Long-term outcomes of minor dissection at the edge of stents detected with intravascular ultrasound

We evaluated the influences of minor edge dissections on late angiographic in-stent restenosis in 327 patients with 348 lesions (281 lesions without edge dissection and 67 lesions [19.3%] with edge dissection); the angiographic restenosis rate was 29.9% in the lesions with edge dissections versus 25.3% without edge dissections (p = 0.540). The minor non-flow-limiting dissections at the edge of stents may not be associated with the development of late angiographic in-stent restenosis.     

Right-sided myxomas with extramedullary hematopoiesis and ossification in Carney complex

The authors report the case of multiple right-sided myxomas in a 42-year-old man with Carney complex. He had previously been diagnosed as Cushing's syndrome and undergone resection of pituitary adenoma at the age of 21. After 10 years, bilateral adrenalectomy had been performed with recurrence of Cushing's syndrome. Recently, he complained of palpitation and intracardiac masses were detected. On physical examination, he had nevi on the lips and in the oral cavity. A tiny eyelid nodule was noted and histopathological analysis confirmed the diagnosis of skin myxoma. Thyroid ultrasonography revealed multiple hypoechoic nodules, which were confirmed pathologically as follicular adenomas. Scrotal ultrasonography also revealed small multiple testicular tumors. Echocardiography demonstrated intracardiac masses in right atrium and right ventricle. Right atriotomy revealed a right atrial mass attached to the annulus of the tricuspid valve and another mass arising from the interatrial septum. In right ventricle, a polypoid mass arose from the anterior leaflet of the tricuspid valve. Also, there were multiple tiny to small masses on the interatrial septum. The masses were completely excised and the tricuspid valve was repaired with annuloplasty. Histopathological analysis confirmed myxomas with foci of extramedullary hematopoiesis and ossification.     

A case of spontaneous biloma complicated with choledocholithiasis and chronic cholecystitis]

A biloma is an encapsulated bile collection outside the biliary tree. Most cases of biloma are caused by iatrogenic injury or trauma. Intrahepatic rupture of the biliary tree due to nontraumatic cause is a rare event. A 68- year-old man was admitted because of abdominal pain and fever. He had no past history of abdominal surgery, instrumentation or trauma. Computed tomography (CT) scan and magnetic resonance cholangiopancreatography (MRCP) demonstrated a large subcapsular fluid collection in the right liver associated with choledocholithiasis and cholecystitis. Biloma was confirmed by sono-guided percutaneous needle aspiration and was drained through a pigtail catheter. After the successful treatment by percutaneous drainage and endoscopic sphincterotomy, the patient recovered. Here, we report an uncommon case of spontaneous biloma formation in association with choledocholithiasis with a review of literatures.     

Butyl paraben-induced changes in DNA methylation in rat epididymal spermatozoa

Parabens have been shown to affect male rodent reproductive parameters, including testosterone levels and sperm production. In this study, we examined the effect of long-term exposure to butyl paraben (BP) on rat epididymal sperm DNA methylation. Adult male rats were exposed to BP (0, 10, 100 and 1000 mg kg(-1) per day) according to OECD TG407 for a repeated 28-day oral toxicity study. Sperm DNA methylation was examined by differential display random amplification of polymorphic DNA (RAPD) following methylation-specific restriction digestion of DNA. Among the 57 RAPD amplicons, six were methylation specific. Of these, five amplicons increased by 1.4- to 3.8-fold in epididymal sperm DNA at testing dose of BP. This indicates that BP can cause DNA hypermethylation in germ cells from the mitotic through post-meiotic stage in adult rat testes. To our knowledge, this is the first report on the epigenetic modification of sperm DNA by parabens.     

Modulation of Reactive Oxygen Species to Overcome 5-Fluorouracil Resistance

5-Fluorouracil (5-FU) remains to be an important chemotherapeutic drug for treating several cancers when targeted therapy is unavailable. Chemoresistance limits the clinical utility of 5-FU, and new strategies are required to overcome the resistance. Reactive oxygen species (ROS) and antioxidants are balanced differently in both normal and cancer cells. Modulating ROS can be one method of overcoming 5-FU resistance. This review summarizes selected compounds and endogenous cellular targets modulating ROS generation to overcome 5-FU resistance.     

An anthrax lethal factor-neutralizing monoclonal antibody protects rats before and after challenge with anthrax toxin

Lethal factor (LF) is a component of anthrax lethal toxin (LeTx). We generated anti-LF murine monoclonal antibodies (MAbs) that show LeTx-neutralizing activity in vitro and in vivo. Anti-LF MAbs were generated by immunization with recombinant LF, and the MAbs showing LeTx-neutralizing activity in vitro were selected. Two MAbs with the highest affinities, 5B13B1 (dissociation constant [K(d)], 2.62 nM) and 3C16C3 (K(d), 8.18 nM), were shown to recognize the same or closely overlapping epitopes on domain III of LF. The 50% inhibitory concentration of 5B13B1 (0.21 microg/ml) was approximately one-third that of 3C16C3 (0.63 microg/ml) in the in vitro LeTx-neutralization assay. The 5B13B1 antibody, which had the highest neutralizing activity, provided perfect protection against LeTx challenge in an in vivo LeTx neutralization assay using Fisher 344 rats. In addition, the antibody showed pre- and postexposure prophylactic effects in the animal experiments. This is the first report that an MAb binding to domain III of LF has neutralizing activity against LeTx. The 5B13B1 antibody may be useful in prophylaxis against anthrax poisoning.     

