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Sample records for anti-retroviral drug sensitivities

  1. Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors

    International Nuclear Information System (INIS)

    The small molecule CCR5 inhibitors are a new class of drugs for treating infection by human immunodeficiency virus type 1 (HIV-1). They act by binding to the CCR5 co-receptor and preventing its use during HIV-1-cell fusion. Escape mutants can be raised against CCR5 inhibitors in vitro and will arise when these drugs are used clinically. Here, we have assessed the responses of CCR5 inhibitor-resistant viruses to other anti-retroviral drugs that act by different mechanisms, and their sensitivities to neutralizing antibodies (NAbs). The rationale for the latter study is that the resistance pathway for CCR5 inhibitors involves changes in the HIV-1 envelope glycoproteins (Env), which are also targets for NAbs. The escape mutants CC101.19 and D1/85.16 were selected for resistance to AD101 and vicriviroc (VVC), respectively, from the primary R5 HIV-1 isolate CC1/85. Each escape mutant was cross-resistant to other small molecule CCR5 inhibitors (aplaviroc, maraviroc, VVC, AD101 and CMPD 167), but sensitive to protein ligands of CCR5: the modified chemokine PSC-RANTES and the humanized MAb PRO-140. The resistant viruses also retained wild-type sensitivity to the nucleoside reverse transcriptase inhibitor (RTI) zidovudine, the non-nucleoside RTI nevirapine, the protease inhibitor atazanavir and other attachment and fusion inhibitors that act independently of CCR5 (BMS-806, PRO-542 and enfuvirtide). Of note is that the escape mutants were more sensitive than the parental CC1/85 isolate to a subset of neutralizing monoclonal antibodies and to some sera from HIV-1-infected people, implying that sequence changes in Env that confer resistance to CCR5 inhibitors can increase the accessibility of some NAb epitopes. The need to preserve NAb resistance may therefore be a constraint upon how escape from CCR5 inhibitors occurs in vivo

  2. Mechanisms of anti-retroviral drug resistance: implications for novel drug discovery and development.

    Science.gov (United States)

    Emamzadeh-Fard, Sahra; Esmaeeli, Shooka; Arefi, Khalilullah; Moradbeigi, Majedeh; Heidari, Behnam; Fard, Sahar E; Paydary, Koosha; Seyedalinaghi, Seyedahmad

    2013-10-01

    Anti-retroviral drug resistance evolves as an inevitable consequence of expanded combination Anti-retroviral Therapy (cART). According to each drug class, resistance mutations may occur due to the infidel nature of HIV reverse transcriptase (RT) and inadequate drug pressures. Correspondingly, resistance to Nucleoside Reverse Transcriptase Inhibitors (NRTIs) occurs due to incorporation impairment of the agent or its removal from the elongating viral DNA chain. With regard to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), resistance mutations may alter residues of the RT hydrophobic pocket and demonstrate high level of cross resistance. However, resistance to Protease Inhibitors requires complex accumulation of primary and secondary mutations that substitute amino acids in proximity to the viral protease active site. Resistance to novel entry inhibitors may also evolve as a result of mutations that affect the interactions between viral glycoprotein and CD4 or the chemokine receptors. According to the current studies, future drug initiative programs should consider agents that possess higher genetic barrier toward resistance for ascertaining adequate drug efficacy among patients who have failed first-line regimens. PMID:24712673

  3. Effects of Hormonal Contraception on Anti-Retroviral Drug Metabolism, Pharmacokinetics and Pharmacodynamics

    OpenAIRE

    THURMAN, Andrea Ries; Anderson, Sharon; Doncel, Gustavo F.

    2014-01-01

    Among women, human immunodeficiency virus type 1 (HIV-1) infection is most prevalent in those of reproductive age. These women are also at risk of unintended or mistimed pregnancies. Hormonal contraceptives (HCs) are one of the most commonly used methods of family planning world-wide. Therefore concurrent use of HC among women on anti-retroviral medications (ARVs) is increasingly common. ARVs are being investigated and have been approved for pre-exposure prophylaxis (PrEP), and therefore drug...

  4. Perinatal genotoxicity and carcinogenicity of anti-retroviral nucleoside analog drugs

    International Nuclear Information System (INIS)

    The current worldwide spread of the human immunodeficiency virus-1 (HIV-1) to the heterosexual population has resulted in approximately 800 000 children born yearly to HIV-1-infected mothers. In the absence of anti-retroviral intervention, about 25% of the approximately 7000 children born yearly to HIV-1-infected women in the United States are HIV-1 infected. Administration of zidovudine (AZT) prophylaxis during pregnancy reduces the rate of infant HIV-1 infection to approximately 7%, and further reductions are achieved with the addition of lamivudine (3TC) in the clinical formulation Combivir. Whereas clinically this is a remarkable achievement, AZT and 3TC are DNA replication chain terminators known to induce various types of genotoxicity. Studies in rodents have demonstrated AZT-DNA incorporation, HPRT mutagenesis, telomere shortening, and tumorigenicity in organs of fetal mice exposed transplacentally to AZT. In monkeys, both AZT and 3TC become incorporated into the DNA from multiple fetal organs taken at birth after administration of human-equivalent protocols to pregnant dams during gestation, and telomere shortening has been found in monkey fetuses exposed to both drugs. In human infants, AZT-DNA and 3TC-DNA incorporation as well as HPRT and GPA mutagenesis have been documented in cord blood from infants exposed in utero to Combivir. In infants of mice, monkeys, and humans, levels of AZT-DNA incorporation were remarkably similar, and in newborn mice and humans, mutation frequencies were also very similar. Given the risk-benefit ratio, these highly successful drugs will continue to be used for prevention of vertical viral transmission, however evidence of genotoxicity in mouse and monkey models and in the infants themselves would suggest that exposed children should be followed well past adolescence for early detection of potential cancer hazard

  5. The formulation and stability of dispersible or chewable tablets containing anti retroviral drugs / Joseph Willem Labuschagne

    OpenAIRE

    Labuschagne, Joseph Willem

    2006-01-01

    Lamivudine (3TC), Nevirapine (NVP) and Zidovudine (AZT) is indicated as part of antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infected adults and children who present clinical or immunological evidence of progression of the disease. Current dosage forms of these drugs in single or dual-therapy include tablets, coated tablets and oral solutions. Three problem areas are currently experienced with the above mentioned dosage forms. Fi...

  6. EFFECTIVENESS OF FIXED DRUG COMBINATION ANTI-RETROVIRAL THERAPY IN HIV INFECTED CHILDREN: AN EXPLORATIVE STUDY

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    Somasekhar Rao

    2015-10-01

    Full Text Available Over 90 per cent of HIV infected babies were born to HIV positive mothers in Sub-Saharan Africa and worldwide. It is estimated that currently 2.3 million i.e 5.9% are children less than 15 yrs of age infected with HIV. Worldwide, children under age 15 who were newly infected with HIV, more than 90 percent were babies were born to HIV-positive women. An estimated 1500 children get newly infected with HIV each day globally. The scenario is similar at home in Andhra Pradesh, India. This present exploratory study is to find out the effectiveness of fixed drug combination of antiretroviral therapy in children. The results are encouraging and are similar to results from such studies elsewhere.

  7. Genetic variation of the HIV-1 integrase region in newly diagnosed anti-retroviral drug-naïve patients with HIV/AIDS in Korea.

    Science.gov (United States)

    Kim, J-Y; Kim, E-J; Choi, J-Y; Kwon, O-K; Kim, G J; Choi, S Y; Kim, S S

    2011-08-01

    The survival time of HIV/AIDS patients in Korea has increased since HAART (highly active anti-retroviral therapy) was introduced. However, the occurrence of drug-resistant strains requires new anti-retroviral drugs, one of which, an integrase inhibitor (INI), was approved by the US Food and Drug Administration (FDA) in 2007. INIs have been used for therapy in many countries and are about to be employed in Korea. Therefore, it is important to identify basic mutant variants prior to the introduction of INIs in order to estimate their efficacy. To monitor potential drug-resistant INI mutations in Korean HIV/AIDS patients, the polymorphism of the int gene was investigated together with the pol gene using a genotypic assay for 75 randomly selected Korean HIV-1 patients newly diagnosed in 2007. The drug-resistant mutation sequences were analysed using the Stanford HIV DB and the International AIDS Society resistance testing-USA panel (IAS-USA). Seventy strains of Korean subtype B were compared with foreign subtype-B strains, and there were no significantly different variants of the int gene region in the study population. Major mutation sites in the integrase (E92Q, F121Y, G140A/S, Y143C/R, Q148H/R/K and N155H) were not detected, and only a few minor mutation sites (L74M, V151I, E157Q, V165I, I203M, S230N and D232N) were identified in 21 strains (28%). Resistance due to mutations in the pol gene was observed in a single strain (1.3%) resistant to protease inhibitors (PIs) and in four strains (5.3%) resistant to reverse transcriptase inhibitors (RTIs). In summary, this demonstrates that INIs will be susceptible to drug naïve HIV/AIDS patients in Korea. PMID:20946407

  8. Nurses' perceptions about Botswana patients' anti-retroviral therapy adherence

    OpenAIRE

    Valerie J. Ehlers; Esther Kip; Van der Wal, Dirk M.

    2009-01-01

    Anti-retroviral drugs (ARVs) are supplied free of charge in Botswana. Lifelong adherence to anti-retroviral therapy (ART) is vital to improve the patient’s state of well-being and to prevent the development of strains of the human immunodef ciency virus (HIV) that are resistant to ART. Persons with ART-resistant strains of HIV can spread these to other people, requiring more expensive ART with more severe side-effects and poorer health outcomes. The purpose of this exploratory, descriptive, q...

  9. Current trends in highly active anti-retroviral therapy in an anti-retroviral therapy centre attached to a remote government medical college of Maharashtra, India: a retrospective study

    OpenAIRE

    Pravin S. Rathod; Praveenkumar T Patil; Rekha P. Lohar; A.W. Patil

    2016-01-01

    Background: Highly active anti-retroviral therapy (HAART) became the keystone of national AIDS program. There is lack of awareness and inadequate training about drug safety monitoring among health care professionals in India. Hence, the present study was carried out to study current trends in HAART and pattern of associated adverse drug reactions. Methods: A retrospective observational study was conducted at an anti-retroviral therapy (ART) Centre. A total of 151 HIV/AIDS Patients (old and...

  10. Nurses' perceptions about Botswana patients' anti-retroviral therapy adherence

    Directory of Open Access Journals (Sweden)

    Valerie J. Ehlers

    2009-04-01

    Full Text Available Anti-retroviral drugs (ARVs are supplied free of charge in Botswana. Lifelong adherence to anti-retroviral therapy (ART is vital to improve the patient’s state of well-being and to prevent the development of strains of the human immunodef ciency virus (HIV that are resistant to ART. Persons with ART-resistant strains of HIV can spread these to other people, requiring more expensive ART with more severe side-effects and poorer health outcomes. The purpose of this exploratory, descriptive, qualitative study was to determine nurses’ perspectives on Botswana patients’ anti-retroviral therapy (ART adherence, and to identify factors which could promote or hinder ART adherence. Four ART sites were randomly selected and all 16 nurses providing ART services at these sites participated in semi-structured interviews. These nurses indicated that patients’ ART adherence was inf uenced by service-related and patient-related factors. Service-related factors included the inaccessibility of ART clinics, limited clinic hours, health workers’ inability to communicate in patients’ local languages, long waiting times at clinics and delays in being informed about their CD4 and viral load results. Nurses could not trace defaulters nor contact them by phone, and also had to work night shifts, disrupting nurse-patient relationships. Patient-related factors included patients’ lack of education, inability to understand the significance of CD4 and viral load results, financial hardships, non-disclosure and non-acceptance of their HIV positive status, alcohol abuse, the utilisation of traditional medicines and side effects of ART. The challenges of lifelong ART adherence are multifaceted involving both patient-related and service-related factors. Supplying free ARVs does not ensure high levels of ART adherence.

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    Anti-retrovirale middels (ARMs word gratis verskaf in Botswana. Lewenslange getroue nakoming van ARM voorskrifte is

  11. A prospective study, to determine adverse effects of anti-retroviral agents in rural tertiary care teaching hospital

    OpenAIRE

    Swapnil Chudaman Jaykare; Jyoti Ramchandra Patil; Vijay Motiram Motghare; Sudhir Laxmanrao Padwal; Vinod Shivajirao Deshmukh; Harshal Nutanrao Pise

    2016-01-01

    Background: Acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV). Objective of this study was to evaluate the adverse drug reaction profile of anti-retroviral drugs in HIV patients in terms of causality, severity and preventability. Methods: Patients newly started on ART were followed prospectively for a period of initial six months and were interviewed in person during their routine follow-up or visit following ...

  12. An audit on virological efficacy of anti-retroviral therapy in a specialist infectious disease clinic.

    LENUS (Irish Health Repository)

    Reyad, A

    2009-06-01

    We have assessed the efficacy of anti retroviral therapy (ART) using undetectable viral load (VL) (<50 RNA copies\\/ml) as a marker of virological success, in patients who have Human Immunodeficiency Virus (HIV) attending the Department of Infectious Disease. A cross-sectional review of patients\\' case notes was used to obtain their demographics and treatment details. 79% (253) of the hospital case notes of clinic population was available for analysis, which represents 90% of those receiving ART in the clinic. 166\\/253 of the cohort were receiving treatment at the time of this study and 95% (157\\/166) of these were on treatment for greater than 6 months. The total virological success rate is 93%, which is comparable to other centres and are as good as those from published clinical trials. 56% of those on therapy who have virological failure were Intravenous Drug Users (IVDUs). Case by case investigation for those with treatment failure is warranted.

  13. In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

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    Brendan A I Payne

    Full Text Available Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31P-MRS to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX histochemistry. We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate resynthesis was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers: τ½ ADP (half-life of adenosine diphosphate clearance, HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3, HIV-uninfected 1.16±0.05×10(-3, p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX defects within individual cells. Basal energy requirements may nevertheless be increased.

  14. "Every drug goes to treat its own disease…" - a qualitative study of perceptions and experiences of taking anti-retrovirals concomitantly with anti-malarials among those affected by HIV and malaria in Tanzania

    DEFF Research Database (Denmark)

    Mangesho, Peter E; Reynolds, Joanna; Lemnge, Martha; Vestergaard, Lasse S; Chandler, Clare I R

    2014-01-01

    . However, perceptions of drug strength appeared to compel some people not enrolled in the clinical study to take the drugs at separate times to avoid anticipated harm to the body. CONCLUSIONS: Management of HIV and malaria concurrently often requires individuals to cross the domains of different disease...

  15. Usuários de drogas injetáveis e terapia anti-retroviral: percepções das equipes de farmácia Injecting drug users and antiretroviral therapy: perceptions of pharmacy teams

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    Chizuru Minami Yokaichiya

    2007-12-01

    adherence to antiretroviral therapy by injecting drug users living with HIV/AIDS. METHODS: Qualitative study through focus groups and thematic discourse analysis of pharmacists, technicians and assistants with more than six months of experience with medication supply, in 15 assisting units for STD/AIDS in the city of São Paulo, in 2002. RESULTS: Three groups were formed, totaling 29 participants, originating from 12 out of the 15 existing services, and including 12 university level professionals and 17 high-school level professionals. The groups concluded that the pharmacy has an important role in the antiretroviral drug supply, which is reflected in the treatment adherence, because trust-based relationships can be built up through their procedures. In spite of this, they pointed out that such building-up does not take place through excessively bureaucratic activities. This has negative repercussions for all patients, especially for injecting drug users, considered "difficult people". Such concept sums up their behavior: they are supposed to be confused and incapable to adhere to treatment, and have limited understanding. Staff members, however, affirm they treat these patients equally. They do not realize that, by this acting, the specific needs of injecting drug users may become invisible in the service. There is also the possibility that stigmatizing stereotypes may be created, resulting in yet another barrier to the work on adherence. CONCLUSIONS: Although the pharmacy is recommended as a potentially favorable place to listen to and form bonds with users, the results show objective and subjective obstacles to render it suitable for the work on adherence.

  16. Tratamiento antirretroviral en pacientes con sida y micobacteriosis Anti-retroviral treatment in patients with AIDS and mycobacterial diseases

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    Marcelo E. Corti

    2005-08-01

    Full Text Available La tuberculosis y otras micobacteriosis constituyen asociaciones o coinfecciones frecuentes en pacientes con sida y se asocian con una elevada mortalidad. En esta revisión se actualizan los tratamientos de las principales enfermedades micobacterianas asociadas al sida (tuberculosis y micobacteriosis por Mycobacterium avium, con especial énfasis en las interacciones farmacológicas entre antimicobacterianos, principalmente rifampicina y claritromicina, y fármacos antirretrovirales. Se analizan los esquemas de tratamiento, su duración, la quimioprofilaxis primaria y secundaria y el momento óptimo de iniciación del tratamiento antirretroviral. Finalmente se describe el síndrome inflamatorio de reconstitución inmune y su tratamiento.Tuberculosis and other mycobacterial diseases are frequent coinfections in AIDS patients with an increased related mortality. In this review we have updated the treatment of the main mycobacterial diseases (tuberculosis and Mycobacterium avium disease, under the scope of pharmacological interactions between antimycobacterial drugs, specially rifampicin and clarithromycin, and anti-retroviral drugs. Antimycobacterial treatment schemes, their duration, primary and secondary chemoprophylaxis and the optimal time to start the anti-retroviral therapy are analized. Finally, the immnune reconstitution inflammatory syndrome and its treatment are discussed.

  17. The occurrence of anti-retroviral compounds used for HIV treatment in South African surface water

    International Nuclear Information System (INIS)

    The study and quantification of personal care products, such as pharmaceuticals, in surface water has become popular in recent years; yet very little description of these compounds’ presence in South African surface water exists in the literature. Antiretrovirals (ARVs), used to treat human immunodeficiency virus (HIV) are rarely considered within this field. A new method for the simultaneous quantification of 12 antiretroviral compounds in surface water using the standard addition method is described. Water samples were concentrated by a generic automated solid phase extraction method and analysed by ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Substantial matrix effect was encountered in the samples with an average method detection limit of 90.4 ng/L. This is the first reported countrywide survey of South African surface water for the quantification of these compounds with average concentrations ranging between 26.5 and 430 ng/L. - Highlights: • An LC-MS/MS method for the detection of 12 antiretroviral drugs was developed. • The compounds were detected in South African surface water for the first time. • Targets occurred in the low to mid ng/L range. • Nevirapine occurred ubiquitously across all the samples tested. • Matrix effect was corrected for using a modified standard addition method. - This work represents the first quantitative description of anti-retrovirals, as a group, in surface water using a modified standard addition method and UHPLC-MS/MS

  18. Cancellers - Exploring the Possibility of Receptor Decoy Traps As a Superior Anti-Retroviral Strategy.

    Science.gov (United States)

    Jeremiah, Sundararaj Stanley; Ohba, Kenji; Yamamoto, Naoki

    2016-01-01

    The global Human Immunodeficiency Virus (HIV) pandemic is still spreading due to the lack of ideal anti-retroviral measures and their availability. Till date, all attempts to produce an efficient vaccine have ended with unsatisfactory results. The highly active anti-retroviral therapy (HAART) is the only effective weapon currently available and is widely being used for curtailing the HIV pandemic. However, the HAART is also expected to fail in the near future due to the emergence and dissemination of antiviral resistance. This review sheds light on the reasons for the failure of the conventional anti-viral measures against HIV and the novel anti-retroviral strategies currently being developed. The various principles to be considered for the success of a novel anti-retroviral strategy are elaborately emphasized and an innovative concept is proposed on these lines. The proposed concept intends to use receptor decoy traps (RDT) called cancellers which are erythrocytes expressing the HIV entry receptors on their surface. If successfully developed, the cancellers would be capable of active targeting of the free HIV particles leading to the trapping of the viruses within the canceller, resulting in the neutralization of infectivity of the trapped virus. The possible ways of translating this concept into reality and the probable hurdles that can be encountered in the process are subsequently discussed. Also, the scope of cancellers in therapeutic and/or preventive strategies against HIV infection is envisaged upon their successful development. PMID:25882216

  19. Clients’ Satisfaction with Anti Retroviral Therapy Services at Hamidia Hospital Bhopal

    OpenAIRE

    Bhagat Vimal Kishor, Pal D K, Lodha Rama S, Bankwar Vishal

    2011-01-01

    Background: The HIV/AIDS pandemic is a major public health problem with an estimated 33.33 million people living with the virus globally. Free antiretroviral treatment was initiated in India 2004. Patients’ satisfaction is one of the commonly used outcome measures of patient care. Objective: To assess the satisfaction of people living with HIV/AIDS with services provided at anti retroviral therapy Centre Hamidia Hospital Bhopal. Material and Methods: A hospital based cross-sectional study was...

  20. Supporting children to adhere to anti-retroviral therapy in urban Malawi: multi method insights

    OpenAIRE

    Phiri Sam; Chiunguzeni Darles; Nyirenda Jean; Makwiza Ireen; Weigel Ralf; Theobald Sally

    2009-01-01

    Abstract Background Ensuring good adherence is critical to the success of anti-retroviral treatment (ART). However, in resource-poor contexts, where paediatric HIV burden is high there has been limited progress in developing or adapting tools to support adherence for HIV-infected children on ART and their caregivers. We conducted formative research to assess children's adherence and to explore the knowledge, perceptions and attitudes of caregivers towards children's treatment. Methods All chi...

  1. Anti-retroviral strategies for AIDS and related diseases

    OpenAIRE

    Wainberg, Mark A.; Dascal, Andre; Mendelson, Jack

    1991-01-01

    The replication cycle of human immunodeficiency virus type 1 (HIV-1) and other retroviruses consists of four stages: attachment of the virus to specific receptors on the cell surface; uncoating of the viral nucleic acid and conversion to DNA; production of viral RNA and proteins; and assembly and liberation of progeny virus from the cell. Each of these steps represents a potential target for antiviral chemotherapy. Combinations of drugs which act against different steps in the viral replicati...

  2. HIV reverse transcriptase gene mutations in anti-retroviral treatment naïve rural people living with HIV/AIDS

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    K Mohanakrishnan

    2015-01-01

    Full Text Available This study is designed to find out the mutational variations of reverse transcriptase (RT gene of HIV, after the traditional drug usage among anti-retroviral therapy naïve rural people living with HIV/AIDS. HIV Reactive patients, who were exposed for indigenous medicines such as Siddha, Ayurveda etc., for a minimum period of 6 months were taken for this study. Among 40 patients, two samples (5.55% demonstrated high-level mutational resistance variations for nucleoside RT inhibitor (NRTI and non-NRTI. The predominant polymorphisms detected were K122E (91.7%, V60I (91.7%, V35T (89%, Q207E (89%, D177E (89%, T200A (86.1%, S48T (83.33%, K173A (80.6%.

  3. Predictors of mortality among HIV-infected patients initiating anti retroviral therapy at a tertiary care hospital in Eastern India

    Institute of Scientific and Technical Information of China (English)

    Ananya Bhowmik; Subhasis Bhandari; Rajyasree De; Subhasish Kamal Guha

    2012-01-01

    Objective: To assess early mortality and identify its predictors among the ART naive HIV-infected patients initiating anti retroviral therapy (ART) available free of cost at the ART Centres.Methods: A retrospective cohort analysis of routinely collected programme data was done for assessing mortality of all ART naive adult patients who received first-line ART at a government tertiary care hospital in eastern India during 1st March 2009 and 28th February 2010. Bivariate and multiple regression analyses of the baseline demographic, clinical and laboratory records using SPSS 15.0 were done to identify independent predictors of mortality. Results: The mortality rate at one year was estimated to be 7.66 (95% CI 5.84-9.83) deaths/100 patient-years and more than 50% of the deaths occurred during first three months of ART initiation with a median time interval of 73 days. Tuberculosis was the major cause of death. ART naive patients with baseline serum albumin <3.5 mg/dL were eight (OR 7.9; 95% CI: 3.8-16.5) at risk of death than those with higher serum albumin levels and patients with CD4 count <100 cells/μL were two times (OR 2.2;95% CI: 1.1-4.4) at risk of death compared to higher CD4 counts. Conclusions: Risk of mortality is increased when ART is initiated at advanced stages of immunosuppression denoted by low serum albumin levels and CD4 cell counts. This highlights the importance of early detection of HIV infection, early management of opportunistic infections including tuberculosis and timely initiation of the antiretroviral drugs in the resource-limited countries, now available free in the Indian national ART programme.

  4. Examining the relationship between psychological distress and adherence to anti-retroviral therapy among Ugandan adolescents living with HIV.

