Objective: Pullulan derivatives (PD) can be used to make self-assembled hydrogel nanoparticles which are responsive to ionic strength. The aim of this study is to evaluate the potential of PD as a retaining carrier of radioisotope inside tumors. Materials and Methods: Four types of PD were evaluated which included pullulan acetate (PA), succinylated PA (SPA), PA-DTPA and SPA-DTPA conjugates. They were radiolabeled with Tc-99m. Labelling efficiencies were determined at 30 min, 1, 2, 4 and 12 hours after radiolabeling. CT-25 colon cancer cells were subcutaneously injected into Balb/c mice. After 2 weeks of subcutaneous injection, Tc-99m-labelled PD (Tc-99m-PD) were injected into the tumors. Whole body images of mice were obtained at 30 min, 1, 2, and 12 hr after intratumoral injection. All twenty mice were grouped into four groups by largest diameter; control A (largest diameter = 5 mm, n = 5), control B (largest diameter = 10 mm, n = 5), pullulan A (largest diameter = 5 mm, n = 5), pllulan B (largest diameter = 10 mm, n = 5). Dynamic images were obtained for 1 hour after intratumoral injection. Static images were obtained at 1 hr, 2 hr, 3 hr and 4 hr after intratumoral injection with Tc-99m pertechnetate and Tc-99m-PA. Target-to-background ratios and retention rates were calculated. Results: Labeling efficiencies of PA, SPA, PA-DTPA and SPA-DTPA were $94.5{\pm}5.9%,\;97.8{\pm}3.5%\;94.2{\pm}3.8%,\;and\;92.5{\pm}6.2%$, respectively (p>0.05). Percent retention rates (%RR) of PA and PA-DTPA were significantly higher than those of control, however, those of SP-DTPA and SPA became similar to control at 4 and 12 hr, respectively. %RR of pullulan A and pullulan B at 1, 4 and 8 hr is significantly higher than that of control (p < 0.05). However, %RR between pullulan A and pullulan B were similar. Conclusion: The lonic strength dependent PD-nanoparticles are retained in the tumor. No difference of %RR according to tumor size was noted. Therapeutic application of PD labelled with beta- or alpha- emitting radionuclides can be expected.
Nam, Hae-Seong;Koh, Won-Jung;Suh, Gee Young;Chung, Man Pyo;Kwon, O Jung;Kim, Hojoong
Tuberculosis and Respiratory Diseases
/
v.65
no.5
/
pp.390-395
/
2008
Background: Since the early 1980s, interferon-alpha ($IFN-{\alpha}$) has been used as adjuvant therapy in pediatric patients with recurrent respiratory papillomatosis (RRP). However, its efficacy in adults needs to be validated. Since 2002, Samsung Medical Center's guidelines have mandated regular injection of $IFN-{\alpha}$ in patients with RRP to prevent recurrence. To evaluate these guidelines, patient data were investigated. Methods: Five patients diagnosed as having RRP by bronchoscopy and histopathology were included. After initial bronchoscopic intervention, including laser cauterization, all patients received subcutaneous injection of 6 million units of $IFN-{\alpha}$ every 2 months. Further bronchoscopic intervention was carried out as needed. Patients were regularly evaluated using bronchoscopy or computed tomography. Results: The median age of the patients was 44 years (range 13~68), and the median duration of papillomatosis was 31 years (range 1~45). Three and two patients had juvenile-onset and adult-onset disease, respectively. Two patients had a history of tracheostomy at the time of diagnosis. The median duration of $IFN-{\alpha}$ therapy was 56 months (range 12~66). Two patients showed complete remission at 12 and 36 months after $IFN-{\alpha}$ injection, respectively. The other three patients showed partial remission, and the number of laser therapy sessions was significantly reduced.Conclusion: Intermittent $IFN-{\alpha}$ injection is effective in patients with long-standing RRP and can reduce the number of laser therapy sessions required in their treatment.
