• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.104-110
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• 2009

Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutations in the phenylalanine catabolic enzyme, phenylalanine hydroxylase (PAH). The use of phenylalanine ammonia-lase (PAL) by oral and parenteral routes as a therapeutic drug for PKU has been severely limited due to inactivation by intestinal proteolysis and immune reactions. PEGylation was applied to PAL to reduce the degrees of antigenicity and proteolytic inactivation. Kinetic experiments with native PAL and pegylated PALs were performed, and pH stability, temperature stability, and protease susceptibility were evaluated. Enzyme linked immunosorbent assay (ELISA) was carried out to measure the immune complex between pegylated PALs and antiserum that had been extracted from a PAL-immunized mouse. Pegylated PAL, especially branched pegylated PAL (10 kDa, 1:32), was more active for phenylalanine and more stable in pancreatic proteases than native PAL. Native PAL was optimal at pH 8.5, corresponding to the average pH range of the small intestine; the same finding was noted for pegylated PALs. All linear and branched pegylated PALs had low reactivity with mouse antiserum, especially the 1:16 formulation with linear 5-kDa PEG and the 1:32 formulation with branched 10-kDa PEG. Therefore, we suggest the 1:32 formulation with branched 10-kDa PEG as the most promising formulation for enzyme replacement therapy.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.19 no.1
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• pp.31-37
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• 2008

Patients with impaired ability to eat require nutritional support enterally or parenterally. Gastrostomy is a preferred method because total parenteral nutrition has many complications and high cost. Surgical gastrostomy has been a traditional and well-established method prior to the development of percutaneous gastrostomy. Since then, percutaneous gastrostomy has been established as an effective, safe, easy technique with a low morbidity and mortality rate. Consequently, percutaneous gastrostomy has been the first method for long-term enteral nutrition. The purpose of this review is to describe the techniques, indications, complications of percutaneous radiologic gastrostomy/gastrojejunostomy and to compare with endoscopic method.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.2
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• pp.83-95
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• 2016

Hepatitis C virus (HCV) infection is a major medical challenge affecting around 200 million people worldwide. The main site of HCV replication is the hepatocytes of the liver. HCV is a positive enveloped RNA virus from the flaviviridae family. Six major HCV genotypes are implicated in the human infection. In developed countries the children are infected mainly through vertical transmission during deliveries, while in developing countries it is still due to horizontal transmission from adults. Minimal nonspecific and brief symptoms are initially found in approximately 15% of children. Acute and chronic HCV infection is diagnosed through the recognition of HCV RNA. The main objective for treatment of chronic HCV is to convert detected HCV viremia to below the detection limit. Children with chronic HCV infection are usually asymptomatic and rarely develop severe liver damage. Therefore, the benefits from current therapies, pegylated-Interferon plus ribavirin, must be weighed against their adverse effects. This combined treatment offers a 50-90% chance of clearing HCV infection according to several studies and on different HCV genotype. Recent direct acting antiviral (DAA) drugs which are well established for adults have not yet been approved for children and young adults below 18 years. The most important field for the prevention of HCV infection in children would be the prevention of perinatal and parenteral transmission. There are areas of focus for new lines of research in pediatric HCV-related disease that can be addressed in the near future.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.20 no.1
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• pp.55-60
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• 2017

Intestinal hypoganglionosis is a rare innervation disorder that provides numerous nutritional, medical and surgical challenges. In this case report, we present a case of a newborn with intestinal hypoganglionosis leading to intestinal failure and intestinal failure-associated liver disease who responded to $Omegaven^{TM}$, a fat emulsion comprised of omega-3 fatty acids. $Omegaven^{TM}$ has been shown to be beneficial in the management of cholestatic liver injury. Clinical success with $Omegaven^{TM}$ was seen in this patient with a clear decrease in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and complete resolution of cholestasis with a direct bilirubin of zero within two weeks of initiation of $Omegaven^{TM}$. No current guidelines for the diagnosis and management of hypoganglionosis are available. We recommend a multidisciplinary approach and the use of novel therapies such as fat emulsions composed of omega-3 fatty acids for improved patient outcomes. Appropriate compassionate use protocols should be obtained from the Food and Drug Administration prior to initiation of $Omegaven^{TM}$.

• Archives of Reconstructive Microsurgery
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• v.22 no.1
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• pp.1-6
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• 2013

Rats and mice are commonly used in experimental laboratories and anesthetic drugs are important for researchers to understand the details. Administration of fluids helps to stabilize the experimental animals before anesthesia via intravenously through the lateral vein in rats and in case of difficulty in catheterization and maintenance, fluids are usually administered as boluses. Large volumes of cool fluids will rapidly lead to hypothermia and all parenteral fluids must be warmed to body temperature before administration. Premedication with a sedative may ease induction with volatile anesthetic drugs. The first choice for rodent anesthesia is complete inhalational anesthesia. The second option is using injectable anesthesia. Recovery from the volatile agents that have been used rapid when the agent is no longer administered. Anesthetic monitoring equipment is an infant-size bell sthethoscope that can be used to ausculate the heart and lungs. Supplemental heating should be provided to reduce the heat loss supply and maintain core body temperature. The kinds of drugs, characteristics, route of administration and care after surgery were reviewed and summarized from the references. Anesthetic drugs, maintenance, monitoring and aftercare are important in the laboratories to keep the animal safe in all experimental procedures.

