Oral administration of insulin by means of liposomes in animal experiments

International Nuclear Information System (INIS)

Tragl, K.H.; Pohl, A.; Kinast, H.

1979-01-01

Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved. (author)

Effects of sub acute oral administration of aqueous extract of ...

African Journals Online (AJOL)

The study evaluates the effects of sub acute oral administration (28 days) of aqueous extract of Stereospermum kunthianum stem bark on the body weight and haematological indices of rats. Treatments were administered by oral gavage once daily for a total of 28 days. The first group (control) received distilled water (5 ...

Effect of titanium dioxide nanoparticles on the cardiovascular system after oral administration.

Science.gov (United States)

Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Luan, Xianguo; Wang, Haifang; Jia, Guang

2015-12-03

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various consumer products, especially food and personal care products. Compared to the well-characterized adverse cardiovascular effect of inhaled ambient ultrafine particles, research on the health response to orally administrated TiO2 NPs is still limited. In our study, we performed an in vivo study in Sprague-Dawley rats to understand the cardiovascular effect of TiO2 NPs after oral intake. After daily gastrointestinal administration of TiO2 NPs at 0, 2, 10, 50 mg/kg for 30 and 90 days, heart rate (HR), blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage. Mild and temporary reduction of HR and systolic blood pressure as well as an increase of diastolic blood pressure was observed after daily oral administration of TiO2 NPs for 30 days. Injury of cardiac function was observed after daily oral administration of TiO2 NPs for 90 days as reflected in decreased activities of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH) and creatine kinase (CK). Increased white blood cells count (WBC) and granulocytes (GRN) in blood as well as increased concentrations of tumor necrosis factor α (TNF α) and interleukin 6 (IL-6) in the serum indicated inflammatory response initiated by TiO2 NPs exposure. It was hypothesize that cardiac damage and inflammatory response are the possible mechanisms of the adverse cardiovascular effects induced by orally administrated TiO2 NPs. Data from our study suggested that even at low dose of TiO2 NPs can induce adverse cardiovascular effects after 30 days or 90 days of oral exposure, thus warranting concern for the dietary intake of TiO2 NPs for consumers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fourteen days oral administration of therapeutic dosage of some ...

African Journals Online (AJOL)

Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

DEFF Research Database (Denmark)

Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

2007-01-01

After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-g......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

Development of Alginate Microspheres Containing Chuanxiong for Oral Administration to Adult Zebrafish

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Li-Jen Lin

2016-01-01

Full Text Available Oral administration of Traditional Chinese Medicine (TCM by patients is the common way to treat health problems. Zebrafish emerges as an excellent animal model for the pharmacology investigation. However, the oral delivery system of TCM in zebrafish has not been established so far. This issue was addressed by development of alginate microparticles for oral delivery of chuanxiong, a TCM that displays antifibrotic and antiproliferative effects on hepatocytes. The delivery microparticles were prepared from gelification of alginate containing various levels of chuanxiong. The chuanxiong-encapsulated alginate microparticles were characterized for their solubility, structure, encapsulation efficiency, the cargo release profile, and digestion in gastrointestinal tract of zebrafish. Encapsulation of chuanxiong resulted in more compact structure and the smaller size of microparticles. The release rate of chuanxiong increased for alginate microparticles carrying more chuanxiong in simulated intestinal fluid. This remarkable feature ensures the controlled release of encapsulated cargos in the gastrointestinal tract of zebrafish. Moreover, chuanxiong-loaded alginate microparticles were moved to the end of gastrointestinal tract after oral administration for 6 hr and excreted from the body after 16 hr. Therefore, our developed method for oral administration of TCM in zebrafish is useful for easy and rapid evaluation of the drug effect on disease.

Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

Science.gov (United States)

Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

[An oral function improvement program utilizing health behavior theories ameliorates oral functions and oral hygienic conditions of pre-frail elderly persons].

Science.gov (United States)

Sakaguchi, Hideo

2014-06-01

Oral function improvement programs utilizing health behavior theories are considered to be effective in preventing the need for long-term social care. In the present study, an oral function improvement program based upon health behavior theories was designed, and its utility was assessed in 102 pre-frail elderly persons (33 males, 69 females, mean age: 76.9 +/- 5.7) considered to be in potential need of long-term social care and attending a long-term care prevention class in Sayama City, Saitama Prefecture, Japan. The degree of improvement in oral functions (7 items) and oral hygienic conditions (3 items) was assessed by comparing oral health before and after participation in the program. The results showed statistically significant improvements in the following oral functions: (1) lip functions (oral diadochokinesis, measured by the regularity of the repetition of the syllable "Pa"), (2) tongue functions, (3) tongue root motor skills (oral diadochokinesis, measured by the regularity of the repetition of the syllables "Ta" and "Ka"), (4) tongue extension/retraction, (5) side-to-side tongue movement functions, (6) cheek motor skills, and (7) repetitive saliva swallowing test (RSST). The following measures of oral hygiene also showed a statistically significant improvement: (1) debris on dentures or teeth, (2) coated tongue, and (3) frequency of oral cleaning. These findings demonstrated that an improvement program informed by health behavior theories is useful in improving oral functions and oral hygiene conditions.

Conscious sedation by oral administration of midazolam in paediatric dental treatment.

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Erlandsson, A L; Bäckman, B; Stenström, A; Stecksén-Blicks, C

2001-01-01

Midazolam is a short-acting benzodiazepine with rapid onset, short duration of action and minimal side effects. The aim of this study was to evaluate the oral administration of midazolam as pre-operative sedation in the dental treatment of uncooperative pediatric patients. Included in the study were 160 children with a mean age of 6.7 +/- 2.6 years (1-14 years), 83 boys and 77 girls. All the patients had been referred for specialist treatment due to behavioral management problems. Treatment was performed in 250 sessions. All the children received an oral dose of 0.2 mg/kg body weight of midazolam. Acceptance of treatment was evaluated according to Rud & Kisling. Local anesthesia followed by restorative treatment and/or extractions constituted more than 90% of the performed treatments. Of the 250 sessions, 63% were performed with total acceptance and 30% with doubtful acceptance. In 7%, no treatment could be performed. No serious complications were registered during or after treatment. All the children were able to leave the clinic one hour after treatment. In conclusion, we consider oral administration of midazolam a safe form of premedication. The route of administration, the short waiting-time and half-life, in combination with a level of sedation that allows treatment to be performed, are the principal advantages of conscious sedation with orally administered midazolam.

Anti-tumour immune effect of oral administration of Lactobacillus

Indian Academy of Sciences (India)

Our results indicated that oral administration with L. plantarum inhibited CT26 cell ... (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. ... College of Animal Science and Technology, Jilin Agricultural University, ...

Evaluation of student nurses' perception of preparedness for oral medication administration in clinical practice: a collaborative study.

Science.gov (United States)

Aggar, Christina; Dawson, Sonja

2014-06-01

Attainment of oral medication administration skills and competency for student nurses is challenging and medication errors are common. The ability of nurses to master a clinical skill is dependent upon educational instruction and practice. The aim of this study was to evaluate nursing students' perception of preparedness for oral medication administration in two practice environments and determine possible relationship between student demographics and their perceived preparedness for oral medication administration. This was a cross sectional, exploratory study. Eighty-eight second year students from a baccalaureate nursing course from two metropolitan Australian tertiary institutions participated. Student nurses' perception of preparedness for oral medication administration was measured via a self-administered, adapted, and validated questionnaire. The overall mean Total Preparedness Score was 86.2 (range 71-102). There was no significant difference for perceived total preparedness to administer oral medications between the two facilities. Whilst there was no significant relationship established between student demographics and their perceived preparedness to administer oral medications, four single questions related to clinical practice were shown to be significant. Low fidelity simulated teaching environments that incorporate time management and post medication situations, may improve student nurses' perceived preparedness for oral medication administration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pharmacokinetics and skin concentrations of lincomycin after intravenous and oral administration to cats

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Gabriela A. Albarellos

2013-10-01

Full Text Available The aim of the present study was to describe the plasma pharmacokinetic profile and skin concentrations of lincomycin after intravenous administration of a 15% solution and oral administration of 300 mg tablets at a dosing rate of 15 mg/kg to cats. Susceptibility of staphylococci (n = 31 and streptococci (n = 23 strains isolated from clinical cases was also determined. Lincomycin plasma and skin concentrations were determined by microbiological assay using Kocuria rhizophila ATCC 9341 as test microorganism. Susceptibility was established by the antimicrobial disc diffusion test. Individual lincomycin plasma concentration–time curves were analysed by a non-compartmental approach. After intravenous administration, volume of distribution, body clearance and elimination half-life were 0.97 L/kg ± 0.15 L/kg, 0.17 L/kg ± 0.06 L/h.kg and 4.20 h ± 1.12 h, respectively. After oral administration, peak plasma concentration, time of maximum plasma concentration and bioavailability were 22.52 µg/mL ± 10.97 µg/mL, 0.80 h ± 0.11 h and 81.78% ± 24.05%, respectively. Two hours after lincomycin administration, skin concentrations were 17.26 µg/mL ± 1.32 µg/mL (intravenous and 16.58 µg/mL ± 0.90 µg/mL (oral. The corresponding skin: plasma ratios were 2.08 ± 0.47 (intravenous and 1.84 ± 0.97 (oral. The majority of staphylococci and streptococci tested in this study were susceptible to lincosamides (87.09% and 69.56%, respectively. In conclusion, lincomycin administered orally at the assayed dose showed a good pharmacokinetic profile, with a long elimination half-life and effective skin concentration. Therefore, it could be a good first option for treating skin infections in cats.

Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

Science.gov (United States)

Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

2015-12-01

Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

2012-08-01

To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects.

Science.gov (United States)

Abbas, Richat; Hug, Bruce A; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

2011-04-01

The primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low-molecular-weight, orally administered, irreversible pan-ErbB (ErbB-1, -2, -4) receptor tyrosine kinase inhibitor, during co-administration with ketoconazole, a potent CYP3A4 inhibitor. This was an open-label, randomized, two-period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of C(max) (neratinib+ketoconazole): C(max) (neratinib alone), and AUC(neratinib+ketoconazole): AUC(neratinib alone) were assessed. Twenty-four subjects were enrolled. Compared with neratinib administered alone, co-administration of ketoconazole increased neratinib C(max) by 3.2-fold (90% CI: 2.4, 4.3) and AUC by 4.8-fold (3.6, 6.5). Median t(max) was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 lh(-1) to 87.1 lh(-1) and increased mean elimination half-life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co-administration with ketoconazole). Co-administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib C(max) by 3.2-fold and AUC by 4.8-fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

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Ravi S.Talluri

2009-10-01

Full Text Available Objective: To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods: Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine- D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results: Following i.v. administration, the area under the curve (AUC in µM*min of generated ACV was in the order of LACV › LDACV › DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 µM*min, respectively. DLACV exhibited poor oral absorption. Cmax (µM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions: LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

Science.gov (United States)

Talluri, Ravi S.; Gaudana, Ripal; Hariharan, Sudharshan; Mitra, Ashim K.

2009-01-01

Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration. PMID:23861607

Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir following Intravenous and Oral Administrations in Rats: A study Involving in vivo corneal Uptake of Acyclovir following Oral Dosing

Directory of Open Access Journals (Sweden)

Ravi S. Talluri

2009-01-01

Full Text Available Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine-D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. C max (μM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

Oral administration of Allium sativum extract protects against infectious bursal disease in chickens

Directory of Open Access Journals (Sweden)

Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

2015-12-01

Full Text Available Garlic (Allium sativum, Liliaceae has been safely used for more than 5000 years, and research on garlic extract is rapidly increasing because of its multiple biological functions. The in vivo effects of oral administration of garlic mixture (GM, water-soluble extract on infectious bursal disease virus (IBDV-infected specific pathogen free male white leghorn chicken were examined through histopathological, immunohistochemical, and Western blot analyses, and enzyme-linked immunosorbent assay. The results confirmed the protective effects of oral administration of 5 mg·kg-1 BW GM (Group GM1 on bursal lesions after IBDV infection. In particular, protein expression of IBDV in the bursa decreased in Group GM1, indicating that GM administration decreased IBDV replication in the bursa. Furthermore, immunoglobulin M- and A-bearing B lymphocytes significantly increased 7 days post infection in bursae in Group GM1 (P<0.01, suggesting that the oral administration of 5 mg·kg-1 GM offers moderate protection against B cell destruction after IBDV infection. During infection, the concentration of bursal interferon gamma (IFN-g increased and peaked in Group GM1 earlier than in Group T (IBDV-exposed, demonstrating that GM administration prompted the production of IFN-g to protect against IBDV infection.

Studies on the absorption of iron after oral administration in piglets

International Nuclear Information System (INIS)

Thoren-Tolling, K.

1975-01-01

72 newborn piglets from 9 litters were used to determinate the retention and distribution in the body of labelled iron given either orally as ferrous fumarate (100 mg Fe 2+ ) or iron dextran (200 mg Fe 3+ ), or by injection as iron dextran (100 mg Fe 3+ ). About 25-30 % of the radioiron from a single oral dose of labelled ferrous fumarate (100 mg Fe 2+ ), and about 55-60 % from a single oral dose of labelled iron dextran (200 mg Fe 3+ ) were absorbed by the body. As iron is excreted throughout the experiment, only about 20% and 40-50% respectively of the radio-iron from these iron compounds were recovered 3 weeks after treatment. The total amounts of labelled iron retained in the body after oral administration of the same doses of these iron compounds, alone or in combination, were compared. A slight retardation of the absorption of ferrous iron was observed when iron dextran was administered simultaneeously. The absorption of iron dextran was not influenced by the simultaneous administration of ferrous fumarate. The importance of the liver as the main iron storage site was shown, and the rapid utilization of iron from storage sites, about 2-3 weeks after treatment was demonstrated. The concentration of labelled iron in urine and some lymphglands was measured. Only minute quantities of radio-iron were excreted in the urine throughout the entire experiment. The lymph nodes seem to act as iron stones after administration of iron dextran. The importance of the lymphatic tissue in absorption and storage of labelled iron is discussed. (author)

Reducing radiation exposure during oral I-131 therapy administration

International Nuclear Information System (INIS)

Trujillo, J.; Krinsky, S.; Wilson, B.; Teague, E.

1982-01-01

A new, closed-system method to reduce air-, direct-, and incidental-contamination during therapeutic administration of oral I-131 was experimentally evaluated on twelve patients. We studied a standard control population using the routine practice of drinking the solution through a straw and compared results with our new technique. Various measurements were performed throughout all phases of dose administration to assess the relative difference of the two approaches. Using the closed system method before and during iodine administration revealed between 100 and 1000 times less activity per millimeter of air sample; whereas, the direct radiation exposure values were higher for the control population. Both the experimental and control methods had similar levels of incidental contamination

Oral dosing by voluntary  administration of jellybeans. Refinement and reduction of variability

DEFF Research Database (Denmark)

Pakula, Malgorzata Maria; Dagnæs-Hansen, Frederik

2016-01-01

Administration of substances by oral gavage is a common procedure in biomedical research involving laboratory animals, however although highly efficient, the procedure includes fixation of the animals and is technically challenging. Oral gavage is a precise way to dose animals, however it may ind...

Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

Science.gov (United States)

Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

2009-01-01

The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

Pharmacokinetics of [3H]levamisole in pigs after oral and intramuscular administration

International Nuclear Information System (INIS)

Galtier, P.; Escoula, L.; Alvinerie, M.

1983-01-01

A single oral (10 mg/kg of body weight) or IM (7.5 mg/kg) dose of [ 3 H]levamisole was administered to pigs. Liquid scintillation counting and high performance liquid chromatography were used to determine total radioactivity and drug levels in plasma, duodenal and cecal contents, bile, and urine for 24 and 72 hours after dosing. Pharmacokinetic analysis indicated a 1-compartment open model with higher plasma bioavailability of levamisole after IM injection. Biological half-lives for elimination of the drug were 9.3 and 6.9 hours after oral and IM administration, respectively. Anthelmintic concentrations were higher in intestinal contents after oral gavage than after IM injection. The drug appeared extensively metabolized in all body fluids and particularly in bile, regardless of the route of administration. Biliary excretion of radioactivity and unchanged levamisole represented only slight percentages of the administered dose (approx 0.4% and 4.2%, respectively, in 72 hours). In contrast, about 60% and 20% of the dose were eliminated via urine as tritiated materials and unchanged drug. The choice of the most efficacious route of administration is discussed in regard to localization of helminthic disease

Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

2013-03-01

To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

Two cases of "cannabis acute psychosis" following the administration of oral cannabis

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Pin Marie

2005-04-01

Full Text Available Abstract Background Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. Case presentations We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. Conclusion While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

Factors Associated with Choking During Meals; a Risk Indicator for Repetitive Fevers in The Elderly Community

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Takeshi Nishiyama

2017-04-01

Full Text Available Background: Choking during meals is a common symptom in the elderly, however the factors associated with it have not been fully clarified. In this study, we examined the factors associated with choking during meals. Methods: The oral health status and practices that promote oral health conditions was surveyed in 1305 community dwelling elderly using a self-administered questionnaire. Eight items including satisfaction with their oral condition, denture fit, chewing ability, tooth brushing frequency, dental visits, exercises to train muscles for chewing and swallowing, choking during meals, and repetitive fever were selected for analysis. Results: 25.1% of the subjects experienced choking during meals, which was significantly associated with repetitive fever occurrence. Differences in satisfaction levels with their oral condition, denture fit, chewing ability, and tooth brushing frequency were observed between groups with and without choking. Age, satisfaction level, and chewing ability were significantly associated with choking during meals. Conclusions: This study demonstrated that choking during meals is a risk indicator for repetitive fever in the elderly living in community settings. Poor chewing ability and dissatisfaction with their oral condition were risk factors associated with choking. These results suggest that training the elderly to eat efficiently and safely and improving oral conditions is necessary for those who suffer from choking during meals to prevent repetitive fever.

Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2013-06-01

To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

20 CFR 416.1448 - Deciding a case without an oral hearing before an administrative law judge.

Science.gov (United States)

2010-04-01

... § 416.1448 Deciding a case without an oral hearing before an administrative law judge. (a) Decision... the decision is based. (b) Parties do not wish to appear. (1) The administrative law judge may decide... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing...

20 CFR 404.948 - Deciding a case without an oral hearing before an administrative law judge.

Science.gov (United States)

2010-04-01

....948 Deciding a case without an oral hearing before an administrative law judge. (a) Decision wholly... is based. (b) Parties do not wish to appear. (1) The administrative law judge may decide a case on... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing...

Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

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Ehsan Zayerzadeh

2016-07-01

Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

Pharmacokinetics of ketoprofen enantiomers following intravenous and oral administration to exercised Thoroughbred horses.

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Knych, Heather K; Arthur, Rick M; Steinmetz, Stacy; McKemie, Dan S

2016-01-01

Ketoprofen (KTP) is currently only available as an injectable formulation for intravenous administration to horses. The primary goal of the study reported here was to characterize the pharmacokinetics of KTP, including determination of bioavailability following oral administration of the currently available injectable formulation as well as a paste formulation. KTP was administered intravenously and orally, and blood and urine samples were collected at various time points up to 96 h. KTP enantiomer concentrations were determined using LC–MS/MS, and pharmacokinetic analyses were performed. Mean ± standard error values for systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.345 ± 0.033 [R(−) KTP] and 0.167 ± 0.016 [S(+) KTP] L/kg/h, 0.344 ± 0.044 [R(−) KTP] and 0.298 ± 0.025 [S(+) KTP] L/kg, and 2.49 ± 0.077 [R(−) KTP] and 2.86 ± 0.102 [S(+) KTP] h, respectively. Oral bioavailability was calculated as 69.5 ± 10.3% and 88.2 ± 15.9% for R(−) KTP and S(+) KTP, respectively, following administration of the injectable formulation and 53.0 ± 6.0 and 53.0 ± 16.0% for the R(−) KTP and S(+) KTP, respectively, following administration of KTP paste.

A novel, ecologically relevant, highly preferred, and non-invasive means of oral substance administration for rodents.

Science.gov (United States)

Sobolewski, Marissa; Allen, Joshua L; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A

2016-01-01

Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

Oral administration of Rauwolfia vomitoria extract has no untoward ...

African Journals Online (AJOL)

The effect of ethanolic extract of leaf and root of Rauwolfia vomitoria on kidney and liver functions in rats was investigated. Rats were given daily oral administration of ethanolic extracts of either root or leaf of R. vomitoria at two different concentrations (1.0 and 2.0 g/kg body weight) for a period of 14 days. Some biochemical ...

Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.

Science.gov (United States)

Owczarzak, Vicki; Haddad, Joseph

2006-08-01

To examine whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. A prospective, randomized control study. Seventy-five children aged 1 to 5 were recruited for this study. Each child was assigned randomly to receive either rectal or oral postoperative pain medication. A journal with eight questions was kept for 10 days after the operation, and an overall survey of five questions was filled out at the first postoperative visit. Postoperative pain was adequately controlled in those patients receiving suppositories when compared with those patients receiving oral pain medication. Adverse effects and total number of doses given per day were similar. Parents found the suppositories easy to administer, and more parents would switch or consider switching from oral pain medication to suppositories if given the choice. The suppositories achieved equivalent pain control as oral medication with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration. If given the choice for future surgeries, many parents would switch or consider switching from oral pain medication to suppositories.

Pharmacokinetics of (/sup 3/H)levamisole in pigs after oral and intramuscular administration

Energy Technology Data Exchange (ETDEWEB)

Galtier, P.; Escoula, L.; Alvinerie, M.

1983-04-01

A single oral (10 mg/kg of body weight) or IM (7.5 mg/kg) dose of (/sup 3/H)levamisole was administered to pigs. Liquid scintillation counting and high performance liquid chromatography were used to determine total radioactivity and drug levels in plasma, duodenal and cecal contents, bile, and urine for 24 and 72 hours after dosing. Pharmacokinetic analysis indicated a 1-compartment open model with higher plasma bioavailability of levamisole after IM injection. Biological half-lives for elimination of the drug were 9.3 and 6.9 hours after oral and IM administration, respectively. Anthelmintic concentrations were higher in intestinal contents after oral gavage than after IM injection. The drug appeared extensively metabolized in all body fluids and particularly in bile, regardless of the route of administration. Biliary excretion of radioactivity and unchanged levamisole represented only slight percentages of the administered dose (approx 0.4% and 4.2%, respectively, in 72 hours). In contrast, about 60% and 20% of the dose were eliminated via urine as tritiated materials and unchanged drug. The choice of the most efficacious route of administration is discussed in regard to localization of helminthic disease.

Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

Science.gov (United States)

Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

2017-05-01

To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

A Novel, Ecologically Relevant, Highly Preferred, and Non-invasive Means of Oral Substance Administration for Rodents

OpenAIRE

Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

2016-01-01

Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if ...

Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

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Tomohiro Osaki

2015-08-01

Full Text Available N-acetyl-d-glucosamine (GlcNAc is a monosaccharide that polymerizes linearly through (1,4-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001. To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism.

Oral administration of yessotoxin stabilizes E-cadherin in mouse colon

International Nuclear Information System (INIS)

Callegari, Federica; Sosa, Silvio; Ferrari, Sara; Soranzo, Maria Rosa; Pierotti, Silvia; Yasumoto, Takeshi; Tubaro, Aurelia; Rossini, Gian Paolo

2006-01-01

YTX has been shown to disrupt the E-cadherin-catenin system in cultured epithelial cells, raising some concern that ingestion of seafood contaminated by YTX might favour tumour spreading and metastasis formation in vivo. In order to probe whether YTX might affect cadherin systems in vivo, we have set up a study involving repeated oral dosing of the toxin in mice (1 mg/kg/day, for 7 days) and analysis of E-cadherin and N-cadherin in tissue extracts obtained at the end of the dosing scheme, as well as 1 and 3 months after YTX administration. We found that the E-cadherin pools obtained from lung and kidney were not altered by YTX in any of our experimental conditions. Extracts from mouse colon contained intact E-cadherin and an E-cadherin fragment of about 90 kDa (ECRA 9 ), displaying a molecular alteration resembling that caused by YTX in cultured cells. We found that the relative proportion of ECRA 9 , as compared to intact E-cadherin, was higher in colon extracts from control mice than from YTX-treated animals, indicating that oral administration of YTX to mice stabilizes E-cadherin of mouse colon. No significant difference could be detected in samples prepared from colons obtained 30 or 90 days after termination of YTX treatment. Oral administration of YTX to mice did not lead to a significant increase in the fragments of E-cadherin detectable in serum, neither it altered the N-cadherin pool of mouse heart. Electron microscopy analysis showed no substantial ultrastructural differences between controls and YTX-treated mice. Our findings show that ingestion of food contaminated by YTX poses a low risk of disruption of the E-cadherin system in vivo

PHARMACOKINETICS OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE AFTER ORAL ADMINISTRATION OF TABLETS TO RABBITS.

Science.gov (United States)

Kasperek, Regina; Zimmer, Łukasz; Jawień, Wojciech; Poleszak, Ewa

2015-01-01

Non-compartmental pharmacokinetic analysis of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) after oral administration of composed tablets to rabbits was developed. HPLC method for determination of DIC and PAP in rabbit plasma was developed and validated. Chromatographic separation of DIC, PAP and the IS was achieved on a Zorbax SB C18 5-µm column (150 mm x 4.6 mm) using methanol-water (55:45, v/v) as mobile phase at a flow rate of 0.8 mL/min. Pharmacokinetic analysis showed that oral administration of a tablet composed of DIC and PAP do not change the pharmacokinetic parameters such as MRT, MAT, Cl and bioavailability of the active substances compared with single administration of DIC and PAP after single dose.

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

Science.gov (United States)

Muñoz, J; Soblechero, P; Duque, F J; Macías-García, B; Ruiz, P; Zaragoza, C; Barrera, R

2017-11-01

Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Effects of Oral Administration of Nicotine on Organ Weight, Serum ...

African Journals Online (AJOL)

This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0mg/kg (high dose) body weight of ...

Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

Science.gov (United States)

Kai, Shuken; Kondo, Eiji; Kawaguchi, Yasuyuki; Kitamura, Nobuto; Yasuda, Kazunori

2013-01-01

Aim To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. Method Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. Results The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.

Science.gov (United States)

Knych, Heather K; Mama, Khursheed R; Steffey, Eugene P; Stanley, Scott D; Kass, Philip H

2017-10-01

OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

Nursing Administrators' Views on Oral Health in Long-Term Care Facilities: An exploratory study.

Science.gov (United States)

Urata, Janelle Y; Couch, Elizabeth T; Walsh, Margaret M; Rowe, Dorothy J

2018-04-01

Purpose: To explore the knowledge, attitudes, and practices of supervising nurse administrators (SNAs) regarding the oral care provided to long-term care facility (LTCF) residents and the role of dental professionals in those facilities. Methods: The investigators of this study partnered with the National Association of Nursing Administrators to send this cross-sectional study consisting of a 35-item electronic survey to its members whose email addresses were in their database. Online software tabulated responses and calculated frequencies (percentages) of responses for each survey item. Results: Of the 2,359 potential participants, 171 (n=171) completed the survey for a 7% response rate. Only 25% of the respondents were familiar with the expertise of dental hygienists (DHs), however once informed, the majority were interested in having DHs perform oral health staff trainings, oral screenings, and dental referrals and initiate fluoride varnish programs. Most respondents correctly answered the oral health-related knowledge items, understood that oral health is important to general health, but reported that the LTCF residents' oral health was only "good" or "fair." Fewer than half, (48%) of the SNAs were "very satisfied" with the quality of oral care provided to the residents. While more than half reported that they had no dentist on staff or on-site dental equipment, 77% reported that they would consider on-site mobile oral care services. Oral health training for staff was provided primarily by registered nurses, however only 32% reported including identification of dental caries as part of the in-service training. Conclusion: This exploratory study lays the foundation for more extensive research investigating various strategies to improve the oral health of LTCF residents, including increased collaboration between DHs and SNAs. Copyright © 2018 The American Dental Hygienists’ Association.

Distribution of enrofloxacin in intestinal tissue and contents of healthy pigs after oral and intramuscular administrations

DEFF Research Database (Denmark)

Wiuff, C.; Lykkesfeldt, J.; Aarestrup, Frank Møller

2002-01-01

The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum...... administration, and maximum concentrations in tissue and plasma were determined later than after i.m. administration. No difference between route of administration was observed in the intestinal content. Enrofloxacin concentrations in faeces during a 5-day dosing regimen with i.m. and p.o. administration were....... On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route....

Repetition and the Concept of Repetition

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Arne Grøn

2013-11-01

Full Text Available This paper offers a description of the meaning of the category of repetition. Firstly, it is pointed out that Constantin uses repetition as a concept that means the creation of epochs; the passing from Greece to Modernity is accomplished distinguishing between recollection, a concept that looks back to the past, and repetition, a concept that looks forward to future. Secondly, it is showed that the category of repetition, as a religious category, relates with what Climacus calls “ethic despair” and with what Vigilius calls “second ethics”; it is through repetition that it can be understood that sin finds its place in ethics and these shows the tension between it and dogmatics. And thirdly, it is showed that the descovery of the new category of repetition is a rediscovery of what Kierkegaard calls category of spirit; repetition has for its object the individuality, and coming to be oneself is what Kierkegaard undertands as liberty. At the end of the paper it is questioned if the category of repetition is inconsistent with the book Repetition.

Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration.

Science.gov (United States)

Gharibi, S; Kimble, B; Vogelnest, L; Barnes, J; Stadler, C K; Govendir, M

2017-12-01

The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (V ss ) were 0.15 (0.13-0.18) L hr -1  kg -1 and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t 1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (C max ; median: 0.72, range: 0.55-0.93 μg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas. © 2017 John Wiley & Sons Ltd.

Labeling of red blood cells with Tc-99m after oral administration of SnCl2. Concise communication

International Nuclear Information System (INIS)

Patel, M.C.; Parab, P.B.; Samuel, A.M.; Ganatra, R.D.

1979-01-01

In vivo labeling of red blood cells with Tc-99m was possible after prior oral administration of SnCl 2 , both in rats and human volunteers. Absorption of oral SnCl 2 was low but sufficient for more than 95% labeling efficiency. Prior i.v. administration of stannous chloride is known to induce in vivo labeling of red blood cells with pertechnetate. We have observed that such labeling is possible even after oral administration of stannous chloide. Nearly 95% of the circulating radioactivity and 93.7% of the administered radioactivity was in RBCs 30 min after i.v. injection of /sup 99m/TcO 4 - in rats that were fed 5 mg of stannous chloride (3.13 mg Sn 2+ ion) 2 hr before injection. Red blood cells from four human volunteers could bind pertechnetate, both in vitro and in vivo, after oral administration of 100 mg of SnCl 2 . We have obtained a blood-pool image of the human heart by labeling the RBCs in vivo by this method. We have also studied various parameters affecting the in vivo binding of RBCs with Tc-99m - such as the amount of orally administered SnCl 2 , the time of injection of radionuclide after oral SnCl 2 , and the optimum time for the imaging

Detection of capecitabine (Xeloda®) on the skin surface after oral administration

Science.gov (United States)

Huang, Mao-Dong; Fuss, Harald; Lademann, Jürgen; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora

2016-04-01

Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500 mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10 ppb (2±0.5 pM) before capecitabine administration to 27.7±11.8 ppm (14.6±6.5 nM) after application, ptoxic effect as a possible pathomechanism of PPE.

Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

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Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

2017-07-01

Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

Novel oral administrated paclitaxel micelles with enhanced bioavailability and antitumor efficacy for resistant breast cancer.

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Zhang, Ting; Luo, Jingwen; Fu, Yao; Li, Hanmei; Ding, Rui; Gong, Tao; Zhang, Zhirong

2017-02-01

Paclitaxel (PTX) is a widely used antineoplastic drug in clinic. Due to poor aqueous solubility, it is administrated by intravenous infusion of cremophor EL containing formulation with serious adverse effects. The low oral bioavailability is a great challenge for oral formulation development. In addition, P-gp mediated multidrug resistance limit its clinical use in various resistant cancers. In this study, a novel super-antiresistant PTX micelle formulation for oral administration was developed. A P-gp inhibitor, bromotetrandrine (W198) was co-encapsulated in the micelle. The micelles were composed of Solutol HS 15 and d-a-tocopheryl polyethylene glycol succinate to avoid Cremophor EL induced toxicity. The micelles were round with a mean particle size of ∼13nm and an encapsulation efficiency of ∼90%. A series of in vitro evaluations were performed in non-resistant MCF-7 cells and resistant MCF-7/Adr cells. The super-antiresistant PTX micelles showed higher cell uptake efficiency, significantly increased cytotoxicity and antimitotic effect in drug resistant MCF-7/Adr cells when compared with Taxol and other PTX micelle formulations. Compared with Taxol, the super-antiresistant PTX micelles significantly improved bioavailability after oral administration in rats, and inhibited tumor growth in multidrug resistance xenografted MCF-7/Adr nude mice. In summary, the noval super-antiresistant PTX micelles showed a great potential for oral delivery of PTX against resistant breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

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Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

2012-08-01

To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.

Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

DEFF Research Database (Denmark)

Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

2015-01-01

OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline....... In conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival....

Pharmacokinetics of dexmedetomidine combined with methadone following oral-transmucosal and intramuscular administration in dogs

Directory of Open Access Journals (Sweden)

Federica Di Cesare

2017-05-01

Full Text Available Oral-transmucosal (OTM drug delivery refers to noninvasive and painless administration of medical preparations through any oral cavity membrane to achieve systemic effects (Sattar et al., 2014. Regarding sedative drugs, OTM administration is very attractive in veterinary medicine, especially for patients difficult to inject and restrain (Messenger et al., 2016. This study aims to compare the pharmacokinetics of dexmedetomidine after OTM and intramuscular (IM administration combined with methadone. After obtaining Ethical Committee approval and owner’s written consent, eight dogs, were administered with dexmedetomidine (10 mg/kg and methadone (0.4 mg/kg by OTM and other 4 dogs by IM route. Blood samples were collected at prefixed times up to four hours. Dexmedetomidine was quantified by a validated HPLC-MS method. On dexmedetomidine concentrations, a pharmacokinetic analysis was carried out with a noncompartmental approach (Phoenix WinNonlin® 7.0, Pharsight, Cary, NC. Mean ± SD terminal half-lives of dexmedetomidine were 187.42 ± 109.66 and 94.78 ± 34.08 min after OTM and IM administration, respectively. Maximum serum (Cmax concentrations were 0.83 ± 0.32 and 9.09 ± 2.46 ng/mL for OTM and IM administration, respectively. Time to maximum concentration (Tmax were 44.38 ± 32.16 and 21.25±11.39 min by OTM and IM administration, respectively. Area under the curve from 0 to the last measured concentration (AUClast were 103.75 ± 30.23 and 614.87 ± 77.15 min*ng/mL for OTM and IM administration, respectively. Cmax, Tmax and AUClast values by OTM route demonstrate a lower and delayed absorption of the drug compared to IM. To complete the study, the pharmacokinetic analysis of methadone is foreseen, so as a clinical trial to compare the clinical effects of the combination of dexmedetomidine and methadone by OTM and IM administration and to establish an effective dosage of oral-transumucosal route in dogs for this association.

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.

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Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

2016-01-01

Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future

Protective effect of oral administration of transgenic tobacco seeds against verocytotoxic Escherichia coli strain in piglets.

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Rossi, Luciana; Dell'Orto, Vittorio; Vagni, Simona; Sala, Vittorio; Reggi, Serena; Baldi, Antonella

2014-03-01

The use of transgenic plants as delivery system for antigenic proteins is attractive for its simplicity and increases likelihood for local immune response at sites of infection. The aim of this study was to evaluate the protective effect of oral administration of tobacco seeds, expressing the FedA, the major protein of the F18 adhesive fimbriae, and B subunit of verocytotoxin, against verocytotoxin-producing E. coli (VTEC) strain in piglets. Forty-three early weaned piglets, were randomly divided into 4 experimental groups: 3 test groups and a control. Treatment groups orally received a bolus, with different dose of tobacco seeds on 0, 1, 2, 14 days post primary administration. After challenge, with 1*10(10) CFU of O138 Escherichia coli strain, piglets showed clinical scores significantly higher in the control group compared to orally immunized groups (P administration of recombinant tobacco seeds expressing antigenic proteins against VTEC strains can induce a protective effect against challenger strain in piglets.

Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis).

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Guzman, David Sanchez-Migallon; Flammer, Keven; Paul-Murphy, Joanne R; Barker, Steven A; Tully, Thomas N

2011-09-01

Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (Amazon

The role of repetition and reinforcement in school-based oral health education-a cluster randomized controlled trial.

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Haleem, Abdul; Khan, Muhammad Khalil; Sufia, Shamta; Chaudhry, Saima; Siddiqui, Muhammad Irfanullah; Khan, Ayyaz Ali

2016-01-04

Repetition and reinforcement have been shown to play a crucial role in the sustainability of the effect of Oral Health Education (OHE) programs. However, its relevance to school-based OHE imparted by different personnel is not depicted by the existing dental literature. The present study was undertaken to determine the effectiveness of the repeated and reinforced OHE (RR-OHE) compared to one-time OHE intervention and to assess its role in school-based OHE imparted by dentist, teachers and peers. The study was a cluster randomized controlled trial that involved 935 adolescents aged 10-11 years. Twenty four boys' and girls' schools selected at random in two towns of Karachi, Pakistan were randomly assigned to three groups to receive OHE by dentist (DL), teachers (TL) and peer-leaders (PL). The groups received a single OHE session and were evaluated post-intervention and 6 months after. The three groups were then exposed to OHE for 6 months followed by 1 year of no OHE activity. Two further evaluations at 6-month and 12-month intervals were conducted. The data were collected by a self-administered questionnaire preceded by a structured interview and followed by oral examination of participants. The adolescents' oral health knowledge (OHK) in the DL and PL groups increased significantly by a single OHE session compared to their baseline knowledge (p strategy. Although the OHK scores of the DL and PL groups decreased significantly at 12-month evaluation of RR-OHE (p play a key role in school-based OHE irrespective of educators. The trained teachers and peers can play a complementary role in RR-OHE.

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

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Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

2010-04-01

To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

Oral administration of myostatin-specific recombinant Saccharomyces cerevisiae vaccine in rabbit.

Science.gov (United States)

Liu, Zhongtian; Zhou, Gang; Ren, Chonghua; Xu, Kun; Yan, Qiang; Li, Xinyi; Zhang, Tingting; Zhang, Zhiying

2016-04-29

Yeast is considered as a simple and cost-effective host for protein expression, and our previous studies have proved that Saccharomyces cerevisiae can deliver recombinant protein and DNA into mouse dendritic cells and can further induce immune responses as novel vaccines. In order to know whether similar immune responses can be induced in rabbit by oral administration of such recombinant S. cerevisiae vaccine, we orally fed the rabbits with heat-inactivated myostatin-recombinant S. cerevisiae for 5 weeks, and then myostatin-specific antibody in serum was detected successfully by western blotting and ELISA assay. The rabbits treated with myostatin-recombinant S. cerevisiae vaccine grew faster and their muscles were much heavier than that of the control group. As a common experimental animal and a meat livestock with great economic value, rabbit was proved to be the second animal species that have been successfully orally immunized by recombinant S. cerevisiae vaccine after mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Corticosteroid administration in oral and orthognathic surgery: a systematic review of the literature and meta-analysis

DEFF Research Database (Denmark)

Dan, Anne E B; Thygesen, Torben H; Pinholt, Else M

2010-01-01

was made. The primary predictor variable was CS administration and the outcome variables were edema, pain, and infection. A meta-analysis was performed. The risk of other side effects was evaluated through a simple review. RESULTS: In oral surgery, most clinical trials showed a significant decrease...... toward a neuroregeneration effect, but no statistical analysis could be performed. Regarding the risk of other side effects, in oral surgery, a minimal risk of chronic adrenal suppression was seen; in orthognathic surgery, an elevated risk of avascular osteonecrosis, steroid-induced psychosis......, and adrenal suppression was seen. There were no reports of decreased healing. CONCLUSION: These findings suggest that the administration of CS in oral surgery decreases edema and pain significantly, with no higher risk of infection and with a minimum risk of other side effects....

Oral administration of piperine for the control of aflatoxin intoxication in rats.

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Gagini, Thalita B; Silva, Robson E; Castro, Isabela S; Soares, Breno A; Lima, Marco E F; Brito, Marilene F; Mazur, Carlos; Direito, Glória M; Danelli, Maria das Graças M

2010-04-01

Aflatoxins are mycotoxins that have important toxic effects on human and animal health, even if consumed at low doses. The oral administration of piperine (1.12 mg/kg) during 23 days in rats seemingly interfered with the toxicity of aflatoxins, decreasing hepatic injuries and the leukocyte depletion in experimentally intoxicated animals.

Protection from radiation injury through oral administration of PF4 gene carried by attenuated salmonella

International Nuclear Information System (INIS)

Zhao Lihua; Liu Bin; Yu Xiaofei; Zhang Lei; Han Zhongchao

2005-01-01

Objective: To investigate the in vivo radiation protection effect of PF4 by oral administration of attenuated salmonella as the carrier in mice. Methods: The eukaryotic vector pIRES2-EGFP-carried PF4 gene was transferred into an aroA-autotrophic mutant of salmonella typhimurium (SL3261), which was administered orally to BALBPc mice at 1x10 8 PFu once every interval three days. At 12 hours after the third oral administration the mice were subjected to a total body irradiation (TBI) of 700 cGy by a 60 Co source. The protective effect of SL3261/PF4 was determined by detection GFP ( green fluorescence protein) expression in tissues, peripheral blood count, culture of bone marrow colony-forming cells and survival time of mice. Results: Expression of GFP could be detected in the liver, spleen, intestine, kidney, peripheral blood and bone marrow. On days 7 and 14 after irradiation, Compared to controls, there were obvious differences in number of bone marrow mononuclear cells, CFU-GM (granulocyte-macrophage colony-forming unit ) and HPP-CFC (high proliferating potential-colony-forming cells) of mice treated with SL3261/PF4 (P<0.05) as well as prolongation of the survival time. Conclusion: These data demonstrate for the first time that PF4 protects mice from TBI injury and accelerates recovery of hematopoiesis by oral administration of attenuated salmonella carrying PF4 gene. (authors)

Oral and nasal administration of chicken type II collagen suppresses adjuvant arthritis in rats with intestinal lesions induced by meloxicam.

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Zheng, Yong-Qiu; Wei, Wei; Shen, Yu-Xian; Dai, Min; Liu, Li-Hua

2004-11-01

To investigate the curative effects of oral and nasal administration of chicken type II collagen (CII) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions. AA model in Sprague-Dawley (SD) rats with or without intestinal lesions induced by meloxicam was established and those rats were divided randomly into six groups which included AA model, AA model+meloxicam, AA model+oral CII, AA model+nasal CII, AA model+ meloxicam+oral C II and AA model+meloxicam+nasal CII (n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund's adjuvant (CFA), and then treated with chicken CII intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis. Intragastrical administration of meloxicam (1.5 mg/kg) induced multiple intestinal lesions in AA rats. There was a significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01) and AA model group (P<0.01) compared with normal group. DAO activities of intestinal homogenates in AA+meloxicam group were significantly less than those in AA rats (P<0.01). There was a significant increase of intestinal MPO activities in AA+meloxicam group compared with normal control (P<0.01). Oral or nasal administration of CII (20 microg/kg) could suppress the secondary hind paw swelling(P<0.05 for oral CII; P<0.01 for nasal CII), synoviocyte proliferation (P<0.01) and histopathological degradation in AA rats, but they had no significant effects on DAO and MPO changes. However, oral administration of CII (20 microg/kg) showed the limited efficacy on arthritis in AA+meloxicam model and the

Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration.

