• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8377-8382
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9355-9360
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• 2014

Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. In this study, we evaluate the efficacy of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting HER2 expression profile in OSCC model in rat. Results: DOX-MTX- nanoparticle complexes caused significant decrease in mRNA level of HER2 compared to untreated cancers (p<0.05) and this finding was more pronounced with the IV mode (p<0.000). Surprisingly, HER2 mRNA was not affected in DOX treated as compared to the control group (p>0.05). On the other hand, in the DOX-MTX NP treated group, fewer tumors characterized with advanced stage and decreased HER2 paralleled improved clinical outcome (P<0.05). Moreover, the effectiveness of the oral route in the group treated with nanodrug accounted for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Furthermore, there was no significant difference in mRNA level of HER2 (p>0.05). Conclusions: Influence of HER2 gene expression is a new feature and mechanism of action observed only in dual action DOX-MTX-NPs treated groups. Down-regulation of HER2 mRNA as a promising marker and prognosticator of OSCC adds to the cytotoxic benefits of DOX in its new formulation. Both oral and IV application of this nanodrug could be used, with no preferences in term of their safety or toxicity. As HER2 is expressed abundantly by a wide spectrum of tumors, i DOX-MTX NPs may be useful for a wide-spectrum of lesions. However, molecular mechanisms underlying HER2 down regulation induced by DOX-MTX NPs remain to be addressed.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.141-145
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• 1995

Omeprazole, a proton pump inhibitor, was given intravenously (iv), orally (po), intraperitoneally (ip), hepatoportalvenously (pv), and intrarectally (ir) to rats at a dose of 72mg/kg in order to investigate the bioavailability of the drug, The extent of bioavailabilities of omeprazole administered through pv, ip, po, and ir routes were 88.5, 79.4, 40,8, and 38.7%, respectively. Pharmacokinetic analysis in this study and literatures (Regardh et al., 1985 : Watanabe et al., 1994) implied significant dose-dependency in hepatic first-pass metabolism, clearance and distribution, and acidic degradation in gastric fluid. The high bioavailability from the pv administration (88.5%) means that only 11.5% of dose was extracted by the first-pass metabolism through the liver at this dose (72 mg/kg). The low bioavailability from the oral administration (40.8%) in spite of minor hepatic first-pass extraction indicates low transport of the drug from GI lumen to portal vein. From the literature (Pilbrant and Cederberg, 1985), acidic degradation in gastric fluid was considered to be the major cause of the low transport. Thus, enteric coating of oral preparations would enhance the oral bioavailability substantially. The bioavailability of the drug from the rectal route, in which acidic degradation and hepatic first-pass metabolism may not occur, was low (38.7%) but comparable to that from the oral route (40.8 %) indicating poor transport across the rectal membrane. In this case, addition of an appropriate absorption enhancer would improve the bioavailability. Rectal route seems to be an possible alternative to the conventional oral route for omeprazole administration.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.427-436
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• 1993

The pharmacokinetics and relationship between in vitro dissolution and in vivo fraction absorbed were investigated after intravenous(iv) injection of omeprazole(OMZ), oral administration of OMZ capsules and rectal administration of 8 types of suppositories. The plasma concentration of OMZ (C$_{p}$)-time (t) curve after iv. administration fitted a two-compartment open model and the equation which best fitted the pharmacokinetics of OMZ was $C_{p}$ = 13.936 $e^{-8.78t}$+2.973 $e^{-0.716t}$. The bioavailabilities of OMZ in Witepsol H15 base (Supp-2) and PEG 4000 base (Supp-6) suppositories were 40.7% and 33.4%, respectively, which are higher(p<0.001) than 13% of oral administration of capsule. The avoidance fractions of the first-pass metabolism for Supp-2 and Supp-6 suppositiories were 31.8% and 23.4%, respectively, suggesting that the rectal application of OMZ may be a more adequate route of administration than oral one.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.210-214
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• 2008

