Repair of potentially lethal damage by total and quiescent cells in solid tumors following a neutron capture reaction

Purpose: We analyzed the time-course of changes in the sensitivity of total (proliferating + quiescent and quiescent (Q) cell populations within solid tumors in situ following a neutron capture reaction and compared it with that after γ-ray irradiation. Methods: After continuous labeling of proliferating cells with BrdU for 5 days, mice bearing SCC VII tumors received thermal neutron irradiation with or without a ¹⁰B-labeled compound (sodium [¹⁰B]borocaptate, BSH, or dl-p-[¹⁰B]boronophenylalanine, BPA), or γ-ray irradiation. From 5 min to 72 h after treatment, tumors were excised, minced, and trypsinized. Cell suspensions were incubated for 48 h with the cytokinesis blocker cytochalasin-B. The micronucleus frequency for BrdU-unlabeled cells, Q cells at treatment, was then determined by immunofluorescence staining for BrdU. The micronucleus frequency for total cells was obtained from tumors that had not been pretreated with BrdU labeling. The sensitivity was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (micronucleus frequency). Results: Overall, Q cells showed greater repair capacities than total cells. γ-Ray irradiation and neutron irradiation with BPA induced larger repair capacities in each cell population. In contrast, thermal neutron irradiation without a ¹⁰B-labeled compound induced the smallest repair capacity in both cell populations. The use of a ¹⁰B-labeled compound, especially BPA, widened the difference in sensitivity between total and Q cells, resulted in an increase in repair capacity in both cell populations, and made the repair patterns of the two cell populations look like those induced by γ-ray irradiation. Conclusion: Differences in sensitivity and repair patterns following the neutron capture reaction were thought to depend on differences in the distribution of the ¹⁰B-labeled compound between the proliferating and Q cell populations. Received: 18 February 1999 / Accepted: 4 June 1999     

Recent progress in the treatment of cardiovascular disease using olmesartan

Angiotensin II (Ang II) evokes inflammatory responses and plays a central role in atherosclerosis mediated by Ang II type 1 (AT₁) receptor. AT₁ receptor blockers (ARBs) prevent the diverse effects of Ang II. Unique molecule-specific, or off-target effects of ARBs are due to their slightly different structures, although all ARBs have common, or class, effects. In nonsignificant coronary stenotic lesions, it is important that we use aggressive medical treatments using ARBs in addition to statins and oral hypoglycemic agents, to induce the regression and stabilization of coronary plaque. This review focuses on current evidence regarding the molecule-specific effects of ARB olmesartan to prevent the increase in coronary atheroma volume.     

A case of Wilson’s disease with characteristic laparoscopic findings

A 44-year-old male was pointed out liver function abnormality by medical check-up. Blood examination and computed tomography showed liver cirrhosis. Then, he was referred to our hospital for further examination. After blood test, viral markers revealed previous infection of hepatitis B virus (HBV). We estimated the etiology of his liver disease as previous HBV infection. On laparoscopic examination, his liver surface was nodular with mixed yellowish nodules and ash gray to copper-colored nodules in the diameter of 3–10 mm. There were large regenerative nodules in segments 3 and 4. Large regenerative nodules and irregular steatosis were contradictory to HBV-related liver cirrhosis, so then we supposed Wilson’s disease. The amount of copper excretion in the urine was 326.6 μg (>100 μg/24 h). After D-penicillamine administration, urinary copper excretion increased to 2151.5 μg/24 h. Though hepatic copper concentration was 174.5 μg/g wet tissue (>200 μg/g wet tissue), his laboratory data fulfilled the Leipzig diagnostic criteria proposed by EASL. Laparoscopic examination with liver biopsy has advantages to survey many disease-specific findings on liver surface and to obtain adequate liver sample. Laparoscopic examination is one of the effective procedures for diagnosing relatively rare liver disease like Wilson’s disease.     

Intra-articular nodular fasciitis of the knee: a rare cause of recurrent hemarthrosis

A 20-year-old man presented with pain and recurrent hemarthrosis in the right knee. Magnetic resonance imaging of the knee showed a lesion with homogeneous low signal intensity on T1-weighted images and a heterogeneous, low to high signal intensity on T2-weighted images. At arthroscopy, the mass was located between the posterior cruciate ligament and the posterior knee joint capsule. The tumor was excised through a posterior approach and histologically diagnosed as a nodular fasciitis. Intra-articular nodular fasciitis is a very rare clinicopathologic entity. The current case showed the unique clinical feature of recurrent hemarthrosis at initial presentation, which has not been previously reported.     

Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

Aldosterone is implicated in the pathogenesis of several cardiovascular diseases, including ischemia reperfusion (I/R) and myocardial infarction, and also causes oxidative stress and inflammation in cardiovascular systems. Benidipine, a long-acting T- and L-type calcium channel blocker, reduces infarct size following myocardial I/R in rabbits. Benidipine also inhibits the production of aldosterone in vitro. However, the precise mechanism of this phenomenon in vivo remains unknown. We therefore evaluated whether benedipine has a beneficial role through the regulation of oxidative stress in myocardial I/R. C57BL/6J mice were subjected to 30?min of left ascending coronary I/R. Benidipine was administered orally at 3?mg?kg(-1) daily for 3 weeks without any changes in hemodynamic variables. Benidipine significantly reduced infarction size (13.4±2.5%) compared with controls (25.5±3.6%). Urinary 8-hydroxy-2' deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, increased significantly after I/R. I/R induced increases in 8-OHdG were significantly lower with benidipine. Local myocardial 8-OHdG was also elevated in I/R, but this augmentation was significantly suppressed with benidipine. The plasma aldosterone concentration (PAC) significantly increased 2 days after I/R and remained elevated at least 7 days after I/R. Treatment with benidipine significantly decreased I/R-induced elevation of the PAC. I/R-induced markers of fibrosis in hearts also reduced in benidipine. These results suggest that the administration of benidipine reduces myocardial infarct size as well as systemic oxidative stress after I/R. These phenomena are partially linked to reduced plasma aldosterone levels.     

