 cells that had been treated with D2 O over the course of 72 h. RESULTS: In cells treated with 4% D2 O, the deuterium enrichment of alanine increased to approximately 0.9% over time, while that of cells treated with 0.017% D2 O increased to approximately 0.006%. The rate of protein synthesis calculated by fitting the increase of deuterium excess to rise-to-plateau kinetics was similar regardless of the concentration of D2 O. When C2C12 cells treated with insulin and rapamycin were analyzed 24 h after the addition of 0.017% D2 O, protein turnover was found to be accelerated by insulin, but this effect was offset by co-treatment with rapamycin. CONCLUSION: The derivative-free measurement of the hydrogen isotope ratio of protein-bound alanine using EA-IRMS can be applied to the evaluation of protein turnover. The proposed method is an accessible option for many laboratories to perform highly sensitive IRMS-based evaluations of protein metabolic turnover.

Anti­tumor effects of anti­epileptic drugs in malignant glioma cells.

Patients with glioblastoma frequently suffer epileptic seizures and often require anticonvulsant therapy during the treatment course. The present study investigated four common antiepileptic drugs, perampanel, carbamazepine (CBZ), sodium valproate (VPA) and levetiracetam (LEV), which are expected to have antitumor effects, and determined the most beneficial drug for the treatment of malignant glioma by comparing antitumor effects such as inhibition of cell proliferation and suppression of migration and invasion (using Transwell assays). The inhibition of cell growth was investigated using six malignant glioma cell lines (A­172, AM­38, T98G, U­138MG, U­251MG and YH­13). Significant inhibition of cell proliferation was observed in all six cell lines treated with perampanel, three cell lines treated with CBZ, four cell lines treated with VPA and two cell lines treated with LEV at the therapeutic blood concentration levels for the drugs to be used as antiepileptics. Further antitumor effects in combination with temozolomide were investigated using T98G and U­251MG cell lines, and were confirmed in both cell lines with perampanel and in T98G cells with LEV, but not observed with CBZ and VPA. Cell migration was significantly suppressed in both T98G and U­251MG cell lines with perampanel, but not with CBZ, VPA or LEV. To investigate the mechanisms by which perampanel suppresses the migration of malignant glioma cells, the expression of mRNA related to epithelial­mesenchymal transition following perampanel treatment was analyzed using reverse transcription­quantitative PCR in the T98G and U­251MG cell lines. The expression of Rac1 and RhoA, which constitute the cytoskeleton that enhances cell motility, were reduced in both cell lines. Furthermore, the expression of the mesenchymal marker N­cadherin, which promotes cell migration and infiltration, was decreased, but the expression of the epithelial marker E­cadherin, which strengthens cell­cell adhesion and reduces cell motility, was increased. Furthermore, the expression of matrix metalloproteinase­2, a proteolytic enzyme, was reduced. These effects may reduce cell motility and increase adhesion between cells, suggesting that perampanel treatment suppressed cell migration. In conclusion, the present study suggests that perampanel may be more beneficial in terms of antitumor efficacy than other antiepileptic drugs for the treatment of malignant glioma.

Anti-tumor effects of perampanel in malignant glioma cells.

