Identifying prognostic predictors for postoperative pituitary neuroendocrine tumour recurrence: an integrated clinical, radiological, and immunohistochemistry assessment.

OBJECTIVE: Pituitary neuroendocrine tumours (PitNETs) are the second most common type of intracranial tumour. Several studies have explored the prognostic factors for PitNETs. However, prognostic factors for postoperative PitNET recurrence remain not fully understood. This study aimed to explore potential prognostic factors for PitNET recurrence, such as surrounding tissue invasion and the extent of surgical resection in patients with postoperative PitNETs. METHODS: We included 106 patients who underwent PitNET surgery between 2013 and 2018, dividing them into two groups: those with recurrence and those without recurrence. Tumours were classified based on demographics, neuroradiological, and immunohistological characteristics. Univariate and multivariate analyses were used to determine factors predicting recurrence. Kaplan-Meier plots and log-rank tests were used to analyse each independent factor based on the cumulative 5-year recurrence rate. RESULTS: During the 5-year follow-up period, 29.2% of the patients (n = 31) had disease recurrence. Univariate analysis showed that predictors of recurrence included cavernous and sphenoid sinus invasions, optic chiasm compression, larger tumour volume, giant adenoma >4 cm, and gross total resection (GTR). Multivariate analysis showed that lactotroph tumour type, sphenoid sinus invasion, and GTR were independent predictors. Kaplan-Meier analysis revealed significant differences in the 5-year recurrence rate among the three independent predictors, with significantly lower recurrence rate in patients with lactotroph tumours and GTR, and a significantly higher recurrence risk in patients with sphenoid sinus invasion. CONCLUSIONS: Lactotroph tumour type, sphenoid sinus invasion, and GTR are independent predictors of postoperative PitNET recurrence. This study provides insights into the factors affecting postoperative PitNET recurrence.

PitNETs are the second most common intracranial tumour typePrognostic factors for postoperative PitNET recurrence remain not fully understoodWe explored potential prognostic factors in patients with postoperative PitNETsProlactin secretion and GTR failure were independent recurrence predictorsProliferative factors did not correlate with recurrence.

Significant perioperative parameters affecting postoperative complications within 30 days following craniotomy for primary malignant brain tumors.

BACKGROUND: The occurrence of postoperative complications within 30 days (PC1M) of a craniotomy for the removal of a primary malignant brain tumor has been associated with a poor prognosis. However, it is still unclear to early predict the occurrence of PC1M. This study aimed to identify the potential perioperative predictors of PC1M from its preoperative, intraoperative, and 24-h postoperative parameters. METHODS: Patients who had undergone craniotomy for primary malignant brain tumor (World Health Organization grades III and IV) from January 2011 to December 2020 were enrolled from a databank of Kaohsiung Veterans General Hospital, Taiwan. The patients were classified into PC1M and nonPC1M groups. PC1M was defined according to the classification by Landriel et al. as any deviation from an uneventful 30-day postoperative course. In both groups, data regarding the baseline characteristics and perioperative parameters of the patients, including a new marker-kinetic estimated glomerular filtration rate, were collected. Logistic regression was used to analyze the predictability of the perioperative parameters. RESULTS: The PC1M group included 41 of 95 patients. An American Society of Anesthesiologists score of > 2 (aOR, 3.17; 95% confidence interval [CI], 1.19-8.45; p = 0.021), longer anesthesia duration (aOR, 1.16; 95% CI, 0.69-0.88; p < 0.001), 24-h postoperative change in hematocrit by > - 4.8% (aOR, 3.45; 95% CI, 1.22-9.73; p = 0.0019), and 24-h postoperative change in kinetic estimated glomerular filtration rate of < 0 mL/min (aOR, 3.99; 95% CI, 1.52-10.53; p = 0.005) were identified as independent risk factors for PC1M via stepwise logistic regression analysis. When stratified according to the age of ≥ 65 years (OR, 11.55; 95% CI, 1.30-102.79; p = 0.028), the reduction of kinetic estimated glomerular filtration rate was more robustly associated with a higher risk of PC1M. CONCLUSIONS: Four parameters were demonstrated to significantly influence the risk of PC1M in patients undergoing primary malignant brain tumor removal. Measuring and verifying these markers, especially kinetic estimated glomerular filtration rate, would help early recognition of PC1M risk in clinical care.