    Science.gov (United States)

    Mutumba, Massy; Musiime, Victor; Lepkwoski, James M; Harper, Gary W; Snow, Rachel C; Resnicow, Ken; Bauermeister, Jose A

    2016-07-01

    Psychological distress is common among adolescents living with HIV (ALHIV) worldwide, and has been associated with non-adherence to anti-retroviral therapy (ART), leading to poor virologic suppression, drug resistance, and increased risk for AIDS morbidity and mortality. However, only a few studies have explored the relationship between psychological distress and ART adherence among adolescents in sub-Saharan Africa. The paper examines the relationship between psychological distress and ART adherence, and effect of psychosocial resources on ART adherence. We conducted a cross-sectional survey of 464 ALHIV (aged 12-19; 53% female) seeking HIV care at a large HIV treatment center in Kampala, Uganda. ALHIV were recruited during routine clinic visits. Three self-reported binary adherence measures were utilized: missed pills in the past three days, non-adherence to the prescribed medical regimen, and self-rated adherence assessed using a visual analog scale. Psychological distress was measured as a continuous variable, and computed as the mean score on a locally developed and validated 25-item symptom checklist for Ugandan ALHIV. Psychosocial resources included spirituality, religiosity, optimism, social support, and coping strategies. After adjusting for respondents' socio-demographic characteristics and psychosocial resources, a unit increase in psychological distress was associated with increased odds of missing pills in past 3 days (Odds Ratio(OR) = 1.75; Confidence Interval (CI): 1.04-2.95), not following the prescribed regimen (OR = 1.63; CI: 1.08-2.46), and lower self-rated adherence (OR = 1.79; CI: 1.19-2.69). Psychosocial resources were associated with lower odds for non-adherence on all three self-report measures. There is a need to strengthen the psychosocial aspects of adolescent HIV care by developing interventions to identify and prevent psychological distress among Ugandan ALHIV. PMID:27294696

  5. Immune reconstitution inflammatory syndrome in HIV-infected patients with mycobacterial infections starting highly active anti-retroviral therapy

    International Nuclear Information System (INIS)

    AIM: To describe the radiological appearances of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected patients with mycobacterial infections starting highly active anti-retroviral therapy (HAART). MATERIALS AND METHODS: Five consecutive HIV infected patients with IRIS due to mycobacterial infection were studied. Intercurrent infection and poor drug compliance were excluded as causes of presentation. The chest radiological appearances at the time of starting HAART and at the time of diagnosis of IRIS were compared. RESULTS: In these five patients there was clinical and radiological deterioration, occurring between 10 days and 7 months after starting HAART, leading to unmasking of previously undiagnosed mycobacterial infection or to worsening of mycobacterial disease. All five patients had HAART-induced increases in CD4+ T lymphocyte counts and reductions in peripheral blood HIV 'viral load'. Chest radiographic abnormalities due to IRIS included marked mediastinal lymphadenopathy in three patients--severe enough to produce tracheal compression in two patients (one of whom had stridor)--and was associated with new pulmonary infiltrates in two patients. The other two patients had new infiltrates, which in one patient was associated with a pleural effusion. CONCLUSION: These cases illustrate the diverse chest radiographic appearances of IRIS occurring after HAART in patients with mycobacterial and HIV co-infection. Marked mediastinal lymphadenopathy occurred in three of these five patients (with associated tracheal narrowing in two patients); four patients developed pulmonary infiltrates and one had an effusion. The cases further highlight that the onset of IRIS may be delayed for several months after HAART is started

  6. Immune reconstitution inflammatory syndrome in HIV-infected patients with mycobacterial infections starting highly active anti-retroviral therapy

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    Buckingham, S.J.; Haddow, L.J.; Shaw, P.J.; Miller, R.F. E-mail: rmiller@gum.ucl.ac.uk

    2004-06-01

    AIM: To describe the radiological appearances of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected patients with mycobacterial infections starting highly active anti-retroviral therapy (HAART). MATERIALS AND METHODS: Five consecutive HIV infected patients with IRIS due to mycobacterial infection were studied. Intercurrent infection and poor drug compliance were excluded as causes of presentation. The chest radiological appearances at the time of starting HAART and at the time of diagnosis of IRIS were compared. RESULTS: In these five patients there was clinical and radiological deterioration, occurring between 10 days and 7 months after starting HAART, leading to unmasking of previously undiagnosed mycobacterial infection or to worsening of mycobacterial disease. All five patients had HAART-induced increases in CD4+ T lymphocyte counts and reductions in peripheral blood HIV 'viral load'. Chest radiographic abnormalities due to IRIS included marked mediastinal lymphadenopathy in three patients--severe enough to produce tracheal compression in two patients (one of whom had stridor)--and was associated with new pulmonary infiltrates in two patients. The other two patients had new infiltrates, which in one patient was associated with a pleural effusion. CONCLUSION: These cases illustrate the diverse chest radiographic appearances of IRIS occurring after HAART in patients with mycobacterial and HIV co-infection. Marked mediastinal lymphadenopathy occurred in three of these five patients (with associated tracheal narrowing in two patients); four patients developed pulmonary infiltrates and one had an effusion. The cases further highlight that the onset of IRIS may be delayed for several months after HAART is started.

  7. Recurrent cryptococcal immune reconstitution inflammatory syndrome in an HIV-infected patient after anti-retroviral therapy: a case report

    OpenAIRE

    Hu, Zhiliang; Wei, Hongxia; Meng, Fanqing; Xu, Chuanjun; Cheng, Cong; Yang, Yongfeng

    2013-01-01

    Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) in HIV-infected patients presents as a clinical worsening or new presentation of cryptococcal disease as a result of anti-retroviral therapy mediated immune restoration. Recurrent C-IRIS is a rare condition. Recently, recurrent C-IRIS involving the central nervous system, which is thought to require prolonged or alternative immunosuppressive therapy, has been described. Here, we present an unusual case of recurrent C-IRIS, sequ...

  8. IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS)-ASSOCIATED BURKITT LYMPHOMA FOLLOWING COMBINATION ANTI-RETROVIRAL THERAPY IN HIV-INFECTED PATIENTS

    OpenAIRE

    Vishnu, Prakash; Dorer, Russell P.; Aboulafia, David M

    2014-01-01

    HIV/AIDS-associated immune reconstitution inflammatory syndrome (IRIS) is defined as a paradoxical worsening or unmasking of infections and autoimmune diseases, following initiation of combination anti-retroviral therapy (cART). More recently, the case definition of IRIS has been broadened to include certain malignancies including Kaposi’s sarcoma, and less frequently Hodgkin’s and non-Hodgkin’s lymphoma (NHL). Here in we describe 3 patients infected with HIV who began cART and within a media...

  9. Helminthic Infections Rates and Malaria in HIV-Infected Pregnant Women on Anti-Retroviral Therapy in Rwanda

    OpenAIRE

    Ivan, Emil; Crowther, Nigel J.; Mutimura, Eugene; Osuwat, Lawrence Obado; Janssen, Saskia; Grobusch, Martin P

    2013-01-01

    Background Within sub-Saharan Africa, helminth and malaria infections cause considerable morbidity in HIV-positive pregnant women and their offspring. Helminth infections are also associated with a higher risk of mother-to-child HIV transmission. The aim of this study was to determine the prevalence of, and the protective and risk factors for helminth and malaria infections in pregnant HIV-positive Rwandan women receiving anti-retroviral therapy (ART). Methodology and principle findings Pregn...

  10. Helminthic Infections Rates and Malaria in HIV-Infected Pregnant Women on Anti-Retroviral Therapy in Rwanda

    OpenAIRE

    Emil Ivan; Nigel J Crowther; Eugene Mutimura; Lawrence Obado Osuwat; Saskia Janssen; Grobusch, Martin P.

    2013-01-01

    BACKGROUND: Within sub-Saharan Africa, helminth and malaria infections cause considerable morbidity in HIV-positive pregnant women and their offspring. Helminth infections are also associated with a higher risk of mother-to-child HIV transmission. The aim of this study was to determine the prevalence of, and the protective and risk factors for helminth and malaria infections in pregnant HIV-positive Rwandan women receiving anti-retroviral therapy (ART). METHODOLOGY AND PRINCIPLE FINDINGS: Pre...

  11. Home Based Care Services as Strategy to Support Anti-Retroviral Adherence: The Case of Musoma Municipal, Mara region

    OpenAIRE

    Rwezaura, Pamela Kokusima

    2012-01-01

    A descriptive qualitative study was conducted to assess whether Home Based Care services can be used as a strategy to support Anti-retroviral adherence for People living with HIV/AIDS (PLWHA) in Musoma Municipality, Mara region in March 2012. Six public health facilities that are providing ARVs were included in the study; this included the regional hospital, two dispensaries and three health centers. With the national ART scale up, the poor health infrastructures are faced with poor retention...

  12. Identifying risk factors of immune reconstitution inflammatory syndrome in AIDS patients receiving highly active anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Bo He

    2013-04-01

    Full Text Available Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%. Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p < 0.001 and persistently lower CD4+ cell count (p < 0.001 compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4+ cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy.

  13. Economic evaluation of task-shifting approaches to the dispensing of anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Foster Nicola

    2012-09-01

    Full Text Available Abstract Background A scarcity of human resources for health has been identified as one of the primary constraints to the scale-up of the provision of Anti-Retroviral Treatment (ART. In South Africa there is a particularly severe lack of pharmacists. The study aims to compare two task-shifting approaches to the dispensing of ART: Indirectly Supervised Pharmacist’s Assistants (ISPA and Nurse-based pharmaceutical care models against the standard of care which involves a pharmacist dispensing ART. Methods A cross-sectional mixed methods study design was used. Patient exit interviews, time and motion studies, expert interviews and staff costs were used to conduct a costing from the societal perspective. Six facilities were sampled in the Western Cape province of South Africa, and 230 patient interviews conducted. Results The ISPA model was found to be the least costly task-shifting pharmaceutical model. However, patients preferred receiving medication from the nurse. This related to a fear of stigma and being identified by virtue of receiving ART at the pharmacy. Conclusions While these models are not mutually exclusive, and a variety of pharmaceutical care models will be necessary for scale up, it is useful to consider the impact of implementing these models on the provider, patient access to treatment and difficulties in implementation.

  14. Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.

    Science.gov (United States)

    Mowatt, L

    2013-01-01

    HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590

  15. Adesão à terapêutica anti-retroviral por indivíduos com HIV/AIDS assistidos em uma instituição do interior paulista Adhesión a la terapéutica anti-retroviral por los individuos con VIH/SIDA de uno servicio del interior paulista Adhesion to anti-retroviral therapy by individuals with HIV/AIDS attended at an institution in the interior of São Paulo

    Directory of Open Access Journals (Sweden)

    Elucir Gir

    2005-10-01

    -retrovirales desde hace en promedio 5 años. La cantidad diaria de comprimidos anti-retrovirales varió de 3 a 24. Como principales dificultades de la adhesión mencionaron: sabor, tamaño, cantidad, olor de los comprimidos (40,0%; efectos colaterales (14,4%; factores psicológicos (13,7%; diferentes horarios de medicación (10,8%. Cuanto a las facilidades, el 26,2% relató horarios coincidentes de los comprimidos; el 16,4% ninguna facilidad y el 16,0% ingestión condicionada a algún hábito. Esos datos requieren de la enfermería mayor vigilancia supervisada, acciones educativas e intervenciones.Inadequate adherence to highly active anti-retroviral therapy (HAART provokes important secondary effects in people living with aids. The objective was to identify the factors that make HAART adherence easy or difficult, according to aids patients attended at a university hospital in the state of São Paulo, Brazil. We interviewed 200 diagnosed aids patients using HAART for at least 6 months. Patients were interviewed individually, using a semi-structured design. Qualitative and quantitative analysis was used. 59% of the participants were men; average age was 38.2 years; 51% did not finish basic education; 50.5% did not perform any remunerated work. Patients had been using anti-retroviral agents for an average time of 5 years. The number of anti-retroviral pills ranged from 3 to 24. The main difficulties mentioned for adherence were: taste, size, number, smell of pills (40.0%; intense collateral effects (14.4%; psychological factors (13.7%; different times to take the pills (10.8%. Patients mentioned the following facilitators: coincidence of times to take the drugs (26.2%, no facility (16.4%, and administration associated to some habit (16.0%. The nursing group needs to reinforce supervised surveillance, educational and intervention actions.

  16. Cost-effectiveness of anti-retroviral therapy at a district hospital in southern Ethiopia

    Directory of Open Access Journals (Sweden)

    Robberstad Bjarne

    2009-07-01

    Full Text Available Abstract Background As the resource implications of expanding anti-retroviral therapy (ART are likely to be large, there is a need to explore its cost-effectiveness. So far, there is no such information available from Ethiopia. Objective To assess the cost-effectiveness of ART for routine clinical practice in a district hospital setting in Ethiopia. Methods We estimated the unit cost of HIV-related care from the 2004/5 fiscal year expenditure of Arba Minch Hospital in southern Ethiopia. We estimated outpatient and inpatient service use from HIV-infected patients who received care and treatment at the hospital between January 2003 and March 2006. We measured the health effect as life years gained (LYG for patients receiving ART compared with those not receiving such treatment. The study adopted a health care provider perspective and included both direct and overhead costs. We used Markov model to estimate the lifetime costs, health benefits and cost-effectiveness of ART. Findings ART yielded an undiscounted 9.4 years expected survival, and resulted in 7.1 extra LYG compared to patients not receiving ART. The lifetime incremental cost is US$2,215 and the undiscounted incremental cost per LYG is US$314. When discounted at 3%, the additional LYG decreases to 5.5 years and the incremental cost per LYG increases to US$325. Conclusion The undiscounted and discounted incremental costs per LYG from introducing ART were less than the per capita GDP threshold at the base year. Thus, ART could be regarded as cost-effective in a district hospital setting in Ethiopia.

  17. Effects of PPARγ and RBP4 gene variants on metabolic syndrome in HIV-infected patients with anti-retroviral therapy.

    Directory of Open Access Journals (Sweden)

    Yuan-Pin Hung

    Full Text Available BACKGROUND: PPARγ and RBP4 are known to regulate lipid and glucose metabolism and insulin resistance. The influences of PPARγ (C1431T and Pro12Ala and RBP4 (-803GA polymorphisms on metabolic syndrome in HIV-infected patients receiving anti-retroviral therapy were examined in this study. MATERIALS AND METHODS: A cross-sectional study of HIV-1 infected adults with antiretroviral therapy for more than one year in the National Cheng Kung University Hospital was conducted. The gene polymorphisms were determined by quantitative PCR. RESULTS: Ninety-one patients were included in the study. Eighty-two (90.1% patients were males with a mean age of 44.4 years. For the C1431T polymorphism in PPARγ, while patients with the T allele (48.4% had trends toward lower rate of hypertriglyceridemia, the borderline significance together with insignificant power did not support the protective effect of the T allele against development of hypertriglyceridemia. For the Pro12Ala polymorphism in PPARγ, although patients with the Pro/Ala genotype (8.8% had a higher level of serum LDL (138.0 vs. 111.5 mg/dl, P = 0.04 and trends toward higher rates of hypercholesterolemia and serum LDL>110 mg/dl, these variables were found to be independent of the Pro/Ala genotype in the multivariate analysis. For the -803GA polymorphism in RBP4, patients with the A allele (23.1% more often had insulin resistance (HOMA>3.8; 33.3 vs. 8.7%, P = 0.01 and more often received anti-hypoglycemic drugs (14.3 vs. 1.4%, P = 0.04. The detrimental effect of the A allele in RBP4 -803GA polymorphism on development of insulin resistance was supported by the multivariate analysis adjusting for covariates. CONCLUSION: The impacts of PPARγ C1431T and Pro12Ala polymorphisms on metabolism in HIV-infected patients are not significant. RBP4 -803GA polymorphism has increased risk of insulin resistance in HIV-infected patients with anti-retroviral therapy.

  18. Hypermetabolic subcutaneous fat in patients on highly active anti-retroviral therapy treatment: Subtle finding with implications

    International Nuclear Information System (INIS)

    Lipodystrophy (LD) is a serious complication of highly active anti-retroviral therapy, characterized by peripheral fat wasting, central adiposity and metabolic changes. Since the disfiguration caused by LD is permanent, the focus of management is on early detection to arrest progression. We report a case where ancillary finding of increased fluorine-18 fluoro-2-deoxyglucose (F-18 FDG) uptake in the sub-cutaneous fat helped early detection of LD and led to early intervention to arrest progression. Though F-18 FDG positron emission tomography/computed tomography scan is not recommended to diagnose LD, conscious reporting of this finding when present can greatly influence patient management

  19. Incidence of WHO stage 3 and 4 conditions following initiation of Anti-Retroviral Therapy in resource limited settings

    OpenAIRE

    Curtis, Andrea J.; Marshall, Catherine S; Spelman, Tim; Greig, Jane; ELLIOT, Julian H.; Shanks, Leslie; du Cros, Philipp; Casas, Esther C; Da Fonseca, Marcio Silveria; O'Brien, Daniel P.

    2012-01-01

    Objectives To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS). Design/Setting A descriptive analysis of routine program data collected prospectively from 25 Médecins Sans Frontières supported HIV treatment programs in eight countries between 2002 and 2010. Subjects/Participants 35,349 study participants with median follow-up on ART of 1.33 years (IQR 0.51–2.41). Outcome Measures Incidence in 100 per...

  20. Cost estimates of HIV care and treatment with and without anti-retroviral therapy at Arba Minch Hospital in southern Ethiopia

    Directory of Open Access Journals (Sweden)

    Robberstad Bjarne

    2009-04-01

    Full Text Available Abstract Background Little is known about the costs of HIV care in Ethiopia. Objective To estimate the average per person year (PPY cost of care for HIV patients with and without anti-retroviral therapy (ART in a district hospital. Methods Data on costs and utilization of HIV-related services were taken from Arba Minch Hospital (AMH in southern Ethiopia. Mean annual outpatient and inpatient costs and corresponding 95% confidence intervals (CI were calculated. We adopted a district hospital perspective and focused on hospital costs. Findings PPY average (95% CI costs under ART were US$235.44 (US$218.11–252.78 and US$29.44 (US$24.30–34.58 for outpatient and inpatient care, respectively. Estimates for the non-ART condition were US$38.12 (US$34.36–41.88 and US$80.88 (US$63.66–98.11 for outpatient and inpatient care, respectively. The major cost driver under the ART scheme was cost of ART drugs, whereas it was inpatient care and treatment in the non-ART scheme. Conclusion The cost profile of ART at a district hospital level may be useful in the planning and budgeting of implementing ART programs in Ethiopia. Further studies that focus on patient costs are warranted to capture all patterns of service use and relevant costs. Economic evaluations combining cost estimates with clinical outcomes would be useful for ranking of ART services.

  1. Supporting children to adhere to anti-retroviral therapy in urban Malawi: multi method insights

    Directory of Open Access Journals (Sweden)

    Phiri Sam

    2009-07-01

    Full Text Available Abstract Background Ensuring good adherence is critical to the success of anti-retroviral treatment (ART. However, in resource-poor contexts, where paediatric HIV burden is high there has been limited progress in developing or adapting tools to support adherence for HIV-infected children on ART and their caregivers. We conducted formative research to assess children's adherence and to explore the knowledge, perceptions and attitudes of caregivers towards children's treatment. Methods All children starting ART between September 2002 and January 2004 (when ART was at cost in Malawi were observed for at least 6 months on ART. Their adherence was assessed quantitatively by asking caregivers of children about missed ART doses during the previous 3 days at monthly visits. Attendance to clinic appointments was also monitored. In June and July 2004, four focus group discussions, each with 6 to 8 caregivers, and 5 critical incident narratives were conducted to provide complementary contextual data on caregivers' experiences on the challenges to and opportunities of paediatric ART adherence. Results We followed prospectively 47 children who started ART between 8 months and 12 years of age over a median time on ART of 33 weeks (2–91 weeks. 72% (34/47 never missed a single dose according to caregivers' report and 82% (327/401 of clinic visits were either as scheduled, or before or within 1 week after the scheduled appointment. Caregivers were generally knowledgeable about ART and motivated to support children to adhere to treatment despite facing multiple challenges. Caregivers were particularly motivated by seeing children begin to get better; but faced challenges in meeting the costs of medicine and transport, waiting times in clinic, stock outs and remembering to support children to adhere in the face of multiple responsibilities. Conclusion In the era of rapid scale-up of treatment for children there is need for holistic support strategies that focus

  2. Anti-retroviral drug design based on structure analysis of proteases

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich; Dohnálek, Jan; Dušková, Jarmila; Konvalinka, Jan; Hradilek, Martin; Souček, Milan; Sedláček, Juraj; Brynda, Jiří; Buchtelová, E.

    1998-01-01

    Roč. 5, B (1998), s. 437-438. ISSN 1211-5894. [European Crystallographic Meeting /18./. Praha, 15.08.1998-20.08.1998] R&D Projects: GA ČR GA203/97/P031; GA AV ČR IAA4050811 Subject RIV: CE - Biochemistry

  3. Rinossinusites em crianças infectadas pelo HIV sob terapia anti-retroviral Rhinosinusitis in HIV-infected children undergoing antiretroviral therapy

    OpenAIRE

    Carlos Diógenes Pinheiro Neto; Raimar Weber; Bernardo Cunha Araújo-Filho; Ivan Dieb Miziara

    2009-01-01

    A associação dos inibidores de protease (IP) à terapia anti-retroviral provocou mudanças importantes na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto desta associação na prevalência de rinossinusite (RS) e na contagem sérica de linfócitos CD4 em crianças infectadas pelo HIV. CASUÍSTICA E MÉTODOS: A forma de estudo foi cross-sectional com 471 crianças infectadas pelo HIV. Em 1996, inibidores de protease foram liberados para terapia anti-retroviral. Dest...

  4. Evaluation of Potential Anti-Pathogenic and Anti-Retroviral Effects of a Proprietary Bioactive Silicate Alka-Vita™/Alka-V6™/Alkahydroxy™ (AVAH

    Directory of Open Access Journals (Sweden)

    D Townsend

    2010-12-01

    Full Text Available Summary: Alka-Vita™/Alka-V6™/Alkahydroxy™ (AVAH, a modified sodium silicate dietary supplement manufactured by Cisne Enterprises Inc. (Odessa, TX was evaluated for its in vitro anti-retroviral and anti-pathogenic effects. Effects on nitric oxide (NO dependent antiviral activities were measured in neutrophils using standard assays. Assays for inhibition of HIV-II reverse transcriptase (RT, HIV-II protease (PR and glucohydrolase [glucuronidase (GH-1 and glucosidase (GH-2] important for viral replication, coat assembly and virulence respectively, were performed using standard kits. Higher NO (~ 2 fold was detected in neutrophil medium indicating an increase NO mediated antipathogeic activity. Results suggest that the product significantly decreased HIV-RT activity in a dose dependent manner (ED50= 20.4 mM. HIV-PR activity decreased (IC50=14.6 mM with increasing product concentration. The product also decreased the HIV-II virulence by inhibiting the GH-1 (IC50= 34.29 mM and GH-2 (IC50=14.6 mM activity which decreased protein glucosylation and glucuronylation. Changes in surface EPS carbohydrates assed in Pseudomonas aeruginosa suggested a modulatory effect on various carbohydrates and therefore the composition of EPS. Industrial relevance: Pathologies caused by retroviral agents and microorganisms are prevalent both in developed and developing countries.  Indiscriminate use of single target medical drugs has resulted in the development of resistance in these pathogens. Development of novel therapeutic  agents that can effect multiple intrinsic and extrinsic targets in host and the pathogen may prove to be more effective and are less likely to promote drug induced selection. The effectiveness of Alka-Vita™/Alka-V6™/Alkahydroxy™ (AVAH in mitigating various virulence and survival pathways in pathogens is promising. Additionally, it was also effective in inducing a NO mediated immune response.

  5. Cognitive and Behavioural Correlates of Non-Adherence to HIV Anti-Retroviral Therapy: Theoretical and Practical Insight for Clinical Psychology and Health Psychology

    Science.gov (United States)

    Begley, Kim; McLaws, Mary-Louise; Ross, Michael W.; Gold, Julian

    2008-01-01

    This cross-sectional study identified variables associated with protease inhibitor (PI) non-adherence in 179 patients taking anti-retroviral therapy. Univariate analyses identified 11 variables associated with PI non-adherence. Multiple logistic regression modelling identified three predictors of PI non-adherence: low adherence self-efficacy and…

  6. Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

    DEFF Research Database (Denmark)

    Sharma, S; Babiker, A G; Emery, S; Gordin, F M; Lundgren, J D; Neaton, J N; Bakowska, E; Schechter, M; Wiselka, M J; Wolff, Mathias

    OBJECTIVES: The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of...

  7. Les Determinants du Desir De Grossesse chez les Femmes Seropositives sous Traitement AntiRetroviral dans le District de Rwamagana

    OpenAIRE

    Claudien Uwanyirigira; Cyprien Munyanshongore

    2013-01-01

    L’étude vise à analyser les déterminants du désir de grossesse chez les femmes séropositives sous traitement anti-retroviral, afin de contribuer à la réduction de la transmission du virus de la mère à l’enfant. Elle a pour objectifs spécifiques de déterminer la proportion des grossesses chez les femmes à sérologie VIH positive, d’évaluer l’attitude du personnel de santé à l’égard des messages à donner aux femmes séropositives sous ARVs en ce qui concerne le désir de la grossesse, et relever l...

  8. Terapêutica anti-retroviral: interacções medicamentosas a nível molecular

    OpenAIRE

    Horta, Pedro Filipe Castela

    2011-01-01

    A SIDA (causada pelo VIH) é um problema de saúde pública, uma vez que se manifesta por todos os países e afecta cerca de 33,3 milhões de pessoas. Contudo, desde 1999 verifica-se uma diminuição na incidência da infecção em causa e do número de mortes por SIDA, sendo a evolução da terapia anti-retroviral a principal responsável por esse declínio. Os anti-retrovirais podem ser classificados de acordo com o seu mecanismo de acção em: inibidores nucleósidos da transcriptase reversa; inibidores ...

  9. Eventos adversos relacionados à profilaxia anti-retroviral em acidentes ocupacionais Adverse events relating to antiretroviral prophylaxis for occupational accidents

    Directory of Open Access Journals (Sweden)

    Eduardo Alexandrino Servolo Medeiros

    2007-04-01

    Full Text Available O objetivo do estudo foi descrever os eventos adversos clínicos e laboratoriais secundários ao uso dos agentes anti-retrovirais em indivíduos submetidos à quimioprofilaxia. Foram avaliados 37 funcionários de um hospital universitário submetidos à quimioprofilaxia com quatro esquemas de medicação anti-retroviral após exposição ocupacional a fluidos de pacientes contaminados com infecção pelo vírus da imunodeficiência humana. Trinta e dois (86,5% desenvolveram eventos adversos clínicos ou laboratoriais. A profilaxia teve que ser suspensa em dois profissionais (5,4% em virtude das reações ocorridas. Os eventos adversos relacionados à quimioprofilaxia para infecção por HIV em funcionários de saúde, vítimas de acidente ocupacional foram freqüentes. Porém, raramente foi necessário retirar a medicação anti-retroviral.The objective of the study was to describe adverse events detected clinically or in the laboratory that were secondary to the use of antiretroviral agents among individuals undergoing antiretroviral prophylaxis. Evaluations were performed on 37 teaching hospital employees who underwent prophylaxis using four regimens of antiretroviral medication following occupational exposition to contaminated fluids from patients with human immunodeficiency virus infection. Thirty-two (86.5% developed adverse events detected clinically or in the laboratory. The prophylaxis administered to two professionals (5.4% had to be suspended because of the reactions that occurred. Adverse events relating to prophylaxis for HIV infection in health care workers who were victims of occupational accidents were frequent. However, it was rarely necessary to withdraw the antiretroviral medication.