Glioblastoma has a poor prognosis even after multimodal treatment, such as surgery, chemotherapy and radiation therapy. Patients with glioblastoma frequently develop epileptic seizures during the clinical course of the disease and often require antiepileptic drugs. Therefore, agents with both antiepileptic and antitumoral effects may be very useful for glioblastoma treatment. Perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist, is an antiepileptic drug that is widely used for intractable epilepsy. The present study aimed to assess the potential antitumoral effects of perampanel using malignant glioma cell lines. The cell proliferation inhibitory effect was evaluated using six malignant glioma cell lines (A-172, AM-38, T98G, U-138MG, U-251MG and YH-13). A dose-dependent inhibitory effect of perampanel on cell viability was demonstrated; however, the sensitivity of cells to perampanel varied and further antitumoral effects were demonstrated in combination with temozolomide (TMZ) in certain malignant glioma cells. Furthermore, cell cycle distribution and apoptosis induction analyses were performed in T98G and U-251MG cells using a fluorescence activated cell sorter (FACS) and the expression levels of apoptosis-related proteins were evaluated using western blotting. No significant change was demonstrated in the proportions of cells in the G0/G1, S and G2/M phases under 1.0 µM perampanel treatment, whereas induction of apoptosis was demonstrated using FACS at 10 µM perampanel and western blotting at 1.0 µM perampanel in both glioma cell lines. Overexpression of SERPINE1 may be related to poor prognosis in patients with gliomas. The combination of 1.0 µM perampanel and 5.0 µM tiplaxtinin, a SERPINE1 inhibitor, demonstrated further reduced cell viability in perampanel-resistant U-138MG cells, which have high expression levels of SERPINE1. These results indicated that the antitumor effect of perampanel may not be expected for malignant gliomas with higher expression levels of SERPINE1. The findings of the present study suggested that the antiepileptic drug perampanel may also have an antitumor effect through the induction of apoptosis, which is increased when combined with TMZ in certain malignant glioma cells. These findings also suggested that SERPINE1 expression may be involved in perampanel susceptibility. These results may lead to new therapeutic strategies for malignant glioma.

Evaluating Cranial Growth in Japanese Infants Using a Three-dimensional Scanner: Relationship between Growth-related Parameters and Deformational Plagiocephaly.

In this study, we aimed to evaluate the longitudinal changes in the cranial shape of healthy Japanese infants using a three-dimensional scanner and construct a normal values database for the growth process. Preterm infants (gestational age < 37 weeks), infants with neonatal asphyxia (5-minute Apgar score of <7), and patients who started helmet therapy for deformational plagiocephaly were excluded from this study. The first scan was performed at approximately 1 month of age, followed by two scans conducted at 3 and 6 months of age. The parameters considered were as follows: cranial length, width, height, circumference, volume, cranial vault asymmetry index, and cephalic index. A cranial vault asymmetry index >5% was defined as deformational plagiocephaly. Changes in each parameter were examined using repeated-measures analysis of variance classified by sex and deformational plagiocephaly status. The rate of increase in each parameter was also examined. In total, 88 infants (45 boys and 43 girls) were included in this study. All growth-related parameters were noted to increase linearly with time. Sex differences were observed in all parameters except cranial length. Deformational plagiocephaly was found to have no effect on growth-related parameters. Cranial volume increased by 60% from 1 to 6 months of age. The growth almost uniformly influenced the rate of increase in volume in each coordinate axis direction. Overall, the mean trends in three-dimensional parameters in infants up to 6 months of age were obtained using a three-dimensional scanner. These trends could be used as a guide by medical professionals involved in cranioplasty.

α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube.

There is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced by co-exposure to TNFα and IFNγ. The phosphorylation of AMPK or ERK1/2 was significantly altered 30 min after HICA treatment under normal conditions. The basal protein synthesis rates measured by a deuterium-labeling method were significantly lowered by the HICA treatment under normal and cachexic conditions. Conversely, myotube atrophy induced by TNFα/IFNγ co-exposure was significantly improved by the HICA pretreatment, and this improvement was accompanied by the inhibition of iNOS expression and IL-6 production. Moreover, HICA also suppressed the TNFα/IFNγ co-exposure-induced secretion of 3-methylhistidine. These results demonstrated that HICA decreases basal protein synthesis under normal or cachexic conditions; however, HICA might attenuate skeletal muscle atrophy via maintaining a low level of protein degradation under cachexic conditions.

Natural-Course Evaluation of Infants with Positional Severe Plagiocephaly Using a Three-Dimensional Scanner in Japan: Comparison with Those Who Received Cranial Helmet Therapy.