The pharmacokinetic parameters and bioavailability of pranoprofen from the gel were measured to determine the enhancing effect of octanoic acid on the transdermal absorption of pranoprofen in rats. 8 mg/kg of pranoprofen was administered from gel with octanoic acid (the enhancer group) or that without octanoic acid (the control group) via the transdermal route, and the results were compared with those obtained from the intravenously (0.5 mg/kg, IV group) or orally administered group (4 mg/kg, oral group). The AUC of the control, the enhancer, the IV, and the oral groups were $20.2{\pm}5.1$, $50.7{\pm}12.7$, $19.9{\pm}2.5$, and $70.5{\pm}17.6\;ug/ml{\cdot}h$ respectively. The average $C_{max}$ of the control and the enhancer group were $0.93{\pm}0.23$ and $2.82{\pm}0.71\;ug/ml$, respectively, and the mean $T_{max}$ of the control and the enhancer group was 7.00 h. The relative bioavailability of the transdermally administered pranoprofen gel containing octanoic acid was approximately 2.50 times higher than the control group, showing a relatively constant, sustained blood concentration with minimal fluctuation. This suggests that it might be feasible to develop a pranoprofen gel preparation containing an enhancer for the transdermal administration, which is more convenient dosage form than the oral dosage forms.

• Journal of the korean academy of Pediatric Dentistry
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• v.37 no.2
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• pp.213-217
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• 2010

The use of chloral hydrate and hydroxyzine for oral sedation is most effective in children aged less than 36 months and weighing less than 15 kg. Children who do not belong to this category may show frequent movements due to shallow sedation level, and it can lead to sedation failures. One of the solutions to such sedation failure is conversion to deeper sedation. But, it is not so much of an option, since inhalation anesthetics and devices are required. In this case, conversion from oral sedation to intravenous sedation was successfully achieved without causing injection pain while searching for an intravenous route, by using EMLA cream (Eutectic Mixture of Local Anesthesia). A patient aged 46 months and weighing 15 kg visited the Pediatric Department of Dankook University Dental Hospital. Treatment under TSD(Tell Show Do) was offered, but due to the parent's request, oral sedative measures were taken. Considering prompt converting from oral sedation to iv sedation in case the oral sedation fails, EMLA cream was apllied preemptively. Adequate sedation level could not be achieved after 90 minutes of oral administration, therefore, under the parent's consent, intravenous route was prepared after conscious sedation by $N_2O-O_2$. During treatment, $ETCO_2$, $SPO_2$ and heart rate was monitored every 5 minutes. The patient showed stable vital signs and did not show any movements. The whole procedure took two and a half hours in total, and the treatment was completed without any adverse effects.

• Quality Improvement in Health Care
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• v.9 no.2
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• pp.230-240
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• 2002

Background : The purpose of this study was to develop, implement and evaluate the pharmacist intervention program designed to identify and correctly adjust the dosage of $H_2$-receptor antagonists ($H_2RA$) in renally impaired patients and promote timely conversion of $H_2RA$ from IV to PO therapy. Methods : The study population consisted of renally impaired patients who received $H_2RA$ therapy from April 9 to May 8, 2001 at Hallym Medical Center. Each morning a specifically developed software program identified patients with serum creatinine (Scr) greater than 1.2 mg/dl or age greater than 65 years. The pharmacist, then screened the pharmacy profiles of the identified patients to determine if the patient was on $H_2RA$. For these patients on $H_2RA$ with renal impairement the creatinine clearance (CrCl) was calculated using Cockroft & Gault equation. The pharmacist determined the proper dosage for each identified patients based on the calculated CrCl and the oral dosage that would be appropriate for whom IV therapy was no longer indicated. Result : A total of 149 cases (101 patients) were monitored during the study period. The dosage was inappropriately prescribed for renal function in 61 of 149 cases (41%), and of those, pharmacist made recommendations for 58 cases of which 33 cases (57%) were accepted by the physicians. The administration route of H2RA was inappropriately used as IV in 22 of 53 cases (42%), and pharmacist made recommendations for those 22 cases of which 15 cases (68%) were accepted. Conclusion : Monitoring of patients with renal dysfunction by a pharmacist improved the dosing of $H_2RA$ and a dosing program of patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.174-183
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• 1996