  10. Rinossinusites em crianças infectadas pelo HIV sob terapia anti-retroviral Rhinosinusitis in HIV-infected children undergoing antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Carlos Diógenes Pinheiro Neto

    2009-02-01

    Full Text Available A associação dos inibidores de protease (IP à terapia anti-retroviral provocou mudanças importantes na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto desta associação na prevalência de rinossinusite (RS e na contagem sérica de linfócitos CD4 em crianças infectadas pelo HIV. CASUÍSTICA E MÉTODOS: A forma de estudo foi cross-sectional com 471 crianças infectadas pelo HIV. Em 1996, inibidores de protease foram liberados para terapia anti-retroviral. Desta forma, dois grupos de crianças foram formados: as que não fizeram uso de IP e as que fizeram uso desta droga após 1996. A prevalência de RS e a contagem sérica de linfócitos CD4 foram comparadas entre estes grupos. RESULTADOS: 14,4% das crianças infectadas pelo HIV apresentaram RS. A RS crônica foi mais prevalente que a RS aguda em ambos os grupos. Crianças menores de 6 anos tratadas com a associação de IP apresentaram maior prevalência de RS aguda. A associação de IP esteve associada à maior contagem de linfócitos CD4 séricos com menor prevalência de RS crônica. CONCLUSÕES: A terapia com IP esteve associada ao aumento na contagem de linfócitos CD4. Crianças abaixo dos 6 anos em uso de IP apresentaram menor tendência à cronificação da doença.The association of protease inhibitors (PI to antiretroviral therapy has generated sensible changes in morbidity and mortality of HIV-infected patients. AIM: Aims at evaluating the impact of this association on the prevalence of rhinosinusitis (RS and CD4+ lymphocyte count in HIV-infected children. METHODS: Retrospective cross-sectional study of the medical charts of 471 HIV-infected children. In 1996, protease inhibitors were approved for use as an association drug in antiretroviral therapy. Children were divided into two groups: one which did not receive PI and another which received PI after 1996. The prevalence of RS and CD4+ lymphocyte counts were compared between these groups

  11. Dental Caries Prevalence in Human Immunodeficiencyb Virus Infected Patients Receiving Highly Active Anti-Retroviral Therapy in Kermanshah, Iran

    Directory of Open Access Journals (Sweden)

    Loghman Rezaei-Soufi

    2014-03-01

    Full Text Available Objective: Introduction of new approaches for the treatment of human immunodeficiency virus (HIV infection such as anti-retroviral medicines has resulted in an increase in the life expectancy of HIV patient. Evaluating the dental health status as a part of their general health care is needed in order to improve the quality of life in these patients. The aim of this study was to compare the root and crown caries rate in HIV patients receiving highly active antiretroviral therapy (HAART with that rate in HIV patients without treatment option. Materials and Methods: This cross sectional study consisting of 100 individuals of both genders with human immunodeficiency virus were divided into two groups: i. group 1 (treatment group including 50 patients with acquired immunodeficiency syndrome (AIDS receiving HAART and ii. group 2 (control group including 50 HIV infected patients not receiving HAART. Dental examinations were done by a dentist under suitable light using periodontal probe. For each participant, numbers of decay (D, missed (M, filled (F, Decayed missed and filled teeth (DMFT, decay surface (Ds, missed surface (Ms, filled surface (Fs, Decayed missed and filled surfaces (DMFS, and tooth and root caries were recorded. Data were analyzed using Chi-square test and independent t test using SPSS 13.0, while p-value of <0.05 was considered statistically significant in all analysis. Results: The mean and standard deviation (SD of decayed, missed and filled teeth of those who were on highly active antiretroviral therapy was 6.86 ± 3.57, 6.39 ± 6.06 and 1.89 ± 1.93, respectively. There was no significant difference between these values regarding to the treatment of patients. The mean and standard deviation of DMFT, DMFS and the number of decayed root surfaces were 15.14 ± 6.09, 56.79 ± 28.56, and 4.96 ± 2.89 in patients treated by anti-retroviral medicine which were not significantly different compared to those without this treatment

  12. The effect of socio-economic status on adherence to Anti-retroviral therapy

    OpenAIRE

    Akindele, Rasaq Akintunde; Fasanu, Adeniyi Olanipekun; Mabayoje, Victor Olatunji; Adisa, Patricia Olukorede; Adeniran Samuel ATIBA; Babatunde, Samuel Olusegun

    2015-01-01

    Background: Human Immunodeficiency Virus infection is a pandemic disease threatening public health for decades now. With the advent of antiretroviral drugs (ARDs) being taken on long term basis, it is important to examine factors that could affect adherence to these medicationsObjectives: To determine relationship between socio-economic status of sero-positive HIV patients on antiretroviral drugs and their adherence to these drugsMethods:  This is a descriptive cross sectional study. One hund...

  13. Cost estimates of HIV care and treatment with and without anti-retroviral therapy at Arba Minch Hospital in southern Ethiopia

    OpenAIRE

    Robberstad Bjarne; Jerene Degu; Bikilla Asfaw; Lindtjorn Bernt

    2009-01-01

    Abstract Background Little is known about the costs of HIV care in Ethiopia. Objective To estimate the average per person year (PPY) cost of care for HIV patients with and without anti-retroviral therapy (ART) in a district hospital. Methods Data on costs and utilization of HIV-related services were taken from Arba Minch Hospital (AMH) in southern Ethiopia. Mean annual outpatient and inpatient costs and corresponding 95% confidence intervals (CI) were calculated. We adopted a district hospita...

  14. Acceptance of Anti-Retroviral Therapy among Patients Infected with HIV and Tuberculosis in Rural Malawi Is Low and Associated with Cost of Transport

    OpenAIRE

    Rony Zachariah; Anthony David Harries; Marcel Manzi; Patrick Gomani; Roger Teck; Mit Phillips; Peter Firmenich

    2006-01-01

    BACKGROUND: A study was conducted among newly registered HIV-positive tuberculosis (TB) patients systematically offered anti-retroviral treatment (ART) in a district hospital in rural Malawi in order to a) determine the acceptance of ART b) conduct a geographic mapping of those placed on ART and c) examine the association between "cost of transport" and ART acceptance. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cross-sectional analysis was performed on routine program data for the period...

  15. Acceptance of anti-retroviral therapy among patients infected with HIV and tuberculosis in rural Malawi is low and associated with cost of transport.

    OpenAIRE

    Zachariah, Rony; Harries, A. D.; Manzi, M.; Gomani, P; Teck, R; Philips, Mit; Firmenich, Peter

    2006-01-01

    BACKGROUND: A study was conducted among newly registered HIV-positive tuberculosis (TB) patients systematically offered anti-retroviral treatment (ART) in a district hospital in rural Malawi in order to a) determine the acceptance of ART b) conduct a geographic mapping of those placed on ART and c) examine the association between "cost of transport" and ART acceptance. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cross-sectional analysis was performed on routine program data for the period...

  16. Circulating heat shock protein 60 levels are elevated in HIV patients and are reduced by anti-retroviral therapy.

    Directory of Open Access Journals (Sweden)

    Itaru Anraku

    Full Text Available Circulating heat shock protein 60 (Hsp60 and heat shock protein 10 (Hsp10 have been associated with pro- and anti-inflammatory activity, respectively. To determine whether these heat shock proteins might be associated with the immune activation seen in HIV-infected patients, the plasma levels of Hsp60 and Hsp10 were determined in a cohort of 20 HIV-infected patients before and after effective combination anti-retroviral therapy (cART. We show for the first time that circulating Hsp60 levels are elevated in HIV-infected patients, with levels significantly reduced after cART, but still higher than those in HIV-negative individuals. Hsp60 levels correlated significantly with viral load, CD4 counts, and circulating soluble CD14 and lipopolysaccharide levels. No differences or correlations were seen for Hsp10 levels. Elevated circulating Hsp60 may contribute to the immune dysfunction and non-AIDS clinical events seen in HIV-infected patients.

  17. Mitochondrial DNA Haplogroups influence lipoatrophy after Highly Active Anti-retroviral Therapy

    OpenAIRE

    Hendrickson, Sher L.; Kingsley, Lawrence A; Ruiz-Pesini, Eduardo; Poole, Jason C.; Jacobson, Lisa P.; Palella, Frank J.; Bream, Jay H.; Wallace, Douglas C.; O’Brien, Stephen J.

    2009-01-01

    Although highly active retroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors (NRTIs). The clinical symptoms of lipoatrophy resemble those of inherited mit...

  18. Effect of Micronutrient and Probiotic Fortified Yogurt on Immune-Function of Anti-Retroviral Therapy Naive HIV Patients  

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    J. Dik F. Habbema

    2011-10-01

    Full Text Available Background: Micronutrient supplementation has been shown to reduce the progression of HIV but does not have an effect on the intestinal barrier or the intestinal microbiota of HIV patients. Studies have suggested that probiotics could potentially complement micronutrients in preserving the immune-function of HIV patients. Objective: Assess the impact of micronutrient supplemented probiotic yogurt on the immune function of HIV patients. Design: We performed a randomized, double blind, controlled trial with CD4 count as primary outcome among HIV patients naïve to anti-retroviral treatment. Secondary outcomes included hematological parameters, incidence of diarrhea and clinical symptoms. A total of 112 HIV patients were randomized to receive a micronutrient fortified yogurt with (n = 55 or without additional probiotic Lactobacillus rhamnosus GR-1 (n = 57 for four weeks. Results: An average decline in CD4 count of −70 cells/μL (95% CI: −154 to −15 was observed in the micronutrient, probiotic group versus a decrease of −63 cells/μL (95% CI: −157 to −30 in the micronutrient control group (p = 0.9. Additional probiotic supplementation was well tolerated and not associated with adverse events. No difference between groups was detected in incidence of diarrhea or clinical symptoms. An improvement of hemoglobin levels was observed for all subjects, based upon a mean difference from baseline of 1.4 g/L (SD = 6 (p = 0.02. Conclusion: The addition of probiotics to a micronutrient fortified yogurt was well tolerated by HIV patients but was not associated with a further increase in CD4 count after one month.

  19. The effects of decentralizing anti-retroviral services in Nigeria on costs and service utilization: two case studies.

    Science.gov (United States)

    Johns, Benjamin; Baruwa, Elaine

    2016-03-01

    Nigeria launched a 'hub and spoke' decentralization pilot in March 2010 for the provision of anti-retroviral therapy (ART). In this programme, stable ART patients at hospitals (hubs) were referred to primary health care centres (spokes) for the continued provision of ART. The objectives of this study are to compare the cost of ART care provided through the two levels of care. We also assess if decentralization was associated with changes in patients' service utilization. Data were collected from facilities and patient records from Kaduna and Cross Rivers States. Costs were collected from the provider perspective. In Cross River, 398 patients and 528 from Kaduna were included in the retrospective cohort. The analysis utilizes separate fixed effect regressions for each state to assess differences in costs and service utilization among patients that decentralized. Uptake of decentralized services was ∼3% in Cross Rivers and ∼9% in Kaduna among active ART patients in April 2011. Patients electing to decentralize had 40% (95% CI: 13% to 67%) higher costs in Cross Rivers and 29% (-44% to -14%) lower costs in Kaduna as compared with patients that did not decentralize. Lower costs in Kaduna appear to result from shifting care to less expensive cadres of health workers (task shifting) rather than decentralization. Decentralization of health services is a complicated process and broad generalizations across settings and processes, concerning whether or not it reduces unit costs, are likely over-simplifications. Similarly, decentralization of ART services does not automatically increase access to ART care, and may limit access to ART laboratory services. This study is limited by not including costs incurred above the facility level, such as training, or costs borne by patients. PMID:25989806

  20. Compreensão de informações relativas ao tratamento anti-retroviral entre indivíduos infectados pelo HIV HIV patients' understanding of information on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Maria das Graças Braga Ceccato

    2004-10-01

    Full Text Available Para avaliar a compreensão das informações sobre a terapia anti-retroviral entre portadores do HIV/AIDS atendidos em serviços públicos de referência, em Belo Horizonte, Minas Gerais, Brasil, foi realizada análise transversal por meio de entrevistas com pacientes, após a primeira dispensação de anti-retrovirais. A orientação recebida dos profissionais de saúde e o nível de compreensão pelo paciente foram investigados, sendo este classificado como insuficiente se houvesse discordância igual ou superior a 30,0% entre a resposta do paciente e a informação contida na prescrição para itens selecionados. Divergências entre as informações da prescrição e as relatadas pelos 358 pacientes foram observadas. O nível de compreensão das informações sobre anti-retrovirais prescritos foi classificado como insuficiente para 26,3%. Os resultados obtidos revelam proporção importante de pacientes com lacunas na compreensão de informações sobre a terapêutica anti-retroviral combinada. É necessário implementar estratégias para aumentar a qualidade das orientações fornecidas a esses pacientes. O enfoque multidisciplinar no atendimento aos pacientes poderá contribuir para reverter a situação observada.To assess the understanding of information related to antiretroviral therapy among HIV-infected patients enrolled in public AIDS services (Belo Horizonte, Minas Gerais State, Brazil, a cross-sectional analysis was carried out, based on interviews with patients after initial provision of antiretroviral drugs. The study evaluated the information on antiretroviral therapy provided by healthcare professionals and the patients' level of understanding in relation to prescription information. This level was classified as insufficient if there was disagreement of more than 30.0% between the information reported by the patient and the written prescription. Divergence between prescriptions and information reported by 358 interviewed

  1. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Bacha Tigist

    2012-08-01

    to have treatment failure retrospectively by the authors based on their records. Hence, they were not detected and these patients were not offered second line ARTs. Conclusions Having chronic malnutrition, low CD4 at base line, chronic diarrhea after initiation of first line ART, substitution of ART drugs and age less than 3 years old were found to be independent predictors of first line ART failure in children. Most of the first line ART failure cases were not detected early and those that were detected were not switched to second line drugs in a timely fashion. Children with the above risk factors should be closely monitored for a timely switch to second line highly active anti-retroviral therapy.

  2. Retention of HIV-Infected Children in the First 12 Months of Anti-Retroviral Therapy and Predictors of Attrition in Resource Limited Settings: A Systematic Review

    OpenAIRE

    Abuogi, Lisa L.; Smith, Christiana; Elizabeth J. McFarland

    2016-01-01

    Current UNAIDS goals aimed to end the AIDS epidemic set out to ensure that 90% of all people living with HIV know their status, 90% initiate and continue life-long anti-retroviral therapy (ART), and 90% achieve viral load suppression. In 2014 there were an estimated 2.6 million children under 15 years of age living with HIV, of which only one-third were receiving ART. Little literature exists describing retention of HIV-infected children in the first year on ART. We conducted a systematic sea...

  3. Determinantes da aderência à terapia anti-retroviral combinada em Brasília, Distrito Federal, Brasil, 1999-2000

    OpenAIRE

    Carvalho Cláudio Viveiros de; Duarte Diva Barnabé; Merchán-Hamann Edgar; Bicudo Eliana; Laguardia Josué

    2003-01-01

    A aderência ao tratamento é um dos principais problemas relacionados à terapia anti-retroviral, já que a tomada incompleta dos medicamentos pode levar à resistência viral. Efeitos colaterais podem interferir com a qualidade de vida dos pacientes. Buscou-se estimar níveis de aderência à terapia e investigar seus determinantes, através de um estudo transversal. Definiram-se dois pontos de corte como boa aderência: a tomada de pelo menos 80% ou de 95% da medicação conforme a prescrição. Realizar...

  4. Incidence of WHO stage 3 and 4 conditions following initiation of anti-retroviral therapy in resource limited settings.

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    Andrea J Curtis

    Full Text Available OBJECTIVES: To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART in resource limited settings (RLS. DESIGN/SETTING: A descriptive analysis of routine program data collected prospectively from 25 Médecins Sans Frontières supported HIV treatment programs in eight countries between 2002 and 2010. SUBJECTS/PARTICIPANTS: 35,349 study participants with median follow-up on ART of 1.33 years (IQR 0.51-2.41. OUTCOME MEASURES: Incidence in 100 person-years of WHO stage 3 or 4 conditions during 5 periods after ART initiation. Diagnoses of conditions were made according to WHO criteria and relied upon clinical assessments supported by basic laboratory investigations. RESULTS: The incidence of any WHO clinical stage 3 or 4 condition over 3 years was 40.02 per 100 person-years (31.77 for stage 3 and 8.25 for stage 4. The incidence of stage 3 and 4 conditions fell by over 97% between months 0-3 and months 25-36 (77.81 to 2.40 for stage 3 and 28.70 to 0.64 for stage 4. During months 0-3 pulmonary tuberculosis was the most common condition diagnosed in adults (incidence 22.24 per 100 person-years and children aged 5-14 years (25.76 and oral candidiasis was the most common in children <5 years (25.79. Overall incidences were higher in Africa compared with Asia (43.98 versus 12.97 for stage 3 and 8.98 versus 7.05 for stage 4 conditions, p<0.001. Pulmonary tuberculosis, weight loss, oral and oesophageal candidiasis, chronic diarrhoea, HIV wasting syndrome and severe bacterial infections were more common in Africa. Extra-pulmonary tuberculosis, non-tuberculous mycobacterial infection, cryptococcosis, penicilliosis and toxoplasmosis were more common in Asia. CONCLUSIONS: The incidence of WHO stage 3 and 4 conditions during the early period after ART initiation in RLS is high, but greatly reduces over time. This is likely due to both the benefits of ART and deaths of the sickest patients occurring shortly

  5. Incidence of WHO Stage 3 and 4 Conditions following Initiation of Anti-Retroviral Therapy in Resource Limited Settings

    Science.gov (United States)

    Curtis, Andrea J.; Marshall, Catherine S.; Spelman, Tim; Greig, Jane; Elliot, Julian H.; Shanks, Leslie; Du Cros, Philipp; Casas, Esther C.; Da Fonseca, Marcio Silveria; O’Brien, Daniel P.

    2012-01-01

    Objectives To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS). Design/Setting A descriptive analysis of routine program data collected prospectively from 25 Médecins Sans Frontières supported HIV treatment programs in eight countries between 2002 and 2010. Subjects/Participants 35,349 study participants with median follow-up on ART of 1.33 years (IQR 0.51–2.41). Outcome Measures Incidence in 100 person-years of WHO stage 3 or 4 conditions during 5 periods after ART initiation. Diagnoses of conditions were made according to WHO criteria and relied upon clinical assessments supported by basic laboratory investigations. Results The incidence of any WHO clinical stage 3 or 4 condition over 3 years was 40.02 per 100 person-years (31.77 for stage 3 and 8.25 for stage 4). The incidence of stage 3 and 4 conditions fell by over 97% between months 0–3 and months 25–36 (77.81 to 2.40 for stage 3 and 28.70 to 0.64 for stage 4). During months 0–3 pulmonary tuberculosis was the most common condition diagnosed in adults (incidence 22.24 per 100 person-years) and children aged 5–14 years (25.76) and oral candidiasis was the most common in children <5 years (25.79). Overall incidences were higher in Africa compared with Asia (43.98 versus 12.97 for stage 3 and 8.98 versus 7.05 for stage 4 conditions, p<0.001). Pulmonary tuberculosis, weight loss, oral and oesophageal candidiasis, chronic diarrhoea, HIV wasting syndrome and severe bacterial infections were more common in Africa. Extra-pulmonary tuberculosis, non-tuberculous mycobacterial infection, cryptococcosis, penicilliosis and toxoplasmosis were more common in Asia. Conclusions The incidence of WHO stage 3 and 4 conditions during the early period after ART initiation in RLS is high, but greatly reduces over time. This is likely due to both the benefits of ART and deaths of the sickest patients occurring shortly after ART

  6. Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

    DEFF Research Database (Denmark)

    Baxter, J D; Dunn, D; White, E;

    2015-01-01

    .8%) and Africa (0.1%). The overall prevalence of TDR was 10.1%, more commonly to nonnucleoside reverse transcriptase inhibitors (4.5%) and nucleoside reverse transcriptase inhibitors (4%) compared with protease inhibitors (2.8%). The most frequent TDR mutations observed were M41L, D67N/G/E, T215F...

  7. Les Determinants du Desir De Grossesse chez les Femmes Seropositives sous Traitement AntiRetroviral dans le District de Rwamagana

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    Claudien Uwanyirigira

    2013-06-01

    Full Text Available L’étude vise à analyser les déterminants du désir de grossesse chez les femmes séropositives sous traitement anti-retroviral, afin de contribuer à la réduction de la transmission du virus de la mère à l’enfant. Elle a pour objectifs spécifiques de déterminer la proportion des grossesses chez les femmes à sérologie VIH positive, d’évaluer l’attitude du personnel de santé à l’égard des messages à donner aux femmes séropositives sous ARVs en ce qui concerne le désir de la grossesse, et relever les facteurs déterminant le désir d’avoir des enfants après la mise ne route d’un traitement par antirétroviraux . Il s’agit d’une étude descriptive transversale. Elle a été conduite auprès de 260 femmes infectées par le VIH sous ARVs et suivies dans les FOSA, ayant les services de VCT/PMTCT et des ARVs. L’étude montre que 26,9% des femmes ont été enceintes après avoir été informées de leur statut sérologique positif pour le VIH et que 38,5% des femmes séropositives sous traitement anti-rétroviral désirent avoir des enfants dans le futur. La majorité des femmes (82,7% reconnaissent l’importance de l’utilisation des contraceptifs alors que le pourcentage des femmes qui connaissent l’importance d’utiliser les ARVs pendant la grossesse et l’accouchement pour réduire le risque de transmission de la mère à l’enfant est de 76,9%. Les facteurs déterminant le désir de la grossesse parmi les femmes séropositives sont : La confiance attribuée aux anti-rétroviraux, la parité c’est-à-dire les femmes qui n’ont pas eu d’enfant ont un désir de maternité deux fois supérieur que les femmes qui ont eu au moins un enfant, et la non utilisation des méthodes contraceptives chez les femmes à sérologie VIH positives pour réduire le risque de transmission de la mère à l’enfant. Nous recommandons de renforcer l’intégration des activités de santé de la reproduction et de Planning

  8. Price Sensitivity of Demand for Prescription Drugs

    DEFF Research Database (Denmark)

    Skipper, Lars; Simonsen, Marianne; Skipper, Niels

    This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression ...... education and income are, however, more responsive to the price. Also, essential drugs that prevent deterioration in health and prolong life have lower associated average price sensitivity.......This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression...... kink design. Thus, within a unifying framework we uncover price sensitivity for different subpopulations and types of drugs. The results suggest low average price responsiveness with corresponding price elasticities ranging from -0.08 to -0.25, implying that demand is inelastic. Individuals with lower...

  9. Patentes farmacêuticas e saúde pública: desafios à política brasileira de acesso ao tratamento anti-retroviral Pharmaceutical patents and public health: challenges for the Brazilian antiretroviral treatment policy

    Directory of Open Access Journals (Sweden)

    Constance Marie Milward de Azevedo Meiners

    2008-07-01

    Full Text Available O preço elevado de medicamentos patenteados tem intensificado o debate em torno do impacto do regime da propriedade intelectual sobre o acesso a tratamentos de saúde, merecendo destaque o caso do HIV/AIDS. A política brasileira de tratamento anti-retroviral, parte de um programa nacional que integra medidas de prevenção e promoção da saúde, permitiu o alcance de uma ampla cobertura com qualidade, tendo sido apontada como modelo para outros países. Não obstante, conforme amadurece o Programa Nacional de DST e AIDS, os gastos com a incorporação de anti-retrovirais patenteados ao esquema terapêutico para pacientes em tratamento atinge um peso, cada vez maior, em seu orçamento. O presente artigo toma em conta os desafios apresentados pelas patentes farmacêuticas à saúde pública e discute possíveis caminhos para a sustentação da política de acesso universal e gratuito ao tratamento contra HIV/AIDS no Brasil.The high prices of patented drugs have fueled the debate regarding the impact of the intellectual property system on access to treatment, with a special focus on HIV/AIDS. The Brazilian policy for antiretroviral treatment, part of a comprehensive program that includes both disease prevention and health promotion activities, has allowed the country to meet goals for coverage and quality and has been considered a model for other countries. However, as the Brazilian STD/AIDS Program reaches maturity, the increasing incorporation of patented drugs into the AIDS treatment regimen imposes an increasing burden on the country's health budget. This article discusses the public health challenges raised by pharmaceutical patents and discusses possible ways to sustain the national policy for free, universal access to HIV/AIDS treatment.

  10. Influência da terapêutica anti-retroviral na história natural da infecção por VIH

    OpenAIRE

    Prata, Margarida Isabel Ribeiro Beato

    2009-01-01

    O número de indivíduos que controlam o VIH, mercê de uma terapêutica anti-retroviral (TARV) mais eficaz, tem vindo a aumentar nas últimas décadas. Ao longo deste trabalho, pretende demonstrar-se qual o efeito da TARV nos doentes infectados com o VIH. São apresentadas exposições relativas à História Natural da Infecção, ao Diagnóstico e Monitorização e, ainda, aos Princípios Gerais da TARV. Servem estes textos para preparar a apresentação de um caso concreto, seguido da sua Discussão e das...

  11. Price Sensitivity of Demand for Prescription Drugs

    DEFF Research Database (Denmark)

    Simonsen, Marianne; Skipper, Lars; Skipper, Niels

    2016-01-01

    We investigate price sensitivity of demand for prescription drugs, using drug purchase records for the entire Danish population. We identify price responsiveness by exploiting variation in prices caused by kinked reimbursement schemes and implement a regression kink design. The results suggest some...... price responsiveness with corresponding price elasticities ranging from −0.2 to −0.7. Individuals with chronic disease and especially individuals above the age of 65 respond less to the price of drugs....

  12. Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review.

