Histological changes in the rabbit kidney induced by transarterial injection of a hypertonic sodium chloride solution

PURPOSE: To evaluate histological changes in normal renal tissue induced by the injection of a hypertonic liquid. MATERIALS AND METHODS: Transarterial injection was performed in 17 healthy rabbits at various rates of infusion and amounts of isotonic and hypertonic (7%) sodium chloride solutions. In group 1, 10 cc of isotonic sodium chloride solution was injected. In groups 2 and 3, 1-10 cc of hypertonic solution was injected at rates of 1.0 cc/sec and 0.05 cc/sec, respectively. After 20 minutes of hemostasis, renal weight measurements and histological examinations were performed. In three rabbits that received 10 cc of 7% sodium chloride, lung samples were also obtained, and histological changes were reviewed. RESULTS: There was no tissue injury in group 1, and in groups 2 and 3 the histological changes for infusions of 4-10 cc were greater than those of 1-3 cc. There was no vascular endothelial cell damage in any case. None of the histological changes were dose dependent, and the lungs showed no clear histological alterations. CONCLUSION: Higher doses of a hypertonic sodium chloride solution cause irreversible histological changes in the rabbit kidney.     

Imaging of intraneural edema by using gadolinium-enhanced MR imaging: experimental compression injury

BACKGROUND AND PURPOSE: Compressive and entrapment neuropathies are diseases frequently observed on routine clinical examination. A definitive diagnosis based on clinical symptoms and neurologic findings alone is difficult in many cases, however, and electrophysiologic measurement is used as a supplementary diagnostic method. In this study, we examined to use protein tracers (Evans blue albumin or horseradish peroxidase) and gadolinium-enhanced MR imaging to determine the changes of blood-nerve barrier permeability in compressive neuropathies. METHODS: In dogs, the median nerve was compressed for 1 hour by using five kinds of clips with various strengths (7.5-90-g force). After clip removal, the combined tracers of Evans blue albumin and gadolinium or horseradish peroxidase was administered intravenously as a tracer. After the animals were euthenized, we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve under fluorescence microscopy. The horseradish peroxidase-injected specimens were observed by transmission electron microscopy. RESULTS: On enhanced MR imaging, intraneural enhancement was caused by 60- and 90-g-force compression after 1 hour. Marked extravasation of protein tracers in the nerve occurred where there was compression by 60- and 90-g-force compression, and capillaries in the nerve showed the opening of tight junction and an increase of vesicular transport under the electron microscopy. This situation indicated breakdown of the blood-nerve barrier, with consequent edema formation and was seen as enhancement on MR imaging. CONCLUSION: Gadolinium-enhanced MR imaging can detect morphologic and functional changes of blood-nerve barrier in the nerve induced by mechanical compression.     

Relation between vertical orientation and stability of acetabular component in the dysplastic hip simulated by nonlinear three-dimensional finite element method

In acetabular dysplasia, more vertical orientation of the acetabular component is often used to minimize the superolateral bone grafting. This study was designed to determine the effects of vertical orientation of the cup on the stability and polyethylene wear of the acetabular component in uncemented total hip arthroplasty (THA). Three-dimensional finite element models of the hemipelvis with dysplastic acetabulum were developed. Metal-backed hemispherical cups were placed in the true acetabulum with abduction angles of 35, 45, 55, and 65 degrees. It was found that more vertical orientation of the cup was associated with larger relative motion of the metal shell between the acetabulum and metal shell. Furthermore, tilting and torsional shear stresses in the model of the cup abduction angle of 65 degrees were found to be 1.7 times larger than that in the model with 35 degrees at the bone-metal shell interface. More vertically oriented cups caused larger contact stresses at the articulating surfaces of the polyethylene liners. The results suggest that the abduction angle of the acetabular component significantly influences cup loosening and polyethylene wear in THA.     