Science.gov (United States)

Milman, Garry; Barnes, Allan J; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deana L; Gorelick, David A; Huestis, Marilyn A

2011-08-01

Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n = 360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ(9)-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography-mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges for THC, 11-hydroxy-THC, and cannabidiol were 0.25-50 ng/mL; cannabinol 1-50 ng/mL; and THCCOOH 5-500 pg/mL. THCCOOH was the most prevalent analyte in 344 specimens (96.9%), with concentrations up to 1,390.3 pg/mL. 11-hydroxy-THC, cannabidiol, and cannabinol were detected in 1, 1, and 3 specimens, respectively. THC was detected in only 13.8% of specimens. The highest THC concentrations were obtained at admission (median 1.4 ng/mL, range 0.3-113.6) from previously self-administered smoked cannabis. A total of 2.5 and 3.7% of specimens were THC-positive at the recommended Substance Abuse and Mental Health Services Administration (2 ng/mL) and Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) (1 ng/mL) confirmation cutoffs, respectively. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines. Measurement of THCCOOH may improve the detection and interpretation of OF cannabinoid tests and minimize the possibility of OF contamination from passive inhalation of cannabis smoke.

Safety of 8-weeks oral administration of Arctium lappa L.

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Bok, So-Hyeon; Cho, Seung Sik; Bae, Chun-Sik; Park, Dae-Hun; Park, Kyung-Mok

2017-09-01

Recently, worldwide dietary reference intakes have been considered an important guideline for public health. Some governments and the World Health Organization (WHO) provide guidelines concerning dietary intake. Although an ingredient may have a history of use as a culinary material, changes in the environment over time suggest that the acceptable maximum intake each of food/culinary material should be regularly evaluated. Arctium lappa L. has been used as a culinary material for many centuries in Korea and Japan and some recent studies have reported related therapeutic effects. However, there are no reports on the safety of repeated oral administration. In this study, we evaluated the safety of a 8-weeks repeated oral intake of A. lappa . We concluded that treatment with lappa , which was within the safety range, resulted in body weight decrease and blood glucose suppression.

Pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses.

Science.gov (United States)

Tsujimura, Koji; Yamada, Masayuki; Nagata, Shun-ichi; Yamanaka, Takashi; Nemoto, Manabu; Kondo, Takashi; Kurosawa, Masahiko; Matsumura, Tomio

2010-03-01

We investigated the pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. Following an oral dose of famciclovir at 20 mg/kg, maximum plasma concentrations of penciclovir occurred between 0.75 and 1.5 hr (mean 0.94 + or - 0.38 hr) after dosing and were in the range 2.22 to 3.56 microg/ml (mean 2.87 + or - 0.61 microg/ml). The concentrations of penciclovir declined in a biphasic manner after the peak concentration was attained. The mean half-life of the rapid elimination phase was 1.73 + or - 0.34 hr whereas that of the slow elimination phase was 34.34 + or - 13.93 hr. These pharmacokinetic profiles observed were similar to those of another antiherpesvirus drug, acyclovir, previously reported in horses following oral dosing of its prodrug valacyclovir.

Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

International Nuclear Information System (INIS)

Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

2008-01-01

Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent

Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

Science.gov (United States)

Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

2016-10-15

Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

Science.gov (United States)

Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

2017-06-01

The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

Excretion and metabolism of 1-nitropyrene in rats after oral or intraperitoneal administration

International Nuclear Information System (INIS)

Dutcher, J.S.; Sun, J.D.; Bechtold, W.E.; Unkefer, C.J.

1985-01-01

The metabolism and excretion of 1-nitropyrene (NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal (ip) or oral administration was studied. Radiolabeled NP was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of [ 14 C]NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered 14 C was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3-8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37 0 C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible. 29 references, 8 figures

Oral administration of a medium containing both D-aspartate-producing live bacteria and D-aspartate reduces rectal temperature in chicks.

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Do, P H; Tran, P V; Bahry, M A; Yang, H; Han, G; Tsuchiya, A; Asami, Y; Furuse, M; Chowdhury, V S

2017-10-01

1. The aim of this study was to investigate the effects on the rectal temperature of young chicks of the oral administration of a medium that contained both live bacteria that produce D-aspartate (D-Asp) and D-Asp. 2. In Experiment 1, chicks were subjected to chronic oral administration of either the medium (containing live bacteria and 2.46 μmol D-Asp) or water from 7 to 14 d of age. Plasma-free amino acids as well as mitochondrial biogenic gene expression in the breast muscle were analysed. In Experiment 2, 7-d-old chicks were subjected to acute oral administration of the above medium or of an equimolar amount of D-Asp to examine their effect on changes in rectal temperature. In Experiment 3, after 1 week of chronic oral administration of the medium, 14-d-old chicks were exposed to either high ambient temperature (HT; 40 ± 1°C, 3 h) or control thermoneutral temperature (CT; 30 ± 1°C, 3 h) to monitor the changes in rectal temperature. 3. Chronic, but not acute, oral administration of the medium significantly reduced rectal temperature in chicks, and a chronic effect also appeared under HT conditions. 4. Chronic oral administration of the medium significantly reduced the mRNA abundance of the avian uncoupling protein (avUCP) in the breast muscle, but led to a significant increase in avian adenine nucleotide translocator (avANT) mRNA in the same muscle. 5. (a) These results indicate that the medium can reduce body temperature through the decline in avUCP mRNA expression in the breast muscle that may be involved in reduced mitochondrial proton leaks and heat production. (b) The increase in avANT further suggests a possible enhancement of adenosine triphosphate (ATP) synthesis.

Extensive metabolism and route-dependent pharmacokinetics of bisphenol A (BPA) in neonatal mice following oral or subcutaneous administration

International Nuclear Information System (INIS)

Draganov, Dragomir I.; Markham, Dan A.; Beyer, Dieter; Waechter, John M.; Dimond, Stephen S.; Budinsky, Robert A.; Shiotsuka, Ronald N.; Snyder, Stephanie A.; Ehman, Kimberly D.; Hentges, Steven G.

2015-01-01

Orally administered bisphenol A (BPA) undergoes efficient first-pass metabolism to produce the inactive conjugates BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). This study was conducted to evaluate the pharmacokinetics of BPA, BPA-G and BPA-S in neonatal mice following the administration of a single oral or subcutaneous (SC) dose. This study consisted of 3 phases: (1) mass-balance phase in which effective dose delivery procedures for oral or SC administration of 3 H-BPA to postnatal day three (PND3) mice were developed; (2) pharmacokinetic phase during which systemic exposure to total 3 H-BPA-derived radioactivity in female PND3 mice was established; and (3) metabolite profiling phase in which 50 female PND3 pups received either a single oral or SC dose of 3 H-BPA. Blood was collected from 5 pups/route/time-point at various times post-dosing, the blood plasma samples were pooled by group, and time-point and samples were profiled by HPLC with fraction collection. Fractions were analyzed for total radioactivity and data used to reconstruct radiochromatograms and to integrate individual peaks. The identity of the BPA, BPA-G, and BPA-S peaks was confirmed using authentic standards and LC–MS/MS analysis. The result of this study revealed that female PND3 mice have the capacity to metabolize BPA to BPA-G, BPA-S and other metabolites after both routes of administration. Systemic exposure to free BPA is route-dependent as the plasma concentrations were lower following oral administration compared to SC injection

Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration.

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Kimble, B; Black, L A; Li, K M; Valtchev, P; Gilchrist, S; Gillett, A; Higgins, D P; Krockenberger, M B; Govendir, M

2013-10-01

The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate. © 2013 John Wiley & Sons Ltd.

Oral gadopentetate dimeglumine administration as a negative gastrointestinal contrast agent to improve image quality of MR cholangiopancreatography

International Nuclear Information System (INIS)

Chen Yi; Xu Yikai; Zhao Yuhui; Wang Guisheng

2008-01-01

Objective: To choose optimal concentration and volume of Gd-DTPA solution as a oral gastrointestinal negative contrast agent for MRCP. To evaluate the role of Gd-DTPA solution in improving image quality of MRCP. Methods: In vitro experiment: Gd-DTPA solution was made with different concentrations. T 1 WI, T 2 WI, two-dimensional single slice fast spin echo sequence and three-dimensional half-fourier acquisition single-shot fast spin echo sequence were performed to measure the signal intensity of these contrast agents respectively, so Gd-DTPA solution with the optimal concentration can be decided as oral negative gastrointestinal contrast agent on MRCP. Clinical study: The Gd-DTPA solution with optimal concentration and volume was regarded as an oral negative gastrointestinal contrast agent of MRCP. Twenty- four' patients were performed with MRCP before and after (5-10 minutes and 10-15 minutes) administration of oral negative gastrointestinal contrast agent and image quality was analyzed. Statistical analysis was performed using analysis of variance with SPSS 10.0. Results: When the concentration of Gd-DTPA solution was ≤0.01 mol/L, the contrast agent was hyperintense on T 1 WI. On T 2 WI, when the concentration was ≥0.015 mol/L, it was as hypointense as basic ground; On 2D FSE MRCP images, controls were hyperintense and the contrast agent with concentration ranging from 0.0025 mol/L to 0.03 mol/L was hypointense. On 3D HEAST MRCP image, controls were hyperintense and when the concentration of Gd-DTPA was ≥0.01 mol, the contrast agent was hypointense. The Gd-DTPA solution with the concentration of 0.01 mol/L and the volume of 100 ml was chosen as MRCP oral negative gastrointestinal contrast agent. On MRCP images after oral administration of the contrast agent, in 10-15 minutes, the average grade scores within 24 patients of the intrahepatic bile duct, the common hepatic bile duct, the gall bladder, the common bile duct and pancreatic duct (the average grade

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

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Wen-bin He

2018-01-01

Full Text Available To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood–brain barrier and promotes synaptic functions in the hippocampus.

Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

Science.gov (United States)

Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

2015-06-01

Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

Science.gov (United States)

Liu, JunLi; Wang, YiHu; Song, ShuJun; Wang, XiJie; Qin, YaYa; Si, ShaoYan; Guo, YanChuan

2015-01-01

Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

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JunLi Liu

Full Text Available Collagen peptides (CPs and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8 for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg; OVX + calcium citrate (75 mg/kg. After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

Halloysite Nanotubes-Induced Al Accumulation and Fibrotic Response in Lung of Mice after 30-Day Repeated Oral Administration.

Science.gov (United States)

Wang, Xue; Gong, Jiachun; Rong, Rui; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

2018-03-21

Natural halloysite (Al 2 Si 2 O 5 (OH) 4 · nH 2 O) nanotubes (HNT) are clay materials with hollow tubular structure and are widely applied in many fields. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility; however, the in vivo toxicity of HNTs remains unclear. In this study, the biodistribution and pulmonary toxicity of the purified HNTs in mice were investigated after intragastric administration for 30 days. HNTs have high stability in biological conditions. Oral administration of HNTs caused significant Al accumulation predominantly in the lung with relative slight effects on Si biodistribution. Oral administration of HNTs stimulated the growth of the mice at low dose (5 mg/kg BW) with no pulmonary toxicity but inhibited the mouse growth and resulted in oxidative stress and inflammation in lung at high dose (50 mg/kg BW). In addition, oral HNTs at high dose could be absorbed from the gastrointestinal tract and deposited in lung and could also induce pulmonary fibrosis.

Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

Science.gov (United States)

Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

1990-01-01

The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

OpenAIRE

Wen-bin He; Kazuho Abe; Tatsuhiro Akaishi

2018-01-01

To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to...

5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

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Iwao Sasaki

2010-09-01

Full Text Available 5-Fluorouracil (5-FU is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.

In vivo analysis of supersaturation/precipitation/absorption behavior after oral administration of pioglitazone hydrochloride salt; determinant site of oral absorption.

Science.gov (United States)

Tanaka, Yusuke; Sugihara, Masahisa; Kawakami, Ayaka; Imai, So; Itou, Takafumi; Murase, Hirokazu; Saiki, Kazunori; Kasaoka, Satoshi; Yoshikawa, Hiroshi

2017-08-30

The purpose of this study was to evaluate in vivo supersaturation/precipitation/absorption behavior in the gastrointestinal (GI) tract based on the luminal concentration-time profiles after oral administration of pioglitazone (PG, a highly permeable lipophilic base) and its hydrochloride salt (PG-HCl) to rats. In the in vitro precipitation experiment in the classic closed system, while the supersaturation was stable in the simulated gastric condition, PG drastically precipitated in the simulated intestinal condition, particularly at a higher initial degree of supersaturation. Nonetheless, a drastic and moderate improvement in absorption was observed in vivo at a low and high dose of PG-HCl, respectively. Analysis based on the luminal concentration of PG after oral administration of PG-HCl at a low dose revealed that most of the dissolved PG emptied from the stomach was rapidly absorbed before its precipitation in the duodenum. At a high dose of PG-HCl, PG partly precipitated in the duodenum but was absorbed to some extent. Therefore, the extent of the absorption was mainly dependent on the duodenal precipitation behavior. Furthermore, a higher-than expected absorption after oral administration of PG-HCl from in vitro precipitation study may be due to the absorption process in the small intestine, which suppresses the precipitation by removal of the drug. This study successfully clarify the impact of the absorption process on the supersaturation/precipitation/absorption behavior and key absorption site for a salt formulation of a highly permeable lipophilic base based on the direct observation of in vivo luminal concentration. Our findings may be beneficial in developing an ideal physiologically based pharmacokinetic model and in vitro predictive dissolution tools and/or translating the in silico and in vitro data to the in vivo outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

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He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

2015-04-22

Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright �

Pharmacokinetics of /sup 3/H-pipethiaden after single oral and intravenous administration in rats

Energy Technology Data Exchange (ETDEWEB)

Lapka, R.; Franc, Z.; Smolik, S.

1985-01-01

Tritium labelled anti-migraine drug 4-(1-methyl-4-piperidyliden)-4,9-duhydrothieno(2,3-c)-2-benzothiepine (pipethiaden) was prepared. After oral and intravenous administration to rats not only the courses of total radioactivity in plasma and various organs were determined, but by means of TLC-radiometry also the levels of pipethiaden itself. After the oral dose 1.35 mg/kg the plasma levels of pipethiaden did not exceed 3.5 ng/ml. Some pharmacokinetic parameters (e.g. t/sub 1/2/el-4h) were calculated by compartmental analysis of plasma levels.

Oral Administration of Recombinant Lactococcus lactis Expressing the Cellulase Gene Increases Digestibility of Fiber in Geese.

Science.gov (United States)

Zhou, Haizhu; Gao, Yunhang; Gao, Guang; Lou, Yujie

2015-12-01

Enhancing cellulose digestibility in animals is important for improving the utilization of forage, which can decrease the amount of food used in animal production. The aim of the present study was to achieve recombinant expression of the cellulase gene in Lactococcus lactis and evaluate the effects of oral administration of the recombinant L. lactis on fiber digestibility in geese. Cellulase (Cell) and green fluorescent protein (GFP) genes were cloned into a L. lactis expression vector (pNZ8149) to construct the recombinant expression plasmid (pNZ8149-GFP-Cell). Then, the recombinant expression plasmid was transformed into L. lactis (NZ3900) competent cells by electroporation to obtain recombinant L. lactis (pNZ8149-GFP-Cell/NZ3900) in which protein expression was induced by Nisin. Expression of GFP and Cell by the recombinant L. lactis was confirmed using SDS-PAGE, fluorescence detection, and Congo red assays. A feeding experiment showed that oral administration of pNZ8149-GFP-Cell/NZ3900 significantly increased the digestibility of dietary fiber in geese fed either a maize stalk diet or a rice chaff diet. Therefore, oral administration of recombinant L. lactis cells expressing the cellulase gene increases fiber digestibility in geese, offering a way to increase the utilization of dietary fiber in geese.

The Effects of Fat-soluble Vitamin Administration on Plasma Vitamin Status of Nursing Pigs Differ When Provided by Oral Administration or Injection

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Y. D. Jang

2014-05-01

Full Text Available Four experiments were conducted to investigate the effect of fat-soluble vitamin administration to sows or newborn pigs on plasma vitamin status. In Exp. 1 and 2, a total of 24 and 43 newborn pigs were allotted to control and vitamin treatments (vitamin D3 with variable addition of vitamins A and E orally or by i.m. injection. In Exp. 3, pigs from Exp. 2 were allotted to 2 treatments (±vitamins D3 and E in drinking water for 14 d postweaning. In Exp. 4, twenty-four gestating sows were used for 2 treatments (±injection of a vitamin D3/A/E product 2 wk prepartum. In Exp. 1 and 2, when vitamin D3 was administrated orally or by i.m. injection on d 1 of age, pigs had increased plasma 25-hydroxycholecalciferol (25-OH D3 concentration 10 d after administration compared with control pigs (p<0.05. The injectable administration with vitamin D3 and E was able to achieve higher plasma 25-OH D3 (p<0.05 and α-tocopherol (p<0.05 concentrations than oral administration. At weaning, the pigs in the injection group had higher plasma 25-OH D3 concentration than those in the other groups in both studies (p<0.05. In Exp. 3, water supplementation of vitamin D3 and E postweaning increased plasma 25-OH D3 and α-tocopherol concentrations at d 14 postweaning (p<0.01. In Exp. 4, when sows were injected with the vitamin D3 product prepartum, serum 25-OH D3 concentrations of sows at farrowing (p<0.01, and in their progeny at birth (p<0.01 and weaning (p<0.05 were increased. These results demonstrated that fat-soluble vitamin administration to newborn pigs increased plasma 25-OH D3 concentration regardless of administration routes and α-tocopherol concentration by the injectable route, and that water supplementation of vitamin D3 and E to nursery pigs increased plasma 25-OH D3 and α-tocopherol concentrations. Additionally, injecting sows with vitamin D3 prepartum increased 25-OH D3 in sows and their offspring. If continued research demonstrates that the serum levels of

Distribution and binding of [14C]acrylamide to macromolecules in SENCAR and BALB/c mice following oral and topical administration

International Nuclear Information System (INIS)

Carlson, G.P.; Weaver, P.M.

1985-01-01

To determine if differences in acrylamide distribution or its binding to DNA could be responsible for the reported higher incidence of skin papillomas observed after oral administration compared to topical application, [ 14 C]acrylamide was administered by topical application and oral intubation to male SENCAR and BALB/mice. Portions of lung, liver, stomach, testes, and skin were removed, and 14 C was measured at 15 min, 30 min, 1, 6, 12, 24, and 48 hr. Binding to DNA, RNA, and protein was measured at 6 and 48 hr. Following oral administration, few strain differences in distribution or binding were noted. After topical application, SENCAR mice generally showed higher tissue concentrations than did the BALB/c mice at the early time periods but not at the later ones. Comparing the two routes, comparable concentrations were observed in all tissues except the skin where the amount of [ 14 C]acrylamide after topical application was approximately 100 times that observed after oral administration. At 48 hr, binding to DNA was sevenfold higher after topical than after oral administration. The effect of route on papilloma formation cannot be explained, therefore, on the basis of either a difference in distribution or binding to DNA in the target organ. The binding of acrylamide to DNA in skin was similar in both SENCAR and BALB/c mice indicating that the much greater susceptibility of the SENCAR mice to tumorigenesis cannot be explained simply on the basis of distribution or macromolecular binding

The route of administration (oral vs intravenous) does not influence dose or outcome in Graves' disease and unifocal autonomy

International Nuclear Information System (INIS)

Schneider, Peter; Biko, Johannes; Haenscheid, Heribert; Hilliger, Stephan; Koutsampelas, Christos; Kranzfelder, Michael; Ladner, Stephan; Reiners, Christoph

2005-01-01

In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome. Fifty-four patients suffering from Graves' disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test. No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%. The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this. (orig.)

Non-invasive diagnosis of isolated chylopericardium using precordial pericardial imaging after oral administration of 131I-triolein

International Nuclear Information System (INIS)

Fujiseki, Yoshiki; Katsura, Tadahiko; Goto, Masakatsu; Kawanishi, Katsuyuki

1982-01-01

Chylopericardium is a rare disease and affects both sexes equally from neonate to adult. Usually, there are abnormal connections between the pericardial cavity and thoracic lymphatic systems. These connections are detected by (1) recovery of orally administered Sudan III from pericardial fluid, (2) evidence of radioactivity in the pericardial fluid by paracentesis after oral administration of 131 I-labeled triolein, and (3) lymphangiography. However, these method are technically difficult and invasive, thus sometimes dangerous for children. We employed precordial pericardial imaging after oral administration of 131 I-labeled triolein on a 9-year-old Japanese girl wth isolated chylopericardium before and after surgery. Abnormal connections and the back-ward flow to the pulmonary lymphatics were demonstrated by this method. This is an easy, non-invasive, reliable and safe method for detecting the abnormal connections of pericardial and lymphatic systems in children with chylopericardium. (author)

Administrative Challenges to the Integration of Oral Health With Primary Care: A SWOT Analysis of Health Care Executives at Federally Qualified Health Centers.

Science.gov (United States)

Norwood, Connor W; Maxey, Hannah L; Randolph, Courtney; Gano, Laura; Kochhar, Komal

Inadequate access to preventive oral health services contributes to oral health disparities and is a major public health concern in the United States. Federally Qualified Health Centers play a critical role in improving access to care for populations affected by oral health disparities but face a number of administrative challenges associated with implementation of oral health integration models. We conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis with health care executives to identify strengths, weaknesses, opportunities, and threats of successful oral health integration in Federally Qualified Health Centers. Four themes were identified: (1) culture of health care organizations; (2) operations and administration; (3) finance; and (4) workforce.

The Effect of "Massed" Task Repetitions on Complexity, Accuracy and Fluency: Does It Transfer to a New Task?

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Ahmadian, Mohammad Javad

2011-01-01

To date, research results suggest that task repetition positively affects oral task performance. However, researchers have not yet shown the extension of the benefits of repeating the same task to performance of a new task. This article first provides an overview of the currently available research findings on task repetition and then presents the…

TRANSDERMAL ADMINISTRATION OF THE DOPAMINE AGONIST N-0437 AND 7 ESTER PRODRUGS - COMPARISON WITH ORAL-ADMINISTRATION IN THE 6-OHDA TURNING MODEL

NARCIS (Netherlands)

DENDAAS, [No Value; TEPPER, PG; ROLLEMA, H; HORN, AS

1990-01-01

The potent and selective D2-agonist N-0437 [2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin] undergoes considerable first-pass metabolism after oral administration due to glucuronidation of the phenolic group. In an attempt to improve its bioavailability, seven ester prodrugs of N-0437 were

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

Science.gov (United States)

He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

2018-01-01

To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Metabolic fate of poly-(lactic-co-glycolic acid-based curcumin nanoparticles following oral administration

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Harigae T

2016-06-01

Full Text Available Takahiro Harigae,1 Kiyotaka Nakagawa,1 Taiki Miyazawa,2 Nao Inoue,3 Fumiko Kimura,1 Ikuo Ikeda,3 Teruo Miyazawa4,5 1Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; 2Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 3Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, 4Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center, 5Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan Purpose: Curcumin (CUR, the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid-based CUR nanoparticles (CUR-NP have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG, the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability.Methods: Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells.Results: Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with

Pharmacokinetics of enrofloxacin following oral and subcutaneous administration in the common ringtail possum (Pseudocheirus peregrinus).

Science.gov (United States)

Scheelings, T F; Devi, J L; Woodward, A P; Whittem, T

2015-10-01

[Correction added on 23 March 2015, after first online publication: Terminal half-life values of enrofloxacin is corrected in the fourth sentence of the abstract] Clinically healthy common ringtail possums (n = 5) received single doses of 10 mg/kg enrofloxacin orally and then 2 weeks later subcutaneously. Serial plasma samples were collected over 24 h for each treatment phase, and enrofloxacin concentrations were determined using a validated HPLC assay. Pharmacokinetic parameters were determined by noncompartmental analysis. Following oral administration, plasma concentrations were of therapeutic relevance (Cmax median 5.45 μg/mL, range 2.98-6.9 μg/mL), with terminal-phase half-life (t½ ) shorter than in other species (median 3.09 h, range 1.79-5.30 h). In contrast, subcutaneous administration of enrofloxacin did not achieve effective plasma concentrations, with plasma concentrations too erratic to fit the noncompartmental model except in one animal. On the basis of the AUC:MIC, enrofloxacin administered at 10 mg/kg orally, but not subcutaneously, is likely to be effective against a range of bacterial species that have been reported in common ringtail possums. © 2015 John Wiley & Sons Ltd.

Penetration and delivery characteristics of repetitive microjet injection into the skin.

Science.gov (United States)

Römgens, Anne M; Rem-Bronneberg, Debbie; Kassies, Roel; Hijlkema, Markus; Bader, Dan L; Oomens, Cees W J; van Bruggen, Michel P B

2016-07-28

Drugs can be delivered transdermally using jet injectors, which can be an advantageous route compared to oral administration. However, these devices inject large volumes deep into the skin or tissues underneath the skin often causing bruising and pain. This may be prevented by injecting smaller volumes at lower depth in a repetitive way using a microjet injection device. Such a device could be used to apply drugs in a controllable and sustainable manner. However, the efficacy of microjet injection has been rarely examined. In this study, the penetration and delivery capacity was examined of a repetitive microjet injection device. Various experiments were performed on epidermal and full-thickness ex vivo human as well as ex vivo porcine skin samples. Results revealed that microjets with a velocity exceeding 90m/s penetrated an epidermal skin sample with a delivery efficiency of approximately 96%. In full-thickness human skin, the delivery efficiency drastically decreased to a value of approximately 12%. Experiments on full-thickness skin revealed that the microjets penetrated to a depth corresponding to the transition between the papillary and reticular dermis. This depth did not further increase with increasing number of microjets. In vivo studies on rats indicated that intact insulin was absorbed into the systemic circulation. Hence, the microjet injection device was able to deliver medication into the skin, although the drug delivery efficiency should be increased. Copyright © 2016 Elsevier B.V. All rights reserved.

Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

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Giuseppe Benagiano

2009-04-01

Full Text Available Giuseppe Benagiano, Sabina Carrara, Valentina FilippiDepartment of Gynaecology and Obstetrics, Sapienza University, Rome, ItalyAbstract: The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic and peripheral (cervical mucus and endometrium levels. Levonorgestrel (LNG, alone or in combination with ethinyl estradiol (EE, is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years

Recovery Effects of Oral Administration of Glucosylceramide and Beet Extract on Skin Barrier Destruction by UVB in Hairless Mice

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Yoshihiro Tokudome

2017-10-01

Full Text Available Purified glucosylceramide from beet extract (beet GlcCer and beet extract containing an equal amount of GlcCer were administered orally to ultra violet B (UVB-irradiated mice, and differences in the protective effects against skin barrier dysfunction caused by UVB irradiation were compared. In the beet GlcCer group, epidermal thickening and the decrease in stratum corneum (SC ceramide content caused by UVB irradiation were reduced. In the group that was orally administered beet extract containing glucosylceramide, effects similar to those in the beet GlcCer group were observed. Oral administration of beet GlcCer had no obvious effects against an increase in TEWL or decrease in SC water content after UVB irradiation, but there was improvement in the beet extract group. Oral administration of beet GlcCer is effective in improving skin barrier function in UVB-irradiated mice. Beet extract contains constituents other than GlcCer that are also effective in improving skin barrier function.

Preclinical Studies on Intestinal Administration of Antisense Oligonucleotides as a Model for Oral Delivery for Treatment of Duchenne Muscular Dystrophy

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Maaike van Putten

2014-01-01

Full Text Available Antisense oligonucleotides (AONs used to reframe dystrophin mRNA transcripts for Duchenne muscular dystrophy (DMD patients are tested in clinical trials. Here, AONs are administered subcutaneously and intravenously, while the less invasive oral route would be preferred. Oral delivery of encapsulated AONs supplemented with a permeation enhancer, sodium caprate, has been successfully used to target tumor necrosis factor (TNF-α expression in liver. To test the feasibility of orally delivered AONs for DMD, we applied 2′-O-methyl phosphorothioate AONs (with or without sodium caprate supplementation directly to the intestine of mdx mice and compared pharmacokinetics and -dynamics with intravenous, intraperitoneal, and subcutaneous delivery. Intestinally infused AONs were taken up, but resulted in lower plasma levels compared to other delivery routes, although bioavailability could be largely improved by supplementation of sodium caprate. After intestinal infusion, AON levels in all tissues were lower than for other administration routes, as were the ratios of target versus nontarget organ levels, except for diaphragm and heart where comparable levels and ratios were observed. For each administration route, low levels of exon skipping in triceps was observed 3 hours post-AON administration. These data suggest that oral administration of naked 2′-O-methyl phosphorothioate AONs may be feasible, but only when high AON concentrations are used in combination with sodium caprate.

Repetitive Stress Injuries

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... Safe Videos for Educators Search English Español Repetitive Stress Injuries KidsHealth / For Teens / Repetitive Stress Injuries What's ... t had any problems since. What Are Repetitive Stress Injuries? Repetitive stress injuries (RSIs) are injuries that ...

Administración de medicamentos por vía oral: Interacciones medicamento - alimento Oral drug administration: drug-food interactions

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Nélida Barrueco

2008-03-01

Full Text Available Introducción: la vía oral de administración de medicamentos es la vía más cómoda, segura y económica. Sin embargo, pueden existir interacciones con otros fármacos o con alimentos que alteren la eficacia y seguridad de los mismos. Objetivo: desarrollar un programa de información dirigido a enfermeros y enfermeras sobre la administración de medicamentos por vía oral. Método: se seleccionan los medicamentos más utilizados en el área de cardiología pediátrica, revisándose para cada principio activo la administración en relación con alimentos o productos medicinales y otros aspectos relacionados con la administración por vía oral. Resultados: se elabora una tabla informativa sobre un total de 28 principios activos. Discusión: Los farmacéuticos de hospital se han integrado recientemente en los equipos multidisciplinares y desde esta posición tienen la oportunidad de desarrollar diferentes programas de atención farmacéutica, educación sanitaria e información encaminadas a prevenir problemas relacionados con los medicamentos, aumentar su uso seguro y disminuir los riesgos asociados a cualquier tratamiento farmacológico. Las prescripciones médicas generalmente no indican el horario y la forma de administración de los medicamentos, dejando a enfermeros y enfermeras la responsabilidad de su organización. Por esto deben estar informados de cómo y cuándo se deben administrar los medicamentos, lo que permite garantizar su uso seguro y disminuir los riesgos asociados al tratamiento.Background: The easiest, safest and cheapest way to administrate drugs is by mouth (PO. Nevertheless, there may be interactions, either with other drugs or with food, which can modify efficacy and security of the drug itself. Objective: the development of a nursing information program about the administration of drugs PO. Method: we selected the most used drugs corresponding to the pediatric cardiology area, looking for the best administration

Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration.

Science.gov (United States)

Wang, Xue; Gong, Jiachun; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

2018-06-01

Halloysite (Al 2 Si 2 O 5 (OH) 4 ·nH 2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury. © 2018 Wiley Periodicals, Inc.

Calcium metabolism in children suffering from homozygous β-thalassaemia after oral administration of 47Ca

International Nuclear Information System (INIS)

Liakakos, D.; Vlachos, P.; Anoussakis, C.; Constantinides, C.; Tsakalosos, I.; Alexandra Hospital, Athens

1976-01-01

The study of calcium metabolism in ten thalassaemic children comperatively with controls after oral administration of 47 Ca has shown diminished intestinal absorption. It is suggested that this finding is propably related in part with the pathogenesis of the osteoporosis in thalassaemia. (orig.) [de

Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

Science.gov (United States)

Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas

2013-10-01

The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Interaction of titanium dioxide nanoparticles with glucose on young rats after oral administration.

Science.gov (United States)

Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Chen, Tian; Li, Yang; Zhang, Wenxiao; Gao, Xin; Li, Ping; Wang, Haifang; Jia, Guang

2015-10-01

Titanium dioxide nanoparticles (TiO2 NPs) have a broad application prospect in replace with TiO2 used as a food additive, especially used in sweets. Understanding the interaction of TiO2 NPs with sugar is meaningful for health promotion. We used a young animal model to study the toxicological effect of orally administrated TiO2 NPs at doses of 0, 2, 10 and 50 mg/kg per day with or without daily consumption of 1.8 g/kg glucose for 30 days and 90 days. The results showed that oral exposure to TiO2 NPs and TiO2 NPs+glucose both induced liver, kidney, and heart injuries as well as changes in the count of white and red blood cells in a dose, time and gender-dependent manner. The toxicological interactions between orally-administrated TiO2 NPs and glucose were evident, but differed among target organs. These results suggest that it is necessary to limit dietary co-exposure to TiO2 NPs and sugar. Nanotechnology has gained entrance in the food industry, with the presence of nanoparticles now in many food items. Despite this increasing trend, the potential toxic effects of these nanoparticles to human remain unknown. In this article, the authors studied titanium dioxide nanoparticles (TiO2 NPs), which are commonly used as food additive, together with glucose. The findings of possible adverse effects on liver, kidney, and heart might point to a rethink of using glucose and TiO2 NPs combination. Copyright © 2015 Elsevier Inc. All rights reserved.

[Studies on calf salmonellosis. 4. Oral and parenteral immunization with live (Smd) and killed antigens].

Science.gov (United States)

Meyer, H; Steinbach, G; Hartmann, H; Hauke, H; Koch, H; Stelzner, A; Linde, K; Schmerbauch, A; Kiupel, H

1977-01-01

Reported are results obtained from studies into oral and parenteral immunisation of calf. The approaches had included the use of live (Smd) or dead antigen from Salmonella (S.) dublin and a combination of the two immunisation methods. Live antigen (Smd) was superior to thermally activated dead antigen, when the oral route was used to prevent S.-dublin injection of calves. The above findings were supported by results from analogous studies in which S. typhimurium and S. dublin or live antigen (Smd) or dead antigen, made of the two, had been applied to mice. (One single subcutaneous) parenteral administration did hardly reveal any difference in favour of live vaccine (Smd). Parenteral administration of live or dead antigen proved to be less effective than repeated oral immunisation, particularly when live vaccine (Smd) was used. Immunity not less than up to six months of age against S. dublin wild strain infection can be provided for young calves by oral immunisation, with Smd vaccine (5. 1010 to 1. 1011 live germs/d) being given on ten consecutive days. Calves orally immunised with live antigen (ten repetitive applications of Smd mutants) are likely to develop an antibody titre (H-agglutinins) against S. dublin. Parenteral boostering,using live antigen, has been accompanied by sensitisation due to oral live antigen administration as well as by dose dependence, as was seen from the bactericidal values. Sensitisation was established from orally immunised calves up to three months old (typical booster reaction). Some of it was attributabale to confrontation with wild strains of Salmonella. The H-agglutinin titres of animals aged threemonths in a calf herd with salmonelloses in which all animals had been orally Smd-immunised were close to those recorded from calves in stocks with no salmonellosis occurrence. Under the conditions of oral immunisation, there had obviously been no action of the wild strain which might have triggered intensive antibody formation.

Effect of Oral Administration of “Gadagi” Tea on Lipid Profile in Rats ...

African Journals Online (AJOL)

Abstract: Effect of oral administration of “Gadagi” tea on lipid profile was assessed in 50 healthy male albino rats which were grouped and administered with different doses(mg/kg) i.e low dose (380mg/kg, 415mg/kg, 365mg/kg,. 315mg/kg for “sak”, ”sada” and “magani” respectively), standard dose (760mg/kg, 830mg/kg, ...

HTO oral administration in mice: Pt. 1

International Nuclear Information System (INIS)

Yamamoto, O.; Yokoro, K.; Seyama, T.; Kinomura, A.; Nomura, T.

1990-01-01

Tritiated water in various concentrations was orally administered continuously to (C57BL/6N and C3H/He)F 1 female mice in a closed animal chamber. Tritium radioactivity in various organ tissues was measured periodically after initiating tritiated water intake using an automatic sample combustion system and a liquid scintillation counter. After 7 days the specific radioactivity reached a plateau. Within a range of 1.48 x 10 11 to 5.92 x 10 11 Bq/dm 3 as the concentration of tritiated water in drinking water, the time of death after initiating the administration was about 2 weeks, a typical time for haematopoietic death. A linear relationship of times of death with tritiated water concentrations in drinking water was observed, on a log-log scale, between 1.85 x 10 10 Bq/dm 3 and 1.48 x 10 11 Bq/dm 3 . At concentrations lower than 9.25 x 10 9 Bq/dm 3 , mice no longer died from haematopoietic failure. The authors conclude, therefore, that there should be a threshold dose rate for haematopoietic death. (author)

Oral Administration of Shark Type II Collagen Suppresses Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Rats

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Wenhui Wu

2012-03-01

Full Text Available Objective: Shark type II collagen (SCII is extracted as a glycoprotein from the cartilage of blue shark (Prionace glauca. We aim to confirm the effects of oral tolerance of SCII on inflammatory and immune responses to the ankle joint of rheumatoid-arthritis rats induced by Complete Freund’s Adjuvant (CFA. Materials and Methods: The onset of rheumatoid arthritis (RA was observed 14 ± x days after injection of CFA. Rats in the control group were treated with acetic acid by oral administration (0.05 mmol kg−1d−1, days 14–28, while rats in experimental groups were treated by oral administration with SCII (1 or 3 mg kg−1d−1, days 14–28, Tripterygium wilfordii polyglycosidium (TWP (10 mg kg−1d−1, days 14–28, and bovine type II collagen from US (US-CII (1 mg kg−1d−1, days 14–28, respectively. The severity of arthritis was evaluated by the articular swelling. The immunological indexes observed included delayed type hypersensitivity (DTH reaction, the level of interleukins 10 (IL-10 in rat blood serum and morphological characterization. Mixed lymphocyte culture (MLC was performed to investigate the relationship between T cell apoptosis and specific immune tolerance induced by SCII. Results: Treatment with SCII for 2 weeks significantly attenuated the acute inflammation. The rats orally administrated with SCII at the level of 3 mg kg−1d−1 (SCII 3 and US-CII had decreased DTH reaction compared with rats in control group. Rats treated with SCII 3 had the highest level of IL-10 with 102 pg/mL. SCII with concentration of 10 μg/L could help to significantly enhance level of Fas/Apo-1 in T cell in vitro. The result of histological staining indicated that the recovery of the articular membranes of ankle joint in SCII 3 group was greatly enhanced. Conclusions: Our results suggest that appropriate dose of SCII can not only ameliorate symptoms but also modify the disease process of Complete-Freunds-Adjuvant-induced arthritis. Oral

Effects of Immediate Repetition in L2 Speaking Tasks: A Focused Study

Science.gov (United States)

Bei, Gavin Xiaoyue

2013-01-01

This paper reports on a focused investigation into the immediate effects of oral narrative task repetition by two adult EFL learners of intermediate and high proficiency. Two participants performed a narrative speaking task after watching a cartoon video clip and repeated their performance three times, followed by a retrospective report in an…

Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome.

Science.gov (United States)

Umezaki, Y; Badran, B W; Gonzales, T S; George, M S

2015-08-01

Burning mouth syndrome (BMS) is a persistent and chronic burning sensation in the mouth in the absence of any abnormal organic findings. The pathophysiology of BMS is unclear and its treatment is not fully established. Although antidepressant medication is commonly used for treatment, there are some medication-resistant patients, and a new treatment for medication-resistant BMS is needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technology approved by the US Food and Drug Administration (FDA) for the treatment of depression. Recent studies have found beneficial effects of TMS for the treatment of pain. A case of BMS treated successfully with daily left prefrontal rTMS over a 2-week period is reported here. Based on this patient's clinical course and a recent pain study, the mechanism by which TMS may act to decrease the burning pain is discussed. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Comparison between the Effects of Oral and Intramuscular Administration of Shin’iseihaito (Xinyiqingfeitang in a Streptococcus pyogenes-Induced Murine Sinusitis Model

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Masaaki Minami

2018-01-01

Full Text Available Streptococcus pyogenes (S. pyogenes is a species of Gram-positive coccoid bacteria having many virulence factors. Its capsule and exotoxins can cause upper respiratory tract infections such as sinusitis. The general treatment for S. pyogenes-induced sinusitis is administration of antibiotics such as penicillin and macrolides; however, a serious problem associated with these antibiotics is their attenuated effect. Shin’iseihaito (Xinyiqingfeitang, a formula of Japanese traditional Kampo medicine and traditional Chinese medicine, has been used for the treatment of sinusitis. In general, formulas of Japanese traditional Kampo medicine are orally administered. This is in contrast to certain formulas of traditional Chinese medicine, which are being recently administered intramuscularly or intravenously. Regarding these traditional Chinese medicine formulas, the injection methodology is reported to be more effective than oral intake. In this study, we compared the efficacy between orally and intramuscularly administered Shin’iseihaito against S. pyogenes-induced sinusitis. We evaluated the antibacterial effect of Shin’iseihaito extract (SSHT against S. pyogenes by K-B disk diffusion assay. Furthermore, we investigated the nasal colonization of S. pyogenes, determined cytokine (TNF-α, IL-1β, and IL-6 levels, and conducted a splenocyte proliferative assay in a murine sinusitis model. SSHT displayed direct anti-S. pyogenes activity. Intramuscular administration of SSHT decreased the nasal colonization of S. pyogenes compared with oral administration. Thymidine uptake analysis revealed that the proliferation of splenocytes from S. pyogenes-infected mice under intramuscular SSHT treatment was upregulated compared to that of splenocytes from S. pyogenes-infected mice under oral SSHT treatment. We also found that TNF-α, IL-1β, and IL-6 levels in the nasal discharge from intramuscularly treated S. pyogenes-infected mice were lower than those from

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

International Nuclear Information System (INIS)

Gulyas, Balazs; Halldin, Christer; Sandell, Johan; Farde, Lars; Sovago, Judit; Cselenyi, Zsolt; Vas, Adam; Kiss, Bela; Karpati, Egon

2002-01-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [ 11 C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [ 11 C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [ 11 C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine.

Science.gov (United States)

Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

Science.gov (United States)

COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATEMichael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas11US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

Science.gov (United States)

Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

2017-11-01

Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

Toxicokinetics of the ciguatoxin P-CTX-1 in rats after intraperitoneal or oral administration.

Science.gov (United States)

Bottein, Marie-Yasmine Dechraoui; Wang, Zhihong; Ramsdell, John S

2011-06-18

Ciguatoxins are voltage-gated selective algal toxins responsible for ciguatera fish poisoning. In this study we evaluate the toxicokinetics of one of the most common ciguatoxins found in the Pacific, the P-CTX-1, in rat after an oral or intraperitoneal (ip) dose of 0.26 μg/kg body weight. We report levels of ciguatoxin activity assessed over time in blood, urine and feces, and at 4 days in liver, muscle and brain, using the functional in vitro N2A cytotoxicity assay. Following exposure, the ciguatoxin activity exhibited a rapid systemic absorption that was followed by a bi-exponential decline, and data best fit a two-compartment model analysis. Maximum blood concentrations were reached at 1.97 and 0.43 h after the oral and ip dose, respectively. Ciguatoxin elimination from blood was slow with terminal half lives (t(½)β) estimated at 82 h for oral and 112 h for ip dosing. Ciguatoxin activity remained in liver, muscle and brain 96 h after ip and oral administration. While smaller amounts appeared in the urine, the main excretion route was feces, with peak rates reaching > 10 pg P-CTX-1 equivalents/h in both routes of administration. Assay guided fractionation showed the presence in the feces and liver of peaks of activity corresponding to the P-CTX-1 and to other less polar metabolites. In conclusion, biologically active ciguatoxins are detectable in blood, liver, muscle and brain, and continued to be excreted in urine and feces 4 days following exposure. Blood, as well as urine and feces may be useful matrices for low-invasive testing methods for ciguatera clinical cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice

International Nuclear Information System (INIS)

Conney, Allan H.; Zhou, Sherry; Lee Maojung; Xie Jianguo; Yang, Chung S.; Lou Yourong; Lu Yaoping

2007-01-01

Oral administration of green tea or a caffeine solution, but not decaffeinated green tea, inhibits UVB-induced complete carcinogenesis in SKH-1 mice. Oral administration of green tea, coffee or a caffeine solution for 2 weeks enhanced UVB-induced increases in apoptosis in the epidermis, but these treatments had no effect in non-UVB treated normal epidermis. Our results suggest that administration of green tea, coffee and caffeine may inhibit UVB-induced carcinogenesis - at least in part - by enhancing UVB-induced apoptosis. Plasma levels of caffeine observed after its oral administration at cancer-preventive dose levels were within the range observed in moderate coffee drinkers. Topical applications of caffeine to mice previously treated with UVB for 20 weeks (high risk mice without tumors) inhibited the formation of tumors and stimulated apoptosis in the tumors but not in areas of the epidermis away from tumors. The selective effects of caffeine administration to stimulate UVB-induced apoptosis or apoptosis in tumors but not in normal epidermis or in areas of the epidermis away from tumors is of considerable interest, but the reasons for the selective effects of caffeine on apoptosis in DNA damaged tissues are unknown. Further studies are needed to determine mechanisms of these effects of caffeine and to determine the effects of caffeine administration on sunlight-induced actinic keratoses and squamous cell carcinomas in humans

Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity

Directory of Open Access Journals (Sweden)

Silvia I. Cazorla

2018-04-01

Full Text Available The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431 and L. paracasei CNCM I-1518 (Lp 1518 to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus. Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old to old age (180 days old. Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.