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    Matthew Arentz

    Full Text Available INTRODUCTION: Use of antiretroviral therapy (ART during treatment of drug susceptible tuberculosis (TB improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB. METHODS: We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events. RESULTS: Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR 3.4, 95% CI 1.6-7.4 and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6 during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3 and less than 50 cells/mm(3, and when correcting for drug resistance pattern. LIMITATIONS: We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias. DISCUSSION: While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

  13. Retention of HIV-Infected Children in the First 12 Months of Anti-Retroviral Therapy and Predictors of Attrition in Resource Limited Settings: A Systematic Review

    Science.gov (United States)

    Smith, Christiana; McFarland, Elizabeth J.

    2016-01-01

    Current UNAIDS goals aimed to end the AIDS epidemic set out to ensure that 90% of all people living with HIV know their status, 90% initiate and continue life-long anti-retroviral therapy (ART), and 90% achieve viral load suppression. In 2014 there were an estimated 2.6 million children under 15 years of age living with HIV, of which only one-third were receiving ART. Little literature exists describing retention of HIV-infected children in the first year on ART. We conducted a systematic search for English language publications reporting on retention of children with median age at ART initiation less than ten years in resource limited settings. The proportion of children retained in care on ART and predictors of attrition were identified. Twelve studies documented retention at one year ranging from 71–95% amongst 31877 African children. Among the 5558 children not retained, 4082 (73%) were reported as lost to follow up (LFU) and 1476 (27%) were confirmed to have died. No studies confirmed the outcomes of children LFU. Predictors of attrition included younger age, shorter duration of time on ART, and severe immunosuppression. In conclusion, significant attrition occurs in children in the first 12 months after ART initiation, the majority attributed to LFU, although true outcomes of children labeled as LFU are unknown. Focused efforts to ensure retention and minimize early mortality are needed as universal ART for children is scaled up. PMID:27280404

  14. Microfinance and HIV mitigation among people living with HIV in the era of anti-retroviral therapy: emerging lessons from Cote d'Ivoire.

    Science.gov (United States)

    Holmes, Kathleen; Winskell, Kate; Hennink, Monique; Chidiac, Sybil

    2011-01-01

    The effects of HIV/AIDS have been far-reaching in Africa. Beyond adverse health outcomes and the tremendous toll on life, AIDS has serious economic impacts on households, increasing livelihood insecurity while simultaneously depleting socio-economic resources. Although microfinance is believed to have the potential to mitigate the economic impacts of HIV by helping affected households and communities better prepare for and cope with HIV-related economic shocks, little empirical research exists on this subject. This qualitative study examines the socio-economic impacts of economic strengthening activities on people living with HIV (PLHIV) in the era of increased access to anti-retroviral therapy to determine if savings-led, community-managed microfinance is a justified activity for HIV programmes. Findings from a village savings and loan programme, implemented by CARE International in Cote d'Ivoire, revealed that when appropriate medical treatment is available PLHIV are capable of participating in and benefit from microfinance activities, which increased HIV-positive clients' access to money and economic self-sufficiency. By bringing individuals with similar experiences together, savings and loan groups also acted as self-support groups providing psychosocial support while reducing stigmatisation and increasing members' sense of dignity and self-worth. PMID:20936558

  15. Evaluation of the Impact of Anti-Retroviral Therapy on the Prevalence of Oral Lesions in Human Immunodeficiency Virus Infected Patients

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    P. Davoodi

    2013-10-01

    Full Text Available Introduction & Objective: Oral lesions have important diagnostic and prognostic roles in HIV infected patients. It seems that HAART reduces the prevalence of oral lesions. The aim of the present study was to evaluate the prevalence of oral lesions in HIV infected patients on/not on HAART. Materials & Methods: In this retrospective study, 40 HIV infected patients receiving HAART and 40 who were not on HAART were evaluated in Behavioral Consultation Center in Kermanshah. The diagnosis of the oral lesions was recorded by using established presump-tive clinical criteria. Data were gathered and analyzed using SPSS version 16 by chi-square test. Results: In the current study 80 HIV infected patients with mean age of 38.86 were chosen. 72.5% and 27.5% of participants were male and female respectively. The most common le-sions in those receiving HAART were hairy leukoplakia, hairy tongue and oral pigmentation. However the prevalence of these lesions had declined in comparison to those who were not on HAART but the difference was not significant (P>0.05. Although comparing lesions in the two groups showed no significant difference, the total number of lesions significantly reduced in patients receiving HAART (P=0.046 Conclusion: According to the results of the present study using anti retroviral therapy leaded to reduction in the oral lesions in HIV infected patients. However, more research in this field seems necessary. (Sci J Hamadan Univ Med Sci 2013; 20 (3:215-222

  16. Crystalluria in HIV/AIDS patients on highly active anti-retroviral therapy in the Kumasi metropolis; a cross sectional study

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    Richard K. D. Ephraim

    2014-01-01

    Full Text Available Background: Crystalluria is associated with some highly active anti-retroviral therapies (HAART′s used in the management of HIV/AIDS. Aims: This study used light microscopy to establish the prevalence of crystalluria among HIV/AIDS patients on HAART and identified the routine crystals present in their urine. Materials and Methods: In this simple randomised cross-sectional study, 200 HIV/AIDS participants, comprising 150 on HAART and 50 HAART-naοve were recruited from the HIV clinic at the Komfo Anokye Teaching Hospital (KATH. Urine and blood samples were collected, for urinalysis and the determination of the CD4 count, respectively. A well-structured pre-tested questionnaire was used to obtain socio-demographic data and clinical history of the participants. Results: The prevalence of crystalluria was higher among HIV-infected persons on HAART than those not on HAART (6.7% vs 4%; P = 0.733. Calcium oxalate and triple phosphate crystals were the crystal types present in their urine (3.5% and 2.5%, respectively and was present only in HIV subjects on first line of treatment (without protease inhibitors. Participants aged between 40-50 years and those with hypersthenuria and acidic urine had the highest amount of crystalluria (41.6%, 83.3%, and 58.3%, respectively. Conclusion: HAART is associated with crystalluria in HIV patients. Light microscopy will be of disgnostic value in resource limited settings.

  17. Metabolic changes associated with antiretroviral therapy in HIV-positive patients Alteraciones metabólicas asociadas a la terapia anti-retroviral en pacientes HIV-positivos Alterações metabólicas associadas à terapia anti-retroviral em pacientes HIV-positivos

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    Sabrina Esteves de Matos Almeida

    2009-04-01

    Full Text Available OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (pOBJETIVO: Evaluar las alteraciones metabólicas asociadas a la terapia anti-retroviral potente en pacientes HIV-positivos e identificar factores de riesgo asociados. MÉTODOS: Estudio retrospectivo con 110 pacientes HIV-positivos que estaban en terapia anti-retroviral potente (HAART en la ciudad de Porto Alegre (Sur de Brasil, entre enero de 2003 y marzo de 2004. Los datos colectados incluyen variables demográficas, tabaquismo, diabetes mellitas, niveles de colesterol y triglicéridos, fase de la infección viral, terapia anti-retroviral y co-infección con hepatitis C. El análisis multivariado para medidas repetidas (General Linear Model procedure for Repeated Measures fue utilizada para analizar la interacción entre el efecto de uso de HAART y el uso de inhibidores de proteasa o co-infección por hepatitis C. RESULTADOS: Fueron observados aumentos significativos en los niveles de colesterol total, triglicéridos y glucosa posterior al tratamiento con HAART (pOBJETIVO: Avaliar as alterações metabólicas associadas à terapia anti-retroviral potente em pacientes HIV-positivos e identificar fatores de risco associados. MÉTODOS: Estudo retrospectivo com 110

  18. Estudo da Adesão à Quimioprofilaxia Anti-retroviral para a Infecção por HIV em Mulheres Sexualmente Vitimadas Study of Adherence to Antiretroviral Chemoprophylaxis for HIV Infection in Sexually Abused Women

    Directory of Open Access Journals (Sweden)

    Jefferson Drezett

    1999-10-01

    Full Text Available Objetivos: embora não existam dados apropriados para estabelecer sua eficácia, alguns serviços tem utilizado, profilaticamente, a terapia anti-retroviral para o HIV nos casos de violência sexual. O objetivo deste estudo foi avaliar a aceitabilidade, tolerância e adesão a um esquema quimioprofilático para o HIV. Pacientes e método: foram avaliadas 62 mulheres vítimas de estupro e/ou atentado violento ao pudor com coito ectópico anal. Os agressores foram referidos como desconhecidos. A profilaxia foi iniciada dentro das primeiras 48 h da violência e mantida por 4 semanas, sendo administrados diariamente: zidovudina, 600 mg; indinavir, 2.400 mg e lamivudina, 300 mg. Resultados: a taxa de descontinuidade foi de 24,2%, sendo em 12 casos (80% decorrente de intolerância gástrica. Os efeitos colaterais estiveram presentes em 43 casos (69,4%, sendo as náuseas e vômitos os mais freqüentes. A complexidade posológica e o tempo de uso foram fatores possivelmente associados ao uso inadequado das drogas, ocorrendo em 10,6% dos casos. Conclusão: a taxa de descontinuidade da quimioprofilaxia foi semelhante à observada em outras indicações.Purpose: some medical institutions have been prophylactically ministrating anti-HIV therapy in cases of sexual violence, although there are no appropriate basic facts to establish its efficacy. The aim of the present study was to evaluate the acceptance, tolerance and adhesion of these women under a chemoprophylaxis plan for HIV. Methods: sixty-two women victims of rape and/or anal intercourse with unknown aggressors have been evaluated. Prophylaxis has been started within the first 48 h after violence and maintained for 4 weeks, with daily administration of zidovudine, 600 mg; indinavir, 2,400 mg and lamivudine, 300 mg. Results: the discontinuance rate was 24.2%, withe 12 cases (80% due to gastric intolerance. The side effects were present in 43 cases (69.4%, including nausea and vomitting as the most

  19. Effector Kinase Coupling Enables High-Throughput Screens for Direct HIV-1 Nef Antagonists with Anti-retroviral Activity

    OpenAIRE

    Emert-Sedlak, Lori A; Narute, Purushottam; Shu, Sherry T.; Poe, Jerrod A.; Shi, Haibin; Yanamala, Naveena; Alvarado, John Jeff; Lazo, John S.; Yeh, Joanne I.; Johnston, Paul A.; Smithgall, Thomas E

    2013-01-01

    HIV-1 Nef, a critical AIDS progression factor, represents an important target protein for antiretroviral drug discovery. Because Nef lacks intrinsic enzymatic activity, we developed an assay that couples Nef to the activation of Hck, a Src-family member and Nef effector protein. Using this assay, we screened a large, diverse chemical library and identified small molecules that block Nef-dependent Hck activity with low micromolar potency. Of these, a diphenylpyrazolo compound demonstrated sub-...

  20. Fatores associados à interrupção de tratamento anti-retroviral em adultos com AIDS: Rio Grande do Norte, Brasil, 1999 - 2002 Cofactors of antiretroviral treatment interruption in cases of adults with AIDS: Rio Grande do Norte, Brazil, 1999-2002

    Directory of Open Access Journals (Sweden)

    Ana Maria de Brito

    2006-04-01

    Full Text Available OBJETIVO: Com o intuito de analisar os fatores associados à interrupção do tratamento anti-retroviral em adultos com AIDS, no Rio Grande do Norte, Brasil, realizou-se estudo nas unidades locais de referência no atendimento à AIDS. MÉTODOS: Tomou-se como critério de não interrupção o comparecimento a pelo menos 80% das visitas programadas à farmácia para o recebimento das drogas prescritas, por um período de seis meses consecutivos, após a data da prescrição. RESULTADOS: O estudo compreendeu 498 casos, dos quais 52,4% já chegaram a um serviço especializado com alguma condição indicativa de imunodeficiência. O percentual total de não interrupção foi de 64,1%. Não foi encontrada associação com as variáveis sexo, categoria de exposição e contagem de CD4+, nem com o tipo de esquema anti-retroviral. Os resultados da análise multivariada revelaram associações significativas entre interrupção e início do tratamento após internamento hospitalar, uso de drogas, tratamento psiquiátrico, baixo grau de escolaridade e idade de 25 a 34 anos. CONCLUSÃO: Os resultados sugerem que a interrupção do tratamento é um problema crítico nos seis primeiros meses seguintes ao início da terapia anti-retroviral em indivíduos virgens de tratamento, e, especialmente, entre os adultos jovens, com história prévia de tratamento psiquiátrico, que usam ou fizeram uso de drogas lícitas ou ilícitas até um ano antes de iniciar o tratamento com anti-retrovirais, que iniciam a terapia após internamento hospitalar e têm baixo nível de escolaridade.BACKGROUND: The purpose of this study is to determine factors associated to the interruption of antiretroviral treatment in adults with AIDS in the State of Rio Grande do Norte, Brazil. METHODS: This was a population-based study, using data from the State's sources of vital statistics. Interruption was calculated using data on the number of programmed visits to the pharmacies, taking into

  1. Chemical Library Screens Targeting an HIV-1 Accessory Factor/Host Cell Kinase Complex Identify Novel Anti-retroviral Compounds

    OpenAIRE

    Emert-Sedlak, Lori; Kodama, Toshiaki; Lerner, Edwina C.; Dai, Weixiang; Foster, Caleb; Day, Billy W.; Lazo, John S.; Smithgall, Thomas E

    2009-01-01

    Nef is an HIV-1 accessory protein essential for AIDS progression and an attractive target for drug discovery. Lack of a catalytic function makes Nef difficult to assay in chemical library screens. We developed a high-throughput screening assay for inhibitors of Nef function by coupling it to one of its host cell binding partners, the Src-family kinase Hck. Hck activation is dependent upon Nef in this assay, providing a direct readout of Nef activity in vitro. Using this screen, a unique diphe...

  2. Prevalence and clinical and laboratory characteristics of kidney disease in anti-retroviral-naive human immunodeficiency virus-infected patients in South-South Nigeria

    Directory of Open Access Journals (Sweden)

    U H Okafor

    2016-01-01

    Full Text Available Since the emergence of acquired immune deficiency syndrome (AIDS about three decades ago, several renal disorders have been reported as common complications of human immunodeficiency virus (HIV infection. These renal disorders result from diverse etiologies. The aim of this cross-sectional study was to determine the prevalence and clinical and laboratory characteristics of anti-retroviral-naοve HIV-infected patients with impaired kidney disorder in South-South Nigeria. This study was conducted on patients presenting at the University of Benin Teaching Hospital, Benin City in South-South Nigeria for six months. The patients′ demographic data and clinical, hematological and biochemical parameters were assessed. Their glomerular filtration rate (GFR was calculated and the protein excretion was assessed from the protein- creatinine ratio. Data were analyzed using statistical software program SPSS version 15.0. Threehundred and eighty-three patients with a mean age of 35.39 ± 8.78 years and a male: female ratio of 1:1 were studied; 53.3% had evidence of kidney disorder. The main clinical features in patients with kidney disorder were evidence of fluid retention, urinary symptoms, pallor and encephalopathy. The mean systolic and diastolic blood pressures were 115.33 ± 17.17 and 72.33 ± 14.31 mm Hg, respectively. The mean estimated GFR was 52.5 mL/min/1.73 m 2 . Patients with kidney disorder had higher proteinuria (P = 0.001, lower mean CD4 cell count and packed cell volume (P = 0.019 and 0.001, respectively. Kidney disorder is a common complication in HIV-infected patients, and they have clinical and laboratory anomalies. Screening of HIV/AIDS patients at the time of diagnosis will facilitate early diagnosis of kidney disorders in them.

  3. Determinantes da aderência à terapia anti-retroviral combinada em Brasília, Distrito Federal, Brasil, 1999-2000

    Directory of Open Access Journals (Sweden)

    Cláudio Viveiros de Carvalho

    2003-04-01

    Full Text Available A aderência ao tratamento é um dos principais problemas relacionados à terapia anti-retroviral, já que a tomada incompleta dos medicamentos pode levar à resistência viral. Efeitos colaterais podem interferir com a qualidade de vida dos pacientes. Buscou-se estimar níveis de aderência à terapia e investigar seus determinantes, através de um estudo transversal. Definiram-se dois pontos de corte como boa aderência: a tomada de pelo menos 80% ou de 95% da medicação conforme a prescrição. Realizaram-se entrevistas semi-estruturadas em uma amostra seqüencial de 150 pacientes atendidos no Hospital-Dia de Brasília. Observou-se que a média de aderência foi 85,8%. As variáveis que se mostraram significativamente associadas à baixa aderência foram: idade, escolaridade, situação de emprego, rendas pessoal e familiar, uso de substâncias ilícitas, estrutura familiar e/ou comunitária, presença de infecção oportunista no momento do diagnóstico e ocorrência de efeitos colaterais relacionados à terapia. As razões de prevalência variaram de 1,6 a 4,5. Concluiu-se que variáveis sócio-econômicas e de hábitos tiveram maior força de associação com o nível de aderência do que as relacionadas com a doença ou com o tratamento.

  4. Multi-scale modeling of HIV infection in vitro and APOBEC3G-based anti-retroviral therapy.

    Directory of Open Access Journals (Sweden)

    Iraj Hosseini

    2012-02-01

    Full Text Available The human APOBEC3G is an innate restriction factor that, in the absence of Vif, restricts HIV-1 replication by inducing excessive deamination of cytidine residues in nascent reverse transcripts and inhibiting reverse transcription and integration. To shed light on impact of A3G-Vif interactions on HIV replication, we developed a multi-scale computational system consisting of intracellular (single-cell, cellular and extracellular (multicellular events by using ordinary differential equations. The single-cell model describes molecular-level events within individual cells (such as production and degradation of host and viral proteins, and assembly and release of new virions, whereas the multicellular model describes the viral dynamics and multiple cycles of infection within a population of cells. We estimated the model parameters either directly from previously published experimental data or by running simulations to find the optimum values. We validated our integrated model by reproducing the results of in vitro T cell culture experiments. Crucially, both downstream effects of A3G (hypermutation and reduction of viral burst size were necessary to replicate the experimental results in silico. We also used the model to study anti-HIV capability of several possible therapeutic strategies including: an antibody to Vif; upregulation of A3G; and mutated forms of A3G. According to our simulations, A3G with a mutated Vif binding site is predicted to be significantly more effective than other molecules at the same dose. Ultimately, we performed sensitivity analysis to identify important model parameters. The results showed that the timing of particle formation and virus release had the highest impacts on HIV replication. The model also predicted that the degradation of A3G by Vif is not a crucial step in HIV pathogenesis.

  5. Atividade anti-retroviral e propriedades farmacocinéticas da associação entre lamivudina e zidovudina Antiretroviral activity and pharmacokinetics properties of lamivudine and zidovudine association

    Directory of Open Access Journals (Sweden)

    Jacqueline de Souza

    2004-03-01

    Full Text Available A lamivudina (3TC e a zidovudina (ZDV são agentes anti-retrovirais indicados para o tratamento de infecção pelo HIV. Eles são análogos nucleosídeos, que passam por reações intracelulares de fosforilação e atuam inibindo a enzima transcriptase reversa. Os compostos trifosforilados formados se ligam à cadeia de DNA pró-viral impedindo sua replicação. A terapêutica anti-retroviral utilizando apenas um fármaco ocasiona, freqüentemente, a seleção de cepas resistentes. Os efeitos adversos provocados pela ZDV são mais comuns em pacientes com doença em estágio avançado, sendo o principal deles a mielossupressão. A 3TC é bem tolerada, mas sua toxicidade aumenta proporcionalmente ao acréscimo da dose. Quanto à farmacocinética, ambos são facilmente absorvidos passivamente e biotransformados em compostos ativos trifosforilados. Eles são amplamente distribuídos, penetram livremente nos tecidos a partir da circulação sistêmica. Difundem-se através da placenta da circulação materna para a circulação fetal. O principal caminho metabólico da ZDV é a glicuronidação, cerca de 60 a 70% do fármaco é inativado por essa via. Ela é eliminada rapidamente, sendo sua meia-vida de eliminação da ordem de 1 a 1,5 h. Apenas 5% a 10% da 3TC são biotransformados em um metabólito trans-sulfóxido inativo. Sua meia-vida de eliminação é de 8,5 a 11,5 h, sendo que 70% do fármaco são excretados de forma inalterada na urina até 24 h após a dose.Lamivudine (3TC and zidovudine (ZDV are antiretroviral drugs used in the treatment of HIV infection. They are nucleoside analogues that inhibit HIV-1 reverse transcriptase. These drugs are anabolized intracellularly by a stepwise process and form an active triphosphate anabolite, which is used by HIV-1 reverse transcriptase and effectively terminates chain extension. The use of monotherapy is associated with a delay in the emergence of resistant mutants. The combination therapy would

  6. Acceptance of anti-retroviral therapy among patients infected with HIV and tuberculosis in rural Malawi is low and associated with cost of transport.

    Directory of Open Access Journals (Sweden)

    Rony Zachariah

    Full Text Available BACKGROUND: A study was conducted among newly registered HIV-positive tuberculosis (TB patients systematically offered anti-retroviral treatment (ART in a district hospital in rural Malawi in order to a determine the acceptance of ART b conduct a geographic mapping of those placed on ART and c examine the association between "cost of transport" and ART acceptance. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cross-sectional analysis was performed on routine program data for the period of February 2003 to July 2004. Standardized registers and patient cards were used to gather data. The place of residence was used to determine road distances to the Thyolo district hospital. Cost of transport from different parts of the district was based on the known cost for public transport to the road-stop closest to the patient's residence. Of 1,290 newly registered TB patients, 1,003(78% underwent HIV-testing of whom 770 (77% were HIV-positive. 742 of these individuals (pulmonary TB = 607; extra-pulmonary TB = 135 were considered eligible for ART of whom only 101(13.6% accepted ART. Cost of transport to the hospital ART site was significantly associated with ART acceptance and there was a linear trend in association between cost and ART acceptance (chi(2 for trend = 25.4, P<0.001. Individuals who had to pay 50 Malawi Kwacha (1 United States Dollar = 100 Malawi Kwacha, MW or less for a one-way trip to the Thyolo hospital were four times more likely to accept ART than those who had to pay over 100 MW (Adjusted Odds ratio = 4.0, 95% confidence interval: 2.0-8.1, P<0.001. CONCLUSIONS/SIGNIFICANCE: ART acceptance among TB patients in a rural district in Malawi is low and associated with cost of transport to the centralized hospital based ART site. Decentralizing the ART offer from the hospital to health centers that are closer to home communities would be an essential step towards reducing the overall cost and burden of travel.

  7. Acceptance of Anti-Retroviral Therapy among Patients Infected with HIV and Tuberculosis in Rural Malawi Is Low and Associated with Cost of Transport

    Science.gov (United States)

    Zachariah, Rony; Harries, Anthony David; Manzi, Marcel; Gomani, Patrick; Teck, Roger; Phillips, Mit; Firmenich, Peter

    2006-01-01

    Background A study was conducted among newly registered HIV-positive tuberculosis (TB) patients systematically offered anti-retroviral treatment (ART) in a district hospital in rural Malawi in order to a) determine the acceptance of ART b) conduct a geographic mapping of those placed on ART and c) examine the association between “cost of transport” and ART acceptance. Methodology/Principal Findings A retrospective cross-sectional analysis was performed on routine program data for the period of February 2003 to July 2004. Standardized registers and patient cards were used to gather data. The place of residence was used to determine road distances to the Thyolo district hospital. Cost of transport from different parts of the district was based on the known cost for public transport to the road-stop closest to the patient's residence. Of 1,290 newly registered TB patients, 1,003(78%) underwent HIV-testing of whom 770 (77%) were HIV-positive. 742 of these individuals (pulmonary TB = 607; extra-pulmonary TB = 135) were considered eligible for ART of whom only 101(13.6%) accepted ART. Cost of transport to the hospital ART site was significantly associated with ART acceptance and there was a linear trend in association between cost and ART acceptance (X2 for trend = 25.4, P<0.001). Individuals who had to pay 50 Malawi Kwacha (1 United States Dollar = 100 Malawi Kwacha, MW) or less for a one-way trip to the Thyolo hospital were four times more likely to accept ART than those who had to pay over 100 MW (Adjusted Odds ratio = 4.0, 95% confidence interval: 2.0–8.1, P<0.001). Conclusions/Significance ART acceptance among TB patients in a rural district in Malawi is low and associated with cost of transport to the centralized hospital based ART site. Decentralizing the ART offer from the hospital to health centers that are closer to home communities would be an essential step towards reducing the overall cost and burden of travel. PMID:17205125

  8. Humanized mice recapitulate key features of HIV-1 infection: a novel concept using long-acting anti-retroviral drugs for treating HIV-1

    OpenAIRE

    Nischang, Marc; Sutmuller, Roger; Gers-Huber, Gustavo; Audigé, Annette; Li, Duo; Rochat, Mary-Aude; Baenziger, Stefan; Hofer, Ursula; Schlaepfer, Erika; Regenass, Stephan; Amssoms, Katie; Stoops, Bart; Van Cauwenberge, Anja; Boden, Daniel; Kraus, Guenter

    2012-01-01

    BACKGROUND: Humanized mice generate a lymphoid system of human origin subsequent to transplantation of human CD34+ cells and thus are highly susceptible to HIV infection. Here we examined the efficacy of antiretroviral treatment (ART) when added to food pellets, and of long-acting (LA) antiretroviral compounds, either as monotherapy or in combination. These studies shall be inspiring for establishing a gold standard of ART, which is easy to administer and well supported by the mice, and for s...