The productions of beta-exotoxin from sixteen Bacillus thuringiensis strains were examined by Micrococus flava primarily, and then measured by spectrophotometer during culturing in Conner and Hansen mineral salts medium at 28$^{\circ}C$. Also the toxic effects of the toxin to mice were checked. The growth of Bacillus thuringiensis K2 and BTK2-T1, -T13, -T33 and -T40 got into stationary phase at 6 hour culture and then maintained it up to 48 hours without severe fluctuation. The production of beta-exotoxin from the strains, BTK2, BTK2-T1, -T13, -T17 and -T33 appeared at 6 hour culture and the amounts of the toxin were about 40 $\mu\textrm{g}$/$m\ell$ at 6 hour culture, approximately 70 $\mu\textrm{g}$/$m\ell$ at 12 hours, approximately 85$\mu\textrm{g}$/$m\ell$ from 24 hours to 48 hours. At 48 hour-culture, BTK2 produced 80 $\mu\textrm{g}$/$m\ell$ of beta-exotoxin (5.5$\times$10$^{8}$ cells/$m\ell$, BTK2-T13 produced 84 $\mu\textrm{g}$/$m\ell$ (4.3$\times$10$^{8}$ cells/$m\ell$), BTK2-T17 produced 87$\mu\textrm{g}$/$m\ell$ (1.4$\times$10$^{8}$ cells/$m\ell$), and BTK2-T33 produced 84 $\mu\textrm{g}$/$m\ell$ (4.9$\times$10$^{8}$ cells/$m\ell$). All other serotypes also produced beta-exotoxin. At 48 hour culture, BTK-37 produced 88$\mu\textrm{g}$/$m\ell$ (6.1$\times$10$^{8}$ cells/$m\ell$), BTK-35 produced 81 $\mu\textrm{g}$/$m\ell$), and the rest of them produced less than 70 $\mu\textrm{g}$/$m\ell$. To check the toxicity of beta-exotoxin and B. thuringiensis, the cultured media with microorganisms were inoculated to mice by per os, intraperiloneal, subcutaneous and intracerebral injection, and nasal cavity inoculation for 30 days. However, the toxin did not kill all of the treated mice.
In the present study toxicity and immunostimulating activity of the lectin(KML-C), which was extracted from Korean mistletoe(Viscum album coloratum) were investigated in swine. To determine the toxicity, lectin was injected into thigh or cervical muscles of 4-week-old piglets(Landrace) and observed clinically and pathologically. For determination of the immnunostimulating activity, lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine of Aujeszky's disease virus(ADV)(NYJ1-87) which was inactivated by 0.2% formalin was injected into the cervical muscle of antibody-negative piglets in the same age group. Subpopulation of the immune cells and serum neutralizing(SN) antibodies in the piglets were examined after vaccination, and resistance of the piglets against challenge by virulent NYJ1-87 was further examined. The results were also compared with those from piglets injected with aluminum hydroxide [$Al(OH)_3$]-adjuvanted vaccine of inactivated NYJ1-87 and NYJ1-87 vaccine without adjuvant, and the results are as follows. By injection of lectin with $30{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets died after signs such as dyspnea, fever, systemic erythema and subcutaneous hemorrhages, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with $7{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets showed signs such as edema and cutaneous hemorrhage in the injected area, lameness and depression, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with 1, 3 and $5{\mu}g/kg$ of body weight to the thigh muscle of each one piglet, signs such as congestion, induration and grayish coloration in the injected area, depression and inappetence were observed in all piglets. Toxic changes were also observed in the liver and kidney of piglets by lectin of 3 and $5{\mu}g$. By injection of lectin with 0.5 and $0.7{\mu}g/kg$ of body weight to the cervical muscle of each 9 piglets, all piglets were clinically normal and there were no significant changes in blood counts and chemistry values. Whereas, epithelial swelling and vacuolation of convoluted tubules were observed from one piglet injected with lectin of $0.7{\mu}g$, and necrosis and fibrosis of muscular fiber were observed in the muscle of one piglet injected with lectin of $0.5{\mu}g$. Only population of sIgM+ B lymphocytes increased among immune cells in all of 15 piglets immunized with lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine, while compared to those in $Al(OH)_3$-adjuvanted vaccine and vaccine without adjuvant. No additional stimulation to the immune cells was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. In piglets immunized with lectin-adjuvanted vaccine, SN titers in reciprocal values for loge were 1.3-4.0 at 1-4 weeks after vaccination, which was similar to those with 1.0-3.3 by vaccine without adjuvant but lower than those with 2.0-5.7 by $Al(OH)_3$-adjuvanted vaccine. Also, no additional increase in the SN titers was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. Piglets immunized with lectin-adjuvanted vaccine were resistant to challenge by the virulent NYJ1-87 at 4 weeks after vaccination, and the SN titers reached to 5.0 one week after challenge, which was higher than those with 4.0 by vaccine without adjuvant but somewhat lower than those with 7.7 by $Al(OH)_3$-adjuvanted vaccine.
