No abstract available.
Colon* ; Colonic Neoplasms* ; Dimenhydrinate* ; Oncogenes* ; Rats, Wistar*

PURPOSE: To understand the pathogenesis of the disease that presents abnormally proliferated vascular endothelial cells, a model of DMH(1,2-dimethylhydrazine)-induced abnormal proliferation of HUVECs(Human Umbilical Vein Endothelial Cells) was made. We indirectly determined that Protein Kinase C(PKC) restricts the cellular proliferation and inhibits the manifestation of growth factor by using several inhibiting substances of the transmitter through our previous studies. Thereupon, we attempted to observe direct enzymatic activities of PKC and its correlation with the abnormal proliferation of vascular endothelial cells. METHODS: 10(5) HUVECs cells were applied to 6 individual well plates in three different groups; A control group cultured without treatment, a group concentrated with 0.75x10(-8)M DMH only, and a group treated with DMH & 5x10(-9)M Calphostin C, inhibitor of PKC. In analyzing the formation of intracellular PKC enzyme, protein separation was performed, and separated protein was quantitatively measured. PKC enzyme reaction was analyzed through Protein Kinase C Assay System (Promega, USA), and the results were analyzed according to Beer's law. RESULTS: Enzymatic activity of PKC presented the highest in all reaction time of a group concentrated only with DMH, and the lowest in the control group. The group treated with DMH and the inhibitor revealed statistically lower enzymatic activity than group only with DMH in all reaction time, although higher than the control group. CONCLUSION: From the enzymatic aspect, most active and immediate reaction of the PKC was observed in the group concentrated with DMH only. The group treated with DMH & PKC inhibitor showed meaningful decrease. Accordingly, PKC holds a significant role in DMH-induced abnormal proliferation of vascular endothelial cells.
Cell Proliferation ; Dimenhydrinate ; Endothelial Cells* ; Jurisprudence ; Protein Kinase C* ; Protein Kinases* ; Reaction Time ; Umbilical Veins

BACKGROUND/AIMS: The purpose of this study was to investigate the malignant potential of aberrant crypt foci (ACF) by measuring the multiplicity of crypts and lectin expression in the early and late stages of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. METHODS: Six-week-old Wistar rats were injected subcutaneously with DMH for 27 weeks. We classified ACF according to the number of crypts per ACF as a few crypts (< or =3 crypts, FC ACF) or numerous crypts (> or =4 crypts, NC ACF). Immunohistochemistry was used to evaluate lectin expression. RESULTS: In the early stage, FC ACF (590/1,902, 31.0%) occurred more frequently than NC ACF (35/449, 7.8%); whereas in the late stage, NC ACF (176/449, 39.2%) occurred more frequently than FC ACF (324/1,902, 17.0%). The number of ACF peaked at 15 to 20 weeks. The ratio of NC/FC ACF increased gradually during carcinogenesis. The expression of both UEA1 and PNA was higher in NC ACF than FC ACF. Lectin expression increased in the late stage compared with the early stage. CONCLUSIONS: The expression of lectin was higher in NC ACF and ACF in the late stage. Therefore, ACF with higher multiplicities in the late stage may have more malignant potential in DMH-induced colon carcinogenesis.
1,2-Dimethylhydrazine ; Aberrant Crypt Foci ; Animals ; Colon ; Dimenhydrinate ; Immunohistochemistry ; Peanut Agglutinin ; Rats ; Rats, Wistar

Many studies for verifying angiogenesis have been in progress, especially in the field of abnormal vascular proliferation to explain the pathogenesis and to develop a treatment of several diseases. In our previous experiments, endothelial cell proliferations were induced by DMH stimulation in vitro, and the 177 factors(142 up- regulated and 35 down-regulated factors) were identified. Among the up-regulated factors, 9 substances (EFEMP1, CTGF, CYR61, ITGbeta1, FHL2, SERPINE1, MYC, PTTG1 and MSH6) were selected, which were related to cell proliferation and showed high signal intensities. The RNA was isolated from HUVECs at the time of 0, 6, 12, 24 hours after the DMH treatment, and RNA of control group HUVECs was also isolated. Genetic information of selected molecules was used to make primer for each, and RT-PCR was performed to analyze both groups. In control and treatment groups, each substance presented variety of manifestation degree according to time differences. EFEMP1, CTGF, CYR61, ITGbeta1, FHL2 and MYC were related to abnormal vascular proliferation steadily and SERPINE1, PTTG1 and MSH6 were related secondarily. CTGF was related to both normal and abnormal proliferation, but it played a more significant role in abnormal proliferation from earlier stage. EFEMP1, CYR61, ITGbeta1, FHL2 and MYC were similar to CTGF, although the relation appeared lately. Further study should be performed to analyze the expressions and the interactions of growth factors, which could be utilized in the new therapeutic development.
Cell Proliferation ; Dimenhydrinate ; Dimethylhydrazines ; Endothelial Cells* ; Intercellular Signaling Peptides and Proteins ; RNA ; Umbilical Veins