Protection against kainate neurotoxicity by ginsenosides: attenuation of convulsive behavior, mitochondrial dysfunction, and oxidative stress

We previously demonstrated that kainic acid (KA)-mediated mitochondrial oxidative stress contributed to hippocampal degeneration and that ginsenosides attenuated KA-induced neurotoxicity and neuronal degeneration. Here, we examined whether ginsenosides affected KA-induced mitochondrial dysfunction and oxidative stress in the rat hippocampus. Treatment with ginsenosides attenuated KA-induced convulsive behavior dose-dependently. KA treatment increased lipid peroxidation and protein oxidation and decreased the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio to a greater degree in the mitochondrial fraction than in the hippocampal homogenate. KA treatment resulted in decreased Mn-superoxide dismutase expression and diminished the mitochondrial membrane potential. Furthermore, KA treatment increased intramitochondrial Ca(2+) and promoted ultrastructural degeneration in hippocampal mitochondria. Treatment with ginsenosides dose-dependently attenuated convulsive behavior and the KA-induced mitochondrial effects. Protection appeared to be more evident in mitochondria than in tissue homogenates. Collectively, the results suggest that ginsenosides prevent KA-induced neurotoxicity by attenuating mitochondrial oxidative stress and mitochondrial dysfunction.     

Clonazepam release from poly(DL-lactide-co-glycolide) nanoparticles prepared by dialysis method

Aim of this work is to prepare poly(DL-lactide-co-glycolide) (PLGA) nanoparticles by dialysis method without surfactant and to investigate drug loading capacity and drug release. The size of PLGA nanoparticles was 269.9±118.7 nm in intensity average and the morphology of PLGA nanoparticles was spherical shape from the observation of SEM and TEM. In the effect of drug loading contents on the particle size distribution, PLGA nanoparticles were monomodal pattern with narrow size distribution in the empty and lower drug loading nanoparticles whereas bi- or trimodal pattern was showed in the higher drug loading ones. Release of clonazepam from PLGA nanoparticles with higher drug loading contents was slower than that with lower loading contents.     

A trace component of ginseng that inhibits Ca2+ channels through a pertussis toxin-sensitive G protein.

A crude extract from ginseng root inhibits high-threshold, voltage-dependent Ca2+ channels through an unknown receptor linked to a pertussis toxin-sensitive G protein. We now have found the particular compound that seems responsible for the effect: it is a saponin, called ginsenoside Rf (Rf), that is present in only trace amounts within ginseng. At saturating concentrations, Rf rapidly and reversibly inhibits N-type, and other high-threshold, Ca2+ channels in rat sensory neurons to the same degree as a maximal dose of opioids. The effect is dose-dependent (half-maximal inhibition: 40 microM) and it is virtually eliminated by pretreatment of the neurons with pertussis toxin, an inhibitor of G(o) and Gi GTP-binding proteins. Other ginseng saponins--ginsenosides Rb1, Rc, Re, and Rg1--caused relatively little inhibition of Ca2+ channels, and lipophilic components of ginseng root had no effect. Antagonists of a variety of neurotransmitter receptors that inhibit Ca2+ channels fail to alter the effect of Rf, raising the possibility that Rf acts through another G protein-linked receptor. Rf also inhibits Ca2+ channels in the hybrid F-11 cell line, which might, therefore, be useful for molecular characterization of the putative receptor for Rf. Because it is not a peptide and it shares important cellular and molecular targets with opioids, Rf might be useful in itself or as a template for designing additional modulators of neuronal Ca2+ channels.     

Ginsenoside Rf, a trace component of ginseng root, produces antinociception in mice

Ginseng root, a traditional oriental medicine, contains more than a dozen biologically active saponins called ginsenosides, including one present in only trace amounts called ginsenoside-Rf (Rf). Previously, we showed that Rf inhibits Ca²⁺ channels in mammalian sensory neurons through a mechanism requiring G-proteins, whereas a variety of other ginsenosides were relatively ineffective. Since inhibition of Ca²⁺ channels in sensory neurons contributes to antinociception by opioids, we tested for analgesic actions of Rf. We find dose-dependent antinociception by systemic administration of Rf in mice using two separate assays of tonic pain: in the acetic acid abdominal constriction test, the ED₅₀ was 56±9 mg/kg, a concentration similar to those reported for aspirin and acetaminophen in the same assay; in the tonic phase of the biphasic formalin test, the ED₅₀ was 129±32 mg/kg. Rf failed to affect nociception measured in three assays of acute pain: the acute phase of the formalin test, and the thermal (49°C) tail-flick and increasing-temperature (3°C/min) hot-plate tests. The simplest explanation is that Rf inhibits tonic pain without affecting acute pain, but other possibilities exist. Seeking a cellular explanation for the effect, we tested whether Rf suppresses Ca²⁺ channels on identified nociceptors. Inhibition was seen on large, but not small, nociceptors. This is inconsistent with a selective effect on tonic pain, so it seems unlikely that Ca²⁺ channel inhibition on primary sensory neurons can fully explain the behavioral antinociception we have demonstrated for Rf.