• Polymer(Korea)
• /
• v.30 no.6
• /
• pp.556-562
• /
• 2006

Quarternized poly(4-vinyl pyridine)s have been prepared by the reaction of poly (4-vinyl pyridine)s (Mw=50 kg/mol and 200 kg/mol) and alkylating agents varying the carbon numbers of the alkyl groups (m):dimethyl sulfate (m=1) as well as bromoalkane (m= 5, 8, 12, 16, and 22) was used as an alkylating agent. The degree of alkylation was determined by using an elemental analysis and NMR spectroscopy. As a result, polyelectrolytes were obtained by the almost full alkylation of poly (4-vinyl pyridine)s. The critical aggregation concentration (CAC) was determined by measuring the change of turbidity occurred by addition of sodium dodecyl sulfate (SDS) into aqueous solution of quarternized poly-(4-vinyl pyridine)s, and the dependence of molecular weight of polymer, the length of N-alkyl group and concentration of NaCl upon CAC was investigated. As a result, as the molecular weight or the length of alkyl group was increased, less amount of SDS Gould induce the aggregation.

• Applied Microscopy
• /
• v.23 no.1
• /
• pp.35-55
• /
• 1993

cis-Dichlorodiammineplatinum (II) (cis-Platin), a metallic compound, has widely been used as an effective anticancer chemotherapeutic agent. The precise mechanism of action of this agent is still unknown, but it is postulated that cis-Platin may act on the cancer cell like bifunctional alkylating agents. Although this agent is very beneficial to the patients with cervical cancer, germinoma of testis, neuroblastoma and others, it may also damage to the normal cell so that many side effects; severe hemorrhagic enterocolitis, bone marrow depression, renal damage and liver damage will develope. This experiment has been undertaken to pursue the cytotoxic effects of the cis-Platin on the ultrastructures of the interalveolar septum in the mouse lung. A total of 55 healthy male mice of ICR strain were used as experimental animals and divided into 5 mice of normal control group and 50 mice of cis-Platin treated group. The mice of cis-Platin treated group were sacrificed by carotid exsanguination at 6, 12, 24 hours, 3 days and 7 days after intraperitoneal injection of 6.0 mg of cis-Platin ($Abiplatin^R$ Abic Co. Ltd.) per kg of mouse body weight. The specimen obtained from the lower lobe of left lung were sliced into $1mm^3$ and prefixed with 2% glutaraldehyde -2.5% paraformaldehyde solution prepared with Millonig's phosphatae buffer solution (pH 7.4) at $4^{\circ}C$ for 3-4 hours. After postfixation with 1% osmium tetroxide solution all specimens were embedded in Epon 812. Ultrathin sections about $600-800{\AA}$ in thickness were stained with uranyl acetate and lead citrate and observed with Hitachi-600 electron microscope. The results obtained were as follows: 1. Local swellings with increase of electron density and number of pinocytic vesicles in the cytoplasms of the type I pneumocyte and endothelial cell of the blood air barrier in interalveolar septum of cis-platin treated mice were observed. 2. Cisternae of rough endoplasmic reticulum were dilated and sacculated in association with detachment of membrane bound ribosomes of the type II pneumocyte in interalveolar septum of cis-Platin treated mice. 3. Swollon mitochondria with uneven electron density of their matrix were observed in the type II pneumocyte of interalveolar septum in the cis-Platin treated mice. 4. The lamellae of lammelar bodies in type II pneumocyte of interalveolar septum in cis-Platin treated mice were devoided or transformed into homogeneous electron dense material. It is consequently suggested that cis-Platin would induce the cellular edema of type I pneumocyte and endothelial cell, and degenerative changes of cytoplasmic organelles of the type II pneumocyte in the interalveolar septum of the mouse lung.

