• Journal of Chest Surgery
• /
• v.32 no.3
• /
• pp.287-293
• /
• 1999

Background: Medical treatment of multiple drug resistant(MDR) pulmonary tuberculosis has been quite unsuccessful. We analyzed our experience to identify the benefits and complications of the pulmonary resection in MDR pulmonary tuberculosis. Material and Method: A retrospective review was performed in 27 patients who unerwent pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Mean age was 40 years and the average history of diagnosis prior to surgery was 3.1 years. All had resistance to an average of 4.4 drugs, and received second line drugs selected according to the drug sensitivity test. Most patients (93%) had cavitary lesions as the main focus. Bilateral lesions were identified in 19 patients (70%), however, the main focus was recognized in one side of the lung. Eleven patients (41%) were converted to negative sputum smear and/or culture before surgery. Result: Pneumonectomy was performed in 9 patients, lobectomy in 16 and segmentectomy in 2. There was no operative mortality. Morbidity had occurred in 7 patients (26%), prolonged air leak in 3 patients, reoperation due to bleeding in 2, bronchopleural fistula in 1, and reversible neurologic defect in 1. Median follow up period was 15 months (3-45 months). Sputum negative conversion was initially achieved in 22 patients (82%), and with continuous postopertive chemotherapy negative conversion was achieved in other 4 patients (14%). Only one pneumonectized patient (4%) failed due to considerable contralateral cavity. Conclusion: For patients with localized MDR pulmonary tuberculosis and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.

• Tuberculosis and Respiratory Diseases
• /
• v.57 no.3
• /
• pp.226-233
• /
• 2004

Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

• Tuberculosis and Respiratory Diseases
• /
• v.80 no.2
• /
• pp.159-168
• /
• 2017

Background: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. Methods: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. Results: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. Conclusion: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.

• Natural Product Sciences
• /
• v.20 no.1
• /
• pp.1-6
• /
• 2014

P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.

• Microbiology and Biotechnology Letters
• /
• v.47 no.4
• /
• pp.651-661
• /
• 2019

Targeting the pathogen viability using drugs is associated with development of drug resistance due to selective pressure. Hence, there is an increased interest in developing agents that target bacterial virulence. In this study, the inhibitory effect of ciclopirox, an antifungal agent with iron chelation potential, on the microbial virulence factors was evaluated in 26 clinical MDR Pseudomonas aeruginosa isolates collected from Alexandria Main University Hospital, a tertiary hospital in Egypt. Treatment with 9 ㎍/ml ciclopirox inhibited the hemolytic activity in 70% isolates, reduced pyocyanin production, decreased protease secretion in 46% isolates, lowered twitching and swarming motility, and decreased biofilm formation by 1.5- to 4.5-fold. The quantitative real-time PCR analysis revealed that treatment with ciclopirox downregulated the expression levels of alkaline protease (aprA) and pyocyanin (phzA1). Ciclopirox is used to treat hematological malignancies and the systemic administration of ciclopirox is reported to have adequate oral absorption with a satisfactory drug safety profile. It is important to calculate the appropriate clinical dose and therapeutic index to reposition ciclopirox from a topical antifungal agent to a promising virulence-modifying agent agent against P. aeruginosa, a problematic Gram-negative pathogen.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.16
• /
• pp.6935-6938
• /
• 2014

Gastric cancer (GC) is one of the most common malignancies worldwide. The ABCB1 protein, a member of the ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, considerably influences the distribution of drugs across cell membranes as well as multidrug resistance (MDR) of antineoplastic drugs. In contrast to the extensive knowledge on the pharmacological action of ABCB1 protein, the correlation between the clinical-pathological data and ABCB1 protein expression in patients with GC remains unclear. The aim was to investigate association between ABCB1 expression and overall survival in GC patients. Human tumor fragments from 57 GC patients were examined by immunohistochemistry assay. We observed lower survival rate of patients with GC who were positive for ABCB1 expression (p=0.030). Based on these observations, we conclude that GC patients with positive ABCB1 protein immunohistochemical expression in their tumors suffer shorter overall survival.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2003.04a
• /
• pp.102-102
• /
• 2003

The present study has been undertaken to characterize availability of camellia(Camellia japonica L.) as a medicinal plant with antineoplastic and chemosensitizing activities. The crude extracts from fresn camellia flower, young leaves and nutraceutical tea of camellia leaf and flower buds were evaluated on their potential activities against various human cancer cells and multidrug resistance to cancer cells in vitro. The range of cytotoxicity displayed from 120$\mu\textrm{g}$/mL to 200$\mu\textrm{g}$/mL. Catemix 1(CT-1) mixed with camellia and green tea showed high toxicity(respectively IC$\sub$50/=l16$\mu\textrm{g}$/mL, 129$\mu\textrm{g}$/mL) against AML-2/WT, acute myelogenous leukemia cell and MCF-7, brest adenocarcinoma pleual effusion cell. Generally camellia tea mixed with green tea showed higher cytotoxicity than the other camellia teas mixed with some herbs(CH). Methanol extract of steamed camellia tea and roasted camellia tea had a chemosensitizing effect to reverse Pgp-mediated MDR. In addition, camellia flower tea of insignificant cytotoxicity, chemosensitizing effect were increased remarkably chemosensitizing effect in mixed flower tea with some herbs.