  9. Sensitive radioenzymatic assay for catechol drugs

    International Nuclear Information System (INIS)

    This assay measures picogram quantities of catechol drugs and endogenous catecholamines in body tissues and fluids. The catechols are converted to their 3H-O-methyl metabolites during incubation with 3H-S-adenosylmethionine then separated by solvent extraction and thin-layer chromatography. Most drugs containing the catechol structure can be radiolabeled and separated from norepinephrine and epinephrine by this technique to provide simultaneous measurement of endogenous and exogenously administered catechols. The disposition of isoproterenol in tissues and fluids of man and experimental animals is measured to illustrate the utility of this assay. The reactivity of several commonly administered catechol drugs with COMT is described and the possible implications discussed

  10. Gene sensitizes cancer cells to chemotherapy drugs

    Science.gov (United States)

    NCI scientists have found that a gene, Schlafen-11 (SLFN11), sensitizes cells to substances known to cause irreparable damage to DNA.  As part of their study, the researchers used a repository of 60 cell types to identify predictors of cancer cell respons

  11. FORMULATION AND EVALUATION OF GASTRO RETENTIVE DRUG DELIVERY SYSTEM OF STAVUDINE

    OpenAIRE

    Voleti. Vijaya Kumar; Shaik. Harun Rasheed; N. Raghu Ram; G. Silpa rani; Lemati Srinivasa Rao

    2011-01-01

    The present study was designed to formulate and evaluate hydro dynamically balanced Floating Drug Delivery Systems as controlled release modules, which prolongs the release rate of the drugs. Stavudine is an anti- retroviral, reverse transcriptase inhibitor (Nucleoside). Stavudine triphosphate inhibits the HIV reverse transcriptase by competing with natural substrate, thymidine triphosphate. It also causes termination of DNA synthesis by incorporating into it. Formulation of Stavudine as gast...

  12. Towards an understanding of the side effects of anti-HIV drugs using Caenorhabditis elegans

    OpenAIRE

    Smith, R L

    2016-01-01

    Since the discovery of HIV-1 as a cause for AIDS, many antiretroviral drugs - such as the nucleoside reverse transcriptase inhibitors (NRTIs) and the protease inhibitors (PIs) - have been developed to target viral replication. The therapeutic use of a combination of drugs, more commonly known as Highly Active Anti-Retroviral Therapy (HAART), has significantly improved the quality and length of patient lives. Overshadowing this success, however, is the problem that HIV-1 infected patients are ...

  13. Adesão e não-adesão à terapia anti-retroviral: as duas faces de uma mesma vivência Adhesión y no adhesión a la terapia antiretroviral: las dos caras de una misma vivencia Adhesion and non adhesion to anti-retroviral therapy: the two faces of a same experience

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Cardoso Nogueira da Silva

    2009-04-01

    Full Text Available O objetivo do estudo foi compreender, a partir da perspectiva de portadores e familiares, os aspectos que influenciam na adesão à terapêutica anti-retroviral. Trata-se de um estudo descritivo, de natureza qualitativa, desenvolvido no período de junho de 2006 a julho de 2007, junto a 10 indivíduos portadores do HIV/Aids, acompanhados pelo Serviço de Atendimento Especializado em Aids de Campo Mourão - PR e seus familiares. Constituem fatores facilitadores da adesão: adoção de estratégias para lembrar horários e mascarar o gosto do medicamento, ausência de efeitos colaterais, número reduzido de medicamentos a serem ingeridos e capacidade para reconhecê-los, lembrança dos sintomas da doença e o apoio da rede social. A ausência destes fatores pode culminar na não-adesão.El objetivo del estudio fue comprender, a partir de la perspectiva de portadores y familiares, los aspectos que influyen en la adhesión a la terapéutica antiretroviral. Se trata de un estudio descriptivo, de naturaleza cualitativa, desarrollado en el período de junio de 2006 a julio de 2007, junto a 10 individuos portadores del VIH/SIDA, acompañados por el Servicio de Atención Especializado en SIDA de Campo Mourão - PR y sus familiares. Constituyen factores que facilitan la adhesión: adopción de estrategias para recordar horarios y enmascarar el sabor del medicamento, ausencia de efectos colaterales, número reducido de medicamentos a ser ingeridos y capacidad para reconocerlos, recuerdo de los síntomas de la enfermedad y el apoyo de la red social. La ausencia de estos factores puede culminar en la no-adhesión.The objective of the study was to understand, from the perspective of HIV bearers and family, the aspects that influence in the adhesion to the antiretroviral therapy. It is a descriptive study, of qualitative nature, carried out from June 2006 to July 2007, with 10 HIV/Aids positive individuals, attended at the Service of Specialized Care on Aids

  14. Biological studies of matrix metalloproteinase sensitive drug delivery systems

    DEFF Research Database (Denmark)

    Johansen, Pia Thermann

    for delivery of drugs to specific tissues or cells utilizing biological knowledge of cancer tissue is getting increased attention. In this thesis a novel matrix metalloproteinase-2 (MMP-2) sensitive poly-ethylene glycol (PEG) coated liposomal drug delivery system for treatment of cancer was developed......Cancer, which is a group of diseases characterized by cells with elevated replication rate and compromised DNA damage response, is often treated with cytotoxic drugs, chemotherapeutics, inducing DNA damage that results in cell death. The use of chemotherapeutics in the clinic, however, is limited...... due to severe side effects as a result of drug distribution to healthy tissues. To enhance ecacy of treatment and improve life quality of patients, tumor specific drug delivery strategies, such as liposome encapsulated drugs, which accumulate in tumor tissue, has gained increased attention. Several...

  15. The Drug Sensitivity of Cyclosporine A Combined with Antineoplastic Drugs in Retinoblastoma in Vitro

    Institute of Scientific and Technical Information of China (English)

    Wanli Liu; Zhongyao Wu

    2005-01-01

    Purpose: To study cyclosporine A inhibition on the fresh retinoblastoma cells in vitro and increasing the drug sensitivity after combined with different antineoplastic drugs.Methods: To study the growth curve of cyclosporine A on 27 samples of primary retinoblastoma cells by MTT assay and to study the change of the drug sensitivity by cyclosporine A combined with seven antineoplastic drugs.Results: The average IC50 of cyclosporine A on the 27 retinoblastoma cells is 67.81μg/ml and the average inhibitive rate of these samples is 26.1% when cyclosporine A is in the concentration of 2μg/ml. The inhibitive rates all got improved after the seven antineoplastic drugs combined with cyclosporine A and the increasing average inhibitive rate is more than 5.Conclusion: Cyclosporine A can inhibit retinoblastoma cells in vitro and its inhibitive effect is dose dependent. Moreover it can enhance the inhibition of multiple antineoplastic drugs on retinoblastoma cells.

  16. Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs)

    DEFF Research Database (Denmark)

    Kolte, L; Gaardbo, J C; Skogstrand, K;

    2008-01-01

    Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores...... if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38......(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly...

  17. Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs

    DEFF Research Database (Denmark)

    Kolte, L.; Gaardbo, J.C.; Skogstrand, K.;

    2009-01-01

    This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive...... T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38(+)human...... leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly higher in...

  18. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy

    OpenAIRE

    Bacha Tigist; Tilahun Birkneh; Worku Alemayehu

    2012-01-01

    Abstract Background The emergence of resistance to first line antiretroviral therapy (ART) regimen leads to the need for more expensive and less tolerable second line drugs. Hence, it is essential to identify and address factors associated with an increased probability of first line ART regimen failure. The objective of this article is to report on the predictors of first line ART regimen failure, the detection rate of ART regime failure, and the delay in switching to second line ART drugs. M...

  19. Beneficiary price sensitivity in the Medicare prescription drug plan market.

    Science.gov (United States)

    Frakt, Austin B; Pizer, Steven D

    2010-01-01

    The Medicare stand-alone prescription drug plan (PDP) came into existence in 2006 as part of the Medicare prescription drug benefit. It is the most popular plan type among Medicare drug plans and large numbers of plans are available to all beneficiaries. In this article we present the first analysis of beneficiary price sensitivity in the PDP market. Our estimate of elasticity of enrollment with respect to premium, -1.45, is larger in magnitude than has been found in the Medicare HMO market. This high degree of beneficiary price sensitivity for PDPs is consistent with relatively low product differentiation, low fixed costs of entry in the PDP market, and the fact that, in contrast to changing HMOs, beneficiaries can select a PDP without disrupting doctor-patient relationships. PMID:19191252

  20. Oral pre-exposure prophylaxis by anti-retrovirals raltegravir and maraviroc protects against HIV-1 vaginal transmission in a humanized mouse model.

    Directory of Open Access Journals (Sweden)

    C Preston Neff

    Full Text Available Sexual HIV-1 transmission by vaginal route is the most predominant mode of viral transmission, resulting in millions of new infections every year. In the absence of an effective vaccine, there is an urgent need to develop other alternative methods of pre-exposure prophylaxis (PrEP. Many novel drugs that are currently approved for clinical use also show great potential to prevent viral sexual transmission when administered systemically. A small animal model that permits rapid preclinical evaluation of potential candidates for their systemic PrEP efficacy will greatly enhance progress in this area of investigation. We have previously shown that RAG-hu humanized mouse model permits HIV-1 mucosal transmission via both vaginal and rectal routes and displays CD4 T cell loss typical to that seen in the human. Thus far systemic PrEP studies have been primarily limited to RT inhibitors exemplified by tenofovir and emtricitabine. In these proof-of-concept studies we evaluated two new classes of clinically approved drugs with different modes of action namely, an integrase inhibitor raltegravir and a CCR5 inhibitor maraviroc as potential systemically administered chemo-prophylactics. Our results showed that oral administration of either of these drugs fully protects against vaginal HIV-1 challenge in the RAG-hu mouse model. Based on these results both these drugs show great promise for further development as orally administered PrEPs.

  1. Different combination of drugs regarding the damage on organs targeting salt sensitivity or non-salt-sensitive hypertension

    Institute of Scientific and Technical Information of China (English)

    吴琪

    2013-01-01

    Objective To study the damage on organs from salt sensitivity hypertension or non-salt-sensitive hypertension and the selection of drug combination.Methods 120 hypertensive patients including 60 cases salt-sensitive(SS)

  2. Oral Pre-Exposure Prophylaxis by Anti-Retrovirals Raltegravir and Maraviroc Protects against HIV-1 Vaginal Transmission in a Humanized Mouse Model

    OpenAIRE

    Neff, C. Preston; Ndolo, Thomas; Tandon, Apurva; Habu, Yuichiro; Akkina, Ramesh

    2010-01-01

    Sexual HIV-1 transmission by vaginal route is the most predominant mode of viral transmission, resulting in millions of new infections every year. In the absence of an effective vaccine, there is an urgent need to develop other alternative methods of pre-exposure prophylaxis (PrEP). Many novel drugs that are currently approved for clinical use also show great potential to prevent viral sexual transmission when administered systemically. A small animal model that permits rapid preclinical eval...

  3. Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure.

    OpenAIRE

    Lodi, S; Phillips, A; Fidler, S.; Hawkins, D.; Gilson, R; McLean, K.; Fisher, M; Post, F.; Johnson, A M; Walker-Nthenda, L.; Dunn, D; Porter, K; on behalf of the UK Register of HIV

    2013-01-01

    Background: The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation. Methods: Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-...

  4. Impact of Anti-Retroviral Treatment and Cotrimoxazole Prophylaxis on Helminth Infections in HIV-Infected Patients in Lambaréné, Gabon

    OpenAIRE

    Janssen, Saskia; Hermans, Sabine; Knap, Martijn; Moekotte, Alma; Rossatanga, Elie G.; Adegnika, Akim A.; Bélard, Sabine; Hänscheid, Thomas; Grobusch, Martin P

    2015-01-01

    Background Foci of the HIV epidemic and helminthic infections largely overlap geographically. Treatment options for helminth infections are limited, and there is a paucity of drug-development research in this area. Limited evidence suggests that antiretroviral therapy (ART) reduces prevalence of helminth infections in HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole preventive therapy (CTX-P) is associated with a reduced prevalence of helminth infections. Metho...

  5. Multiple cutaneous sensitization to nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Gonzalo, M A; Revenga, F

    1996-01-01

    The use of topical nonsteroidal anti-inflammatory drugs is widespread (particularly in countries bordering the Mediterranean). Compared to their wide use, the incidence of published adverse cutaneous effects appears minimal, although they are increasing. Most of them are a form of allergic contact dermatitis (ACD). Multiple sensitization and/or cross-reactions are rarely reported. Interestingly, our patient presented ACD with diclofenac and etofenamate (both from different chemical groups) and, furthermore, patch tests were positive with bencydamine and indomethacin (both indolacetic acid derivatives), piroxicam and fepradinol. We think that our results could not be explained due to cross-reactivity, and that multiple sensitization was more likely. PMID:8864624

  6. Pessoas vivendo com HIV/AIDS: variáveis associadas à adesão ao tratamento anti-retroviral Persons living with HIV/AIDS: factors associated with adherence to antiretroviral treatment

    Directory of Open Access Journals (Sweden)

    Eliane Maria Fleury Seidl

    2007-10-01

    Full Text Available O estudo objetivou descrever o comportamento de adesão ao tratamento anti-retroviral em pessoas vivendo com HIV/AIDS e investigar preditores da adesão entre as variáveis escolaridade, presença de efeitos colaterais, interrupção anterior da terapia anti-retroviral (TARV por conta própria, auto-estima, expectativa de auto-eficácia, estratégias de enfrentamento, suporte social e satisfação com a relação profissional de saúde-usuário. Adesão foi medida pelo auto-relato da perda do número de comprimidos/cápsulas dos medicamentos anti-retrovirais na última semana e mês, sendo considerada satisfatória na ocorrência de omissão inferior a 5% do total prescrito. Participaram 101 pessoas, 60,4% homens, idades entre 20 a 71 anos (M = 37,9 anos, 73,3% sintomáticos. A coleta de dados incluiu entrevista e instrumentos auto-aplicáveis. A maioria (n = 73; 72,3% relatou adesão igual ou superior a 95%. Nos resultados da regressão logística, interrupção anterior da TARV e expectativa de auto-eficácia foram preditores significativos da adesão. Faz-se necessária a qualificação da assistência pela constituição de equipes interdisciplinares, para o desenvolvimento de abordagens adequadas às dificuldades médicas e psicossociais de adesão das pessoas vivendo com HIV/AIDS.This study aimed to describe the adherence of persons living with HIV/AIDS to antiretroviral therapy (ART and to investigate adherence predictors among the following: level of schooling, presence of side effects, current or previous interruption of ART by the persons themselves, self-esteem, self-efficacy expectation, coping strategies, social support, and satisfaction with the health professional-patient relationship. Adherence was measured by self-reported number of ART pills/capsules missed during the previous week and previous month, evaluated as satisfactory when less than 5%. 101 HIV+ adults took part in this study, 60.4% males, ranging from 20 to 71 years

  7. Specific Elimination of Latently HIV-1 Infected Cells Using HIV-1 Protease-Sensitive Toxin Nanocapsules

    Science.gov (United States)

    Wen, Jing; Yan, Ming; Liu, Yang; Li, Jie; Xie, Yiming; Lu, Yunfeng; Kamata, Masakazu; Chen, Irvin S. Y.

    2016-01-01

    Anti-retroviral drugs suppress HIV-1 plasma viremia to undetectable levels; however, latent HIV-1 persists in reservoirs within HIV-1-infected patients. The silent provirus can be activated through the use of drugs, including protein kinase C activators and histone deacetylase inhibitors. This “shock” approach is then followed by “kill” of the producing cells either through direct HIV-1-induced cell death or natural immune mechanisms. However, these mechanisms are relatively slow and effectiveness is unclear. Here, we develop an approach to specifically target and kill cells that are activated early in the process of virus production. We utilize a novel nanocapsule technology whereby the ricin A chain is encapsulated in an inactive form within a polymer shell. Specificity for release of the ricin A toxin is conferred by peptide crosslinkers that are sensitive to cleavage by HIV-1 protease. By using well-established latent infection models, J-Lat and U1 cells, we demonstrate that only within an HIV-1-producing cell expressing functional HIV-1 protease will the nanocapsule release its ricin A cargo, shutting down viral and cellular protein synthesis, and ultimately leading to rapid death of the producer cell. Thus, we provide proof of principle for a novel technology to kill HIV-1-producing cells without effects on non-target cells. PMID:27049645

  8. Mechanisms mediating the effects of alcohol and HIV anti-retroviral agents on mTORC1,mTORC2 and protein synthesis in myocytes

    Institute of Scientific and Technical Information of China (English)

    Ly; Q; Hong-Brown; Abid; A; Kazi; Charles; H; Lang

    2012-01-01

    Alcoholism and acquired immune deficiency syndrome are associated with severe muscle wasting.This impairment in nitrogen balance arises from increased protein degradation and a decreased rate of protein synthesis.The regulation of protein synthesis is a complex process involving alterations in the phosphorylation state and protein-protein interaction of various components of the translation machinery and mammalian target of rapamycin(mTOR) complexes.This review describes mechanisms that regulate protein synthesis in cultured C2C12 myocytes following exposure to either alcohol or human immunodeficiency virus antiretroviral drugs.Particular attention is given to the upstream regulators of mTOR complexes and the downstream targets which play an important role in translation.Gaining a better understanding of these molecular mechanisms could have important implications for preventing changes in lean body mass in patients with catabolic conditions or illnesses.

  9. Stimuli-sensitive hydrogels: A novel ophthalmic drug delivery system

    Directory of Open Access Journals (Sweden)

    Singh Vinod

    2010-01-01

    Full Text Available Background: Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change. Aim: To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration. Materials and Methods: Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits. Statistical Analysis: Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study. Results: Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained. Conclusions: Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.

  10. Distribution and drug sensitivity of pathogens in diabetic foot ulcer secretions

    Institute of Scientific and Technical Information of China (English)

    李惠琴

    2013-01-01

    Objective To investigate the distribution and drug sensitivity of pathogens isolated from diabetic foot ulcer(DFU) secretions. Methods A retrospective study was carried out on the distribution and drug sensitivity of pathogens isolated from the secretions of 218 DFU

  11. Oral manifestations of HIV infection in children and adults receiving highly active anti-retroviral therapy [HAART] in Dar es Salaam, Tanzania

    Directory of Open Access Journals (Sweden)

    Mikx Frans HM

    2006-08-01

    Full Text Available Abstract Background The aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+ cell count. Methods Participants were 532 HIV infected patients, 51 children and 481 adults, 165 males and 367 females. Children were aged 2–17 years and adults 18 and 67 years. Participants were recruited consecutively at the Muhimbili National Hospital (MNH HIV clinic from October 2004 to September 2005. Investigations included; interviews, physical examinations, HIV testing and enumeration of CD4+ T cells. Results A total of 237 HIV-associated oral lesions were observed in 210 (39.5% patients. Oral candidiasis was the commonest (23.5%, followed by mucosal hyperpigmentation (4.7%. There was a significant difference in the occurrence of oral candidiasis (χ2 = 4.31; df = 1; p = 0.03 and parotid enlargement (χ2 = 36.5; df = 1; p = 0.04 between children and adults. Adult patients who were on HAART had a significantly lower risk of; oral lesions (OR = 0.32; 95% CI = 0.22 – 0.47; p = 0.005, oral candidiasis (OR = 0.28; 95% CI = 0.18 – 0.44; p = 0.003 and oral hairy leukoplakia (OR = 0.18; 95% CI = 0.04 – 0.85; p = 0.03. There was no significant reduction in occurrence of oral lesions in children on HAART (OR = 0.35; 95% CI = 0.11–1.14; p = 0.15. There was also a significant association between the presence of oral lesions and CD4+ cell count 3 (χ2 = 52.4; df = 2; p = 0.006 and with WHO clinical stage (χ2 = 121; df = 3; p = 0.008. Oral lesions were also associated with tobacco smoking (χ2 = 8.17; df = 2; p = 0.04. Conclusion Adult patients receiving HAART had a significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia. There was no significant change in occurrence of oral lesions in children

  12. ph Sensitive hydrogel as colon specific drug delivery

    International Nuclear Information System (INIS)

    γ-radiation induced graft copolymerization and crosslinking was for the synthesis of ph-sensitive hydrogels composed of poly (vinyl pyrrolidone) acrylic acid. The prepared hydrogels were subjected to swelling test to evaluate the effects of ph and ionic strength of the surrounding solution. Drastic changes in the swelling parameters where observed by changing the surrounding solution ph values. The release of ibuprofen from hydrogels was monitored as a function of time at ph 1 and ph 7 in order to evaluate the prepared copolymer ability for colon- specific drug carrier uses.

  13. Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART Análise da protease e transcriptase reversa do HIV-1 em crianças com falha terapêutica em uso de terapia anti-retroviral altamente eficaz (HAART

    Directory of Open Access Journals (Sweden)

    Daisy Maria Machado

    2005-02-01

    Full Text Available The aim of this study was to evaluate the genotypic resistance profiles of HIV-1 in children failing highly active antiretroviral therapy (HAART. Forty-one children (median age = 67 months receiving HAART were submitted to genotypic testing when virological failure was detected. cDNA was extracted from PBMCs and amplified by nested PCR for the reverse transcriptase and protease regions of the pol gene. Drug resistance genotypes were determined from DNA sequencing. According to the genotypic analysis, 12/36 (33.3% and 6/36 (16.6% children showed resistance and possible resistance, respectively, to ZDV; 5/36 (14% and 4/36 (11.1%, respectively, showed resistance and possible resistance to ddI; 4/36 (11.1% showed resistance to 3TC and D4T; and 3/36 (8.3% showed resistance to Abacavir. A high percentage (54% of children exhibited mutations conferring resistance to NNRTI class drugs. Respective rates of resistance and possible resistance to PIs were: RTV (12.2%, 7.3%; APV (2.4%, 12.1%; SQV(0%, 12.1%; IDV (14.6%, 4.9%, NFV (22%, 4.9%, LPV/RTV (2.4%, 12.1%. Overall, 37/41 (90% children exhibited virus with mutations related to drug resistance, while 9% exhibited resistance to all three antiretroviral drug classes.O objetivo deste estudo foi avaliar o perfil de resistência genotípica do HIV-1 em crianças com falha terapêutica ao tratamento anti-retroviral (HAART. Quarenta e uma crianças (idade mediana = 67 meses em uso de HAART foram submetidas ao teste de genotipagem no momento da detecção de falha ao tratamento. Foi realizada extração de cDNA de células periféricas mononucleares e amplificação do mesmo (regiões da transcriptase reversa e protease do gene pol através de PCR-nested. O perfil genotípico foi determinado através do seqüenciamnto de nucleotídeos. De acordo com a análise genotípica, 12/36 (33,3% e 6/36 (16,6% crianças apresentaram, respectivamente, resistência e possível resistência ao AZT; 5/36 (14% e 4/36 (11

  14. Suplementação de N-acetilcisteína em pacientes infectados pelo HIV submetidos ao primeiro tratamento anti-retroviral: Avaliação do efeito sobre a carga viral, TNF-α, IL-6, IL-8, β2-microglobulina, IgA, IgG e IgM, haptoglobina e α1-glicoproteína ácida N-acetylcysteine supplementation of HIV-infected patients under the first anti-retroviral treatment: Evaluation of the effect on viral load, TNF-α, IL-6, IL-8, β2-microglobulin, IgA, IgG, IgM, haptoglobin and α1-acid glycoprotein

    Directory of Open Access Journals (Sweden)

    Aricio Treitinger

    2002-03-01

    Full Text Available Indivíduos infectados pelo vírus da imunodeficiência humana (HIV- 1 apresentam aumento progressivo da carga viral, da destruição do sistema de defesa imune celular e alterações imunológicas e inflamatórias, incluindo a elevação dos níveis séricos do fator de necrose tumoral alfa (TNF-α, interleucina 8 (IL-8, β2- microglobulina, IgA, IgG e IgM, haptoglobina e α1-glicoproteína ácida.O objetivo deste estudo foi avaliar os níveis séricos destes marcadores em indivíduos submetidos ao primeiro tratamento antiretroviral, suplementados ou não com N-acetilcisteína. Participaram deste estudo, duplo cego controlado por placebo, que teve a duração de 180 dias, 24 indivíduos que iniciaram a terapia antiretroviral O Grupo Estudo foi constituído por 11 indivíduos, que receberam suplementação de 600 mg/dia de Nacetilcisteína enquanto o Grupo Controle foi constituído por 13 indivíduo que receberam placebo. Os níveis dos marcadores avaliados foram determinados no dia anterior ao início do tratamento a que foram submetidos e após 60, 120 e 180 dias. Verificou-se diminuição significativa dos níveis de TNF-α (p=0,0001, IL-6 (p>0,05, IL-8 (p=0,0001, β2-microglobulina (p=0,0005, IgA (p=0,007, IgG (p=0,001, IgM (p=0,0001, haptoglobina (p=0,0001 e α1-glicoproteína ácida (p=0.012 em decorrência do tratamento anti-retroviral. A suplementação com N-acetilcisteína, na dose utilizada neste estudo, não teve efeitos aditivos ou sinérgicos sobre as variáveis analisadas. Em conclusão, a suplementação de pacientes HIV-positivos com 600 mg/dia de N-acetilcisteína não proporcionou benefícios adicionais àqueles decorrentes do tratamento anti-retroviral.Human immunodeficiency virus infection is associated with a progressive elevation of viral load and with a continuous destruction of the immune cellular defense system which is marked by immunological and inflammatory disorders characteristic of HIV-infected individuals. These

  15. Longitudinal comparison between plasma and seminal HIV-1 viral loads during antiretroviral treatment Comparação longitudinal entre cargas virais seminais e plasmáticas do HIV-1 durante terapia anti-retroviral

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    Lauro Ferreira da Silva Pinto Neto

    2003-12-01

    Full Text Available This study was designed to investigate the impact of anti-retroviral therapy on both plasma and seminal HIV-1 viral loads and the correlation between viral loads in these compartments after treatment. Viral load, CD4+ and CD8+ T-cell counts were evaluated in paired plasma and semen samples from 36 antiretroviral therapy-naïve patients at baseline and on days 45, 90, and 180 of treatment. Slopes for blood and seminal viral loads in all treated patients were similar (p = 0.21. Median HIV-1 RNA titers in plasma and semen at baseline were 4.95 log10 and 4.48 log10 copies/ml, respectively. After 180 days of therapy, the median viral load declined to 3.15 log10 copies/ml (plasma and 3.2 log10 copies/ml (semen. At this timepoint 22 patients presented HIV-1 viral load below 400 copies/ml in either plasma or semen, but only 9 had viral loads below 400 copies/ml in both compartments.Este estudo foi desenhado para investigar o impacto do tratamento com anti-retrovirais na evolução das cargas virais plasmáticas e seminais do HIV-1. A carga viral do HIV-1 e a contagem de linfócitos T CD4+ e CD8+ foi determinada em amostras pareadas de sangue e sêmen de 36 pacientes virgem de tratamento nos dias 0, 45, 90 e 180 após o início da terapia. As curvas de declínio das cargas virais plasmática e seminal foram semelhantes (p= 0.21. As medianas da carga viral plasmática e seminal no pré-tratamento (dia 0 foram 4.95 e 4.48 log10 cópias/ml, respectivamente. Seis meses após o início da terapia, a mediana da carga viral plasmática era 3.15 log10 cópias/ml e a seminal 3.2 log10 cópias/ml. Neste mesmo periodo, 22 pacientes apresentavam carga viral abaixo de 400 cópias/ml no plasma e/ou sêmen, enquanto apenas 9 pacientes apresentavam carga viral abaixo do limite de detecção nos dois compartimentos.