Park, Sookyoung;Won, Jinyoung;Park, Kanghui;Hong, Yonggeun
Journal of Life Science
/
v.28
no.7
/
pp.819-826
/
2018
Orostachys japonicus (OJ) is a medicinal herb with immunoregulatory, anti-aging, anti-oxidative, and many other therapeutic properties. The purpose of this study was to elucidate the anti-cancer property of cultivated OJ. SW480 cell viability was significantly reduced by cumulative exposure to OJ extract. We also observed inhibitory effects of OJ after 72 hr through the growth and migration of SW480 cells using scratch assay. SW480 cells in OJ-free medium began to move into the scratch site at 24 hr; however, cells in medium containing OJ did not migrate into the scratch site until 48 hr. Male C57BL/6 mice (4 weeks old) were orally administered OJ extract for 31 days before injection of SW480 cells. At 7, 14, and 28 days after subcutaneous injection of SW480 cells, tumor weight and volume were analyzed. The body weight of the OJ-treated group was continuously increased during administration of the OJ extract relative to the control group. Injection of SW480 cells caused a reduction in body weight in all groups; however, the OJ-treated group exhibited a significant increase in body weight after 14 days. Tumor weight and volume were lower in the OJ-treated group than in the control group after 28 days. Although these results suggest that OJ suppresses the proliferation and migration of human colon cancer cells, additional studies are required to provide preclinical evidence before launching clinical trials evaluating OJ as an anti-cancer biohealth product.
Purpose: Thallium behaves similarly to potassium in vivo. Potassium channel opener (K-opener) opens ATP-sensitive $K^+$-channel located at cell membrane, resulting in potassium efflux from cytosol. We have previously reported that K-opener can alter biokinetics of Tl-201 in cultured cells and in vivo. Malignant tumor cells have high Na-K ATPase activity due to increased metabolic activities and dedifferentiation, and differential delineation of malignant tumor can be possible with Tl-201 imaging. K-opener may affect tumoral uptake of Tl-201 in vivo. To investigate the effects of pinacidil (one of the potent K-openers) on the localization of the tumor with Tl-201 chloride, we evaluated the changes in biodistribution of Tl-201 with pinacidil treatment in tumor-bearing mice. Materials and Methods: Baltic mice received subcutaneous implantation of murine breast cancer cells in the thigh and were used for biodistribution study 3 weeks later. $100{\mu}g$ of pinacidil dissolved in $200{\mu}l$ DMSO/PBS solution was injected intravenously via tail vein at 10 min after 185 KBq ($5{\mu}Ci$) Tl-201 injection. Percentage organ uptake and whole body retention ratio of Tl-201 were measured at various periods after injection, and values were compared between control and pinacidil-treated mice. Results: Pinacidil treatment resulted in mild decrease in blood levels of Tl-201, but renal uptakes were markedly decreased at 30-min, 1- and 2-hour, compared to control group. Hepatic, intestinal and muscular uptake were not different. Absolute percentage uptake and tumor to blood ratios of Tl-201 were lower in pinacidil treated mice than in the control group at all time points measured. Whole body retention ratio of Tl-201 was lower in pinacidil treated mice ($58{\pm}4%$ ), than in the control group ($67{\pm}3%$) at 24 hours after with injection of $100{\mu}g$ pinacidil. Conclusion: K-opener did not enhance, but rather decreased absolute tumoral uptake and tumor-to-blood ratios of Tl-201. Decreased whole body retention ratio and renal uptake were observed with pinacidil treatment in tumor-bearing mice.
