• Title/Summary/Keyword: Non-pharmaceutical treatment

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Effect of Cold Adaptation on the Improved Viability of Lactobacillus crispatus KLB46 (Lactobacillus crispatus KLB46의 생균제제화를 위한 저온 전처리시 증지의 효과)

  • 김주현;이석용;장정은;김승철;윤현식;소재성
    • KSBB Journal
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    • v.16 no.6
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    • pp.626-631
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    • 2001
  • Lactobacilli have been considered to play important roles in the health of human vagina. They secrete inhibitory substances to prevent vaginal infection by pathogenic organisms. In a previous study, we have isolated several lactobacilli from Korean woman and one of them (KLB46) was selected and indentified as Lactobacillu crispatus which showed high antimicrobial activity. In this study. cold adaptation prior to subsequent stresses exposure was examined whether L. crispatus KLB46 maintain the viability better than the non-adapted calls under stresses. For pharmaceutical formulation, the lyophilization process is required where stresses such as freezing/thawing and dehydration are routinely applied. Formulated L. crispatus KLB46 can be used for ecological treatment of bacterial vaginosis. The response of cold-adapted cells to other environmental stresses such as acid, heat, ethanol, NaCl, and H$_2$O$_2$ was also examined. The results showed that cold-adapted cells maintained higher survival rate compared with the non-adapted cells (freezing-thawing. 3-folds; dehydration: 3-folds; acid, 3-folds; heat, 10-folds). However, we did net observe any positive effect of cold adaptation on other stresses such as ethanol, NaCl and H$_2$O$_2$. When chloramphenicol was added during cold adaptation, adaptation effect was abolished. This confirms that de novo protein synthesis is necessary during the adaptation process. Moreover, we have identified cold shock protein homolog that codes for a major cold shock protein by PCR amplification using degenerate primers.

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Long-term evaluation of teeth and implants during the periodic maintenance in patients with viral liver disease

  • Yoon, Da-Le;Kim, Yong-Gun;Cho, Jin-Hyun;Lee, Sang-Kyu;Lee, Jae-Mok
    • The Journal of Advanced Prosthodontics
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    • v.8 no.4
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    • pp.321-328
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    • 2016
  • PURPOSE. This study was designed to investigate the maintenance of teeth and implants in patients with viral liver disease. MATERIALS AND METHODS. 316 patients without any significant systemic disease were selected as a control group. Liver disease group was consisted of 230 patients. Necessary data were collected using clinical records and panoramic radiographs. Then, the patients were subdivided into 2 groups based on the type of active dental therapy received before maintenance period (Pre-Tx). Analysis for finding statistically significant difference was performed based on the need for re-treatment of active dental therapy (Re-Tx) and change in the number of teeth (N-teeth) and implants (N-implants). RESULTS. Comparing to control group, the patients with liver disease showed higher value on N-teeth, N-implants, and Re-Tx. Statistically significant differences were found on N-teeth (P=.000) and Re-Tx (P=.000) in patients with non-surgical Pre-Tx. Analysis based on severity of liver disease showed that N-teeth and Re-Tx were directly related to severity of liver disease regardless of received type of Pre-Tx. Significant differences were found on N-teeth (P=.003) and Re-Tx (P=.044) in patients with non-surgical Pre-Tx. CONCLUSION. In this study, it was concluded that liver disease might influence the loss of teeth and cause the relapse of dental disease during maintenance period in patients. A significant positive relationship between tooth and implant loss and severity of liver disease seems to exist.

Effects of Polysaccharide Ginsan from Panax ginseng on Liver Function

  • Song, Jie-Young;Medea-Akhalaia;Alexander-Platonov;Kim, Hyung-Doo;Jung, In-Sung;Han, Young-Soo;Yun, Yeon-Sook
    • Archives of Pharmacal Research
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    • v.27 no.5
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    • pp.531-538
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    • 2004
  • Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-a, IL-1$\beta$, IL-2, IL-6, IL-12, IFN-${\gamma}$ and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1$^{st}$-5$^{th}$ days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7-2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.d.

In Vivo Kinetics and Biodistribution of a HIV-1 DNA Vaccine after Administration in Mice

  • Kim, Byong-Moon;Lee, Dong-Sop;Choi, Jae-Hoon;Kim, Chae-Young;Son, Mi-Won;Suh, You-Suk;Baek, Kwan-Hyuck;Park, Ki-Seok;Sung, Young-Chul;Kim, Won-Bae
    • Archives of Pharmacal Research
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    • v.26 no.6
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    • pp.493-498
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    • 2003
  • In this study we have investigated the pharmacokinetics and tissue distribution of GX-12, a multiple plasmid DNA vaccine for the treatment of HIV-1 infection. Plasmid DNA was rapidly degraded in blood with a half-life of 1.34 min and was no longer detectable at 90 min after intravenous injection in mice. After intramuscular injection, plasmid DNA concentration in the injection site rapidly declined to less than 1 % of the initial concentration by 90 min post-injection. However, sub-picogram levels (per mg tissue) were occasionally detected for several days after injection. The relative proportions of the individual plasm ids of GX-12 remained relatively constant at the injection site until 90 min post-injection. The concentration of plasmid DNA in tissues other than the injection site peaked at 90 min post-injection and decreased to undetectable levels at 8 h post-injection. The rapid in vivo degradation of GX-12 and absence of persistence in non-target tissues suggest that the risk of potential gene-related toxicities by GX-12 administration, such as expression in non-target tissues, insertional mutagenesis and germline transmission, is minimal.

