ABSTRACT
Chitosan-graft-polyethylenimine [CHI-g-PEI] copolymer has been used for the improvement of low transfection efficiency of chitosan. The present study aims to test the pulmonary toxicity and efficiency of CHI-g-PEI as an aerosol gene carrier. Mice were exposed to aerosol containing green-fluorescent protein [GFP]-polyethylenimine [PEI] or GFP-CHI-g-PEI complexes for 30 min during the development of our nose-only exposure chamber [NOEC] system. CHI-g-PEI-mediated aerosol delivery demonstrated 15.65% enhancement of the fluorescence intensity. Compared to PEI, CHI-g-PEI showed no significant pulmonary toxicity. In summary, using CHI-g-PEI is safe and shows high transfection in aerosol gene delivery to animals, and enhanced efficiency was achieved through our aerosol gene delivery system. Therefore, CHI-g-PEI and this system would be applicable to future study for aerosol gene therapy
Subject(s)
Chitosan/analogs & derivatives , Gene Expression , Chitosan/chemistry , Gene Transfer Techniques , Mice , Green Fluorescent ProteinsABSTRACT
Aluminum nanoparticles (Al-NPs) are one of the most widely used nanomaterial in cosmetics and medical materials. For this reason, Al-NP exposure is very likely to occur via inhalation in the environment and the workplace. Nevertheless, little is known about the mechanism of Al-NP neurotoxicity via inhalation exposure. In this study, we investigated the effect AL-NPs on the brain. Rats were exposed to Al-NPs by nasal instillation at 1 mg/kg body weight (low exposure group), 20 mg/kg body weight (moderate exposure group), and 40 mg/kg body weight (high exposure group), for a total of 3 times, with a 24-hr interval after each exposure. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated that the presence of aluminum was increased in a dose-dependent manner in the olfactory bulb (OFB) and the brain. In microarray analysis, the regulation of mitogen-activated protein kinases (MAPK) activity (GO: 0043405), including Ptprc, P2rx7, Map2k4, Trib3, Trib1, and Fgd4 was significantly over-expressed in the treated mice than in the controls (p = 0.0027). Moreover, Al-NPs induced the activation of ERK1 and p38 MAPK protein expression in the brain, but did not alter the protein expression of JNK, when compared to the control. These data demonstrate that the nasal exposure of Al-NPs can permeate the brain via the olfactory bulb and modulate the gene and protein expression of MAPK and its activity.
Subject(s)
Animals , Mice , Rats , Aluminum , Body Weight , Brain , Inhalation , Inhalation Exposure , Mass Spectrometry , Microarray Analysis , Mitogen-Activated Protein Kinases , Nanoparticles , Nanostructures , Olfactory Bulb , p38 Mitogen-Activated Protein Kinases , PlasmaABSTRACT
The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at 1.93 x 10(7) particles/cm3, 1.09 x 10(10) nm2/cm3, 2.72 x 10(11) nm3/cm3, and 2854.62 microg/m3, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.
Subject(s)
Animals , Mice , Blotting, Western , Bronchoalveolar Lavage , Inhalation , Lung , Nanoparticles , Protein Kinases , SilverABSTRACT
Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery.
Subject(s)
Animals , Male , Mice , Administration, Inhalation , Aerosols , Gene Expression Regulation , Gene Knockdown Techniques , Genetic Therapy/methods , Gene Transfer Techniques , Genes, Reporter , Injections, Intraperitoneal , Luciferases/genetics , Lung Diseases/chemically induced , Mice, Transgenic , Naphthalenes/administration & dosage , Proto-Oncogene Proteins c-akt/administration & dosageABSTRACT
Inorganic phosphate (Pi) plays a critical role in diverse cellular functions, and regulating the Pi balance is accomplished by sodium-dependent Pi co-transporter (NPT). Pulmonary NPT has recently been identified in mammalian lungs. However, to date, many of the studies that have involved Pi have mainly focused on its effect on bone and kidney. Therefore, current study was performed to discover the potential effects of low Pi on the lung of developing transgenic mice expressing the renilla/firefly luciferase dual reporter gene. Two-weeks old male mice divided into 2 groups and these groups were fed either a low PI diet or a normal control diet (normal: 0.5% Pi, low: 0.1% Pi) for 4 weeks. After 4 weeks of the diet, all the mice were sacrificed. Their lungs were harvested and analyzed by performing luciferase assay, Western blotting, kinase assay and immunohistochemistry. Our results demonstrate that low Pi affects the lungs of developing mice by disturbing protein translation, the cell cycle and the expression of fibroblast growth factor-2. These results suggest that optimally regulating Pi consumption may be important to maintain health.