Human urinary excretion profile after smoking and oral administration of [14C]delta 1-tetrahydrocannabinol

International Nuclear Information System (INIS)

Johansson, E.; Gillespie, H.K.; Halldin, M.M.

1990-01-01

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of [ 14 C]delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of 14 C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of 14 C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively

Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

Science.gov (United States)

Kawahara, Tomohiro; Makizaki, Yutaka; Oikawa, Yosuke; Tanaka, Yoshiki; Maeda, Ayako; Shimakawa, Masaki; Komoto, Satoshi; Moriguchi, Kyoko; Ohno, Hiroshi; Taniguchi, Koki

2017-01-01

Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in mice administered

Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

Directory of Open Access Journals (Sweden)

Tomohiro Kawahara

Full Text Available Human rotavirus (RV infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1, which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in

Prevention of Infectious Mastitis by Oral Administration of Lactobacillus salivarius PS2 During Late Pregnancy.

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Fernández, Leónides; Cárdenas, Nivia; Arroyo, Rebeca; Manzano, Susana; Jiménez, Esther; Martín, Virginia; Rodríguez, Juan Miguel

2016-03-01

Previous studies have shown that oral administration of lactobacilli can be an efficient approach to treat lactational infectious mastitis. In this trial, we have evaluated the potential of Lactobacillus salivarius PS2 to prevent this condition when orally administered during late pregnancy to women who had experienced infectious mastitis after previous pregnancies. In this study, 108 pregnant women were randomly assigned to one of 2 groups. Those in the probiotic group (n = 55) ingested daily 9 log10 colony-forming units of L. salivarius PS2 from approximately week 30 of pregnancy until delivery, whereas those in the placebo group (n = 53) received a placebo. The occurrence of mastitis was evaluated during the first 3 months after delivery. Globally, 44 of 108 women (41%) developed mastitis; however, the percentage of women with mastitis in the probiotic group (25% [n = 14]) was significantly lower than in the control group (57% [n = 30]). When mastitis occurred, the milk bacterial counts in the probiotic group were significantly lower than those obtained in the placebo group. Oral administration of L. salivarius PS2 during late pregnancy appears to be an efficient method to prevent infectious mastitis in a susceptible population. NCT01505361. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

New Guinea communities without writing and views of primary orality.

NARCIS (Netherlands)

de Vries, L.J.

2003-01-01

Discursive and cognitive practices of primary oral societies have been described to a significant extent in terms of additive parataxis, context-bound concreteness and formulaic-repetitive style. Such qualifications as a rule did not emerge from empirical study of specific primary oral societies in

Pharmacokinetics and brain distribution of tetrahydropalmatine and tetrahydroberberine after oral administration of DA-9701, a new botanical gastroprokinetic agent, in rats.

Science.gov (United States)

Jung, Ji Won; Kwon, Yong Sam; Jeong, Jin Seok; Son, Miwon; Kang, Hee Eun

2015-01-01

DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

Science.gov (United States)

Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

2014-03-01

The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

Oral verrucous carcinoma complicating a repetitive injury by the ...

African Journals Online (AJOL)

Here we reported a case of VC of oral cavity a particularly very aggressive, arising from prosthesis injury. Regardless of the treatment modality, given new insights into the possible aggressivity of this tumor, radiotherapy associated to chemotherapy may be a more appropriate primary treatment compared with the significant ...

Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

Science.gov (United States)

Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

2015-09-01

Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. Copyright © 2015 Elsevier B.V. All rights reserved.

Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy.

Science.gov (United States)

Talamo, Giampaolo; Liao, Jason; Bayerl, Michael G; Claxton, David F; Zangari, Maurizio

2010-03-01

Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of patients undergoing BMAB. Eighty-four consecutive adult patients underwent BMAB after local anesthesia with 5 mL of lidocaine hydrochloride 1% aqueous solution in the left posterior superior iliac crest. Analgesia was obtained with acetaminophen 650 mg and oxycodone 10 mg, and anxiolysis was obtained with lorazepam 2 mg, all drugs given once orally 30 min before the procedure. We assessed the pain level with the Wong-Baker Faces Pain Rating Scale, which distinguishes six levels of pain, from 0 to 5. The 34 patients who received an oral administration of analgesia and anxiolysis reported pain at lower levels, i.e., in the range of 0-2, more frequently than the 50 patients who underwent BMAB without analgesia/anxiolysis (78% vs 64%, respectively). Among several predictors analyzed using a multivariate regression model, three were found to be associated with decreased pain level: the use of analgesia/anxiolysis, male sex, and increase in age (all with p values <0.05). Length of the extracted bone specimen, body mass index, and need of a spinal needle for anesthesia in obese patients did not predict for pain level. An oral administration of prophylactic regimen of analgesia and anxiolysis, at the above-mentioned doses, produced a statistically significant reduction of the perception of pain in patients undergoing BMAB, but its effect did not seem to provide a major and clinically significant reduction of pain level.

Interest of repetitive transcranial magnetic stimulation of the motor cortex in the management of refractory cancer pain in palliative care: Two case reports.

Science.gov (United States)

Nizard, Julien; Levesque, Amélie; Denis, Nathalie; de Chauvigny, Edwige; Lepeintre, Aurélie; Raoul, Sylvie; Labat, Jean-Jacques; Bulteau, Samuel; Maillard, Benoît; Buffenoir, Kevin; Potel, Gilles; Lefaucheur, Jean-Pascal; Nguyen, Jean Paul

2015-06-01

Non-drug treatments should be systematically associated to the medical analgesic treatment during the terminal phase of cancer. Patient 1, a 23-year-old woman, presented an adenocarcinoma of the rectum, with liver and lung metastases. Pain was initially treated by oral morphine and a combination of pregabalin and amitriptyline. Ketamine and intrathecal administration of morphine were both ineffective. Patient 2, a 69-year-old woman, presented a cutaneous T-cell lymphoma. She was admitted to the palliative care unit with mixed pain related to cutaneous lymphomatous infiltration. World Health Organization (WHO) step 3 analgesics had not been tolerated. Both patients received five consecutive 20-min sessions of repetitive transcranial magnetic stimulation to the right motor cortex. Patient 1 experienced a marked improvement of her pain over the days following the first repetitive transcranial magnetic stimulation session. Medical treatment was able to be rapidly decreased by about 50%, which restored an almost normal level of consciousness and lucidity. Patient 2's pain was also markedly decreased over the days following these five consecutive sessions, and repetitive transcranial magnetic stimulation also appeared to have had a beneficial effect on the patient's anxiety and mood. In the context of palliative care of cancer patients experiencing refractory pain that is difficult to control by the usual treatments, motor cortex repetitive transcranial magnetic stimulation, due to its noninvasive nature, can be used as an adjuvant therapy to improve various components of pain, including the emotional components. By reducing the doses of analgesics, repetitive transcranial magnetic stimulation decreases the severity of their adverse effects and improves the patient's quality of life. © The Author(s) 2015.

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

Energy Technology Data Exchange (ETDEWEB)

Gulyas, Balazs [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm (Sweden); Halldin, Christer; Sandell, Johan; Farde, Lars [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Sovago, Judit; Cselenyi, Zsolt [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Vas, Adam; Kiss, Bela; Karpati, Egon [Chemical Works of Gedeon Richter Ltd., Budapest (Hungary)

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [{sup 11}C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [{sup 11}C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [{sup 11}C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and

Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

Science.gov (United States)

Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

2015-01-01

Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Task Repetition on Learners' Attention Orientation in L2 Oral Production

Science.gov (United States)

Fukuta, Junya

2016-01-01

Task repetition facilitates learners' performance, at least temporarily: Since learners are already familiar with the content of the task at the initial enactment, they are capable of focusing their attention on linguistic form during the following enactment. However, the analysis in previous studies treated various aspects of "form" as…

Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

Science.gov (United States)

Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

2011-01-01

Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

Safety of fluralaner oral solution, a novel systemic antiparasitic treatment for chickens, in laying hens after oral administration via drinking water.

Science.gov (United States)

Prohaczik, Angella; Menge, Monika; Huyghe, Bruno; Flochlay-Sigognault, Annie; Traon, Gaëlle Le

2017-08-08

Poultry mites are the most significant pest affecting production systems in the egg-laying industry. Fluralaner is a novel systemic insecticide and acaricide that is effective against poultry mites (Dermanyssus gallinae, Ornithonyssus sylviarum) in chickens after oral administration. This study investigated the safety of oral administration of a 1% solution of fluralaner in drinking water to laying hens at the recommended treatment dose and at multiples of this dose. One hundred-twenty healthy 28-week-old laying hens, weighing 1.4-2.1 kg at first administration, were included in the study, and allocated to 4 treatment groups of 30 hens each receiving daily doses of 0, 0.5, 1.5 and 2.5 mg fluralaner/kg body weight, equivalent to 0, 1, 3, and 5 times the recommended dose of fluralaner. The product was administered via drinking water on a total of six occasions, as 3-day treatment periods twice with an interval of 4 days with no treatment (treatment on days 1, 2, 3 and 8, 9, 10), representing 3 times the recommended number of administrations. Hens supplied with non-medicated drinking water served as controls. During the study, all hens were clinically observed, and their health was carefully monitored including body weight, food and water consumption, hematology, clinical chemistry, and withdrawal reflex test. Eggs laid over the study were evaluated for main characteristics (e.g. weight, shape, strength, shell thickness and soundness, albumen height, yolk color, Haugh unit and presence of blood and/or meat spots). Following euthanasia of the hens at the end of the second treatment period (day 11) or 18 days later (day 29), complete gross post-mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology

Concomitant administration of nitrous oxide and remifentanil reduces oral tissue blood flow without decreasing blood pressure during sevoflurane anesthesia in rabbits.

Science.gov (United States)

Kasahara, Masataka; Ichinohe, Tatsuya; Okamoto, Sota; Okada, Reina; Kanbe, Hiroaki; Matsuura, Nobuyuki

2015-06-01

To determine whether continuous administration of nitrous oxide and remifentanil—either alone or together—alters blood flow in oral tissues during sevoflurane anesthesia. Eight male tracheotomized Japanese white rabbits were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF) were recorded in the absence of all test agents and after administration of the test agents (50 % nitrous oxide, 0.4 μg/kg/min remifentanil, and their combination) for 20 min. Nitrous oxide increased SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except DBP. Combined administration of nitrous oxide and remifentanil recovered SBP, DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained lower than control values. Our findings suggest that concomitant administration of nitrous oxide and remifentanil reduces blood flow in oral tissues without decreasing blood pressure during sevoflurane anesthesia in rabbits.

Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

Energy Technology Data Exchange (ETDEWEB)

Johansson, E.; Gillespie, H.K.; Halldin, M.M. (BMC, Uppsala (Sweden))

1990-05-01

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.

Pharmacokinetics of oxiracetam and its degraded substance (HOPAA after oral and intravenous administration in rats

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Xinhuan Wan

2014-12-01

Full Text Available The pharmacokinetics of oxiracetam and its degraded substance (4-hydroxy-2-oxo-1-pyrrolidine acetic acid, HOPAA after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method. Three groups of rats after an overnight fasted received 10 g/kg (n = 6 oxiracetam suspensions orally, and 2 g/kg (n = 6 normal or degraded oxiracetam injections intravenously via a caudal tail vein, respectively. Before the pharmacokinetic experiment, a simple safety evaluation test was conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice. There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within two weeks, demonstrating that HOPAA was non-toxic in mice. Following intravenous administration of the normal injections, the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase. The values of t1/2 were 3.1 ± 1.5 h for oxiracetam and 0.8 ± 0.2 h for HOPAA, and the mean residence times (MRT were 1.2 ± 0.1 h and 0.8 ± 0.1 h, respectively. Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections. Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes, and both had a longer t1/2 and MRT than those of intravenous administration. Contents of HOPAA in three groups were calculated based on AUC0–t values of the two analytes. The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetam at the same time for every group. Additionally, the values of absolute bioavailability of oxiracetam were about 8.0% and 7.4% calculated by the normal or degraded oxiracetam injections, which were far less than the value of 75% reported in literature, indicating the necessity of further study.

Développement et évaluation de nanoparticules bioadhésives pour l'administration orale de petides

OpenAIRE

Hecq, Julien

2017-01-01

Ces dernières années, le nombre d’agents thérapeutiques issus des biotechnologies n’a cessé d’augmenter. Parmi ceux-ci, plus de 85% sont administrés par voie parentérale, principalement par injection sous-cutanée ou intraveineuse. Cette forme d’administration ne favorisant pas la compliance des patients, de nombreuses recherches ont été effectuées afin de trouver des alternatives à ces voies invasives, telles que la voie intranasale, pulmonaire, transdermique ou orale. Cette dernière a pour a...

Assessment of the Variation Associated with Repeated Measurement of Gastrointestinal Transit Times and Assessment of the Effect of Oral Ranitidine on Gastrointestinal Transit Times Using a Wireless Motility Capsule System in Dogs

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Jonathan A. Lidbury

2012-01-01

Full Text Available This study aimed to evaluate the variation associated with repeated measurement of gastrointestinal (GI transit times and the effect of oral ranitidine on GI transit times in healthy dogs using a wireless motility capsule (WMC system. Eight privately owned healthy adult dogs were enrolled, and one developed diarrhea and was removed from the study. For the first 3 repetitions, each dog was fed a standard meal followed by oral administration of a WMC. For the 4th repetition, each dog was given ranitidine hydrochloride (75 mg PO every 12 hours prior to and during assessment of GI transit times. Mean between-subject coefficients of variation for gastric emptying time (GET, small and large bowel transit time (SLBTT, and total transit time (TTT were 26.9%, 32.3%, and 19.6%, respectively. Mean within-subject coefficients of variation for GET, SLBTT, and TTT were 9.3%, 19.6%, and 15.9%, respectively. Median GET, SLBTT, and TTT without ranitidine were 719, 1,636, and 2,735 minutes, respectively. Median GET, SLBTT, and TTT with ranitidine were 757, 1,227, and 2,083 minutes, respectively. No significant differences in GI transit times were found between any of the 4 repetitions. Under these experimental conditions, no significant effects of oral ranitidine on GI transit times were observed.

Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo

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Victoria A. Meliopoulos

2016-11-01

Full Text Available The disease mechanisms associated with the onset of astrovirus diarrhea are unknown. Unlike other enteric virus infections, astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human astrovirus serotype 1 (HAstV-1 capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey astrovirus 2 (TAstV-2 capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3 from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction.

Deposition of a model substance, Tc E-HIDA, in the oral cavity after administration of lozenges, chewing gum and sublingual tablets

DEFF Research Database (Denmark)

Christrup, Lona Louring; Davis, S.S.; Melia, C.D.

1990-01-01

The deposition and clearance of a model substance, Tc E-HIDA, in the oral cavity/upper oesophagus and in the stomach after administration of lozenges, chewing gum and sublingual tablets has been followed by gamma scintigraphy in a group of healthy male volunteers. Following administration...

Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model

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Parayath NN

2016-08-01

Full Text Available Neha N Parayath,1 Hayley Nehoff,1 Samuel E Norton,2 Andrew J Highton,2 Sebastien Taurin,1,3 Roslyn A Kemp,2 Khaled Greish1,4 1Department of Pharmacology and Toxicology, 2Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; 3Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA; 4Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Oral administration of paclitaxel (PTX, a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid (SMA. Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg compared to the commercially available PTX formulation (PTX [Ebewe]. In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe. In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer. Keywords: oral delivery, anticancer nanomedicine, CT-26, enhanced permeability and retention (EPR effect, HUVEC, antiangiogenic

Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

International Nuclear Information System (INIS)

Taillefer, R.; Lette, J.; Phaneuf, D.C.; Leveille, J.; Lemire, F.; Essiambre, R.

1986-01-01

Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing

Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.

Science.gov (United States)

Corado, Carley R; McKemie, Daniel S; Knych, Heather K

2017-06-01

Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug administration. Urine samples were collected from 12 horses up to 120 h post administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using non-compartmental analysis. The C max , T max , and the t 1/2 of dextromethorphan were 519.4 ng/mL, 0.55 h, and 12.4 h respectively. The area under the curve of dextromethorphan, free dextrorphan, and conjugated dextrorphan were 563.8, 2.19, and 6,691 h*ng/mL respectively. In addition to free and glucuronidated dextrorphan, several additional glucuronide metabolites were identified in plasma, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan. Dextromethorphan was found to be eliminated from the urine predominately as the O-demethylated metabolite, dextrorphan. Several additional metabolites including several novel hydroxy-dextrorphan metabolites were also detected in the urine in both free and glucuronidated forms. No significant undesirable behavioural effects were noted throughout the duration of the study. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of oral administration of terephthalic acid on testicular functions of rats

International Nuclear Information System (INIS)

Cui Lunbiao; Dai Guidong; Xu Lichun; Wang Shouling; Song Ling; Zhao Renzhen; Xiao Hang; Zhou Jianwei; Wang Xinru

2004-01-01

To investigate the toxic effect of terephthalic acid (TPA) on testicular functions of rats, male Sprague-Dawley rats were orally administered TPA in diet at the levels 0 (control), 0.2, 1 and 5% for 90 days. Testicular functions were assessed by histopathology, testicular sperm head counts, daily sperm production, sperm motility (measured by computer-assisted sperm analysis, CASA), biochemical indices (marker testicular enzymes), and serum testosterone. Oral feeding with terephthalic acid did not cause body and testes weight loss in TPA-treated groups. Histopathologically, damages of spermatogenic cells and Sertoli cells were observed by electron microscope, testicular sperm head counts, daily sperm production, and activities of sorbitol dehydrogenase (SDH) were decreased significantly in the 5% TPA group. The motility of spermatozoa was reduced significantly in all treated groups, which was correlated with administration doses. Serum testosterone concentrations were not declined in treated groups. In conclusion, TPA can cause impairment of testicular functions. The primary sites of action may be spermatogenic cells and Sertoli cells. The results of the present study provide first information of TPA on testicular functions in male rats

Tissue distribution of berberine and its metabolites after oral administration in rats.

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Xiang-Shan Tan

Full Text Available Berberine (BBR has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n-IT-TOF as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg. The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1, berberrubine (M2 and jatrorrhizine (M4, which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t (area under the concentration-time curve for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.

Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration

DEFF Research Database (Denmark)

Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik

2014-01-01

The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine...

Prophylactic administration of an extract from Plantaginis Semen and its major component aucubin inhibits mechanical allodynia caused by paclitaxel in mice

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Tsugunobu Andoh

2016-07-01

Full Text Available The chemotherapeutic agent paclitaxel (PTX causes peripheral neuropathy as a major dose-limiting side effect, and this peripheral neuropathy is difficult to control. Our previous report showed that prophylactic repetitive administration of goshajinkigan (牛車腎氣丸 niú chē shèn qì wán, but not hachimijiogan (八味地黃丸 bā wèi dì huáng wán, which lacks two of the constituents of goshajinkigan, inhibited PTX-induced mechanical allodynia in mice. Thus, the herbal medicines Plantaginis Semen (車前子 chē qián zǐ or Achyranthis Radix (牛膝 niú xī may contribute to the inhibitory action of goshajinkigan on the exacerbation of PTX-induced mechanical allodynia [Andoh et al, J. Tradit. Complement. Med. 2014; 4: 293–297]. Therefore, in this study, we examined whether an extract of Plantaginis Semen (EPS or Achyranthis Radix (EAR would relieve PTX-induced mechanical allodynia in mice. A single intraperitoneal injection of PTX caused mechanical allodynia, which peaked on day 14 after injection. Repetitive oral administration of EPS, but not EAR, starting from the day after PTX injection significantly inhibited the exacerbation of PTX-induced mechanical allodynia. Repetitive intraperitoneal injection of aucubin, one of the main components of EPS, starting from the day after PTX injection also significantly reduced PTX-induced mechanical allodynia. However, repetitive intraperitoneal injection of geniposide acid (a precursor of aucubin or catalpol (a metabolite of aucubin did not prevent the exacerbation of mechanical allodynia. These results suggest that prophylactic administration of EPS is effective for preventing the exacerbation of PTX-induced allodynia. Aucubin may contribute to the inhibitory action of EPS on the exacerbation of PTX-induced allodynia.

Oral controlled release drug delivery system and Characterization of oral tablets; A review

OpenAIRE

Muhammad Zaman; Junaid Qureshi; Hira Ejaz; Rai Muhammad Sarfraz; Hafeez ullah Khan; Fazal Rehman Sajid; Muhammad Shafiq ur Rehman

2016-01-01

Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes dif...

Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration

International Nuclear Information System (INIS)

Voelkel, Wolfgang; Colnot, Thomas; Schauer, Ute M.D.; Broschard, Thomas H.; Dekant, Wolfgang

2006-01-01

3-(4-Methylbenzylidene)camphor (4-MBC) is an UV-filter frequently used in sunscreens and cosmetics. Equivocal findings in some screening tests for hormonal activity initiated a discussion on a possible weak estrogenicity of 4-MBC. In this study, the toxicokinetics and biotransformation of 4-MBC were characterized in rats after oral administration. Male and female Sprague-Dawley rats (n = 3 per group) were administered single oral doses of 25 or 250 mg/kg bw of 4-MBC in corn oil. Metabolites formed were characterized and the kinetics of elimination for 4-MBC and its metabolites from blood and with urine were determined. Metabolites of 4-MBC were characterized by 1 H NMR and LC-MS/MS as 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. After oral administration of 4-MBC, only very low concentrations of 4-MBC were present in blood and the peak concentrations of 3-(4-carboxybenzylidene)camphor were approximately 500-fold above those of 4-MBC; blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection. Blood concentration of 4-MBC and 3-(4-carboxybenzylidene)camphor peaked within 10 h after 4-MBC administration and then decreased with half-lives of approximately 15 h. No major differences in peak blood levels between male and female rats were seen. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine. However, urinary excretion of 4-MBC-metabolites represents only a minor pathway of elimination for 4-MBC, since most of the applied dose was recovered in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor

Contribution of the pre-SMA to the production of words and non-speech oral motor gestures, as revealed by repetitive transcranial magnetic stimulation (rTMS).

Science.gov (United States)

Tremblay, Pascale; Gracco, Vincent L

2009-05-01

An emerging theoretical perspective, largely based on neuroimaging studies, suggests that the pre-SMA is involved in planning cognitive aspects of motor behavior and language, such as linguistic and non-linguistic response selection. Neuroimaging studies, however, cannot indicate whether a brain region is equally important to all tasks in which it is activated. In the present study, we tested the hypothesis that the pre-SMA is an important component of response selection, using an interference technique. High frequency repetitive TMS (10 Hz) was used to interfere with the functioning of the pre-SMA during tasks requiring selection of words and oral gestures under different selection modes (forced, volitional) and attention levels (high attention, low attention). Results show that TMS applied to the pre-SMA interferes selectively with the volitional selection condition, resulting in longer RTs. The low- and high-attention forced selection conditions were unaffected by TMS, demonstrating that the pre-SMA is sensitive to selection mode but not attentional demands. TMS similarly affected the volitional selection of words and oral gestures, reflecting the response-independent nature of the pre-SMA contribution to response selection. The implications of these results are discussed.

Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats

DEFF Research Database (Denmark)

Poulsen, Steen Seier; Nexø, Ebba

1986-01-01

The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist. After 25 and 50 days of treatment, synthetic human...... EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more...... human EGF/URO is a potent inhibitor of gastric acid secretion when administered intravenously, but had no effect on acid secretion when given intraduodenally, which suggests that the effect of synthetic human EGF/URO is a direct action on the duodenal mucosa. In conclusion, this study showed that oral...

Design and development of a lead jar for oral administration of radioiodine In hyperthyroid patients

International Nuclear Information System (INIS)

Rahman, M.S.; Paul, A.K.; Rahman, H.A.; Begum, F.

2005-01-01

Full text: Nuclear Medicine practices involve use of radioisotopes for diagnosis and treatment of diseases. Radioiodine is one of such radioisotopes, being used in the diagnosis and treatment of diseases since 1942. Handling of radioiodine involves radiation hazards both for the patients as well as for the technologists. Though radioiodine is supplied in a lead container, for treatment purpose, it is administered after dispensing into a glass jar that does not adequately protect radiation hazards. For this reason, we designed and developed a lead jar and radioiodine is dispensed into that lead jar to minimize radiation hazards. For oral administration of radioiodine to hyperthyroid patients, a lead jar was designed and developed with lead in Centre for Nuclear Medicine and Ultrasound, Khulna in December 2004 by own expertise and technologies in such a way that a glass jar could be introduced into that lead jar. The thickness of lead was 4.04 mm and the thickness of glass jar was 0.7 mm and thus the whole thickness of lead jar became 4.74 mm. The desired dose of radioiodine (8 mCi) that should be given to the patients were dispensed into that lead jar and administered orally to the patients. Radiation levels in 10 such cases were measured by Mini-Rad Series-1000 survey meter at 0.5 meter, 1 meter and 3 meters distances both lead jar and glass jar. The mean radiation level of lead jar and glass jar during oral administration of 8 mCi of Na 131 I solution in 10 cases at 0.5 meter, 1 meter and 3 meters distances were 62.4 ± 1.96 microSv/h, 17.7 ±1.95 microSv/h, 3.39 ± .12 microSv/h and 20.3± 2.16 microSv/h, 79.8 ± 0.79 microSv/h, 1.97 ± 0.23 microSv/h respectively. We have found that radiation level reduced by 67.47%, 61.58%, and 41.89% with lead jar at 0.5 meter, 1 meter and 3 meters distances. In conclusion, the locally designed and developed lead jar is safe, easy to handle and reduces radiation burden significantly in oral administration of radioiodine to

LC determination and pharmacokinetic study of the main phenolic components of Portulaca oleracea L. extract in rat plasma after oral administration.

Science.gov (United States)

Cheng, Zhongzhe; Wang, Dong; Zhang, Wenjie; Du, Yang; Wang, Yunjiao; Zhai, Yanjun; Ying, Xixiang; Kang, Tingguo

2012-01-01

This study investigated the pharmacokinetics of hesperidin (HP), ferulic acid (FA) and p-coumaric acid (CA) in rat plasma after oral administration of Portulaca oleracea L. extract (POE). The plasma concentrations were determined by HPLC with vitexin-2″-O-rhamnoside (VR) as internal standard. The calibration curves were linear over the range 0.1-5 µg mL(-1), 0.1-5 µg mL(-1)and 0.015-3 µg mL(-1) for HP, FA and CA, respectively. The validated method was suitable to the pharmacokinetic study of HP, FA and CA in rats after oral administration at a single dose of POE.

Effect of oral administration of carprofen on intraocular pressure in normal dogs.

Science.gov (United States)

Meekins, J M; Overton, T L; Rankin, A J; Roush, J K

2016-08-01

The aim of this study was to determine the effect of oral administration of carprofen on intraocular pressure in normal dogs. Twelve young adult beagle dogs were randomly assigned to treatment (n = 6) or control (n = 6) groups. After an 11-day acclimation period, the treatment group received approximately 2.2 mg/kg carprofen per os every 12 h for 7 days, and the control group received a placebo gel capsule containing no drug per os every 12 h for 7 days. Intraocular pressure (IOP) was measured by a rebound tonometer at three time points per day (8 am, 2 pm, and 8 pm) during the acclimation (days 1-11) and treatment (days 12-18) phases and for 48 h (days 19-20) after the completion of treatment. There was no statistically significant change in IOP for either eye in the dogs receiving oral carprofen during the treatment phase (days 12-18). After day 4, no significant daily IOP changes were seen in control group dogs. Carprofen administered orally every 12 h for 7 days had no effect on IOP in normal beagle dogs. An acclimation period to frequent IOP measurements of at least 5 days is necessary to establish baseline IOP values and minimize possible anxiety-related effects on IOP measurements. © 2016 John Wiley & Sons Ltd.

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

Science.gov (United States)

Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

2008-01-01

To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration.

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Newmeyer, Matthew N; Swortwood, Madeleine J; Taylor, Megan E; Abulseoud, Osama A; Woodward, Thomas H; Huestis, Marilyn A

2017-08-01

Establishing science-based driving per se blood Δ 9 -tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers' performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4 mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5-3.5 h post-dose). Occasional smokers' odds of exhibiting ≥2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3-18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1-1.5) and 1.5 (1.3-1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2-0.6) mm at 1.5 h and 0.5 (0.2, 0.2-0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users' performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers' impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Residual veterinary antibiotics in pig excreta after oral administration of sulfonamides.

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Qiu, Jinrong; Zhao, Tao; Liu, Qingyun; He, Jinhua; He, Dechun; Wu, Genyi; Li, Yongtao; Jiang, Chengai; Xu, Zhencheng

2016-04-01

Sulfonamides (SAs) are applied widely as feed additives in the farming of livestock and poultry. It can lead to the excretion of large amounts of SAs in manure and result in persistent environmental pollution. We evaluated the fate of four SAs, sulfamerazine (SM1), sulfachloropyridazine (SCP), sulfadimoxine (SDM') and sulfaquinoxaline (SQ), from oral administration to excretion in urine and feces in pigs. The four SAs were added to homemade feed to make them reach the required concentration gradient, which were 0, 50 and 100 mg/kg (low, normal and high concentrations, respectively). In different treatments, excretions of the four SAs were 35.68-86.88 %. With regard to total excretion, the order was SQ > SCP > SM1 > SDM' for all treatments. The concentration of SAs in the feed had significant effects on the amount of the four SAs excreted every day. The concentration of SAs in feces and in the urine for different treatments was 15.03-26.55 and 14.54-69.22 %, respectively. In each treatment, excretions of SCP, SDM' and SQ in feces were lower than that in urine. The four SAs remained longer in urine than in feces. Excretions in urine and feces were lower if SAs were administered orally rather than by injection.

Renal, gastrointestinal, and hemostatic effects of oral administration of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis).

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Dijkstra, Bas; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Owens, Sean D; Hass, Carlyle; Kass, Philip H; Paul-Murphy, Joanne R

2015-04-01

To investigate renal, gastrointestinal, and hemostatic effects associated with oral administration of multiple doses of meloxicam to healthy Hispaniolan Amazon parrots (Amazona ventralis). 12 Hispaniolan Amazon parrots. Birds were assigned to receive meloxicam oral suspension (1.6 mg/kg, PO, q 12 h) and 2.5 mL of tap water inserted into the crop by use of a gavage tube (n = 8) or the equivalent volume of tap water only (control group; 4) for 15 days. Urine and feces were collected 2 hours after treatment administration each day. Feces were evaluated for occult blood. Results of a CBC and serum biochemical analysis and measured N-acetyl-β-d-glucosaminidase (NAG) activity and whole blood clotting time were evaluated before, during, and after completion of treatments. Results of urinalysis and measured urine NAG activity were also evaluated. Birds treated with meloxicam had a significant increase in number of WBCs and decrease in PCV from before to after treatment. The PCV also decreased significantly, compared with results for the control group; however, WBC count and PCV for all birds remained within reference ranges throughout the study. One parrot treated with meloxicam had a single high value for urine NAG activity. Meloxicam administered orally at the dosage used in this study caused no apparent negative changes in several renal, gastrointestinal, or hemostatic variables in healthy Hispaniolan Amazon parrots. Additional studies to evaluate adverse effects of NSAIDs in birds will be needed.

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis.

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Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún; Treldal, Charlotte; Jensen, Kenneth; Jensen, Anders Bonde; Kristensen, Claus Andrup; Jacobsen, Jette; Kreilgaard, Mads; Petersen, Janne; Andersen, Ove

2017-01-01

The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Repetition and Translation Shifts

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Simon Zupan

2006-06-01

Full Text Available Repetition manifests itself in different ways and at different levels of the text. The first basic type of repetition involves complete recurrences; in which a particular textual feature repeats in its entirety. The second type involves partial recurrences; in which the second repetition of the same textual feature includes certain modifications to the first occurrence. In the article; repetitive patterns in Edgar Allan Poe’s short story “The Fall of the House of Usher” and its Slovene translation; “Konec Usherjeve hiše”; are compared. The author examines different kinds of repetitive patterns. Repetitions are compared at both the micro- and macrostructural levels. As detailed analyses have shown; considerable microstructural translation shifts occur in certain types of repetitive patterns. Since these are not only occasional; sporadic phenomena; but are of a relatively high frequency; they reduce the translated text’s potential for achieving some of the gothic effects. The macrostructural textual property particularly affected by these shifts is the narrator’s experience as described by the narrative; which suffers a reduction in intensity.

Studies on portal systemic circulation by oral administration of 201Tl enclosed enteric coated capsule

International Nuclear Information System (INIS)

Tonami, Norihisa; Nakajima, Kenichi; Watanabe, Naoto

1986-01-01

Thallium-201 enclosed enteric coated capsule was prepared and administered orally to evaluate portal systemic circulation in 11 control subjects and 31 patients with various liver diseases by investigating scintigraphic appearance and the heart-to-liver uptake ratio (H/L ratio). In 10 patients with liver cirrhosis and one with chronic hepatitis, the results of H/L ratio were compared to those obtained by 201 Tl per-rectal administration. 1. It was fundamentally confirmed that 201 Tl enclosed enteric coated capsule was not broken down in the artificial gastric juice, but nearly completely melted 15 minutes after soaking in the artificial intestinal juice. 2. Clinical study was successfully completed in 36 out of 42 cases (86 %). Unsuccessful cases were found in 2 with capsule collapse in the stomach and 4 with its poor moving to the duodenum. 3. In control subjects the liver was clearly visualized and the mean value of H/L ratio was 0.32 which is lower than that of 201 Tl per-rectal administration previously reported. H/L ratio in patients with chronic and acute hepatitis was nearly equal to that in control subjects. H/L ratio in patients with liver cirrhosis was slightly higher than that in control subjects, but there was no significant difference between them. In cases with esophageal varices, H/L ratio was not so high compared to that in control subjects. Out of 7 patients showing high H/L ratio more than 0.8 in 201 Tl per-rectal administration, only one showed similar high ratio (1.07) in oral administration of 201 Tl enclosed enteric coated capsule. In this case the shunting from superior mesenteric vein to inferior vena cava connection was confirmed. From these results, it was considered that the shunting volume of superior mesenteric vein through esophageal varices is small. 4. A possibility of a new administration of radioisotope with enteric coated capsule was emphasized. (author)

Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced hepatotoxicity in rats.

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Adeneye, A A; Benebo, A S

2007-01-01

Alcoholic liver disease remains a major cause of liver failure worldwide with no available curative or prophylactic therapy as at present. High dose metformin is reported to ameliorate liver injuries in both human and animal models of acute and chronic alcoholic liver injuries. The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. In the present study, ameliorating effect of 200 mg/ kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats for 2 weeks of the experiment. The body weight of each rat was taken on days 1, 7, and 14 of the experiment, respectively. On day 15, fasted blood samples for plasma lipids and liver enzyme markers were collected via cardiac puncture from the rats under diethyl ether anaesthesia. Results showed that administration of graded oral doses of 50% ethanol for 14 days significantly (pcholesterol (PTC), high density lipoprotein (HDL-c), and low density lipoprotein (LDL-c). However, these elevations were significantly (pascorbic acid co-administration protected the liver against the deleterious effects of chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to be due mainly to the metformin molecule of the drug combination. However, further studies would be required to evaluate the mechanisms underlying the observed effects.

Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium.

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Liu, Tao; Lewis, Tamorah; Gauda, Estelle; Gobburu, Jogarao; Ivaturi, Vijay

2016-08-01

Conducting and analyzing clinical trials in vulnerable neonates are extremely challenging. The aim of this analysis is to develop a morphine population pharmacokinetics (PK) model using data collected during a randomized control trial in neonates with abstinence syndrome (NAS). A 3-compartment morphine structural PK model after intravenous (IV) administration from previously published work was utilized as prior, whereas an allometric scaling method with physiological consideration was used to extrapolate a PK profile from adults to pediatrics. The absorption rate constant and bioavailability were estimated in NAS after oral administration of diluted tincture of opium (DTO). Goodness-of-fit plots along with normalized prediction distribution error and bootstrap method were performed for model evaluation. We successfully extrapolated the PK profile from adults to pediatrics after IV administration. The estimated first-order absorption rate constant and bioavailability were 0.751 hour(-1) and 48.5%, respectively. Model evaluations showed that the model can accurately and precisely describe the observed data. The population pharmacokinetic model we derived for morphine after oral administration of DTO is reasonable and acceptable; therefore, it can be used to describe the PK and guide future studies. The integration of the previous population PK knowledge as prior information successfully overcomes the logistic and practical issue in vulnerable neonate population. © 2016, The American College of Clinical Pharmacology.

Failure mode and effects analysis applied to the administration of liquid medication by oral syringes

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Eva María Guerra-Alia

2017-11-01

Full Text Available To carry out a Failure Mode and Effects Analysis (FMEA to the use of oral syringes. Methods: A multidisciplinary team was assembled within the Safety Committee. The stages of oral administration process of liquid medication were analysed, identifying the most critical and establishing the potential modes of failure that can cause errors. The impact associated with each mode of failure was calculated using the Risk Priority Number (RPN. Preventive actions were proposed. Results: Five failure modes were identified, all classified as high risk (RPN> 100. Seven of the eight preventive actions were implemented. Conclusions: The FMEA methodology was a useful tool. It has allowed to know the risks, analyse the causes that cause them, their effects on patient safety and the measures to reduce them

Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

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Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

2017-11-01

Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

Development of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.

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Passerini, Nadia; Albertini, Beatrice; Sabatino, Marcello Di; Corace, Giuseppe; Luppi, Barbara; Canistro, Donatella; Vivarelli, Fabio; Cirillo, Silvia; Soleti, Antonio; Merizzi, Giulia; Paolini, Moreno

2016-10-15

The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC), is an innovative non- radical scavenger used with success in numerous disease models such as inflammation, neurological disorders, hepatitis and diabetes. The pharmacological treatments have been performed by the intraperitoneal route of administration, representing to date, the main limit for the drug use. The aim of this study was to develop a delivery system that allows the oral administration of IAC while maintaining its therapeutic efficacy. Solid Lipid Microparticles (SLMs) containing a theoretical 18% (w/w) of IAC have been produced by the spray congealing technology; three formulations have been tested (A, B and C) using different low melting point carriers (stearic acid, Compritol(®) HD5ATO and carnauba wax) alone or in combination. All IAC loaded SLMs exhibited a spherical shape, encapsulation efficiency higher than 94% and particle size suitable for the oral route. Administered per os at different dosages in an inflammation rat model, all SLMs demonstrated their efficacy in reducing oedema and alleviating pain, compared to the gold standards Indomethacin and Paracetamol. These results suggested that the SLMs are an efficacious delivery system for the oral administration of IAC, potentially useful for the treatment of others diseases related to an over production of free radicals. Copyright © 2016 Elsevier B.V. All rights reserved.

Effective multiple oral administration of reverse genetics engineered infectious bursal disease virus in mice in the presence of neutralizing antibodies.

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Hornyák, Ákos; Lipinski, Kai S; Bakonyi, Tamás; Forgách, Petra; Horváth, Ernő; Farsang, Attila; Hedley, Susan J; Palya, Vilmos; Bakács, Tibor; Kovesdi, Imre

2015-01-01

Despite spectacular successes in hepatitis B and C therapies, severe hepatic impairment is still a major treatment problem. The clinically tested infectious bursal disease virus (IBDV) superinfection therapy promises an innovative, interferon-free solution to this great unmet need, provided that a consistent manufacturing process preventing mutations or reversions to virulent strains is obtained. To address safety concerns, a tissue culture adapted IBDV vaccine strain V903/78 was cloned into cDNA plasmids ensuring reproducible production of a reverse engineered virus R903/78. The therapeutic drug candidate was characterized by immunocytochemistry assay, virus particle determination and immunoblot analysis. The biodistribution and potential immunogenicity of the IBDV agent was determined in mice, which is not a natural host of this virus, by quantitative detection of IBDV RNA by a quantitative reverse transcriptase-polymerase chain reaction and virus neutralization test, respectively. Several human cell lines supported IBDV propagation in the absence of visible cytopathic effect. The virus was stable from pH 8 to pH 6 and demonstrated significant resistance to low pH and also proved to be highly resistant to high temperatures. No pathological effects were observed in mice. Single and multiple oral administration of IBDV elicited antibodies with neutralizing activities in vitro. Repeat oral administration of R903/78 was successful despite the presence of neutralizing antibodies. Single oral and intravenous administration indicated that IBDV does not replicate in mammalian liver alleviating some safety related concerns. These data supports the development of an orally delivered anti-hepatitis B virus/ anti-hepatitis C virus viral agent for human use. Copyright © 2015 John Wiley & Sons, Ltd.

Roles of repetitive sequences

Energy Technology Data Exchange (ETDEWEB)

Bell, G.I.

1991-12-31

The DNA of higher eukaryotes contains many repetitive sequences. The study of repetitive sequences is important, not only because many have important biological function, but also because they provide information on genome organization, evolution and dynamics. In this paper, I will first discuss some generic effects that repetitive sequences will have upon genome dynamics and evolution. In particular, it will be shown that repetitive sequences foster recombination among, and turnover of, the elements of a genome. I will then consider some examples of repetitive sequences, notably minisatellite sequences and telomere sequences as examples of tandem repeats, without and with respectively known function, and Alu sequences as an example of interspersed repeats. Some other examples will also be considered in less detail.

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

Science.gov (United States)

Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

2018-06-01

There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

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Mohamed Aboubakr

2014-01-01

Full Text Available The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV and oral (PO dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β and mean residence time (MRT were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot in renal damaged ducks (0.20 L kg−1 h−1 was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1. Following PO administration, the peak serum concentration (Cmax was higher in renal damaged than in healthy ducks and was achieved at maximum time (tmax of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el at a significant slower rate (3.94 h in renal damaged than in healthy ducks (2.89 h. The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for Cmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after oral administration

DEFF Research Database (Denmark)

Liu, Wenli; Wang, Xiaona; Chen, Ruilian

2016-01-01

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from...... and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application...

Oral Administration of Heat-Killed Lactobacillus gasseri OLL2809 Reduces Cedar Pollen Antigen-Induced Peritoneal Eosinophilia in Mice

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Toshihiro Sashihara

2008-01-01

Conclusions: We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis.

The effects of prolonged oral administration of gold nanoparticles on the morphology of hematopoietic and lymphoid organs

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Bucharskaya, Alla B.; Pakhomy, Svetlana S.; Zlobina, Olga V.; Maslyakova, Galina N.; Navolokin, Nikita A.; Matveeva, Olga V.; Khlebtsov, Boris N.; Bogatyrev, Vladimir A.; Khlebtsov, Nikolai G.; Tuchin, Valery V.

2017-02-01

Currently, the usage of gold nanoparticles as photosensitizers and immunomodulators for plasmonic photothermal therapy has attracted a great attention of researches and end-users. In our work, the influence of prolonged peroral administration of gold nanoparticles (GNPs) with different sizes on the morphological changes of hematopoietic and lymphoid organs was investigated. The 24 white outbred male rats weighing 180-220 g were randomly divided into groups and administered orally for 30 days the suspension of gold nanospheres with diameters of 2, 15 and 50 nm at a dosage of 190 μg/kg of animal body weight. To prevent GNPs aggregation in a tissue and enhance biocompatibility, they were functionalized with thiolated polyethylene glycol. The withdrawal of the animals from the experiment and sampling of spleen, lymph nodes and bone marrow tissues for morphological study were performed a day after the last administration. In the spleen the boundary between the red and white pulp was not clearly differ in all experimental groups, lymphoid follicles were significantly increased in size, containing bright germinative centers represented by large blast cells. The stimulation of lymphocyte and myelocytic series of hematopoiesis was recorded at morphological study of the bone marrow. The number of immunoblasts and large lymphocytes was increased in all structural zones of lymph nodes. The more pronounced changes were found in the group with administration of 15 nm nanoparticles. Thus, the morphological changes of cellular components of hematopoietic organs have size-dependent character and indicate the activation of the migration, proliferation and differentiation of immune cells after prolonged oral administration of GNPs.