The Antimicrobial Effects of Colistin Encapsulated in Chelating Complex Micelles for the Treatment of Multi-Drug-Resistant Gram-Negative Bacteria: A Pharmacokinetic Study.

Background: Infections caused by multi-drug-resistant Gram-negative bacteria (MDR-GNB) are an emerging problem globally. Colistin is the last-sort antibiotic for MDR-GNB, but its toxicity limits its clinical use. We aimed to test the efficacy of colistin-loaded micelles (CCM-CL) against drug-resistant Pseudomonas aeruginosa and compare their safety with that of free colistin in vitro and in vivo. Materials and methods: We incorporated colistin into chelating complex micelles (CCMs), thus producing colistin-loaded micelles (CCM-CL), and conducted both safety and efficacy surveys to elucidate their potential uses. Results: In a murine model, the safe dose of CCM-CL was 62.5%, which is much better than that achieved after the intravenous bolus injection of 'free' colistin. With a slow drug infusion, the safe dose of CCM-CL reached 16 mg/kg, which is double the free colistin, 8 mg/kg. The area under the curve (AUC) levels for CCM-CL were 4.09- and 4.95-fold higher than those for free colistin in terms of AUC0-t and AUC0-inf, respectively. The elimination half-lives of CCM-CL and free colistin groups were 12.46 and 102.23 min, respectively. In the neutropenic mice model with carbapenem-resistant Pseudomonas aeruginosa pneumonia, the 14-day survival rate of the mice treated with CCM-CL was 80%, which was significantly higher than the 30% in the free colistin group (p < 0.05). Conclusions: Our results showed that CCM-CL, an encapsulated form of colistin, is safe and effective, and thus may become a drug of choice against MDR-GNB.

Lumbar paraspinal atypical spindle cell/pleomorphic lipomatous tumor: A report of a rare case.

The atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) was classified as a new tumor by the World Health Organization (WHO) in 2020. The tumor is benign and commonly occurs in the limbs. Paraspinal presentations are rare. A 38-year-old man presented at our clinic complaining of sudden onset back pain. No neurological deficit was found. The magnetic resonance imaging (MRI) revealed a well-defined heterogeneous mass in the left psoas muscle, from L1 to L3 extending over the L1 and L2 neuroforamen. The tumor was totally excised. Pathology led to an ASPLT diagnosis. Clinical symptoms improved and there was no postsurgical neurological deficit. This case of ASPLT, located in an uncommon location and present an unusual cluster of symptoms, could be treated by surgical excision, usually the first-treatment strategy. Totally, removal was achieved because there was a clear morphological margin. The risk of metastatic dissemination was minimal, though there remains a nonnegligible risk of local recurrence.

Rapid Onset of Relapsing Longitudinally Extensive Transverse Myelitis After Lumbar Spinal Surgery.

A 58-year-old woman experienced relapsing acute longitudinally extensive transverse myelitis that developed rapidly in 3 days after lumbar surgery. The patient had a history of systemic lupus erythematosus with acute transverse myelitis and had undergone plasmapheresis 16 years ago. New neurologic deficits including paraplegia of the lower limbs, sensory alterations, and bowel incontinence presented 3 days postoperatively. Magnetic resonance imaging revealed a long-segment hyperintense signal over the thoracic spine on T2-weighted imaging. Intravenous pulse therapy with high-dose corticosteroid was first used for 5 days but was ineffective. Plasmapheresis after pulse therapy resulted in improved neurologic deficit. The patient then underwent 6 months of rehabilitation therapy but was partially wheelchair bound. She no longer had bladder and bowel incontinence.

Hydroxytyrosol [2-(3,4-dihydroxyphenyl)-ethanol], a natural phenolic compound found in the olive, alters Ca2+ signaling and viability in human HepG2 hepatoma cells.

