• Title/Summary/Keyword: Resistance mechanisms

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Difficult Clinical Problems of Treatment in Depression (우울증 치료에서의 어려운 문제들)

  • Min, Kyung-Joon
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.37-46
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    • 2001
  • Whenever a clinician manages the patients with depression, he may meet various problems that make it difficult to treat them. Even though he has good skills and knowledge about depression, some barriers will be appear during his practice. In general, the difficulties in treating depression are treatment-resistance, adverse effects of antidepressants, pregnancy in female patients, comorbid medical conditions, poor compliance, drug-drug interactions, and so on, which are related with pharmacological treatments. Here, only the two of them, the treatment-resistant depression and difficult problems concerned with pregnancy, were discussed. Some level of treatment resistance is the norm rather than the exception. As the treatment failure stems from inadequate treatment, it is important that the clinician should prescribe medications with sufficient doseage and adequate duration. And to overcome the treatment resistant depression the polypharmacy is necessary, in that case, the side effects and toxicities should be explored and managed immediately. So the clinician have to learn more about the pharmacokinetic and pharmacodynamic mechanisms of each drugs used in treatment of depression. When the risk of the fetus by the exposure is higher than the risk of untreated maternal psychiatric disorder, psychotropic medications should be used during pregnancy. Women who are maintained on psychotropics and become pregnant, as well as women with the new onset of psychiatric symptoms during pregnancy, should be carefully reassessed. However, data concerning the potential risk of long-term behavioral changes following prenatal exposure to psychotropics is rare, so further longitudinal follow-up studies are needed.

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Pathways Regulating the pbgP Operon and Colistin Resistance in Klebsiella pneumoniae Strains

  • Choi, Myung-Jin;Kim, Sunju;Ko, Kwan Soo
    • Journal of Microbiology and Biotechnology
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    • v.26 no.9
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    • pp.1620-1628
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    • 2016
  • In this study, we investigated colistin resistance mechanisms associated with the regulation of the pbgP operon in Klebsiella pneumoniae, using four isogenic pairs of colistin-susceptible strains and their colistin-resistant derivatives and two colistin-resistant clinical isolates. Amino acid sequence alterations of PhoPQ, PmrAB, and MgrB were investigated, and mRNA expression levels of phoQ, pmrB, pmrD, and pbgP were measured using quantitative real-time PCR. The phoQ and pmrB genes were deleted from two colistin-resistant derivatives, 134R and 063R. We found that phoQ, pmrD, and pbgP were significantly upregulated in all colistin-resistant derivatives. However, pmrB was significantly upregulated in only two colistin-resistant derivatives and one clinical strain. pmrB was not overexpressed in the other strains. The minimum inhibitory concentration of colistin was drastically lower in both phoQ- and pmrB-deleted mutants from a colistin-resistant derivative (134R) that was overexpressing phoQ and pmrB. However, colistin susceptibility was restored only in a phoQ-deleted mutant from a colistin-resistant derivative (063R) without overexpression of pmrB. In conclusion, two different regulations of the pbgP operon may associate with the development of colistinresisant K. pneumoniae.

Estrogen Receptor α Roles in Breast Cancer Chemoresistance

  • Xu, Chao-Yang;Jiang, Zhi-Nong;Zhou, Ying;Li, Jia-Jia;Huang, Li-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4049-4052
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    • 2013
  • Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor ${\alpha}$, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. $ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive $ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of $ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

Role of general esterases in deltamethrin resistance mechanism of diamondback moth, Plutrlla xylostella L. (배추좀나방(Pulltella xylostella L.)의 deltamethrin 저항성 기작에 관한 에스테라제의 역할)

  • 김용균;장동걸
    • Korean journal of applied entomology
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    • v.35 no.1
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    • pp.74-79
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    • 1996
  • General esterases were analysed quantitatively and qualitatively to see their role in deltamethrin resistance mechanisms of the diamondback moth, Plutella xylostella L. Selection with 0.1 g of deltamethrin in each generation induced the moth to decrease susceptibility to the insecticide and to increase esterase activities of the fourth instar larvae. Both characters were highly correlated so that the correlation coefficient (r) between LDSo @g) of deltamethrin and esterase activities (~M/min/pg) was 0.9918 (P=0.0082). Nondenaturing PAGE (6%) separated 17 esterase bands from the whole body extracts of the fourth instar larvae. Deltamethrin-selected populations had fewer esterase bands than had the unselected. Four esterase bands (E3, E4, Ell, and E13) were, however, specific to deltamethrin-selected populations.