This study aimed to clarify the natural course of positional plagiocephaly using a three-dimensional (3D) scanner and investigate the effectiveness of cranial helmet therapy (CHT). One hundred infants with severe plagiocephaly who visited our institutions between April 2020 and March 2021 were included. Cranial shape was measured using an Artec Eva 3D scanner. A cranial asymmetry (CA) >12 mm was diagnosed as severe plagiocephaly. An infant whose CA subsided to <12 mm was considered to have improved naturally or by CHT. The difference in CA between the second and initial scans was defined as the improvement value (median scan interval was two months). In the natural-course group comprising 56 infants with severe plagiocephaly, 37 (66%) with a median CA of 15.6 mm exhibited no improvement after two months. In the scan age- and evaluation interval-matched case-control study, the CA value in the CHT group improved by three times that in the natural-course group (-4.6 mm [n = 33] vs. -1.55 mm [n = 24], p < 0.001). Severe plagiocephaly did not improve naturally in 66% of the cases. Therefore, CHT should be considered if the CA is >12 mm on the initial evaluation.

Venous hypertension caused by a meningioma involving the sigmoid sinus: case report.

BACKGROUND: Intracranial venous hypertension has been associated with a few cases of meningioma secondary to compression of the venous sinus. This is the rare case of small meningioma involving the sigmoid sinus leading to intracranial venous hypertension mimicking venous thrombosis. CASE PRESENTATION: A 39-year-old woman suffered visual dysfunction due to bilateral papilledema. Noncontrast head computed tomography (CT) showed no intracranial space-occupying lesions or hydrocephalus. Cerebrospinal fluid examination revealed high opening pressure. Various image inspections such as three-dimensional CT angiography, magnetic resonance imaging, and cerebral angiography demonstrated a small 2.5-cm lesion causing subtotal occlusion of the dominant right sigmoid sinus. No improvement of clinical manifestations was observed after medical treatment for 6 months, so right presigmoid craniectomy was performed. Operative findings revealed that the tumor was located predominantly involving the sigmoid sinus. The pathological diagnosis was fibrous meningioma. Postoperative fundoscopic examination showed improvement of bilateral papilledema. CONCLUSIONS: We treated a patient presenting with intracranial hypertension due to a small meningioma involving the sigmoid sinus. This unusual case suggests that early surgical strategies should be undertaken to relieve the sinus obstruction.

Massive intracranial hemorrhage caused by intraventricular meningioma: case report.

BACKGROUND: Meningiomas are the most common benign intracranial tumors, and commonly comprise high-vascularizing but slow-growing tumors. On the other hand, meningiomas arising from the ventricular system are of rare occurrence, and spontaneous hemorrhage is an infrequent event. CASE PRESENTATION: We describe here the rare clinical manifestations of a 28-year-old female with acute intracranial hemorrhage located in the trigone of the lateral ventricle who was initially thought to have suffered an acute cerebrovascular accident, but was subsequently confirmed to have a benign intraventricular meningioma. To clarify the clinical features of such a rare course of meningioma, we also present a short literature review of acute intracranial hemorrhage caused by intraventricular meningioma. CONCLUSIONS: Ventricular meningioma presenting with hemorrhage such as acute stroke is a rare event, but recognition of such a pathogenesis is important. Although further accumulation of clinical data is needed, we suggest that early surgery should be undertaken in patients with lateral ventricular meningioma, even if it is not so large or asymptomatic.

Inorganic Iron Supplementation Rescues Hematological Insufficiency Even Under Intense Exercise Training in a Mouse Model of Iron Deficiency with Anemia.

Iron deficiency anemia (IDA) due to malnutrition and/or blood loss is a common condition, especially in women of reproductive age. Intense exercise can induce anemia via an inflammatory response, but whether intense exercise affects the efficacy of iron supplementation to treat IDA is unclear. Here, we show in a mouse model of IDA that acute intense swimming increased IL-6 levels in the blood, but did not affect the maximum elevation of plasma iron following oral administration of 0.5 mg/kg Bw iron. However, compared with the control group without intense exercise, acute intense swimming was associated with a significant decrease in plasma iron 2 and 4 h after iron loading that could be attributed to rapid iron absorption in peripheral tissues. In the chronic experiment, IDA mice administered 0.36, 1.06, or 3.2 mg/kg Bw iron per day that were subjected to 11 intense swimming sessions over 3 weeks showed significantly decreased recovery levels for hemoglobin and red blood cell count during the early phase of the experimental period. At the end of the experimental period, significant, dose-dependent effects of iron, but not the main effect of intense exercise, were seen for recovery of hemoglobin and red blood cell counts, consistent with the acute exercise study. These results suggested that intense exercise in the presence of IDA does not inhibit iron absorption from the gastrointestinal tract and that iron supplementation can enhance the recovery process even after intense exercise.