BACKGROUND: Motion sickness is one of the major problems of aerospace medical concern. Vestibule plays an important role in giving rise to motion sickness. Drugs preventing motion sickness have a suppressive effect on the vestibular function through the antagonistic effect to some receptors in vesibular nuclei and vomiting center of central nervous system. We identified and quantified the effects of anti-motion sickness drugs on vestibule-ocular reflex in healthy human subjects. METHODS: Fourty-five healthy male subjects were grouped to one of placebo, dimenhydrinate 50 mg, scopolamine (1 patch), or both scopolamine and dimenhydrinate group, and received rotation chair test before and after drug administration to obtain Vestibulo-ocular reflex (VOR) gain and phase in sinusoidal harmonic acceleration (SHA) with frequencies of 0.01, 0.02, 0.04 and 0.08 Hz. The delta gain and the delta phase by the drug administration were obtained and analyzed as pharmacodynamic effects. RESULTS: Baseline gain and phase data were not different by the groups in all SHA frequencies. VOR gains were significantly decreased by 0.15~0.17 after dimenhydrinate administration. In the scopolamine group, there were significant decreases in 0.04 and 0.08 Hz by 0.14 and 0.15, respectively, but no difference in 0.01 and 0.02 Hz was observed. Increasing tendency in VOR phase lead was observed, especially in dimenhydrinate, but not significantly. There was no additive effect on the reduction of VOR gain when the two drugs were co-administered. CONCLUSION: We quantitatively characterized how much the VOR parameters were changed by the drugs with different kinds of mechanism. Dimenhydrinate reduced the VOR gain by around 0.16. However, scopolamine probably has a minimal or no additive effect on VOR suppression.
Acceleration ; Central Nervous System ; Dimenhydrinate ; Humans* ; Male ; Motion Sickness ; Reflex ; Reflex, Vestibulo-Ocular ; Scopolamine Hydrobromide ; Vomiting

BACKGROUND AND OBJECTIVES: Dimenhydrinate is known to act on the vestibular system, causing vestiular suppression. But the effects related with therapeutic dosage on eye tracking tests and vestibulo-ocular reflex (VOR) are not clear yet. We performed this study to evaluate the effects of dimenhyrinate on eye tracking tests and VOR. MATERIALS AND METHODS: Twenty five healthy subjects, comprising of 12 men and 13 women between the ages of 15 and 69 (mean age=39) participated in this study. The assessment included saccade test, smooth pursuit test, optokinetic nystagmus test for eye tracking test and sinusoidal harmonic acceleration test for VOR test. Each test was performed before, and 2 hours and 4 hours after the oral intake of dimenhydrinate (therapeutic dosage: 50 mg). The subjects were kept alert by performing a calculation task and communicating with the investigator during tests. RESULTS: Analysis of results showed that latency was prolonged after 2 hours but was returned to initiae value after 4 hours. Gain was not changed in the saccade test as well as in the smooth pursuit test. Mean slow phase eye velocity (SPEV) decreased after 4 hours in optokinetic nystagmus test. Gain and phase lead decreased only at 0.01 Hz in sinusoidal harmonic acceleration test. CONCLUSION: Dimenhydrinate had minimal effects on eye tracking tests and VOR when the patient's alertness was kept during test.
Acceleration ; Dimenhydrinate* ; Female ; Humans ; Male ; Nystagmus, Optokinetic ; Pursuit, Smooth ; Reflex, Vestibulo-Ocular ; Research Personnel ; Saccades

PURPOSE: Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, have been known to take a role in signal transduction pathway of angiogenesis. The authors confirmed that PKC is the most noticeable mediator for abnormal proliferation of vascular endothelial cells through in vitro study model using the inhibitors, targeting the formation of three co-enzymes. In this study, we would investigate which isoform of PKC play an important role in abnormal angiogenesis of vascular endothelial cell. METHODS: In 96 well plates, 10(4) HUVECs(human umbilical vein endothelial cells) were evenly distributed. Two groups were established; the control group without administration of DMH(1,2-dimethylhydrazine) and the DMH group with administration of 7.5x10(-9)M DMH. RNA was extracted from vascular endothelial cell of each group and expression of the PKC isoform was analyzed by RT-PCR(reverse transcriptase-polymerase chain reaction) method. RESULTS: RT-PCR analysis showed that PKCalpha, -betaI, -betaII, -eta, -micron and -zeta were expressed in vascular endothelial cells of each group. DMH incresed the expression of PKCalpha and PKCmicron, and decreased PKCbetaI, PKCbetaII expression dominantly. CONCLUSION: Based on the result of this study, it was suggested that PKCalpha and PKCmicron may have significant role in abnormal proliferation of vascular endothelial cell.
1,2-Dimethylhydrazine* ; Cell Proliferation ; Dimenhydrinate ; Endothelial Cells* ; Oxidoreductases ; Protein Kinase C* ; Protein Kinases* ; RNA ; Signal Transduction ; Tyrosine ; Umbilical Veins