Hepatotoma is the leading type of primary liver cancer in adults and third cause of death in the world. Hydroxytyrosol is a natural phenol existing in olive (Olea europaea L.). Hydroxytyrosol is the chief ingredient of olive oil, which was early deemed to be the most robust antioxidant in olive oil. Hydroxytyrosol is known to inhibit various types of cancer by different methods. This study was aimed to delineate the action of hydroxytyrosol on viability and [Ca2+]i in HepG2 hepatoma cells. Fura-2 was used to detect [Ca2+]i, and WST-1 assays were applied to explore cell cytotoxicity. Hydroxytyrosol elicited [Ca2+]i raises. Eliminating external Ca2+ diminished the Ca2+ signal by 30%. Hydroxytyrosol-evoked Ca2+ influx was diminished by 20% by three inhibitors of store-operated Ca2+ channels and by a protein kinase C activator and an inhibitor. In the absence of Ca2+, thapsigargin eradicated hydroxytyrosol-provoked [Ca2+]i raises. Suppression of phospholipase C (PLC) with U73122, a PLC inhibitor, did not inhibit hydroxytyrosol-elicited [Ca2+]i raises. Hydroxytyrosol reduced cell viability. This cytotoxic action was not reversed by preincubation with BAPTA/AM, a cytosolic Ca2+ binder. In sum, in HepG2 hepatoma cells, hydroxytyrosol elicited [Ca2+]i raises by provoking PLC-unrelated discharge of Ca2+ from ER and Ca2+ influx through PKC-sensitive store-operated Ca2+ entry. In addition, hydroxytyrosol elicited Ca2+-dissociated cytotoxicity.

Adult Posterior Fossa Anaplastic Ependymoma, Case Series and Literature Review.

OBJECTIVE: Ependymomas are rare central nervous system tumors. The current treatment strategy is gross total tumor removal. Whether adjuvant therapy will be beneficial is controversial. We retrospectively analyzed 3 cases of World Health Organization (WHO) grade III posterior fossa anaplastic ependymomas treated with different treatment modalities. We aimed to identify possible treatment options for infratentorial WHO grade III anaplastic ependymoma in adults. METHODS: We performed a retrospective analysis of 3 patients diagnosed with infratentorial anaplastic ependymomas in our institution from 2016 to 2020. The demographic data were documented. This case series of 3 patients does not meet the Department of Health and Human Services definition of research and does not need Institutional Review Board approval. All patients' informed consents have been obtained. RESULTS: One patient underwent subtotal tumor resection combined with adjuvant radiotherapy and Gamma Knife radiosurgery while the other 2 patients underwent gross total tumor removal combined with Gamma Knife radiosurgery or adjuvant radiotherapy. Tumors recurred in the first patient 20 months later, while the other 2 patents did not develop recurrence. The modified Rankin scale scores of these patients were 1, 0, and 0. All patients are followed up with regular magnetic resonance imaging at our facility. CONCLUSIONS: The strategy for treating WHO grade III anaplastic ependymomas is controversial, but gross total tumor resection remains the key element. Adjuvant stereotactic radiosurgery after tumor removal might be considered if radiotherapy is not an option. The role of chemotherapy is unclear, and the use of chemotherapy should be tailored to individual patients.

Application of 3D-Printed Model in the Cervical Spine Osteochondroma Surgery: A Case Report.

A 73-year-old woman having a throat lump sensation and dysphagia for the past several months presented at our otorhinolaryngology outpatient clinic. A physical examination disclosed a protruding subepithelial mass over the right tonsil fossa. The mass was not tender and had no mucosal lesions or signs of active infection. Therefore, we arranged face and neck computed tomography scans, which reported a solitary osseous lesion over the anterior-right aspect of the C1-2 joint. Considering the rarity and unfamiliar anatomy of this disease, we built a 3D-printed model to assist with the surgical rehearsal of the procedure as well as with a preoperation discussion with the patient and her family. We arranged a combined Otolaryngology-Neurosurgery department approach after discussion with the neurosurgeon and successfully removed the lesion without sacrificing the overlying longus capitis muscle. The pathology examination revealed no evidence of malignancy. The final diagnosis was cervical spine solitary osteochondroma. The patient had a complete recovery of both oral cavity and normal swallowing function. No tumor recurred during the 3-year follow-up. On the basis of this case, in-house 3D-printing technology can offer a rapid, reliable model for an interdisciplinary team to use to enhance personalized presurgical planning, thus providing better patient engagement during hospitalization.

Secondary Pituitary Abscess from Mite.