Antitumor effects of ribavirin in combination with TMZ and IFN-ß in malignant glioma cells.

The prognosis of gioblastoma, the standard chemotherapy agent for which is temozolomide (TMZ), remains poor despite recent advances in multimodal treatments. Therefore, it is necessary to identify and develop novel therapeutics for this malignant disease. Ribavirin, an anti-viral agent which is one of the standard agents for treatment of chronic hepatitis C in combination with interferon (IFN), was recently revealed to have an antitumor potential towards various tumor cells, including malignant glioma cells. The aim of the present study was to examine the antitumor effect of ribavirin in combination with TMZ and IFN-ß on glioma cells and to evaluate the possibility that such combinations might represent a novel candidate for glioblastoma therapy. The combination of ribavirin with TMZ and IFN-ß displayed a significant cell growth inhibitory effect with a ribavirin dose-dependency, including a relatively low concentration of ribavirin, on not only TMZ-sensitive but also TMZ-resistant malignant glioma cells. The antitumor efficacy of such a combination further indicated a synergistic interaction when assessed by the Chou-Talalay method. Furthermore, flow cytometry analysis suggested that apoptosis induction was one of the possible biological processes underlying the synergistic antitumor effect of these triple combination treatments. Therefore, such combinations may be potentially important in the clinical setting for glioblastoma treatment, although further detailed studies, e.g. on the adverse effects, are required.

Tectal Low-Grade Glioma with H3 K27M Mutation.

BACKGROUND: In the revised World Health Organization 2016 classification of central nervous system tumors, "diffuse midline glioma, H3 K27M-mutant" has been added as a new diagnostic entity. However, some confusion exists concerning this diagnostic entity because H3 K27M-mutant diffuse midline glioma is diagnosed with grade IV regardless of morphologic phenotype. Furthermore, the significance of H3 K27M mutation in tumors that aren't typical "diffuse midline glioma, H3 K27M-mutant," such as those with an unusual location and nontypical histology, remains unclear. CASE DESCRIPTION: To elucidate further such unusual tumors, we describe here a rare case of pediatric low-grade glioma located in the tectum, which was morphologically a pilocytic astrocytoma (PA) with genetically H3 K27M mutation but no microvascular proliferation, necrosis, mitoses, or other genetic alterations, insofar as we were able to observe. At the latest follow-up, 28 months after surgery, radiotherapy, and chemotherapy, the patient was found to be free from any neurologic deficits and MRI demonstrated that the tumor was stable without tumor regrowth. This case might be identified as "diffuse midline glioma, H3 K27M-mutant", grade IV, when applying only the current World Health Organization 2016 classification. In addition, we discuss the morphologically benign gliomas harboring the H3 K27M mutation based on the literature. CONCLUSIONS: We describe here a rare case and present a short literature review of circumscribed/nondiffuse gliomas, particularly in PA with H3 K27M mutation. However, the significance of H3 K27M mutation for PA remains unclear, so further studies and clinical data are needed to elucidate the biology and optimal treatment of such tumors.

Repeated stretch-shortening contraction of the triceps surae attenuates muscle atrophy and liver dysfunction in a rat model of inflammation.