Subject(s)
Animals , Male , Mice , Blotting, Western , Carrier Proteins/metabolism , Immunohistochemistry , Lung/drug effects , Mice, Transgenic , Phosphoproteins/metabolism , Phosphorus, Dietary/administration & dosage , Phosphorylation , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Sodium-Phosphate Cotransporter Proteins, Type IIa/metabolismABSTRACT
Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.
Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Benzylisoquinolines/pharmacology , Carcinoma/drug therapy , Cell Line, Tumor , Dose-Response Relationship, Drug , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Lung Neoplasms/drug therapyABSTRACT
The authors report a primary intramedullary spinal cord lymphoma in a 49-year-old man who presented with right arm pain, voiding difficulty and progressive walking difficulty. Preoperative cervical spinal CT and MRI studies were highly suggestive of spinal stenosis with compressive myelopathy but histopathological study of the specimen after surgery revealed spinal cord lymphoma. As no tumorous lesion was found other than the spinal cord, he was given 6000 rad of radiation under the diagnosis of primary CNS lymphoma. The neurologic deficits improved partially after the surgery but delete right arm pain persisted. One year later, follow up studies showed neither local nor systemic tumor recurrence.
Subject(s)
Humans , Middle Aged , Arm , Diagnosis , Follow-Up Studies , Lymphoma , Magnetic Resonance Imaging , Neurologic Manifestations , Recurrence , Spinal Cord Compression , Spinal Cord , Spinal Stenosis , WalkingABSTRACT
A 62-year-old woman, who presented with dipolipia, was found to have a giant aneurysm of the right internal carotid artery. Gradual ligation of the right internal carotid artery was followed by nausea and vomiting 10 days after the complete ligation. Follow up MRI showed intraluminal thrombus formation of the aneurysm and right temporo-occipital infarction.
Subject(s)
Female , Humans , Middle Aged , Aneurysm , Carotid Artery, Internal , Cerebral Arteries , Cerebral Infarction , Follow-Up Studies , Infarction , Ligation , Magnetic Resonance Imaging , Nausea , Thrombosis , VomitingABSTRACT
A retrospective analysis of 219 mild head injured patients who were admitted to Chung-Ang University Hospital from January 1990 to December 1991 was made to correlate outcome to initial Glasgow coma scale(GCS) score, combined injuries and radiologic findings. The results were as follows: 1) The young males were most frequently affected. 2) The most common cause was motor vehicle accident followed by fall. 3) The most common combined injury was cervical sprain followed by subgaleal hematoma. 4) The skull fractures were shown in 29.2% but there was no correlation between outcome and skull fracture. 5) The most common abnormal CT finding was the subdural hematoma(20.3%). 6) The positive blood alcohol test was not correlated with the outcome. 7) The majority of the patients(91.8%) made a good recovery. 8) Thirteen patients(5.9%) were performed cranial operation under the diagnosis of epidural hematoma(5 patients), subdural hematoma(4 patients), contusion and FCCD.
Subject(s)
Humans , Male , Coma , Contusions , Craniocerebral Trauma , Diagnosis , Glasgow Coma Scale , Glasgow Outcome Scale , Head , Hematoma , Motor Vehicles , Prognosis , Retrospective Studies , Skull Fractures , Sprains and StrainsABSTRACT
A 18-year-old girl, who presented with painful scalp mass on occipital region, was found in have a congential dermal sinus. At surgery, upon incision of the occipital muscle fascia, pus poket was encountered and it was connected with thickened occipito-cervical dura through the small foramen on midline occiptial bone. The pathogenesis and principles of management are briefly reviewed.