AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study.

Neuronavigation has become an effective therapeutic modality and is used routinely for intra-axial tumor removal. This retrospective study was conducted to evaluate the clinical impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas. Between 1990 and 2002, 76 adult patients with pathologically confirmed malignant astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated using neuronavigation with conventional microneurosurgery and the other 34 were treated with conventional microneurosurgery alone. Postoperative early MRI with contrast enhancement was done, and gross total resection was defined as the complete absence of residual tumor. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80), use of neuronavigation, and gross total resection were significantly associated with longer survival. However, when the data were submitted to multivariate analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were independent prognostic factors. The median survival periods of patients receiving gross total resection (vs. partial resection) and neuronavigation (vs. no neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The percentage of a gross total resection was significantly higher in the neuronavigation group compared to that in the no-navigation group (64.3 % vs. 38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in 6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without neuronavigation, respectively, although this difference was not statistically significant. Our results showed that neuronavigation increases the radicality in the resection of malignant astrocytomas and is objectively useful for improving survival time.     

Portsite and intraabdominal metastases of unsuspected gallbladder carcinoma after laparoscopic cholecystectomy: Report of a case

We herein report a rare case of portsite metastasis of gallbladder carcinoma which occurred after laparoscopic cholecystectomy. A 64-year-old man underwent laparoscopic cholecystectomy at another hospital for symptomatic cholecystolithiasis. The histological examination revealed an adenocarcinoma of the gallbladder infiltrating the entire wall. Despite the physician's advice the patient refused any additional treatment. Thirteen months after surgery he visited our hospital because of a palpable mass at the scar of the right trocar incision. The nodule was removed and histological examination confirmed metastasis from the gallbladder carcinoma.     

Ultrastructure of capillary permeability in human brain tumor: primary meningeal malignant melanoma

The tumor vessels of a primary meningeal malignant melanoma were studied by electron microscopy. There were numerous endothelial fenestrae and basal lamina abnormalities in the intrinsic tumor capillaries. They resembled the tumor vessels found in nonglial tumors, but were distinctly different from those seen in glial tumors with nonfenestrated capillaries. These findings were anticipated because leptomeninges have fenestrated capillaries.     

Factor VIII lability, protein C and other vitamin K-dependent proteins

The stability of factor VIII was studied in plasmas from patients on long-term warfarin therapy. The percent residual factor VIII activity (F.VIII:C) after incubation at 37 degrees C for 4 hr was higher in warfarinized patients than in normal subjects; 76.9 +/- 10.8% (mean +/- SD) of the initial F.VIII:C in the patients versus 61.6 +/- 5.8% in normal subjects (p less than 0.001). On the whole, neither protein C nor vitamin K-dependent coagulation factors except factor VII activity (F.VII:C) correlated with the residual F.VIII:C. There was a negative and weak correlation between the residual F.VIII:C at 4 hr and either the initial F.VIII:C or F.VII:C. Another experiment using protein C depleted plasma showed a relatively enhanced stability of F.VIII:C in the protein C deficiency. These results indicate that factor VIII is more stable in warfarinized plasma, and that protein C and vitamin K-dependent coagulation factors are not the sole, main factor responsible for such a phenomenon.     

Comparative promoting activities of phosphate salts on rat two-stage bladder carcinogenesis under conditions of equivalent urinary Na+ or K+ levels.

Promoting effects of Na or K phosphate salts on rat two-stage bladder carcinogenesis were compared. Animals were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and thereafter received 1.4% Na3PO4, 2.0% NaH2PO4, 1.0% K3PO4, or 2.5% KH2PO4, these dietary concentrations being selected because they result in approximately equal levels of Na+ and K+ in the urine, equivalent to moderate natriuresis or kaluresis in comparison with our previous data. Treatment with Na3PO4 or K3PO4 induced significant increase in urinary pH compared with control values, whereas urinary pH in the NaH2PO4 and KH2PO4 groups was comparable to control values. With regard to preneoplastic lesion development, both incidences and multiplicity were significantly increased in the groups given Na3PO4 or K3PO4 compared with both controls and NaH2PO4 or KH2PO4 groups, respectively. Furthermore, treatment with Na3PO4 significantly increased multiplicity of papillomas, accompanied by a tendency to increased incidence. No statistically significant difference in promoting potential between Na3PO4 and K3PO4 groups was evident. The present results thus suggest that tumor promotion under conditions of moderate natriuresis or kaluresis depends primarily on high urinary pH.     

