Cell-penetrating peptides meditated encapsulation of protein therapeutics into intact red blood cells and its application.

Red blood cells (RBCs) based drug carrier appears to be the most appealing for protein drugs due to their unmatched biocompatability, biodegradability, and long lifespan in the circulation. Numerous methods for encapsulating protein drugs into RBCs were developed, however, most of them induce partial disruption of the cell membrane, resulting in irreversible alterations in both physical and chemical properties of RBCs. Herein, we introduce a novel method for encapsulating proteins into intact RBCs, which was meditated by a cell penetrating peptide (CPP) developed in our lab-low molecular weight protamine (LMWP).

Co-administration of protein drugs with gold nanoparticles to enable percutaneous delivery.

An interesting nanoscale interfacial phenomenon mediated by gold nanoparticles (Au-NPs) was found, in that co-administration with Au-NPs enables percutaneous delivery of protein drugs. The Au-NPs with a mean size of 5 nm were revealed to be skin permeable, presumably due to the nano-bio interaction with skin lipids and the consequent induction of transient and reversible openings on the stratum corneum. Importantly, when simultaneously applied with Au-NPs, the protein drugs were also granted the ability to penetrate the skin barrier and migrate into the deep layers.

Effects of repeated hair washing and a single hair dyeing on concentrations of methamphetamine and amphetamine in human hairs.

The effects of repeated hair washing and a single hair dyeing on concentrations of methamphetamine (MA) and amphetamine (AM) in hair samples of MA addicts were studied. Thirty-one MA positive hair samples collected from male (n = 24, 24-51 yrs) and female abusers (n = 7, 17-46 yrs) were evaluated for MA and AM concentration's changes after repeated hair washing and a single hair dyeing. Thirty-one MA positive hair samples, no additional treatment hair sample group (NAT), were treated in vitro with liquid soap or three kinds of hair dyes which were black, brown and yellow color hair dye, respectively.

ATTEMPTS system: a macromolecular prodrug strategy for cancer drug delivery.

In order to reduce systemic toxicity and effectively deliver macromolecular drug into tumor cells, a system termed "ATTEMPTS" (antibody targeted, [protamine] triggered, electrically modified prodrug-type strategy) was developed in our laboratory. This approach was adapted from our previously reported heparin/protamine-based system for controlled delivery of protease drugs such as tissue- specific plasminogen activator (tPA). In this "ATTEMPTS" system, the cell-permeable protein drugs are synthesized by conjugating proteins to cell-penetrating peptides (CPPs).

Specific down regulation of 3T3-L1 adipocyte differentiation by cell-permeable antisense HIF1alpha-oligonucleotide.

Hypoxia is a strong modulator of angiogenesis, accelerating adipose tissue expansion, suggesting that hypoxia inducible factor 1alpha (HIF1alpha) can be a novel target for anti-obesity. We conjugated antisense-HIF1alpha-oligonucleotide (ASO) with low molecular weight protamine (LMWP), a cell-penetrating peptide, to enhance its ability to block hypoxic-angiogenesis, thereby eliciting an anti-obesity effect. Nano-sized ASO-LMWP (AS-L) conjugates enhanced cellular uptake of ASO without yielding a cytotoxic effect and protected the ASO against enzymatic attack and chemical reduction.

L-Asparaginase encapsulated intact erythrocytes for treatment of acute lymphoblastic leukemia (ALL).

As a primary drug for the treatment of acute lymphoblastic leukemia (ALL), encapsulation of L-asparaginase (ASNase) into red blood cells (RBC) has been popular to circumvent immunogenicity from the exogenous protein. Unlike existing methods that perturbs RBC membranes, we introduce a novel method of RBC-incorporation of proteins using the membrane-translocating low molecular weight protamine (LMWP). Confocal study of fluorescence-labeled LMWP-ovalbumin, as a model protein conjugate, has shown significant fluorescence inside RBCs.

Postmortem blood concentrations of organophosphorus pesticides.

Cases involving acute fatalities due to ingestion of organophosphorus pesticides (OPs), such as chlorpyrifos, diazinon, malathion and parathion, are presented. Solid-phase extraction (SPE) and gas chromatography/mass spectrometry (GC/MS) were used for the analysis of OPs in postmortem blood. After extraction with an Oasis HLB cartridge, the eluent was evaporated to dryness under a nitrogen stream at 35 degrees C, reconstituted with ethanol, and then analyzed by GC/MS.

Preliminary in vivo evaluation of the protein transduction domain-modified ATTEMPTS approach in enhancing asparaginase therapy.

Asparaginase (ASNase) is an enzyme drug presently approved for the induction of remission in the treatment of patients with acute lymphoblastic leukemia (ALL). The cytotoxic effect of ASNase is derived from its ability to deplete asparagine, an essential amino acid required by certain types of leukemia cells for protein synthesis and survival. Despite its efficacy in enhancing disease remission rate and prolonging complete remission duration in ALL patients, ASNase therapy is nevertheless confounded by a number of serious toxic effects, particularly to organs associated with high protein production (e.