Hwang, Jung Hye;Chung, Man Pyo;Kang, Eun Hae;Kim, Kyung Chan;Lee, Byoung-Hoon;Koh, Won-Jung;Suh, Gee Young;Kim, Hojoong;Lee, Kyung Soo;Han, Joungho;Kwon, O Jung
Tuberculosis and Respiratory Diseases
/
v.56
no.6
/
pp.619-627
/
2004
Background : Corticosteroids in combination with cytotoxic drugs are the mainstays of therapy for idiopathic pulmonary fibrosis (IPF). However, there has been no regimen showing any survival benefit. The aim of this study was to describe a short-term clinical experience on interferon gamma-1b (IFN-${\gamma}1b$) therapy for IPF, as an antifibrotic agent. Methods : Medical records of 27 patients who were treated with IFN-${\gamma}1b$ (2 million IU, 3 times a week, subcutaneous injection) were retrospectively reviewed. Treatment response was assessed using ATS/ERS criteria in 17 patients who received IFN-${\gamma}1b$ for more than 6 months. In addition, we compared the efficacy of IFN-${\gamma}1b$ therapy with that of cyclophosphamide${\pm}$prednisolone therapy (n=26). Results : The median age of IFN-${\gamma}$ treated group (M:F=19:8) was 59 years (44-74 years). Compared to the patients who showed a stable response at 6 months (n=12), the deteriorated group (n=5) had worse baseline lung function (FVC, $55.4{\pm}11.3%$ vs. $70.7{\pm}10.9%$, p=0.019; DLco, $50.3{\pm}7.3%$ vs. $76.9{\pm}19.6%$, p=0.014). Lower baseline $PaO_2$ on room air breathing was observed in the deteriorated group ($68.6{\pm}7.8mmHg$ vs. $91.4{\pm}6.6mmHg$ p=0.001). Subcutaneous IFN-${\gamma}1b$ did not show better efficacy than prednisolone. Five patients discontinued IFN-${\gamma}$ because of severe side effects. ARDS developed in one patient, who eventually died. Conclusion : The administration of IFN-${\gamma}1b$ is not desirable for patients diagnosed with IPF with poor lung function. Long-term and large-scaled clinical studies are needed for its efficacy in IPF.
This study was conducted to determination of the endocrine distruptor function of 'Parabens' by dosing ethyl paraben, propyl paraben, isopropyl paraben, butyl paraben and isobutyl paraben to the immature SD rats. 18 groups were given vehicle control group, negative control group (Dibutyl phthalate), postive control group ($1'7-{\alpha}$ Ethynylestrdiol) and each paraben groups involved 3 dose level. Rats were injected with 62.5, 250 and 1,000mg/kg from postnatal day 19 till 21 once a day in subcutaneous and a total 3, times. There was no treatment related death. but, subcutaneous nodule, edema, alopecia and scrub formation on injection site was observed. These signs was become worse in high dose level. these signs was cause from physical stimulation by test substance which parabens were mix with com oil as vehicle. In the analysis of organ weights, absolute and relative weights of brain, spleen, liver, thymus, heart, kidneys, adrenals, ovaries and vagina were no difference with control group. but, wet and blotted weight of uterus was increased in every high dose parabens treat group. Especially, all dose level of isobutyl paraben was showed increment of uterus weight. uterus dilatation of parabens treated group was observed in gross anatomic pathology and these result was agree with wet and blotted weight of uterus. In the result of this study, estrogenic effect as endocrine distruptor was observed in ethyl paraben, propyl paraben, isopropyl paraben, butyl paraben and isobutyl paraben. and it was considered isobutyl paraben has highest estrogrnic effect under the condition of this study.
