• Natural Product Sciences
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• 제13권1호
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• pp.33-39
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• 2007

Eleven polyhydroxyursane triterpenoids (PHUTs) were tested to determine their cytoprotective, immunosuppressive and anti-inflammatory effects. To compare the bioactivities of $19{\alpha}$-hydroxyursane-type triterpenoids {23-hydroxytormentic acid (6), its methyl ester (7), tormentic acid (8), niga-ichigoside $F_1$ (9),euscaphic acid (10) and kaji-ichigoside $F_1$ (11)} of the Rosaceae crude drugs (Rubi Fructus and Rosa rugosae Radix) with PHUTs possessing no $19{\alpha}-hydroxyl$ of Centella asiatica (Umbelliferae), the four PHUTs, asiaticoside (1), madecassoside (2), asiatic acid (3), and madecassic acid (4) were isolated from C. asiatica and 23-hydroxyursolic acid (5) from Cussonia bancoensis. Cytoprotective effects were assessed by measuring cell viabilities against cisplatin-induced cytotoxocity in $LLC-PK_1$, cells (proximal tubule, pig kidney) to determine whether these agents have protective effects against nephrotoxicity caused by cisplatin. The inhibitory effect of 11 PHUTS on nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ were evaluated by measuring nitrite accumulation in lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cells, and their anti-inflammatory effects were tested in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model. Six MHUTs (compounds 1, 2, 4, 6, 10, and 11) exhibited higher cell viabilities during cisplatin-induced cytotoxicity testing even at a concentration of $200\;{\mu}g/ml$ than cisplatin only-treated group, suggesting that ese compounds have the potentcytoprotective efffcts. Compounds 1 and 3 of the C. asiatica and niga-ichigoside $F_1$ exhibited no inhibitory effect on NO and/or $PGE_2$ production whereas other PHUTs produced mild to significant NO and/or $PGE_2$ production.The four compounds (2, 5, 9, and 10) potently inhibited mouse ear edema induced by TPA whereas two compounds (1 and 3) had no activity in this test. These results suggest that many PHUTs are potentchemopreventives. Structure-activity relationship (SAR) was also discussed in each assay with regard to the significant role of OHs at the position of 2, 3, 6, 19, and 23 and to the glycoside linkage at the 28-carboxyl.

• IMMUNE NETWORK
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• 제3권2호
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• pp.150-155
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• 2003

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.

• Clinical and Experimental Pediatrics
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• 제53권7호
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• pp.745-752
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• 2010

Purpose: There is currently little evidence to support intravenous immune globulin (IVIG) therapy for pediatric myocarditis. The purpose of our retrospective study was to assess the effects of IVIG therapy in patients with presumed myocarditis on survival and recovery of ventricular function and to determine the factors associated with its poor outcome. Methods: We reviewed all consecutive cases of patients with myocarditis with left ventricular dysfunction verified by echocardiogram who had visited 3 university hospitals between January 2000 and September 2009. These patients were divided into 2 groups. Group 1 consisted of 23 patients (69.6%) who received IVIG alone or IVIG in combination with steroids, and group 2 consisted of 10 patients (30.3%) who received neither IVIG nor other immunosuppressive agents. Clinical manifestations, laboratory results, echocardiographic findings, and outcomes were compared between these 2 groups. Results: One year after the initial presentation, the difference in the probability of survival did not show statistical significance in IVIGtreated patients ($P$=0.607). Of the echocardiographic parameters on admission, a shortening fraction of less than 15% was associated with unremitting cardiac failure. Furthermore, anemic patients were more likely to have elevated N-terminal fragment levels of the B-type natriuretic peptide (NT-proBNP) in the progressed group ($P$=0.036). Conclusion: There was no difference between the IVIG-treated patients and the control patients in the degree of recovery of left ventricular function and survival. Prospective, randomized, clinical studies are needed to elucidate the effects of IVIG treatment during the acute stage of myocarditis on ultimate outcomes.

• Journal of Dental Anesthesia and Pain Medicine
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• 제17권2호
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• pp.113-119
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• 2017

Background: The purpose of this study was to investigate the distribution of systemic diseases and medications in patients older than 65 years of age who visited the hospital for implant treatment, as well as to investigate basic information about surgical complications that may occur after insured implant treatment. Method: A total of 126 patients over 65 years of age were treated for implant surgery from October 1, 2013 to October 30, 2016. Electronic chart review was conducted to obtain medical records, which included sex, age, systemic diseases, medication(s) being taken, and control of the medications. Five patients were excluded due to lack of medical records giving information about systemic disease. Results: Of the 126 patients, 112 (88.9%) were taking medication due to systemic disease and 9 patients (7.1%) were not. The sex distribution was 71 women and 55 men and the highest proportion of patients were between 65 and 69 years old. The most common diseases were, from most to least frequent, hypertension, cardiovascular disease, diabetes, and osteoporosis. The drug groups that can cause major complications after dental treatment were classified as hemorrhagic, osteoporotic, and immunosuppressive agents, and were taken by 45 (35.7%), 22 (17.5%) and 4 (3.2%) patients, respectively. Conclusion: Given that 88.9% of the elderly patients who were eligible for insurance implant treatment had systemic disease, it is necessary to carefully evaluate patients' medical histories and their general conditions in order to prevent emergencies during implant surgery.