  16. AIDS na infância: acometimento cardíaco com e sem a terapia anti-retroviral tríplice combinada AIDS in childhood: cardiac involvement with and without triple combination antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Maria do Carmo Soares Alves Cunha

    2008-01-01

    Full Text Available OBJETIVO: Descrever a prevalência de alterações cardíacas ao ecocardiograma em crianças com AIDS acompanhadas em serviço de referência aos 18±6 meses do diagnóstico confirmado de AIDS. MÉTODOS: Estudo transversal, com corte aos 18±6 meses do diagnóstico de AIDS. Incluídas 93 crianças com diagnóstico confirmado de AIDS por transmissão vertical, sem doença maligna, que, na avaliação cardiológica, realizaram ecocardiograma (eco. De forma exploratória avaliaram-se as alterações cardíacas nos pacientes sem uso (G1 e com uso (G2 de terapia combinada anti-retroviral. RESULTADOS: Quando do diagnóstico de AIDS, as crianças tinham em média 3,07 anos e 50,50% eram do sexo feminino. Esquema de terapia combinado com anti-retrovirais foi utilizado por 47 pacientes (G2. O acometimento cardíaco esteve presente em 40 crianças (43,00%. A presença de disfunção ventricular esquerda (G1:39,10%;G2:10,60% e o aumento isolado de ventrículo esquerdo (G1:6,60%;G2:14,90% foram os achados mais freqüentes. Observou-se associação significativa entre os grupos sem e com terapia anti-retroviral combinada quanto à presença de disfunção ventricular esquerda (RP=3,42; [1,41-8,26]; p =0,02 e de desnutrição (RP=1,79; [1,00-3,20]; p=0,04. CONCLUSÃO: O acometimento cardíaco foi freqüente nas crianças com AIDS, sendo a disfunção ventricular esquerda a alteração mais observada ao ecocardiograma. Houve diferença estatisticamente significativa entre os grupos com e sem tratamento tríplice combinado quanto à presença de disfunção ventricular esquerda e de desnutrição.OBJECTIVE: To describe the prevalence of cardiac abnormalities in the echocardiogram of children with AIDS followed up in a reference service at 18±6 months of AIDS confirmed diagnosis. METHODS: A cross-section study with a cohort after 18±6 months of AIDS diagnosis. The study included a total of 93 children with a confirmed diagnosis of AIDS with vertical

  17. Roles of sildenafil in enhancing drug sensitivity in cancer.

    Science.gov (United States)

    Shi, Zhi; Tiwari, Amit K; Patel, Atish S; Fu, Li-Wu; Chen, Zhe-Sheng

    2011-06-01

    The phenomenon of multidrug resistance (MDR) has decreased the hope for successful cancer chemotherapy. The ATP-binding cassette (ABC) transporter superfamily is the largest transmembrane family. The overexpression of ABC transporters is a major determinant of MDR in cancer cells both in vitro and in vivo. Unfortunately, until recently, most of the strategies used to surmount ABC-transporter-mediated MDR have had limited success. An ideal modulator of MDR would be one that has a low liability to induce toxicity and alter the pharmacokinetic profile of antineoplastic drugs. Sildenafil, an inhibitor of cGMP-specific phosphodiesterase type 5, was found to significantly reverse ABC-transporter-mediated MDR. Our results indicate that sildenafil has differential inhibitory effects on ABC transporters: It significantly decreases the efflux activity of ABCB1 and ABCG2, but has no significant effects on ABCC1. Emerging evidence indicates that sildenafil and other phosphodiesterase type 5 inhibitors may enhance the sensitivity of certain types of cancer to standard chemotherapeutic drugs. PMID:21610107

  18. Microfluidic Synthesis of pH-Sensitive Multicompartmental Microparticles for Multimodulated Drug Release.

    Science.gov (United States)

    Kim, Hyeon Ung; Choi, Dae Gun; Roh, Yoon Ho; Shim, Min Suk; Bong, Ki Wan

    2016-07-01

    Stimuli-responsive carriers releasing multiple drugs have been researched for synergistic combinatorial cancer treatment with reduced side-effects. However, previously used drug carriers have limitations in encapsulating multiple drug components in a single carrier and releasing each drug independently. In this work, pH-sensitive, multimodulated, anisotropic drug carrier particles are synthesized using an acid-cleavable polymer and stop-flow lithography. The particles exhibit a faster drug release rate at the acidic pH of tumors than at physiological pH, demonstrating their potential for tumor-selective drug release. The drug release rate of the particles can be adjusted by controlling the monomer composition. To accomplish multimodulated drug release, multicompartmental particles are synthesized. The drug release profile of each compartment is programmed by tailoring the monomer composition. These pH-sensitive, multicompartmental particles are promising drug carriers enabling tumor-selective and multimodulated release of multiple drugs for synergistic combination cancer therapy. PMID:27197594

  19. Structural Aspects of Drug Resistance and Inhibition of HIV-1 Reverse Transcriptase

    OpenAIRE

    Sarafianos, Stefan G.; Eleftherios Michailidis; Kirby, Karen A.; Bruno Marchand; Kamalendra Singh

    2010-01-01

    HIV-1 Reverse Transcriptase (HIV-1 RT) has been the target of numerous approved anti-AIDS drugs that are key components of Highly Active Anti-Retroviral Therapies (HAART). It remains the target of extensive structural studies that continue unabated for almost twenty years. The crystal structures of wild-type or drug-resistant mutant HIV RTs in the unliganded form or in complex with substrates and/or drugs have offered valuable glimpses into the enzyme’s folding and its interactions with DNA a...

  20. Adherence to antiretroviral therapy: a qualitative study with physicians from Rio de Janeiro, Brazil Aderência à terapia anti-retroviral: um estudo qualitativo com médicos no Rio de Janeiro, Brasil

    Directory of Open Access Journals (Sweden)

    Monica Malta

    2005-10-01

    Full Text Available Brazil provides free antiretroviral (ARV therapy to some 150,000 individuals living with HIV/ AIDS. ARV regimens require optimal adherence to achieve undetectable viral loads and to avoid viral resistance. Physicians play a key role to foster ARV adherence, but until now little is known about the communication between physicians/ people living with HIV/AIDS in this setting. In-depth interviews were conducted with 40 physicians treating people living with HIV/AIDS at six public reference centers in Rio de Janeiro, Brazil. Interview topics included: experiences in the treatment of people living with HIV/AIDS, relationship and dialogue with patients, barriers/facilitators to adherence, and effectiveness of available services. Barriers to ARV adherence were mainly related to the low quality of patient-provider relationship. Other barriers were related to "chaotic" patients' lifestyles, and inadequate knowledge and/or negative beliefs about HIV/AIDS and ARV effectiveness. It is necessary to improve networking between services, establish agile referral systems, and improve health professionals' integration. These structural changes could contribute to improved adherence, resulting in improved quality of life for people living with HIV/AIDS.O Brasil fornece gratuitamente terapia anti-retroviral (ARV para cerca de 150 mil pessoas vivendo com HIV/ AIDS. A terapia ARV requer aderência ótima, visando alcançar carga viral indetectável e evitar resistência viral. Os médicos desempenham papel central quanto à aderência à ARV, mas há escassa informação sobre a comunicação entre médicos/pessoas vivendo com HIV/ AIDS. Entrevistas em profundidade foram realizadas com 40 médicos assistentes de seis hospitais de referência do Rio de Janeiro, Brasil. Tópicos da entrevista incluíram: experiências relativas ao tratamento de pessoas vivendo com HIV/AIDS, relacionamento/diálogo com pacientes, barreiras/facilitadores para aderência aos servi

  1. Enteropatógenos relacionados à diarréia em pacientes HIV que fazem uso de terapia anti-retroviral Enteropathogens relating to diarrhea in HIV patients on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Áurea Regina Telles Pupulin

    2009-10-01

    Full Text Available A etiologia do processo diarréico na AIDS pode ser causada por vírus, bactérias, fungos, protozoários e helmintos, assim como pelo próprio HIV. Este trabalho avaliou enteropatogenos relacionados à diarréia em pacientes HIV que fazem uso de terapia anti-retroviral. Os métodos parasitológicos utilizados foram Faust, Hoffmann e Kinyoun. O isolamento e cultura dos fungos foram realizados conforme metodologia recomendada por NCCLS M27-A standard. A identificação das espécies de leveduras foi realizada através da reação em cadeia da polimerase. O isolamento de bactérias, foi feito em agar Mac Conkey e agar SS, a identificação das espécies através do Enterokit B (Probac do Brasil e métodos bioquímicos. Foram avaliados 49 pacientes, 44,9% apresentaram enteroparasitas, 48,1% Candida sp com 61,5% Candida albicans, 7,6% Candida sp e 30,7% Candida não- albicans. Foram isoladas bactérias de 72% dos pacientes, 49% Escherichia coli, 13% Salmonella parathyphi, Klebsiella sp ou Proteus e 6% Citrobacter freundii ou Yersinia sp. Houve alta prevalência de Candida sp nos pacientes HIV com diarréia e foram isoladas espécies não albicans cuja presença pode ser entendida como cúmplice ou causa da infecção.The etiology of the diarrheic process in AIDS may be caused by viruses, bacteria, fungi, protozoa or helminths, as well as HIV itself. This study evaluated enteropathogens relating to diarrhea in HIV patients who were on antiretroviral therapy. The parasitological methods used were Faust, Hoffmann and Kinyoun. Isolation and culturing of fungi were carried out in accordance with the methodology recommended by the NCCLS M27-A standard. The yeast species were identified using the polymerase chain reaction (PCR. Bacteria were isolated on MacConkey and SS agar and the species were identified using Enterokit B (Probac do Brasil and biochemical methods. Forty-nine patients were evaluated: 44.89% presented enteroparasites and 48.1% presented

  2. Adesão à terapia antiretroviral para HIV/AIDS Adhesión a la terapia anti-retroviral para el vih/sida Adherence to the antiretroviral therapy for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Maria Rosa Ceccato Colombrini

    2006-12-01

    Full Text Available A não-adesão à terapêutica antiretroviral altamente eficaz (HAART é considerada, no plano individual, como um dos mais ameaçadores perigos para a efetividade do tratamento da pessoa com HIV/aids e para a disseminação de vírus-resistência, no plano coletivo. Assim, o objetivo deste estudo foi analisar, mediante revisão de literatura, os fatores de risco para não-adesão à HAART, além de agrupá-los e relacioná-los à pessoa em tratamento, à doença, ao tratamento e ao serviço de saúde e suporte social. A literatura aponta para a necessidade da realização de estudos que avaliem aspectos socioculturais, crenças, qualidade do serviço prestado, relações do cliente com a equipe multiprofissional e outros referentes à raça e aos efeitos colaterais dos anti-retrovirais. Estes estudos visam a favorecer o estabelecimento de estratégias que melhorem a adesão dos clientes à HAART, ao mesmo tempo em e que contribuem para a construção e exercício da cidadania.La no adhesión a la terapéutica anti-retroviral altamente eficaz (HAART es considerada, en el plano individual, como uno de los más amenazadores peligros para la efectividad del tratamiento de la persona con VIH/SIDA y para la diseminación del virus-resistencia, en el plano colectivo. Así, el objetivo de este estudio fue analizar, mediante revisión de la literatura, los factores de riesgo para la no adhesión a la HAART, además de agruparlos y relacionarlos a la persona en tratamiento, a la enfermedad, al tratamiento y al servicio de salud y soporte social. La literatura apunta hacia la necesidad de realizar estudios que evalúen aspectos socioculturales, creencias, calidad del servicio prestado, relaciones del cliente con el equipo multi-profesional y otros referentes a la raza y a los efectos colaterales de los anti-retrovirales. Estos estudios visan a favorecer el establecimiento de estrategias que mejoren la adhesión de los clientes a la HAART, al mismo tiempo

  3. Development of an in vitro drug sensitivity assay for Trichuris muris first-stage larvae

    OpenAIRE

    Wimmersberger, David; Tritten, Lucienne; Keiser, Jennifer

    2013-01-01

    Background Trichuriasis represents a major public health problem in the developing world and is regarded as a neglected disease. Albendazole and mebendazole, the two drugs of choice against trichuriasis display only moderate cure rates, hence alternative drugs are needed. To identify candidate compounds, in vitro drug sensitivity testing currently relies on the adult Trichuris muris motility assay. The objective of the present study was to develop a simple and cost-effective drug sensitivity ...

  4. Terapia anti-retroviral: fatores que interferem na adesão de crianças com HIV/AIDS Terapia anti-retroviral: factores que interfieren en la adherencia de niños con VIH/SIDA Antiretroviral therapy: factors interfering in the adherence of children with HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Ana Claúdia Feitosa

    2008-09-01

    difficult, evidencing reports about drug forms, time of medication intake, collateral effects, shortage in the free drugs distribution, difficulty to get regular access to the health service and financial problems. The importance was revealed of getting to know the social context the child is inserted in and the difficulties in the use of antiretroviral drugs, so as to intervene efficiently and permit a better quality of life for the children.

  5. Protein microarray: sensitive and effective immunodetection for drug residues

    Directory of Open Access Journals (Sweden)

    Zer Cindy

    2010-02-01

    Full Text Available Abstract Background Veterinary drugs such as clenbuterol (CL and sulfamethazine (SM2 are low molecular weight ( Results The artificial antigens were spotted on microarray slides. Standard concentrations of the compounds were added to compete with the spotted antigens for binding to the antisera to determine the IC50. Our microarray assay showed the IC50 were 39.6 ng/ml for CL and 48.8 ng/ml for SM2, while the traditional competitive indirect-ELISA (ci-ELISA showed the IC50 were 190.7 ng/ml for CL and 156.7 ng/ml for SM2. We further validated the two methods with CL fortified chicken muscle tissues, and the protein microarray assay showed 90% recovery while the ci-ELISA had 76% recovery rate. When tested with CL-fed chicken muscle tissues, the protein microarray assay had higher sensitivity (0.9 ng/g than the ci-ELISA (0.1 ng/g for detection of CL residues. Conclusions The protein microarrays showed 4.5 and 3.5 times lower IC50 than the ci-ELISA detection for CL and SM2, respectively, suggesting that immunodetection of small molecules with protein microarray is a better approach than the traditional ELISA technique.

  6. [Immunotropic and antihypoxant therapy of experimental drug-sensitive and drug-resistant tuberculosis].

    Science.gov (United States)

    Sukhanov, D S; Vinogradova, T I; Demidik, S N; Zabolotnyh, N V; Vasilieva, S N; Kovalenko, A L; Vitovskaya, M L

    2013-01-01

    The results of pre-clinical research of cycloferon, remaxol and runihol on the model of experimental generalized tuberculosis, caused by the MBT with a different spectrum of drug sensitivity are presented. A considerable increase of the curative effect of the therapy with the used of cycloferon and remaxol. There was manifested the strengthening of lung clearance from the office, reducing the prevalence of specific inflammation in the lungs of the index of lung damage, stimulation of sorption and destructive ability of peritoneal macrophages, inhibited in the course of development of experimental tuberculosis infection. Runihol has no impact on the effectiveness of chemotherapy in the absence of a stimulating influence on the phagocytic function of the peritoneal macrophages. PMID:23805718

  7. Triclosan Derivatives: Towards Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Freundlich, Joel S.; Wang, Feng; Vilchèze, Catherine; Gulten, Gulcin; Langley, Robert; Schiehser, Guy A.; Jacobus, David P.; Jacobs, Jr., William R.; Sacchettini, James C.; (Einstein); (TAM); (Jacobus)

    2009-06-30

    Isoniazid (INH) is a frontline antitubercular drug that inhibits the enoyl acyl carrier protein reductase InhA. Novel inhibitors of InhA that are not cross-resistant to INH represent a significant goal in antitubercular chemotherapy. The design, synthesis, and biological activity of a series of triclosan-based inhibitors is reported, including their promising efficacy against INH-resistant strains of M. tuberculosis. Triclosan has been previously shown to inhibit InhA, an essential enoyl acyl carrier protein reductase involved in mycolic acid biosynthesis, the inhibition of which leads to the lysis of Mycobacterium tuberculosis. Using a structure-based drug design approach, a series of 5-substituted triclosan derivatives was developed. Two groups of derivatives with alkyl and aryl substituents, respectively, were identified with dramatically enhanced potency against purified InhA. The most efficacious inhibitor displayed an IC{sub 50} value of 21 nM, which was 50-fold more potent than triclosan. X-ray crystal structures of InhA in complex with four triclosan derivatives revealed the structural basis for the inhibitory activity. Six selected triclosan derivatives were tested against isoniazid-sensitive and resistant strains of M. tuberculosis. Among those, the best inhibitor had an MIC value of 4.7 {mu}g mL{sup -1} (13 {mu}M), which represents a tenfold improvement over the bacteriocidal activity of triclosan. A subset of these triclosan analogues was more potent than isoniazid against two isoniazid-resistant M. tuberculosis strains, demonstrating the significant potential for structure-based design in the development of next generation antitubercular drugs.

  8. Pressure-sensitive adhesives for transdermal drug delivery systems.

    Science.gov (United States)

    Tan; Pfister

    1999-02-01

    Adhesives are a critical component in transdermal drug delivery (TDD) devices. In addition to the usual requirements of functional adhesive properties, adhesives for TDD applications must have good biocompatibility with the skin, chemical compatibility with the drug, various components of the formulation, and provide consistent, effective delivery of the drug. This review discusses the three most commonly used adhesives (polyisobutylenes, polyacrylates and silicones) in TDD devices, and provides an update on recently introduced TDD products and recent developments of new adhesives. PMID:10234208

  9. Price Sensitivity of Demand for Prescription Drugs: Exploiting a Regression Kink Design

    DEFF Research Database (Denmark)

    Simonsen, Marianne; Skipper, Lars; Skipper, Niels

    This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression ...... education and income are, however, more responsive to the price. Also, essential drugs that prevent deterioration in health and prolong life have lower associated average price sensitivity.......This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression...... kink design. Thus, within a unifying framework we uncover price sensitivity for different subpopulations and types of drugs. The results suggest low average price responsiveness with corresponding price elasticities ranging from -0.08 to -0.25, implying that demand is inelastic. Individuals with lower...

  10. Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.

    LENUS (Irish Health Repository)

    Doherty, Ben

    2014-01-01

    KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer.

  11. Usuários de drogas injetáveis e terapia anti-retroviral: percepções das equipes de farmácia Injecting drug users and antiretroviral therapy: perceptions of pharmacy teams

    OpenAIRE

    Chizuru Minami Yokaichiya; Wagner dos Santos Figueiredo; Lilia Blima Schraiber

    2007-01-01

    OBJETIVO: Compreender as percepções das equipes de farmácia sobre seu papel nos desafios assistenciais e adesão aos anti-retrovirais de usuários de drogas injetáveis vivendo com HIV/Aids. MÉTODOS: Estudo qualitativo por grupos focais e análise temática das falas produzidas com farmacêuticos, técnicos e auxiliares com experiência superior a seis meses na dispensação de medicamentos, de 15 unidades assistenciais de DST/Aids do município de São Paulo, em 2002. RESULTADOS: Formaram-se três grupos...

  12. Stealth anti-CD4 conjugated immunoliposomes with dual antiretroviral drugs--modern Trojan horses to combat HIV.

    Science.gov (United States)

    Ramana, Lakshmi Narashimhan; Sharma, Shilpee; Sethuraman, Swaminathan; Ranga, Udaykumar; Krishnan, Uma Maheswari

    2015-01-01

    Highly active antiretroviral therapy (HAART) is the currently employed therapeutic intervention against AIDS where a drug combination is used to reduce the viral load. The present work envisages the development of a stealth anti-CD4 conjugated immunoliposomes containing two anti-retroviral drugs (nevirapine and saquinavir) that can selectively home into HIV infected cells through the CD4 receptor. The nanocarrier was characterized using transmission electron microscopy, FTIR, differential scanning calorimetry, particle size and zeta potential. The cell uptake was also evaluated qualitatively using confocal microscopy and quantitatively by flow cytometry. The drug to lipid composition was optimized for maximum encapsulation of the two drugs. Both drugs were found to localize in different regions of the liposome. The release of the reverse transcriptase inhibitor was dominant during the early phases of the release while in the later phases, the protease inhibitor is the major constituent released. The drugs delivered via anti-CD4 conjugated immunoliposomes inhibited viral proliferation at a significantly lower concentration as compared to free drugs. In vitro studies of nevirapine to saquinavir combination at a ratio of 6.2:5 and a concentration as low as 5 ng/mL efficiently blocked viral proliferation suggesting that co-delivery of anti-retroviral drugs holds a greater promise for efficient management of HIV-1 infection. PMID:25500283

  13. Shear-stress sensitive lenticular vesicles for targeted drug delivery

    Science.gov (United States)

    Holme, Margaret N.; Fedotenko, Illya A.; Abegg, Daniel; Althaus, Jasmin; Babel, Lucille; Favarger, France; Reiter, Renate; Tanasescu, Radu; Zaffalon, Pierre-Léonard; Ziegler, André; Müller, Bert; Saxer, Till; Zumbuehl, Andreas

    2012-08-01

    Atherosclerosis results in the narrowing of arterial blood vessels and this causes significant changes in the endogenous shear stress between healthy and constricted arteries. Nanocontainers that can release drugs locally with such rheological changes can be very useful. Here, we show that vesicles made from an artificial 1,3-diaminophospholipid are stable under static conditions but release their contents at elevated shear stress. These vesicles have a lenticular morphology, which potentially leads to instabilities along their equator. Using a model cardiovascular system based on polymer tubes and an external pump to represent shear stress in healthy and constricted vessels of the heart, we show that drugs preferentially release from the vesicles in constricted vessels that have high shear stress.

  14. Cell wall perturbation sensitizes fungi to the antimalarial drug chloroquine

    OpenAIRE

    Islahudin, Farida; Khozoie, Combiz; Bates, Steven; Ting, Kang-Nee; Pleass, Richard J.; Avery, Simon V.

    2013-01-01

    Chloroquine (CQ) has been a mainstay of antimalarial drug treatment for several decades. Additional therapeutic actions of CQ have been described, including some reports of fungal inhibition. Here we investigated the action of CQ in fungi, including the yeast model Saccharomyces cerevisiae. A genomewide yeast deletion strain collection was screened against CQ, revealing that bck1Δ and slt2Δ mutants of the cell wall integrity pathway are CQ hypersensitive. This phenotype was rescued with sorbi...

  15. Drug Predictive Cues Activate Aversion-Sensitive Striatal Neurons That Encode Drug Seeking

    OpenAIRE

    Wheeler, Daniel S.; Robble, Mykel A.; Hebron, Emily M.; Dupont, Matthew J.; Ebben, Amanda L.; Wheeler, Robert A

    2015-01-01

    Drug-associated cues have profound effects on an addict's emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking. In all exper...