Hydrogen absorption behavior of beta titanium alloy in acid fluoride solutions

Hydrogen absorption behavior of a beta titanium alloy in acid fluoride solutions has been analyzed by hydrogen thermal desorption. The amount of absorbed hydrogen increased with immersion time in a 2.0% acidulated phosphate fluoride (APF) solution. In the case of an immersion time of 60 h, the amount of absorbed hydrogen exceeded 10000 mass ppm. In contrast, the amount of hydrogen absorbed in the 0.2% APF solution was several times smaller than that in the 2.0% APF solution for the same immersion time. For immersion in a 0.2% APF solution, hydrogen absorption saturated after 48 h. The surface topography and corrosion products on the surface of the specimen immersed in the 2.0% APF solution were different from those in the 0.2% APF solution. During the later stage of immersion, the amount of absorbed hydrogen markedly increased under higher applied stress, although the applied stress did not enhance hydrogen absorption during the early stage of immersion. These results of hydrogen absorption behavior are consistent with the delayed fracture characteristics of the beta titanium alloy.     

Azithromycin reverses anticancer drug resistance and modifies hepatobiliary excretion of doxorubicin in rats

The present study aims to investigate whether azithromycin reverses P-glycoprotein-dependent anticancer drug resistance in vitro and modifies the hepatobiliary excretion of doxorubicin, a substrate for P-glycoprotein in vivo. Azithromycin increased dose-dependently the intracellular accumulation of doxorubicin in adriamycin-resistant human myelogenous leukemia cells (K562/ADR) with no effect on the expression of P-glycoprotein in the cells. However, the inhibitory effect was much weaker than that of cyclosporin A and was comparable to that of erythromycin. When Sprague-Dawley (SD) rats, which have drug transporting P-glycoprotein and multidrug resistance-associated protein 2 (Mrp2) in the bile canalicular membrane of hepatocytes, received an infusion of doxorubicin, the steady-state biliary clearance of doxorubicin was significantly decreased for 40 min after a single intravenous injection of azithromycin. However, azithromycin did not increase the plasma concentration of doxorubicin. The biliary clearance of doxorubicin in Eisai hyperbilirubinemic rats (EHBRs), which have a hereditary deficiency in Mrp2, was significantly decreased compared with that in Sprague-Dawley rats, suggesting the involvement of Mrp2 in the biliary excretion of doxorubicin. The present findings suggest that azithromycin overcomes P-glycoprotein-dependent anticancer drug resistance of tumors by inhibiting the binding of doxorubicin to P-glycoprotein in K562/ADR cells and inhibits the hepatobiliary excretion of drugs that are substrates for P-glycoprotein and Mrp2.     

Effects of SEA0400, a novel inhibitor of the Na+/Ca2+ exchanger, on myocardial stunning in anesthetized dogs

Activation of the Na+/Ca2+ exchanger may contribute to Ca2+ overload during reperfusion after transient ischemia. We examined the effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion injury (myocardial stunning). Myocardial stunning was induced by a 15-min occlusion of the left anterior descending coronary artery followed by a 4-h reperfusion in anesthetized open-chest dogs. Reperfusion gradually restored myocardial percent segment shortening but remained depressed during a 4-h reperfusion period. A bolus intravenous injection of SEA0400 (0.3 or 1.0 mg/kg), given 1 min before reperfusion, improved significantly the recovery of percent segment shortening in the ischemic/reperfused myocardium. SEA0400 did not affect the hemodynamics and electrocardiogram parameters. In addition, SEA0400 did not affect reperfusion-induced change in coronary blood flow. These results suggest that the Na+/Ca2+ exchanger is involved in the stunned myocardium of dogs after reperfusion, and that SEA0400 has a protective effect against myocardial stunning in dogs.     

Proof of the mysterious efficacy of ginseng: basic and clinical trials: suppression of adrenal medullary function in vitro by ginseng