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Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting

  • Eun, Kiyoung;Ham, Seok Won;Kim, Hyunggee
    • BMB Reports
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    • v.50 no.3
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    • pp.117-125
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    • 2017
  • Most of the cancers are still incurable human diseases. According to recent findings, especially targeting cancer stem cells (CSCs) is the most promising therapeutic strategy. CSCs take charge of a cancer hierarchy, harboring stem cell-like properties involving self-renewal and aberrant differentiation potential. Most of all, the presence of CSCs is closely associated with tumorigenesis and therapeutic resistance. Despite the numerous efforts to target CSCs, current anti-cancer therapies are still impeded by CSC-derived cancer malignancies; increased metastases, tumor recurrence, and even acquired resistance against the anti-CSC therapies developed in experimental models. One of the most forceful underlying reasons is a "cancer heterogeneity" due to "CSC plasticity". A comprehensive understanding of CSC-derived heterogeneity will provide novel insights into the establishment of efficient targeting strategies to eliminate CSCs. Here, we introduce findings on mechanisms of CSC reprogramming and CSC plasticity, which give rise to phenotypically varied CSCs. Also, we suggest concepts to improve CSC-targeted therapy in order to overcome therapeutic resistance caused by CSC plasticity and heterogeneity.

Wear Characterization of $Al/Al_2O_3$ Composites Reinforced with Hybrid of Carbon Fibers and SiC Whiskers (탄소섬유와 SiC 휘스커를 혼합한 $Al/Al_2O_3$ 복합재료의 마멸특성)

  • 봉하동;송정일;한경섭
    • Transactions of the Korean Society of Mechanical Engineers
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    • v.19 no.7
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    • pp.1619-1629
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    • 1995
  • The Al/Al$_{2}$O$_{3}$ SiC and Al/Al$_{2}$O$_{3}$/C hybrid metal matrix composites (MMCs) were fabricated by squeeze infiltration method. Uniform distribution of reinforcements were found in the microstructure of metal matrix composites. Mechanical tests were carried out under various test conditions to clearly identify mechanical behavior of MMCs, and the wear mechanism of Al/Al$_{2}$O$_{3}$/(SiC or C) hybrid metal matrix composites were investigated. The tensile strength and hardness of hybrid composites was resulted in increasing compared with those of the unreinforced matrix alloy. Wear resistance was strongly dependent upon kinds of fiber, volume fraction and sliding speed. The wear resistance of metal matrix composites was remarkably improved by the addition of reinforcements. Especially, the wear resistance of the hybrid composites of carbon fibers was more effective than in the composites reinforced with alumina and SiC whiskers of reinforcements. This was due to the effect of carbon fiber on the solid lubrication. Wear mechanisms of hybrid composites were suggested from wear surface analyses. The major wear mechanism of hybrid composites was the abrasive wear at low to intermediate sliding speed, and the melting wear at intermediate to high sliding speed.