NEW FINDINGS: What is the central question of this study? Is stretch-shortening contraction effective to attenuate skeletal muscle atrophy and hepatic dysfunction in a rat model of peptidoglycan-polysaccharide (PG-PS)-induced inflammation (PG-PS rat)? What are the main findings and their importance? Stretch-shortening contraction attenuates skeletal muscle atrophy in the trained leg and increases circulating interleukin-10 in PG-PS rats. Stretch-shortening contraction also ameliorates liver dysfunction in PG-PS rats, possibly via increased blood interleukin-10. These findings are important because they suggest that stretch-shortening contraction is effective to maintain liver function in addition to exercised skeletal muscle mass. ABSTRACT: Stretch-shortening contraction (SSC) is an effective modality to improve skeletal muscle mass. However, the beneficial effects of SSC in the presence of chronic inflammation remain unclear. Here, we imposed five SSC sessions unilaterally on the triceps surae in young female Lewis rats. Rats were injected with vehicle or peptidoglycan-polysaccharide (PG-PS) to induce long-lasting inflammation. The PG-PS reduced gastrocnemius muscle mass in both legs, but that of the SSC-trained leg was significantly greater than that of the contralateral leg. Circulating pro-inflammatory cytokines, such as IL-1ß, were significantly increased by PG-PS injection, even if carrying out SSC. The circulating anti-inflammatory cytokine IL-10 increased with SSC in both healthy and inflammatory conditions. Stretch-shortening contraction also prevented increases in serum aspartate aminotransferase activity and plasma free phenylalanine concentration induced by PG-PS, in comparison to the control resistance exercise consisting of isometric contractions. Moreover, aspartate aminotransferase and phenylalanine concentrations demonstrated a significant and negative correlation with IL-10/IL-1ß values (r = -0.61, P = 0.017, and r = -0.66, P = 0.008, respectively). These results suggest that SSC training is effective to reduce both muscle atrophy and the hepatic dysfunction induced by PG-PS, mediated, at least in part, through an increase in circulating IL-10.

A Case of Tuberculum Sellae Chordoid Meningioma Treated via Extended Endoscopic Endonasal Trans-sphenoidal Surgery.

A 68-year-old female was admitted to our hospital with right-sided hemianopsia. Magnetic resonance imaging (MRI) demonstrated a well-enhanced tuberculum sellae region tumor. The patient underwent surgical tumor resection via an extended endoscopic endonasal trans-sphenoidal approach and the tumor was totally removed. The mass was extremely soft and there was no clear attachment between it and the dura mater. Furthermore, the histopathological findings obtained for the tumor during intra-operative rapid diagnosis were divergent from typical meningioma. We therefore diagnosed the tumor intra-operatively as a pituitary adenoma. However, the post-operative pathological diagnosis for the tumor was chordoid meningioma (CM). CM is a rare subtype of meningioma, and most of such tumors arise in the convexity. In the preoperative MRI in the present case, meningioma was suspected; however, since we did not consider CM for differential diagnosis, we failed to reach an accurate diagnosis during the operation. Tuberculum sellae CM is very rare, and only a few cases have been reported previously. The surgical strategy will differ greatly depending on whether the tumor is a meningioma or a pituitary adenoma, especially when treatment involves the dura mater. The pre and/or intra-operative diagnosis is thus very important for developing an accurate treatment strategy. We report here the details of our rare case and describe the intra-operative features of tuberculum sellae CM.

Antitumor effect of lenalidomide in malignant glioma cell lines.