Antimicrobial peptide CAP18 and its effect on Yersinia ruckeri infections in rainbow trout Oncorhynchus mykiss (Walbaum): comparing administration by injection and oral routes

DEFF Research Database (Denmark)

Chettri, Jiwan Kumar; Mehrdana, F.; Hansen, Egon Bech

2017-01-01

The antimicrobial peptide CAP18 has been demonstrated to have a strong in vitro bactericidal effect on Yersinia ruckeri, but its activity in vivo has not been described. In this work, we investigated whether CAP18 protects rainbow trout Oncorhynchus mykiss (Walbaum) against enteric red mouth...... the conventional antibiotic oxolinic acid. Oral administration of CAP18 to trout did not prevent infection. The proteolytic effect of secretions on the peptide CAP18 in the fish gastrointestinal tract is suggested to account for the inferior effect of oral administration....

Administración oral de preparado parenteral de vitamina K en anticoagulación excesiva por warfarina Oral administration of intravenous preparation of Vitamin K for excessive anticoagulation due to warfarin

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Yoleima Lozada

2012-04-01

Full Text Available La warfarina es frecuentemente usada en la terapia anticoagulante actual, su acción debe ser monitorizada usando el tiempo de protrombina expresado como International Normalized Ratio (INR; cuando se excede el rango de seguridad se puede administrar vitamina K (Vit-K, preferentemente por vía oral. Dicha presentación no está disponible en Venezuela. Se realizó un ensayo clínico, doble ciego, donde a 20 pacientes, edad 18-60 años, sin sangrado e INR inicial de 6 a 10 inclusive; les fue suspendida la warfarina e inmediatamente agrupados al azar a recibir dosis única de Vit-K (oral 1.25mg de Vit-K fraccionada de una presentación parenteral o placebo. El punto final primario, INR Anticoagulation therapy with warfarin, a common clinical practice, needs to be monitored using protombine time expressed as the International Normalized Ratio (INR; when safety range is exceeded, Vitamin K (Vit-K could be administered with preference orally. In Venezuela the specific oral preparation for Vit-K is not available. This is a double blinded, randomized, placebo controlled, clinical trial; 20 patients, age 18-60 year with initial INR ≥ 6, ≤10, were randomized to oral Vit-K 1.25mg (prepared from intravenous presentation or placebo plus withholding warfarin. INR < 3.5 at 24 hours of treatment (the primary end point was achieved by 70% among Vit-K, and 20% among placebo patients; given an absolute risk reduction (ARR, of 50% (CI95%: 14.4-85.6 ρ = 0.028, NNT 2 (CI95%: 1.3 - 6.9. No adverse events were recorded including INR < 2 at 24 hours of treatment administration. Our results are consistent with studies where specific oral presentation of Vit-K was used. The results indicate that oral administration of Vit-K, prepared from an intravenous Vit-K preparation, is safe and more effective to revert excessive anticoagulation than simply withholding warfarin, in places where specific preparation of oral Vit-K is not available or too expensive.

A Nonword Repetition Task for Speakers with Misarticulations: The Syllable Repetition Task (SRT)

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Shriberg, Lawrence D.; Lohmeier, Heather L.; Campbell, Thomas F.; Dollaghan, Christine A.; Green, Jordan R.; Moore, Christopher A.

2009-01-01

Purpose: Conceptual and methodological confounds occur when non(sense) word repetition tasks are administered to speakers who do not have the target speech sounds in their phonetic inventories or who habitually misarticulate targeted speech sounds. In this article, the authors (a) describe a nonword repetition task, the Syllable Repetition Task…

Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

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Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

2015-01-01

We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin.

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Ishii, Yuki; Sugimoto, Saho; Izawa, Naoki; Sone, Toshiro; Chiba, Katsuyoshi; Miyazaki, Kouji

2014-07-01

Recent studies have shown that some probiotics affect not only the gut but also the skin. However, the effects of probiotics on ultraviolet (UV)-induced skin damage are poorly understood. In this study, we aim to examine whether oral administration of live Bifidobacterium breve strain Yakult (BBY), a typical probiotic, can attenuate skin barrier perturbation caused by UV and reactive oxygen species (ROS) in hairless mice. The mice were orally supplemented with a vehicle only or BBY once a day for nine successive days. Mouse dorsal skin was irradiated with UV from days 6 to 9. The day after the final irradiation, the transepidermal water loss (TEWL), stratum corneum hydration, and oxidation-related factors of the skin were evaluated. We elucidated that BBY prevented the UV-induced increase in TEWL and decrease in stratum corneum hydration. In addition, BBY significantly suppressed the UV-induced increase in hydrogen peroxide levels, oxidation of proteins and lipids, and xanthine oxidase activity in the skin. Conversely, antioxidant capacity did not change regardless of whether BBY was administered or not. In parameters we evaluated, there was a positive correlation between the increase in TEWL and the oxidation levels of proteins and lipids. Our results suggest that oral administration of BBY attenuates UV-induced barrier perturbation and oxidative stress of the skin, and this antioxidative effect is not attributed to enhancement of antioxidant capacity but to the prevention of ROS generation.

TISSUE DISTRIBUTION OF INORGANIC ARSENIC (AS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV)

Science.gov (United States)

TISSUE DISTRIBUTION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV). E M Kenyon1, L M Del Razo2, and M F Hughes1. 1NHEERL, ORD, US EPA, RTP, NC, USA; 2CINVESTAV-IPN, Mexico City, Mexico.The relationship o...

Evaluation of pancreatic lipase activity by simple urine analysis after oral administration of a new iodine-131-labeled triglyceride

International Nuclear Information System (INIS)

Kropp, J.; Knapp, F.F. Jr.; Weyenberg, A.; McPherson, D.W.; Ambrose, K.R.; Callahan, A.P.; Bergmann, K. von; Biersack, H.J.

1994-01-01

A new iodine-131-labeled triglyceride analogue called ''MIPAG'' [1,2-dipalmitoyl-3-[(15-p-iodophenyl) pentadecan-1-oyl]rac-glycerol] has been prepared in which 15-(p-iodophenyl)pentadecanoic acid (IPPA) is attached to position-3. MIPAG has been developed for the evaluation of pancreatic exocrine function by simple urine analysis and has been evaluated in rats and humans. After oral administration, IPPA is released from the triglyceride by the action of pancreatic lipases followed by intestinal absorption and the principal IPPA metabolite (p-iodobenzoic acid. IBA) is primarily excreted in the urine. Excretion in the urine and feces was evaluated in rats, as well as the biodistribution in various organs over 21 days. Twenty patients without pancreatic disease (normals) and four patients with pancreatic insufficiency were also investigated. Following oral administration of 30 μCi of MIPAG, urine was collected for two successive 24-h periods. Blood samples were drawn and thin-layer chromatographic (TLC) analysis was performed on the serum lipid extracts. Urine from normals contained 44.9%±7.7% and 61.8%±8.4% of the administered activity after 24 and 48 h, respectively. The patients with pancreatic insufficiency excreted 13.1%±5.6% and 18.9%±6.2%, respectively, which was significantly decreased (P<0.001) compared with normals. The TLC profiles showed an increasing proportion of IBA with time. Urine analysis after oral administration of MIPAG thus appears to be an attractive new technique for the evaluation of pancreatic lipase activity by a simple urine analysis. (orig.)

Oxotremorine treatment reduces repetitive behaviors in BTBR T+ tf/J mice

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Dionisio A. Amodeo

2014-08-01

Full Text Available Repetitive behaviors with restricted interests is one of the core criteria for the diagnosis of autism spectrum disorder (ASD. Current pharmacotherapies that target the dopaminergic or serotonergic systems have limited effectiveness in treating repetitive behaviors. Previous research has demonstrated that administration of muscarinic cholinergic receptor (mAChR antagonists can exacerbate motor stereotypies while mAChR agonists reduce stereotypies. The present study determined whether the mAChR agonist, oxotremorine affected repetitive behaviors in the BTBR T+ tf/J (BTBR mouse model of autism. To test the effects of oxotremorine on repetitive behaviors, marble burying and grooming behavior were measured in BTBR mice and compared to that in C57BL/6J (B6 mice. The effects of oxotremorine on locomotor activity was also measured. Thirty minutes before each test, mice received an intraperitoneal injection of saline, 0.001 mg or 0.01 mg of oxotremorine methiodide. Saline- treated BTBR mice exhibited increased marble burying and self-grooming behavior compared to that of saline-treated B6 mice. Oxotremorine significantly reduced marble burying and self-grooming behavior in BTBR mice, but had no significant effect in B6 mice. In addition, oxotremorine did not affect locomotor activity in BTBR mice, but significantly reduced locomotor activity in B6 mice at the 0.01 mg dose. These findings demonstrate that activation of mAChRs reduces repetitive behavior in the BTBR mouse and suggest that treatment with a mAChR agonist may be effective in reducing repetitive behaviors in ASD.

A 5-month toxicity study of the ethanol extract of the leaves of Heliotropium indicum in Sprague Dawley rats after oral administration.

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Owolabi, M A; Oribayo, O O; Ukpo, G E; Mbaka, G O; Akindehin, O E

2015-01-01

Heliotropium indicum Linn. (Boraginaceae) is used in Nigerian traditional medicine to treat tuberculosis with treatment lasting for 3 months; however, information on its toxicity is scarce. This study investigated the safety of the leaves of Heliotropium indicum after a 5 month oral administration. The leaves of H. indicum were dried; extracted in 70% ethanol and concentrated to dryness. Swiss mice were administered orally with single doses of the extract (0.5 to 12.0 g/kg b.wt /day); mortality was examined for up to 14 days. In another study, the plant material (0.5 to 2.0 g/kg b.wt /day) were administered daily by oral gavage to Sprague Dawley rats. Body weight was monitored weekly, hematological, biochemical and organ parameters were determined at the end of the 1st, 2nd and 5th months of extract administration. The oral administration of the ethanol extract of H. indicum caused dose-dependent mortality. The LD50 was 9.78 g/kg b.wt for the Swiss mice; no harmful effect was observed on the liver and kidney except the testes which exhibited considerable inflammatory changes at the highest dose of 2.0 g/kg b.wt./day after the 5th month treatment. No significant difference (P>0.05) was shown in the enzyme study, marginal increase occurred in some haematological parameters. The increase in body weight of the treated rats after its initial reduction was consistent and significantly different (P<0.05) from their initial body weight. Prolonged administration of the crude leaf extract of H. indicum is considered to be safe and nontoxic at the doses studied. However, there is a probability of a negative effect on the testes at a higher dose of the extract.

Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats.

Science.gov (United States)

Porters, Nathalie; Bosmans, Tim; Debille, Mariëlla; de Rooster, Hilde; Duchateau, Luc; Polis, Ingeborgh

2014-01-01

To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range. There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing. In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Studies on portal systemic circulation by oral administration of /sup 201/Tl enclosed enteric coated capsule

Energy Technology Data Exchange (ETDEWEB)

Tonami, Norihisa; Nakajima, Kenichi; Watanabe, Naoto and others

1986-03-01

Thallium-201 enclosed enteric coated capsule was prepared and administered orally to evaluate portal systemic circulation in 11 control subjects and 31 patients with various liver diseases by investigating scintigraphic appearance and the heart-to-liver uptake ratio (H/L ratio). In 10 patients with liver cirrhosis and one with chronic hepatitis, the results of H/L ratio were compared to those obtained by /sup 201/Tl per-rectal administration. 1. It was fundamentally confirmed that /sup 201/Tl enclosed enteric coated capsule was not broken down in the artificial gastric juice, but nearly completely melted 15 minutes after soaking in the artificial intestinal juice. 2. Clinical study was successfully completed in 36 out of 42 cases (86 %). Unsuccessful cases were found in 2 with capsule collapse in the stomach and 4 with its poor moving to the duodenum. 3. In control subjects the liver was clearly visualized and the mean value of H/L ratio was 0.32 which is lower than that of /sup 201/Tl per-rectal administration previously reported. H/L ratio in patients with chronic and acute hepatitis was nearly equal to that in control subjects. H/L ratio in patients with liver cirrhosis was slightly higher than that in control subjects, but there was no significant difference between them. In cases with esophageal varices, H/L ratio was not so high compared to that in control subjects. Out of 7 patients showing high H/L ratio more than 0.8 in /sup 201/Tl per-rectal administration, only one showed similar high ratio (1.07) in oral administration of /sup 201/Tl enclosed enteric coated capsule. In this case the shunting from superior mesenteric vein to inferior vena cava connection was confirmed. From these results, it was considered that the shunting volume of superior mesenteric vein through esophageal varices is small. 4. A possibility of a new administration of radioisotope with enteric coated capsule was emphasized.

The ethics of in vivo calibrations in oral health surveys.

Science.gov (United States)

Andrade, Flávia Reis de; Narvai, Paulo Capel; Montagner, Miguel Ângelo

2016-01-01

To analyze the ethics of in vivo calibration, using the discourse of the administrators of the National Oral Health Survey (SBBrasil 2010) as a starting point. This is a qualitative research involving semi-structured individual interviews with 12 members of the Steering Group and Technical Advisory Committee of the Ministry of Health, and two coordinators, one State and the other Municipal. The discourse of the collective subject technique was used for data analysis. When asked about the experiences of SBBrasil 2010, which included ethical aspects, respondents identified the forms of standardization and training of teams who collected field data. For them, there is little scientific evidence to ethically support the way the training stage, including calibration, is carried out in oral health epidemiological surveys, as a certain unease can be predicted in participants of these studies. The ethics of a research also derives from its methodological rigor; the training process; and calibration in particular, is a fundamental technical and ethical requirement in surveys such as the SBBrasil 2010. The unease of the volunteers in face of test repetition does not ethically invalidate the in vivo calibration, but mechanisms to minimize it must be developed.

Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

International Nuclear Information System (INIS)

Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

1997-01-01

The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

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Perelló, Maria; González-Foruria, Iñaki; Castillo, Paola; Martínez-Florensa, Mario; Lozano, Francisco; Balasch, Juan; Carmona, Francisco

2017-06-01

Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm 3 vs 276.75 ± 94.30 mm 3 and 145.33 ± 38.20 mm 3 , respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm 2 ) versus group 2 (1.35 ± 0.43 mm 2 ) and control (2.84 ± 0.60 mm 2 ; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

Suspected adverse reactions to oral administration of a praziquantel-pyrantel combination in captive cheetahs (Acinonyx jubatus).

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Whitehouse-Tedd, Katherine M; Smith, Liesl; Budd, Jane A; Lloyd, Christopher G

2017-11-15

OBJECTIVE To characterize adverse reactions to oral administration of a combination of praziquantel and pyrantel embonate or pyrantel pamoate, with or without oxantel embonate, in captive cheetahs (Acinonyx jubatus). DESIGN Retrospective case series and case-control study. ANIMALS 16 captive cheetahs with signs of adverse reaction to oral administration of praziquantel and pyrantel, with or without oxantel embonate (affected group), and 27 cheetahs without such reactions (unaffected group), all from 3 independent facilities. PROCEDURES Medical records and postmortem findings for affected cheetahs were reviewed and compared with those of unaffected animals. Anthelmintic doses administered, age, and sex of cheetahs were compared between groups. RESULTS 3 reactions in affected cheetahs were fatal, whereas the remainder ranged from mild to severe. Postmortem examination failed to reveal any disease processes or conditions to explain the deaths. No differences in anthelmintic dose were identified between affected and unaffected cheetahs for all facilities combined, and no correlation existed between dose and reaction severity. No association with sex was detected, but affected cheetahs were significantly younger than unaffected cheetahs. This difference was not significant after controlling for facility. CONCLUSIONS AND CLINICAL RELEVANCE Cheetahs were concluded to have had an adverse reaction to the praziquantel-pyrantel combination because of temporal proximity of onset of clinical signs to dose administration, similarity of signs to those reported for toxicosis in other species for these drugs, and a lack of other disease process or environmental explanatory factors. A highly cautious approach to the use of this drug combination is recommended for cheetahs.

Sequential gadolinium-enhanced magnetic resonance angiography of the aortoiliac and the femoropopliteal arteries with repetitive administration of low-dose contrast agent

International Nuclear Information System (INIS)

Ito, Koichiro; Kumazaki, Tatsuo

2000-01-01

To obtain a wide-range contrast MR angiography in a single examination, we performed two sequential administrations of low-dose (0.08 mmol/kg) gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with three dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady-state (3D IR-fast SPGR) sequence. Signal characteristics of the sequence were estimated by computed simulations and an in vitro study. A clinical study of 19 examinations was done with sequential MR angiography of the aortoiliac and femoropopliteal arteries. Great signal differences were observed between the high and low Gd concentrations. Higher Gd concentrations generated significantly stronger signals. Greater signals were produced at TIs of longer than 150 msec than at shorter than 100 msec. In the clinical study, the arteries were visualized with sufficient signals even with a small amount of contrast agent. Contrast-to-noise ratios between the arteries and surrounding skeletal muscles or fat tissues ranged from 10.5±9.6 to 4.7±2.2 and 6.6±2.8 to -3.1±11.2, respectively. No venous enhancement was found with diluted contrast agent on the second MR angiography. Two consecutive contrast MR angiographies can be obtained with repetitive administration of low-dose contrast agent. (author)

Sequential gadolinium-enhanced magnetic resonance angiography of the aortoiliac and the femoropopliteal arteries with repetitive administration of low-dose contrast agent

Energy Technology Data Exchange (ETDEWEB)

Ito, Koichiro [Nippon Medical School, Inba, Chiba (Japan). Chiba Hokusoh Hospital; Kumazaki, Tatsuo

2000-12-01

To obtain a wide-range contrast MR angiography in a single examination, we performed two sequential administrations of low-dose (0.08 mmol/kg) gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with three dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady-state (3D IR-fast SPGR) sequence. Signal characteristics of the sequence were estimated by computed simulations and an in vitro study. A clinical study of 19 examinations was done with sequential MR angiography of the aortoiliac and femoropopliteal arteries. Great signal differences were observed between the high and low Gd concentrations. Higher Gd concentrations generated significantly stronger signals. Greater signals were produced at TIs of longer than 150 msec than at shorter than 100 msec. In the clinical study, the arteries were visualized with sufficient signals even with a small amount of contrast agent. Contrast-to-noise ratios between the arteries and surrounding skeletal muscles or fat tissues ranged from 10.5{+-}9.6 to 4.7{+-}2.2 and 6.6{+-}2.8 to -3.1{+-}11.2, respectively. No venous enhancement was found with diluted contrast agent on the second MR angiography. Two consecutive contrast MR angiographies can be obtained with repetitive administration of low-dose contrast agent. (author)

Oral administration of heat-killed Lactobacillus gasseri OLL2809 reduces cedar pollen antigen-induced peritoneal eosinophilia in Mice.

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Sashihara, Toshihiro; Ikegami, Shuji; Sueki, Natsuko; Yamaji, Taketo; Kino, Kohsuke; Taketomo, Naoki; Gotoh, Minoru; Okubo, Kimihiro

2008-12-01

Lactobacillus gasseri OLL2809 strongly stimulates the production of interleukin (IL)-12 (p70) by innate immune cells. Thus, it is expected to ameliorate allergic diseases. We investigated whether the oral administration of heat-killed L. gasseri OLL2809 suppressed eosinophilia in cedar pollen antigen-challenged mice. BALB/c mice sensitized with Japanese cedar pollen extract were intraperitoneally challenged with the same extract. The mice were orally given heat-killed L. gasseri OLL2809 at doses of 0.5, 1, or 2mg/day throughout the experimental period (21 d). After 24 hours of the challenge, the eosinophil number and cytokine levels in the peritoneal lavage fluid and the serum antigen-specific IgG levels were determined. On administering varying amounts of heat-killed L. gasseri OLL2809, the number of eosinophils among the total number of cells was significantly reduced in all groups. In addition, the eosinophil number significantly decreased, and the eosinophil-suppression rate significantly increased by 44% in the 2-mg group. Although the serum immunoglobulin (Ig) G2a and IgG1 levels were not affected, the IgG2a/IgG1 ratio increased significantly in the 2-mg group compared with that of the control group. Furthermore, the administration of heat-killed L. gasseri OLL2809 resulted in the induction of IL-2 and reduction in granulocyte-macrophage colony-stimulating factor levels in peritoneal lavage fluid. We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis.

Absorption, distribution, metabolism and excretion of selenium following oral administration of elemental selenium nanoparticles or selenite in rats

DEFF Research Database (Denmark)

Löschner, Katrin; Hadrup, Niels; Hansen, Marianne

2014-01-01

A suspension of nanoparticles of BSA-stabilized red amorphous elemental selenium (Se) or an aqueous solution of sodium selenite was repeatedly administered by oral gavage for 28 days at 0.05 mg/kg bw/day (low dose) or at 0.5 mg/kg bw/day (high dose) as Se to female rats. Prior to administration...

Pharmacokinetics of Alternative Administration Routes of Melatonin

DEFF Research Database (Denmark)

Zetner, D.; Andersen, L. P.H.; Rosenberg, J.

2016-01-01

Background: Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin. Methods: A systematic literature search was performed...... and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration routes except oral and intravenous. Results: 10 studies were included in the review. Intranasal....... Subcutaneous injection of melatonin displayed a rapid absorption rate compared to oral administration. Conclusion: Intranasal administration of melatonin has a large potential, and more research in humans is warranted. Transdermal application of melatonin has a possible use in a local application, due to slow...

Comparative pharmacokinetics of swertiamarin in rats after oral administration of swertiamarin alone, Qing Ye Dan tablets and co-administration of swertiamarin and oleanolic acid.

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Xu, Gui-li; Li, Hong-liang; He, Jian-chang; Feng, En-fu; Shi, Pan-pan; Liu, Yue-qiong; Liu, Chang-xiao

2013-08-26

Qing Ye Dan is a well-known herbal drug that is widely used to treat viral hepatitis in the Yi and Hani minority regions in the Yunnan province of China. An LC-MS/MS method was developed to determine the levels of swertiamarin in rat plasma. Swertiamarin and naringin (internal standard, IS) were extracted from rat plasma using solid-phase extraction (SPE) to purify the samples. The pharmacokinetics of the following different administration methods of swertiamarin in rats were studied: oral administration of swertiamarin alone, a Qing Ye Dan tablet (QYDT) and co-administration of swertiamarin and oleanolic acid, with each method delivering approximately 20mg/kg of swertiamarin. Non-compartmental pharmacokinetic profiles were constructed by using the software DAS (version 2.1.1), and the pharmacokinetic parameters were compared using an unpaired Student's t-test. The results showed that the pharmacokinetic parameters Cmax, AUC0-∞, Vz/F and CLz/F were significantly different (P<0.05) among the three types of swertiamarin administration. The data indicate that oleanolic acid and the other ingredients present in QYDT could affect the pharmacokinetic behaviour of swertiamarin in rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

ORAL MYIASIS CONVERTING TO ORAL SQUAMOUS CELL CARCINOMA

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Akshay

2015-10-01

Full Text Available INTRODUCTION: Oral Myiasis, a condition of infestation of the body by fly larvae (maggots is a rare pathology in humans. It is associated with poor oral hygiene, alcoholism, senility, suppurating lesions, severe halitosis. It is seen frequently in tropical countries and hot climatic regions. The reported cases in literature of oral Myiasis associated with oral cancer are few. The treatment is a mechanical removal of the maggots but a systemic treatment with Ivermectin, a semi - synthetic macrolide antibiotic, has been used successfully for treatment for oral m yiasis. We present a case of 55 yr old male alcoholic patient with oral myiasis with extensive proliferative growth of oral cavity. Our patient was managed with manual debridement and administration of systemic ivermect in along with antibiotic coverage. Incisional biopsy of the proliferative lesion showed well differentiated squamous cell carcinoma. Thus our patient showed presence of oral myiasis in association with oral squamous cell carcinoma.

Computer versus lecture: a comparison of two methods of teaching oral medication administration in a nursing skills laboratory.

Science.gov (United States)

Jeffries, P R

2001-10-01

The purpose of this study was to compare the effectiveness of both an interactive, multimedia CD-ROM and a traditional lecture for teaching oral medication administration to nursing students. A randomized pretest/posttest experimental design was used. Forty-two junior baccalaureate nursing students beginning their fundamentals nursing course were recruited for this study at a large university in the midwestern United States. The students ranged in age from 19 to 45. Seventy-three percent reported having average computer skills and experience, while 15% reported poor to below average skills. Two methods were compared for teaching oral medication administration--a scripted lecture with black and white overhead transparencies, in addition to an 18-minute videotape on medication administration, and an interactive, multimedia CD-ROM program, covering the same content. There were no significant (p lecture groups by education or computer skills. Results showed significant differences between the two groups in cognitive gains and student satisfaction (p = .01), with the computer group demonstrating higher student satisfaction and more cognitive gains than the lecture group. The groups were similar in their ability to demonstrate the skill correctly. Importantly, time on task using the CD-ROM was less, with 96% of the learners completing the program in 2 hours or less, compared to 3 hours of class time for the lecture group.

Haben repetitive DNA-Sequenzen biologische Funktionen?

Science.gov (United States)

John, Maliyakal E.; Knöchel, Walter

1983-05-01

By DNA reassociation kinetics it is known that the eucaryotic genome consists of non-repetitive DNA, middle-repetitive DNA and highly repetitive DNA. Whereas the majority of protein-coding genes is located on non-repetitive DNA, repetitive DNA forms a constitutive part of eucaryotic DNA and its amount in most cases equals or even substantially exceeds that of non-repetitive DNA. During the past years a large body of data on repetitive DNA has accumulated and these have prompted speculations ranging from specific roles in the regulation of gene expression to that of a selfish entity with inconsequential functions. The following article summarizes recent findings on structural, transcriptional and evolutionary aspects and, although by no means being proven, some possible biological functions are discussed.

Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration.

Science.gov (United States)

Feng, Ru; Zhao, Zhen-Xiong; Ma, Shu-Rong; Guo, Fang; Wang, Yan; Jiang, Jian-Dong

2018-01-01

Berberine (BBR) is considered a multi-target drug that has significant advantages. In contrast to its significant pharmacological effects in clinic, the plasma level of BBR is very low. Our previous work revealed that dihydroberberine (dhBBR) could be an absorbable form of BBR in the intestine, and butyrate is an active metabolite that is generated by gut bacteria in rats. In this study, for the first time we describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR by single (50 mg/kg) or multiple doses (50 mg/kg/d) for 7 days. GC-MS, GC, LC-MS/MS, and LC/MS n -IT-TOF were used to detect dhBBR, butyrate and BBR as well as its Phase I and II metabolites, respectively. The results showed that dhBBR was not detected in dog plasma but was excreted in small amounts in the feces of dogs examined on days 3 and 7. Butyrate was generated by gut bacteria and increased by 1.3- and 1.2-fold in plasma or feces, respectively, after 7 days of BBR treatment compared to the levels before treatment. Changes of intestinal bacterial composition were analyzed by 16S rRNA genes analysis. The results presented that dogs treated with BBR for 7 days increased both the abundance of the butyrate- and the nitroreductases- producing bacteria. We also identified chemical structures of the Phase I and II metabolites and analyzed their contents in beagle dogs. Eleven metabolites were detected in plasma and feces after BBR oral administration (50 mg/kg) to dogs, including 8 metabolites of Phase I and III metabolites of Phase II. The pharmacokinetic profile indicated that the concentration of BBR in plasma was low, with a C max value of 36.88 ± 23.45 ng/mL. The relative content of glucuronic acid conjugates (M11) was higher than those of other metabolites (M1, M2, M12, and M14) in plasma. BBR was detected in feces, with high excreted amounts on day 3 (2625.04 ± 1726.94 μg/g) and day 7 (2793.43 ± 488.10 μg/g). In summary, this is the first study to

Effects of long-term light, darkness and oral administration of melatonin on serum levels of melatonin

OpenAIRE

Naser Farhadi; Majid Gharghani; Zahra Farhadi

2016-01-01

Background: Continuous light or darkness has various effects on different systems. In the present research work, the effects of constant light and darkness exposure of male rats and oral administration of exogenous melatonin on the serum levels of melatonin have been studied. Methods: Thirty adult male Wistar rats were divided into six groups of: (1) Control, (2) melatonin, (3) light, (4) light and melatonin, (5) darkness, and (6) darkness and melatonin. All groups were placed according to...

Preclinical and clinical pharmacology of oral anticancer drugs

NARCIS (Netherlands)

Oostendorp, R.L.

2009-01-01

Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for

Oral administration of prednisone to control refractory vertigo in Ménière's disease: a pilot study.

Science.gov (United States)

Morales-Luckie, Elizabeth; Cornejo-Suarez, Arnulfo; Zaragoza-Contreras, Miguel A; Gonzalez-Perez, Oscar

2005-09-01

To establish whether the oral administration of moderate doses of prednisone reduces refractory vertigo in Ménière's disease. Blinded, randomized, controlled trial. Tertiary referral center. Patients with Ménière's disease with limited vertigo control (Class C) and severe disability (Scale 3). Two groups (n = 8 per group) were treated orally with either diphenidol (25 mg/d) plus acetazolamide (250 mg/48 h) (control group), or the same treatment plus prednisone (0.35 mg/kg) daily for 18 weeks (prednisone group). The variables evaluated were the frequency and duration of vertigo, tinnitus, aural fullness, and audiographic parameters. The clinical surveillance was performed for 12 months after prednisone withdrawal. The frequency and duration of vertigo episodes were reduced by 50% and 30%, respectively, by prednisone treatment. Prednisone-treated patients manifested a significant reduction in tinnitus. No changes were observed in aural fullness or hearing. No metabolic or infectious disorders were observed. Oral prednisone helps to control refractory vertigo in Ménière's disease. These preliminary data suggest that prednisone can be a good noninvasive antivertigo management regimen for these patients.

Pharmacokinetics of enrofloxacin after oral, intramuscular and bath administration in crucian carp (Carassius auratus gibelio).

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Shan, Q; Fan, J; Wang, J; Zhu, X; Yin, Y; Zheng, G

2018-02-01

The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C max ) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half-life (T 1/2β ) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration-time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration. © 2017 John Wiley & Sons Ltd.

[Variations in hyperbilirrubinemia in low birth weight newborns under phototherapy and continous or discontinous agar oral administration (author's transl)].

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Colomer, J; Moya, M; Marco, V; De Paredes, C; Escrivá, F; Vila, R

1975-06-01

Therapeutic attitude in hyperbilirrubinemia is always worth because other infrequent complications but not for this, less important. Phototherapy innocuousness, largely demonstrated, fosters its profilactic use at beginning and not only for those babies with serum bilirrubin over 10 mg % in the first day of life. Previously we have reported positive results with agar oral administration without collateral effects. On this grounds we have planned the following experience in a homogenous group of L.B.W.: one group was fed with agar previously to each formula administration; other group received the same amount of agar but divided in only three administrations in 24 hours; the last group received continuous phototherapy for 96 hours with a white cold fluorescent light from a source of 8-Vita-lite lamp of 40 watts with a intensity of 500 foot candle and 30 lumens. All of these babies weighed less than 2.500 g. and were between 10 and 90 percentil of Lubschenko diagram. They were fed with the same formula and same time table with no infusions, rejecting all that presented any type of pathology. Obstetric conditions were basically identical. This population was randomly divided in four groups. 1) Control group with no profilaxis, but with identical bilirrubin andhematocrit determinations. 2) Group with continuous agar oral administration, 125 mg. before each of the seven formula feeding. 3) Group with discontinuous agar administration, 250 mg. before three of the seven formula feeding. 4) Group with continuous phototherapy for 96 hours. These is initial identification of the groups with statistic signification, and after that a quantitative and sequential evolution of bilirrubin is analized in each group.

Pharmacokinetics and metabolism of cyadox and its main metabolites in beagle dogs following oral, intramuscular and intravenous administration

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Adeel Sattar

2016-08-01

Full Text Available Cyadox (Cyx is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO, intramuscular (IM and intravenous (IV routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females were administered Cyx through PO (40 mg kg-1 b.w., IM (10 mg kg-1 b.w. and IV (10 mg kg-1 b.w. routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1, cyadox-1-monoxide (Cy2, N-(quinoxaline-2-methyl-cyanide acetyl hydrazine (Cy4 and quinoxaline-2-carboxylic acid (Cy6 in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC of Cyx after PO, IM and IV administration were 1.22 h×µg mL-1, 6.3 h×µg mL-1, and 6.66 h×µg mL-1, while mean resident times (MRT were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

Comparison of the enhancement of plasma glucose levels in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats by oral administration of sucrose or maple syrup.

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Nagai, Noriaki; Ito, Yoshimasa; Taga, Atsushi

2013-01-01

Maple syrup is used as a premium natural sweeter, and is known for being good for human health. In the present study, we investigate whether maple syrup is suitable as a sweetener in the management of type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. OLETF rats develop type 2 diabetes mellitus by 30 weeks of age, and 60-week-old OLETF rats show hyperglycemia and hypoinsulinemia via pancreatic β-cell dysfunction. The administration of sucrose or maple syrup following an OGT test increased plasma glucose (PG) levels in OLETF rats, but the enhancement in PG following the oral administration of maple syrup was lower than in the case of sucrose administration in both 30- and 60-week-old OLETF rats. Although, the insulin levels in 30-week-old OLETF rats also increased following the oral administration of sucrose or maple syrup, no increase in insulin levels was seen in 60-week-old OLETF rats following the oral administration of either sucrose or maple syrup. No significant differences were observed in insulin levels between sucrose- and maple syrup-administered OLETF rats at either 30 or 60 weeks of age. The present study strongly suggests that the maple syrup may have a lower glycemic index than sucrose, which may help in the prevention of type 2 diabetes.

The antinociceptive effects of Monechma ciliatum and changes in EEG waves following oral and intrathecal administration in rats

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Meraiyebu, Ajibola B.; Adelaiye, Alexander B.; O, Odeh S.

2010-02-01

The research work was carried out to study the effect of Oral and Intrathecal Monechma Ciliatum on antinociception and EEG readings in Wistar Rats. Traditionally the extract is given to women in labour believed to reduce pain and ease parturition, though past works show that it has oesteogenic and oxytotic effects. The rats were divided into 5 major groups. Group 1 served as oral control group while groups 2 and 3 served as oral experimental groups and were treated with 500mg/kg and 1000mg/kg monechma ciliatum respectively. Group 4 served as intrathecal control group treated with intrathecal dextrose and group 5 received 1000mg/kg Monechma Ciliatrum intrathecally. The antinociceptive effect was analysed using a Von Frey's aesthesiometer. Monechma Ciliatum showed significant antinociceptive effect both orally and intrathecally, although it had a greater effect orally and during the first 15 minutes of intrathecal administration. EEG readings were also taken for all the groups and there was a decrease in amplitude and an increase in frequency for high dose (1000mg/ml) experimental groups and the mid brain electrodes produced a change from theta waves (3.5 - 7 waves per second) to alpha waves (7.5 - 13 waves per second) as seen in relaxed persons and caused decreased amplitudes and change in distribution seen in beta waves. Properties similarly accentuated by sedativehypnotic drugs.

Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat

Energy Technology Data Exchange (ETDEWEB)

Gonçalves, Daniela [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Alves, Gilberto, E-mail: gilberto@fcsaude.ubi.pt [CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal); Fortuna, Ana [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Soares-da-Silva, Patrício [Department of Research and Development, BIAL – Portela & Ca S.A., Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado (Portugal); MedInUP – Center for Drug Discovery and Innovative Medicines, University Porto, Porto (Portugal); Falcão, Amílcar [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal)

2017-05-15

Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n = 8 per group) were orally treated with single (30, 60 or 90 mg/kg) or multiple (30 mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24 h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration ≤ 2 h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30–90 mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58–4.50 h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. - Highlights: • Opicapone is relatively rapid absorbed after oral administration to rats. • Systemic exposure to opicapone increases approximately in a dose-proportional manner. • Opicapone and BIA 9-1079 show a small systemic accumulation after multiple-dosing.

Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects.

Science.gov (United States)

Laizure, S Casey; Meibohm, Bernd; Nelson, Kembral; Chen, Feng; Hu, Zhe-Yi; Parker, Robert B

2017-12-01

To determine the disposition and effects of caffeine after administration using a new dosage form (AeroShot) that delivers caffeine by inspiration of a fine powder into the oral cavity and compare it to an equivalent dose of an oral solution (energy drink) as the reference standard. Healthy human subjects (n = 17) inspired a 100 mg caffeine dose using the AeroShot device or consumed an energy drink on separate study days. Heart rate, blood pressure and subject assessments of effects were measured over an 8-h period. Plasma concentrations of caffeine and its major metabolites were determined by liquid chromatography-mass spectrometry. Pharmacokinetic, cardiovascular and perceived stimulant effects were compared between AeroShot and energy drink phases using a paired t test and standard bioequivalency analysis. Caffeine disposition was similar after caffeine administration by the AeroShot device and energy drink: peak plasma concentration 1790 and 1939 ng ml -1 , and area under the concentration-time curve (AUC) 15 579 and 17 569 ng ml -1 × h, respectively, but they were not bioequivalent: AeroShot AUC of 80.3% (confidence interval 71.2-104.7%) and peak plasma concentration of 86.3% (confidence interval 62.8-102.8%) compared to the energy drink. Female subjects did have a significantly larger AUC compared to males after consumption of the energy drink. The heart rate and blood pressure were not significantly affected by the 100 mg caffeine dose, and there were no consistently perceived stimulant effects by the subjects using visual analogue scales. Inspiration of caffeine as a fine powder using the AeroShot device produces a similar caffeine profile and effects compared to administration of an oral solution (energy drink). © 2017 The British Pharmacological Society.

Beneficial Effects of Long-Term Administration of an Oral Formulation of Angiotensin-(1–7 in Infarcted Rats

Directory of Open Access Journals (Sweden)

Fúlvia D. Marques

2012-01-01

Full Text Available In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang-(1–7 in hydroxypropyl β-cyclodextrin (HPβCD, in infarcted rats. Myocardial infarction (MI was induced by left coronary artery occlusion. HPβCD/Ang-(1–7 was administered for 60 days (76 μg/Kg/once a day/gavage starting immediately before infarction. Echocardiography was utilized to evaluate usual cardiac parameters, and radial strain method was used to analyze the velocity and displacement of myocardial fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was utilized to evaluate the fibrotic signaling involved in the remodeling process. Once-a-day oral HPβCD/Ang-(1–7 administration improved the cardiac function and reduced the deleterious effects induced by MI on TGF-β and collagen type I expression, as well as on the velocity and displacement of myocardial fibers. These findings confirm cardioprotective effects of Ang-(1–7 and indicate HPβCD/Ang-(1–7 as a feasible formulation for long-term oral administration of this heptapeptide.

Repetition and lag effects in movement recognition.

Science.gov (United States)

Hall, C R; Buckolz, E

1982-03-01

Whether repetition and lag improve the recognition of movement patterns was investigated. Recognition memory was tested for one repetition, two-repetitions massed, and two-repetitions distributed with movement patterns at lags of 3, 5, 7, and 13. Recognition performance was examined both immediately afterwards and following a 48 hour delay. Both repetition and lag effects failed to be demonstrated, providing some support for the claim that memory is unaffected by repetition at a constant level of processing (Craik & Lockhart, 1972). There was, as expected, a significant decrease in recognition memory following the retention interval, but this appeared unrelated to repetition or lag.

Prediction of the Maximum Number of Repetitions and Repetitions in Reserve From Barbell Velocity.

Science.gov (United States)

García-Ramos, Amador; Torrejón, Alejandro; Feriche, Belén; Morales-Artacho, Antonio J; Pérez-Castilla, Alejandro; Padial, Paulino; Haff, Guy Gregory

2018-03-01

To provide 2 general equations to estimate the maximum possible number of repetitions (XRM) from the mean velocity (MV) of the barbell and the MV associated with a given number of repetitions in reserve, as well as to determine the between-sessions reliability of the MV associated with each XRM. After determination of the bench-press 1-repetition maximum (1RM; 1.15 ± 0.21 kg/kg body mass), 21 men (age 23.0 ± 2.7 y, body mass 72.7 ± 8.3 kg, body height 1.77 ± 0.07 m) completed 4 sets of as many repetitions as possible against relative loads of 60%1RM, 70%1RM, 80%1RM, and 90%1RM over 2 separate sessions. The different loads were tested in a randomized order with 10 min of rest between them. All repetitions were performed at the maximum intended velocity. Both the general equation to predict the XRM from the fastest MV of the set (CV = 15.8-18.5%) and the general equation to predict MV associated with a given number of repetitions in reserve (CV = 14.6-28.8%) failed to provide data with acceptable between-subjects variability. However, a strong relationship (median r 2  = .984) and acceptable reliability (CV  .85) were observed between the fastest MV of the set and the XRM when considering individual data. These results indicate that generalized group equations are not acceptable methods for estimating the XRM-MV relationship or the number of repetitions in reserve. When attempting to estimate the XRM-MV relationship, one must use individualized relationships to objectively estimate the exact number of repetitions that can be performed in a training set.

Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA damage and plasma lipid peroxidation induced by TSA in vivo.

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Chan, Shu-Ting; Lin, Yi-Chin; Chuang, Cheng-Hung; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

2014-01-01

Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation.

Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS.

Science.gov (United States)

Li, Shuping; Teng, Liang; Liu, Wei; Cheng, Xuemei; Jiang, Bo; Wang, Zhengtao; Wang, Chang-Hong

2016-09-01

Context The β-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats.

Oral administration of Saccharomyces boulardii ameliorates carbon tetrachloride-induced liver fibrosis in rats via reducing intestinal permeability and modulating gut microbial composition.

Science.gov (United States)

Li, Ming; Zhu, Lin; Xie, Ao; Yuan, Jieli

2015-02-01

To investigate the effects of orally administrated Saccharomyces boulardii (S. boulardii) on the progress of carbon tetrachloride (CCl4)-induced liver fibrosis, 34 male Wistar rats were randomly divided into four experimental groups including the control group (n = 8), the cirrhotic group (n = 10), the preventive group (n = 8), and the treatment group (n = 8). Results showed that the liver expression levels of collagen, type I, alpha 1 (Col1A1), alpha smooth muscle actin (αSMA), transforming growth factor beta (TGF-β) and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) increased significantly in cirrhotic rats compared with control and decreased by S. boulardii administration. Treatment of S. boulardii also attenuated the increased endotoxin levels and pro-inflammatory cytokines in CCl4-treated rats. And, these were associated with the changes of intestinal permeability and fecal microbial composition. Our study suggested that oral administration of S. boulardii can promote the liver function of CCl4-treated rats, and the preventive treatment of this probiotic yeast may decelerate the progress of liver fibrosis.

Oral or parenteral administration of replication-deficient adenoviruses expressing the measles virus haemagglutinin and fusion proteins: protective immune responses in rodents.

Science.gov (United States)

Fooks, A R; Jeevarajah, D; Lee, J; Warnes, A; Niewiesk, S; ter Meulen, V; Stephenson, J R; Clegg, J C

1998-05-01

The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F) proteins were placed under the control of the human cytomegalovirus immediate early promoter in a replication-deficient adenovirus vector. Immunofluorescence and radioimmune precipitation demonstrated the synthesis of each protein and biological activity was confirmed by the detection of haemadsorption and fusion activities in infected cells. Oral as well as parenteral administration of the H-expressing recombinant adenovirus elicited a significant protective response in mice challenged with MV. While the F-expressing adenovirus failed to protect mice, cotton rats immunized with either the H- or F-expressing recombinant showed reduced MV replication in the lungs. Antibodies elicited in mice following immunization with either recombinant had no in vitro neutralizing activity, suggesting a protective mechanism involving a cell-mediated immune response. This study demonstrates the feasibility of using oral administration of adenovirus recombinants to induce protective responses to heterologous proteins.