  16. Sensitivity Analysis of a Pharmacokinetic Model of Vaginal Anti-HIV Microbicide Drug Delivery.

    Science.gov (United States)

    Jarrett, Angela M; Gao, Yajing; Hussaini, M Yousuff; Cogan, Nicholas G; Katz, David F

    2016-05-01

    Uncertainties in parameter values in microbicide pharmacokinetics (PK) models confound the models' use in understanding the determinants of drug delivery and in designing and interpreting dosing and sampling in PK studies. A global sensitivity analysis (Sobol' indices) was performed for a compartmental model of the pharmacokinetics of gel delivery of tenofovir to the vaginal mucosa. The model's parameter space was explored to quantify model output sensitivities to parameters characterizing properties for the gel-drug product (volume, drug transport, initial loading) and host environment (thicknesses of the mucosal epithelium and stroma and the role of ambient vaginal fluid in diluting gel). Greatest sensitivities overall were to the initial drug concentration in gel, gel-epithelium partition coefficient for drug, and rate constant for gel dilution by vaginal fluid. Sensitivities for 3 PK measures of drug concentration values were somewhat different than those for the kinetic PK measure. Sensitivities in the stromal compartment (where tenofovir acts against host cells) and a simulated biopsy also depended on thicknesses of epithelium and stroma. This methodology and results here contribute an approach to help interpret uncertainties in measures of vaginal microbicide gel properties and their host environment. In turn, this will inform rational gel design and optimization. PMID:27012224

  17. Drug predictive cues activate aversion-sensitive striatal neurons that encode drug seeking.

    Science.gov (United States)

    Wheeler, Daniel S; Robble, Mykel A; Hebron, Emily M; Dupont, Matthew J; Ebben, Amanda L; Wheeler, Robert A

    2015-05-01

    Drug-associated cues have profound effects on an addict's emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking. In all experiments, rats were divided into two groups (paired and unpaired), and trained to self-administer cocaine in the presence of a tone that signaled the immediate availability of the drug. For rats in the paired group, self-administration sessions were preceded by a taste cue that signaled delayed drug availability. Assessments of hedonic responses indicated that this delay cue became aversive during training. Both the self-administration behavior and the immediate cue were subsequently extinguished in the absence of cocaine. After extinction of self-administration behavior, the presentation of the aversive delay cue reinstated drug seeking. In vivo electrophysiology and voltammetry recordings in the nucleus accumbens measured the neural responses to both the delay and immediate drug cues after extinction. Interestingly, the presentation of the delay cue simultaneously decreased dopamine signaling and increased excitatory encoding of the immediate cue. Most importantly, the delay cue selectively enhanced the baseline activity of neurons that would later encode drug seeking. Together these observations reveal how cocaine cues can modulate not only affective state, but also the neurochemical and downstream neurophysiological environment of striatal circuits in a manner that promotes drug seeking. PMID:25948270

  18. Delivering anti-cancer drugs with endosomal pH-sensitive anti-cancer liposomes.

    Science.gov (United States)

    Moku, Gopikrishna; Gulla, Suresh Kumar; Nimmu, Narendra Varma; Khalid, Sara; Chaudhuri, Arabinda

    2016-04-22

    Numerous prior studies have been reported on the use of pH-sensitive drug carriers such as micelles, liposomes, peptides, polymers, nanoparticles, etc. that are sensitive to the acidic (pH = ∼6.5) microenvironments of tumor tissues. Such systems have been primarily used in the past as effective drug/gene/microRNA carriers for releasing their anti-cancer payloads selectively to tumor cells/tissues. Herein, we report on the development of new liposomal drug carriers prepared from glutamic acid backbone-based cationic amphiphiles containing both endosomal pH-sensitive histidine as well as cellular uptake & solubility enhancing guanidine moieties in their polar head-group regions. The most efficient one among the four presently described endosomal pH-sensitive liposomal drug carriers not only effectively delivers potent anti-cancer drugs (curcumin & paclitaxel) to mouse tumor, but also significantly contributes to inhibiting mouse tumor growth. The findings in the in vitro mechanistic studies are consistent with apoptosis of tumor cells being mediated through increased cell cycle arrest in the G2/M phase. Findings in the FRET assay and in vitro drug release studies conducted with the liposomes of the most efficient pH-sensitive lipid demonstrated its pH dependent fusogenic and controlled curcumin release properties. Importantly, the presently described liposomal formulation of curcumin & paclitaxel enhanced overall survivability of tumor bearing mice. To the best of our knowledge, the presently described system (curcumin, paclitaxel and liposomal carrier itself) is the first of its kind pH-sensitive liposomal formulation of potent chemotherapeutics in which the liposomal drug itself exhibits significant mouse tumor growth inhibition properties. PMID:26806172

  19. Integrating Domain Specific Knowledge and Network Analysis to Predict Drug Sensitivity of Cancer Cell Lines.

    Science.gov (United States)

    Kim, Sebo; Sundaresan, Varsha; Zhou, Lei; Kahveci, Tamer

    2016-01-01

    One of fundamental challenges in cancer studies is that varying molecular characteristics of different tumor types may lead to resistance to certain drugs. As a result, the same drug can lead to significantly different results in different types of cancer thus emphasizing the need for individualized medicine. Individual prediction of drug response has great potential to aid in improving the clinical outcome and reduce the financial costs associated with prescribing chemotherapy drugs to which the patient's tumor might be resistant. In this paper we develop a network based classifier (NBC) method for predicting sensitivity of cell lines to anticancer drugs from transcriptome data. In the literature, this strategy has been used for predicting cancer types. Here, we extend it to estimate sensitivity of cells from different tumor types to various anticancer drugs. Furthermore, we incorporate domain specific knowledge such as the use of apoptotic gene list and clinical dose information in our method to impart biological significance to the prediction. Our experimental results suggest that our network based classifier (NBC) method outperforms existing classifiers in estimating sensitivity of cell lines for different drugs. PMID:27607242

  20. Drug sensitivity patterns of HHV8 carrying body cavity lymphoma cell lines

    Directory of Open Access Journals (Sweden)

    Konya Jozsef

    2011-10-01

    Full Text Available Abstract Background Primary effusion lymphoma (PEL is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected men with severe immunosuppression and other HHV8-associated diseases such as Kaposi's sarcoma (KS. The prognosis for those infected is poor, with a median survival of less than 6 months in most cohorts. Sustained complete remission is rare. High-dose chemotherapy regimens are used to improve remission rate and survival. The aim of the present study was to compare the drug sensitivity pattern of the available primary effusion (body cavity based lymphoma-derived cell lines in order to find additional, potentially effective drugs that are not included in current chemotherapy treatment protocols. Methods We have analyzed 11 cell lines against 27 frequently used cytostatic drugs in short term (3 days survival assays using automated high throughput confocal microscopy. Results All cell lines showed a distinct, individual drug sensitivity pattern. Considering the in vitro used and clinically achieved drug concentration, Vinorelbine, Paclitaxel, Epirubicin and Daunorubicin were the most effective drugs. Conclusions We suggest that inclusion of the above drugs into PEL chemotherapy protocols may be justified. The heterogeneity in the drug response pattern however indicated that assay-guided individualized therapy might be required to optimize therapeutic response.

  1. Glycolysis Inhibition Inactivates ABC Transporters to Restore Drug Sensitivity in Malignant Cells

    OpenAIRE

    Ayako Nakano; Daisuke Tsuji; Hirokazu Miki; Qu Cui; Salah Mohamed El Sayed; Akishige Ikegame; Asuka Oda; Hiroe Amou; Shingen Nakamura; Takeshi Harada; Shiro Fujii; Kumiko Kagawa; Kyoko Takeuchi; Akira Sakai; Shuji Ozaki

    2011-01-01

    Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC) transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA) suppressed ATP production in malignant cells, and restored the retention of daunorubic...

  2. PRECLINICAL DRUG TRIALS IN THE mdx MOUSE: ASSESSMENT OF RELIABLE AND SENSITIVE OUTCOME MEASURES

    OpenAIRE

    SPURNEY, CHRISTOPHER F.; Gordish-Dressman, Heather; Alfredo D Guerron; Sali, Arpana; Gouri S Pandey; Rawat, Rashmi; van der Meulen, Jack H; Cha, Hee-Jae; Pistilli, Emidio E.; Partridge, Terence A.; Hoffman, Eric P; Nagaraju, Kanneboyina

    2009-01-01

    The availability of animal models for Duchenne muscular dystrophy has led to extensive preclinical research on potential therapeutics. Few studies have focused on reliability and sensitivity of endpoints for mdx mouse drug trials. Therefore, we sought to compare a wide variety of reported and novel endpoint measures in exercised mdx and normal control mice at 10, 20, and 40 weeks of age. Statistical analysis as well as power calculations for expected effect sizes in mdx preclinical drug trial...

  3. Lactate as a Novel Quantitative Measure of Viability in Schistosoma mansoni Drug Sensitivity Assays

    OpenAIRE

    Howe, Stephanie; Zöphel, Dorina; Subbaraman, Harini; Unger, Clemens; Held, Jana; Engleitner, Thomas; Hoffmann, Wolfgang H.; Kreidenweiss, Andrea

    2014-01-01

    Whole-organism compound sensitivity assays are a valuable strategy in infectious diseases to identify active molecules. In schistosomiasis drug discovery, larval-stage Schistosoma allows the use of a certain degree of automation in the screening of compounds. Unfortunately, the throughput is limited, as drug activity is determined by manual assessment of Schistosoma viability by microscopy. To develop a simple and quantifiable surrogate marker for viability, we targeted glucose metabolism, wh...

  4. A pH-Sensitive Injectable Nanoparticle Composite Hydrogel for Anticancer Drug Delivery

    OpenAIRE

    Yuanfeng Ye; Xiaohong Hu

    2016-01-01

    According to previous reports, low pH-triggered nanoparticles were considered to be excellent carriers for anticancer drug delivery, for the reason that they could trigger encapsulated drug release at mild acid environment of tumor. Herein, an acid-sensitive β-cyclodextrin derivative, namely, acetalated-β-cyclodextrin (Ac-β-CD), was synthesized by acetonation and fabricated to nanoparticles through single oil-in-water (o/w) emulsion technique. At the same time, camptothecin (CPT), a hydrophob...

  5. Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs

    DEFF Research Database (Denmark)

    Kolte, L.; Gaardbo, J.C.; Skogstrand, Kristin;

    2008-01-01

    Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores...... if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38......(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly...

  6. Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

    Science.gov (United States)

    Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

    2016-05-01

    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. PMID:26939698

  7. Tetrathiomolybdate sensitizes ovarian cancer cells to anticancer drugs doxorubicin, fenretinide, 5-fluorouracil and mitomycin C

    International Nuclear Information System (INIS)

    Our recent study showed that tetrathiomolybdate (TM), a drug to treat copper overload disorders, can sensitize drug-resistant endometrial cancer cells to reactive oxygen species (ROS)-generating anticancer drug doxorubicin. To expand these findings in the present study we explore TM efficacy in combination with a spectrum of ROS-generating anticancer drugs including mitomycin C, fenretinide, 5-fluorouracil and doxorubicin in ovarian cancer cells as a model system. The effects of TM alone or in combination with doxorubicin, mitomycin C, fenretinide, or 5-fluorouracil were evaluated using a sulforhodamine B assay. Flow cytometry was used to detect the induction of apoptosis and ROS generation. Immunoblot analysis was carried out to investigate changes in signaling pathways. TM potentiated doxorubicin-induced cytotoxicity and modulated key regulators of apoptosis (PARP, caspases, JNK and p38 MAPK) in SKOV-3 and A2780 ovarian cancer cell lines. These effects were linked to the increased production of ROS, as shown in SKOV-3 cells. ROS scavenging by ascorbic acid blocked the sensitization of cells by TM. TM also sensitized SKOV-3 to mitomycin C, fenretinide, and 5-fluorouracil. The increased cytotoxicity of these drugs in combination with TM was correlated with the activity of ROS, loss of a pro-survival factor (e.g. XIAP) and the appearance of a pro-apoptotic marker (e.g. PARP cleavage). Our data show that TM increases the efficacy of various anticancer drugs in ovarian cancer cells in a ROS-dependent manner

  8. Triclosan derivatives: Towards potent inhibitors of drug-sensitive and drug-resistant Mycobacterium tuberculosis

    OpenAIRE

    Joel S. Freundlich; Wang, Feng; Vilchèze, Catherine; Gulten, Gulcin; Langley, Robert; Schiehser, Guy A.; Jacobus, David P.; Jacobs, William R.; Sacchettini, James C.

    2009-01-01

    Triclosan has been previously shown to inhibit InhA, an essential enoyl acyl carrier protein reductase of mycolic acid biosynthesis, whose inhibition leads to the lysis of Mycobacterium tuberculosis. Using a structure-based drug design approach, a series of 5-substituted derivatives of triclosan was developed. Two groups of triclosan derivatives with alkyl and aryl substituents, respectively, were identified with dramatically enhanced potency against purified InhA. The most efficacious inhibi...

  9. New double-walled PH-sensitive hydrogel systems containing nanoparticle drug for colon-specific drug delivery

    International Nuclear Information System (INIS)

    Double-walled (DW) with a Core of mixture of nano or microparticles of carboxymethyl cellulose sodium (CMC) salt and model drug olsalazine [3, 3-azobis (6-hydroxy benzoic acid)] (OSZ) as an azo derivatives of 5-aminosalicylic acid (5-ASA) and an external coat of cross-linked copolymers of (acrylamido methyl) cellulose acetate butyrate (AMCAB) and methacrylic acid (MAA) with various amounts of 1, 6-hexandiol diacrylate (HDD) are considered cross-linking agents (CA). The core with nano composite was prepared by freeze drying method and then used as nuclei for subsequent shell copolymerization. The structure of core was characterized with scanning electron microscopy. The double-walled hydrogels were characterized by differential scanning colorimetry and FT-IR. Studies of drug release were carried out in enzyme-free , simulated gastric and intestinal fluids (SGF and SIF, respectively). The drug-release profiles indicated that the amount of drug released depended ed on the shell layer composition. The releasing was modulated by the amount of cross-linking in shell layer. Bused on the great difference in hydrolysis rates at pH 1 and 7.4, these pH-sensitive hydrogels appear to be good candidates, for colon-specific drug delivery

  10. Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database

    International Nuclear Information System (INIS)

    The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer. We related the cytotoxic activity of each of commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and carboplatin (CBDCA)) to corresponding expression pattern in each of the cell lines using a modified NCI program. We performed gene expression analysis in lung cancer cell lines using cDNA filter and high-density oligonucleotide arrays. We also examined the sensitivity of these cell lines to these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity correlation data, we separately analyzed two sets of lung cancer cell lines, namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion. On the other hand, docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into one large cluster. These results suggest that chemotherapy regimens including gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Gene expression-drug sensitivity correlations, as provided by the NCI program, may yield improved therapeutic options for treatment of specific tumor types

  11. Thermo-sensitive and photoluminescent hydrogels: Synthesis, characterization, and their drug-release property

    International Nuclear Information System (INIS)

    Multifunctional hydrogels that simultaneously possess semi-interpenetrating networks structure, strong photoluminescence, and temperature sensitivity were successfully fabricated based on the crosslink of poly(acrylamide) (PAAm) in the presence of poly(N-isopropylacrylamide) (PNIPAM) and CdTe quantum dots (QDs) at a mild condition. With the increase of external temperature, the photoluminescence (PL) intensity and emission peak of the hydrogels gradually decreased and red-shifted, respectively. Decreasing the temperature, the PL intensity and emission peak of the hydrogels could back to their initial values again. Moreover, drug-release experiments on the multifunctional hydrogels demonstrated that the release rate can be tuned by the environmental temperature and the content of PNIPAM. In addition, biocompatible hyperbranched polyglycerol functionalized QDs (QD-HPGs) instead of pristine QDs can also be incorporated into the hydrogels, affording biocompatible hydrogels which could still exhibit temperature-sensitive photoluminescence and drug-release behaviors. Highlights: → Multifunctional hydrogels that simultaneously possess semi-interpenetrating networks structure, strong photoluminescence, and thermo-sensitive optical and drug-release behaviors were presented for the first time. → These multifunctional hydrogels can be facilely fabricated through the crosslink of poly(acrylamide) in the presence of poly(N-isopropylacrylamide) and CdTe quantum dots at a mild condition. → It is believed that the multifunctional hydrogels will find potential applications in thermo-sensitive devices and drug delivery.

  12. Nosocomial Infections and Drug Susceptibility Patterns in Methicillin Sensitive and Methicillin Resistant Staphylococcus aureus

    OpenAIRE

    Sharma, Nitish Kumar; Garg, Raina; Baliga, Shrikala; Bhat K., Gopalkrishna

    2013-01-01

    Aim: Staphylococcus aureus is one of the leading causes of nosocomial infections and is known for its ability to develop resistance to antibiotics. The drug susceptibility pattern of Methicillin Sensitive S. aureus (MSSA) and Methicillin Resistant S. aureus (MRSA) may vary.

  13. Study on Drug Delivery Systems (II) : Synthesis of Stimule Sensitive Polymers for Intelligent Drug Delivery Systems

    OpenAIRE

    Kaetsu, Isao; Morita, Yasuji

    1991-01-01

    [Abstract] The stimule-sensitive and responsive hydrogels were synthesized by radiation polymerization. The effects of copolymer composition, hydrolysis and crosslinking monomers on the electrical responsiveness were investigated and compared with those on the temperature responsiveness. It was observed that the content of electrolytic component strongly affected on the stimule responsiveness and the responses showed a maximum at a certain copolymer composition. It was suggested that the resp...

  14. Polypyrrole nanoparticles for tunable, pH-sensitive and sustained drug release

    Science.gov (United States)

    Samanta, Devleena; Meiser, Jana L.; Zare, Richard N.

    2015-05-01

    We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (~15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.

  15. Does the drug sensitivity of malaria parasites depend on their virulence?

    Directory of Open Access Journals (Sweden)

    Chan Brian HK

    2008-12-01

    Full Text Available Abstract Background Chemotherapy can prompt the evolution of classical drug resistance, but selection can also favour other parasite traits that confer a survival advantage in the presence of drugs. The experiments reported here test the hypothesis that sub-optimal drug treatment of malaria parasites might generate survival and transmission advantages for virulent parasites. Methods Two Plasmodium chabaudi lines, one derived from the other by serial passage, were used to establish avirulent and virulent infections in mice. After five days, infections were treated with various doses of pyrimethamine administered over 1 or 4 days. Virulence measures (weight and anaemia, parasite and gametocyte dynamics were followed until day 21. Results All treatment regimes reduced parasite and gametocyte densities, but infections with the virulent line always produced more parasites and more gametocytes than infections with the avirulent line. Consistent with our hypothesis, drug treatment was disproportionately effective against the less virulent parasites. Treatment did not affect the relative transmission advantage of the virulent line. Neither of the lines contained known mutations conferring classical drug resistance. Conclusion Drug-sensitivity of malaria parasites can be virulence-dependent, with virulent parasites more likely to survive sub-optimal treatment. If this proves to be general for a variety of drugs and parasite species, selection imposed by sub-optimal drug treatment could result in the evolution of more aggressive malaria parasites.

  16. Synthesis, characterization, and controllable drug release of pH-sensitive hybrid magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Lilin [Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084 (China); Yuan Jinying [Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084 (China)], E-mail: yuanjy@mail.tsinghua.edu.cn; Yuan Weizhong; Sui Xiaofeng [Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084 (China); Wu Sizhu [Key Laboratory of Science and Technology of Controlled Chemical Reactions, Beijing University of Chemical Technology, Beijing 100029 (China); Li Zhaolong [Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084 (China); Shen Dezhong [Department of Chemistry, Tsinghua University, Beijing 100084 (China)

    2009-09-15

    The synthesis of magnetite nanoparticles coated with pH-sensitive poly((2-dimethylamino) ethyl methacrylate) (PDMAEMA) via atom transfer radical polymerization (ATRP) for use as novel potential carriers for targeted drug delivery and controllable release is reported. The organic/inorganic hybrid nanoparticles were obtained with a narrow molecular weight distribution. The pH-sensitivity of the nanoparticles was investigated by the measurement of the pH dependence of hydrodynamic radius and the superparamagnetism was illustrated by vibrating sample magnetometer (VSM). The behavior of model drug phenolphthalein released from the nanoparticles indicated that the rate of drug release could be effectively controlled by altering the pH values of the environment.

  17. Synthesis and evaluation of sensitizer drug photorelease chemistry: Micro-optic method applied to singlet oxygen generation and drug delivery

    Science.gov (United States)

    Ghosh, Goutam

    This thesis summarizes a new micro-optic method for singlet oxygen generation and sensitizer drug delivery, which include i) synthesis and evaluation of a first generation device for drug delivery from native and fluorinated silica probe tips, ii) synthesis of PEG conjugated sensitizers to study phototoxicity in ovarian cancer cells, and iii) synthesis and evaluation of tris-PEGylated chlorin conjugated fluorinated silica for its future integration into the device to use as a 2nd generation device. A first generation micro-optic device was developed that works by sparging O2 gas and light generating cytotoxic singlet oxygen that cleaves the covalently attached drug (sensitizer) from the probe tip at the distal end of the fiber. The aim is to develop a 1st and 2nd generation device for site specific delivery of photosensitizer and singlet oxygen to overcome the challenges involved in systemic administration of the sensitizer. Synthesis and evaluation of drug (pheophorbide-a) delivery applying micro-optic method from native and fluorinated silica probe tip was achieved. The amount of sensitizer photocleavage depends on the loading level of sensitizer onto the probe tips. We also found that photorelease efficiency depends on the nature of the solvents where sensitizer is photocleaved. For example, no photorelease was observed in an aqueous solvent where sensitizer remained adsorbed to the native silica probe-tip. But, 90% photocleavage was obtained in octanol. A significant amount of photosensitizer (formate ester of pyropheophorbide- a) diffused into the liposome when photocleavage study was carried out in liposome. Substantial increase of photorelease was observed in organic solvent when pyropheophorbide-a (PPa) sensitizer was attached to the partially fluorinated porous Vycor glass. We also explored sensitizer photorelease from the fluorinated silica surface at various temperatures and we found that autocatalytic photorelease happened at room temperature and above

  18. Release study of Naproxen, A Modern drug from pH Sensitive Pullulan Acetate Microsphere

    Directory of Open Access Journals (Sweden)

    Mishra Bishwambhar

    2012-12-01

    Full Text Available The current study represents the latest and new advances in the investigations and applications of the pullulan the wonderful biomaterial which is produced from microbes (generally Aureobasidium sps. and its derivatives for its applications in the development of various therapeutic formulations. Basically pullulan is an exo-polysacharides which is non-carcinogenic, non-immunogenic and non-mutagenic without having any types of toxicological activities. Similar to dextran and other biopolymer it can be used as a plasma expander. The model drug for this studies i.e Naproxen was used which is one of the most potent non-steroid and anti-inflammatory drug for the treatment of various bone related diseases .In our study we have prepared pH sensitive naproxen-pullulan delivery system in which Pullulan acetate was synthesized by treating 2.5 gm of crude pullulan with 25 ml of formamide at 50°C. For the loading of drug 50 mg of Pullulan acetate was dissolved 5 ml of dichloromethane and to it 80 mg of Naproxen was added. The drug loading efficiency of the prepared microparticle was found to be 80%. The microsphere was also showing a pH sensitive swelling behaviour in Phosphate Buffer Saline (PBS buffer. The release profile of the drug loaded microsphere reveals that pH of the medium was influencing it at in vitro condition. Moreover the released amount of drug from the pullulan based microsphere at pH 7.2 was 75 times more than that at the pH 1.2. Therefore Pullulan acetate loaded with Naproxen is a useful polymerised materials for the development and formulation of pH sensitive drug.

  19. Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung; Ro, Jungsil [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of); Yoon, Sungpil, E-mail: yoons@ncc.re.kr [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

  20. Modulating cell-to-cell variability and sensitivity to death ligands by co-drugging

    Science.gov (United States)

    Flusberg, Deborah A.; Sorger, Peter K.

    2013-06-01

    TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) holds promise as an anti-cancer therapeutic but efficiently induces apoptosis in only a subset of tumor cell lines. Moreover, even in clonal populations of responsive lines, only a fraction of cells dies in response to TRAIL and individual cells exhibit cell-to-cell variability in the timing of cell death. Fractional killing in these cell populations appears to arise not from genetic differences among cells but rather from differences in gene expression states, fluctuations in protein levels and the extent to which TRAIL-induced death or survival pathways become activated. In this study, we ask how cell-to-cell variability manifests in cell types with different sensitivities to TRAIL, as well as how it changes when cells are exposed to combinations of drugs. We show that individual cells that survive treatment with TRAIL can regenerate the sensitivity and death-time distribution of the parental population, demonstrating that fractional killing is a stable property of cell populations. We also show that cell-to-cell variability in the timing and probability of apoptosis in response to treatment can be tuned using combinations of drugs that together increase apoptotic sensitivity compared to treatment with one drug alone. In the case of TRAIL, modulation of cell-to-cell variability by co-drugging appears to involve a reduction in the threshold for mitochondrial outer membrane permeabilization.

  1. The absence of functional glucosylceramide synthase does not sensitize melanoma cells for anticancer drugs.

    Science.gov (United States)

    Veldman, Robert Jan; Mita, Alain; Cuvillier, Olivier; Garcia, Virginie; Klappe, Karin; Medin, Jeffrey A; Campbell, John D; Carpentier, Stéphane; Kok, Jan Willem; Levade, Thierry

    2003-06-01

    Conversion of ceramide, a putative mediator of anticancer drug-induced apoptosis, into glucosylceramide, by the action of glucosylceramide synthase (GCS), has been implicated in drug resistance. Herein, we compared GM95 mouse melanoma cells deficient in GCS activity, with cells stably transfected with a vector encoding GCS (GM95/GCS). Enzymatic and metabolic analysis demonstrated that GM95/GCS cells expressed a fully functional enzyme, resulting in normal ceramide glycosylation. However, cytotoxicity assays, as well as caspase activation and cytochrome c release studies, did not reveal any difference between the two cell lines with respect to their sensitivity toward doxorubicin, vinblastine, paclitaxel, cytosine arabinoside, or short-chain ceramide analogs. Administration of doxorubicin resulted in ceramide accumulation in both cell lines, with similar kinetics and amplitude. Although glucosylceramide formation was detected in doxorubicin-treated GM95/GCS cells, metabolism of drug-induced ceramide did not appear to be instrumental in cell survival. Furthermore, N-(n-butyl)deoxynojirimycin, a potent and non-toxic GCS inhibitor, had no chemosensitizing effect on wild-type melanoma cells. Altogether, both genetic and pharmacological alterations of the cellular ceramide glycosylation capacity failed to sensitize melanoma cells to anticancer drugs, therefore moderating the importance of ceramide glucosylation in drug-resistance mechanisms. PMID:12692077

  2. Inhibition of CYP2B6 by Medicinal Plant Extracts: Implication for Use of Efavirenz and Nevirapine-Based Highly Active Anti-Retroviral Therapy (HAART) in Resource-Limited Settings.

