Vascular endothelial growth factor immobilized on platinum microcoils for the treatment of intracranial aneurysms: experimental rat model study

Platinum microcoils coated with immobilized recombinant human vascular endothelial growth factor (rhVEGF) were prepared and the effectiveness for the embolization of aneurysms was investigated using a rat model. Platinum coils were prepared by successive deposition of cationic polyethyleneimine and anionic heparin, and VEGF was immobilized through affinity interaction with heparin. Unmodified, heparin-coated, or rhVEGF-immobilized platinum coil segments were inserted into the ligated external carotid arteries at the bifurcation of the common carotid artery (CCA) of adult female rats. The bifurcation segments of the CCA were harvested 2 weeks after the coil placement. rhVEGF-immobilized coils showed significantly greater endothelial formation at the aneurysm orifice and cell infiltration in the aneurysm body compared with the unmodified and heparin-coated coils. The percentage of sac occlusion was significantly greater in the rhVEGF-immobilized group (77.53 +/- 27.58%) than in the heparin-coated group (44.81 +/- 38.30%) and unmodified group (34.99 +/- 28.15%). Scanning electron microscopy showed a tendency for more fibrotic and cellular collections on the coil surface and more tissue mass filling in the coil lumen in the rhVEGF-immobilized group. Platinum microcoils coated with immobilized rhVEGF may be effective for the obliteration of aneurysms.     

Intense (18)F-FDG uptake in brown fat can be reduced pharmacologically.

Physiologic (18)F-FDG uptake in areas of supraclavicular fat in humans ("USA-Fat") has recently been recognized as (18)F-FDG uptake in apparent brown adipose tissue (BAT) using fused PET/CT technology. In this study, we evaluated (18)F-FDG uptake in BAT of rats to determine whether pharmacologic or physiologic interventions affect the uptake, knowing that BAT has a high density of adrenergic innervation. METHODS: Seven- to 8-wk-old female Lewis rats receiving intravenous (18)F-FDG injections were examined under various conditions to evaluate (18)F-FDG biodistribution into interscapular BAT and major organs. In series 1, rats were given ketamine-based anesthesia or were exposed to cold (4 degrees C for 4 h) to determine whether these interventions increased (18)F-FDG uptake in BAT. In series 2, anesthetized rats (ketamine-based anesthesia) were given propranolol, reserpine, or diazepam intraperitoneally before (18)F-FDG injection to determine whether the drug reduced (18)F-FDG uptake in BAT. The control and treated groups in series 2 were also evaluated with (18)F-FDG PET/CT imaging. RESULTS: In series 1, anesthesia or exposure to cold increased (18)F-FDG uptake in BAT to levels 14-fold and 4.9-fold, respectively, greater than the control nonstimulated values. BAT uptake was high, comparable to that in the brain. In series 2, (18)F-FDG uptake in BAT was significantly decreased to less than 30% of the control level after propranolol or reserpine (P < 0.05). Diazepam did not significantly decrease (18)F-FDG uptake in BAT. (18)F-FDG PET/CT findings reflected these biodistribution data: The control and diazepam groups exhibited intense (18)F-FDG uptake in BAT, whereas the propranolol and reserpine groups showed only faint to mild (18)F-FDG uptake in BAT. Among several organs whose (18)F-FDG uptake was affected after predosing drugs, the heart exhibited considerable decreases in tracer uptake with propranolol or reserpine. CONCLUSION: This rodent study demonstrated that BAT can exhibit high (18)F-FDG uptake under stimulated conditions including exposure to cold and that propranolol or reserpine treatment can remarkably reduce the high (18)F-FDG uptake in BAT. The effect of these drugs on (18)F-FDG uptake in human BAT, as well as on tracer accumulation in other organs, should carefully be evaluated clinically to minimize the USA-Fat artifact.     

Functional characterization of single nucleotide polymorphisms with amino acid substitution in CYP1A2, CYP2A6, and CYP2B6 found in the Japanese population

As a part of the studies conducted by the Pharma SNPs Consortium (PSC), the enzyme activities of CYP1A2, CYP2A6 and CYP2B6 variants with altered amino acids as a result of single nucleotide polymorphisms (SNPs) found among the Japanese population were analyzed under a unified protocol using the same lots of reagents by the laboratories participating in the PSC. Mutations in CYP1A2, CYP2A6 and CYP2B6 were introduced by site-directed mutagenesis and the wild type and mutated CYP molecules were expressed in Escherichia coli. The expressed cytochrome P450s were purified and the enzyme activities were measured in reconstitution systems. CYP1A2 and CYP1A2Gln478His did not show any differences in 7-ethoxyresorufin O-deethylase activity. CYP2A6 and CYP2A6Glu419Asp metabolized coumarin to form 7-hydroxycoumarin in a similar manner, whereas CYP2A6Ile471Thr showed low activity compared to the wild-type CYP2A6. CYP2B6, CYP2B6Pro167Ala and CYP2B6Arg487Cys showed the same activity for 7-ethoxy-4-triflouromethyl-coumarin O-deethylation. However, CYP2B6Gln172His was roughly twice as active as CYP2B6 and the other CYP2B6 variants for 7-ethoxy-4-triflouromethylcoumarin O-deethylation activity. Although higher inter- and intra-laboratory variations were observed for the calculated Km and V(max) values because the studies were conducted in several different laboratories, the degree of variations was reduced by the increased number of analyses and the adoption of a simple analysis system.     