Twelve pigs were used to investigate the effects of polyclonal antibody candidate against abdominal (AAb) and subcutaneous adipocyte membrane proteins (SAb) on body weight, fecaldigestibility and blood metabolites. When AAb and SAb developed by Choi et al. (2010) were injected to pigs, the numerical increase in BW (body weight) occurred at 4 weeks post-treatment, but BW for an entire period was also increased, indicating that the BW increase may not be affected by the antibodies injection. Antibodies treatment did not affect (P>0.05) fecal digestibility of dry matter, crude protein, crude fat and crude fiber. Fecal digestibility of crude ash for control (no treatment) at 2 weeks decreased, and that for non-immunized serum treatmentgroup at 4 weeks post-treatment increased, respectively (P<0.05). However, fecal digestibility of crude ash for AAb and SAb groups did not significantly change. At 4 weeks after the antibodies treatment, blood urea N concentration for AAb and SAb groups was significantly increased (P<0.05). However, these increases may not be caused by the antibodies treatment because similar pattern in blood urea N concentration occurred before the antibodies treatment. Antibodies treatment did not affect concentration of plasma glucose and triglycerides (P<0.05). Compared with control, concentration of plasma total cholesterol for AAb and SAb groups at 4 weeks post-treatment was significantly (P<0.05) decreased. This may suggest that body fat reduction possibly occurs. In conclusion, the AAb and the SAb developed by Choi et al. (2010) may have safety in nutritional physiological metabolism in pigs. Further study on in vivo fat reduction of the antibodies against abdominal and subcutaneous adipocytes of pigs should be required for fat-reduced pork production.
The study was carried out to evaluate the effect of exogenous bovine somatotropin on water metabolism in relation to mammary function in early lactation of crossbred Holstein cattle. Ten, 87.5% crossbred Holstein cattle were divided into two groups of 5 animals each. At day 60 of lactation, the control group was given placebo while animals in the experimental group were given recombinant bovine somatotropin (rbST) by subcutaneous injection with 500 mg of rbST (14-days prolonged-release rbST). In rbSTtreated animals, milk yield increased 19.8%, which coincided with a significant increase in water intake (p<0.01), while DM daily intake was not different when compared to the control animals. Water turnover rate as absolute values significantly increased (p<0.05), while the biological half-life of water did not change in rbST-treated animals. Total body water (TBW) and total body water space (TOH) as absolute values significantly increased (p<0.01) in rbST-treated animals, while it was decreased in the control animals. Absolute values of empty body water (EBW) markedly increased (p<0.05), which was associated with an increase in the extracellular fluid (ECF) volume. Absolute values of plasma volume and blood volume were also significantly increased (p<0.05) in rbST-treated animals. The increase in mammary blood flow in rbST-treated animals was proportionally higher than an increase in milk production. The plasma IGF-1 concentration was significantly increased (p<0.01) in rbST-treated animals when compared with those of control animals during the treatment period. Milk fat concentration increased during rbST treatment, while the concentrations of both protein and lactose in milk were not affected. The present results indicate that rbST exerts its effect on an increase in both TBW and EBW. An increased ECF compartment in rbST-treated animals might partly result from the decrease in fat mass during early lactation. The action of rbST on mammary blood flow might not be mediated solely by the action of IGF-1 for increase in blood flow to mammary gland. An elevation of body fluid during rbST treatment in early lactation may be partly a result of an increase in mammary blood flow in distribution of milk precursors to the gland.
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