• The Korean Journal of Food & Health Convergence
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• v.5 no.4
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• pp.13-17
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• 2019

Amiodarone hydrochloride is an antiarrhythmic agent which has low aqueous solubility and presents bioavailability problem. These properties are a challenge for the pharmaceutical industry. Inclusion of lipophilic compound in the hydrophobic core of micelles, i.e. self-assembled structures based on surfactants in aqueous solution, is one way of increasing the solubility. Intravenous formulation of amiodarone hydrochloride with polysorbate 80 as a detergent and benzyl alcohol as a co-solvent is used in medical practice. This paper aimed to study the effect of polysorbate 80 and benzyl alcohol on the water solubility of amiodarone hydrochloride. Formation of mixed micelles consisting of nonionic surfactant polysorbate 80 and cationic amiodarone with chloride counterion was investigated by fluorescence spectroscopy. Benzyl alcohol was found to decrease the stability of the mixed micelles and lead to crystallization of amiodarone hydrochloride. The greatest amounts of crystals formed at 4℃ for 30 days in the model drug solutions with polysorbate 80 concentrations of 100.1 mg/mL and 97.9 mg/mL. A change of the polysorbate 80 concentration and avoidance the use of benzyl alcohol are recommended to improve the stability of the parenteral dosage form. These results can open new perspectives in the optimization of amiodarone intravenous formulations.

• Korean Journal of Bronchoesophagology
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• v.17 no.1
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• pp.46-49
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• 2011

Background and Objectives Cervical necrotizing fasciitis is a fulminant disease associated with necrosis of connective tissue, spread along the fascial plane, and high mortality. We analyzed the clinical characteristics and treatment outcome of this rare fatal disease. Materials and Methods We retrospectively reviewed the medical records of 19 patients treated for cervical necrotizing fasciitis from January 1999 to January 2009. Mean age was 53.7 years. Results The most common predisposing illness was tonsillitis (36.8%), followed by odontogenic infection (15.7%). Diabetes mellitus was most common underlying disease. Liver cirrhosis and chronic renal failure were found in 2 patients each. All patients were treated with combination of parenteral antibiotics and wide surgical debridement by transcervical and/or thoracotomy approach. Multiple surgical debridements were performed in 7 patients. Tracheotomy was performed in most of the patients (88.8%). Period of total hospitalization and Intensive care unit was 23 days and 10.1 days. Two patients died of disease and overall survival rate was 89.4%. Conclusion Early surgical management and care in intensive care unit are essential for cervical necrotizing fasciitis. Possible complications such as respiratory failure, mediastinitis or sepsis should be carefully evaluated.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.572-584
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• 2002

Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.

• YAKHAK HOEJI
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• v.46 no.5
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• pp.337-342
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• 2002

Propofol(2,6-diisopropyl phenol) is a phenol derivative that is chemically distinct from other intravenous sedative hypnotics. It has been extensively used as a short term anesthetic agent, because of the rapid onset and short duration of action. Propofol microemulsion system was prepared with different concentrations of ethyl oleate, $Solutol^{(R)}$ HS 15 and $Kollidon^{(R)}$ 17 PF. Propofol microemulsions were studied by transmittance, viscosity, particle size, in vitro release and pharmacokinetics. The range of transmittance of A group with 4% ethyl oleate and that of B group with 5% ethyl oleate were 92.6~95.1 and 91.3~94.2%, respectively. Transmittance 1~2% decreased as concentration of $Kollidon^{(R)}$ 17 PF was increased and increased 0.8~3.3% when 10 times diluted with normal saline. The viscosity of A and B group were in the range of 3.9~4.1 mPaㆍsec and 4.4~5.3 mPaㆍsec, respectively. The particle sizes of A and B group increased as amount of $Kollidon^{(R)}$ 17 PF. Also, release of propofol was slowly increased as the amount of $Kollidon^{(R)}$ 17 PF was increased. Propofol plasma concentration by i.v injection showed 2-compartment model. Pharmacokinetics of A-5 was similar to that of commercial emuision(POFOL).

• Journal of The Korean Society of Clinical Toxicology
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• v.5 no.2
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• pp.119-122
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• 2007

Paraquat poisoning is a fatal type of herbicide intoxication. It is characterized by multi-organ failure and pulmonary fibrosis with respiratory failure. Intravenous and intramuscular injection of paraquat is rarely described. However, We encountered two fatal cases of acute poisoning caused by paraquat injection. Two patients were admitted to our emergency unit after intravenous and intramuscular injection of 23.8% paraquat (about 476 mg of paraquat). A 37-year-old man diluted 2 ml of 23.8% paraquat solution with 1 ml of normal saline and injected it both intravenously into his left antecubital fossa and intramuscularly into his abdomen in a suicide attempt. He died 5 days later from respiratory failure and acute renal failure. A 92-year-old man was injected intravenously into his right antecubital fossa by his grandson with 2 ml of 23.8% paraquat solution diluted with 1 ml of normal saline. He died 2 days later from early circulatory collapse and multi-organ failure (metabolic acidosis, acute renal failure, coagulopathy). Intravenous and intramuscular injection with a small quantity of paraquat resulted in fatal toxicity in our patients.