• Korean Journal of Bronchoesophagology
• /
• v.5 no.2
• /
• pp.164-173
• /
• 1999

Background : cis-Diamminedichloroplatinum(Ⅱ)(cis-platin) has been exhibited similar to bifunctional alkylating agents in the cell and known as an effective anticancer drug. Although this agent is very beneficial to the cancer patients, it may also damage to the normal cell. Many side effects were developed. Objectives : This experiments was undertaken to pursue the effect of cis-Platin on the mucous variation of the trachea. Materials and Methods : The male of Sprague-Dawley strain were used as and experimental animals. The experimental animals were killed at 1, 3 days and 1, 2 and 3 weeks after the third injection of cis-Platin was administered 1.5mg/kg to intraperitoneal injection at once a week for three weeks. The trachea was fixed to neutral formaline and stained with alcian blue(pH 1.0)-PAS, alcian blue(pH 2.5)-PAS double stains and these preparation observed with light microscope. Results : 1. In the trachea stained with alcian blue(pH 2.5)-PAS double stain, the epithelial cells were constricted in the 1 week, In the 1st day, 3rd day and 1st week, acidic mucopolysaccharide was increased but in the 2nd week, neutral mucopolysaccharide was increase. 2. In the trachea stained with alcian blue(pH 1.0)-PAS double stain, the 1st and 3rd day exhibited sulfa mucopolysaccharide with moderately or weakly positive reaction. In the 1st week the sulfa mucopolysaccharide with strongly positive reaction was increased. In the 2nd and 3rd week, the sulfa mucopolysaccharide with weakly positive and non-sulfa or neutral mucopolsaccharide with negative reaction were modified. Conclusion : It is consequently suggested that cis-Platin induces reversible toxic damage to tracheal cells including goblet cell.

• International Journal of Oral Biology
• /
• v.39 no.4
• /
• pp.229-236
• /
• 2014

Reactive oxygen species (ROS) and nitrogen species (RNS) are implicated in cellular signaling processes and as a cause of oxidative stress. Recent studies indicate that ROS and RNS are important signaling molecules involved in nociceptive transmission. Xanthine oxidase (XO) system is a well-known system for superoxide anions ($O{_2}^{{\cdot}_-}$) generation, and sodium nitroprusside (SNP) is a representative nitric oxide (NO) donor. Patch clamp recording in spinal slices was used to investigate the role of $O{_2}^{{\cdot}_-}$ and NO on substantia gelatinosa (SG) neuronal excitability. Application of xanthine and xanthine oxidase (X/XO) compound induced membrane depolarization. Low concentration SNP ($10{\mu}M$) induced depolarization of the membrane, whereas high concentration SNP (1 mM) evoked membrane hyperpolarization. These responses were significantly decreased by pretreatment with phenyl N-tert-butylnitrone (PBN; nonspecific ROS and RNS scavenger). Addition of thapsigargin to an external calcium free solution for blocking synaptic transmission, led to significantly decreased X/XO-induced responses. Additionally, X/XO and SNP-induced responses were unchanged in the presence of intracellular applied PBN, indicative of the involvement of presynaptic action. Inclusion of GDP-${\beta}$-S or suramin (G protein inhibitors) in the patch pipette decreased SNP-induced responses, whereas it failed to decrease X/XO-induced responses. Pretreatment with n-ethylmaleimide (NEM; thiol-alkylating agent) decreased the effects of SNP, suggesting that these responses were mediated by direct oxidation of channel protein, whereas X/XO-induced responses were unchanged. These data suggested that ROS and RNS play distinct roles in the regulation of the membrane excitability of SG neurons related to the pain transmission.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.24 no.1
• /
• pp.87-99
• /
• 1998

We have studied the effects of red ginseng root extract on the derease of MMS-induced gemotoxicity in cultured NIH3T3 cells. The increase in survival and the recovery from DNA synthesis inhibition in MMS-treated cells as a function of normal medium incubation time was potentiated, at a rate higher than those in UV-irradiated cells, by the presence of the ginseng extract. The extract also increased the MMS-induced excision repair as determined by unscheduled DNA synthesis. The amount of MMS-induced DNA single strand breads that are accumulated by polymerase inhibitors was increased, but as a rate lower rate than in UV-induced strand break, by the presence of the extract. These results suggest that the red ginseng extract increase MMS-induced repair and could be used as a reagent for protectiong alkylating agent-induced genotoxicity and cytotoxicity.