[Functional respiratory and blood gas analytical studies of the effects of fenspiride, in oral and intramuscular administration, in chronic bronchopneumopathic subjects].

Science.gov (United States)

Cascella, D; Raffi, G B; Caudarella, R; Gennari, P; Caprara, C; Cipolla, C

1979-12-01

A group of 20 chronic bronchopneumopathics was treated for 15 days with fenspiride orally and i.m. The behaviour of a set of functional respiratory and haemogasanalytic parameters was monitored at various times (basic, 5th, 10th and 15th days). Progressive, significant improvements in VC, FEV1, RV and in related parameters were observed. These were attributed to the drug's anti-inflammatory effect in the respiratory ways as well as to its direct antibronchospastic action. Stress is laid on the excellent clinical tolerance of fenspiride following its oral and i.m. administration.

If you negate, you may forget: negated repetitions impair memory compared with affirmative repetitions.

Science.gov (United States)

Mayo, Ruth; Schul, Yaacov; Rosenthal, Meytal

2014-08-01

One of the most robust laws of memory is that repeated activation improves memory. Our study shows that the nature of repetition matters. Specifically, although both negated repetition and affirmative repetition improve memory compared with no repetition, negated repetition hinders memory compared with affirmative repetition. After showing participants different entities, we asked them about features of these entities, leading to either "yes" or "no" responses. Our findings show that correctly negating an incorrect feature of an entity elicits an active forgetting effect compared with correctly affirming its true features. For example, after seeing someone drink a glass of white wine, answering "no" to "was it red wine?" may lead one to greater memory loss of the individual drinking wine at all compared with answering "yes" to "was it white wine?" We find this negation-induced forgetting effect in 4 experiments that differ in (a) the meaning given for the negation, (b) the type of stimuli (visual or verbal), and (c) the memory measure (recognition or free recall). We discuss possible underlying mechanisms and offer theoretical and applied implications of the negation-induced forgetting effect in relation to other known inhibition effects. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Effect of oral nitroethane and 2-nitropropanol administration on methane-producing activity and volatile fatty acid production in the ovine rumen

Energy Technology Data Exchange (ETDEWEB)

Anderson, R.C.; Callaway, T.R.; Schultz, C.L.; Edrington, T.S.; Harvey, R.B.; Nisbet, D.J. [United States Department of Agriculture, Agricultural Research Service, Food and Feed Safety Research Unit, College Station, TX (United States); Carstens, G.E.; Miller, R.K. [Texas A and M University, College Station, TX (United States). Department of Animal Science

2006-12-15

Strategies are sought to reduce economic and environmental costs associated with ruminant methane emissions. The effect of oral nitroethane or 2-nitropropanol administration on ruminal methane-producing activity and volatile fatty acid production was evaluated in mature ewes. Daily administration of 24 and 72 mg nitroethane/kg body weight reduced (P < 0.05) methane-producing activity by as much as 45% and 69% respectively, when compared to control animals given no nitroethane. A daily odes of 120 mg 2-nitropropanol/kg body weight was needed to reduce (P < 0.05) methane-producing activity by 37% from that of untreated control animals. Reductions in methane-producing activity may have been diminished by the last day (day 5) of treatment, presumably due to ruminal adaptation. Oral administration of nitroethane or 2-nitropropanol had little or no effect on accumulations or molar proportions of volatile fatty acids in ruminal contents collected from the sheep. These results demonstrate that nitroethane was superior to 2-nitropropanol as a methane inhibitor and that both nitrocompounds reduced ruminal methanogenesis in vivo without redirecting the flow of reductant generated during fermentation to propionate and butyrate. (author)

Oral delivery of Angiotensin-converting enzyme 2 and Angiotensin-(1-7) bioencapsulated in plant cells attenuates pulmonary hypertension.

Science.gov (United States)

Shenoy, Vinayak; Kwon, Kwang-Chul; Rathinasabapathy, Anandharajan; Lin, Shina; Jin, Guiying; Song, Chunjuan; Shil, Pollob; Nair, Anand; Qi, Yanfei; Li, Qiuhong; Francis, Joseph; Katovich, Michael J; Daniell, Henry; Raizada, Mohan K

2014-12-01

Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics. © 2014 American Heart Association, Inc.

Molecular buckets: cyclodextrins for oral cancer therapy

OpenAIRE

Calleja, P. (Patricia); Huarte, J. (Judit); Agüeros, M. (Maite); Ruiz-Gaton, L. (Luisa); Espuelas, S. (Socorro); Irache, J.M. (Juan Manuel)

2012-01-01

The oral route is preferred by patients for drug administration due to its convenience, resulting in improved compliance. Unfortunately, for a number of drugs (e.g., anticancer drugs), this route of administration remains a challenge. Oral chemotherapy may be an attractive option and especially appropriate for chronic treatment of cancer. However, this route of administration is particularly complicated for the administration of anticancer drugs ascribed to Class IV of the Biopharmaceutical C...

Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

Science.gov (United States)

Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

2011-12-15

Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

Oral administration of Lactococcus lactis-expressing heat shock protein 65 and tandemly repeated IA2P2 prevents type 1 diabetes in NOD mice.

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Liu, Kun-Feng; Liu, Xiao-Rui; Li, Guo-Liang; Lu, Shi-Ping; Jin, Liang; Wu, Jie

2016-06-01

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of insulin-secreting β cells upon autoreactive T cell attack. Oral administration of autoantigens is an attractive approach to treating T1DM, but an effective carrier should be used in order to protect antigens. Lactococcus lactis, a safe engineering strain, was used for this task in the present study. Two recombinant L. lactis expressing protein HSP65-6IA2P2 were used and be investigated the effects and mechanisms against T1DM in NOD mice. Our findings demonstrate that recombinant L. lactis strains can successfully both deliver antigens to intestinal mucosa and maintain the epitopes for a long time in NOD mice. Oral administration of recombinant L. lactis could prevent hyperglycemia, improve glucose tolerance, and reduce insulitis by inhibiting antigen-specific proliferation of T cells, augmenting regulatory immune reactions, and balancing ratios of Th17/Tregs and Th1/Th2. These results prove that orally administrated L. lactis expressing HSP65-6IA2P2 is an effective approach for the prevention of T1DM in NOD mice. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

A multigenerational family study of oral and hand motor sequencing ability provides evidence for a familial speech sound disorder subtype

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Peter, Beate; Raskind, Wendy H.

2011-01-01

Purpose To evaluate phenotypic expressions of speech sound disorder (SSD) in multigenerational families with evidence of familial forms of SSD. Method Members of five multigenerational families (N = 36) produced rapid sequences of monosyllables and disyllables and tapped computer keys with repetitive and alternating movements. Results Measures of repetitive and alternating motor speed were correlated within and between the two motor systems. Repetitive and alternating motor speeds increased in children and decreased in adults as a function of age. In two families with children who had severe speech deficits consistent with disrupted praxis, slowed alternating, but not repetitive, oral movements characterized most of the affected children and adults with a history of SSD, and slowed alternating hand movements were seen in some of the biologically related participants as well. Conclusion Results are consistent with a familial motor-based SSD subtype with incomplete penetrance, motivating new clinical questions about motor-based intervention not only in the oral but also the limb system. PMID:21909176

Disposition Kinetics of Amoxicillin in Healthy, Hepatopathic and Nephropathic Conditions in Chicken after Single Oral Administration

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Moloy Kumar Bhar

2010-12-01

Full Text Available Fifteen broiler chickens (COBB 400 of 42 days of age weighing 1.8 to 2.0 kg were equally divided into 3 groups, each consisting of 5 birds. Hepatopathy was induced by oral administration of paracetamol while nephropathy was induced by intravenous administration of uranyl nitrate. Kinetic study was investigated in healthy, hepatopathic and nephropathic birds following single oral administration of amoxicillin at 40 mg kg-1. Blood samples were collected at different time schedule. Plasma concentrations of amoxicillin in healthy, hepatopathic and nephropathic birds were 41.90 ± 5.59, 9.93 ± 0.76 and 38.75 ± 6.08 µg ml-1, respectively at 1 hr; 15.34 ± 1.99, 18.57 ± 1.66 and 67.40 ± 2.62 µg ml-1, respectively at 4 hr and 2.03 ± 0.28, 15.54 ± 0.82 and 30.63 ± 1.58 µg ml-1, respectively at 24 hr. Maximum plasma concentration was detected at 1 hr in healthy birds (41.90 ± 5.59 µg ml-1 , at 8 hr in hepatopathic birds (23.51 ± 1.64 µg ml-1 and at 4 hr in nephropathic birds (67.40 ± 2.62 µg ml-1. The drug could not be detected in plasma beyond 24 hr in healthy, 72 hr in both hepatopathic and nephropathic birds. The concentration of amoxicillin was significantly (P < 0.01 higher in most of the samples of hepatopathic and nephropathic birds compared to healthy birds. Significant higher values (P < 0.01 of t1/2 K, AUC, and MRT and lower values of K and ClB in the hepatopathic and nephropathic birds in comparison to healthy birds were observed.

SYNCHRONOUS CMC, WORKING MEMORY, AND L2 ORAL PROFICIENCY DEVELOPMENT

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J. Scott Payne

2005-09-01

Full Text Available Recently a number of quasi-experimental studies have investigated the potential of a cross-modality transfer of second language competency between real-time, conversational exchange via text and speech (Abrams, 2003; Beauvious, 1998; Kost, 2004; Payne & Whitney, 2002. Payne and Whitney employed Levelt's (1989 model of language production and concepts from working memory as a rationale for a hypothesized connection between synchronous computer-mediated communication (SCMC and second language (L2 speech and as a basis for predicting the differential contributions of SCMC to the L2 oral proficiency development.This study extends the psycholinguistic framework reported in Payne and Whitney (2002 with discourse and corpus analytic techniques to explore how individual differences in working memory capacity may affect the frequency of repetition and other patterns of language use in chatroom discourse. Working memory capacity was measured by a reading span and nonword repetition test. Oral proficiency was measured with a speaking task that solicited a 5-minute speech sample and was scored based on a holistic scale. The data collected from 20 chat sessions were analyzed for occurrences of repetition and relexicalization, as well as language output measures. Findings suggest a connection between working memory and language output as measured in this study.

Optical imaging of absorption and distribution of RITC-SiO2 nanoparticles after oral administration

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Lee CM

2014-12-01

Full Text Available Chang-Moon Lee,1 Tai Kyoung Lee,2–5 Dae-Ik Kim,1,6 Yu-Ri Kim,7 Meyoung-Kon Kim,7 Hwan-Jeong Jeong,2–5 Myung-Hee Sohn,2–5 Seok Tae Lim2–5 1Department of Biomedical Engineering, Chonnam National University, Yeosu, Jeollanam-Do, Republic of Korea; 2Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 3Cyclotron Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 4Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 5Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 6School of Electrical, Electronic Communication, and Computer Engineering, Chonnam National University, Yeosu, Jeollanam-Do, Republic of Korea; 7Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seounbuk-Gu, Seoul, Republic of Korea Purpose: In this study, we investigated the absorption and distribution of rhodamine B isothiocyanate (RITC-incorporated silica oxide nanoparticles(SiNPs (RITC-SiNPs after oral exposure, by conducting optical imaging, with a focus on tracking the movement of RITC-SiNPs of different particle size and surface charge. Methods: RITC-SiNPs (20 or 100 nm; positively or negatively charged were used to avoid the dissociation of a fluorescent dye from nanoparticles via spontaneous or enzyme-catalyzed reactions in vivo. The changes in the nanoparticle sizes and shapes were investigated in an HCl solution for 6 hours. RITC-SiNPs were orally administered to healthy nude mice at a dose of 100 mg/kg. Optical imaging studies were performed at 2, 4, and 6 hours after oral administration. The mice were sacrificed at 2, 4, 6, and 10 hours post-administration, and ex vivo imaging studies were performed

Oral transmucosal drug delivery for pediatric use.

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Lam, Jenny K W; Xu, Yingying; Worsley, Alan; Wong, Ian C K

2014-06-01

The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed. © 2013.

Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus).

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Black, L A; Krockenberger, M B; Kimble, B; Govendir, M

2014-02-01

Clinically normal koalas (n = 12) received a single dose of 10 mg/kg fluconazole orally (p.o.; n = 6) or intravenously (i.v.; n = 6). Serial plasma samples were collected over 24 h, and fluconazole concentrations were determined using a validated HPLC assay. A noncompartmental pharmacokinetic analysis was performed. Following i.v. administration, median (range) plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.31 (0.11-0.55) L/h/kg and 0.92 (0.38-1.40) L/kg, respectively. The elimination half-life (t1/2 ) was much shorter than in many species (i.v.: median 2.25, range 0.98-6.51 h; p.o.: 4.69, range 2.47-8.01 h), and oral bioavailability was low and variable (median 0.53, range 0.20-0.97). Absorption rate-limited disposition was evident. Plasma protein binding was 39.5 ± 3.5%. Although fluconazole volume of distribution (Varea ) displayed an allometric relationship with other mammals, CL and t1/2 did not. Allometrically scaled values were approximately sevenfold lower (CL) and sixfold higher (t1/2 ) than observed values, highlighting flaws associated with this technique in physiologically distinct species. On the basis of fAUC/MIC pharmacodynamic targets, fluconazole is predicted to be ineffective against Cryptococcus gattii in the koala as a sole therapeutic agent administered at 10 mg/kg p.o. every 12 h. © 2013 John Wiley & Sons Ltd.

31 CFR 103.83 - Oral communications.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Oral communications. 103.83 Section... AND REPORTING OF CURRENCY AND FOREIGN TRANSACTIONS Administrative Rulings § 103.83 Oral communications... response to oral requests. Oral opinions or advice by Treasury, the Customs Service, the Internal Revenue...

A double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]-basimglurant and absolute bioavailability after oral administration and concomitant intravenous microdose administration of [13C6]-labeled basimglurant in humans.

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Guerini, Elena; Schadt, Simone; Greig, Gerard; Haas, Ruth; Husser, Christophe; Zell, Manfred; Funk, Christoph; Hartung, Thomas; Gloge, Andreas; Mallalieu, Navita L

2017-02-01

1. The emerging technique of employing intravenous microdose administration of an isotope tracer concomitantly with an [ 14 C]-labeled oral dose was used to characterize the disposition and absolute bioavailability of a novel metabotropic glutamate 5 (mGlu5) receptor antagonist under clinical development for major depressive disorder (MDD). 2. Six healthy volunteers received a single 1 mg [ 12 C/ 14 C]-basimglurant (2.22 MBq) oral dose and a concomitant i.v. tracer dose of 100 μg of [ 13 C 6 ]-basimglurant. Concentrations of [ 12 C]-basimglurant and the stable isotope [ 13 C 6 ]-basimglurant were determined in plasma by a specific LC/MS-MS method. Total [ 14 C] radioactivity was determined in whole blood, plasma, urine and feces by liquid scintillation counting. Metabolic profiling was conducted in plasma, urine, blood cell pellet and feces samples. 3. The mean absolute bioavailability after oral administration (F) of basimglurant was ∼67% (range 45.7-77.7%). The major route of [ 14 C]-radioactivity excretion, primarily in form of metabolites, was in urine (mean recovery 73.4%), with the remainder excreted in feces (mean recovery 26.5%). The median t max for [ 12 C]-basimglurant after the oral administration was 0.71 h (range 0.58-1.00) and the mean terminal half-life was 77.2 ± 38.5 h. Terminal half-life for the [ 14 C]-basimglurant was 178 h indicating presence of metabolites with a longer terminal half-life. Five metabolites were identified with M1-Glucuronide as major and the others in trace amounts. There was minimal binding of drug to RBCs. IV pharmacokinetics was characterized with a mean ± SD CL of 11.8 ± 7.4 mL/h and a Vss of 677 ± 229 L. 4. The double-tracer technique used in this study allowed to simultaneously characterize the absolute bioavailability and disposition characteristics of the new oral molecular entity in a single study.

Repetitive Questioning Exasperates Caregivers

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R. C. Hamdy MD

2018-01-01

Full Text Available Repetitive questioning is due to an impaired episodic memory and is a frequent, often presenting, problem in patients with Alzheimer’s disease (amnestic type. It is due to the patients’ difficulties learning new information, retaining it, and recalling it, and is often aggravated by a poor attention span and easy distractibility. A number of factors may trigger and maintain repetitive questioning. Caregivers should try to identify and address these triggers. In the case discussion presented, it is due to the patient’s concerns about her and her family’s safety triggered by watching a particularly violent movie aired on TV. What went wrong in the patient/caregiver interaction and how it could have been avoided or averted are explored. Also reviewed are the impact of repetitive questioning, the challenges it raises for caregivers, and some effective intervention strategies that may be useful to diffuse the angst that caregivers experience with repetitive questioning.

Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration.

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Nicholas A Young

Full Text Available Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

Biodistribution study with combined administration of BPA and BSH for BNCT in the hamster cheek pouch oral cancer model

International Nuclear Information System (INIS)

Garabalino, M A; Heber, E M; Monti Hughes, A; Pzzi, E C C; Molinari, A J; Niggg, D W; Bauer, W; Trivillin, V A; Schwint, A E

2012-01-01

We previously proved the therapeutic potential of the chemically non-selective boron compound decahydrodecaborate (GB-10) as a stand-alone boron carrier for BNCT in the hamster cheek pouch oral cancer model with no toxic effects in normal or precancerous tissue. Although GB-10 is not taken up selectively by oral tumor tissue, selective tumor lethality would result from selective aberrant tumor blood vessel damage. Furthermore, BNCT efficacy was enhanced when GB-10 and boronophenylalanine (BPA) were administered jointly. The fact that sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically as a stand-alone boron agent for BNCT of brain tumors and in combination with BPA for recurrent head and neck malignancies makes it a particularly interesting boron compound to explore. Based on the working hypothesis that BSH would conceivably behave similarly to GB-10 in oral cancer, we previously performed biodistribution studies with BSH alone in the hamster cheek pouch oral cancer model. The aim of the present study was to perform biodistribution studies of BSH + BPA administered jointly in the hamster cheek pouch oral cancer model as a starting point to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology and optimize therapeutic efficacy. The right cheek pouch of Syrian hamsters was subjected to topical administration of a carcinogen twice a week for 12 weeks. Once the exophytic tumors, i.e. squamous cell carcinomas, had developed, the animals were used for biodistribution studies with BSH + BPA. Three administration protocols with different proportions of each of the compounds were assessed: 1. BSH, 50 mg 10 B/kg, iv + BPA, 15.5 mg 10 B/kg, ip; 2. BSH, 34.5 mg 10 B/kg, iv + BPA, 31 mg 10 B/kg, ip; 3. BSH, 20 mg 10 B/kg, iv + BPA, 46.5 mg 10 B/kg, ip. Groups of animals were euthanized 4 h after the administration of BSH and 3 h after the administration of BPA. Samples of blood, tumor, precancerous and normal pouch and other tissues with

Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

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Ge, Zhaohui; Liang, Qionglin; Wang, Yiming; Luo, Guoan

2014-01-01

Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters C max and AUC0–∞ (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint. PMID:25610474

Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

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Zhaohui Ge

2014-01-01

Full Text Available Pharmacokinetic characters of rhynchophylline (RIN, gastrodin (GAS, and gastrodigenin (p-hydroxybenzyl alcohol, HBA were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT and gouteng (rhynchophylla alkaloids, EPG. At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters Cmax and Cmax⁡ and AUC0–∞ (P<0.05 were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint.

High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfontiamine.

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Frank, T; Bitsch, R; Maiwald, J; Stein, G

2000-06-01

The influence of either orally administered S-benzoylthiamine-O-monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was tested in a randomised, two-group comparison study in 20 end-stage renal disease (ESRD) patients. Main outcome measures were the pharmacokinetics of thiamine diphosphate (TDP) in blood, the in vitro erythrocyte transketolase activity, its activation coefficient (alpha-ETK) and the TDP concentration in erythrocytes. After ingestion of a single dose of either 100 mg thiamine nitrate (corresponding to 305 micromol thiamine) or 100 mg benfotiamine (corresponding to 214 micromol thiamine), the blood levels of thiamine phosphate esters were analysed by means of high-performance liquid chromatography for a 24-h period. The TDP concentration in erythrocytes was calculated using the haematocrit and TDP concentration in blood. Erythrocyte transketolase activity and alpha-ETK were measured before and 10 h after administration. The pharmacokinetics of TDP in blood were compared with healthy subjects of other studies retrieved from database query. Regarding the blood concentrations of TDP, the patients with ESRD had a 4.3 times higher area under the concentration time curve after benfotiamine administration than after thiamine nitrate. After benfotiamine administration, the peak plasma concentration of TDP exceeded that in healthy subjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration in erythrocytes increased from 158.7+/-30.9 ng/ml initially to 325.8+/-50.9 ng/ml after administration of benfotiamine and from 166.2+/-51.9 ng/ml to 200.5+/-50.0 ng/ml after thiamine nitrate administration. The ratio between the maximum erythrocyte TDP concentration and basal concentration was 2.66+/-0.6 in the benfotiamine group and 1.44+/-0.2 in the group receiving thiamine nitrate (P benfotiamine intake (P = 0.02) and from 3.71+/-0.8 microkat/l to 4.02+/-0.7 microkat/l after thiamine nitrate intake (P = 0.08). Likewise, alpha

Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs.

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Messenger, Kristen M; Hopfensperger, Marie; Knych, Heather K; Papich, Mark G

2016-04-01

To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. 12 healthy adult dogs. In phase 1, detomidine was administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m(2)) or detomidine gel by OTM administration (0.5 mg/m(2)), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

Positive Foci of Glutathione S‐Transferase Placental Form in the Liver of Rats Given Furfural by Oral Administration

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Shimizu, Akio; Nakamura, Yoshiyasu; Harada, Masaoki; Ono, Tetsuo; Sato, Kiyomi; Inoue, Tohru; Kanisawa, Masayoshi

1989-01-01

We observed GST‐P‐positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural‐containing diet (20–30 rag/kg diet) for 15–150 days, and killed 14 days after terminating furfural feeding. Immuno‐histochemical investigation of GST‐P‐positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural‐induced cirrhosis on chemical hepatocarcino‐genesis. PMID:2507483

Effect of flavonoid-containing extracts on the growth of transplanted sarcoma 45, peripheral blood and bone marrow condition after oral and intramuscular administration in rats

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Nikita A. Navolokin

2017-08-01

Full Text Available Objective — Discovery of the apoptosis-inducing effects of flavonoid vagonin allowed to make an assumption of existence of similar effect in others flavonoids. This study of the effects of extracts from Gratīola officinālis, Helichrýsum arenárium and diploid forms of Zea mays on bone marrow and blood leucocytes at intramuscular and oral administration was carried out on rats bearing sarcoma 45. Earlier, the apoptosis-inducing effects were detected for these extracts but the toxic effects of extracts on blood and bone marrow have not been studied. Therefore, the aim of this study was to investigate the effects of these extracts on white blood cell count and bone marrow morphology. Material and Methods — The experiments were carried out on 48 male Wistar albino rats according to University's Animal Ethics Committee (Protocol № 13, 2011, Saratov, Russia and the relevant national agency regulating experiments on animals. We evaluated white blood cell count and bone marrow morphology in animals after oral and intramuscular administration of extracts. A growth rate of tumor was also ranked. Results — Oral and intramuscular administration of extracts from flavonoid-containing plants Zea mays and Gratīola officinālis causes normalization of myelocytic germ parameters in bone marrow of tumor-bearing rats and increase of lymphocyte percent in white blood cell count of blood and myelogram. Conclusion — Absence of toxic effects and normalization of myelocytic germ parameters in bone marrow of tumor-bearing rats after oral and intramuscular administration of extracts from flavonoid-containing plants Zea mays and Gratīola officinālis allows to recommend further study of the antitumor effect of these extracts.

Effect of intermittent oral administration of ponazuril on experimental Sarcocystis neurona infection of horses.

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Mackay, Robert J; Tanhauser, Susan T; Gillis, Karen D; Mayhew, Ian G; Kennedy, Tom J

2008-03-01

To evaluate the effect of intermittent oral administration of ponazuril on immunoconversion against Sarcocystis neurona in horses inoculated intragastrically with S neurona sporocysts. 20 healthy horses that were seronegative for S neurona-specific IgG. 5 control horses were neither inoculated with sporocysts nor treated. Other horses (5 horses/group) each received 612,500 S neurona sporocysts via nasogastric tube (day 0) and were not treated or were administered ponazuril (20 mg/kg, PO) every 7 days (beginning on day 5) or every 14 days (beginning on day 12) for 12 weeks. Blood and CSF samples were collected on day - 1 and then every 14 days after challenge for western blot assessment of immunoconversion. Clinical signs of equine protozoal myeloencephalitis (EPM) were monitored, and tissues were examined histologically after euthanasia. Sera from all challenged horses yielded positive western blot results within 56 days. Immunoconversion in CSF was detected in only 2 of 5 horses that were treated weekly; all other challenged horses immunoconverted within 84 days. Weekly administration of ponazuril significantly reduced the antibody response against the S neurona 17-kd antigen in CSF. Neurologic signs consistent with EPM did not develop in any group; likewise, histologic examination of CNS tissue did not reveal protozoa or consistent degenerative or inflammatory changes. Administration of ponazuril every 7 days, but not every 14 days, significantly decreased intrathecal anti-S neurona antibody responses in horses inoculated with S neurona sporocysts. Protocols involving intermittent administration of ponazuril may have application in prevention of EPM.

Computer-Related Repetitive Stress Injuries

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... Staying Safe Videos for Educators Search English Español Computer-Related Repetitive Stress Injuries KidsHealth / For Parents / Computer-Related Repetitive Stress Injuries What's in this article? ...

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

DEFF Research Database (Denmark)

Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún

2017-01-01

The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single...... bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit....

Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain.

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Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

2005-09-01

Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (degrees C), as well as suprathreshold tonic heat pain intensity (46.5 degrees C for 1 min) measured by 0-10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI -8.8, 42.8), P = 0.19), pressure (2.2 mmHg (-28.7, 33.2), P = 0.89) and heat (-0.3 degrees C (-1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities -0.4 NPS units (95% CI -1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the 'weak' opioid-treated subgroup and the 'strong' opioid-treated subgroup again revealed insignificant results. These results suggest that the administration of 'commonly used' dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients

Immunization with r-Lactococcus lactis expressing outer membrane protein A of Shigella dysenteriae type-1: evaluation of oral and intranasal route of administration.

Science.gov (United States)

Yagnik, B; Sharma, D; Padh, H; Desai, P

2017-02-01

To evaluate the comparative immunogenic potential of food grade Lactococcus lactis expressing outer membrane protein A (OmpA) of Shigella dysenteriae type-1 (SD-1) when administered either orally or intranasally. OmpA of SD-1 was cloned and expressed first in Escherichia coli and then in L. lactis. Presence of recombinant gene was confirmed by restriction enzyme digestion and immunoblot analysis. Using immobilized metal affinity chromatography, OmpA was purified from recombinant E. coliBL21 (DE3) and subcutaneously administered in BALB/c mice. Detection of OmpA-specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA) confirmed the immunogenicity of OmpA. In order to establish r-L. lactis as a mucosal delivery vehicle, it was administered orally and nasally in BALB/c mice. Serum IgG and faecal IgA were assessed through ELISA to compare the relative potential of immunization routes and immunogenic potential of r-L. lactis. Immunization via the oral route proved superior to intranasal exposure. Recombinant L. lactis expressing OmpA of SD-1 was found to be immunogenic. Oral administration of r-L. lactis elicited higher systemic and mucosal immune response when compared with the nasal route. Using food grade recombinant L. lactis has implications in the development of a prophylactic against multidrug-resistant Shigella, which can be used as a prospective vaccine candidate. Evaluating mucosal routes of immunization demonstrated that the oral route of administration elicited better immune response against OmpA of Shigella. © 2016 The Society for Applied Microbiology.

Alginate Microencapsulation for Oral Immunisation of Finfish: Release Characteristics, Ex Vivo Intestinal Uptake and In Vivo Administration in Atlantic Salmon, Salmo salar L.

Science.gov (United States)

Ghosh, Bikramjit; Nowak, Barbara F; Bridle, Andrew R

2015-12-01

This study examined the feasibility of alginate microcapsules manufactured using a low-impact technology and reagents to protect orally delivered immunogens for use as immunoprophylactics for fish. Physical characteristics and protein release kinetics of the microcapsules were examined at different pH and temperature levels using a microencapsulated model protein, bovine serum albumin (BSA). Impact of the microencapsulation process on contents was determined by analysing change in bioactivity of microencapsulated lysozyme. Feasibility of the method for oral immunoprophylaxis of finfish was assessed using FITC-labelled microcapsules. These were applied to distal intestinal explants of Atlantic salmon (Salmo salar) to investigate uptake ex vivo. Systemic distribution of microcapsules was investigated by oral administration of FITC-labelled microcapsules to Atlantic salmon fry by incorporating into feed. The microcapsules produced were structurally robust and retained surface integrity, with a modal size distribution of 250-750 nm and a tendency to aggregate. Entrapment efficiency of microencapsulation was 51.2 % for BSA and 43.2 % in the case of lysozyme. Microcapsules demonstrated controlled release of protein, which increased with increasing pH or temperature, and the process had no significant negative effect on bioactivity of lysozyme. Uptake of fluorescent-labelled microcapsules was clearly demonstrated by intestinal explants over a 24-h period. Evidence of microcapsules was found in the intestine, spleen, kidney and liver of fry following oral administration. Amenability of the microcapsules to intestinal uptake and distribution reinforced the strong potential for use of this microencapsulation method in oral immunoprophylaxis of finfish using sensitive immunogenic substances.

The role of short-term memory impairment in nonword repetition, real word repetition, and nonword decoding: A case study.

Science.gov (United States)

Peter, Beate

2018-01-01

In a companion study, adults with dyslexia and adults with a probable history of childhood apraxia of speech showed evidence of difficulty with processing sequential information during nonword repetition, multisyllabic real word repetition and nonword decoding. Results suggested that some errors arose in visual encoding during nonword reading, all levels of processing but especially short-term memory storage/retrieval during nonword repetition, and motor planning and programming during complex real word repetition. To further investigate the role of short-term memory, a participant with short-term memory impairment (MI) was recruited. MI was confirmed with poor performance during a sentence repetition and three nonword repetition tasks, all of which have a high short-term memory load, whereas typical performance was observed during tests of reading, spelling, and static verbal knowledge, all with low short-term memory loads. Experimental results show error-free performance during multisyllabic real word repetition but high counts of sequence errors, especially migrations and assimilations, during nonword repetition, supporting short-term memory as a locus of sequential processing deficit during nonword repetition. Results are also consistent with the hypothesis that during complex real word repetition, short-term memory is bypassed as the word is recognized and retrieved from long-term memory prior to producing the word.

Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

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Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R; Murray, Jeannie A; Barnes, Allan J; Huestis, Marilyn A

2013-09-01

Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

[Purification of arsenic-binding proteins in hamster plasma after oral administration of arsenite].

Science.gov (United States)

Wang, Wenwen; Zhang, Min; Li, Chunhui; Qin, Yingjie; Hua, Naranmandura

2013-01-01

To purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)). Arsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step. The three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE. The three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

Enhancement of brain serotonin by long term oral administration of tryptophan produces no effect on food intake

International Nuclear Information System (INIS)

Haider, S.; Akhtar, N.; Kidwai, I.M.; Haleem, D.J.

1999-01-01

L-tryptophan (TRP) is widely used to enhance serotonin mediate brain functions. In the Present study effects of oral administration of TRP (100mg/kg) daily for 5 weeks, were investigated on the food intake, growth rate and brain indole amine metabolism in young rats. TRP ingestion significantly increased growth rate but did not alter food intake in rats. The levels of TRP and 5-hydroxytryptamine (5-HT) were higher in the hypothalamus of TRP treated rats. Increases of 5-hydroxyindole acetic acid (5-HIAA) were hot significant. TRP, 5-HT and 5-HIAA all increased in the rest of the brain of TRP treated rats. The present study shows that long term TRP administration thorough increases brain 5-ht metabolism and turnover but functional responses to 5-ht are not necessarily increases. (author)

Which route of antibiotic administration should be used for third molar surgery? A split-mouth study to compare intramuscular and oral intake.

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Crincoli, V; Di Comite, M; Di Bisceglie, M B; Petruzzi, M; Fatone, L; De Biase, C; Tecco, S; Festa, F

2014-01-01

To compare the effectiveness of two different routes of antibiotic administration in preventing septic complications in patients undergoing third molar extraction. Twenty-four healthy patients requiring bilateral surgical removal of impacted mandibular third molars were successfully enrolled for this study. Depth of impaction, angulation, and relationship of the lower third molars with the mandibular branch had to be overlapping on both sides. A split-mouth design was chosen, so each patient underwent both the first and second surgeries, having for each extraction a different antibiotic route of administration. The second extraction was carried out 1 month later. To compare the effects of the two routes of antibiotic administration, inflammatory parameters, such as edema, trismus, pain, fever, dysphagia and lymphadenopathy were evaluated 2 and 7 days after surgery. Side effects of each therapy were evaluated 48 h after surgery. Oral and intramuscular antibiotic therapies overlap in preventing post-operative complications in dental surgery (p>0.05), even if the oral intake, seems to promote the onset of significant gastrointestinal disorders (p=0.003). This study could help dentists in their ordinary practice to choose the right route of antibiotic administration in the third molar surgery. At the same effectiveness, the higher cost and the minor compliance of the patient seem not to justify a routine antibiotic intramuscular therapy, reserving it for patients with gastrointestinal disorders.

Oral controlled release drug delivery system and Characterization of oral tablets; A review

Directory of Open Access Journals (Sweden)

Muhammad Zaman

2016-01-01

Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

Synergy Repetition Training versus Task Repetition Training in Acquiring New Skill.

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Patel, Vrajeshri; Craig, Jamie; Schumacher, Michelle; Burns, Martin K; Florescu, Ionut; Vinjamuri, Ramana

2017-01-01

Traditionally, repetitive practice of a task is used to learn a new skill, exhibiting as immediately improved performance. Research suggests, however, that a more experience-based rather than exposure-based training protocol may allow for better transference of the skill to related tasks. In synergy-based motor control theory, fundamental motor skills, such as hand grasping, are represented with a synergy subspace that captures essential motor patterns. In this study, we propose that motor-skill learning through synergy-based mechanisms may provide advantages over traditional task repetition learning. A new task was designed to highlight the range of motion and dexterity of the human hand. Two separate training strategies were tested in healthy subjects: task repetition training and synergy training versus a control. All three groups showed improvements when retested on the same task. When tested on a similar, but different set of tasks, only the synergy group showed improvements in accuracy (9.27% increase) compared to the repetition (3.24% decline) and control (3.22% decline) groups. A kinematic analysis revealed that although joint angular peak velocities decreased, timing benefits stemmed from the initial feed-forward portion of the task (reaction time). Accuracy improvements may have derived from general improved coordination among the four involved fingers. These preliminary results warrant further investigation of synergy-based motor training in healthy individuals, as well as in individuals undergoing hand-based rehabilitative therapy.

Enhanced bioavailability of opiates after intratracheal administration

International Nuclear Information System (INIS)

Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

1986-01-01

Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities [codeine (84%), ethylmorphine (100%), and morphine (87%)] of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability

Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

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Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

2017-09-01

Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

Detection and pharmacokinetics of grapiprant following oral administration to exercised Thoroughbred horses.

Science.gov (United States)

Knych, Heather K; Seminoff, Kelsey; McKemie, Dan S

2018-03-25

Traditional therapeutic options for the treatment of lameness associated with inflammation in performance horses include administration of cyclooxygenase enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use of these drugs can adversely impact the health of the horse, anti-inflammatories with a more favorable safety profile are warranted. Grapiprant is a newly approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and safety in other species and which may be a valuable alternative to traditional NSAIDs used in the horse. The objectives of the current study were to describe drug concentrations and the pharmacokinetics of grapiprant in exercised Thoroughbred horses and to develop an analytical method that could be used to regulate its use in performance horses. To that end, grapiprant, at a dose of 2 mg/kg was administered orally to 12 exercised Thoroughbred horses. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry. Grapiprant remained above the LOQ of the assay (0.005 ng/mL) in serum for 72 hours post administration and urine concentrations were above the LOQ until 96 hours. The C max , T max and elimination half-life were 31.9 ± 13.9 ng/mL, 1.5 ± 0.5 hours and 5.86 ± 2.46 hours, respectively. The drug was well tolerated in all horses at a dose of 2 mg/kg. Results support further study of this compound in horses. Furthermore, development of a highly sensitive analytical method demonstrate that this compound can be adequately regulated in performance horses. Copyright © 2018 John Wiley & Sons, Ltd.

Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes

DEFF Research Database (Denmark)

Hostrup, Morten; Kalsen, Anders; Auchenberg, Michael

2016-01-01

Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max : 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were....... deltoideus were measured, followed by three repeated Wingate tests. Exercise performance at 110% of VO2max was determined on a bike ergometer. Acute administration of salbutamol increased peak power during first Wingate test by 4.1 ± 1.7% (P ....05) peak power during first and second Wingate test by 6.4 ± 2.0 and 4.2 ± 1.0%. Neither acute nor 2-week administration of salbutamol had any effect on MVC, exercise performance at 110% of VO2max or on isometric endurance. No differences were observed in the placebo group. In conclusion, salbutamol...

Evaluation of an oral transmucosal administration of dexmedetomidine-butorphanol and dexmedetomidine-methadone in dogs.

Directory of Open Access Journals (Sweden)

Daniela Gioeni

2017-05-01

Full Text Available Oral transmucosal (OTM delivery is a simple and painless method for sedative administration in veterinary medicine and allows a rapid absorption without a first-pass metabolism by the liver (Porters et al. 2014.. OTM is particularly useful in aggressive animals (Santos et al. 2010. The aim of this study is to evaluate the efficacy of the OTM route in dogs for sedative administration in comparison with intramuscular (IM injection. 24 mix-bread dogs undergoing soft tissue surgery or diagnostic procedures were randomly divided in 4 groups (n = 6: two groups received OTM administration of dexmedetomidine (10 µg/kg-1 together with butorphanol (0.2 mg/kg-1, BTF-OTM group or methadone (0.2mg/kg-1, MTD-OTM group; two groups received intramuscular (IM administration of dexmedetomidine (5 µg/kg-1 together with butorphanol (0.2 m/kg-1, BTF-IM group or methadone (0.2 mg/kg-1, MTD-IM. Heart rate (HR, respiratory rate (RR, sedation score (Gruney et al. 2009 and side effects were recorded 10 (T10, 20 (T20 and 30 (T30 minutes after premedication. Induction was performed at T30 with titrate-to-effect propofol administration and the dosage required was recorded. At each time point BTF-IM group showed a statistically lower HR compared to BTF-OTM; RR was statistically lower at T10 in MTD-OTM group (21.33 ± 8.64 pm compared to BTF-OTM (46.16 ± 17.98; Dogs in group MTD-IM reached a higher sedation scores at each time point compared to MTD-OTM. The induction dose of propofol appears comparable among groups. Marked vasoconstriction was observed after OTM administration, as probably related to α2-agonists use. Emesis and sialorrhea occurred in two subjects of MTD-OTM group while only one dog presented sialorrhea in BTF-OTM group. In conclusion, OTM administration appears effective and easy to perform; it takes a longer time to achieve a good sedation score, probably related to a gradual absorption of drugs that also leads to a more gradual hemodynamic effects.

Pharmacokinetics of repeated oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Souza, Marcy J; Gerhardt, Lillian; Cox, Sherry

2013-07-01

To determine the pharmacokinetics of tramadol hydrochloride (30 mg/kg) following twice-daily oral administration in Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots. Tramadol hydrochloride was administered to each parrot at a dosage of 30 mg/kg, PO, every 12 hours for 5 days. Blood samples were collected just prior to dose 2 on the first day of administration (day 1) and 5 minutes before and 10, 20, 30, 60, 90, 180, 360, and 720 minutes after the morning dose was given on day 5. Plasma was harvested from blood samples and analyzed by high-performance liquid chromatography. Degree of sedation was evaluated in each parrot throughout the study. No changes in the parrots' behavior were observed. Twelve hours after the first dose was administered, mean ± SD concentrations of tramadol and its only active metabolite M1 (O-desmethyltramadol) were 53 ± 57 ng/mL and 6 ± 6 ng/mL, respectively. At steady state following 4.5 days of twice-daily administration, the mean half-lives for plasma tramadol and M1 concentrations were 2.92 ± 0.78 hours and 2.14 ± 0.07 hours, respectively. On day 5 of tramadol administration, plasma concentrations remained in the therapeutic range for approximately 6 hours. Other tramadol metabolites (M2, M4, and M5) were also present. On the basis of these results and modeling of the data, tramadol at a dosage of 30 mg/kg, PO, will likely need to be administered every 6 to 8 hours to maintain therapeutic plasma concentrations in Hispaniolan Amazon parrots.

Colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai in patients with ulcerative colitis: a report of two cases.

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Kondo, Satoru; Araki, Toshimitsu; Okita, Yoshiki; Yamamoto, Akira; Hamada, Yasuhiko; Katsurahara, Masaki; Horiki, Noriyuki; Nakamura, Misaki; Shimoyama, Takahiro; Yamamoto, Takayuki; Takei, Yoshiyuki; Kusunoki, Masato

2018-03-16

Orally administered Qing-dai, called indigo naturalis in Latin, is reportedly useful for the treatment of ulcerative colitis. We herein describe two patients with ulcerative colitis who developed colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai. In Case 1, a 35-year-old man developed colitis similar to ischemic colitis with bloody stool that recurred each time he ingested Qing-dai. He had no signs of recurrence upon withdrawal of Qing-dai. In Case 2, a 43-year-old woman underwent ileocecal resection for treatment of an intussusception 2 months after beginning oral administration of Qing-dai. Edema and congestion but no ulceration were present in the mucosa of the resected specimen. Both patients exhibited abdominal pain with bloody diarrhea, and abdominal computed tomography showed marked wall edema affecting an extensive portion of the large bowel.

Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [13C8]‐evacetrapib as a tracer

Science.gov (United States)

Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G.; Royalty, Jane; Ortega, Demetrio; Pack, Brian W.; Begum, Syeda L.; Annes, William F.; Lin, Qun; Small, David S.

2015-01-01

This open‐label, single‐period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130‐mg evacetrapib oral dose and 4‐h intravenous (IV) infusion of 175 µg [13C8]‐evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [13C8]‐evacetrapib using high‐performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration‐time curve (AUC) from zero to infinity (AUC[0‐∞]) and to the last measureable concentration (AUC[0‐tlast]), were calculated. Bioavailability was calculated as the ratio of least‐squares geometric mean of dose‐normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2–47.6%) for AUC(0‐∞) and 44.3% (90% CI: 41.8–46.9%) for AUC(0‐tlast). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a 13C‐labeled IV microdose tracer at about 1/1000th the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability. PMID:26639670

Evaluation of bowel distension and bowel wall visualization according to patient positions during administration of oral contrast media for CT enterography.

Science.gov (United States)

Lee, Seul Bi; Kim, Seung Ho; Son, Jung Hee; Baik, Ji Yeon

2017-12-01

To compare small bowel distension and bowel wall visualization among three different patients' positions (supine, sitting and right decubitus) during administration of oral contrast media in preparation for CT enterography (CTE). A total of 150 consecutive patients (104 males and 46 females; mean age 34.6 years, range 15-78 years) who were scheduled to undergo CTE were recruited. Patients were randomly allocated into the three position groups during oral contrast media administration, and there were 50 patients in each group. Two blinded radiologists independently scored the luminal distension and visualization of the bowel wall using a continuous 5-point scale (1: worst and 5: best) at the jejunum and ileum. The Mann-Whitney U test was used to evaluate differences between any two groups among the three positions for bowel distension and wall visualization. For ileal distension, the supine and sitting positions performed better than the right decubitus position [for reader 1, mean: 3.4/3.2/2.9 (hereafter, supine/sitting/right decubitus in order), p = 0.002/0.033; for reader 2, 3.3/3.0/2.6, p 0.05, respectively). For bowel wall visualization, the supine and sitting positions were superior to the right decubitus position for the ileum when scored by one reader (4.0/3.8/3.4, p = 0.001/0.015). Supine and sitting positions during the administration of oral contrast media provided better ileal distension than the right decubitus position in obtaining CTE. Advances in knowledge: The performance of CTE largely depends on adequate luminal distension and wall visualization. As the terminal ileum is the predominant site of small bowel pathology for inflammatory bowel disease, the supine or sitting position would be preferable for patients who are suspected of having small bowel pathology.

