Intraventricular aneurysms--three case reports

Three rare cases of purely intraventricular aneurysms are described, including a unique aneurysm in the fourth ventricle. A 30-year-old female, a 47-year-old male, and an 11-year-old girl presented with disturbance of consciousness due to massive intraventricular hemorrhage. Digital subtraction angiography revealed an idiopathic peripheral aneurysm in the fourth ventricle in the first patient, and aneurysms in the lateral ventricle associated with moyamoya disease in the latter two patients. The former two aneurysms were treated surgically and histologically confirmed to be pseudoaneurysms. The latter aneurysm disappeared spontaneously within 2 months after onset. The aneurysm in the lateral ventricle was resected via a parietal corticotomy with stereotactic insertion of an 8-Fr silicone tube to guide the approach route. This method was very useful because computerized neuronavigation was not available. The aneurysm in the fourth ventricle was resected via a midline suboccipital approach with C-1 laminectomy. Conservative treatment is usually recommended initially for patients with intraventricular aneurysm because spontaneous cure often occurs. We recommend direct surgery if the size of the aneurysm remains unchanged, because the risk of surgery has decreased recently owing to new techniques for neuronavigation.     

Revised new brain retractor: characteristics and new indications--technical note

Revisions were made to our new brain retractor with respect as follows. A knob was added to each shaft of the new brain retractor to facilitate handling. The angle between the shaft and the blade can now be adjusted from 60 to 135 degrees, which is useful in deep, narrow operative fields. Three blade lengths (20, 30, and 40 mm) are now available. The new retractor is entirely made from titanium. This revised brain retractor is very useful for the dissection of sylvian and interhemispheric arachnoid membranes, as well as in the extirpation of intracerebral masses via corticotomy.     

Polymeric micellar paclitaxel phosphorylates Bcl-2 and induces apoptotic regression of androgen-independent LNCaP prostate tumors

BACKGROUND: Paclitaxel has been difficult to evaluate in preclinical tumor model systems because its poor solubility requires a Cremophor EL formulation, which results in lethal anaphylaxis. We tested the effectiveness of a novel polymeric micellar paclitaxel on androgen-independent tumor growth in the LNCaP tumor model. METHODS: Athymic male mice bearing LNCaP tumors were castrated and allowed to grow until their PSA levels increased to three times above precastration levels. The animals were then treated with 0.5 mg intravenous polymeric micellar paclitaxel once daily for the first 5 days of a 3-week cycle. In total, three cycles were given. Tumor volume and serum PSA levels were measured weekly to monitor tumor progression. RESULTS: In vitro mitogenic assays demonstrated that polymeric micellar paclitaxel was effective in inhibiting LNCaP cell growth with an IC(50) of 5 nM. Paclitaxel precipitated apoptosis in vitro at a concentration of 1 nm and higher, confirmed by DNA laddering. Western blotting demonstrated that paclitaxel treatment phosphorylated and inactivated Bcl-2. In mice bearing LNCaP tumors treated with micellar paclitaxel, tumors regressed rapidly with the commencement of micellar paclitaxel treatment. Tumor size decreased 91% and PSA level decreased 96% after three cycles of treatment. TUNEL immunostaining of the tumor treated with micellar paclitaxel showed marked apoptosis when compared with the control. No significant side effects or mortality was observed in the micellar paclitaxel group (n = 7). In contrast, all (n = 7) mice treated with conventional Cremophor EL paclitaxel died within 1 day of injection. CONCLUSIONS: The polymeric micellar paclitaxel formulation is water-soluble and capable of inducing complete response in mice bearing androgen-independent LNCaP tumors. The lack of toxicity of polymeric micellar paclitaxel permits in vivo preclinical testing of paclitaxel-based combination regimens.     

The pineal gland is not essential for circadian expression of rat period homologue (rper2) mRNA in the suprachiasmatic nucleus and peripheral tissues

To investigate the functional involvement of the pineal gland in circadian expression of the rat period homolog gene (rPer2) in the suprachiasmatic nucleus (SCN) and peripheral tissues, we performed Northern blot analysis in tissues from pinealectomized rats. The ectomy did not have any significant effects on rPer2 mRNA expression patterns both in a daily light-dark condition and in a constant darkness. These results suggest that the rhythmic secretion of pineal melatonin is not essential for the circadian expression of clock genes in the SCN and other peripheral tissues of rats.     

Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters

PurposeWe have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production.MethodsIntracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs.ResultsBCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time.ConclusionsBCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration.     

Hyperlipidemia as a risk factor for Trousseau syndrome-related cerebral infarction in patients with advanced gastrointestinal cancer

Trousseau syndrome-related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome-related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective cohort study consecutively enrolled 878 patients with unresectable GI cancer who received chemotherapy at the Multidisciplinary Treatment Cancer Center, Kurume University Hospital (Kurume, Japan) between April 2014 and March 2020. Patients with colorectal cancer (n=308) were the most common, followed by those with pancreatic (n=242), gastric (n=222) and biliary tract (n=59) cancer, neuroendocrine tumors (n=34) and duodenal cancer (n=11). Among the 878 patients, Trousseau syndrome-related cerebral infarction occurred in 8 (0.9%) patients with a median age of 70.5 years (range, 58–75 years), and 50% of the patients were male (4/8). In total, 3 patients had gastric cancer, 3 had pancreatic cancer and 2 had biliary tract cancer. A greater percentage of patients with Trousseau syndrome-related cerebral infarction had hyperlipidemia (38.0%) than those without (8.2%; P=0.005). Hyperlipidemia was a risk factor for occurrence of Trousseau syndrome-related cerebral infarction with an odds ratio of 7.009 (95% confidence interval, 1.785-27.513). Trousseau syndrome-related cerebral infarction developed during GI chemotherapy was rare and hyperlipidemia may predict its onset.     

The relationship between intraocular pressure and refractive error adjusting for age and central corneal thickness

PURPOSE: To investigate the relationship between intraocular pressure (IOP) and refractive errors after adjusting for age, central corneal thickness (CCT), and other related factors. METHODS: IOP, CCT and refractive errors were measured in the right eyes of 1855 subjects, aged 40-82 years, in a cross-sectional study design. Subjects were divided into groups by refractive status: hyperopia, emmetropia, mild myopia, moderate myopia, or high myopia. With adjustments for age, CCT, blood pressure, obesity, education, hypertension, diabetes, and smoking status, IOP was estimated for each refractive status using a general linear model. RESULTS: IOP increased with advancing degrees of myopia, even after adjustment for age, CCT, and other related factors (p = 0.011). Estimated IOP of moderate myopia was significantly higher than that of emmetropia (p = 0.022). CONCLUSIONS: Our results confirm the positive association between IOP and increasing degrees of myopia. This finding would support the hypothesis that the relationship between glaucoma and myopia might be pressure mediated.     

Inhibition of homodimerization of Toll-like receptor 4 by curcumin

Toll-like receptors play a key role in sensing microbial components and inducing innate immune responses. Ligand-induced dimerization of TLR4 is required for the activation of downstream signaling pathways. Thus, the receptor dimerization may be one of the first lines of regulation in activating TLR-mediated signaling pathways and induction of subsequent immune responses. LPS induces the activation of NF-kappaB and IRF3 through MyD88- or TRIF-dependent pathways. Curcumin, a polyphenol found in the plant Curcuma longa, has been shown to suppress the activation of NF-kappaB induced by various pro-inflammatory stimuli by inhibiting IKKbeta kinase activity in MyD88-dependent pathway. Curcumin also inhibited LPS-induced IRF3 activation. These results imply that curcumin inhibits both MyD88- and TRIF-dependent pathways in LPS-induced TLR4 signaling. However, in TRIF-dependent pathway, curcumin did not inhibit IRF3 activation induced by overexpression of TRIF in 293T cells. These results suggest that TLR4 receptor complex is the molecular target of curcumin in addition to IKKbeta. Here, we report biochemical evidence that phytochemicals (curcumin and sesquiterpene lactone) inhibit both ligand-induced and ligand-independent dimerization of TLR4. Furthermore, these results demonstrate that small molecules with non-microbial origin can directly inhibit TLRs-mediated signaling pathways at the receptor level. These results imply that the activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain dietary phytochemicals we consume daily.