Determination of impurities in illicit methamphetamine seized in Korea and Japan.

Impurities produced during synthesis of methamphetamine (MA) show different patterns under various synthetic conditions. Valuable information on the origins and smuggling routes can be obtained by using impurities as chemical fingerprints. We have detected more than 100 compounds from 436 MA samples seized in Korea by gas chromatography-flame ionization detector and gas chromatography-mass spectrometer, among which 31 impurities and three additives were identified.

Analysis of ketamine and norketamine in urine by automatic solid-phase extraction (SPE) and positive ion chemical ionization-gas chromatography-mass spectrometry (PCI-GC-MS).

Ketamine (KT) is widely abused for hallucination and also misused as a "date-rape" drug in recent years. An analytical method using positive ion chemical ionization-gas chromatography-mass spectrometry (PCI-GC-MS) with an automatic solid-phase extraction (SPE) apparatus was studied for the determination of KT and its major metabolite, norketamine (NK), in urine. Six ketamine suspected urine samples were provided by the police.

Comparison study of the extraction methods of paraquat in post-mortem human blood samples.

The most important step for Paraquat analysis in post-mortem human blood (PMB) is its extraction from the specimens, as Paraquat is insoluble in organic solvents due to its ionic form. The most common extraction method, solid phase extraction (SPE), has been used for the extraction of Paraquat from PMB. However, SPE procedures are somewhat time-consuming, and resulted in unsatisfactory recovery in our laboratory.

Bronchial washing yield before and after forceps biopsy in patients with endoscopically visible lung cancers.

Background And Objective: The need for routine use of bronchial washing in addition to forceps biopsy has been debated in the diagnosis of endoscopically visible lung tumours. Moreover, the optimal sequence for obtaining bronchial washing and forceps biopsy specimens from endoscopically visible tumours through a flexible bronchoscope has not been well established.

Methods: A multicentre 13-month prospective randomized study was performed.

Monitoring precursor chemicals of methamphetamine through enantiomer profiling.

Smuggling of methamphetamine is affected by enforced regulation and international situation, resulting in changes of precursors and synthetic methods used. Enantiomer ratio of methamphetamine can provide information concerning its precursor and synthetic method. This information is useful for the prevention of smuggling methamphetamine and its precursor, and resultant reduction of methamphetamine abuse.

Analysis of the impurities in the methamphetamine synthesized by three different methods from ephedrine and pseudoephedrine.

Organic impurities of methamphetamine may show different patterns by synthesis. In the present study, we tried to find the impurities reflecting the conditions of synthesis by comparing impurity patterns of the methamphetamine samples synthesized by different methods. Sixteen methamphetamine samples were synthesized from ephedrine and pseudoephedrine by the three different manufacturing methods of Emde, Nagai and Moscow.

Effect of alpha-tocopherol and deferoxamine on methamphetamine-induced neurotoxicity.

Methamphetamine (MA)-induced dopaminergic neurotoxicity is believed to be associated with the increased formation of free radicals. This study examined the effect of alpha-tocopherol (alpha-TC), a scavenger of reactive oxygen species, and deferoxamine (DFO), an iron chelator, on the MA-induced neurotoxicity. Male rats were treated with MA (10 mg/kg, every 2 h for four injections).

Standardization of method for the analysis of dextromethorphan in urine.

Dextromethorphan (DMP), an antitussive, is one of the most popular drugs among the younger generation in Korea. It usually is taken for its hallucinogenic properties and overdoses have been responsible for the fatalities that have been reported frequently. To control the abuse of DMP, the authorities restricted its use through classifying it as a controlled drug on October 2003.

Case of complete recovery of pancytopenia after treatment of hypopituitarism.

We describe a 55-year-old woman who presented with pancytopenia with a normocytic and normochromic anemia which was progressive despite conventional treatments such as folic acid, vitamin B6, and oxymetholone. Her physical findings and history of a previous massive postpartum hemorrhage suggested Sheehan's syndrome, and the pituitary hormonal studies revealed panhypopituitarism. After 4 months of thyroxine and glucocorticoid replacement therapy, her pancytopenia and bone marrow hypoplasia recovered completely.

Lidocaine intoxication: two fatal cases.

We present two fatal cases, a 41-year-old male (case 1) and his 8-year-old daughter (case 2), resulting from acute lidocaine poisoning. Lidocaine was quantified by gas chromatography (GC) analysis using nitrogen-phosphorus detection. The lidocaine concentrations of cases 1 and 2 were: liver, 27.

Interpretations of the TDxFLx calibration data of the abused drugs.

The useful TDxFLx calibration data was obtained for the interpretation of the interactions of the abused drugs to sheep antiserum protein. The antibody of TDxFLx calibrators was prepared from sheep antiserum. Furthermore these data can be used to interpret the abused drug-protein binding phenomena in human body and the TDxFLx screening results of the abused drugs in urine samples.