Oral administration of kefiran exerts a bifidogenic effect on BALB/c mice intestinal microbiota.

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Hamet, M F; Medrano, M; Pérez, P F; Abraham, A G

2016-01-01

The activity of kefiran, the exopolysaccharide present in kefir grains, was evaluated on intestinal bacterial populations in BALB/c mice. Animals were orally administered with kefiran and Eubacteria, lactobacilli and bifidobacteria populations were monitored in faeces of mice at days 0, 2, 7, 14 and 21. Profiles obtained by Denaturing Gradient Gel Electrophoresis (DGGE) with primers for Eubacteria were compared by principal component analysis and clearly defined clusters, correlating with the time of kefiran consumption, were obtained. Furthermore, profile analysis of PCR products amplified with specific oligonucleotides for bifidobacteria showed an increment in the number of DGGE bands in the groups administered with kefiran. Fluorescent In Situ Hybridisation (FISH) with specific probes for bifidobacteria showed an increment of this population in faeces, in accordance to DGGE results. The bifidobacteria population was also studied on distal colon content after 0, 2 and 7 days of kefiran administration. Analysis of PCR products by DGGE with Eubacteria primers showed an increment in the number and intensity of bands with high GC content of mice administered with kefiran. Sequencing of DGGE bands confirmed that bifidobacteria were one of the bacterial populations modified by kefiran administration. DGGE profiles of PCR amplicons obtained by using Bifidobacterium or Lactobacillus specific primers confirmed that kefiran administration enhances bifidobacteria, however no changes were observed in Lactobacillus populations. The results of the analysis of bifidobacteria populations assessed on different sampling sites in a murine model support the use of this exopolysaccharide as a bifidogenic functional ingredient.

Degradation rate of praziquantel and fenbendazole in rainbow trout following oral administration.

Science.gov (United States)

Soukupova-Markova, Zdenka; Doubkova, Veronika; Marsalek, Petr; Svobodova, Zdenka; Papezikova, Ivana; Lang, Stepan; Navratil, Stanislav; Palikova, Miroslava

2015-01-01

The aim of this study was to evaluate and compare the rate of degradation and elimination of praziquantel and fenbendazole antiparasitics following oral administration to salmonids. In addition, we determine whether the length of the legal withdrawal period is sufficient for complete elimination of antiparasitic residue from the body. The use of these drugs in fish is currently considered off-label and data on degradation are not available for rainbow trout. The model species for this experiment was the rainbow trout (Oncorhynchus mykiss) and praziquantel and fenbendazole were chosen for experimental therapy. Both drugs were administered into the gastrointestinal tract using a stomach tube. Concentrations of fenbendazole and praziquantel were established through high performance liquid chromatography-tandem mass spectrometry. Our results show that concentrations of praziquantel and fenbendazole reach their maximum in the body within 24 hours of administration, with concentrations dropping sharply over the following 24 hours. With one exception, when trace amounts of both substances were found in blood plasma, the drugs were completely degraded and eliminated from the body by the end of the experiment (corresponding to 497.6 degree days). Praziquantel and fenbendazole both show a high rate of degradation and elimination from fish. As both substances were eliminated from the body within the required withdrawal period (i.e. within 500 degree days) they can be safely used based on current knowledge of their therapeutic effect for treating helminth infections.

Transabdominal ultrasonography of the small bowel after oral administration of a non-absorbable anechoic solution: Comparison with barium enteroclysis

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Cittadini, Giuseppe; Giasotto, Veronica; Garlaschi, Giacomo; De Cicco, Enzo; Gallo, Alessandra; Cittadini, Giorgio

2001-03-01

AIM: The aim of this study was to determine if oral administration of a non-absorbable anechoic solution conveys any benefit during abdominal ultrasound (US), with special reference to its accuracy. MATERIALS AND METHODS: Fifty-three adult out-patients scheduled for small bowel barium enema (SBE) were included. The day before SBE all patients underwent abdominal US before and after oral administration of an isotonic non-absorbable electrolyte solution containing polyethylene glycol (PEG-ELS). Sensitivity and specificity were evaluated using SBE as a gold standard. RESULTS: After ingestion of PEG-ELS satisfactory distension of the intestinal lumen was obtained (11-25 mm) with sequential visualization of jejunoileal loops in 30.9 {+-} 17.3 min. In 15 out of 53 cases both US and SBE showed bowel changes characteristic of Crohn's disease. In three out of 53 cases both US and SBE showed neoplasms. In one out of 53 cases US was negative, SBE positive for local nodularity and ulcerations typical of Crohn's disease. In one out of 53 cases US was negative, SBE positive for macronodularity consistent with coeliac disease. In five out of 53 cases US was negative, while SBE was positive for mininodularity expressive of lymphoid hyperplasia. In 28 out of 53 cases both examinations were negative. CONCLUSION: PEG-ELS administration allows a thorough US investigation of the small bowel, with fair sensitivity (72%) and excellent specificity (100%). False negative findings are mainly due to lymphoid hyperplasia, a feature of uncertain significance in adults. Cittadini G. et al.(2001)

Inhibition of rat microsomal lipid peroxidation by the oral administration of D002

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Menéndez R.

2000-01-01

Full Text Available The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS. When D002 (5-100 mg/kg body weight was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46% occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40% and brain (28-44% microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans.

Serum disposition of bovine lactoferrin after oral and anal administration and its proteolytic cleavage by gastric transit in rainbow trout (Oncorhynchus mykiss W.).

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Cecchini, Stefano; Caputo, Anna R

2009-01-01

Several studies have shown an immunomodulatory effect of orally administered bovine lactoferrin (LF) in fish, but the process of digestion was not characterized. In the present study, we investigated the fate of bovine LF after oral and anal administration, and studied the appearance of intact LF in the bloodstream and its proteolytic attack during the gastric transit in rainbow trout (Oncorhynchus mykiss) held at 9 degrees C and 18 degrees C. Data obtained showed the presence of intact bovine LF in the bloodstream only after anal administration in fish held at 18 degrees C and the presence of several peptides derived from bovine LF in the gastric content. Immunoblotting analysis showed that only a part of bovine LF-derived peptides reacted with the applied anti-bovine LF antibody. The concentration of intact bovine LF, after 30 min of administration, in the gastric content of fish reared at 18 degrees C, being extremely low, if any, led us to suspect that the immunoregulatory effect of dietary bovine LF shown in fish by several authors is not due to the intact form but to bioactive fragments, originated by the proteolytic attack during the gastric transit, as demonstrated in higher vertebrates.

Toxicologic evaluation of acute and subacute oral administration of Cucurbita maxima seed extracts to rats and swine.

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de Queiroz-Neto, A; Mataqueiro, M I; Santana, A E; Alessi, A C

1994-06-01

The extract prepared from dried seeds of Cucurbita maxima was administered to rats and pigs. Following a single dose or 4 weeks of daily oral administration, the extract produced no changes in serum glucose, urea, creatinine, total protein, uric acid, GOT, GPT, LDH or blood counts. Urine analysis (urea, uric acid, creatinine, total protein, Na and K), as well as histopathological investigation, showed no abnormalities. These results taken as a whole indicate that the seeds of C. maxima as used in Brazilian folk medicine are not toxic for rats and swine.

Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F 18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies

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Kim, Chulhan; Kim, In Hye; Kim, Seo il; Kim, Young Sang; Kang, Se Hun; Moon, Seung Hwan; Kim, Tae Sung; Kim, Seok ki

2011-01-01

We compared alternative routes for 18F fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice. CRL 1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection. There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans. RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.

Oral Administration of Polymer Hyaluronic Acid Alleviates Symptoms of Knee Osteoarthritis: A Double-Blind, Placebo-Controlled Study over a 12-Month Period

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Tashiro, Toshiyuki; Seino, Satoshi; Sato, Toshihide; Matsuoka, Ryosuke; Masuda, Yasunobu; Fukui, Naoshi

2012-01-01

This study was conducted to investigate the efficacy of oral hyaluronic acid (HA) administration for osteoarthritis (OA) in knee joints. Sixty osteoarthritic subjects (Kellgren-Lawrence grade 2 or 3) were randomly assigned to the HA or placebo group. The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months, while the subjects in the placebo group were given placebo. The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment. The subjects' symptoms were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM) score. The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups. This improvement tended to be more obvious with the HA group, and this trend was more obvious with the subjects aged 70 years or less. For these relatively younger subjects, the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration. Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise. PMID:23226979

Oral Administration of Polymer Hyaluronic Acid Alleviates Symptoms of Knee Osteoarthritis: A Double-Blind, Placebo-Controlled Study over a 12-Month Period

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Toshiyuki Tashiro

2012-01-01

Full Text Available This study was conducted to investigate the efficacy of oral hyaluronic acid (HA administration for osteoarthritis (OA in knee joints. Sixty osteoarthritic subjects (Kellgren-Lawrence grade 2 or 3 were randomly assigned to the HA or placebo group. The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months, while the subjects in the placebo group were given placebo. The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment. The subjects’ symptoms were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM score. The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups. This improvement tended to be more obvious with the HA group, and this trend was more obvious with the subjects aged 70 years or less. For these relatively younger subjects, the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration. Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise.

Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

International Nuclear Information System (INIS)

Gonzalez, S.; Pathak, M.A.; Fitzpatrick, T.B.; Cuevas, J.; Villarrubia, V.G.

1997-01-01

Sunburn, immune suppression, photo-aging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photo-protection, are helpful and can be achieved by topical sun-screening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo immunomodulating properties. Its beneficial photo-protective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photo-protective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photo-protective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.,8±0.59 times and MPD increased 2.75±0.5 and 6.8±1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photo-protection of Langherhans cells by oral as well as topical PL. The observed photo-protective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photo-protection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such photo-therapies. (au)

Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

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Gonzalez, S.; Pathak, M.A.; Fitzpatrick, T.B. [Massachusetts General Hospital, Harvard Medical School, Dept. of Dermatology, Boston, MA (United States); Cuevas, J. [Hospital Universitario de Guadalajara, Dept. of Pathology, Guadalajara (Spain); Villarrubia, V.G. [I.F. Cantabria SA, Medical Dept., Immunology Sect., Madrid (Spain)

1997-12-31

Sunburn, immune suppression, photo-aging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photo-protection, are helpful and can be achieved by topical sun-screening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo immunomodulating properties. Its beneficial photo-protective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photo-protective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photo-protective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.,8{+-}0.59 times and MPD increased 2.75{+-}0.5 and 6.8{+-}1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photo-protection of Langherhans cells by oral as well as topical PL. The observed photo-protective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photo-protection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such photo-therapies. (au). 50 refs.

Some pharmacokinetic indices of oral fluconazole administration to koalas (Phascolarctos cinereus) infected with cryptococcosis.

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Govendir, M; Black, L A; Jobbins, S E; Kimble, B; Malik, R; Krockenberger, M B

2016-08-01

Three asymptomatic koalas serologically positive for cryptococcosis and two symptomatic koalas were treated with 10 mg/kg fluconazole orally, twice daily for at least 2 weeks. The median plasma Cmax and AUC0-8 h for asymptomatic animals were 0.9 μg/mL and 4.9 μg/mL·h, respectively; and for symptomatic animals 3.2 μg/mL and 17.3 μg/mL·h, respectively. An additional symptomatic koala was treated with fluconazole (10 mg/kg twice daily) and a subcutaneous amphotericin B infusion twice weekly. After 2 weeks the fluconazole Cmax was 3.7 μg/mL and the AUC0-8 h was 25.8 μg/mL*h. An additional three koalas were treated with fluconazole 15 mg/kg twice daily for at least 2 weeks, with the same subcutaneous amphotericin protocol co-administered to two of these koalas (Cmax : 5.0 μg/mL; mean AUC0-8 h : 18.1 μg/mL*h). For all koalas, the fluconazole plasma Cmax failed to reach the MIC90 (16 μg/mL) to inhibit C. gattii. Fluconazole administered orally at either 10 or 15 mg/kg twice daily in conjunction with amphotericin is unlikely to attain therapeutic plasma concentrations. Suggestions to improve treatment of systemic cryptococcosis include testing pathogen susceptibility to fluconazole, monitoring plasma fluconazole concentrations, and administration of 20-25 mg/kg fluconazole orally, twice daily, with an amphotericin subcutaneous infusion twice weekly. © 2015 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Repetitive Questioning II

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R. C. Hamdy MD

2018-02-01

Full Text Available Repetitive questioning is a major problem for caregivers, particularly taxing if they are unable to recognize and understand the reasons why their loved one keeps asking the same question over and over again. Caregivers may be tempted to believe that the patient does not even try to remember the answer given or is just getting obnoxious. This is incorrect. Repetitive questioning is due to the underlying disease: The patient’s short term memory is impaired and he is unable to register, encode, retain and retrieve the answer. If he is concerned about a particular topic, he will keep asking the same question over and over again. To the patient each time she asks the question, it is as if she asked it for the first time. Just answering repetitive questioning by providing repeatedly the same answer is not sufficient. Caregivers should try to identify the underlying cause for this repetitive questioning. In an earlier case study, the patient was concerned about her and her family’s safety and kept asking whether the doors are locked. In this present case study, the patient does not know how to handle the awkward situation he finds himself in. He just does not know what to do. He is not able to adjust to the new unexpected situation. So he repeatedly wants to reassure himself that he is not intruding by asking the same question over and over again. We discuss how the patient’s son-in-law could have avoided this situation and averted the catastrophic ending.

[Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens extract in beagle dog].

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Wen, Bin-Yu; Li, Jian-Rong

2013-06-01

8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.

Orally-dissolving film for sublingual and buccal delivery of ropinirole.

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Lai, Ka Lun; Fang, Yuan; Han, Hao; Li, Qingqing; Zhang, Shuai; Li, Ho Yin; Chow, Shing Fung; Lam, Tai Ning; Lee, Wai Yip Thomas

2018-03-01

Ropinirole is a very important treatment option for Parkinson's disease (PD), a major threat to the aging population. However, this drug undergoes extensive first-pass metabolism, resulting in a low oral bioavailability. Moreover, the necessity of frequent administration due to the short half-life of ropinirole may jeopardize patient compliance. Indeed, taking this drug in solid oral dosage forms (e.g. Tablet) can be a challenge because of the tremor, rigidity, limited mobility, and impaired drug absorption experienced by PD patients. In light of these, there is a pressing need to devise formulations for the delivery of ropinirole that allow simple and easy administration and fast drug action, as well as avoidance of first-pass metabolism and overcoming the challenge of impaired absorption due to gastrointestinal dysfunctions, etc. Herein, we seek to overcome all these challenges via sublingual or buccal delivery of orally-dissolving films. Accordingly, we aimed to fabricate and characterize orally-dissolving films of ropinirole and assess their in vivo pharmacokinetics after sublingual and buccal administration. The ropinirole oral film was non-toxic and exhibited fast disintegration and dissolution and was physically stable for at least 28 days. Upon buccal/sublingual administration of the oral films, ropinirole reached the systemic circulation within 15 min and bioavailability was significantly improved, which may be attributable to avoidance of first-pass metabolism via absorption through the oral cavity. In conclusion, our ropinirole oral film improved bioavailability after sublingual or buccal administration. This formulation potentially overcomes biopharmaceutical challenges and provide a convenient means of administration of ropinirole or other anti-PD drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Emotional response to musical repetition.

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Livingstone, Steven R; Palmer, Caroline; Schubert, Emery

2012-06-01

Two experiments examined the effects of repetition on listeners' emotional response to music. Listeners heard recordings of orchestral music that contained a large section repeated twice. The music had a symmetric phrase structure (same-length phrases) in Experiment 1 and an asymmetric phrase structure (different-length phrases) in Experiment 2, hypothesized to alter the predictability of sensitivity to musical repetition. Continuous measures of arousal and valence were compared across music that contained identical repetition, variation (related), or contrasting (unrelated) structure. Listeners' emotional arousal ratings differed most for contrasting music, moderately for variations, and least for repeating musical segments. A computational model for the detection of repeated musical segments was applied to the listeners' emotional responses. The model detected the locations of phrase boundaries from the emotional responses better than from performed tempo or physical intensity in both experiments. These findings indicate the importance of repetition in listeners' emotional response to music and in the perceptual segmentation of musical structure.

Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?

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Lee, Dayong; Karschner, Erin L; Milman, Garry; Barnes, Allan J; Goodwin, Robert S; Huestis, Marilyn A

2013-06-01

We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Δ(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH). After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were ≤ 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking. Published by Elsevier Ireland Ltd.

Benefits of oral administration of an electrolyte solution interrupting a prolonged preoperatory fasting period in pediatric patients.

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Moyao-García, D; Corrales-Fernández, M A; Blanco-Rodríguez, G; Sánchez-Hernández, E; Nava-Ocampo, A A

2001-03-01

The aim of this study was to evaluate the benefits of an oral isosmolar solution of electrolytes (ISE) administered to interrupt a prolonged fasting period in children undergoing an elective surgical procedure under general anesthesia. Forty unpremedicated children aged 3 to 12 years, ASA I, undergoing a surgical procedure requiring general anesthesia were assigned randomly to 1 of 2 groups. Group 1 consisted of patients with an overnight fasting period for milk and solids of at least 8 hours. In group 2, patients under a similar fasting period received a volume of 4 mL/kg of an oral ISE 3 hours before completing the fasting period. After anesthetic induction, blood glucose level (BGL) was quantified, and patients underwent an endoscopic examination to obtain the gastric content to determine the residual gastric volume (RGV) and pH levels. In group 1, the RGV was 0.78 +/- 0.44 mL/kg, pH was 1.75 +/- 0.38, and BGL was 86.4 +/- 14.5. In group 2, the RGV was 0.40 +/- 0.29 mL/kg, pH was 3.18 +/- 0.61, and BGL was 85.1 +/- 12.6. Only RGV and pH were significantly different between groups. A prolonged fasting period interrupted with oral ISE administration resulted in an RGV of low risk, without counterbalancing a potential fasting-induced hypoglycemia.

Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice.

Science.gov (United States)

Poo, Haryoung; Pyo, Hyun-Mi; Lee, Tae-Young; Yoon, Sun-Woo; Lee, Jong-Soo; Kim, Chul-Joong; Sung, Moon-Hee; Lee, Seung-Hoon

2006-10-01

The mounting of a specific immune response against the human papillomavirus type 16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7-expressing cancer cells from the cervical mucosa. To induce a mucosal immune response by oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface of Lactobacillus casei by employing a novel display system in which the poly-gamma-glutamic acid (gamma-PGA) synthetase complex A (PgsA) from Bacillus subtilis (chungkookjang) was used as an anchoring motif. After surface expression of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and immunofluorescence microscopy, mice were orally inoculated with L. casei-PgsA-E7. E7-specific serum IgG and mucosal IgA productions were enhanced after oral administration and significantly enhanced after boosting. Systemic and local cellular immunities were significantly increased after boosting, as shown by increased counts of lymphocytes (SI = 9.7 +/- 1.8) and IFN-gamma secreting cells [510 +/- 86 spot-forming cells/10(6)cells] among splenocytes and increased IFN-gamma in supernatants of vaginal lymphocytes. Furthermore, in an E7-based mouse tumor model, animals receiving orally administered L. casei-PgsA-E7 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. These results collectively indicate that the oral administration of E7 displayed on lactobacillus induces cellular immunity and antitumor effects in mice. Copyright 2006 Wiley-Liss, Inc.

Core/shell cellulose-based microspheres for oral administration of Ketoprofen Lysinate.

Science.gov (United States)

Guarino, Vincenzo; Caputo, Tania; Calcagnile, Paola; Altobelli, Rosaria; Demitri, Christian; Ambrosio, Luigi

2018-01-26

Herein, we propose the fabrication of a new carrier with core/shell structure-inner core of cellulose acetate (CA) coated by a micrometric layer of chitosan (CS)-fabricated through an integrated process, which combines Electro Dynamic Atomization (EDA) and layer-by-layer (LbL) technique. We demonstrate that CA based microspheres possess a unique capability to relevantly retain the drugs-that is, Ketoprofen Lysinate (KL)-along the gastric tract, while providing a massive release along the intestine. CS shell slightly influences the morphology and water retention under different pH conditions, improving drug encapsulation without compromising drug release kinetics. In vitro studies in simulated gastric and intestine fluids (SGF, SIF) with physiological enzymes, show a moderate release of LSK during the first 2 h (ca. 20% at pH 2), followed by a sustained release during the next 6 h (ca. 80% at pH 7). The obtained results demonstrate that CA-based microspheres hold strong potential to be used as carriers for a delayed oral administration of anti-inflammatory drugs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

The disposition of 3H-aflatoxin B1 in the rainbow trout (Oncorhynchys mykiss) after oral and intravenous administration

International Nuclear Information System (INIS)

Ngethe, S.; Horsberg, T.E.; Ingebrigtsen, K.

1992-01-01

The disposition of tritiated aflatoxin B1 in the rainbow trout following oral and intravenous administration was studied over a period of 8 days by means of liquid scintillation counting and whole-body autoradiography. The pattern of distribution together with the quantitative measurements were fairly similar in both groups, indicating a high degree of gastrointestinal absorption. The highest concentrations of radioactivity were observed in the bile, liver, kidney, pyloric caeca, uveal tract of the eye and the olfactory rosette. Substantial amounts of radioactivity were still present in the liver, kidney, olfactory rosette and the mucosa of the pyloric caeca 8 days after administration. A major fraction of this radioactivity was not extractable with certain polar and nonpolar solvents, indicating covalently bound metabolites

Evaluation of the radioprotective Effect of the co-oral Administration of Vitamin B12 with Vitamin c on some Haematological and Biochemical Alterations in Male Albino Rats

International Nuclear Information System (INIS)

Abdel-Magied, N.

2013-01-01

The objective of this study was to evaluate the prophylactic efficacy of co-oral administration of vitamin B 12 with vitamin C against radiation induced haematological and biochemical alterations in male albino rats. Male albino rats were divided into six groups (n=8). Group 1: rats were kept as control, Group 2; rats received orally vita-min B 12 (2000μgkg -1 ). Group 3; rats received Vitamin B 12 with Vitamin C (500mgkg -1 ). Group 4; rats whole body exposed to 7Gy of gamma rays. Group 5; rats received vitamin B 12 for 21 successive days before irradiation. Group 6; rats received Vitamin B 12 with Vitamin C for 21 successive days before irradiation. Animals were sacrificed the third day post irradiation. The oral administration of Vitamin B 12 with or with-out Vitamin C enhanced the recovery from radiation-induced haemopoietic injury and some biochemical changes demonstrated by a significant increase (p0.05>) of WBCs, RBCs and Platelets count, Hb content, Hct%, serum erythropoietin and iron levels and a significant reduction (p0.05>) of serum homocysteine level (Hcy), creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities compared to their respective values in irradiated rats. Improvement of oxidative stress in heart and spleen tissues denoted by a significant decrease in lipid peroxidation (MDA) and a significant increase in glutathione (GSH) content was recorded also. The co-oral administration of vitamin B 12 with vitamin C has no effect on the prophylactic efficacy of vitamin B 12

Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.

Science.gov (United States)

Cherniakov, Irina; Izgelov, Dvora; Barasch, Dinorah; Davidson, Elyad; Domb, Abraham J; Hoffman, Amnon

2017-11-28

Nowadays, therapeutic indications for cannabinoids, specifically Δ 9 -tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is that its composition of materials is approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (10.8mg, 10mg respectively) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has

Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model

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Yoshiharu Okamoto

2012-10-01

Full Text Available We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5–40 kDa, intermediate-molecular-weight fucoidan (IMWF: 110–138 kDa and high-molecular-weight fucoidan (HMWF: 300–330 kDa. The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet. The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.

Repetitive learning control of continuous chaotic systems

International Nuclear Information System (INIS)

Chen Maoyin; Shang Yun; Zhou Donghua

2004-01-01

Combining a shift method and the repetitive learning strategy, a repetitive learning controller is proposed to stabilize unstable periodic orbits (UPOs) within chaotic attractors in the sense of least mean square. If nonlinear parts in chaotic systems satisfy Lipschitz condition, the proposed controller can be simplified into a simple proportional repetitive learning controller

Novel porcine repetitive elements

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Nonneman Dan J

2006-12-01

Full Text Available Abstract Background Repetitive elements comprise ~45% of mammalian genomes and are increasingly known to impact genomic function by contributing to the genomic architecture, by direct regulation of gene expression and by affecting genomic size, diversity and evolution. The ubiquity and increasingly understood importance of repetitive elements contribute to the need to identify and annotate them. We set out to identify previously uncharacterized repetitive DNA in the porcine genome. Once found, we characterized the prevalence of these repeats in other mammals. Results We discovered 27 repetitive elements in 220 BACs covering 1% of the porcine genome (Comparative Vertebrate Sequencing Initiative; CVSI. These repeats varied in length from 55 to 1059 nucleotides. To estimate copy numbers, we went to an independent source of data, the BAC-end sequences (Wellcome Trust Sanger Institute, covering approximately 15% of the porcine genome. Copy numbers in BAC-ends were less than one hundred for 6 repeat elements, between 100 and 1000 for 16 and between 1,000 and 10,000 for 5. Several of the repeat elements were found in the bovine genome and we have identified two with orthologous sites, indicating that these elements were present in their common ancestor. None of the repeat elements were found in primate, rodent or dog genomes. We were unable to identify any of the replication machinery common to active transposable elements in these newly identified repeats. Conclusion The presence of both orthologous and non-orthologous sites indicates that some sites existed prior to speciation and some were generated later. The identification of low to moderate copy number repetitive DNA that is specific to artiodactyls will be critical in the assembly of livestock genomes and studies of comparative genomics.

Document retrieval on repetitive string collections.

Science.gov (United States)

Gagie, Travis; Hartikainen, Aleksi; Karhu, Kalle; Kärkkäinen, Juha; Navarro, Gonzalo; Puglisi, Simon J; Sirén, Jouni

2017-01-01

Most of the fastest-growing string collections today are repetitive, that is, most of the constituent documents are similar to many others. As these collections keep growing, a key approach to handling them is to exploit their repetitiveness, which can reduce their space usage by orders of magnitude. We study the problem of indexing repetitive string collections in order to perform efficient document retrieval operations on them. Document retrieval problems are routinely solved by search engines on large natural language collections, but the techniques are less developed on generic string collections. The case of repetitive string collections is even less understood, and there are very few existing solutions. We develop two novel ideas, interleaved LCPs and precomputed document lists , that yield highly compressed indexes solving the problem of document listing (find all the documents where a string appears), top- k document retrieval (find the k documents where a string appears most often), and document counting (count the number of documents where a string appears). We also show that a classical data structure supporting the latter query becomes highly compressible on repetitive data. Finally, we show how the tools we developed can be combined to solve ranked conjunctive and disjunctive multi-term queries under the simple [Formula: see text] model of relevance. We thoroughly evaluate the resulting techniques in various real-life repetitiveness scenarios, and recommend the best choices for each case.

Impact of oral meloxicam administration before and after band castration on feedlot performance and behavioral response in weanling beef bulls.

Science.gov (United States)

Repenning, P E; Ahola, J K; Callan, R J; French, J T; Giles, R L; Bigler, B J; Coetzee, J F; Wulf, L W; Peel, R K; Whittier, J C; Fox, J T; Engle, T E

2013-10-01

Two experiments evaluated the effects of band castration and oral administration of an analgesic in association with castration on performance and behavioral and physiological responses in yearling beef bulls. In Exp. 1 Angus and Charolais-crossbred bull calves (n = 127; 309.8 ± 59.04 kg BW) and in Exp. 2 Hereford, Angus, and Hereford × Angus crossbred bulls (n = 30; 300.8 ± 4.96 kg BW) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) band castration (BAND), 2) band castration with oral administration of meloxicam (BAND-MEL), and 3) sham castration (SHAM). The BAND and SHAM procedures were completed on d 0. The SHAM treatment consisted of all animal manipulations associated with band castration without band application. Meloxicam was administered on d -1, 0, and 1 (1.0, 0.5, and 0.5 mg/kg, respectively) via an oral bolus. Body weight and a subjective chute score (CS) were collected on d -1, 0, 1, 7, 14, and 21 (d 28 Exp. 1 only). In Exp. 2, jugular blood samples were collected immediately before castration and 24 h postcastration for substance P (SP) analysis. In Exp. 2, video documentation on d 0 was used to determine range of vertical head motion (DIST) on a subset of animals during treatment administration. In both experiments, ADG was similar (P ≥ 0.50) between BAND and BAND-MEL, but ADG in SHAM cattle was greater (P castrates in Exp. 1 and 2, respectively. In Exp. 1, CS did not differ (P ≥ 0.26) between BAND and BAND-MEL on any day, but castrates exhibited less desirable CS on d 1 and 28 than SHAM cattle. In Exp. 2, CS was not affected (P ≥ 0.41) by castration or the presence of meloxicam. In Exp. 2, DIST did not differ (P = 0.57) between BAND and BAND-MEL, but when pooled, castrates exhibited greater (P = 0.04) DIST than SHAM. In Exp. 2, plasma SP concentrations were similar between BAND and BAND-MEL (P = 0.81) and between castrates vs. sham cattle (P = 0.67). Results indicate no impact of meloxicam administration on performance

REPETITIVE STRENGTH AMONG STUDENTS OF AGE 14

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Besim Halilaj

2014-06-01

Full Text Available The study involved 82 male students of the primary school “Qamil Ilazi” in Kaçanik-Kosovo.Four movement tests, which test the repetitive strength, were conducted: 1. Pull-up, 2. Sit-Up, 3. Back extension, 4. Push-up.The main goal of this study was to verify the actual motor status, respectively the component of the repetitive strength among students of age 14 of masculine gender. In addition to verifying the actual motor status, another objective was to verify the relationship between the variables employed.Basic statistical parameters show a distribution which is not significantly different from the normal distribution, yielded highly correlative values among the repetitive strength tests. Space factorization resulted in extracting two latent squares defined as repetitive strength of arms factor, and repetitive strength of body factor.

MR imaging of oropharynx and oral cavity

International Nuclear Information System (INIS)

Vogl, T.; Markl, A.F.; Bruning, R.; Greves, G.; Kang, K.; Lissner, J.A.

1988-01-01

The effect of intravenously administered Gd-DTPA on signal intensity, in the oropharynx and oral cavity was analyzed, in comparison with plain imaging the examinations were carried out on 150 patients, with a 1.5-T magnetic resonance (MR) imaging unit. During and after the application of Gd-DTPA, flash images with a repetition time of 30, an echo time of 12 msec, and a 20 0 flip angle were acquired over a period of 7 minutes. In 89 patients, malignant tumors were discovered, located primarily in the oropharynx and oral cavity. Plain MR imaging was equal to or better than computed tomograph in all patients except five. Marked contrast enhancement was observed in carcinomas, sarcomas, and inflammation. The enhancement of signal intensity versus time allowed a better differentiation of histologic features. MR imaging contributes substantially to the imaging of the oropharynx and oral cavity by improved soft-tissue contrast and the capacity for multiplanar imaging

Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract

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Yan Du

2017-09-01

Full Text Available A rapid and sensitive Ultra High Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (UHPLC-ESI-MS/MS method was developed and validated to simultaneously determine the concentration of seven phenolic acids (syringic acid, ferulic acid, caffeic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid in rat plasma after oral administration of Echinacea purpurea extract. After mixing with the internal standard (IS, butylparaben, plasma samples were prepared by liquid–liquid extraction with ethyl acetate. The separation was performed using the Agilent Eclipse Plus C18 column (1.8 μm, 2.1 mm × 50 mm with a gradient system consisting of solution A (0.1% acetic acid in water and solution B (methanol at a flow rate of 0.3 mL/min. The detection was accomplished by a multiple reaction monitoring (MRM mode with electrospray ionization (ESI. The method was validated in terms of linearity, precision, accuracy, extraction recovery, matrix effect and stability. This method was successfully applied to study the pharmacokinetic properties of the seven compounds after oral administration of Echinacea purpurea extract in rats.

Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

Science.gov (United States)

Serrano-Rodríguez, Juan Manuel; Gómez-Díez, Manuel; Esgueva, María; Castejón-Riber, Cristina; Mena-Bravo, Antonio; Priego-Capote, Feliciano; Ayala, Nahúm; Caballero, Juan Manuel Serrano; Muñoz, Ana

2017-10-01

Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and analytical characterization of a new antiparasitic fenbendazole compound tablet and pharmacokinetic investigations after its oral administration to dogs.

Science.gov (United States)

Dai, Cunchun; Qu, Shaoqi; Zhang, Ruili; Zhao, Li; Li, Yuwen; Zhu, Jiajia; Wang, Chunmei; Guo, Hui; Hao, Zhihui

2018-02-01

The objective of this study was to prepare a new compound fenbendazole tablet containing 29.7 % fenbendazole, 1.50 % praziquantel and 0.059 % ivermectin for oral administration. The tablets were successfully prepared using mannitol as filler agent, polyvinyl polypyrrolidone as disintegrant, 5 % povidone (PVAK30) as a binder agent and magnesium stearate as lubricant. The appearance, hardness, fragility, time limit of disintegration and fenbendazole dissolution at 45 min all met the technical standards of the Ministry of Agriculture for the People's Republic of China. We used high performance liquid chromatography and electrospray-mass spectrometry for drug detection. Oral administration of 100 mg/kg fenbendazole, 5 mg/kg praziquantel and 0.2 mg/kg ivermectin using a non-compartmental model defined peak plasma concentrations (Cmax) of 495, 826, 73 ng/mL, and 218 ng/mL for the metabolite oxfendazole, respectively. The area under the curve (AUClast) values for these drugs were 4653, 1045, 1971 and 5525 h×ng/mL, respectively. This study enriches the pharmacokinetic data of compound fenbendazole tablets using dogs as a model system. The new tablet formulation was assimilated quickly and systemically and this study will be beneficial for the clinical application of parasite treatments in dogs.

The Various Forms of Insulin Secretion Response to the Intravenous and Oral Administration of Glucose in Non-Insulin-Dependent Diabetes Mellitus; Les Differentes Modalites de Reponse Insulino-Secretrice Lors de Charges Veineuse et Orale en Glucose dans le Diabete Sucre Non Insulino-Dependant

Energy Technology Data Exchange (ETDEWEB)

Mirouze, J.; Orsetti, A.; Lapinski, H. [Clinique des Maladies Metaboliques et Endocriniennes, Hopital St-Eloi, Montpellier (France)

1970-02-15

On the basis of 68 observations on advanced diabetes mellitus (20 cases), latent diabetes with obesity (12 cases), chemical diabetes with subjective symptoms (26 cases) and 10 observations of obesity without diabetes, the authors have analysed the various forms of insulin secretion response to the intravenous and oral administration of glucose. The response appeared to be totally withdrawn in advanced diabetes mellitus although the patients were still capable of responding to stimulation with glucagon. In the two other forms of diabetes described, the response to stimulation by intravenous administration was less marked than in normal subjects. With oral administration, on the other hand, the response was greater, although the insulin secreted in this case appeared ineffective in cases of obesity but effective in conditions without obesity due to the hypoglycaemic effect. (author) [French] A l'aide de 68 observations de diabete sucre evolue (20 cas), latent avec obesite (12 cas), chimique avec malaises (26 cas) et de 10 observations d'obesite sans diabete, les auteurs analysent les differentes modalites de riposte insulino- secretrice lors des charges en glucose, veineuse et orale. La riposte s'avere totalement effondree dans le diabete evolue, mais susceptible de repondre encore a la stimulation par le glucagon. Dans les deux autres formes de diabete decrites, la stimulation par charge veineuse est reduite par rapport au sujet normal alors qu'elle est majoree apres charge orale mais l'insuline ainsi secretee parait inefficace dans l'obesite et efficace puisque hypoglycemiante lors de malaises sans obesite. (author)

Expression of verocytotoxic Escherichia coli antigens in tobacco seeds and evaluation of gut immunity after oral administration in mouse model

OpenAIRE

Rossi, Luciana; Di Giancamillo, Alessia; Reggi, Serena; Domeneghini, Cinzia; Baldi, Antonella; Sala, Vittorio; Dell'Orto, Vittorio; Coddens, Annelies; Cox, Eric; Fogher, Corrado

2013-01-01

Verocytotoxic Escherichia (E.) coli strains are responsible for swine oedema disease, which is an enterotoxaemia that causes economic losses in the pig industry. The production of a vaccine for oral administration in transgenic seeds could be an efficient system to stimulate local immunity. This study was conducted to transform tobacco plants for the seed-specific expression of antigenic proteins from a porcine verocytotoxic E. coli strain. Parameters related to an immunological response and ...

Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

International Nuclear Information System (INIS)

Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

1986-01-01

RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy

Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

Energy Technology Data Exchange (ETDEWEB)

Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

1986-11-01

RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy.

Evaluation of resting brain conditions measured by two different methods (i.v. and oral administration) with 18F-FDG-PET

International Nuclear Information System (INIS)

Masud, M.; Yamaguchi, Keiichiro; Rikimaru, Hisashi; Tashiro, Manabu; Ozaki, Kaoru; Watanuki, Shoichi; Miyake, Masayasu; Ido, Tatsuo; Itoh, Masatoshi

2001-01-01

Our aim was to evaluate regional differences between brain activity in two resting control conditions measured by 3D PET after administration of FDG through either the intravenous (i.v.) or the oral route. Ten healthy male volunteers engaged in the study as the i.v. group (mean age, 26±9.3 years, ±S.D.) who received FDG intravenously and another 10 volunteers as the oral group (mean age, 27.9±11.3 years, ±S.D.) who received FDG per os. A set of 3D-PET scans (emission and transmission scans) were performed in both groups. To explore possible functional differences between the brains of the two groups, the SPM-96 software was used for statistical analysis. The results revealed that glucose metabolism was significantly higher in the superior frontal gyrus, superior parietal lobule, lingual gyrus and left cerebellar hemisphere in the i.v. group than in the oral group. Metabolically active areas were found in the superior, middle and inferior temporal gyrus, parahippocampal gyrus, amygdaloid nucleus, pons and cerebellum in the oral group when compared with the i.v. group. These differences were presumably induced by differences between FDG kinetics and/or time-weighted behavioral effects in the two studies. This study suggests the need for extreme caution when selecting a pooled control population for designated activation studies. (author)

Detection and Quantification of Flavobacterium psychrophilum-Specific Bacteriophages In Vivo in Rainbow Trout upon Oral Administration: Implications for Disease Control in Aquaculture

DEFF Research Database (Denmark)

Christiansen, Rói Hammershaimb; Dalsgaard, Inger; Middelboe, Mathias

2014-01-01

different methods-bath, oral intubation into the stomach, and phage-coated feed-with special emphasis on the oral route of delivery. Phages could be detected in all the organs investigated (intestine, spleen, brain, and kidney) 0.5 h postadministration, reaching concentrations as high as ∼10(5) PFU mg...... intestine(-1) and ∼10(3) PFU mg spleen(-1) within the first 24 h following the bath and ∼10(7) PFU mg intestine(-1) and ∼10(4) PFU mg spleen(-1) within the first 24 h following oral intubation. The phages were most persistent in the organs for the first 24 h and then decreased exponentially; no phages were...... detected after 83 h in the organs investigated. Phage administration via feed resulted in the detection of phages in the intestine, spleen, and kidney 1 h after feeding. Average concentrations of ∼10(4) PFU mg intestine(-1) and ∼10(1) PFU mg spleen(-1) were found throughout the experimental period (200 h...

Intermittent subcutaneous methadone administration in the management of cancer pain.

Science.gov (United States)

Centeno, Carlos; Vara, Francisco

2005-01-01

Methadone is a strong opioid analgesic that has been used successfully in cancer pain management. The oral route of administration is generally preferred for opioid analgesics. However that route sometimes cannot be used. Experience with continuous subcutaneous methadone infusions has produced local intolerance. The aim of this study was to analyze the use of intermittent subcutaneous methadone injections. Ten patients whose pain was well-controlled with oral methadone (average dose 30 mg, range 10 to 120 mg) participated in the study. A subcutaneous small vein needle (butterfly) was used exclusively for administration of methadone. Over a period of seven days the local discomfort of each injection was evaluated by means of a Verbal Numerical Rating Scale (NRS) and the site of infusion was observed. When any degree of erythema or inflammation was seen, the infusion site was changed. The initial subcutaneous dose was the same as the previously administered oral dose. A daily record was kept of the dose used, level of pain, and toxicity symptoms. This close vigilance was aimed at avoiding dosage errors due to variations among individuals in acceptance to previous oral medication. Changes in dosage were allowed according to standard medical criteria. Two patients were withdrawn from the study due to non-painful irritation at the infusion point. Another eight patients tolerated repeated administration of subcutaneous methadone over seven days. Any local irritation from subcutaneous methadone that occurred was managed satisfactorily by changing the infusion site and limiting doses to 30 mg. In seven of 182 repeat administration, injection site changes were necessitated by local irritation. The NRS for local discomfort was 2/10. The two patients who were intolerant of the subcutaneous injections were receiving injected doses which were significantly higher than the others (42 mg as compared to 25 mg). Dose adjustments needed when changing from the oral to the

Oral health knowledge and attitudes of primary school teachers toward school-based oral health programs in Abha-Khamis, Saudi Arabia

Directory of Open Access Journals (Sweden)

Shreyas Tikare

2017-01-01

Conclusions: The oral health knowledge among primary school teachers was found to be good with positive attitudes toward school-based oral health programs. The most significant barriers in implementing a school oral health program were administrative barriers. There is a need for concerned school authorities and health policy makers to address these barriers and to promote oral health in the community.

Intravenous alcohol self-administration in the P rat.

Science.gov (United States)

Windisch, Kyle A; Kosobud, Ann E K; Czachowski, Cristine L

2014-08-01

Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally "relevant" effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding "non-pharmacological" effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol's effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol

Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

Science.gov (United States)

Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

2017-06-01

Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

Oral cadmium chloride intoxication in mice

DEFF Research Database (Denmark)

Andersen, O; Nielsen, J B; Svendsen, P

1988-01-01

Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect...

Candesartan cilexetil loaded nanodelivery systems for improved oral bioavailability.

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Dudhipala, Narendar; Veerabrahma, Kishan

2017-02-01

Candesartan cilexetil (CC), an antihypertensive drug, has low oral bioavailability due to poor solubility and hepatic first-pass metabolism. These are major limitations in oral delivery of CC. Several approaches are known to reduce the problems of solubility and improve the bioavailability of CC. Among various approaches, nanotechnology-based delivery of CC has potential to overcome the challenges associated with the oral administration. This review focuses on various nano-based delivery systems available and tried for improving the aqueous solubility, dissolution and consequently bioavailability of CC upon oral administration. Of all, solid lipid nanoparticles appear to be promising delivery system, based on current reported results, for delivery of CC, as this system improved the oral bioavailability and possessed prolonged pharmacodynamic effect.

Repetition and Emotive Communication in Music Versus Speech

Directory of Open Access Journals (Sweden)

Elizabeth Hellmuth eMargulis

2013-04-01

Full Text Available Music and speech are often placed alongside one another as comparative cases. Their relative overlaps and disassociations have been well explored (e.g. Patel, 2010. But one key attribute distinguishing these two domains has often been overlooked: the greater preponderance of repetition in music in comparison to speech. Recent fMRI studies have shown that familiarity – achieved through repetition – is a critical component of emotional engagement with music (Pereira et al., 2011. If repetition is fundamental to emotional responses to music, and repetition is a key distinguisher between the domains of music and speech, then close examination of the phenomenon of repetition might help clarify the ways that music elicits emotion differently than speech.

Feature-based motion control for near-repetitive structures

NARCIS (Netherlands)

Best, de J.J.T.H.