A 30-year-old woman experienced nasal stuffiness followed by a progressive headache and reduced visual acuity for 3 weeks. She underwent an endoscopic endonasal transsphenoidal approach for pituitary spindle cell oncocytoma 13 months before the present admission. Magnetic resonance imaging revealed an intrasellar cystic lesion with a suprasellar extension. After endoscopic endonasal transsphenoidal approach for tumor removal, the histologic findings of inflammatory infiltration showed a pituitary abscess. Microscopy revealed mites and fungal hyphae. Cultures from the abscess showed Staphylococcus hyicus, Stenotrophomonas maltophilia, and Aspergillus sp. The patient received a 6-week antibiotic treatment, which completely resolved the clinical symptoms and cleared the magnetic resonance imaging findings.

Prognostic Nomogram of Predictors for Shunt-Dependent Hydrocephalus in Patients with Aneurysmal Subarachnoid Hemorrhage Receiving External Ventricular Drain Insertion: A Single-Center Experience and Narrative Review.

OBJECTIVE: This study aimed to create a prediction model with a radiographic score, serum, and cerebrospinal fluid (CSF) values for the occurrence of shunt-dependent hydrocephalus (SDHC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) and to review and analyze literature related to the prediction of the development of SDHC. METHODS: Sixty-three patients with aSAH who underwent external ventricular drain insertion were included and separated into 2 subgroups: non-SDHC and SDHC. Patient characteristics, computed tomography scoring system, and serum and CSF parameters were collected. Multivariate logistic regression was conducted to illustrate a nomogram for determining the predictors of SDHC. Furthermore, we sorted and summarized previous meta-analyses for predictors of SDHC. RESULTS: The SDHC group had 42 cases. Stepwise logistic regression analysis revealed 3 independent predictive factors associated with a higher modified Graeb (mGraeb) score, lower level of estimated glomerular filtration rate group, and lower level of CSF glucose. The nomogram, based on these 3 factors, was presented with significant predictive performance (area under curve = 0.895) for SDHC development, compared with other scoring systems (AUC = 0.764-0.885). In addition, a forest plot was generated to present the 12 statistically significant predictors and odds ratio for correlations with the development of SDHC. CONCLUSIONS: First, the development of a nomogram with combined significant factors had a good performance in estimating the risk of SDHC in primary patient evaluation and assisted in clinical decision making. Second, a narrative review, presented with a forest plot, provided the current published data on predicting SDHC.

Intracranial solitary fibrous tumor/hemangiopericytoma - A case series.

BACKGROUND: Intracranial solitary fibrous tumor/hemangiopericytoma (HPC) is a rare and aggressive tumor. We conducted this retrospective study to investigate the outcome of patients after treatment, the efficacy of postoperative adjuvant radiotherapy, and the factors not conducive to total resection. METHODS: We conducted a retrospective review of the medical records of patients harboring fresh intracranial solitary fibrous tumor/HPC treated from January 2009 to December 2019 in our hospital. We reviewed their clinical presentations, radiologic appearances, tumor size and location, extent of resection, estimate intraoperative blood loss, treatment modalities and results, and duration of follow-up. RESULTS: There were seven consecutive patients (three males and four females). The ages of the patients at the time of diagnosis ranged from 35 to 77 years (mean: 52.86 years). Five patients (71.43%) got tumor bigger than 5 cm in dimension and only 1 patient (14.29%) underwent gross total tumor resection in the first operation without complication. Five patients (71.43%) underwent postoperative adjuvant radiotherapy. Follow-up period ranged from 4.24 to 123.55 months and the median follow-up period was 91.36 months. Three patients had favorable outcome with Glasgow Outcome Scale (GOS) equal to 4; four patients had unfavorable outcome with GOS equal to 2 or 3. No mortality was happened. CONCLUSION: Gross total tumor resection in the initial surgery is very important to achieve a better outcome. Massive intraoperative bleeding and venous sinus or major vessels adjoining are factors not conducive to total resection. Radiotherapy can be administered as adjuvant therapy for cases showing an aggressive phenotype or not treated with gross total resection.

Investigation of effect of tectorigenin (O-methylated isoflavone) on Ca2+ signal transduction and cytotoxic responses in canine renal tubular cells.