• Archives of Plastic Surgery
• /
• v.37 no.4
• /
• pp.329-334
• /
• 2010

Purpose: Adhesion after flexor tendon injury is a result of fibrosis between tendon and tendon sheath. This, finally interfere with gliding mechanism of tendon and results in functional problem of hands. Therefore, there have been many trials to reduce adhesion around the tendon. However, there is no standard procedure clinically practiced in hospitals. Mitomycin-C is an antineoplastic alkylating agent that decrease fibroblast proliferation and scar formation. It is commonly used in many surgery to reduce postoperative adhesion. This study was designed to observe the effect of Mitomycin-C on preventing adhesion in injured flexor tendon. Methods: The deep flexor tendon of digit 2 and 4 in the left forepaw of 15 New Zealand White rabbits were subjected to partial tenotomy. In study group, injury site was exposed to a single 5-minute application of Mitomycin-C, and in control group was left untreated. Digit 2 and 4 in the right forepaw of each rabbit were considered as nonadhesion control group. After 2 weeks, the animals were sacrificed and digits were amputated for biomechanical test and histological study. Results: In biomechanical study to measure yield point, mean yield point of non-adhesion control was $17.43{\pm}2.33$ and $25.07{\pm}4.03$ for adhesion control, which proves increase of adhesion in adhesion control group (p<0.05) in 95% confidence. In Mitomycin-C group, mean yield point was $12.71{\pm}4.97$. Compared with adhesion control, there was decrease in adhesiveness in Mitomycin-C group (p<0.05) in 95% confidence. In histological study, the result of adhesion control revealed massive adhesions of bony structure, fibrotic tissue and tendon structure with ablation of the border. However in Mitomycin-C group, we could find increased fibrotic tissue, but adhesion is much lesser than adhesion group and borders between structures remain intact. Conclusion: This study suggests that Mitomycin-C can significantly reduce adhesion of injured flexor tendon in rabbit model.

• Journal of Nutrition and Health
• /
• v.36 no.10
• /
• pp.1013-1021
• /
• 2003

Anemia, the condition of the diminished concentration of hemoglobin per erythrocyte is common in patients with cancer and is a frequent complication of myelosuppressive chemotherapy. Cham-Dang-Gui (Angelicae Gigantis Radix) has been used in traditional Korean medicine to treat hematologic deficiencies. In this study, Cyclophosphamide (CYP), an alkylating agent that has a broad spectrum of anti-cancer activities, was intraperitoneally injected into the experimental animals to suppress the bone marrow thereafter, causing anemia. The hemopoietic effects of Cham-Dang-Gui were examined using anemic rat model. Rats were divided into five groups: CON (control group), ANS (CYP-injected + normal diet), AND (CYP-injected + normal diet + Cham-Dang-Gui), ALS (CYP-injected + low iron diet), and ALD (CYP-injected + low iron diet + Cham- Dang-Gui) groups. CYP (30 mg/kg) was intraperitoneally injected to rats for 3 days to induce anemic condition. Saline or Cham-Dang-Gui was administrated orally during the entire experimental period. CYP injection decreased body weight gain and food consumption in comparison with CON group. Oral administration of Cham-Dang-Gui extract with normal iron diet significantly prevented the lower body weight gain. The blood level of hemoglobin, iron status (serum iron, transferrin, ferritin and TIBC) and blood level of vitamin B-12 in Cham-Dang-Gui treated groups were significantly higher than those of Cham-Dang-Gui untreated groups regardless of amount of iron in the diet. Taken together, it could be concluded that the Cham-Dang-Gui extract could improve anemic condition induced by CYP injection by improving hematological value, iron status and vitamin B12 status in rats.

• The Korean Journal of Physiology and Pharmacology
• /
• v.26 no.1
• /
• pp.25-36
• /
• 2022