2011-01-01

In many manufacturing processes, production steps are carried out on repetitive structures which consist of identical features placed in a repetitive pattern. In the production of these repetitive structures one or more consecutive steps are carried out on the features to create the final product.

Value of oral effervescent powder administration for multidetector CT evaluation of esophageal cancer

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Ringe, Kristina I., E-mail: ringe.kristina@mh-hannover.de [Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Meyer, Simone, E-mail: Meyer.simone.rad@mh-hannover.de [Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Ringe, Bastian P., E-mail: Ringe.bastian@mh-hannover.de [Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Winkler, Michael, E-mail: Winkler.michael@mh-hannover.de [Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Wacker, Frank, E-mail: Wacker.frank@mh-hannover.de [Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Raatschen, Hans-Juergen, E-mail: Raatschen.hans-juergen@mh-hannover.de [Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany)

2015-02-15

Highlights: • Oral effervescent powder improves esophageal distension and wall assessment at CT. • This technique improves detection and T staging of esophageal cancer at CT. • It can be easily adopted in clinical routine in patients with esophageal pathology. - Abstract: Purpose: To assess the value of oral effervescent powder (EP) for evaluation of esophageal distension, and for detection and staging of esophageal cancer with contrast-enhanced CT. Materials and methods: 84 patients without esophageal pathology and 52 patients with histological confirmed diagnosis of esophageal cancer were included in this prospective IRB-approved study. Half of the patients in both groups received EP prior to CT. Esophageal distension was assessed by planimetry of the inner (IA) and outer area (OA). Two blinded readers evaluated the datasets separately with regard to diagnosis of esophageal cancer (yes/no) and staging (T0-T4), if applicable. Distension results were compared (t-Test). In patients with cancer sensitivity, specificity, NPV and PPV were calculated. CT staging results were compared to histopathology (Cohen-k). Results: IA and IA/OA were significantly larger after EP as compared to the group without EP (p < 0.05). Sensitivity, specificity, NPV and PPV for cancer detection cancer were as follows: 78%/78%, 98%/98%, 95%/95%, 87%/87% with EP; 60%/68%, 98%/98%, 94%/94%, 80%/83% without EP. Staging with EP was good (k = 0.84/0.67) and moderate without EP (k = 0.58/0.59). Conclusions: Administration of EP prior to CT results in good distension of the esophagus, and improves detection and staging of esophageal cancer, as compared to control studies without EP.

The effects of oral and topical corticosteroid in rabbit corneas.

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Araki-Sasaki, Kaoru; Katsuta, Osamu; Mano, Hidetoshi; Nagano, Takashi; Nakamura, Masatsugu

2016-09-05

To determine the most effective route of administration of corticosteroids in the treatment of ocular surface disease, by characterizing the difference between oral prednisolone and topical dexamethasone administration using an animal model. Pharmacokinetic analyses determined the corticosteroid concentrations in the normal ocular tissues of rabbits after oral or topical administration of corticosteroids using LC-MS/MS. In wound healing analyses, the area of the epithelial defect created by keratectomy using a 6-mm trephine was calculated with an image analyzer using an orally or topically steroid-administrated animal model. The average size of basal epithelial cells, the frequency of mitotic basal epithelial cells, the number of squamous cells, and the number of hypertrophic stromal fibroblasts were determined in the enucleated corneal tissues after wound closure. By slit lamp examination, no remarkable differences were observed between orally and topically administered groups. Pharmacokinetic analyses showed that the distribution of dexamethasone after topical administration was superior to that after oral administration in the cornea. In contrast, both concentrations of corticosteroid applied topically and orally were similar with regards to AUCs (area under the concentration-time curve) in the conjunctiva. Although the healing rate was slower in the topical group, all corneas were almost healed within 96 h in the wound healing analysis. According to the histological analyses of epithelial cells, the average basal cell size was larger, the frequency of mitotic basal cells was greater, and the number of squamous epithelial cell layers was lower in the topically administered group although all of these differences were with no statistical significance. However, the number of hypertrophic stromal fibroblasts in the topically administered group was significantly lower than that in the orally administered group. There are different distributions and effects between

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

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Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo

2014-07-01

Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is

Mechanism of oral tolerance induction to therapeutic proteins.

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Wang, Xiaomei; Sherman, Alexandra; Liao, Gongxian; Leong, Kam W; Daniell, Henry; Terhorst, Cox; Herzog, Roland W

2013-06-15

Oral tolerance is defined as the specific suppression of humoral and/or cellular immune responses to an antigen by administration of the same antigen through the oral route. Due to its absence of toxicity, easy administration, and antigen specificity, oral tolerance is a very attractive approach to prevent unwanted immune responses that cause a variety of diseases or that complicate treatment of a disease. Many researchers have induced oral tolerance to efficiently treat autoimmune and inflammatory diseases in different animal models. However, clinical trials yielded limited success. Thus, understanding the mechanisms of oral tolerance induction to therapeutic proteins is critical for paving the way for clinical development of oral tolerance protocols. This review will summarize progress on understanding the major underlying tolerance mechanisms and contributors, including antigen presenting cells, regulatory T cells, cytokines, and signaling pathways. Potential applications, examples for therapeutic proteins and disease targets, and recent developments in delivery methods are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Grade Repetition and Primary School Dropout in Uganda

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Kabay, Sarah

2016-01-01

Research on education in low-income countries rarely focuses on grade repetition. When addressed, repetition is typically presented along with early school dropout as the "wasting" of educational resources. Simplifying grade repetition in this way often fails to recognize significant methodological concerns and also overlooks the unique…

Analogous selection processes in declarative and procedural working memory: N-2 list-repetition and task-repetition costs.

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Gade, Miriam; Souza, Alessandra S; Druey, Michel D; Oberauer, Klaus

2017-01-01

Working memory (WM) holds and manipulates representations for ongoing cognition. Oberauer (Psychology of Learning and Motivation, 51, 45-100, 2009) distinguishes between two analogous WM sub-systems: a declarative WM which handles the objects of thought, and a procedural WM which handles the representations of (cognitive) actions. Here, we assessed whether analogous effects are observed when participants switch between memory sets (declarative representations) and when they switch between task sets (procedural representations). One mechanism assumed to facilitate switching in procedural WM is the inhibition of previously used, but currently irrelevant task sets, as indexed by n-2 task-repetition costs (Mayr & Keele, Journal of Experimental Psychology: General, 129(1), 4-26, 2000). In this study we tested for an analogous effect in declarative WM. We assessed the evidence for n-2 list-repetition costs across eight experiments in which participants switched between memory lists to perform speeded classifications, mental arithmetic, or a local recognition test. N-2 list-repetition costs were obtained consistently in conditions assumed to increase interference between memory lists, and when lists formed chunks in long-term memory. Further analyses across experiments revealed a substantial contribution of episodic memory to n-2 list-repetition costs, thereby questioning the interpretation of n-2 repetition costs as reflecting inhibition. We reanalyzed the data of eight task-switching experiments, and observed that episodic memory also contributes to n-2 task-repetition costs. Taken together, these results show analogous processing principles in declarative and procedural WM, and question the relevance of inhibitory processes for efficient switching between mental sets.

The Golden Ratio of Gait Harmony: Repetitive Proportions of Repetitive Gait Phases

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Marco Iosa

2013-01-01

Full Text Available In nature, many physical and biological systems have structures showing harmonic properties. Some of them were found related to the irrational number known as the golden ratio that has important symmetric and harmonic properties. In this study, the spatiotemporal gait parameters of 25 healthy subjects were analyzed using a stereophotogrammetric system with 25 retroreflective markers located on their skin. The proportions of gait phases were compared with , the value of which is about 1.6180. The ratio between the entire gait cycle and stance phase resulted in 1.620 ± 0.058, that between stance and the swing phase was 1.629 ± 0.173, and that between swing and the double support phase was 1.684 ± 0.357. All these ratios did not differ significantly from each other (, , repeated measure analysis of variance or from (, resp., t-tests. The repetitive gait phases of physiological walking were found in turn in repetitive proportions with each other, revealing an intrinsic harmonic structure. Harmony could be the key for facilitating the control of repetitive walking. Harmony is a powerful unifying factor between seemingly disparate fields of nature, including human gait.

Impact of Flow Rate, Collection Devices, and Extraction Methods on Tear Concentrations Following Oral Administration of Doxycycline in Dogs and Cats.

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Sebbag, Lionel; Showman, Lucas; McDowell, Emily M; Perera, Ann; Mochel, Jonathan P

2018-04-30

Compare the precision of doxycycline quantification in tear fluid collected with either Schirmer strips or polyvinyl acetal (PVA) sponges following oral drug administration. Three dogs and 3 cats were administered doxycycline orally at a dose of 4.2-5 mg/kg every 12 h for 6 consecutive days. At day 5 and 6, blood and tear fluid were sampled to capture doxycycline trough and maximal concentrations. Tear fluid was collected 3 times (spaced 10 min apart) at each session with the absorbent material placed in the lower conjunctival fornix until the 20-mm mark was reached (Schirmer strip, one eye) or for 1 min (PVA sponge, other eye). Tear extraction was performed with either centrifugation or elution in methanol. Doxycycline concentrations were measured with liquid chromatography-mass spectrometry. Low (100 ng/mL) and high (1,000 ng/mL) tear concentrations measured in vivo were spiked into each absorbent material in vitro to evaluate percentage drug recovery. After oral administration of doxycycline, the drug reached the tear compartment at concentrations of 45.1-900.7 ng/mL in cats and 45.4-632.0 ng/mL in dogs, representing a tear-to-serum ratio of 12% and 16%, respectively. Doxycycline tear concentrations were significantly more precise when tear collection was performed with Schirmer strips rather than PVA sponges (P = 0.007), but were not correlated with tear flow rate. In vitro doxycycline recovery was poor to moderate (<75%). Schirmer strips represent a good option for lacrimal doxycycline quantification, although the collection and subsequent extraction have to be optimized to improve drug recovery.

Subjective duration distortions mirror neural repetition suppression.

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Pariyadath, Vani; Eagleman, David M

2012-01-01

Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression. Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials. Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

Subjective duration distortions mirror neural repetition suppression.

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Vani Pariyadath

Full Text Available Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression.Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli followed by a line presented at a different orientation (oddball stimulus. We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials.Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]tofogliflozin after oral administration and concomitant intravenous microdose administration of [13C]tofogliflozin in humans.

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Schwab, Dietmar; Portron, Agnes; Backholer, Zoe; Lausecker, Berthold; Kawashima, Kosuke

2013-06-01

Human mass balance studies and the assessment of absolute oral bioavailability (F) are usually assessed in separate studies. Intravenous microdose administration of an isotope tracer concomitant to an unlabeled oral dose is an emerging technique to assess F. We report a novel double-tracer approach implemented for tofogliflozin combining oral administration of a radiolabel tracer with concomitant intravenous administration of a stable isotope tracer. Tofogliflozin is a potent and selective sodium/glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus currently in clinical development. The objectives of the present study were to assess the systemic exposure of major circulating metabolites, excretion balance, F and contribution of renal clearance (CLR) to total clearance (CL) of tofogliflozin in healthy subjects within one study applying a novel double-tracer technique. Six healthy male subjects received 20 mg [(12)C/(14)C]tofogliflozin (3.73 MBq) orally and a concomitant microdose of 0.1 mg [(13)C]tofogliflozin intravenously. Pharmacokinetics of tofogliflozin were determined for the oral and intravenous route; the pharmacokinetics of the metabolites M1 and M5 were determined for the oral route. Quantification of [(12)C]tofogliflozin in plasma and urine and [(13)C]tofogliflozin in plasma was performed by selective LC-MS/MS methods. For the pre-selected metabolites of tofogliflozin, M1 and M5, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to plasma and urine samples. Total radioactivity was assessed in plasma, urine and feces. Pharmacokinetic analysis was conducted by non-compartmental methods. The pharmacokinetics of tofogliflozin in healthy subjects were characterized by an F of 97.5 ± 12.3 %, CL of 10.0 ± 1.3 l/h and volume of distribution at steady-state (V(ss)) of 50.6 ± 6.7 l. The main route of elimination of total drug-related material was by excretion into urine (77.0 ± 4.1 % of the dose). The

Field trial of GABA-fortified rice plants and oral administration of milled rice in spontaneously hypertensive rats.

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Kowaka, Emi; Shimajiri, Yasuka; Kawakami, Kouhei; Tongu, Miki; Akama, Kazuhito

2015-06-01

Hypertension is one of the most critical risk factors accompanying cardiovascular diseases. γ-Aminobutyric acid (GABA) is a non-protein amino acid that functions as a major neurotransmitter in mammals and also as a blood-pressure lowering agent. We previously produced GABA-fortified rice lines of a popular Japonica rice cultivar 'Koshihikari' by genetic manipulation of GABA shunt-related genes. In the study reported here, we grew these same novel rice lines in a field trial and administered the milled rice orally to rats. The yield parameters of the transgenic rice plants were almost unchanged compared to those of untransformed cv. 'Koshihikari' plants, while the rice grains of the transgenic plants contained a high GABA content (3.5 g GABA/kg brown rice; 0.75-0.85 GABA g/kg milled rice) in a greenhouse trial. Oral administration of a diet containing 2.5% GABA-fortified rice, with a daily intake for 8 weeks, had an approximately 20 mmHg anti-hypertensive effect in spontaneous hypertensive rats but not in normotensive Wistar-Kyoto rats. These results suggest that GABA-fortified rice may be applicable as a staple food to control or prevent hypertension.

The Developmental Trajectory of Nonword Repetition

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Chiat, Shula

2006-01-01

In line with the original presentation of nonword repetition as a measure of phonological short-term memory (Gathercole & Baddeley, 1989), the theoretical account Gathercole (2006) puts forward in her Keynote Article focuses on phonological storage as the key capacity common to nonword repetition and vocabulary acquisition. However, evidence that…

Administration of Anesthesia

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Full Text Available ... Anesthesia Evaluation Part V Broad Access to Care, Patient Safety and Comfort Oral and maxillofacial surgeons (OMSs) are trained in all aspects of anesthesia administration. Following dental ... evaluate patients for anesthesia, deliver the anesthetic and monitor post- ...

Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats.

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Balap, Aishwarya; Atre, Bhagyashri; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb

2016-05-13

Andrographis paniculata Nees (Acanthacae) is commonly used medicinal plant in the traditional. Unani and Ayurvedic medicinal systems. It has broad range of pharmacological effects such as hepatoprotective, antioxidant, antivenom, antifertility, inhibition of replication of the HIV virus, antimalarial, antifungal, antibacterial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug To evaluate the pharmacokinetic and pharmacodynamic (anti-arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with etoricoxib (ETO) after oral co-administration in wistar rats. After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. Co-administration of ETO with APE and pure AN decreased systemic exposure level of each compound in vivo. The Cmax, AUC, t1/2 of ETO was decreased whereas Vd and CL of ETO was increased significantly after co-administration of ETO with pure AN and APE. In pharmacodynamic study, ETO alone and ETO+APE (10+200mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups ETO+AN, APE and AN alone. The results obtained from this study suggested that ETO, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. Physicians and patients using A. paniculata should have the knowledge about its possible

Global Repetition Influences Contextual Cueing

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Zang, Xuelian; Zinchenko, Artyom; Jia, Lina; Li, Hong

2018-01-01

Our visual system has a striking ability to improve visual search based on the learning of repeated ambient regularities, an effect named contextual cueing. Whereas most of the previous studies investigated contextual cueing effect with the same number of repeated and non-repeated search displays per block, the current study focused on whether a global repetition frequency formed by different presentation ratios between the repeated and non-repeated configurations influence contextual cueing effect. Specifically, the number of repeated and non-repeated displays presented in each block was manipulated: 12:12, 20:4, 4:20, and 4:4 in Experiments 1–4, respectively. The results revealed a significant contextual cueing effect when the global repetition frequency is high (≥1:1 ratio) in Experiments 1, 2, and 4, given that processing of repeated displays was expedited relative to non-repeated displays. Nevertheless, the contextual cueing effect reduced to a non-significant level when the repetition frequency reduced to 4:20 in Experiment 3. These results suggested that the presentation frequency of repeated relative to the non-repeated displays could influence the strength of contextual cueing. In other words, global repetition statistics could be a crucial factor to mediate contextual cueing effect. PMID:29636716

Imbalance between abstract and concrete repetitive thinking modes in schizophrenia.

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Maurage, Pierre; Philippot, Pierre; Grynberg, Delphine; Leleux, Dominique; Delatte, Benoît; Mangelinckx, Camille; Belge, Jan-Baptist; Constant, Eric

2017-10-01

Repetitive thoughts can be divided in two modes: abstract/analytic (decontextualized and dysfunctional) and concrete/experiential (problem-focused and adaptive). They constitute a transdiagnostic process involved in many psychopathological states but have received little attention in schizophrenia, as earlier studies only indexed increased ruminations (related to dysfunctional repetitive thoughts) without jointly exploring both modes. This study explored the two repetitive thinking modes, beyond ruminations, to determine their imbalance in schizophrenia. Thirty stabilized patients with schizophrenia and 30 matched controls completed the Repetitive Response Scale and the Mini Cambridge-Exeter Repetitive Thought Scale, both measuring repetitive thinking modes. Complementary measures related to schizophrenic symptomatology, depression and anxiety were also conducted. Compared to controls, patients with schizophrenia presented an imbalance between repetitive thinking modes, with increased abstract/analytic and reduced concrete/experiential thoughts, even after controlling for comorbidities. Schizophrenia is associated with stronger dysfunctional repetitive thoughts (i.e. abstract thinking) and impaired ability to efficiently use repetitive thinking for current problem-solving (i.e. concrete thinking). This imbalance confirms the double-faced nature of repetitive thinking modes, whose influence on schizophrenia's symptomatology should be further investigated. The present results also claim for evaluating these processes in clinical settings and for rehabilitating the balance between opposite repetitive thinking modes. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacokinetics and Biodistribution of Aurantiamide and Aurantiamide Acetate in Rats after Oral Administration of Portulaca oleracea L. Extracts.

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Chen, Lijiang; Liu, Yang; Jia, Dechao; Yang, Jia; Zhao, Jinhua; Chen, Changlan; Liu, Hongsheng; Liang, Xiao

2016-05-04

Aurantiamide and aurantiamide acetate are the main active constituents of purslane (Portulaca oleracea L.), an edible plant with various biological activities. In this study, we developed a validated UHPLC-MS/MS method to quantitate the concentrations of aurantiamide and aurantiamide acetate in the plasma and various organ tissues of rat as the basis to study their pharmacological profile and distribution in vivo. Aurantiamide and aurantiamide acetate were rapidly absorbed following oral administration, both achieving a Cmax at around 0.2 h. The extent of their metabolisms also varied among different organ tissues, resulting in about 90% reduction in concentrations 4 h after their administration, thus leaving no long-term accumulation in the tissues. This is the first study to examine the pharmacokinetic and biodistribution of aurantiamide and aurantiamide acetate in rat, and our work may serve as the first step toward the investigation of the underlying mechanisms associated with the biological activity of purslane.

COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (IAS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV) AND ARSENITE (ASIII)

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COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV) AND ARSENITE (AsIII). E M Kenyon, L M Del Razo and M F Hughes. U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; ...

Evaluation of resting brain conditions measured by two different methods (i.v. and oral administration) with {sup 18}F-FDG-PET

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Masud, M.; Yamaguchi, Keiichiro; Rikimaru, Hisashi; Tashiro, Manabu; Ozaki, Kaoru; Watanuki, Shoichi; Miyake, Masayasu; Ido, Tatsuo; Itoh, Masatoshi [Tohoku Univ., Sendai (Japan). Cyclotron and Radioisotope Center

2001-02-01

Our aim was to evaluate regional differences between brain activity in two resting control conditions measured by 3D PET after administration of FDG through either the intravenous (i.v.) or the oral route. Ten healthy male volunteers engaged in the study as the i.v. group (mean age, 26{+-}9.3 years, {+-}S.D.) who received FDG intravenously and another 10 volunteers as the oral group (mean age, 27.9{+-}11.3 years, {+-}S.D.) who received FDG per os. A set of 3D-PET scans (emission and transmission scans) were performed in both groups. To explore possible functional differences between the brains of the two groups, the SPM-96 software was used for statistical analysis. The results revealed that glucose metabolism was significantly higher in the superior frontal gyrus, superior parietal lobule, lingual gyrus and left cerebellar hemisphere in the i.v. group than in the oral group. Metabolically active areas were found in the superior, middle and inferior temporal gyrus, parahippocampal gyrus, amygdaloid nucleus, pons and cerebellum in the oral group when compared with the i.v. group. These differences were presumably induced by differences between FDG kinetics and/or time-weighted behavioral effects in the two studies. This study suggests the need for extreme caution when selecting a pooled control population for designated activation studies. (author)

21 CFR 520.1696 - Penicillin oral dosage forms.

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2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

21 CFR 520.45 - Albendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

Repetitive thinking, executive functioning, and depressive mood in the elderly.

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Philippot, Pierre; Agrigoroaei, Stefan

2017-11-01

Previous findings and the depressive-executive dysfunction hypothesis suggest that the established association between executive functioning and depression is accounted for by repetitive thinking. Investigating the association between executive functioning, repetitive thinking, and depressive mood, the present study empirically tested this mediational model in a sample of older adults, while focusing on both concrete and abstract repetitive thinking. This latter distinction is important given the potential protective role of concrete repetitive thinking, in contrast to the depletive effect of abstract repetitive thinking. A sample of 43 elderly volunteers, between 75 and 95 years of age, completed tests of executive functioning (the Stroop test, the Trail Making test, and the Fluency test), and questionnaires of repetitive thinking and depression. Positive correlations were observed between abstract repetitive thinking and depressive mood, and between concrete repetitive thinking and executive functioning; a negative correlation was observed between depressive mood and executive functioning. Further, mediational analysis evidenced that the relation between executive functioning and depressive mood was mediated by abstract repetitive thinking. The present data provide, for the first time, empirical support to the depressive-executive dysfunction hypothesis: the lack of executive resources would favor a mode of abstract repetitive thinking, which in turn would deplete mood. It suggests that clinical intervention targeting depression in the elderly should take into consideration repetitive thinking modes and the executive resources needed to disengage from rumination.

[Oral films as perspective dosage form].

Science.gov (United States)

Walicová, Veronika; Gajdziok, Jan

Oral films, namely buccal mucoadhesive films and orodispersible films represent innovative formulations for administration of a wide range of drugs. Oral films show many advantageous properties and are intended for systemic drug delivery or for local treatment of the oral mucosa. In both cases, the film represents a thin layer, which could be intended to adhere to the oral mucosa by means of mucoadhesion; or to rapid dissolution and subsequent swallowing without the need of liquid intake, in the case of orodispersible films. Main constitutive excipients are film-forming polymers, which must in the case of mucoadhesive forms remain on the mucosa within the required time interval. Oral films are currently available on the pharmaceutical market and could compete with conventional oral dosage forms in the future. oral cavity oral films buccal mucoadhesive films orodispersible films film-forming polymers.

Safety data on 19 vehicles for use in 1 month oral rodent pre-clinical studies: administration of hydroxypropyl-ß-cyclodextrin causes renal toxicity.

Science.gov (United States)

Healing, Guy; Sulemann, Tabassum; Cotton, Peter; Harris, Jayne; Hargreaves, Adam; Finney, Rowena; Kirk, Sarah; Schramm, Carolin; Garner, Clare; Pivette, Perrine; Burdett, Lisa

2016-01-01

Potential new drugs are assessed in pre-clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28 days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl-ß-cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1 month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol®812, 20% (w/v) Kolliphor®RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil®M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation. Copyright © 2015 John Wiley & Sons, Ltd.

Preparation, characterization and bioavailability by oral administration of O/W curcumin nanoemulsions stabilized with lysophosphatidylcholine.

Science.gov (United States)

Chávez-Zamudio, Rubi; Ochoa-Flores, Angélica A; Soto-Rodríguez, Ida; Garcia-Varela, Rebeca; García, Hugo Sergio

2017-09-20

Curcumin is the main and most abundant bioactive component in Curcuma longa L. with documented properties in the prevention and treatment of chronic degenerative and infectious diseases. However, curcumin has low solubility in aqueous media, hence low bioavailability when administered orally. The use of nanoemulsions as carriers can provide a partial solution to bioavailability restrictions. In our study, O/W nanoemulsions of curcumin were prepared using lysophosphatidylcholine, a phospholipid with proven emulsification capacity; nevertheless, such qualities have not been previously reported in the preparation of nanoemulsions. Lysophosphatidylcholine was obtained by enzymatic removal of one fatty acid residue from phosphatidylcholine. The objective of our work was to formulate stable curcumin nanoemulsions and evaluate their bioavailability in BALB/c mice plasma after oral administration. Formulated nanoemulsions had a droplet size mean of 154.32 ± 3.10 nm, a polydispersity index of 0.34 ± 0.07 and zeta potential of -10.43 ± 1.10 mV; stability was monitored for 12 weeks. Lastly, in vivo pharmacokinetic parameters, using BALB/c mice, were obtained; namely, C max of 610 ± 65.0 μg mL -1 and T max of 2 h. Pharmacokinetic data revealed a higher bioavailability of emulsified as opposed to free curcumin. Research regarding other potential emulsifiers that may provide better health benefits and carry nano-encapsulated bioactive compounds more effectively, is necessary. This study provides important data on the preparation and design of nanoencapsulated Curcumin using lysophosphatidylcholine as an emulsifier.

Influence of B-Complex Vitamins on the Pharmacokinetics of Ginsenosides Rg1, Rb1, and Ro After Oral Administration.

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Zheng, Peihe; Chen, Yinbin; Fu, Yangyang; Wang, Hecheng; Wang, Jia; Zheng, Siwen; Xiao, Shengyuan; Wang, Yingping

2017-11-01

After cultivation of ginseng, ginsenosides, which are the major active ingredients of gingeng, were approved for use by the food industry, and began to be used as added functional ingredients to try to improve the quality and price of functional foods. However, the interaction between different types of ginsenosides and nutrients needs further study. We investigated the effect of B-complex vitamins (which are essential nutrients) on the pharmacokinetics of the ginsenosides protopanaxatriol-type saponin Rg 1 , protopanaxadiol-type saponin Rb 1 , and oleanolic acid-type saponin Ro after oral administration. Ginsenosides Rg 1 , Rb 1 , and Ro, with or without B-complex vitamins, respectively, were administered orally to rats to evaluate their pharmacokinetics. The concentration of ginsenosides in plasma was determined by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were fitted using WinNonlin v6.2. After oral coadministration with B-complex vitamins, the area under the concentration-time curve from zero to infinity (AUC 0-∞ ) of ginsenoside Rg 1 was reduced by 70%, that of ginsenoside Rb 1 was reduced by 43%, and that of ginsenoside Ro was reduced by 34%. The AUC 0-∞ of ginsenosides Rg 1 and Rb 1 showed significant differences between different treatments, but the AUC 0-∞ of ginsenoside Ro did not. These results suggest significant ginsenoside-nutrient interactions between ginsenosides Rg 1 , Rb 1 , and B-complex vitamins.

Design of amphotericin B oral formulation for antifungal therapy.

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Liu, Min; Chen, Meiwan; Yang, Zhiwen

2017-11-01

Amphotericin B (AmB) remains the "gold standard" for systemic antifungal therapy, even though new drugs are emerging as the attractive antifungal agents. Since AmB has negligible oral absorption as a consequence of its unfavorable physicochemical characterizations, its use is restricted to parenteral administration which is accompanied by severe side effects. As greater understanding of the gastrointestinal tract has developed, the advanced drug delivery systems are emerging with the potential to overcome the barriers of AmB oral delivery. Much research has demonstrated that oral AmB formulations such as lipid formulations may have beneficial therapeutic efficacy with reduced adverse effects and suitable for clinical application. Here we reviewed the different formulation strategies to enhance oral drug efficacy, and discussed the current trends and future perspectives for AmB oral administration in the treatment of antifungal infections.

THE EFFECTS OF ORAL ADMINISTRATION OF PROPYLENE GLYCOL AND CALCIUM PROPIONATE IN DAIRY COWS

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C. GAVAN

2009-10-01

Full Text Available This study was designed to determine the effects of the oral administration of propylene glycol and calcium propionate on performance of dairy cows. Treatments were 10 l water (control, 10 l water+300 ml propylene glycol (GP and 10 l water+500 g calcium propionate (CP. Animals were mainly of Holstein breeds and were fed and managed in a commercial setting. The cows were divided randomly into an experimental group, n=24 (n=12 with PG and n=12 with CP and a control group, n=11. Cows received the assigned treatment within 10 hours of calving and 24 hours after calving. Health events were recorded during calving and for the first 21 days in milk (DIM. Health examinations were performed on cows that appeared not well. The cows were milked three times daily and milk production was recorded electronically. Milk solid content and somatic cell score were determinate from three consecutive milking weekly till 20 DIM and than monthly till 110 DIM. Retained placenta, hypocalcaemia, displaced abomasums, ketosis and metritis were low in treatment groups (with PG and CP. The cows receiving PG had 2.8 Kg/day grater milk production than control group. The cows receiving CP had 1.7 kg/day grater milk production than control group. Prophylactic administration of PG and CP drenches to Holstein cows may be justified by potentially higher milk yields and reduced health complications.

Hidratación oral continua o a dosis fraccionadas en niños deshidratados por diarrea aguda Oral rehydration in continuous administration or in fractionated doses in dehydrated children with acute diarrhea

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Felipe Mota-Hernández

2002-01-01

Full Text Available Objetivo. Evaluar la seguridad y efectividad de dos técnicas de hidratación oral. Material y métodos. Ensayo clínico aleatorio, hecho en el Servicio de Hidratación Oral del Hospital Infantil de México, Federico Gómez, entre septiembre de 1998 y junio de 1999. Cuarenta pacientes deshidratados por diarrea aguda, menores de cinco años, recibieron suero oral ad libitum (grupo AL y otros cuarenta lo recibieron en dosis fraccionada (grupo DF. Las características clínicas fueron similares en ambos grupos. Los resultados se presentan como promedio y desviación estándar o mediana, según la distribución de frecuencias simples y relativas. Resultados. El promedio de gasto fecal en el grupo AL fue 11.0±7.5 g/kg/h y en el grupo DF 7.1±7.4 (p=0.03. La ingesta de suero, el tiempo de hidratación y la diuresis promedio, fueron similares entre ambos grupos (p>0.05. Seis pacientes del grupo AL y cinco del DF tuvieron gasto fecal alto (>10 g/kg/hora, mejorando con la administración de atole de arroz. Un paciente del grupo AL y dos pacientes del DF tuvieron vómitos persistentes, mejorando con gastroclisis. Ningún paciente requirió rehidratación intravenosa. Conclusiones. Estos resultados sugieren que la administración de suero oral ad libitum, bajo supervisión, es tan segura y efectiva como la técnica de dosis fraccionada para el tratamiento de niños deshidratados por diarrea aguda.Objective. To evaluate the safety and effectiveness of two oral rehydration techniques. Material and Methods. A randomized clinical trial was conducted at the oral rehydration unit of Hospital Infantil de Mexico "Federico Gomez", between September 1998 and June 1999. Forty patients five-year old and younger children, dehydrated due to acute diarrhea, were given oral rehydration solution (ORS ad libitum (AL group; another forty patients received ORS in fractionated doses (FD group. Clinical characteristics were similar in both groups. Results are presented as

Pharmacokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition and Relation to Pharmacodynamic Outcomes.

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Vandrey, Ryan; Herrmann, Evan S; Mitchell, John M; Bigelow, George E; Flegel, Ronald; LoDico, Charles; Cone, Edward J

2017-03-01

Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral ("edible") preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5-3 h post-administration, and lasted 6-8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of

Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

International Nuclear Information System (INIS)

Hao, Hui-fang; Takaoka, Munenori; Bao, Xiao-hong; Wang, Zhi-gang; Tomono, Yasuko; Sakurama, Kazufumi; Ohara, Toshiaki; Fukazawa, Takuya; Yamatsuji, Tomoki; Fujiwara, Toshiyoshi; Naomoto, Yoshio

2012-01-01

Highlights: ► A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. ► TAE226 suppressed proliferation and migration, with a modest effect on adhesion. ► Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. ► TAE226 treatment suppressed the progression of peritoneal dissemination. ► Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken together, a possible strategy for inhibiting peritoneal dissemination by targeting FAK with TAE226 appears to be applicable

Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

Energy Technology Data Exchange (ETDEWEB)

Hao, Hui-fang [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Takaoka, Munenori [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Bao, Xiao-hong [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Wang, Zhi-gang [College of Life Science, Inner Mongolia University, The Key Laboratory of Mammal Reproductive Biology and Biotechnology, Ministry of Education, Hohhot 010021 (China); Tomono, Yasuko [Division of Molecular and Cell Biology, Shigei Medical Research Institute, 2117 Yamada, Okayama 700-0202 (Japan); Sakurama, Kazufumi; Ohara, Toshiaki [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Fukazawa, Takuya; Yamatsuji, Tomoki [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Fujiwara, Toshiyoshi [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Naomoto, Yoshio, E-mail: ynaomoto@med.kawasaki-m.ac.jp [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan)

2012-07-13

Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken

Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.

Science.gov (United States)

Gokbulut, Cengiz; Akar, Ferda; McKellar, Quintin A

2006-07-01

Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is

Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

Science.gov (United States)

2014-01-01

Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.

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Luna, Stelio P L; Basílio, Ana C; Steagall, Paulo V M; Machado, Luciana P; Moutinho, Flávia Q; Takahira, Regina K; Brandão, Cláudia V S

2007-03-01

To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. 36 adult dogs. Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

Directed PCR-free engineering of highly repetitive DNA sequences

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Preissler Steffen

2011-09-01

Full Text Available Abstract Background Highly repetitive nucleotide sequences are commonly found in nature e.g. in telomeres, microsatellite DNA, polyadenine (poly(A tails of eukaryotic messenger RNA as well as in several inherited human disorders linked to trinucleotide repeat expansions in the genome. Therefore, studying repetitive sequences is of biological, biotechnological and medical relevance. However, cloning of such repetitive DNA sequences is challenging because specific PCR-based amplification is hampered by the lack of unique primer binding sites resulting in unspecific products. Results For the PCR-free generation of repetitive DNA sequences we used antiparallel oligonucleotides flanked by restriction sites of Type IIS endonucleases. The arrangement of recognition sites allowed for stepwise and seamless elongation of repetitive sequences. This facilitated the assembly of repetitive DNA segments and open reading frames encoding polypeptides with periodic amino acid sequences of any desired length. By this strategy we cloned a series of polyglutamine encoding sequences as well as highly repetitive polyadenine tracts. Such repetitive sequences can be used for diverse biotechnological applications. As an example, the polyglutamine sequences were expressed as His6-SUMO fusion proteins in Escherichia coli cells to study their aggregation behavior in vitro. The His6-SUMO moiety enabled affinity purification of the polyglutamine proteins, increased their solubility, and allowed controlled induction of the aggregation process. We successfully purified the fusions proteins and provide an example for their applicability in filter retardation assays. Conclusion Our seamless cloning strategy is PCR-free and allows the directed and efficient generation of highly repetitive DNA sequences of defined lengths by simple standard cloning procedures.

21 CFR 520.905 - Fenbendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

Hydroxyurea-induced oral ulceration.

Science.gov (United States)

Badawi, Maha; Almazrooa, Soulafa; Azher, Fatima; Alsayes, Fatin

2015-12-01

Hydroxyurea is an antimetabolite that is widely used in the treatment of many benign and malignant conditions. This drug is usually well tolerated but has a number of side effects that vary in incidence. In cases of clinically significant adverse events, hydroxyurea is usually discontinued either temporarily or permanently, depending on treatment need versus harm caused by side effects. Here, we report a case of oral ulceration associated with hydroxyurea treatment in a patient who had chronic myelogenous leukemia. The patient rapidly developed an oral ulcer 12 days after administration of the drug. Hydroxyurea was discontinued, and the oral lesion appreciably decreased in size and severity. Physicians and dentists should be aware of the association between hydroxyurea and oral lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

Lingual Kinematics during Rapid Syllable Repetition in Parkinson's Disease

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Wong, Min Ney; Murdoch, Bruce E.; Whelan, Brooke-Mai

2012-01-01

Background: Rapid syllable repetition tasks are commonly used in the assessment of motor speech disorders. However, little is known about the articulatory kinematics during rapid syllable repetition in individuals with Parkinson's disease (PD). Aims: To investigate and compare lingual kinematics during rapid syllable repetition in dysarthric…

Lipid-based formulations for oral administration of poorly water-soluble drugs

DEFF Research Database (Denmark)

Mu, Huiling; Holm, René; Müllertz, Anette

2013-01-01

Lipid-based drug delivery systems have shown great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successfully marketed products. Pre-dissolving drugs in lipids, surfactants, or mixtures of lipids and surfactants omits the dissolving....../dissolution step, which is a potential rate limiting factor for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect...

Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits

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Pavithra, B. H.; Jayakumar, K.

2009-01-01

Investigation was carried out in adult New Zealand white rabbits to study the influence of curcumin pre-treatment on pharmacokinetic disposition of norfloxacin following single oral administration. Sixteen rabbits were divided into two groups of eight each consisting of either sex. Animals in group-I were administered norfloxacin (100 mg/kg body weight p.o), while animals in group-II received similar dose of norfloxacin after pre-treatment with curcumin (60 mg/kg body weight per day, 3 days, p.o). Blood samples were drawn from the marginal ear vein into heparin-coated vials at 0 (zero time), 5, 10, 15, 30 min and 1, 2, 4, 6, 12 and 24 h post-treatment. Plasma norfloxacin concentrations were determined by high performance liquid chromatography. The plasma concentration-time profile of norfloxacin was adequately described by a one-compartment open model. The pharmacokinetic data revealed that curcumin-treated animals had significantly (p ≤ 0.05) higher area under the plasma concentration-time curve and area under the first moment of plasma drug concentration-time curve. Prior treatment of curcumin significantly (p ≤ 0.05) increased elimination half-life and volume of distribution of norfloxacin. Further treatment with curcumin reduced loading and maintenance doses by 26% and 24% respectively. PMID:19934593

Oral chemotherapy: food-drug interactions

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Sara Santana Martínez

2015-07-01

Full Text Available Introduction: oral chemotherapy is increasingly used in Oncology. It has important advantages. such as patient comfort. but it also brings new challenges which did not exist with the intravenous therapy. Some of these drugs have interactions with food. leading to changes in their bioavailability. As they are drugs of narrow therapeutic margin. this can lead to alterations in their efficacy and/or toxicity. Objectives: A. Assessing the level of knowledge on the administration of oral cytostatics that present restrictions with meals (drugs that have to be taken with/without food among the outpatients. B. Minimizing the incorrect administration and the risk of food-drug interactions. providing patients with information as to how and when drugs have to be administrated. Methods: once the oral cytostatics with food restrictions were identified. we asked the patients in treatment about the information they had received from the doctor and the way they were taking the medication. We provided those who were taking the drug incorrectly with the right information. In the following visit. it was confirmed if the patients that had been previously taking the cytostatic incorrectly. were taking them in a correct way (intervention accepted/not accepted. Results and conclusions: 40% of the patients interviewed used to take the drug incorrectly. We detected a great diversity depending on the dispensed drug. 95% of the 39 interventions made were accepted. The data obtained suggest the need to reinforce the information that the patient receives. It is important to make sure that the patient understands how and when the oral cytostatic should be administered

21 CFR 520.530 - Cythioate oral liquid.

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2010-04-01

... greyhounds or in animals that are pregnant, sick, under stress, or recovering from surgery. Federal law... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.530 Cythioate oral liquid. (a...

Negative effects of item repetition on source memory.

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Kim, Kyungmi; Yi, Do-Joon; Raye, Carol L; Johnson, Marcia K

2012-08-01

In the present study, we explored how item repetition affects source memory for new item-feature associations (picture-location or picture-color). We presented line drawings varying numbers of times in Phase 1. In Phase 2, each drawing was presented once with a critical new feature. In Phase 3, we tested memory for the new source feature of each item from Phase 2. Experiments 1 and 2 demonstrated and replicated the negative effects of item repetition on incidental source memory. Prior item repetition also had a negative effect on source memory when different source dimensions were used in Phases 1 and 2 (Experiment 3) and when participants were explicitly instructed to learn source information in Phase 2 (Experiments 4 and 5). Importantly, when the order between Phases 1 and 2 was reversed, such that item repetition occurred after the encoding of critical item-source combinations, item repetition no longer affected source memory (Experiment 6). Overall, our findings did not support predictions based on item predifferentiation, within-dimension source interference, or general interference from multiple traces of an item. Rather, the findings were consistent with the idea that prior item repetition reduces attention to subsequent presentations of the item, decreasing the likelihood that critical item-source associations will be encoded.

Detection and quantification of Flavobacterium psychrophilum-specific bacteriophages in vivo in rainbow trout upon oral administration: implications for disease control in aquaculture.

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Christiansen, Rói Hammershaimb; Dalsgaard, Inger; Middelboe, Mathias; Lauritsen, Anne H; Madsen, Lone

2014-12-01

The use of bacteriophages in the treatment and prevention of infections by the fish pathogen Flavobacterium psychrophilum has attracted increased attention in recent years. It has been shown recently that phage delivery via the parenteral route resulted in immediate distribution of phages to the circulatory system and the different organs. However, little is known about phage dispersal and survival in vivo in rainbow trout after delivery via the oral route. Here we examined the dispersal and survival of F. psychrophilum phage FpV-9 in vivo in juvenile rainbow trout after administration by three different methods-bath, oral intubation into the stomach, and phage-coated feed-with special emphasis on the oral route of delivery. Phages could be detected in all the organs investigated (intestine, spleen, brain, and kidney) 0.5 h postadministration, reaching concentrations as high as ∼10(5) PFU mg intestine(-1) and ∼10(3) PFU mg spleen(-1) within the first 24 h following the bath and ∼10(7) PFU mg intestine(-1) and ∼10(4) PFU mg spleen(-1) within the first 24 h following oral intubation. The phages were most persistent in the organs for the first 24 h and then decreased exponentially; no phages were detected after 83 h in the organs investigated. Phage administration via feed resulted in the detection of phages in the intestine, spleen, and kidney 1 h after feeding. Average concentrations of ∼10(4) PFU mg intestine(-1) and ∼10(1) PFU mg spleen(-1) were found throughout the experimental period (200 h) following continuous delivery of phages with feed. These experiments clearly demonstrate the ability of the phages to survive passage through the fish stomach and to penetrate the intestinal barrier and enter the circulatory system after oral delivery, although the quantity of phages found in the spleen was 100- to 1,000-fold lower than that in the intestine. It was also shown that phages could tolerate long periods of desiccation on the feed pellets, with 60

Effects of oral administration of aflatoxin B1 and fumonisin B1 in rabbits (Oryctolagus cuniculus).

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Orsi, R B; Oliveira, C A F; Dilkin, P; Xavier, J G; Direito, G M; Corrêa, B

2007-12-15

The effects of prolonged oral administration (21 days) of fumonisin B(1) (FB(1)) and aflatoxin B(1) (AFB(1)) were studied in male New Zealand rabbits by clinical, pathological, biochemical and sphingolipid analyses. Twenty-four animals were randomly divided into the following four experimental groups: (A) 0 mg FB(1)+0 microg AFB(1)/(kg body weight(bw)day) (control); (B) 0 mg FB(1)+30 microg AFB(1)/(kg bw day); (C) 1.5 mg FB(1)/(kg bw day)+30 microg AFB(1)/(kg bw day); (D) 1.5 mg FB(1)/(kg bw day)+0 microg AFB(1). Animals from group B and principally from group C presented clinical signs of intoxication. Rabbits from group C presented a lower body weight gain than controls. Differences were observed between intoxicated rabbits and controls with respect to absolute and relative liver and kidney weight, hepatic function, serum urea and creatinine levels and Sa/So ratio. The most frequent hepatic and renal injuries were vacuolar degeneration of the liver and kidney as shown by the histopathological and serum biochemical results. Combined administration of AFB(1) and FB(1) resulted in synergistic toxic effects both in the liver and in the kidney, but hepatic injuries were more marked.