Tectorigenin, a traditional Chinese medicine, is isolated from the flower of plants such as Pueraria thomsonii Benth. It is an O-methylated isoflavone, a type of flavonoid. Previous studies have shown that tectorigenin evoked various physiological responses in different models, but the effect of tectorigenin on cytosolic-free Ca2+ levels ([Ca2+]i) and cytotoxicity in renal tubular cells is unknown. Our research explored if tectorigenin changed Ca2+ signal transduction and viability in Madin-Darby Canine Kidney (MDCK) renal tubular cells. [Ca2+]iin suspended cells were measured by applying the fluorescent Ca2+-sensitive probe fura-2. Viability was explored by using water-soluble tetrazolium-1 as a fluorescent dye. Tectorigenin at concentrations of 5-50 µM induced [Ca2+]irises. Ca2+ removal reduced the signal by approximately 20%. Tectorigenin (50 µM) induced Mn2+ influx suggesting of Ca2+ entry. Tectorigenin-induced Ca2+ entry was inhibited by 10% by three inhibitors of store-operated Ca2+ channels, namely, nifedipine, econazole, and SKF96365. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin inhibited 83% of tectorigenin-evoked [Ca2+]irises. Conversely, treatment with tectorigenin abolished thapsigargin-evoked [Ca2+]irises. Inhibition of phospholipase C with U73122 inhibited 50% of tectorigenin-induced [Ca2+]irises. Tectorigenin at concentrations between 10 and 60 µM killed cells in a concentration-dependent fashion. Chelation of cytosolic Ca2+ with 1,2-bis (2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid/acetoxy methyl did not reverse tectorigenin's cytotoxicity. Our data suggest that, in MDCK cells, tectorigenin evoked [Ca2+]irises and induced cell death that was not associated with [Ca2+]irises. Therefore, tectorigenin may be a Ca2+-independent cytotoxic agent for kidney cells.

Cerebellar PACNS in an Elderly Patient Present as a Tumor-Like Mass Lesion: A case Report.

PURPOSE: PACNS has a broad spectrum of clinical manifestations without typical features, and its clinical diagnosis is challenging. We report an elderly patient of cerebellar PACNS (Primary angiitis of central nervous system) presented as a brain tumor by MRI, and primary angiitis was proven by pathology. CASE REPORT: We report an 81-year-old female who complained about vertigo for 3 weeks with right arm dysmetria. There were no other neurologic symptoms/signs, and the patient was free from headache. Brain CT showed a space-occupying lesion over the right cerebellum, and a high-grade glioma was suspected by brain MRI and MRS. The pathologic result of brain biopsy showed granulomatous variant of PACNS. The patient received immunosuppressant therapy as long-term therapy, and had favorable response during a 2-year follow up. CONCLUSION: Due to variations in clinical presentation and nonspecific findings on imaging studies, PACNS is not easily diagnosed, especially in the aged population. PACNS should be considered as one of the differential diagnoses of any CNS dysfunction. PACNS is also an exclusionary diagnosis, so although brain biopsy is limited for its low sensitivity, its application is still important to exclude the possibility of other diseases. Although there have been reports of fulminant cases, PACNS can be treated successfully with immunosuppressant as maintaining therapy.

Exploration of Niflumic Acid's Action on Ca²âº Movement and Cell Viability in Human Osteosarcoma Cells.

Niflumic acid, a drug used for joint and muscular pain, affected Ca²âº signaling in different models. However, the effect of niflumic acid on Ca²âº homeostasis and Ca²âº-related physiology in human osteosarcoma cells is unknown. This study examined the effect of niflumic acid on cytosolic free Ca²âº concentrations ([Ca²âº]i) in MG63 human osteosarcoma cells. Intracellular Ca²âº concentrations in suspended cells were monitored by using the fluorescent Ca²âº-sensitive dye fura- 2. Cell viability was examined by using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio- 1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1). In MG63 cells, niflumic acid at concentrations of 250-750 µM evoked [Ca²âº]i rises concentration-dependently. Niflumic acid-evoked Ca²âº entry was confirmed by Mn²âº-induced quenching of fura-2 fluorescence. This entry was inhibited by nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA), but was not affected by the PKC inhibitor GF109203X. In Ca²âº- free medium, treatment with the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin (TG) inhibited niflumic acid-evoked [Ca²âº]i rises. Conversely, treatment with niflumic acid abolished TG-evoked [Ca²âº]i rises. Inhibition of phospholipase C (PLC) with U73122 also partly reduced niflumic acid-evoked [Ca²âº]i rises. Niflumic acid killed cells at 200-500 µM in a concentration-dependent fashion. Chelating cytosolic Ca²âº with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/ AM (BAPTA/AM) did not reverse niflumic acid-induced cytotoxicity. Collectively, our data suggest that in MG63 cells, niflumic acid induced [Ca²âº]i rises by evoking PLC-dependent Ca²âº release from the endoplasmic reticulum, and Ca²âº entry via PKC-sensitive store-operated Ca²âº entry. Niflumic acid also induced Ca²âº-independent cell death.