BACKGROUND: Antihistamine drugs are used widely in many conditions. Although some antihistamines may cause a photosensitive reaction,many physicians are not awae of it. OBJECTIVE: For examination of the phototoxic potential of antihistamines, we performed the Candida albiecrns test which is simple, cheap, and good for the screening of many drugs. MEHTODS: Thirty microliters of each solute of various antihistamines were applied to the Sabraud dextrose agar plate in which Candida albicans were applied diffusly. Four hours after the application, 60J/cm fo UVA was irradiated for two days. The irradiated. plates and nonirradiated control ones were incubated in a dark room for 48 hours, and examined for lear zones arround the drug, which means a positive results for the phototoxic potential of the drugs. RESULTS: Mequitazine, thiethylperazine, perphenazine and cllorromazine showed positive results, whereas others did not. An additional Candida albicans test using 0.1%, 0.01%, and 0.001% of the positive drugs revealed tht chlorpromazine, thiethylperazine aderphenazine showed positive results at 0.1%, but negative at 0.01 and 0.001%. Mequitazine was niegative at 0.1, 0.01, and 0,001%, Additional studies of the Candida albicans test using 5% and 10% of the diphenhydramine and dimenhydrinate, those were known photosensitizers but they slowed negative results at this study and revealed very weak posit,ive result in 10% diphenhydramine. CONCLUSION: A photosensitive reaction such as photoallergy and persistent light react,ion may be triggered by the phenothiazine antihistamines. Negative result in 1%, and very weak positive results in 10% diphenhydramine may be due to different mechanism of phototoxicity, or the low phototoxic potential of diphenhydrainine.
Agar ; Candida albicans* ; Candida* ; Chlorpromazine ; Dermatitis, Photoallergic ; Dermatitis, Phototoxic* ; Dimenhydrinate ; Diphenhydramine ; Glucose ; Histamine Antagonists ; Mass Screening* ; Perphenazine ; Photosensitizing Agents ; Thiethylperazine

Colon cancer is considered as the precarious forms of cancer in many developed countries, with few to no symptoms; the tumor is often diagnosed in the later stages of cancer. Monoterpenes are a major part of plant essential oils found largely in fruits, vegetables and herbs. The cellular and molecular activities show therapeutic progression that may reduce the risk of developing cancer by modulating the factors responsible for colon carcinogenesis. Colon cancer was induced with DMH with a dose of (20 mg/Kg/body weight) for 15 weeks by subcutaneous injection once in a week. Myrtenal treatment was started with (230 mg/Kg/body weight) by intragastric administration, one week prior to DMH induction and continued till the experimental period of 30 weeks. The Invivo results exhibit the elevated antioxidant and lipid peroxidation levels in DMH treated animals. The Histopathological analysis of colon tissues well supported the biochemical alterations and inevitably proves the protective role of Myrtenal. Treatment with myrtenal to cancer bearing animals resulted in a remarkable increase in the inherent antioxidants and excellent modulation in the morphological and physiological nature of the colon tissue. It is thus concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of colon carcinoma in Wistar albino rats.
Animals* ; Antioxidants ; Carcinogenesis ; Colon* ; Colonic Neoplasms* ; Developed Countries ; Dimenhydrinate ; Fruit ; Injections, Subcutaneous ; Lipid Peroxidation ; Monoterpenes ; Oils, Volatile ; Plants ; Rats ; Vegetables

PURPOSE: DMH(1,2-dimethylhydrazine) has been known to induce vascular neoplasm such as malignant endothelioma in animal experiment, through induction of abnormal proliferation of HUVECs. In our previous studies, 11 types of PKC isoenzymes were determined by RT-PCR and the expression of PKCalpha, and mu was more prominent than other PKC isoenzymes in the DMH-treated group. However, this result was not based on objective assessment. In this study, we further evaluated the role of PKCalpha on the DMH-induced abnormal proliferation of HUVECs by two different methods to identify its presence with high relevance in objective view. PKCmu will be investigated in further study. METHODS: The study was conducted with the cultured HUVECs group(control) and the 0.75x10(-9)M DMH-treated group. After processing protein extraction in 0 and 24 hour, extracted protein was treated of quantitative test through BCA protein assay. In the western blot analysis, electrophoresis was performed in the order of gel preparation, sample preparation, and gel running. Electrotransfer to nitrocellulose membrane and reaction with antibody were done. Detection of PKCalpha was achieved through "Gel Image Analysis System". In the fluorescence immunocytochemical analysis, the grading of radiance of the intracellular PKCalpha particles was detected with confocal microscope after treating with primary and fluorescent secondary antibody in 0 and 24 hours. RESULTS: The Western blot analysis showed increased PKCalpha expression from the specimen obtained in 24 hour of the DMH treatment group when compared to those in control group. Under confocal fluorescence microscope, the emitting radiance in the DMH treated group was brighter at 24 hours as well. CONCLUSION: We believe that PKCalpha plays a role in DMH-induced abnormal proliferation of the vascular endothelium, which may provide insights in understanding the vascular neoplasm.
Animal Experimentation ; Blotting, Western ; Collodion ; Dimenhydrinate ; Electrophoresis ; Endothelium, Vascular ; Fluorescence ; Isoenzymes ; Membranes ; Protein Kinase C ; Running ; Vascular Neoplasms