To identify the effect and mechanism of carbon monoxide (CO) on delayed rectifier K⁺ currents (I_K) of human cardiac fibroblasts (HCFs), we used the wholecell mode patch-clamp technique. Application of CO delivered by carbon monoxidereleasing molecule-3 (CORM3) increased the amplitude of outward K⁺ currents, and diphenyl phosphine oxide-1 (a specific I_K blocker) inhibited the currents. CORM3-induced augmentation was blocked by pretreatment with nitric oxide synthase blockers (L-NG-monomethyl arginine citrate and L-NG-nitro arginine methyl ester). Pretreatment with KT5823 (a protein kinas G blocker), 1H-[1,-2,-4] oxadiazolo-[4,-3-a] quinoxalin-1-on (ODQ, a soluble guanylate cyclase blocker), KT5720 (a protein kinase A blocker), and SQ22536 (an adenylate cyclase blocker) blocked the CORM3 stimulating effect on I_K. In addition, pretreatment with SB239063 (a p38 mitogen-activated protein kinase [MAPK] blocker) and PD98059 (a p44/42 MAPK blocker) also blocked the CORM3's effect on the currents. When testing the involvement of S-nitrosylation, pretreatment of N-ethylmaleimide (a thiol-alkylating reagent) blocked CO-induced I_K activation and DL-dithiothreitol (a reducing agent) reversed this effect. Pretreatment with 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)-21H,23H porphyrin manganese (III) pentachloride and manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (superoxide dismutase mimetics), diphenyleneiodonium chloride (an NADPH oxidase blocker), or allopurinol (a xanthine oxidase blocker) also inhibited CO-induced I_K activation. These results suggest that CO enhances I_K in HCFs through the nitric oxide, phosphorylation by protein kinase G, protein kinase A, and MAPK, S-nitrosylation and reduction/oxidation (redox) signaling pathways.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.2
• /
• pp.429-436
• /
• 1998

Approximately 100 drugs have been reported to affect the lungs adversely. Among these, pulmonary toxicity caused by antieneoplastic agent. is being recognized more frequently. Cyclophosphamide is an immunosuppressive alkylating agent used for the treatment of a wide variety of malignant and nonmalignant diseases. The incidence of pulmonary toxicity is probably less than 1 percent The first case was reported in 1967. Since then, more than 20 well-documented cases of pulmonary toxicity associated with cyclophosphamide have been reported in the literature. In Korea, three patients were identified with cyclophosphamide-induced lung disease. The typical features of toxicity include dyspnea, fever, cough, new parenchymal infiltrates, gas exchangs abnormalities on pulmonary function tests, and pleural thickening on chest roentgenogram. The best approach to management is early diagnosis, discontinuation of the offending drug and administration of corticosteroid therapy. Recently, we experienced a case of diffuse alveolar damage induced by cyclophosphamide. The patient presented with early-onset pulmonary toxicity and died of repiratory failure despite early use of corticosteroid.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.3
• /
• pp.225-231
• /
• 1997

As it has been reported that the depolarization-induced norepinephrine (NE) release is modulated by activation of presynaptic $A_1-adenosine$ heteroreceptor and various lines of evidence indicate the involvement of adenylate cyclase system in $A_1-adenosine$ post-receptor mechanism in hippocampus, it was attempted to delineate the role of adenylate cyclase system in the $A_1-receptor-mediated$ control of NE release in this study. Slices from rat hippocampus were equilibrated with $[^3H]-NE$ and the release of the labelled products was evoked by electrical stimulation.(3 Hz, $5Vcm^{-1}$, 2 ms, rectangular pulses). The influence of various agents on the evoked tritium-outflow was investigated. $N^6-Cyclopentyladenosine$ (CPA), a specific $A_1-adenosine$ receptor agonist, in concentrations Tanging from 0.1 to $10{\mu}M$ decreased the $[^3H]-NE$ release in a dose-dependent mauler without any change of basal rate of release. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, $2{\mu}M$), a selective $A_1-receptor$ antagonist, inhibited the CPA effect. The responses to N-ethylmaleimide $(3&10{\mu}M)$, a SH-alkylating agent of G-protein, were characterized by increments of the evoked NE-release and the CPA effects were completely abolished by NEM pretreatment. Forskolin, a specific adenylate cyclase activator, in concentrations ranging from 0.1 to $30{\mu}M$ increased the evoked and basal rate of NE release in a dose-dependent manner and the CPA effects were inhibited by forskolin pretreatment. Rolipram $(1&10{\mu}M)$, a phosphodiesterase inhibitor, did not affect the evoked NE release but reduced the CPA effect. And 8-bromo-cAMP $(100&300{\mu}M)$, a membrane permeable cAMP analogue inhibited the CPA effect significantly. These results suggest that the $A_1-adenosine$ heteroreceptor plays an important role in NE-release via nucleotide-binding protein $G_i$ in the rat hippocampus and that the adenylate cyclase system might be participated in this process.