Effects of Several Denervation Procedures on Distribution of Calcitonin Gene-Related Peptide and Substance P Immunoreactive in Rat Stomach

The effect of chemical deafferentation, vagotomy(VGX), and gangliosympathectomy (GSX) on the density offibers containing calcitonin gene-related peptide (CGRP)and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation bycapsaicin abolished the density of CGRP-immunoreactive(IR) fibers, not Sub.P-IR fibers. Ten days after VGX,the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reductionof CGRP-IR and Sub.P-IR fibers was seen in submucosaland muscular layers. GSX significantly reduced thedensity of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosaland muscular layers. Pretreatment with6-hydroxydopamine, a neurotoxin for noradrenergicnerves, did not affect the density of CGRP-IR fibers inthe gastric wall. The density of Sub.P-IR fibers in thegastric wall was not affected by GSX. These studiesindicate that the CGRP-IR and Sub.P-IR fibers in themucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and musclelayers, that a major portion of the CGRP-IR fibers inthe mucosa is of both vagal and spinal origin, and thata major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, thepresent results support that CGRP-IR fibers, notSub.P-IR fibers, in the rat stomach arecapsaicin-sensitive.     

Evaluation of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (sandwich therapy) for hepatocellular carcinoma

The significance of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (Sandwich therapy) for resectable hepatocellular carcinoma (HCC) was evaluated. One hundred and thirteen patients with solitary and less than 10 cm sized HCC who underwent radical hepatic resection were chosen for this study. Fifty-three patients received Sandwich therapy before surgery (Group A), and the remaining 60 patients under-went surgery without any preoperative treatments (Group B). Any background factors between two groups were not significantly different. The anticancer effects of this therapy were evaluated by histologic examination in 31 patients who had preoperative Sandwich therapy. In 22 of 31 patients (71%), the main nodules were completely necrotic. The ratios of patients with complete necrosis in daughter nodules were 7/12 (58%), in portal vein tumor emboli, 7/10 (70%), in intracapsular invasions, 11/21 (52%), in extracapsular invasions, 4/11 (36%). The 4-year disease-free survival rates in Group A and Group B were 56% and 27% respectively, and the rate of the former was significantly higher than that of the latter (p less than 0.05). The 4-year survival rates in Group A and Group B were 83% and 53% respectively. The rate of Group A was also significantly higher than that of Group B (p less than 0.01). We concluded that preoperative Sandwich therapy was very significant to obtain successful long-term disease-free survival and survival in regard to relatively early stage HCC.     

Effects of subacute toluene exposure on neuronal and glial marker proteins in rat brain

The behavior of marker proteins of neurons (gamma-enolase) and glial cells (alpha-enolase, beta-S100 protein and creatine kinase-B) was investigated quantitatively by using enzyme immunoassay systems in toluene-exposed rat brains. Three groups of animals were exposed to toluene vapor at 300 ppm, 1000 ppm, and 3000 ppm, respectively, 8 h/day, 6 days/week, for 2 weeks. After subacute repeated solvent exposure, both neuron-specific gamma-enolase and glial marker proteins displayed an overall concentration-dependent increase tendency in separate brain regions. In cerebrum, only the 3000 ppm group showed a significant increase in alpha-enolase by 27% and creatine kinase-B (CK-B) by 26%. alpha-Enolase and gamma-enolase exhibited a pronounced elevation in cerebellum relative to other brain regions, while beta-S100 protein appeared to be the most markedly altered marker in brainstem. The development of gliosis, which is a frequent phenomenon following CNS damage, is presumed to be responsible for the elevation of glial marker content. Energy metabolism disruption in brain tissues may also bring about the compensatory oversynthesis of glycolytic enzymes such as gamma-enolase, alpha-enolase and CK-B. The dose-dependent alteration patterns following toluene exposure suggest the feasibility of using these brain specific markers to evaluate solvent-induced CNS effects.