The effect of gallic acid on cytotoxicity, Ca(2+) homeostasis and ROS production in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes.

Gallic acid, a polyhydroxylphenolic compound, is widely distributed in various plants, fruits and foods. It has been shown that gallic acid passes into blood brain barrier and reaches the brain tissue of middle cerebral artery occlusion rats. However, the effect of gallic acid on Ca(2+) signaling in glia cells is unknown. This study explored whether gallic acid affected Ca(2+) homeostasis and induced Ca(2+)-associated cytotoxicity in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes. Gallic acid (20-40 µM) concentration-dependently induced cytotoxicity and intracellular Ca(2+) level ([Ca(2+)]i) increases in DBTRG-05MG cells but not in CTX TNA2 cells. In DBTRG-05MG cells, the Ca(2+) response was decreased by half by removal of extracellular Ca(2+). In Ca(2+)-containing medium, gallic acid-induced Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (2-APB, econazole and SKF96365). In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin abolished gallic acid-induced [Ca(2+)]i increases. Conversely, incubation with gallic acid also abolished thapsigargin-induced [Ca(2+)]i increases. Inhibition of phospholipase C with U73122 abolished gallic acid-induced [Ca(2+)]i increases. Gallic acid significantly caused cytotoxicity in DBTRG-05MG cells, which was partially prevented by prechelating cytosolic Ca(2+) with BAPTA-AM. Moreover, gallic acid activated mitochondrial apoptotic pathways that involved ROS production. Together, in DBTRG-05MG cells but not in CTX TNA2 cells, gallic acid induced [Ca(2+)]i increases by causing Ca(2+) entry via 2-APB, econazole and SKF96365-sensitive store-operated Ca(2+) entry, and phospholipase C-dependent release from the endoplasmic reticulum. This Ca(2+) signal subsequently evoked mitochondrial pathways of apoptosis that involved ROS production.

CCM-AMI, a Polyethylene Glycol Micelle with Amifostine, as an Acute Radiation Syndrome Protectant in C57BL/6 Mice.

Acute radiation syndrome results from radiation exposure, such as in accidental nuclear disasters. Safe and effective radioprotectants, mitigators, and treatment drugs must be developed as medical countermeasures against radiation exposure. Here, the authors evaluated CCM-Ami, a novel polyethylene glycol micelle encapsulated with amifostine, for its radioprotective properties after total-body irradiation from a 60Co source. Male C57BL/6 mice (6-8 wk old) were intravenously injected with 45 mg kg(-1) of CCM-Ami 90 min before exposure to 7.2 and 8.5 Gy irradiation at a dose rate of 0.04 Gy min(-1). Both survival benefit and hematopoietic protection were observed after prophylactic CCM-Ami administration when compared with the effects measured in excipient control and amifostine groups. Pharmacokinetic results showed that after the intravenous injection, the plasma concentration of WR-1065, the active form of amifostine, was higher in CCM-Ami-treated mice than in amifostine-treated mice. These findings suggest that CCM-Ami-mediated hematopoietic protection plays a key role in enhancing survival of mice exposed to radiation toxicity and thus indicate that CCM-Ami is a radioprotectant that can be used safely and effectively in nuclear disasters.

The involvement of mitochondrial apoptotic pathway in eugenol-induced cell death in human glioblastoma cells.