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCETM

  • Jang, Won-hee;Jung, Kyoung-mi;Yang, Hye-ri;Lee, Miri;Jung, Haeng-Sun;Lee, Su-Hyon;Park, Miyoung;Lim, Kyung-Min
    • Biomolecules & Therapeutics
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    • v.23 no.4
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    • pp.379-385
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    • 2015
  • The eye irritation potential of drug candidates or pharmaceutical ingredients should be evaluated if there is a possibility of ocular exposure. Traditionally, the ocular irritation has been evaluated by the rabbit Draize test. However, rabbit eyes are more sensitive to irritants than human eyes, therefore substantial level of false positives are unavoidable. To resolve this species difference, several three-dimensional human corneal epithelial (HCE) models have been developed as alternative eye irritation test methods. Recently, we introduced a new HCE model, MCTT HCE$^{TM}$ which is reconstructed with non-transformed human corneal cells from limbal tissues. Here, we examined if MCTT HCE$^{TM}$ can be employed to evaluate eye irritation potential of solid substances. Through optimization of washing method and exposure time, treatment time was established as 10 min and washing procedure was set up as 4 times of washing with 10 mL of PBS and shaking in 30 mL of PBS in a beaker. With the established eye irritation test protocol, 11 solid substances (5 non-irritants, 6 irritants) were evaluated which demonstrated an excellent predictive capacity (100% accuracy, 100% specificity and 100% sensitivity). We also compared the performance of our test method with rabbit Draize test results and in vitro cytotoxicity test with 2D human corneal epithelial cell lines.

Preparation and Evaluation of a 4-Branched Polyethylene Glycol Derivative Modified with Exendin-4 and Stearylamine for Extended Hypoglycemic Action

  • Kim, In-Soo;Ma, Kyung-Wan;Bae, Sung-Ho;Yoon, Jeong-Hyun;Oh, Kyung-Taek;Lee, Eun-Seong;Lee, Don-Haeng;Lee, Kang-Choon;Youn, Yu-Seok
    • Journal of Pharmaceutical Investigation
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    • v.40 no.3
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    • pp.175-180
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    • 2010
  • Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol $(PEG)_{5k}$ (Mw: 20 kDa) modified with three stearylamines ($C_{18}-NH_2$) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative ($3C_{18}-4PEG_{5k}$-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged $3C_{18}-4PEG_{5k}$-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore, $3C_{18}-4PEG_{5k}$-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The $HD_{total}$ value ($57.6{\pm}12.3%$) of $3C_{18}-4PEG_{5k}$-Ex4 at a 50 nmol/kg dose was 2-fold greater than that ($31.0{\pm}8.7%$) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with $3C_{18}-4PEG_{5k}$-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment.

Bioequivalence of Alpit Tablet to Algiron Tablet (Cimetropium Bromide 50 mg) (알기론 정(브롬화 시메트로피움 50 mg)에 대한 알피트 정의 생물학적 동등성)

  • Cho, Hea-Young;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.32 no.1
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    • pp.47-54
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    • 2002
  • Cimetropium bromide, a quaternary ammonium compound which is chemically related to scopolamine, exhibits its antispasmodic activity by competing with acetylcholine for the muscarinic receptors of the smooth muscle of gastrointestinal tract. The drug has been used for the treatment of various disorders involving spasms of the musculature of the gastrointestinal, biliary and genitourinary tracts. The purpose of the present study was to evaluate the bioequivalence of two cimetropium bromide tablets, $Algiron^{TM}$ (Boehringer Ingelheim Korea Ltd.) and $Alpit^{TM}$ (Hana Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The cimetropium bromide release from the two cimetropium bromide tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty normal male volunteers, $25.25{\pm}2.10$ years in age and $65.76{\pm}6.39$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three tablets containing 50 mg of cimetropium bromide per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of cimetropium bromide in serum were determined using HPLC method with UV detector. The dissolution profiles of two cimetropium bromide tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t\;and\;C_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the $Algiron^{TM}$ were 2.19%, -5.97% and 3.49%, respectively. Minimum detectable differences $({\Delta})\;at \;{\alpha}=0.05\;and\;1-{\beta}=0.8$ were less than 20% (e.g., 13.71 %, 19.05% and 15.11% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The powers $(1-{\beta})\;at\;{\alpha}=0.05,\;{\Delta}=0.2\;for\;AUC_t$, $C_{max}\;and\;T_{max}$ were 97.79%, 83.22% and 95.60%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.84{\sim}10.21,\;-17.11{\sim}5.18\;and\;-5.35{\sim}12.33\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t\;and\;C_{max}$. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.94{\sim}1.10\;and\;0.85{\sim}1.05\;for\;AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Alpit^{TM}$ tablet is bioequivalent to $Algiron^{TM}$ tablet.