• Toxicological Research
• /
• v.24 no.1
• /
• pp.29-36
• /
• 2008

The present study investigated the anti-proliferative and chemosensitizing effects of Crinum asiaticum var. japonicum against multi-drug resistant (MDR) cancer cells. The 80% methanol extract, chloroform ($CHCl_3$) fraction and butanol (BuOH) fraction of C. asiaticum inhibited the growth of mitoxantrone (MX) resistant HL-60 (HL-60/MX2) cells. When HL-60/MX2 cells were treated with the $CHCl_3$ and BuOH fractions, DNA ladder and sub-G1 hypodiploid cells were observed. Furthermore, the fractions reduced BcI-2 mRNA levels, whereas Bax mRNA levels were increased. These results suggest that the inhibitory effect of C. asiaticum on the growth of the HL-60/MX2 cells might arise from the induction of apoptosis. Treatment of HL-60/MX2 cells with the fractions markedly decreased the mRNA levels of the multi-drug resistance protein-1 and breast cancer resistance protein. The $CHCl_3$ fraction and hexane fraction increased MX accumulation in HL-60/MX2 cells. These results imply that the $CHCl_3$ fraction of C. asiaticum plays a pivotal role as a chemosensitizer. We suggest that components of C. asiaticum might have a therapeutic potential for the treatment of MDR leukemia.

• Korean Journal of Veterinary Service
• /
• v.32 no.1
• /
• pp.49-59
• /
• 2009

At the present study, it was aimed to explore the states of antimicrobial resistant Salmonella spp. isolates from 3,850 pigs (2,732 ileocecocolic lymphnodes and 1,118 cecal contents) and 1,764 cattle (965 cecal lymphnodes and 799 cecal contents) slaughtered in Busan province from December 2000 to November 2001. Among 5,614 samples, 457 of Salmonella spp. were isolated from pig lymphnodes (13.5%), pig cecal contents (4.4%), cattle lymphnodes (3.5%) and cattle cecal contents (0.5%). Salmonella spp. were showed different isolation ratio, that was 10.8% in summer, 9.0% in autumn, 8.4% in spring and 5.0% in winter. As a result of serotyping, B group (65.4%) were identified as the most common in pigs and cattle, in order of $C_1$ (14.0%), $D_1$ (5.5%), $C_2$ (4.2%), $E_1$ (4.2%) and L (3.5%). 34 serotypes were found, among them, Salmonella Typhimurium (S. Typhimurium) (21.0%) was the most common serotype from pigs and cattle. The major serotypes were in order of S. Derby (15.3%), S. Schwarzengrund (14.7%), S. Typhimurium var Copenhagen (9.2%), S. Mbandaka (5.7%), S. Enteritidis (5.5%) and S. Ruiru (3.5%). The most common serotype was S. Typhimurium in pigs, and S. Ruiru in cattle. S. Ruiru was firstly isolated from pigs and cattle in Korea. In antimicrobial susceptibility test, all the isolates were demonstrated susceptibility to norfloxacin and ofloxacin. But the isolates were showed resistance other antibiotics in order of doxycycline (68.3%), tetracycline (67.8%), penicillin (54.5%) and streptomycin (52.5%). S. Typhimurium were exhibited resistance to ampicillin (34.8%), chloramphenicol (36.2%), streptomycin (94.9%), sulfamethoxazole/trimethoprim (34.8%) and tetracycline (97.8%). There were 53 strains (38.4%) which had multi drug resistant (MDR) isolates, resistant to more than 6 antimicrobial agents. The most common resistance patterns of MDR isolates were ampicillin, chloramphenicol, carbenicillin, doxycycline, nalidixic acid, penicillin, streptomycin, sulfamethoxazole/trimethoprim and tetracycline (ACCbDNaPSSuT).

• Microbiology and Biotechnology Letters
• /
• v.49 no.4
• /
• pp.519-527
• /
• 2021

In this study, the hemolysis of Enterococcus faecalis BMSE-HMP strains, isolated from human breast milk, was investigated, and the anti-hemolytic and antimicrobial effects on multidrug-resistant (MDR) bacteria were investigated. The enzyme activity of E. faecalis BMSE-HMP 4 strains was measured, and it was found that the activities of esterase and esterase lipase were the highest. In addition, no hemolytic reaction was observed in any of the isolates. Subsequently, the anti-hemolytic activity against MDR strains causing hemolysis was evaluated. E. faecalis BMSE-HMP002 had the highest anti-hemolytic activity against Staphylococcus aureus CCARM 3855 at 75.71 ± 10.00%. The anti-hemolytic activity against Escherichia coli DC 2 CCARM 0238 and Pseudomonas aeruginosa CCARM 0223 showed that the activity of BMSE-HMP001 was highest at 76.92 ± 2.99% and 87.93 ± 1.93%, respectively. Examination of the antimicrobial effects against the MDR bacteria Staphylococcus spp., Escherichia spp., Pseudomonas spp., Salmonella spp., Klebsiella spp., Enterobacter spp., and E. faecalis BMSE-HMP strains showed antimicrobial effects against both gram-positive and gram-negative strains. Breastfeeding delivers enterococci into the intestinal tract of newborns by lactation, and its usefulness is attracting attention as it has been reported that enterococci have a potential effect on neonatal immune development. In this study, the hemolytic and antimicrobial effects of E. faecalis BMSE-HMP strains on MDR bacteria were investigated, to confirm their potential as useful lactic acid bacteria. Additional studies on the antibiotic resistance and toxicity of the E. faecalis BMSE-HMP strains, isolated in this study, are necessary to prove it safe for use.