The general pharmacological properties of Artemisia extract powder (DA-9601) produced from Artemisia asiatica leaves were investigated in mice, rats, guinea pigs and rabbits. DA-9601 at the dose of 800 mg/kg po had no influences on general behaviour, barbital sleeping time and motor coordination of mice. The material at the oral dose of 800 mg/kg did exhibit neither analgesic action nor hypothermic effect. Anticonvulsant action, muscle relaxant action and the effect on intestinal propulsion were not identified at 800 mg/kg po. In the isolated ileum and trachea of guinea pig, the material did not show direct erect and inhibitory action of chemically or electrically stimulated contraction at the concentration of $2\times10^{-5}$g/ml. The sinus rates of atria and contractility of papillary muscle of guinea pig were not influenced by DA-9601 at a dose of $2\times10^{-5}$g/ml. No influences on blood pressure and respiration were observed at 40 mg/kg iv, in rabbits. However, transient decreases in blood pressure of rabbits were observed as given 120 mg/kg in iv route with slight respiratory depression, and slight diuretic effect could be found without any changes in $Na^+$ and $K^+$ excretion.

• Advances in pediatric surgery
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• v.13 no.1
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• pp.23-29
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• 2007

Tapering enteroplasty was first described by Thomas in 1969 as one method of intestinal anastomosis. The advantages of tapering enteroplasty in the intestinal atresia are: First, it makes end-to-end anastomosis possible between the atretic bowel ends with considerable differences in diameters. Second, it promotes the recover of the postoperative bowel function. Third, it prevents the possibility of the short bowel syndrome by eliminating the need of resecting the dilated bowel. A total of 22 patients with intestinal atresia who underwent tapering enteroplasty from January 1988 to December 2005 at our institute were reviewed. In 3 of 22 cases, tapering enteroplasty was the $2^{nd}$ operation after an initial end-to-oblique anastomosis. We reviewed the following items: age, sex, type and location of intestinal atresia, initial feeding and total enteral feeding start day, the length of hospital stay and complications. The average age of the patients was 7 days. Male to female ratio was 1 to 1.2 (10 cases: 12 cases). We performed the tapering enteroplasty on all types and locations of the intestinal atresia from the duodenum to the colon: type I (n=3), type II (n=4), type IIIA (n=7), type IIIB (n=5), type IIIB and IV (n=1), type IV (n=1) and type C (duodenum) and type IIIB and IV (jejunum). On the average, the oral feeds were started on the postoperative $8.8^{th}$ day, and full caloric intake via the enteric route was achieved on postoperative $13.3^{th}$ day. The average length of hospital stay was 19.6 days. There were 1 case (4.5 %) of anastomotic complication and 2 cases (9 %) of adhesive ileus among 22 patients. The tapering enteroplasty on all types of intestinal atresia is a usefull operative method when there are considerable diameter differences between the atretic bowel ends.

• Korean Journal of Adult Nursing
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• v.25 no.5
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• pp.567-573
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• 2013

Purpose: The purpose of this study was to compared two methods for measuring fluid intake and to assess the most effective method. Methods: Data from 44 hospitalized patients with chronic kidney disease was analyzed. Two methods were used. The liquid method is to measure the daily intake of water in the form of pure water or some other beverage and IV fluid, the liquid-solid method is to measure the daily intake of water which enters by the oral route and IV fluid. Results: The daily intake of fluid was 1483.10mL and 2245.99mL respectively. The fluid output was 1883.72 mL. The Intra-Class Correlation (ICC) between the liquid method and the liquid-solid method and fluid output was 0.64 and 0.69, respectively. The correlation between differences of fluid in two methods and body weight change was r=.47 (p<.001) and r=.56 (p<.001), respectively. Conclusion: The results of this study suggest that there are no difference between the two measuring methods as to reflecting the most close value to fluid output. And the difference between intake and output by two methods is correlated with body weight change. Therefore, it can be suggested that the either method could be useful as patients' fluid intake measurement.