Epigallocatechin Gallate Prevents Autoimmune Diabetes Induced by Multiple Low Doses of Streptozotocin in Mice

  • Song, Eun-Kyung;Hur, Hyeon;Han, Myung-Kwan
    • Archives of Pharmacal Research
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    • v.26 no.7
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    • pp.559-563
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    • 2003
  • Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of $\beta$-cell destruction in insulin-dependent diabetes mellitus. In non insulin-dependent diabetes, cytokines are also associated with impaired $\beta$-cell function in high glucose condition. By the screening of various natural products blocking $\beta$-cell destruction, we have recently found that epigallocatechin gallate (EGCG) can prevent the in vitro destruction of RINm5F cell, an insulinoma cell line, that is induced by cytokines. In that study we suggested that EGCG could prevent cytokine-induced $\beta$-cell destruction by down-regulation of nitric oxide synthase (NOS) through inhibition of NF-kB activation. Here, to verify the in vivo antidiabetogenic effect of EGCG, we examined the possibility that EGCG could also prevent the experimental autoimmune diabetes induced by the treatment of multiple low doses of streptozotocin (MLD-STZ), which is recognized as an inducer of type I autoimmune diabetes. Administration of EGCG (100 mg/day/kg for 10 days) during the MLD-STZ induction of diabetes reduced the increase of blood glucose levels caused by MLD-STZ. Ex vivo analysis of $\beta$-islets showed that EGCG downregulates the MLD-STZ-induced expression of inducible NOS (iNOS). In addition, morphological examination showed that EGCG treatment ameliorated the decrease of islet mass induced by MLD-STZ. In combination these results suggest that EGCG could prevent the onset of MLD-STZ-induced diabetes by protecting pancreatic islets. Our results therefore revealed the possible therapeutic value of EGCG for the prevention of diabetes mellitus progression.

Therapeutic Evaluation of a Topical Unani Formulation, Tila-i Muhāsā in Buthūr Labaniyya (Acne Vulgaris): A Randomized, Controlled Clinical Study

  • Azahar, Mohd;Uddin, Qamar;Kazmi, Munawwar Husain;Khatoon, Faiza;Husain, Nazim
    • CELLMED
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    • v.10 no.2
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    • pp.15.1-15.9
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    • 2020
  • Introduction: Buthūr Labaniyya (Acne vulgaris) is a multifactorial disorder of the pilosebaceous units characterized by non-inflammatory and inflammatory clinical lesions. Several Unani medications have been used for centuries to treat acne. Objectives: Evaluation of safety and efficacy of Tila-i Muhāsā in patients with acne vulgaris Materials and Methods: This clinical study was conducted in patients with acne vulgaris. Patients applied Tila-i Muhāsā or 5% Benzoyl Peroxide (BPO) once daily for 6 weeks. Assessment of efficacy was carried out by Global Acne Grading System (GAGS) and Patient Global Assessment (PGA) scores. In addition, overall severity of acne was evaluated on a 5-point Cook's acne grading scale using photographic standards. Assessment of safety was performed through adverse drug reactions, local dermal tolerability, vital signs, and routine laboratory investigations. Results: A total of 60 patients (30 in each group) completed 6 weeks of treatment. The mean percentage reduction in GAGS score at 6 weeks from baseline in Unani group (66.97%) and BPO group (59.09%) was statistically significant (P<0.0001). After 6 weeks of therapy, the mean percentage reduction in PGA score compared to baseline in Unani group (57.44%) and BPO group (50.23%) was statistically significant (P<0.0001). No serious adverse events were reported in both groups; however, mild adverse events occurred more frequently in BPO group (30%) compared to Unani group (10%). Conclusion: Tila-i Muhāsā was found to be effective and safe in the treatment of acne vulgaris. However, further clinical studies with larger sample size and longer duration of therapy need to be conducted.

Financial Burden of Cancer Drug Treatment in Lebanon

  • Elias, Fadia;Khuri, Fadlo R;Adib, Salim M;Karam, Rita;Harb, Hilda;Awar, May;Zalloua, Pierre;Ammar, Walid
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3173-3177
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    • 2016
  • Background: The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total case-load. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Materials and Methods: Using utilization and spending data accumulated at MOPH during 2008-2013, the cost to the public budget of cancer drugs was assessed per case and per drug type. Results: The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and Non-Hodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Conclusions: Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.