Glioblastoma is a malignant brain tumor exhibiting highly aggressive proliferation and invasion capacities. Despite treatment by aggressive surgical resection and adjuvant therapy including temozolomide and radiation therapy, patient prognosis remains poor. Lenalidomide, a derivative of thalidomide, is known to be an immunomodulatory agent that has been used to treat hematopoietic malignancies. There are numerous studies revealing an antitumor effect of lenalidomide in hematopoietic cells, but not in glioma cells. The present study aimed to demonstrate the antitumor effect of lenalidomide on malignant glioma cell lines. The growth inhibition of malignant glioma cells (A­172, AM­38, T98G, U­138MG, U­251MG, and YH­13) by lenalidomide was assessed using a Coulter counter. The mechanism of the antitumor effect of lenalidomide was examined employing a fluorescence­activated cell sorter, western blot analysis, and quantitative real­time reverse transcriptional polymerase chain reaction (RT­qPCR) in malignant glioma cell lines (A­172, AM­38). The results revealed that the number of malignant glioma cells was decreased in a concentration­dependent manner by lenalidomide. DNA flow cytometric analysis demonstrated an increase in the ratio of cells at the G0/G1 phase following lenalidomide treatment. Western blot analysis and RT­qPCR revealed that p53 activation and the expression of p21 were increased in glioma cells treated with lenalidomide. Western blot analysis revealed that cleavage of PARP did not occur; however, increased expression of Bax protein, cleavage of caspase­9 and cleavage of caspase­3 were confirmed. Analysis by FACS also supported the conclusion that little apoptosis induction occurred following lenalidomide treatment of malignant glioma cell lines. In conclusion, lenalidomide exerts an antitumor effect on glioma cells due to alterations in cell cycle distribution.

Pituitary Apoplexy Accompanying Temporal Lobe Seizure as a Complication.

BACKGROUND: Pituitary apoplexy is an acute clinical syndrome caused by infarction and/or hemorrhage of pituitary adenoma, which typically presents with severe headache, visual deterioration, and endocrine abnormalities. However, temporal lobe seizure (and temporal lobe epilepsy) has not been viewed as a symptom of pituitary apoplexy in the literature. CASE DESCRIPTION: To elucidate further such a rare complication of temporal lobe seizure, we describe here the rare clinical manifestations of a 55-year-old previously healthy man with pituitary apoplexy harboring headache, combined palsies involving cranial nerves III to VI, endocrinologic disturbances, and temporal lobe seizure. In addition, we discuss the temporal lobe seizure (and temporal lobe epilepsy) associated with pituitary adenoma based on the literature. CONCLUSIONS: Although further accumulation of clinical data is needed, we would like to emphasize the importance of recognition of temporal lobe seizure caused by pituitary apoplexy, and to suggest that early surgery could be considered as an option in patients displaying such a rare complication.

Indoleamine 2,3-dioxygenase 1 is highly expressed in glioma stem cells.

Recent research has revealed that glioblastoma (GBM) avoids the immune system via strong expression of indoleamine 2,3-dioxygenase 1 (IDO1). IDO1, an enzyme involved in tryptophan metabolism, is now proposed as a new target in GBM treatment, since several reports have demonstrated that IDO1 expression is related to GBM malignancy. On the other hand, it is well known that glioma stem cells (GSCs) are strongly related to the malignancy of GBM. However, there is as yet no report evaluating the relationship between GSCs and IDO1. We therefore examined the expression levels of IDO1 in GSCs in order to identify a new therapeutic target for GBM based on the immune systems of GSCs. In the present study, we employed human GBM cell lines (U-138MG, U-251MG) and patient-derived GSC model cell lines (0125-GSC, 0222-GSC). GSC model cell lines Rev-U-138MG and Rev-U-251MG were established by culturing U-138MG and U-251MG in serum-free media, while differentiated GBM model cell lines 0125-DGC and 0222-DGC were established by culturing 0125-GSC and 0222-GSC in serum-containing media. The expression levels of stem cell markers (Nanog, Nestin, Oct4 and Sox2) and IDO1 protein and mRNA were determined. Rev-U-138MG and Rev-U-251MG formed spheres and their expression levels of stem cell markers were increased as compared to U-138MG and U-251MG. On the other hand, 0125-DGC and 0222-DGC suffered breakdown of sphere formation, despite the original 0125-GSC and 0222-GSC forming spheres, and their expression levels of the markers were decreased. IDO1 expressions were strongly recognized in Rev-U-138MG, Rev-U-251MG, 0125-GSC and 0222-GSC as compared to U-138MG, U-251MG, 0125-DGC and 0222-DGC. These findings demonstrate that GSCs exhibit treatment resistance with immunosuppression via high expression levels of IDO1, and could represent a novel target for GBM treatment.