Assessment of Risks and Benefits of Using Antibiotics Resistance Genes in Mesenchymal Stem Cell-Based Ex-Vivo Therapy

Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant

Cell Type-specific Knockout with Gli1-mediated Cre Recombination in the Developing Cerebellum

The inducible Cre-loxP system provides a useful tool for inducing the selective deletion of genes that are essential for proper development and enables the study of gene functions in properly developed animals. Here, we show that inducible Cre-loxP driven by the Gli1-promoter can induce cell-type-specific deletion of target genes in cerebellar cortical neurons. We used reporter mice containing the YFP (yellow fluorescence protein) gene at the Gt(ROSA)26Sor locus with a loxP -flanked transcriptional stop sequence, in which successful Cre-mediated excision of the stop sequence is indicated by YFP expression in Cre-expressing cells. Administration of tamoxifen during early postnatal days (P4~7) induces Cre-dependent excision of stop sequences and allows YFP expression in proliferating neuronal progenitor cells in the external granule layer and Bergmann glia in the Purkinje cell layer. A substantial number of YFP-positive progenitor cells in the external granule layer migrated to the internal granule cell layer and became granule cell neurons. By comparison, injection of tamoxifen during late postnatal days (P19~22) induces YFP expression only in Bergmann glia, and most granule cell neurons were devoid of YFP expression. The results indicate that the Gli1 promoter is temporarily active in progenitor cells in the external granule layer during the early postnatal period but constitutively active in Bergmann glia. We propose that the Gli1-mediated CreER system can be applied for the conditional deletion of genes of interest from cerebellar granule cell neurons and/or Bergmann glia.

Cell Type-specific Knockout with Gli1-mediated Cre Recombination in the Developing Cerebellum

The inducible Cre-loxP system provides a useful tool for inducing the selective deletion of genes that are essential for proper development and enables the study of gene functions in properly developed animals. Here, we show that inducible Cre-loxP driven by the Gli1-promoter can induce cell-type-specific deletion of target genes in cerebellar cortical neurons. We used reporter mice containing the YFP (yellow fluorescence protein) gene at the Gt(ROSA)26Sor locus with a loxP -flanked transcriptional stop sequence, in which successful Cre-mediated excision of the stop sequence is indicated by YFP expression in Cre-expressing cells. Administration of tamoxifen during early postnatal days (P4~7) induces Cre-dependent excision of stop sequences and allows YFP expression in proliferating neuronal progenitor cells in the external granule layer and Bergmann glia in the Purkinje cell layer. A substantial number of YFP-positive progenitor cells in the external granule layer migrated to the internal granule cell layer and became granule cell neurons. By comparison, injection of tamoxifen during late postnatal days (P19~22) induces YFP expression only in Bergmann glia, and most granule cell neurons were devoid of YFP expression. The results indicate that the Gli1 promoter is temporarily active in progenitor cells in the external granule layer during the early postnatal period but constitutively active in Bergmann glia. We propose that the Gli1-mediated CreER system can be applied for the conditional deletion of genes of interest from cerebellar granule cell neurons and/or Bergmann glia.

Potential for Dependence on Lisdexamfetamine - In vivo and In vitro Aspects

Although lisdexamfetamine is used as a recreational drug, little research exists regarding its potential for dependence or its precise mechanisms of action. This study aims to evaluate the psychoactivity and dependence profile of lisdexamfetamine using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques are used to assess alterations in the dopamine levels in striatal synaptosomes following administration of lisdexamfetamine. Lisdexamfetamine increased both conditioned place preference and self-administration. Moreover, after administration of the lisdexamfetamine, dopamine levels in the striatal synaptosomes were significantly increased. Although some modifications should be made to the analytical methods, performing high performance liquid chromatography studies on synaptosomes can aid in predicting dependence liability when studying new psychoactive substances in the future. Collectively, lisdexamfetamine has potential for dependence possible via dopaminergic pathway.

Potential for Dependence on Lisdexamfetamine - In vivo and In vitro Aspects

Although lisdexamfetamine is used as a recreational drug, little research exists regarding its potential for dependence or its precise mechanisms of action. This study aims to evaluate the psychoactivity and dependence profile of lisdexamfetamine using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques are used to assess alterations in the dopamine levels in striatal synaptosomes following administration of lisdexamfetamine. Lisdexamfetamine increased both conditioned place preference and self-administration. Moreover, after administration of the lisdexamfetamine, dopamine levels in the striatal synaptosomes were significantly increased. Although some modifications should be made to the analytical methods, performing high performance liquid chromatography studies on synaptosomes can aid in predicting dependence liability when studying new psychoactive substances in the future. Collectively, lisdexamfetamine has potential for dependence possible via dopaminergic pathway.

Dependence Potential of Tramadol: Behavioral Pharmacology in Rodents

Tramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.

Dependence Potential of the Synthetic Cannabinoids JWH-073, JWH-081, and JWH-210: In Vivo and In Vitro Approaches

Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the CB1 receptor (JWH-073, 081, and 210) and Delta9-tetrahydrocannabinol (Delta9-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. Ki values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed CB1 protein membranes to compare dependence potential with CB1 receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except Delta9-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the CB1 receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.

A Large Polypoid Vascular Ectasia Removed by Using a Polypectomy With a Detachable Snare in an Asymptomatic Patient

Vascular ectasia is a well-known cause of lower gastrointestinal bleeding in the elderly. Endoscopically, it usually appears as a flat or elevated bright red lesion. We report on an extremely rare case of a large, pedunculated, polypoid vascular ectasia in an asymptomatic patient. A large pedunculated polypoid mass in the sigmoid colon was observed on colonoscopy during a regular health check-up, and a polypectomy was performed using a detachable snare. In histology, vessels with massive dilation were found mainly in the submucosa, which was consistent with vascular ectasia.

A Case of Propionic Acidemia

Propionic acidemia is an autosomal-recessive inborn error of branched-chain amino acid metabolism. It is caused by deficient activity of propionyl-coenzyme A carboxylase and is characterized by a spectrum of clinical and biochemical findings. It usually manifests in the neonatal period or early infancy. Since Childs et al first described the propionic acidemia of infants in 1961, it has rarely been reported. There have been no previous report of this organic acidemia in Korea. We present a case of propionic acidemia in a 4-day old male, who had poor feeding, dehydration, and hyperammonemia and died at 12 days of age. Diagnosis was established by gas chromatography and mass spectrometry, and this case is the first reported propionic acidemia in literature in Korea. A review of the related literature was included.

A Case of Propionic Acidemia

Propionic acidemia is an autosomal-recessive inborn error of branched-chain amino acid metabolism. It is caused by deficient activity of propionyl-coenzyme A carboxylase and is characterized by a spectrum of clinical and biochemical findings. It usually manifests in the neonatal period or early infancy. Since Childs et al first described the propionic acidemia of infants in 1961, it has rarely been reported. There have been no previous report of this organic acidemia in Korea. We present a case of propionic acidemia in a 4-day old male, who had poor feeding, dehydration, and hyperammonemia and died at 12 days of age. Diagnosis was established by gas chromatography and mass spectrometry, and this case is the first reported propionic acidemia in literature in Korea. A review of the related literature was included.

Ten cases of congenital anomalies diagnosed by prenatal ultrasonography / 대한산부인과학회잡지

No abstract available.