• Tuberculosis and Respiratory Diseases
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• 제43권1호
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• pp.102-107
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• 1996

본 환자는 평소 건강하던 38세 남자환자로 기침의 증상과 X-선상 우측폐에 경화소견을 보인 예였다. CT 유도하 세침 흡인 생검법에 의한 세균학적검사와 조직 검사로 C. neoformans에 의한 폐효모균증으로 진단하여, 6주간 fluconazole 사용후 증상은 소실되었고, X-선상 많이 호전되어 현재 추적 관찰중에 있다.

• Parasites, Hosts and Diseases
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• 제53권1호
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• pp.51-58
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• 2015

Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection.

• 한국임상약학회지
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• 제28권1호
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• pp.24-29
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• 2018

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

• 생약학회지
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• 제17권3호
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• pp.248-254
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• 1986

Effects of vinblastine(VLB) and vincristine(VCR) on cell-mediated immunity(CMI) were studied with the microcytotoxicity test(MCT) after normal or pre-sensitized Balb/c mice had been treated in vivo with a combination of two different doses of VLB or VCR(single dose of 20% and 60% $LD_{50}$, i.p.) at different times (from day -6 to day +4) plus allo-transplantation antigen(allo-TA, cells from C3H mice at day 0). The results were that $LD_{50}$ of VLB for female Balb/c mouse was 7.3mg/kg body weight (i.p.) and $LD_{50}$ of VCR was 4.3mg/kg body weight and that VLB and VCR acted as immunosuppressive agents on the primary CMI when administered after allo-TA(antigen-drug-phase), but showed no effect when administered prior to allo-TA(drug-antigen-phase). Change of doses of VLB and VCR(20% $LD_{50}$, 60% $LD_{50}$) caused quantitative or qualitative variations in the immunomodulating effects of these two drugs. Neither VLB nor VCR had any immunomodulating effect on the secondary CMI. Lastly, the results support that the four parameters (type of drug, sensitization status, time of drug treatment in relation to antigen injection, and drug dosis) are significant for the effects of the VLB and VCR on the CMI, and that VLB and VCR may inhibit the proliferation of antigen-stimulated T effector lymphocytes but not memory-cytotoxic T lymphocytes.

• Tuberculosis and Respiratory Diseases
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• 제82권4호
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• pp.277-284
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• 2019

Idiopathic nonspecific interstitial pneumonia (NSIP) is one of the varieties of idiopathic interstitial pneumonias. Diagnosis of idiopathic NSIP can be done via multidisciplinary approach in which the clinical, radiologic, and pathologic findings were discussed together and exclude other causes. Clinical manifestations include subacute or chronic dyspnea and cough that last an average of 6 months, most of which occur in non-smoking, middle-aged women. The common findings in thoracic high-resolution computed tomography in NSIP are bilateral reticular opacities, traction bronchiectasis, reduced volume of the lobes, and ground-glass opacity in the lower lungs. These lesions can involve diffuse bilateral lungs or subpleural area. Unlike usual interstitial pneumonia, honeycombing is sparse or absent. Pathology shows diffuse interstitial inflammation and fibrosis which are temporally homogeneous, namely NSIP pattern. Idiopathic NSIP is usually treated with steroid only or combination with immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, and mycophenolate mofetil. Prognosis of idiopathic NSIP is better than idiopathic pulmonary fibrosis. Many studies have reported a 5-year survival rate of more than 70%.

• Journal of Microbiology and Biotechnology
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• 제31권1호
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• pp.25-32
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• 2021

Inflammatory reactions activated by lipopolysaccharide (LPS) of gram-negative bacteria can lead to severe septic shock. With the recent emergence of multidrug-resistant gram-negative bacteria and a lack of efficient ways to treat resulting infections, there is a need to develop novel anti-endotoxin agents. Antimicrobial peptides have been noticed as potential therapeutic molecules for bacterial infection and as candidates for new antibiotic drugs. We previously designed the 9-meric antimicrobial peptide Pro9-3 and it showed high antimicrobial activity against gram-negative bacteria. Here, to further examine its potency as an anti-endotoxin agent, we examined the anti-endotoxin activities of Pro9-3 and elucidated its mechanism of action. We performed a dye-leakage experiment and BODIPY-TR cadaverine and limulus amebocyte lysate assays for Pro9-3 as well as its lysine-substituted analogue and their enantiomers. The results confirmed that Pro9-3 targets the bacterial membrane and the arginine residues play key roles in its antimicrobial activity. Pro9-3 showed excellent LPS-neutralizing activity and LPS-binding properties, which were superior to those of other peptides. Saturation transfer difference-nuclear magnetic resonance experiments to explore the interaction between LPS and Pro9-3 revealed that Trp3 and Tlr7 in Pro9-3 are critical for attracting Pro9-3 to the LPS in the gram-negative bacterial membrane. Moreover, the anti-septic effect of Pro9-3 in vivo was investigated using an LPS-induced endotoxemia mouse model, demonstrating its dual activities: antibacterial activity against gram-negative bacteria and immunosuppressive effect preventing LPS-induced endotoxemia. Collectively, these results confirmed the therapeutic potential of Pro9-3 against infection of gram-negative bacteria.