Suppression of glucose absorption by various health teas in rats

The inhibitory effects on the intestinal digestion and absorption of sugar of health teas that claim beneficial dietary and diabetes-controlling effects were compared in rats using portal cannulae. The measured durations were the times during which the elevation of portal glucose levels resulting from continuous intragastric infusion of sucrose or maltose was suppressed by concentrated teas. The teas investigated included salacia oblonga, mulberry, guava, gymunema, taheebo, yacon, and banaba. The duration of the inhibitory effect on the sucrose load of salacia oblonga, mulberry, and guava were 110 min, 20 min, and 10 min, respectively. In contrast, gymunema, taheebo, yacon, and banaba had no significant effect on the continuous infusion of sucrose. These results suggest that there is considerable difference in the efficacy of commercial health teas in influencing glucose absorption.     

Hydrocephalus after intraventricular hemorrhage in eclamptic woman with HELLP syndrome.

We report the first case of an obstructive hydrocephalus after intraventricular hemorrhage in a woman with HELLP syndrome and eclampsia. A 25-year-old primiparaous woman had severe preeclampsia at 36 weeks of gestation. She complained of epigastric pain and nausea. The levels of AST, ALT, and LDH were 539, 560, and 1051 IU/L, respectively; the platelet count was 101 x 109/L. Cesarean section was promptly performed. Intraoperatively, she had a first convulsion. The CT scan revealed only mild brain edema. The platelet count deteriorated to 30 x 109/L at 5 hour after the operation, and she had a second convulsion with an intraventricular hemorrhage. On the 6th post-cesarean day, she complained severe headache followed by coma. The CT scan revealed the enlargement of both lateral ventricles, indicating the occurrence of obstructive hydrocephalus. Drainage into cerebral ventricle was performed, resulting in the recovery of consciousness to a normal level.     

Cytochrome c and tumor necrosis factor-alpha values in serum and cerebrospinal fluid of patients with influenza-associated encephalopathy

Cytochrome c and tumor necrosis factor-alpha concentrations were measured in serum and cerebrospinal fluid samples from 10 patients with influenza-associated encephalopathy. In the acute exacerbation phase, serum tumor necrosis factor-alpha and cytochrome c values were high in patients with a poor prognosis. In the convalescent phase, cerebrospinal fluid cytochrome c values increased remarkably in patients with subsequent brain atrophy.     

Feasibility and clinical significance of endoluminal assessment by transvaginal salpingoscopy during transvaginal hydrolaparoscopy in infertile women

STUDY OBJECTIVE: To investigate the feasibility and clinical usefulness of transvaginal salpingoscopy (TS) during transvaginal hydrolaparoscopy (THL) in infertile women. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: Jichi Medical School, Tochigi, Japan. PATIENTS: One hundred thirty infertile women, aged 22 to 43 years, who underwent THL. INTERVENTIONS: Transvaginal salpingoscopy findings in comparison with THL findings. MEASUREMENTS AND MAIN RESULTS: Transvaginal salpingoscopy could be performed in 41.0% of the attempted tubes. In comparing rates of successful TS in relation to tubal patency, tubal morphology, and past Chlamydia trachomatis infection, patent tubes and normal-appearing tubes classified with normal morphology had a significantly higher TS success rate. However, past C. trachomatis infection did not affect the success of TS. There was a significant correlation between salpingoscopic and laparoscopic findings; however, there were no significant correlations between salpingoscopic findings and C. trachomatis antibody titers. CONCLUSIONS: These findings suggest that TS can be performed simultaneously in some infertile women undergoing THL especially those with patent tubes or with normal-appearing tubes. Further studies are required to show the usefulness of intratubal exploration in assessing tubal infertility.     

Enhancement of immunoreactivity for endothelin-1 and endothelin-converting enzyme-1 in the cadmium-treated rat thoracic aorta

Male rats received daily intraperitoneal injections of cadmium sulfate (2.0 mg/kg) for 3, 6, and 8 days (cadmium-treated groups) or physiological saline for 8 days (control group). The thoracic aortae from both groups were used for electron microscopy and immunocytochemistry for big endothelin (ET)-1, ET-1 and ET-converting enzyme (ECE)-1, and the blood plasma and homogenized thoracic aortae were prepared for assays of big ET-1 and ET-1 concentrations. A remarkable increase in the number of Weibel-Palade (WP) bodies, enhanced immunoreactivities for ET-1 and ECE-1 along the endothelium, and elevated concentrations of ET-1 in the blood plasma as well as in homogenized thoracic aortae were observed in the cadmium-treated groups. However, immunoreactivity for big ET-1 and the plasma and aortic tissue concentrations of big ET-1 did not show any significant changes between the control and cadmium-treated groups. By immunoelectron microscopy, immunoreactivities for ET-1 and ECE-1 were much more pronounced in the increased WP bodies. Since WP bodies are involved in the extracellular release of ET-1 in the manner of a regulated pathway, these findings indicate that cadmium administration induces the enhanced release of ET-1, which is actively processed by ECE-1 in the WP bodies.