Evaluation of renal function following administration of ethane-1-hydroxy-1,1-biphosphonate (EHBP) in animals submitted to oral intoxication with uranyl nitrate

International Nuclear Information System (INIS)

Martinez, A.B.; Mandalunis, P.M.; Bozal, C.B.; Cabrini, Romulo L.; Ubios, A.M.

2003-01-01

Workers involved in the processes of extraction, purification and manufacture of uranium of nuclear plants are occupationally exposed to both natural and enriched uranium. Several chelating agents (TIRON, EDTA, BAI, etc.) have been tested in terms of their capacity to sequester uranium before it reaches its target organs. Our laboratory has studied a first generation biphosphonate, ethane-1-hydroxy-1,1-biphosphonate (EHBP). We have shown that treatment with EHBP induces survival rates of 75% and 100% in adult and suckling rats respectively intoxicated with an intraperitoneal injection of uranyl nitrate. There are no data available to date on the renal function following treatment with EBHP to counteract the toxic effects of an oral lethal dose of uranyl nitrate. The aim of the present study was to assay creatininemia and uremia as end-points to assess renal function. The results obtained reveal that the alterations in renal function induced by oral uranyl nitrate intoxication can be reduced at 48 hours and reverted at 14 days by subcutaneous or oral administration of EHBP. (author)

Comparison of oral and intravenous routes of administration of dipyridamole for thallium imaging of type I diabetics with end-stage renal disease

International Nuclear Information System (INIS)

Boudreau, R.J.; Stony, J.T.; du Cret, R.P.; Kuni, C.C.; Wang, Y.; Wilson, R.F.; Schwartz, J.F.; Castaneda-Zuniga, W.R.

1989-01-01

The authors have frequently seen myocardial infarction after renal transplantation in patient with type I diabetes, and treadmill T1-201 testing in these patients have been inadequate. The authors evaluated dipyridamole (DP) as a substitute for treadmill stress. Because intravenous DP was not approved in the United States at the time of the study, the oral formulation wax used for some patients. The authors have prospectively evaluated 80 uremic diabetics (40 received oral T1-201; 40 received intravenous T1-201). Angiogram and scan observers were blinded. There was not difference in the accuracy of the two routes of administration. Pooling the data gave a sensitivity of 86% and a specificity of 79%. However, their disease prevalence was high (52%), which precluded the use of any screening test. The authors now have recommended angiography for these patients

Oral soft tissue disorders are associated with gastroesophageal reflux disease: retrospective study.

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Watanabe, Masaaki; Nakatani, Eiji; Yoshikawa, Hiroo; Kanno, Takahiro; Nariai, Yoshiki; Yoshino, Aya; Vieth, Michael; Kinoshita, Yoshikazu; Sekine, Joji

2017-08-07

Dental erosion (DE), one of oral hard tissue diseases, is one of the extraoesophageal symptoms defined as the Montreal Definition and Classification of gastroesophageal reflux disease (GERD). However, no study evaluated the relationship between GERD and oral soft tissues. We hypothesized that oral soft tissue disorders (OSTDs) would be related to GERD. The study aimed to investigate the association OSTDs and GERD. GERD patients (105 cases), older and younger controls (25 cases each) were retrospectively examined for oral symptoms, salivary flow volume (Saxon test), swallowing function (repetitive saliva swallowing test [RSST]), teeth (decayed, missing, and filled [DMF] indices), and soft tissues (as evaluation of OSTDs, gingivitis; papillary, marginal, and attached [PMA] gingival indexes, simplified oral hygiene indices [OHI-S], and inflammatory oral mucosal regions). Clinical histories, which included body mass index [BMI], the existence of alcohol and tobacco use, and bruxism, were also investigated. A P value of bruxism, as an exacerbation factor of periodontal disease, in the GERD patients was significantly more frequent than in either control group (P = 0.041). OSTDs were associated with GERD, which was similar to the association between DE and GERD.

[Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study].

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Zhang, Xi-ping; Zhang, Xiang; Yang, Hong-jian; Zou, De-hong; He, Xiang-ming; Yu, Xing-fei; Li, Yong-feng

2015-07-01

To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P drug B and L (P chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.

Pre-Lexical Disorders in Repetition Conduction Aphasia

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Sidiropoulos, Kyriakos; de Bleser, Ria; Ackermann, Hermann; Preilowski, Bruno

2008-01-01

At the level of clinical speech/language evaluation, the repetition type of conduction aphasia is characterized by repetition difficulties concomitant with reduced short-term memory capacities, in the presence of fluent spontaneous speech as well as unimpaired naming and reading abilities. It is still unsettled which dysfunctions of the…

Evidence for the involvement of a nonlexical route in the repetition of familiar words: A comparison of single and dual route models of auditory repetition.

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Hanley, J Richard; Dell, Gary S; Kay, Janice; Baron, Rachel

2004-03-01

In this paper, we attempt to simulate the picture naming and auditory repetition performance of two patients reported by Hanley, Kay, and Edwards (2002), who were matched for picture naming score but who differed significantly in their ability to repeat familiar words. In Experiment 1, we demonstrate that the model of naming and repetition put forward by Foygel and Dell (2000) is better able to accommodate this pattern of performance than the model put forward by Dell, Schwartz, Martin, Saffran, and Gagnon (1997). Nevertheless, Foygel and Dell's model underpredicted the repetition performance of both patients. In Experiment 2, we attempt to simulate their performance using a new dual route model of repetition in which Foygel and Dell's model is augmented by an additional nonlexical repetition pathway. The new model provided a more accurate fit to the real-word repetition performance of both patients. It is argued that the results provide support for dual route models of auditory repetition.

Local, systemic, demographic, and health-related factors influencing pathogenic yeast spectrum and antifungal drug administration frequency in oral candidiasis: a retrospective study.

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Hertel, Moritz; Schmidt-Westhausen, Andrea Maria; Strietzel, Frank-Peter

2016-09-01

In order to identify oral candidiasis patients being at risk of carrying potentially drug-resistant Candida, the aim of the study was to detect local, systemic, demographic, and health-related factors influencing (I) yeast spectrum composition and (II) antifungal administration frequency. Additionally, the aim was to investigate (III) species shift occurrence. Data from 798 patients (496 females, 302 males; mean age 59.7) with oral candidiasis diagnosed based on positive clinical and microbial findings (species identification and CFU count) between 2006 and 2011 were retrospectively analyzed using Pearson's chi(2) test and regression analysis. Among 958 isolates, Candida albicans was the most frequently detected (76.8 %). Also, species intrinsically resistant to azoles were frequently isolated (15.8 and 17.7 % of isolates and patients). (I) Infections only caused by C. albicans were significantly associated with the use of inhalation steroids (p = 0.001) and antibiotics (p = 0.04), super-infection of lichen planus (p = 0.002), and the absence of removable dentures (p oral candidiasis remains C. albicans. Nevertheless, therapeutic problems may be caused by the frequent presence of species intrinsically resistant to azoles, especially in patients wearing dentures.

Depth, temperature, oxygen and salinity profile data from repetitive occupation of a hydrographic station off St. George's, Bermuda from 1954 through 1984 (NODC Accession 0000650)

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National Oceanic and Atmospheric Administration, Department of Commerce — CTD, bottle, and other data were collected from the PANULIRUS and other platforms from repetitive occupations of a hydrographic station off St. George's, Bermuda....

Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study.

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van Dijkhuizen, E H Pieter; Pouw, Juliëtte N; Scheuern, Andrea; Hügle, Boris; Hardt, Sven; Ganser, Gerd; Kümmerle-Deschner, Jasmin Beate; Horneff, Gerd; Holzinger, Dirk; Bulatović Ćalasan, Maja; Wulffraat, Nico M

2016-01-01

Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients. A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO). Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056). The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials.

The development and validation of oral cancer staging using administrative health data

International Nuclear Information System (INIS)

Li-Ting, Chang; Chung-Ho, Chen; Yi-Hsin, Yang; Pei-Shan, Ho

2014-01-01

Oral cancer is a major global health problem. The complexity of histological prognosticators in oral cancer makes it difficult to compare the benefits of different treatment regimens. The Taiwanese National Health database provides an opportunity to assess correlations between outcome and treatment protocols and to compare the effects of different treatment regimens. However, the absence of indices of disease severity is a critical problem. The aim of this study was to ascertain how accurately we could assess the severity of oral cancer at the time of initial diagnosis on the basis of variables in a national database. In the cancer registry database of a medical center in Taiwan, we identified 1067 histologically confirmed cases of oral cancer (ICD9 codes 140, 141 and 143–145) that had been first diagnosed and subjected to initial treatment in this hospital. The clinical staging status was considered as the gold standard and we used concordance (C)-statistics to assess the model’s predictive performance. We added the predictors of treatment modality, cancer subsite, and age group to our models. Our final overall model included treatment regimen, site, age, and two interaction terms; namely, interactions between treatment regimen and age and those between treatment regimen, site, and age. In this model, the C-statistics were 0.82–0.84 in male subjects and 0.96–0.99 in female subjects. Of the models stratified by age, the model that considered treatment regimen and site had the highest C-statistics for the interaction term, this value being greater than 0.80 in male subjects and 0.9 in female subjects. In this study, we found that adjusting for sex, age at first diagnosis, oral cancer subsite, and therapy regimen provided the best indicator of severity of oral cancer. Our findings provide a method for assessing cancer severity when information about staging is not available from a national health-related database

Nanotechnology Based Approaches for Enhancing Oral Bioavailability of Poorly Water Soluble Antihypertensive Drugs

Directory of Open Access Journals (Sweden)

Mayank Sharma

2016-01-01

Full Text Available Oral administration is the most convenient route among various routes of drug delivery as it offers high patient compliance. However, the poor aqueous solubility and poor enzymatic/metabolic stability of drugs are major limitations in successful oral drug delivery. There are several approaches to improve problems related to hydrophobic drugs. Among various approaches, nanotechnology based drug delivery system has potential to overcome the challenges associated with the oral route of administration. Novel drug delivery systems are available in many areas of medicine. The application of these systems in the treatment of hypertension continues to broaden. The present review focuses on various nanocarriers available in oral drug administration for improving solubility profile, dissolution, and consequently bioavailability of hydrophobic antihypertensive drugs.

[Massive residual stones after ESWL for staghorn cystine calculi were completely dissolved by oral administration of alkaline citrate: a case report].

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Nagashima, Masazumi; Udagawa, Koichi; Fujinami, Kiyoshi; Murai, Tetsuo; Noguchi, Kazumi

2007-11-01

A 62-year-old woman was referred to our hospital for bilateral renal stones. Ultrasonography (US) and computed tomography (CT) revealed bilateral staghorn calculi and atrophic left kidney. She had extracorporeal shock-wave lithotripsy (ESWL) for right renal stone during the first 6 months. However, ESWL was not effective and the patient did not want to continue this treatment. Her stone was composed of cystine. We started oral administration of alkaline citrate. Then massive residual stones were completely dissolved during the next 32 months.

Sodium borocaptate (BSH) for Boron Neutron Capture Therapy (BNCT) in the hamster cheek pouch oral cancer model: boron biodistribution at 9 post administration time-points

International Nuclear Information System (INIS)

Garabalino, M.A.; Heber, E.M.; Monti, Hughes A.; Molinari, A.J.; Pozzi, E.C.C.; Trivillin, V.A.; Schwint, Amanda E.

2011-01-01

The therapeutic success of Boron Neutron Capture Therapy (BNCT) depends centrally on boron concentration in tumor and healthy tissue. We previously demonstrated the therapeutic efficacy of boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) as boron carriers for BNCT in the hamster cheek pouch oral cancer model. Given the clinical relevance of sodium mercaptoundecahydro-closo-dodecaborate (BSH) as a boron carrier, the aim of the present study was to expand the ongoing BSH biodistribution studies in the hamster cheek pouch oral cancer model. In particular, we studied 3 additional post-administration time-points and increased the sample size corresponding to the time-points evaluated previously, to select more accurately the post-administration time at which neutron irradiation would potentially confer the greatest therapeutic advantage. BSH was dissolved in saline solution in anaerobic conditions to avoid the formation of the dimer BSSB and its oxides which are toxic. The solution was injected intravenously at a dose of 50 mg 10 B/kg (88 mg BSH / kg). Different groups of animals were killed humanely at 7, 8, and 10 h after administration of BSH. The sample size corresponding to the time-points 3, 4, 6, 9 and 12 h was increased. Samples of blood, tumor, precancerous tissue, normal pouch tissue, cheek mucosa, parotid gland, palate, skin, tongue, spinal cord marrow, brain, liver, kidney, spleen and lung were processed for boron measurement by Optic Emission Spectroscopy (ICP-OES). Boron concentration in tumor peaked to 24-34 ppm, 3-10 h post-administration of BSH, with a spread in values that resembled that previously reported in other experimental models and human subjects. The boron concentration ratios tumor/normal pouch tissue and tumor/blood ranged from 1.3 to 1.8. No selective tumor uptake was observed at any of the time points evaluated. The times post-administration of BSH that would be therapeutically most useful would be 5, 7 and 9 h. The

Recommended oral sodium bicarbonate administration for urine alkalinization did not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer patients.

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Seo, Ho Kyung; Kim, Sung Han; Ahn, Kyung-Ohk; Lee, Sang-Jin; Park, Weon Seo; Kim, Sohee; Hwang, Sang-Hyun; Lee, Do Hoon; Joung, Jae Young; Chung, Jinsoo; Joo, Jungnam; Jeong, Kyung-Chae

2017-11-10

Sodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC. We prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor. Patients with very high-risk and low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations of MMC and its degraded form were measured immediately before and after IVI-MMC. The patients were administered 1.5 g of oral sodium bicarbonate during the preceding evening, in the morning, and immediately before the fourth cycle of the six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH changes was explored with or without oral bicarbonate therapy. Recurrence without progression to muscle-invasive disease was noted in 4 of 26 patients in a 23.7-month follow-up. The mean urinary pH before and after the therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB therapy, respectively. Despite this increase, the concentration of active form of MMC did not change significantly. No correlation was found between urinary pH and MMC concentration. Urine alkalinization by SB administration did not maintain the high concentration of urinary MMC. Urine alkalinization by sodium bicarbonate administration for IVI-MMC did not maintain the high concentration of active urinary MMC in NMIBC.

Appearance of circulating and tissue 14C-lipids after oral 14C-tripalmitate administration in the late pregnant rat

International Nuclear Information System (INIS)

Argiles, J.; Herrera, E.

1989-01-01

Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this time the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland

[Case report: a recurrent gastric cancer in the terminal stage, associated with obstructive jaundice which responded significantly to oral administration of TS-1].

Science.gov (United States)

Tasaka, K; Tomofuzi, Y; Sugihara, Z; Fukuda, H

2001-10-01

TS-1, a novel oral formation of 5-fluorouracil that consists of 1M tegafur (5-FU), 0.4M CDHP and 1M Oxo, is reported to achieve a higher response rate of 49% in patients with advanced gastric cancer in a late phase II study. We report a case of recurrent gastric cancer that responded significantly to the short-term administration of TS-1. A 73-year-old man, who had undergone a curative distal gastrectomy with D2 lymphadenectomy 2 years earlier, had presented with obstructive jaundice resulting from cancerous lymphadenopathy. PTCD was performed for drainage, but cholestasis disappeared completely through the two courses of oral administration of TS-1. The serum level of transaminase and bilirubin remained within normal limits, even with PTCD unequipped, until the patient died of the original disease. The adverse effects observed with the drug were anemia (grade 1) and skin pigmentation (grade 2), both of which improved soon after discontinuing the medication. In conclusion, TS-1 may be well-tolerable and effective in some cases of terminal-stage and/or recurrent gastric cancer, especially those associated with obstructive jaundice arising from the cancerous lymphadenopathy, in that patient QOL can be maintained to a much greater extent.

High-performance liquid chromatographic method for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak-angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma.

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Xie, Ying; Chen, Yi; Lin, Mei; Wen, Jun; Fan, Guorong; Wu, Yutian

2007-05-09

A high-performance liquid chromatographic method was developed and validated for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak-angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma. The coumarin components and the internal standard isopsoralen were extracted from plasma samples with the mixture of tert-butyl methyl ether and n-hexane (4:1, v/v). Chromatographic separation was performed on a C(18) column (200 mm x 4.6mm, 5 microm) with the mobile phase acetonitrile-methanol-water-acetic acid (20:15:65:2, v/v/v/v) at a flow-rate of 1.0 ml/min. Only the peak of oxypeucedanin hydrate and byak-angelicin could be detected in dog plasma after oral administration of ethanol extracts of A. dahurica mainly containing xanthotoxol, osthenol, imperatorin, oxypeucedanin hydrate and byak-angelicin. The calibration curves of oxypeucedanin hydrate and byak-angelicin were linear over a range of 22.08-8830.00 and 6.08-2430.00 ng/ml in dog plasma, respectively. The quantification limit of oxypeucedanin hydrate and byak-angelicin in dog plasma was 22.08 and 6.08 ng/ml, respectively. The intra- and inter-day precision was less than 7.6% and 8.5% and the accuracy was from 91.9% to 106.1%. The lowest absolute recoveries of oxypeucedanin hydrate and byak-angelicin were 85.7% and 87.0%, respectively. The method was successfully applied to the pharmacokinetic studies of oxypeucedanin hydrate and byak-angelicin in dog plasma after oral administration of ethanol extracts from A. dahurica.

Oral Administration of Heat-Killed Mycobacterium manresensis Delays Progression toward Active Tuberculosis in C3HeB/FeJ Mice.

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Cardona, Paula; Marzo-Escartín, Elena; Tapia, Gustavo; Díaz, Jorge; García, Vanessa; Varela, Ismael; Vilaplana, Cristina; Cardona, Pere-Joan

2015-01-01

Low-dose tolerance using heat-killed mycobacteria has been tested as a means of stopping progression toward active tuberculosis (TB) lesions in a human-like murine model using C3HeB/FeJ mice. In the present study, we studied the effect of different treatment schedules with heat-killed non-tuberculous-mycobacteria (NTM) species when given orally, based on the hypothesis of generating oral tolerance. This study included M. manresensis, a new species belonging to the fortuitum group, present in drinking water. Oral treatment with M. manresensis for 2 weeks was able to induce a PPD-specific Tregs population, which has been related to a decrease in the neutrophilic infiltration found in TB lesions. Further mechanistic analysis using PPD-stimulated splenocytes links this 2-week treatment with heat-killed M. manresensis to IL-10 production and memory PPD-specific Tregs, and also to a weak PPD-specific global immune response stimulation, increasing IL-6, TNF, and IFN-γ production. In lungs, this treatment decreased the bacillary load, granulomatous infiltration and pro-inflammatory cytokines (TNF, IFN-γ, IL-6, and IL-17). Oral administration of M. manresensis during standard treatment for TB also significantly reduced the relapse of active TB after ending the treatment. Overall the data suggest that the use of heat-killed M. manresensis could be a new and promising tool for avoiding active TB induction and as adjunctive to TB treatment. This supports the usefulness of generating a new kind of protection based on a complex balanced immune response focused on both destroying the bacilli and including control of an excessive inflammatory response.

Relationship between the number of repetitions and selected percentages of one repetition maximum in free weight exercises in trained and untrained men.

Science.gov (United States)

Shimano, Tomoko; Kraemer, William J; Spiering, Barry A; Volek, Jeff S; Hatfield, Disa L; Silvestre, Ricardo; Vingren, Jakob L; Fragala, Maren S; Maresh, Carl M; Fleck, Steven J; Newton, Robert U; Spreuwenberg, Luuk P B; Häkkinen, Keijo

2006-11-01

Resistance exercise intensity is commonly prescribed as a percent of 1 repetition maximum (1RM). However, the relationship between percent 1RM and the number of repetitions allowed remains poorly studied, especially using free weight exercises. The purpose of this study was to determine the maximal number of repetitions that trained (T) and untrained (UT) men can perform during free weight exercises at various percentages of 1RM. Eight T and 8 UT men were tested for 1RM strength. Then, subjects performed 1 set to failure at 60, 80, and 90% of 1RM in the back squat, bench press, and arm curl in a randomized, balanced design. There was a significant (p squat than the bench press or arm curl at 60% 1RM for T and UT. At 80 and 90% 1RM, there were significant differences between the back squat and other exercises; however, differences were much less pronounced. No differences in number of repetitions performed at a given exercise intensity were noted between T and UT (except during bench press at 90% 1RM). In conclusion, the number of repetitions performed at a given percent of 1RM is influenced by the amount of muscle mass used during the exercise, as more repetitions can be performed during the back squat than either the bench press or arm curl. Training status of the individual has a minimal impact on the number of repetitions performed at relative exercise intensity.

Absorption, Distribution, Metabolism and Excretion of 3-MCPD 1-Monopalmitate after Oral Administration in Rats.

Science.gov (United States)

Gao, Boyan; Liu, Man; Huang, Guoren; Zhang, Zhongfei; Zhao, Yue; Wang, Thomas T Y; Zhang, Yaqiong; Liu, Jie; Yu, Liangli

2017-03-29

Fatty acid esters of monochloropropane 1,2-diol (3-MCPD) are processing-induced toxicants and have been detected in several food categories. This study investigated the absorption, distribution, metabolism, and excretion of 3-MCPD esters in Sprague-Dawley (SD) rats using 3-MCPD 1-monopalmitate as the probe compound. The kinetics of 3-MCPD 1-monopalmitate in plasma was investigated using SD rats, and the results indicated that 3-MCPD 1-monopalmitate was absorbed directly in vivo and metabolized. Its primary metabolites in the liver, kidney, testis, brain, plasma, and urine were tentatively identified and measured at 6, 12, 24, and 48 h after oral administration. Structures were proposed for eight metabolites. 3-MCPD 1-monopalmitate was converted to free 3-MCPD, which formed the phase II metabolites. All of the metabolites were chlorine-related chemical components; most of them existed in urine, reflecting the excretion pattern of 3-MCPD esters. Understanding the metabolism of 3-MCPD esters in vivo is critical for assessing their toxicities.

Induction of oral tolerance with micro-doses of ovomucoid depends on the length of the feeding period

DEFF Research Database (Denmark)

Kjær, Tanja; Frøkiær, Hanne

2002-01-01

Oral administration of antigen induces antigen-specific immunologic tolerance, which is known to be dose-dependent. We studied the influence of continuous oral administration of nanogram and microgram doses of antigen on oral tolerance induction. Mice were continuously exposed to varying doses (1...

Loggerhead oral cavity morphometry study

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Standard external morphometrics and internal oral cavity morphometrics data were collected on wild and captive reared loggerhead sea turtles in size classes ranging...

Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation.

Science.gov (United States)

Reynolds, Anna R; Saunders, Meredith A; Brewton, Honoree' W; Winchester, Sydney R; Elgumati, Ibrahim S; Prendergast, Mark A

2015-09-01

The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored. Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Understanding work related musculoskeletal pain: does repetitive work cause stress symptoms?

DEFF Research Database (Denmark)

Bonde, J. P.; Mikkelsen, S.; Andersen, JH

2005-01-01

for development of regional pain in repetitive work, stress symptoms would likely be on the causal path. AIMS: To examine whether objective measures of repetitive monotonous work are related to occurrence and development of stress symptoms. METHODS: In 1994-95, 2033 unskilled workers with continuous repetitive...... Profile Inventory. RESULTS: Repetitive work, task cycle time, and quantified measures of repetitive upper extremity movements including force requirements were not related to occurrence of stress symptoms at baseline or development of stress symptoms during three years of follow up. CONCLUSIONS......: The findings do not indicate that repetitive work is associated with stress symptoms, but small effects cannot be ruled out. Thus the results question the importance of mental stress mechanisms in the causation of regional pain related to repetitive work. However, the findings should be interpreted...

Inverted U-shaped model: How frequent repetition affects perceived risk

OpenAIRE

Xi Lu; Xiaofei Xie; Lu Liu

2015-01-01

We asked how repeated media reports on technological hazards influence an individual's risk perception. We looked for two contradictory effects, an increasing effect of repetition on perceived risk with the first few repetitions and a decreasing effect with later repetitions, leading to the inverted U-shaped pattern. In an experiment, we demonstrated the inverted U-shaped relationship between the repetition and perceived risk in the context of food risk. The finding broaden...

Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer. Effects on local control, control of metastases, and overall survival

International Nuclear Information System (INIS)

Kurita, Hiroshi; Ohtsuka, Akiko; Kobayashi, Hiroichi; Kurashina, Kenji; Shikama, Naoto; Oguchi, Masahiko

2000-01-01

Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer. (author)

An improved technique for oral administration of solutions of test ...

African Journals Online (AJOL)

Medicut intravenous cannula as an improvised oral cannula to administer solutions of drugs and test substances to experimental rats. Techniques of handling and manipulating the rat with the goal of having the eosophagus as straight as possible ...

Plant-based vaccines for oral delivery of type 1 diabetes-related autoantigens: Evaluating oral tolerance mechanisms and disease prevention in NOD mice.

Science.gov (United States)

Posgai, Amanda L; Wasserfall, Clive H; Kwon, Kwang-Chul; Daniell, Henry; Schatz, Desmond A; Atkinson, Mark A

2017-02-13

Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3 + and LAP + regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy. Recently, dogma was challenged in a report demonstrating oral insulin does not prevent T1D in NOD mice, possibly due to antigen digestion prior to mucosal immune exposure. We used transplastomic plants expressing proinsulin and GAD to protect the autoantigens from degradation in an oral vaccine and tested the optimal combination, dose, and treatment duration for the prevention of T1D in NOD mice. Our data suggest oral autoantigen therapy alone does not effectively influence disease incidence or result in antigen-specific tolerance assessed by IL-10 measurement and Treg frequency. A more aggressive approach involving tolerogenic cytokine administration and/or lymphocyte depletion prior to oral antigen-specific immunotherapy will likely be required to impart durable therapeutic efficacy.

A Phase 1 Pharmacokinetic Study of Cysteamine Bitartrate Delayed-Release Capsules Following Oral Administration with Orange Juice, Water, or Omeprazole in Cystinosis.

Science.gov (United States)

Armas, Danielle; Holt, Robert J; Confer, Nils F; Checani, Gregg C; Obaidi, Mohammad; Xie, Yuli; Brannagan, Meg

2018-02-01

Cystinosis is a rare, metabolic, autosomal recessive, genetic lysosomal storage disorder characterized by an accumulation of cystine in various organs and tissues. Cysteamine bitartrate (CB) is a cystine-depleting aminothiol agent approved in the United States and Europe in immediate-release and delayed-release (DR) formulations for the treatment of nephropathic cystinosis in children and adults. It is recommended that CBDR be administered with fruit juice (except grapefruit juice) for maximum absorption. Omeprazole is a proton pump inhibitor that inhibits gastric acid secretion and, theoretically, may cause the premature release of cysteamine by increasing intragastric pH, thereby affecting the PK of CBDR. This open-label, three-period, randomized study in healthy adult subjects was designed primarily to compare the pharmacokinetics of CBDR capsules after a single oral dose administered with orange juice, water, or multiple oral doses of omeprazole with water at steady state. A total of 32 subjects were randomly assigned to receive study agents in one of two treatment sequences. All subjects completed the study and baseline characteristics of the overall population and the two treatment sequence populations were similar. Peak mean plasma cysteamine concentrations following co-administration of CBDR capsules with orange juice (1892 ng/mL) were higher compared with co-administration with water (1663 ng/mL) or omeprazole 20 mg and water (1712 ng/mL). Mean time to peak plasma concentration was shorter with omeprazole co-administration (2.5 h) compared with orange juice (3.5 h) or water (3.0 h). Statistical comparisons between treatment groups indicated that exposure as assessed by AUC 0-t , AUC 0-∞ , and C max were all within the 80-125% bioequivalence ranges for all comparisons. All treatments were generally well tolerated. Overall, the pharmacokinetics of cysteamine bitartrate DR capsules are not significantly impacted by co-administration with orange juice

TRANSLATION OF ORALITY TRAITS IN LITERARY DIALOGUES

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Lorea Ajanić

2016-01-01

Full Text Available This paper investigates traits of fictive orality and their translations by studying dialogues from Bernhard Schlink’s novel Der Vorleser and their translations into the Croatian and English language. In the first part of the paper the term fictive orality is explained in the context of classification given by Koch and Oesterreicher (1985, which distinguishes between „the language of immediacy” (“Sprache der Nähe” which refers to speech, and “the language of distance” (“Sprache der Distanz” which refers to writing. The ways in which writers create orality in their works, as well as the ways in which it can be recognized in texts, are also represented. In the second part of the paper, selected dialogues from the novel Der Vorleser are analyzed in the source text and in translations. The analysis of dialogues indicates the presence of the following means for expressing fictive orality: punctuation, exclamations, repetition, and descriptions of nonverbal behaviour. These means refer to spoken communication and characters’ emotions – e.g. punctuation is used to express confusion, insecurity, or hesitation in conversations; exclamations are used to express emotions, tone and mood in the analyzed conversations. Additionally, the analysis of translation strategies reveals that the most frequently utilised translation strategies (as proposed by Baker are cultural substitution and paraphrase.

Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration

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Rex Munday

2017-06-01

Full Text Available Ciguatoxins (CTXs, and possibly maitotoxins (MTXs, are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean. The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia, 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS, and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration

Science.gov (United States)

Munday, Rex; Murray, Sam; Rhodes, Lesley L.; Larsson, Michaela E.; Harwood, D. Tim

2017-01-01

Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration. PMID:28665362

Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration.

Science.gov (United States)

Munday, Rex; Murray, Sam; Rhodes, Lesley L; Larsson, Michaela E; Harwood, D Tim

2017-06-30

Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae , G. pacificus , G. honu , and F. paulensis ) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

Repetitive Treatment with Diluted Bee Venom Attenuates the Induction of Below-Level Neuropathic Pain Behaviors in a Rat Spinal Cord Injury Model.

Science.gov (United States)

Kang, Suk-Yun; Roh, Dae-Hyun; Choi, Jung-Wan; Ryu, Yeonhee; Lee, Jang-Hern

2015-07-10

The administration of diluted bee venom (DBV) into an acupuncture point has been utilized traditionally in Eastern medicine to treat chronic pain. We demonstrated previously that DBV has a potent anti-nociceptive efficacy in several rodent pain models. The present study was designed to examine the potential anti-nociceptive effect of repetitive DBV treatment in the development of below-level neuropathic pain in spinal cord injury (SCI) rats. DBV was applied into the Joksamli acupoint during the induction and maintenance phase following thoracic 13 (T13) spinal hemisection. We examined the effect of repetitive DBV stimulation on SCI-induced bilateral pain behaviors, glia expression and motor function recovery. Repetitive DBV stimulation during the induction period, but not the maintenance, suppressed pain behavior in the ipsilateral hind paw. Moreover, SCI-induced increase in spinal glia expression was also suppressed by repetitive DBV treatment in the ipsilateral dorsal spinal cord. Finally, DBV injection facilitated motor function recovery as indicated by the Basso-Beattie-Bresnahan rating score. These results indicate that the repetitive application of DBV during the induction phase not only decreased neuropathic pain behavior and glia expression, but also enhanced locomotor functional recovery after SCI. This study suggests that DBV acupuncture can be a potential clinical therapy for SCI management.

IL-6 Inhibits Upregulation of Membrane-Bound TGF-β 1 on CD4+ T Cells and Blocking IL-6 Enhances Oral Tolerance.

Science.gov (United States)

Kuhn, Chantal; Rezende, Rafael Machado; M'Hamdi, Hanane; da Cunha, Andre Pires; Weiner, Howard L

2017-02-01

Oral administration of Ag induces regulatory T cells that express latent membrane-bound TGF-β (latency-associated peptide [LAP]) and have been shown to play an important role in the induction of oral tolerance. We developed an in vitro model to study modulation of LAP + on CD4 + T cells. The combination of anti-CD3 mAb, anti-CD28 mAb, and recombinant IL-2 induced expression of LAP on naive CD4 + T cells, independent of Foxp3 or exogenous TGF-β. In vitro generated CD4 + LAP + Foxp3 - T cells were suppressive in vitro, inhibiting proliferation of naive CD4 + T cells and IL-17A secretion by Th17 cells. Assessing the impact of different cytokines and neutralizing Abs against cytokines, we found that LAP induction was decreased in the presence of IL-6 and IL-21, and to a lesser extent by IL-4 and TNF-α. IL-6 abrogated the in vitro induction of CD4 + LAP + T cells by STAT3-dependent inhibition of Lrrc32 (glycoprotein A repetitions predominant [GARP]), the adapter protein that tethers TGF-β to the membrane. Oral tolerance induction was enhanced in mice lacking expression of IL-6R by CD4 + T cells and by treatment of wild-type mice with neutralizing anti-IL-6 mAb. These results suggest that proinflammatory cytokines interfere with oral tolerance induction and that blocking the IL-6 pathway is a potential strategy for enhancing oral tolerance in the setting of autoimmune and inflammatory diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

Oral calcitonin

Directory of Open Access Journals (Sweden)

Hamdy RC

2012-09-01

Full Text Available Ronald C Hamdy,1,2 Dane N Daley11Osteoporosis Center, College of Medicine, East Tennessee State University, 2Veterans Affairs Medical Center, Johnson City, TN, USAAbstract: Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget's disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through β-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen® 8-(N-2hydroxy-5-chloro-benzoyl-amino-caprylic acid (5-CNAC (Emisphere Technologies, Cedar Knolls, NJ. Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis failed to

Translation of Syntactic Repetitions as Formal-Aesthetic Marker in Das Brot

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Rosyidah

2017-03-01

Full Text Available Translating repetition as a formal-aesthetic marker in a literary text is a hard task and challenge for translators. The topic of this study is translation of syntactic repetition as formal-aesthetic marker in literary text. The problems examined include: (1 the syntactic repetitions in the source text and (2 the strategies to translate these repetitions carried out by the students. This is a case study with a qualitative approach which is aimed to describe the syntactic repetitions as formal aesthetic markers in the German short story Das Brot written by Wolfgang Borchert and to explain the strategies used by Indonesian students to translate the syntactic repetitions. The research data are repetitive sentences gained from the German short story and from the translated versions done by 60 students. The analysis was carried out interactively and sociosemiotically. The results show that there were repetitions at the sentence level including sentence parts, sentences and content repetition in the source text. The strategies used by the students to translate the repetitions of sentence part and sentence were exact preservation and modified preservation with reduction, implicitation and addition of extra words, avoidance with deletion, explicitation, implicitation, nominalization, and synonymy. In the meantime, content repetitions were translated using the strategy of exact preservation and preservation with modification by adding extra words and using role-based terms of address. Thus, the results lead to two new variations of modified preservation, namely preservation by adding extra words and by changing addressing terms and one new variation of avoidance that is explicitation.

Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

Science.gov (United States)

Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R

2018-03-19

Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.

Grade Repetition in Queensland State Prep Classes

Science.gov (United States)

Anderson, Robyn

2012-01-01

The current study considers grade repetition rates in the early years of schooling in Queensland state schools with specific focus on the pre-schooling year, Prep. In particular, it provides empirical evidence of grade repetition in Queensland state schools along with groups of students who are more often repeated. At the same time, much of the…

Oral Probiotics Alter Healthy Feline Respiratory Microbiota.

Science.gov (United States)

Vientós-Plotts, Aida I; Ericsson, Aaron C; Rindt, Hansjorg; Reinero, Carol R

2017-01-01

Probiotics have been advocated as a novel therapeutic approach to respiratory disease, but knowledge of how oral administration of probiotics influences the respiratory microbiota is needed. Using 16S rRNA amplicon sequencing of bacterial DNA our objective was to determine whether oral probiotics changed the composition of the upper and lower airway, rectal, and blood microbiota. We hypothesized that oral probiotics would modulate the respiratory microbiota in healthy cats, demonstrated by the detection and/or increased relative abundance of the probiotic bacterial species and altered composition of the microbial population in the respiratory tract. Six healthy young research cats had oropharyngeal (OP), bronchoalveolar lavage fluid (BALF), rectal, and blood samples collected at baseline and 4 weeks after receiving oral probiotics. 16S rRNA gene amplicon libraries were sequenced, and coverage, richness, and relative abundance of representative operational taxonomic units (OTUs) were determined. Hierarchical and principal component analyses (PCA) demonstrated relatedness of samples. Mean microbial richness significantly increased only in the upper and lower airways. The number of probiotic OTUs (out of 5 total) that significantly increased in relative abundance vs. baseline was 5 in OP, 3 in BAL and 2 in feces. Using hierarchical clustering, BALF and blood samples grouped together after probiotic administration, and PERMANOVA supported that these two sites underwent significant changes in microbial composition. PERMANOVA revealed that OP and rectal samples had microbial population compositions that did not significantly change. These findings were visualized via PCA, which revealed distinct microbiomes in each site; samples clustered more tightly at baseline and had more variation after probiotic administration. This is the first study describing the effect of oral probiotics on the respiratory microbiota via detection of probiotic species in the airways. Finding

Oral Probiotics Alter Healthy Feline Respiratory Microbiota

Directory of Open Access Journals (Sweden)

Aida I. Vientós-Plotts

2017-07-01

Full Text Available Probiotics have been advocated as a novel therapeutic approach to respiratory disease, but knowledge of how oral administration of probiotics influences the respiratory microbiota is needed. Using 16S rRNA amplicon sequencing of bacterial DNA our objective was to determine whether oral probiotics changed the composition of the upper and lower airway, rectal, and blood microbiota. We hypothesized that oral probiotics would modulate the respiratory microbiota in healthy cats, demonstrated by the detection and/or increased relative abundance of the probiotic bacterial species and altered composition of the microbial population in the respiratory tract. Six healthy young research cats had oropharyngeal (OP, bronchoalveolar lavage fluid (BALF, rectal, and blood samples collected at baseline and 4 weeks after receiving oral probiotics. 16S rRNA gene amplicon libraries were sequenced, and coverage, richness, and relative abundance of representative operational taxonomic units (OTUs were determined. Hierarchical and principal component analyses (PCA demonstrated relatedness of samples. Mean microbial richness significantly increased only in the upper and lower airways. The number of probiotic OTUs (out of 5 total that significantly increased in relative abundance vs. baseline was 5 in OP, 3 in BAL and 2 in feces. Using hierarchical clustering, BALF and blood samples grouped together after probiotic administration, and PERMANOVA supported that these two sites underwent significant changes in microbial composition. PERMANOVA revealed that OP and rectal samples had microbial population compositions that did not significantly change. These findings were visualized via PCA, which revealed distinct microbiomes in each site; samples clustered more tightly at baseline and had more variation after probiotic administration. This is the first study describing the effect of oral probiotics on the respiratory microbiota via detection of probiotic species in the

RPERT: Repetitive-Projects Evaluation and Review Technique

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Remon Fayek Aziz

2014-03-01

Full Text Available Estimating expected completion probability of any repetitive construction project with a specified/certain duration including repetitive identical activities by using program evaluation and review technique is the most essential part in construction areas since the activities were had optimistic, most likely and pessimistic durations. This paper focuses on the calculation of expected completion probability of any repetitive construction project within a specified/certain duration (contract duration by using Line Of Balance technique (LOB in case of single or multiple number of crews integrated with Program Evaluation and Review Technique (PERT. Repetitive-Projects Evaluation and Review Technique (RPERT, which is a simplified software, will generate the expected project completion probability of a specified/certain duration (contract duration. RPERT software is designed by java programming code system to provide a number of new and unique capabilities, including: (1 Viewing the expected project completion probability according to a set of specified durations per each identical activity (optimistic time, most likely time, and pessimistic time in the analyzed project; (2 Providing seamless integration with available project time calculations. In order to provide the aforementioned capabilities of RPERT, the system is implemented and developed in four main modules: (1 A user interface module; (2 A database module; (3 A running module; and (4 A processing module. At the end, an illustrative example will be presented to demonstrate and verify the applications of proposed software (RPERT, by using probabilistic calculations for repetitive construction projects.

Effects of urine alkalization and activated charcoal on the pharmacokinetics of orally administered carprofen in dogs.

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Raekallio, Marja R; Honkavaara, Juhana M; Säkkinen, Mia S; Peltoniemi, S Marikki

2007-04-01

To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs. 6 neutered male Beagles. Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test. Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean +/- SD maximum concentration was 85.9 +/- 11.9 mg/L and 58.1 +/- 17.6 mg/L, and area under the time-concentration curve was 960 +/- 233 mg/L x h and 373 +/- 133 mg/L x h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations. After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.

Oral insulin delivery: existing barriers and current counter-strategies.

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Gedawy, Ahmed; Martinez, Jorge; Al-Salami, Hani; Dass, Crispin R

2018-02-01

The chronic and progressive nature of diabetes is usually associated with micro- and macrovascular complications where failure of pancreatic β-cell function and a general condition of hyperglycaemia is created. One possible factor is failure of the patient to comply with and adhere to the prescribed insulin due to the inconvenient administration route. This review summarizes the rationale for oral insulin administration, existing barriers and some counter-strategies trialled. Oral insulin mimics the physiology of endogenous insulin secreted by pancreas. Following the intestinal absorption of oral insulin, it reaches the liver at high concentration via the portal vein. Oral insulin on the other hand has the potential to protect pancreatic β-cells from autoimmune destruction. Structural modification, targeting a particular tissue/receptor, and the use of innovative pharmaceutical formulations such as nanoparticles represent strategies introduced to improve oral insulin bioavailability. They showed promising results in overcoming the hurdles facing oral insulin delivery, although delivery is far from ideal. The use of advanced pharmaceutical technologies and further research in particulate carrier system delivery predominantly nanoparticle utilization would offer useful tools in delivering insulin via the oral route which in turn would potentially improve diabetic patient compliance to insulin and the overall management of diabetes. © 2017 Royal Pharmaceutical Society.

Oral administration of Moringa oleifera oil but not coconut oil prevents mercury-induced testicular toxicity in rats.

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Abarikwu, S O; Benjamin, S; Ebah, S G; Obilor, G; Agbam, G

2017-02-01

This study was conducted to compare the effects of administration of coconut oil (CO) and Moringa oleifera oil (MO) on testicular oxidative stress, sperm quality and steroidogenesis parameters in rats treated with mercury chloride (HgCl 2 ). After 15 days of oral administration of CO (2 ml kg -1 body weight) and MO (2 ml kg -1 body weight) along with intraperitoneal (i.p.) administration of HgCl 2 (5 mg kg -1 body weight) alone or in combination, we found that CO treatment did not protect against HgCl 2 -induced poor sperm quality (motility, count) as well as decreased testosterone level and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Treatment with CO alone decreased glutathione (GSH), and glutathione peroxidase (GSH-Px) activities and increased malondialdehyde (MDA) level in rat's testis, whereas MO did not change these parameters. Cotreatment with MO prevented HgCl 2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl 2 (2 ml kg -1 body weight + 5 mg kg -1 body weight) on the investigated endpoints. In conclusion, MO and not CO decreased the deleterious effects of HgCl 2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl 2 -induced oxidative damage. © 2016 Blackwell Verlag GmbH.

Safe practices and financial considerations in using oral chemotherapeutic agents.

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Bartel, Sylvia B

2007-05-01

Safe handling practices and financial concerns associated with oral chemotherapy in non-traditional settings are discussed. Oral chemotherapy may pose a risk to patients because of a narrow therapeutic index, complex dosing regimen, dispensing by community pharmacists without prescription order review by an oncology pharmacist or nurse, or self-administration in the home or another nontraditional setting, where patient monitoring is infrequent. Errors in prescribing, dispensing, and administration and patient or caregiver misunderstandings are potential problems with the use of oral chemotherapy that need to be addressed when developing safe practices. Changes in Medicare pharmaceutical reimbursement rates and rules need to be monitored because they have the potential to affect patient care and outcomes. Patient assistance programs and advocacy groups can help alleviate financial concerns associated with oral chemotherapy. Consensus guidelines specific to safe handling of oral chemotherapy in the home or other nontraditional setting need to be developed. Also, healthcare providers must understand reimbursement and provide direction to patients when patient assistance programs or advocacy groups can assist with the financial challenges of oral chemotherapy.

The emergency contraceptive drug, levonorgestrel: a review of post-coital oral and peri-coital vaginal administration for prevention of pregnancy.

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