Seizure Failure of Engine Crankshaft Bearings

  • Ni, X.;Cheng, H.S.
    • Tribology and Lubricants
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    • v.11 no.5
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    • pp.162-171
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    • 1995
  • The application of reciprocating engine crankshaft bearings is of particular importance and interest among the plain bearing, not only because the sheer volume of intemal combustion engines now produced, but because the severe operating conditions they are subjected to. Demands for better performances of crankshaft bearings have provide an important impetus in the development of bearings and bearing materials. As engine design progresses toward higher outpt and higher efficiency, crankshaft bearings must perform under more seveve operating conditions. Higher load, temperature, and speed as well as lower viscosity oil are applied to the bearing sysem, resulting in a smaller minimum oil film thickness. This means more solid-solid contact between the shaft and bearing, and the bearing is exposed to more danger of seizure. Some engines may experience bearing seizure problems. However, understanding about the seizure behavior and mechanism is far from being enough. Seizure resistance of a bearing-shaft system will be affected by the properties of the shaft and bearing, especially their materials and surface texture. Commonly used engine bearing materials include Al-Pb-Si, Al-Sn-Si, Al-Sn, and Cu-Pb with Pb-Sn-Cu overlay. These materials have very different properties. They showed different behaviors dering seizure tests and seizure may occur with different mechanism for different bearing material. Shaft materials also affect the seizure resistance of the system. Surface texture of the bearing and shaft have apparent effects on the lubrication and solid-solid contact pattern, and therefore will affect the seizure behavior of the system. Bearings and shafts which are made of different materials and have different surface textures have been tested and analyzed. Their effects on seizure resistance are discussed and possible seizure mechanisms for different beatings are presented in this paper.

Improvement of the behaviour of composite slabs: A new type of end anchorage

  • Fonseca, Alexandre;Marques, Bruno;Simoes, Rui
    • Steel and Composite Structures
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    • v.19 no.6
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    • pp.1381-1402
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    • 2015
  • The application of composite steel-concrete slabs with profiled steel sheeting has increased, due to the various advantages in relation to reinforced concrete slabs such as, the reduced thickness, the reduced amount of lost formwork needed, as well as the speed of execution. The loss of longitudinal shear resistance is, generally, the governing design mode for simply supported spans of common lengths. For common distributed loadings, the composite behaviour is influenced by the partial shear connection between the concrete and the steel sheeting. The present research work is intended to contribute to improving the ultimate limit state behaviour of composite slabs using end anchorage. Eurocode 4, Part 1.1 (EN 1994-1-1) provides an analytical methodology for predicting the increase of longitudinal resistance, achieved by using shear studs welded through the steel sheeting as the end anchorage mechanism. The code does not supply an analytical methodology for other kinds of end anchorage so, additional tests or studies are needed to prove the effectiveness of these types of anchorage. The influence of end anchorage mechanisms provided by transverse rebars at the ends of simply supported composite slabs is analysed in this paper. Two experimental programmes were carried out, the first to determine the resistance provided by the new end anchorage mechanism and the second to analyse its influence on the behaviour of simply supported composite slabs.

Corrosion Mechanisms of New Wrought Mg-Zn Based Alloys Alloying with Si, Ca and Ag

  • Ben-Hamu, G.;Eliezer, D.;Shin, K.S.;Wagner, L.
    • Corrosion Science and Technology
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    • v.7 no.3
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    • pp.152-157
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    • 2008
  • New wrought magnesium alloys have increasingly been developed in recent years for the automotive industry due to their high potential as structural materials for low density and high strength/weight ratio demands. However, their poor mechanical properties and low corrosion resistance have led to a search for new kinds of magnesium alloys with better strength, ductility, and high corrosion resistance. The main objective of this research is to investigate the corrosion behaviour of new magnesium alloys: Mg-Zn-Ag (ZQ), Mg-Zn-Mn-Si (ZSM) and Mg-Zn-Mn-Si-Ca (ZSMX). These ZQ6X, ZSM6X1, and ZSM651+YCa alloys were prepared using hot extrusion. AC, DC polarization and immersion tests were carried out on the extruded rods. Microstructure was examined using optical and electron microscopy (SEM) and EDS. The addition of silver decreased the corrosion resistance. The additions of silicon and calcium also affected the corrosion behaviour. These results can be explained by the effects of alloying elements on the microstructure of Mg-Zn alloys such as grain size and precipitates caused by the change in precipitation and recrystallisation behaviour.

The emerging role of myeloid-derived suppressor cells in radiotherapy

  • Kang, Changhee;Jeong, Seong-Yun;Song, Si Yeol;Choi, Eun Kyung
    • Radiation Oncology Journal
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    • v.38 no.1
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    • pp.1-10
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    • 2020
  • Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.