A practical prediction model for early hematoma expansion in spontaneous deep ganglionic intracerebral hemorrhage

Objective

Early hematoma expansion is a known cause of morbidity and mortality in patients with intracerebral hemorrhage (ICH). The goal of this study was to identify clinical predictors of ICH growth in the acute stage.

Materials and methods

We studied 201 patients with acute (<6 h) deep ganglionic ICH. Patients underwent CT scan at baseline and hematoma expansion (>33% or >12.5 ml increase) was determined on the second scan performed within 24 h. Fourteen clinical and neuroimaging variables (age, gender, GCS at admission, hypertension, diabetes mellitus, kidney disease, stroke, hemorrhagic, antiplatelet use, anticoagulant use, hematoma density heterogeneity, hematoma shape irregularity, hematoma volume and presence of IVH) were registered. Additionally, blood pressure was registered at initial systolic BP (i-SBP) and systolic BP 1.5 h after admission (1.5 h-SBP). The discriminant value of the hematoma volume and 1.5 h-SBP for hematoma expansion were determined by the receiver operating characteristic (ROC) curves. Factors associated with hematoma expansion were analyzed with multiple logistic regression.

Results

Early hematoma expansion occurred in 15 patients (7.0%). The cut-off value of hematoma volume and 1.5 h-SBP were determined to be 16 ml and 160 mmHg, respectively. Hematoma volume above 16 ml (HV > 16) ([OR] = 5.05, 95% CI 1.32–21.36, p = 0.018), hematoma heterogeneity (HH) ([OR] = 7.81, 95% CI 1.91–40.23, p = 0.004) and 1.5 h-SBP above 160 mmHg (1.5 h-SBP > 160) ([OR] = 8.77, 95% CI 2.33–44.56, p = 0.001) independently predicted ICH expansion. If those three factors were present, the probability was estimated to be 59%.

Conclusions

The presented model (HV > 16, HH, 1.5 h-SBP > 160) can be a practical tool for prediction of ICH growth in the acute stage. Further prospective studies are warranted to validate the ability of this model to predict clinical outcome.     

Fabrication of tough,anisotropic, chemical-crosslinker-free poly(vinyl alcohol) nanofibrous cryogels via electrospinning

PVA hydrogels with anisotropic structures have many biomedical applications; however, the hydrophilicity of PVA nanofibers degrades their mechanical properties, and the residual unreacted chemical crosslinkers are disadvantageous for medical use. Therefore, maintaining the stability of aqueous solutions without using crosslinkers is essential while synthesizing electrospun anisotropic PVA nanofibers. Herein, we developed a novel fabrication method for synthesizing tough, anisotropic, and chemical-crosslinker-free nanofibrous cryogels composed of poly(vinyl alcohol) (PVA) and glycerol (Gly) via electrospinning in conjunction with freeze–thawing treatment. Wide-angle X-ray diffraction, attenuated total reflection Fourier-transform infrared spectroscopy, and differential scanning calorimetry analysis revealed an enhanced crystallinity of the PVA and hydrogen bonds in the PVA/Gly nanofibers after freeze–thawing, thereby leading to improved stability of the PVA/Gly nanofiber in water. The scanning electron microscopy observation and tensile tests revealed that the addition of Gly improved both the orientation and the mechanical properties. The values of the toughness parallel and vertical to the fiber axis direction were 4.20 ± 0.63 MPa and 2.17 ± 0.27 MPa, respectively, thus revealing the anisotropy of this mechanical property. The PVA/Gly nanofibrous cryogel consisted of physically crosslinked biocompatible materials featuring toughness and mechanical anisotropy, which are favorable for medical applications including tissue engineering.

Fabrication of tough, anisotropic, and chemical crosslinker-free nanofibrous cryogels made from poly(vinyl alcohol) and glycerol via electrospinning in conjunction with freeze-thawing treatment which would be favorable for medical applications.     

The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon

The expression of a tight junction (TJ) component protein, claudin-4, in the enteric neurons was investigated in the rat distal colon by immunohistochemistry and RT-PCR. Claudin-4 immunoreactivity was detected in almost all neurofilament-positive enteric neurons both of the submucosal and the myenteric plexuses, and both of the cell bodies and the neurofibers. The immunoreactivity of enteric neurons for claudin-4 was divided into two types: strongly and weakly positive neurons. Especially in the myenteric plexus, the stained neurons were classified by Dogiel's morphological classification of enteric neurons. The strongly stained claudin-4 positive neurons show Dogiel type II morphology, while the weakly stained claudin-4 positive neurons show Dogiel type I morphology. These immunohistochemical data were supported by mRNA expression in the muscle plus submucosa preparation containing the submucosal and myenteric plexuses, as well as mucosa preparation. The physiological function of claudin-4 expressed on enteric neurons is unclear up to now. It is however suggested that claudin-4 expressed on enteric neurons might play roles for the neural activity, for example as insulation between neurofibers. In conclusion, the present study clearly shows that claudin-4 is expressed by enteric neurons. This is the first evidence that the neuron itself expresses the TJ component protein, claudin-4, in the nervous system.