Eugenol, a natural phenolic constituent of clove oil, has a wide range of applications in medicine as a local antiseptic and anesthetic. However, the effect of eugenol on human glioblastoma is unclear. This study examined whether eugenol elevated intracellular free Ca(2+) levels ([Ca(2+)]i) and induced apoptosis in DBTRG-05MG human glioblastoma cells. Eugenol evoked [Ca(2+)]i rises which were reduced by removing extracellular Ca(2+). Eugenol-induced [Ca(2+)]i rises were not altered by store-operated Ca(2+) channel blockers but were inhibited by the PKC inhibitor GF109203X and the transient receptor potential channel melastatin 8 (TRPM8) antagonist capsazepine. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) abolished eugenol-induced [Ca(2+)]i rises. The phospholipase C (PLC) inhibitor U73122 significantly inhibited eugenol-induced [Ca(2+)]i rises. Eugenol killed cells which were not reversed by prechelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM). Eugenol induced apoptosis through increasing reactive oxygen species (ROS) production, decreasing mitochondrial membrane potential, releasing cytochrome c and activating caspase-9/caspase-3. Together, in DBTRG-05MG cells, eugenol evoked [Ca(2+)]i rises by inducing PLC-dependent release of Ca(2+) from the endoplasmic reticulum and caused Ca(2+) influx possibly through TRPM8 or PKC-sensitive channels. Furthermore, eugenol induced the mitochondrial apoptotic pathway.

Intraspinal tumors: analysis of 184 patients treated surgically.

BACKGROUND: Intraspinal tumors are rare central nervous system neoplasms. The reported clinical features of intraspinal tumors have varied in previous studies. We present here the cases of 184 patients with intraspinal tumors treated surgically in our hospital and a review of the literature. METHODS: We conducted a retrospective review of 184 patients with intraspinal tumors who underwent surgical treatment in our institution between 2002 and 2013. Their age, sex, initial presentation, tumor location, level of affected vertebral column, histological diagnosis, and primary origin of the metastatic tumor were reviewed and analyzed. RESULTS: Of these 184 patients, 97 (52.7%) were men and 87 (47.3%) were women. The mean age was 56.3 years (range 7-83 years). A total of 102 (55.4%) had primary tumors, while 82 (44.6%) patients had developed metastatic tumors. The histological diagnosis of the primary tumors included 55 (53.9%) schwannomas, 16 (15.7%) meningiomas, six (5.9%) ependymomas, five (4.9%) neurofibromas, three (2.9%) hemangiomas, two (2.0%) hemagioblastomas, and 15 (14.7%) other tumor types. The most common primary sites of the metastatic tumors were the lung and breast. CONCLUSION: Primary tumors were more numerous than metastastic tumors in our series of patients. For the primary tumors, our study showed a higher proportion of nerve sheath cell tumors (schwannomas and neurofibromas) and fewer meningiomas and neuroepithelial tumors compared with reports from non-Asian countries. In addition, the lung was the most common origin of the metastatic tumors and more than half of these tumors were located at the thoracic spine. Back pain and radicular pain were the most common presentations in patients with intraspinal tumors.

Dyspnea and choking as presenting symptoms in primary medulla oblongata germinoma.

BACKGROUND: The medulla oblongata is the lower half of the brainstem. It contains the cardiac, respiratory, vomiting, and vasomotor centers and deals with autonomic functions such as breathing, heartbeat, and blood pressure. Primary medulla oblongata germinoma is very rare and less than 20 cases have been reported in the English literature. CASE DESCRIPTION: A 22-year-old female without any particular past medical history presented to us in October 2012 with the chief complaint of dyspnea and frequent choking for 1 month. Neurological examination revealed lower cranial nerve palsies and nystagmus. Her brain computed tomography (CT) and brain magnetic resonance imaging (MRI) demonstrated a mass lesion at the dorsal surface of medulla oblongata with extension into the inferior fourth ventricle and foramen magnum. She underwent bilateral suboccipital craniotomy and C1 laminoplasty with the grossly total resection of the tumor. The histological examination of the tumor proved germinoma. Postoperative adjuvant radiotherapy was arranged. The latest brain MRI and whole spine MRI done 1 year after surgery showed neither residual nor recurrent tumor in the whole axis. She is regularly followed-up at our outpatient department and is doing well except having left vocal cord palsy, which occurred before surgery. CONCLUSION: Medulloblastoma, ependymoma, glioma, hemangioblastoma, and cavernous angioma are common intraaxial tumors in the medulla oblongata and fourth ventricle. Intracranial germ cell tumors originate from extragonadal seminal cells and have been found in 0.4-3.4% of patients with primary central nervous system (CNS) tumors in Western countries, while the incidence is reported to be 5-8 times greater in Japan and the Far East. Although germinoma of medulla oblongata is rare and difficult to diagnose preoperatively, it should be included in the differential diagnosis of medulla masses with fourth ventricle extension, especially in Asian population.