The root of Panax ginseng C.A. MEYER has been reported to have an anti-stress action. Therefore, the effects of ginseng components on functions of adrenal medulla, which is one of the most important organs responsive to stress, were investigated in vitro. First, the components of ginseng were mainly divided into two fractions, that is, the saponin-rich and non-saponin fractions. The saponin-rich fraction greatly reduced the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh), whereas the non-saponin fraction did not affect it at all. The protopanaxatriol-type saponins inhibited the ACh-evoked secretion much more strongly than the protopanaxadiol-type. On the other hand, the oleanane-type saponin, ginsenoside-Ro, had no such effect. Recent reports have demonstrated that the saponins in ginseng are metabolized and absorbed in digestive tracts following oral administration of ginseng. All of the saponin metabolites greatly reduced the ACh-evoked secretion. M4 was the most effective inhibitor among the metabolites. M4 blocked ACh-induced Na(+) influx and ion inward current into the chromaffin cells and into the Xenopus oocytes expressing human alpha3beta4 nicotinic ACh receptors, respectively, suggesting that the saponin metabolites modulate nicotinic ACh receptors followed by the reduction of catecholamine secretion. It is highly possible that these effects of ginsenosides and their metabolites are associated with the anti-stress action of ginseng.     

Sentinel lymph node biopsy using periareolar injection of radiocolloid for patients with neoadjuvant chemotherapy-treated breast carcinoma

BACKGROUND: The feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) for patients with breast carcinoma have been investigated primarily for the situation in which the radiocolloid imaging agent is injected peritumorally. No such study has involved periareolar injection of radiocolloid, although the usefulness of this injection technique has been demonstrated in patients with early-stage breast carcinoma who have not been treated with NAC. The objective of the current study was to determine the feasibility and accuracy of SLN biopsy using periareolar injection of radiocolloid for patients with breast carcinoma who were treated with NAC. METHODS: Forty-seven patients with AJCC Stage II or III breast carcinoma who were treated with NAC were enrolled in the study. All patients underwent SLN biopsy, which involved a combination of periareolar injection of radiocolloid (technetium 99m tin colloid) and peritumoral injection of isosulfan blue dye, followed by backup axillary lymph node dissection. SLN metastases were examined by hematoxylin and eosin staining and immunohistochemical analysis using an anticytokeratin antibody. RESULTS: An SLN was identified successfully in 44 patients (94%). Twenty-nine patients (66%) had positive SLNs. Fifteen patients had negative SLNs, and 4 patients had positive non-SLNs. Thus, the false-negative rate was 12.1% (4 of 33 patients). The false-negative rate tended to be higher, although not statistically significantly so, among patients who had clinically positive axillary lymph nodes before and/or after NAC (15.8%; 3 of 19 patients) compared with patients who had clinically negative axillary lymph nodes both before and after NAC (7.1%; 1 of 14 patients). CONCLUSIONS: SLN biopsy using periareolar injection of radiocolloid is feasible after NAC. In patients with clinically negative axillary lymph nodes both before and after NAC, SLN biopsy was capable of predicting axillary lymph node status with an accuracy comparable to the accuracy associated with SLN biopsy for patients with early-stage carcinoma who have not been treated with NAC.     

The effects of cholesterol-3-sulfate (CH-3S) on the phosphorylation of human C3a (hC3a) in vitro and on the ability of hC3a to induce vascular permeability in rats

The phosphorylation of human C3a (hC3a, anaphylatoxin) by two distinct protein kinases (PKA and CK-I) and the effect of cholesterol-3-sulfate (CH-3S) on this phosphorylation were biochemically investigated in vitro. It was found that (i) hC3a functions as a phosphate acceptor for PKA and CK-I, but not for CK-II; (ii) the CK-I-mediated phosphorylation of hC3a requires the presence of 3 microM CH-3S in a manner similar to the phosphorylation of HMG1 (CH-3S-binding protein) by CK-I; and (iii) CH-3S inhibits the PKA-mediated phosphorylation of hC3a in a dose-dependent manner (ID50=approximately 2 microM). As expected, hC3a containing high levels of Arg- and Lys-residues stimulated approx. 3-fold CK-II activity (phosphorylation of alpha-casein) in vitro. However, no significant effect of hC3a on CK-II activity was observed when hC3a was preincubated with CH-3S or fully phosphorylated by PKA in vitro. Furthermore, preincubation of hC3a with CH-3S diminished the ability of hC3a to induce vascular permeability in rats. The results provided here suggest that (i) hC3a is a CH-3S-binding protein; and (ii) CH-3S functions as a potent inhibitor for its physiological activities, including phosphorylation by PKA and CK-I, in vitro.