    Science.gov (United States)

    Thomford, Nicholas E; Awortwe, Charles; Dzobo, Kevin; Adu, Faustina; Chopera, Denis; Wonkam, Ambroise; Skelton, Michelle; Blackhurst, Dee; Dandara, Collet

    2016-01-01

    Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a significant challenge. There is need to evaluate interactions between commonly used medicinal plant extracts and antiretroviral drugs used against HIV/AIDS. Efavirenz (EFV) and nevirapine (NVP) are the major components of HAART both metabolized by CYP2B6, an enzyme that can potentially be inhibited or induced by compounds found in medicinal plant extracts. The purpose of this study was to evaluate the effects of extracts of selected commonly used medicinal plants on CYP2B6 enzyme activity. Recombinant human CYP2B6 was used to evaluate inhibition, allowing the assessment of herb-drug interactions (HDI) of medicinal plants Hyptis suaveolens, Myrothamnus flabellifolius, Launaea taraxacifolia, Boerhavia diffusa and Newbouldia laevis. The potential of these medicinal extracts to cause HDI was ranked accordingly for reversible inhibition and also classified as potential time-dependent inhibitor (TDI) candidates. The most potent inhibitor for CYP2B6 was Hyptis suaveolens extract (IC50 = 19.09 ± 1.16 µg/mL), followed by Myrothamnus flabellifolius extract (IC50 = 23.66 ± 4.86 µg/mL), Launaea taraxacifolia extract (IC50 = 33.87 ± 1.54 µg/mL), and Boerhavia diffusa extract (IC50 = 34.93 ± 1.06 µg/mL). Newbouldia laevis extract, however, exhibited weak inhibitory effects (IC50 = 100 ± 8.71 µg/mL) on CYP2B6. Launaea taraxacifolia exhibited a TDI (3.17) effect on CYP2B6 and showed a high concentration of known CYP450 inhibitory phenolic compounds, chlorogenic acid and caffeic acid. The implication for these observations is that drugs that are metabolized by CYP2B6 when co-administered with these herbal medicines and when adequate amounts of the extracts

  3. Fatores de risco para a não adesão ao tratamento com terapia antiretroviral altamente eficaz Factores de riesgo para la no-adherencia al tratamiento con terapia anti-retroviral altamente eficiente Risk factors for non-compliance to treatment with highly effective antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Maria Rosa Ceccato Colombrini

    2008-09-01

    Full Text Available O estudo objetivou: mensurar a prevalência de não-adesão à terapia anti-retroviral altamente eficaz (HAART em pacientes com AIDS; identificar se alguns fatores relacionados na literatura estavam associados com a não-adesão; estabelecer o valor preditivo dos fatores associados à não-adesão à HAART. Foi realizado um estudo analítico de prevalência (N=60. Foram considerados os três dias anteriores à entrevista e os pacientes classificados como aderentes quando ingeriam 95% ou mais do total de comprimidos prescritos por dia. A adesão foi de 73,3%. A análise de regressão logística multivariada indicou que indivíduos da raça negra apresentaram 6,48 vezes mais risco de não-adesão; aqueles que apresentaram ausência de efeito colateral tiveram um risco 7,6 vezes maior, e a cada comprimido ingerido o risco foi de 1,12. A adesão observada foi maior que a encontrada na literatura. Os fatores sociodemográficos e culturais podem interferir na adesão à HAART.Objetivo del estudio: medir la prevalencia por falta de seguimiento al tratamiento anti-retroviral altamente eficaz (HAART en pacientes con SIDA; identificar si algunos factores relacionados en la bibliografía se encuentran asociados con la falta de seguimiento; establecer el valor preditivo de los factores asociados con la falta de seguimiento al HAART. Para lo cual fue realizado un estudio analitico de prevalencia (N=60, considerándose los tres días anteriores a la entrevista, donde aquellos pacientes con ingesta del 95% o más del total de comprimidos prescritos por día eran clasificados como seguidores del tratamiento. El seguimiento fue de 73,3%. El análisis de regresion logística multi-variable mostró que sujetos de raza negra presentaron 6,48 veces mayor riesgo de no continuar con el tratamiento; aquellos individuos sin efectos colaterales tuvieron un riesgo 7,6 veces mayor, asimismo, cada comprimido ingerido produjo un riesgo de 1,12. El seguimiento observado fue

  4. The sensitivity of human tumour cells to quinone bioreductive drugs: what role for DT-diaphorase?

    Science.gov (United States)

    Robertson, N; Stratford, I J; Houlbrook, S; Carmichael, J; Adams, G E

    1992-08-01

    15 human tumour cell lines (lung, breast and colon) have been evaluated for their sensitivity to the quinone based anti-cancer drugs Mitomycin C, Porfiromycin, and EO9 (3-hydroxymethyl-5-aziridinyl-1-methyl-2-(IH-indole-4,7-dione)prop-beta- en-alpha-ol). Sensitivity has been compared with the intra-cellular levels of DT-diaphorase, an enzyme thought to be important in the reductive activation of these quinones. No correlation exists between levels of DT-diaphorase and sensitivity to Mitomycin C or Porfiromycin. However, for EO9 those cell lines showing highest levels of DT-diaphorase activity tend to be the most sensitive. PMID:1510692

  5. Início da terapia anti-retroviral em estágio avançado de imunodeficiência entre indivíduos portadores de HIV/AIDS em Belo Horizonte, Minas Gerais, Brasil Initiation of antiretroviral therapy in HIV-infected patients with severe immunodeficiency in Belo Horizonte, Minas Gerais State, Brazil

    Directory of Open Access Journals (Sweden)

    José Roberto Maggi Fernandes

    2009-06-01

    Full Text Available O objetivo deste trabalho foi verificar a proporção de início tardio da terapia anti-retroviral (TARV e seus fatores associados. Estudo de corte transversal com pacientes de dois serviços públicos de referência (n = 310 em Belo Horizonte, Minas Gerais, Brasil. Atraso no início da TARV foi definido como ter contagem de linfócitos T CD4+ The main objective was to assess the proportion of delayed initiation of antiretroviral therapy (ART and associated factors. This was a cross-sectional study of 310 patients enrolled in two public health centers in Belo Horizonte, Minas Gerais State, Brazil. Delayed ART initiation was defined as starting treatment with a CD4 count lower than 200 cells/mm³ or clinical symptoms of severe immunodepression at the time of first antiretroviral prescription. The majority of participants were males (63.9%, had no health insurance (76.1%, and started ART less than 120 days after the first medical visit (75.2%. The proportion of delayed ART initiation was 68.4%. Unemployment, referral by a health professional for HIV testing, fewer than two medical visits in the six months prior to ART initiation, and time between first medical visit and ART initiation less than 120 days were independently associated with the outcome. Our results suggest that every patient 13 to 64 years of age should be offered HIV testing, which could increase the rate of early HIV diagnosis, and thus patients that tested positive could benefit from timely follow-up and antiretroviral therapy.

  6. Presynaptic muscarinic receptors: Change of sensitivity during long-term drug treatment

    International Nuclear Information System (INIS)

    The authors investigate some of the characteristics of auto- and heteroreceptors from different brain areas in male rats; their alteration in sensitivity following chronic drug treatment is monitored. The synaptosomes were prelabeled with tritium-choline or tritium-dopamine and the release of tritium-acetylcholine and tritium-DA was studied in superfusion. It is shown that the difference in susceptibility between auto- and heteroreceptors with respect to changes of sensitivity may represent a further criterion to discriminate between muscarinic receptor subtypes

  7. Non-polymeric nano-carriers in HIV/AIDS drug delivery and targeting.

    Science.gov (United States)

    Gupta, Umesh; Jain, Narendra K

    2010-03-18

    Development of an effective drug delivery approach for the treatment of HIV/AIDS is a global challenge. The conventional drug delivery approaches including Highly Active Anti Retroviral Therapy (HAART) have increased the life span of the HIV/AIDS patient. However, the eradication of HIV is still not possible with these approaches due to some limitations. Emergence of polymeric and non-polymeric nanotechnological approaches can be opportunistic in this direction. Polymeric carriers like, dendrimers and nanoparticles have been reported for the targeting of anti HIV drugs. The synthetic pathways as well polymeric framework create some hurdles in their successful formulation development as well as in the possible drug delivery approaches. In the present article, we have discussed the general physiological aspects of the infection along with the relevance of non-polymeric nanocarriers like liposomes, solid lipid nanoparticles (SLN), ethosomes, etc. in the treatment of this disastrous disease. PMID:19913579

  8. On the Comparison of Interpersonal Sensitivity and Assertiveness between Drug-Dependent Persons and Ordinary People

    OpenAIRE

    Babak Vojudi; Nastaran Otared; Hamid poursharifi

    2015-01-01

    Objective: The present study was aimed at comparing interpersonal sensitivity and assertiveness between drug-dependent persons and ordinary people. Method: The research method was causal-comparative. The statistical population of the study consisted of all narcotic addicts of Tabriz City who referred to Addiction Treatment Centers while the research was being conducted. The number of 30 addicted persons was selected through cluster sampling and 30 ordinary persons as control group through con...

  9. Formulation and characterization of sustained release dosage form of moisture sensitive drug

    OpenAIRE

    Patel, Priya; Dave, Abhishek; Vasava, Amit; Patel, Paresh

    2015-01-01

    Objective: The purpose of this study was to prepare sustained release tablet of moisture sensitive drug like Ranitidine Hydrochloride for treatment of gastroesophageal reflux disease along with the improvement of moisture stability to get better therapeutic efficacy. Materials and Methods: Pan coating technique was used for coating of the tablet. Film coating was done using Eudragit RLPO and Eugragit EPO as coating polymer. 32 full factorial design was applied for optimization purpose, and 9 ...

  10. Kinetic Degradation and Controlled Drug Delivery System Studies for Sensitive Hydrogels Prepared by Gamma Irradiation

    International Nuclear Information System (INIS)

    Ternary mixtures of N-vinyle-2-pyrrolidone(NVP ), itaconic acid (IA) and gelatin (G) were gamma irradiated to prepared poly(NVP/IA/G) hydrogels. The equilibrium kinetic swelling, drug release behavior, Scan Electron Microscope (SEM) and the swelling-degradation kinetics were studied. Both the diffusion exponent and the diffusion coefficient increase with increasing content of (IA). Also, the swelling behavior of copolymer hydrogels in response to ph value of the external media was studied, it is noted that the highest swelling values at ph 4. The in vitro drug release behavior of these hydrogels was examined by quantification analysis with a UV/VIS spectrophotometers. Chlorpromazine hydrochloride was loaded into dried hydrogels to investigate the stimuli-sensitive property at the specific ph. The release studies show that the highest value of release was at ph 4 which can be used for drug delivery system

  11. Sensitive, resistant and multi-drug resistant Acinetobacter baumanii at Saudi Arabia hospital eastern region.

    Science.gov (United States)

    Ahmed, Mughis Uddin; Farooq, Reshma; Al-Hawashim, Nadia; Ahmed, Motasim; Yiannakou, Nearchos; Sayeed, Fatima; Sayed, Ali Rifat; Lutfullah, Sualiha

    2015-05-01

    Since the Physicians start use of antibiotics long ago with un-notice drug resistance. However actual problem was recognized about 85 years ago. Antibiotic resistant and Multi-drug resistant bacterial strains are at rise throughout the world. It is physicians and researchers to take scientific research based appropriate action to overcome this ever-spreading problem. This study is designed to find out sensitive (S), resistant (R) and multi-drug resistant (MDR) Acinetobacter baumanii strain along with other isolates in the resident patients of Eastern Region of Saudi Arabia. Pseudomonas aeruginosa is excluded from other gram-negative organisms isolated from different sites as it will be dealt separately. This study is based in was retrospective observations designed to collect data of different stains of Acinetobacter baumanii with reference to their Sensitivity (S), Resistance (R), Multi-Drug Resistance (MDR) along with other Gram negative isolated from different sites (from 1st January 2004 to 31st December 2011) at King Abdulaziz Hospital located Eastern Region of Kingdom of Saudi Arabia (KSA). All necessary techniques were used to culture and perform sensitivity of these isolates. There were 4532 isolates out of which 3018 (67%) were from patients. Out of Acinetobacter baumanii infected were 906 (20%) while other 3626 (80%) isolates were miscellaneous. Numbers of patients or cases were 480 (53%) out of 906 isolates and numbers of patients or cases in other organisms were 2538 (70%) out of 3626 isolates. Acinetobacter baumanii infected patients 221 (46%) were male and 259 (54%) were female and the male and female ratio of 1:1.2. In other organisms this male female ratio was almost same. There was steady rise in number of patients and the hence the isolates from 2004 to 2011. Majority of the bacterial strains were isolated as single organism but some were isolated as double or triple or quadruple or more organisms from different sites. Sensitive, Resistant and

  12. Sensitizing nanoparticle based platinum(IV) drugs by curcumin for better chemotherapy.

    Science.gov (United States)

    Kang, Xiang; Zhao, Chen; Yan, Lesan; Qi, Ruogu; Jing, Xiabin; Wang, Zehua

    2016-09-01

    A polymer-cisplatin(IV) conjugate was prepared by attaching Pt(IV)-COOH to a biodegradable amphiphilic block copolymer containing pendant OH groups. The conjugate can assemble into micelles (M(Pt)) with a mean diameter of ca. 169nm. Further, curcumin (CM) was used to sensitize platinum drug based nanoparticles to overcome cisplatin resistance and enhance antitumor efficacy. In vitro studies showed that M(Pt)/CM combinations had great synergistic effect both on cisplatin sensitive and cisplatin resistant cell lines (A2780 and A2780DDP). In vivo studies showed that M(Pt)/CM had a much lower systemic toxicity and an enhanced antitumor efficacy compared to cisplatin alone or the corresponding cisplatin/CM combinations. Therefore, polymer-cisplatin(IV) conjugate with small molecules that serve as a non-cytotoxic or minimally cytotoxic sensitizer or enhancer provide a promising strategy, which may have potential clinical implications in the near future. PMID:27311131

  13. NOVEL pH-SENSITIVE DRUG DELIVERY SYSTEM BASED ON NATURAL POLYSACCHARIDE FOR DOXORUBICIN RELEASE

    Institute of Scientific and Technical Information of China (English)

    Dian-xiang Lu; Xian-tao Wen; Jie Liang; Xing-dong Zhang; Zhong-wei Gu; Yu-jiang Fan

    2008-01-01

    A novel pH-sensitive nanoparticle drug delivery system (DDS) derived from natural polysaccharide pullulan for doxorubicin (DOX) release was prepared. Pullulan was functionalized by successive carboxymethylization and amidation to introduce hydrazide groups. DOX was then grafted onto pullulan backbone through the pH-sensitive hydrazone bond to form a pullulan/DOX conjugate. This conjugate self-assembled to form nano-sized particles in aqueous solution as a result of the hydrophobic interaction of the DOX. Transmission electron microscope (TEM) and dynamic light scattering (DLS)characterization showed that the nanoparticles were spherical and their size was less than 100 nm. The DOX released from the nanoparticles in a pH-sensitive manner. In vitro cytotoxicity assay indicated the pullulan/DOX nanoparticles showed comparable cytotoxicity effect with free DOX on the 4T1 mouse breast cancer cells.

  14. Design and assembly of pH-sensitive lipidic cubic phase matrices for drug release.

    Science.gov (United States)

    Nazaruk, Ewa; Szlęzak, Monika; Górecka, Ewa; Bilewicz, Renata; Osornio, Yazmin M; Uebelhart, Peter; Landau, Ehud M

    2014-02-11

    Bicontinuous lipidic cubic phases (LCPs) exhibit a combination of material properties that make them highly interesting for various biomaterial applications: they are nontoxic, biodegradable, optically transparent, thermodynamically stable in excess water, and can incorporate active molecules of virtually any polarity. Here we present a molecular system comprising host lipid, water, and designed lipidic additive, which form a structured, pH-sensitive lipidic matrix for hydrophilic as well as hydrophobic drug incorporation and release. The model drug doxorubicin (Dox) was loaded into the LCP. Tunable interactions with the lipidic matrix led to the observed pH-dependent drug release from the phase. The rate of Dox release from the cubic phase at pH 7.4 was low but increased significantly at more acidic pH. A small amount of a tailored diacidic lipid (lipid 1) added to the monoolein LCP modified the release rate of the drug. Phase identity and structural parameters of pure and doped mesophases were characterized by small-angle X-ray scattering (SAXS), and release profiles from the matrix were monitored electrochemically. Analysis of the release kinetics revealed that the total amount of drug released from the LCP matrix is linearly dependent on the square root of time, implying that the release mechanism proceeds according to the Higuchi model. PMID:24443890

  15. Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AML)

    International Nuclear Information System (INIS)

    Chemotherapeutic drug efflux via the P-glycoprotein (P-gp) transporter encoded by the MDR1/ABCB1 gene is a significant cause of drug resistance in numerous malignancies, including acute leukemias, especially in older patients with acute myeloid leukemia (AML). Therefore, the P-gp modulators that block P-gp-mediated drug efflux have been developed, and used in combination with standard chemotherapy. In this paper, the capacity of zosuquidar, a specific P-gp modulator, to reverse chemoresistance was examined in both leukemia cell lines and primary AML blasts. The transporter protein expressions were analyzed by flow cytometry using their specific antibodies. The protein functionalities were assessed by the uptake of their fluorescence substrates in presence or absence their specific modulators. The drug cytotoxicity was evaluated by MTT test. Zosuquidar completely or partially restored drug sensitivity in all P-gp-expressing leukemia cell lines tested and enhanced the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AML blasts with active P-gp. In addition, P-gp inhibition by zosuquidar was found to be more potent than cyclosporine A in cells with highly active P-gp. These in vitro studies suggest that zosuquidar may be an effective adjunct to cytotoxic chemotherapy for AML patients whose blasts express P-gp, especially for older patients

  16. Hepatic drug metabolizing profile of Flinders Sensitive Line rat model of depression.

    Science.gov (United States)

    Kotsovolou, Olga; Ingelman-Sundberg, Magnus; Lang, Matti A; Marselos, Marios; Overstreet, David H; Papadopoulou-Daifoti, Zoi; Johanson, Inger; Fotopoulos, Andrew; Konstandi, Maria

    2010-08-16

    The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague-Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7-ethoxyresorufin-O-dealkylase (EROD) and 16alpha-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(alpha)pyrene (B(alpha)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(alpha)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity. PMID:20595028

  17. Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells

    Directory of Open Access Journals (Sweden)

    Olah Eva

    2006-11-01

    Full Text Available Abstract Background Epstein-Barr virus (EBV is the causative agent of immunosuppression associated lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD, AIDS related immunoblastic lymphomas (ARL and immunoblastic lymphomas in X-linked lymphoproliferative syndrome (XLP. The reported overall mortality for PTLD often exceeds 50%. Reducing the immunosuppression in recipients of solid organ transplants (SOT or using highly active antiretroviral therapy in AIDS patients leads to complete remission in 23–50% of the PTLD/ARL cases but will not suffice for recipients of bone marrow grafts. An additional therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab or EBV-specific cytotoxic T-cells. Chemotherapy is used for the non-responding cases only as the second or third line of treatment. The most frequently used chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there are no cytotoxic drugs that have been specifically selected against EBV induced lymphoproliferative disorders. Methods As lymphoblastoid cell lines (LCLs are well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic drug sensitivity. After three days of incubation, live and dead cells were differentially stained using fluorescent dyes. The precise numbers of live and dead cells were determined using a custom designed automated laser confocal fluorescent microscope. Results Independently of their origin, LCLs showed very similar drug sensitivity patterns against 29 frequently used cytostatic drugs. LCLs were highly sensitive for vincristine, methotrexate, epirubicin and paclitaxel. Conclusion Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified.

  18. A new type of radiotherapeutic sensitizing drug: a clinical trials of sodium glycididazole

    International Nuclear Information System (INIS)

    A new type tumor radiosensitizing drug-Sodium Glycidadizole(CMNa)synthesized since 1984.Now been completed I-III clinical trials.The therapeutic efficacy and toxicity of CMNa combined with conventional radiotherapy for head neck, lung and esophagus cancer patients in phase II trial were recommended. 207 Pts: Head neck cancer(n=84), Esophagus cancer (n=61),lung cancer(n=62) were enrolled, proceeded for clinical trial phase II in five clinical hospitals denoted by National Drug Administration. Thereafter, the Pts were divided into test group (gp,n=104)and control gp(n=101) according to the rule of di blind, random and parallels. Median age of the former was 52.3±12.5; later 54.1±12.3. The Pts of the test gp was injected CMNa 800 mgs/m2/time,3/wks,then conventionally irradiated 2 Gy with 4-6 MV linear accelerator within an hour for 6-7 wks; Whereas the Pts of control gp was the same treatment as test gp but injected with only placebo, no drug. All patients were assessed by CT,or X-ray films. When the radiation doses arrived to the median dosage D4000 cGy after 6-7 wks therapy, the therapeutic efficiency (CR+PR) of the test group(CMNa+RT) increased from the 80.6%(79/98) of control gp to 92.7%(101/109)(p=0.01), and the drug did not increase the radiation effects of normal tissues by irradiation. It showed that the CMNa possessed significantly radiotherapeutic sensitizing efficacy and very low toxicity. Even some Pts were continuously injected CMNa up to 21 times, total dosage 16.8g/m2 , still did not see any remarkable side toxicities and neurotoxicity. With this protocol, injecting CMNa 800 mgs/time,3 times/week before conventional radiation for tumor Pts was safe, could increase the radiosensitization of hypoxia cells in tumor remarkable; whereas no radiosensitizing effects of normal tissues. Thus, CMNa is a new type, highly effective and of lower toxicity radiotherapeutic sensitizing drug that could enhance antitumor effects evidently. We have received the New Drug

  19. Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys1

    Institute of Scientific and Technical Information of China (English)

    Su-qing CHEN; Hai-feng ZHAI; Yan-ying CUI; Jie SHI; Bernard LE FOLL; Lin LU

    2007-01-01

    Aim: Clonidine is an α2 adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus mon-keys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse. Methods: Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic)dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine. Results:Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized re-sponses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previ-ously treated with clonidine. Conclusion: Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may re-duce subsequent effects of drugs of abuse after prolonged abstinence.

  20. Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy

    OpenAIRE

    Hultman, Bo; Mahteme, Haile; Sundbom, Magnus; Ljungman, Martin; Larsson, Rolf; Nygren, Peter

    2014-01-01

    Background   The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC. Methods   Tumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mito­mycin C, doxorubicin and doceta...

  1. On the Comparison of Interpersonal Sensitivity and Assertiveness between Drug-Dependent Persons and Ordinary People

    Directory of Open Access Journals (Sweden)

    Babak Vojudi

    2015-02-01

    Full Text Available Objective: The present study was aimed at comparing interpersonal sensitivity and assertiveness between drug-dependent persons and ordinary people. Method: The research method was causal-comparative. The statistical population of the study consisted of all narcotic addicts of Tabriz City who referred to Addiction Treatment Centers while the research was being conducted. The number of 30 addicted persons was selected through cluster sampling and 30 ordinary persons as control group through convenience sampling method. Gmbryl & Ritchie’s assertiveness questionnaire (1975 and Boyce & Parker’s Interpersonal Sensitivity Measure (IPSM 1989 were used for data collection purposes. Results: The results showed that there was a statistically significant difference between two groups in terms of interpersonal sensitivity and assertiveness. The addicts showed less assertiveness and more interpersonal sensitivity in comparison with their healthy counterparts. Conclusion: The findings show that people who are unable to express themselves and exert sensitivity in interpersonal relationships are more likely at high risk of substance dependence. However, it is possible to prevent these persons from turning to addiction by teaching them these skills.

  2. Overexpression of the human HAP1 protein sensitizes cells to the lethal effect of bioreductive drugs.

    Science.gov (United States)

    Prieto-Alamo, M J; Laval, F

    1999-03-01

    Abasic sites (AP sites) are generated in DNA either directly by DNA-damaging agents or by DNA glycosylases acting during base excision repair. These sites are repaired in human cells by the HAP1 protein, which, besides its AP-endonuclease activity, also possesses a redox function. To investigate the ability of HAP1 protein to modulate cell resistance to DNA-damaging agents, CHO cells were transfected with HAP1 cDNA, resulting in stable expression of the protein in the cell nuclei. The sensitivity of the transfected cells to the toxic effect of various agents, e.g. methylmethane sulfonate, bleomycin and H2O2, was not modified. However, the transfected cells became more sensitive to killing by mitomycin C, porfiromycin, daunorubicin and aziridinyl benzoquinone, drugs that are activated by reduction. To test whether the redox function of HAP1 protein was involved in this increased cytotoxicity, we have constructed a mutated HAP1 protein endowed with normal AP-endonuclease activity but deleted for redox function. When this mutated protein was expressed in the cells, elevated AP-endonuclease activity was measured, but sensitization to the lethal effects of compounds requiring bioreduction was no longer observed. These results suggest that HAP1 protein, besides its involvement in DNA repair, is able to activate bioreduction of alkylating drugs used in cancer chemotherapy. PMID:10190555

  3. Impact of heterozygous mutations in BRCA1 and BRCA2. Sensitivity to genotoxic drugs

    International Nuclear Information System (INIS)

    The carriers of heterozygous mutations in BRCA1 / 2 have a high risk of developing breast cancer. The loss of the normal allele with consequent loss of function is frequently observed in tumor level. Since these genes involved in the cellular response to genetic damage, loss of function can determine differences in sensitivity to genotoxic agents. In this study investigated whether heterozygous mutations in BRCA1 / 2 modify the sensitivity to genotoxic drugs using lymphoblastic cell lines developed from individuals who carry no mutation carriers and heterozygous for BRCA1 / 2. Materials and methods. Chemo sensitivity of the cell lines was compared lymphoblastoid GM13709 (mutation in exon 11 of BRCA1 2187delA), GM14622 (level 607stop mutation in exon 11 of BRCA2) and GM 14453 (normal BRCA1 / 2) from exposure to Adriamycin (0.2-2.5 mM) and Cisplatin (0.625- 80mM) through the test of cell viability based on MTT reduction. It determined the inhibitory concentration 50 (IC50) from curves regression dose-response obtained after 24 hours of drug exposure. It 5 independent experiments performed in triplicate. Results. The line GM14622 was significantly (P = 0.003) more sensitive to Adriamycin (IC50: 0.585 mM) than the Control GM14453 (IC50: 1.364 mM) online while GM13709 was similar to the control (IC50: 1.324 mM) response. Turn the line GM14622 was also significantly (P = 0.01) more sensitive cisplatin (IC50: 12.7 mM) than the line GM14453 (IC50: 28.6mm) and GM13709 had the same response as the (IC50: 28.6 mM) control. Discussion and Conclusions. Our results suggest that mutations deleterious heterozygous BRCA2 may confer increased sensitivity to drugs genotoxic, which may have implications in the management of patients carrying or BRCA2 mutations in women with sporadic breast cancer exhibit low expression of BRCA2

  4. Monitoring drug induced apoptosis and treatment sensitivity in non-small cell lung carcinoma using dielectrophoresis.

    Science.gov (United States)

    Taruvai Kalyana Kumar, Rajeshwari; Liu, Shanshan; Minna, John D; Prasad, Shalini

    2016-09-01

    Non-invasive real time methods for characterizing biomolecular events that contribute towards apoptotic kinetics would be of significant importance in the field of cancer biology. Effective drug-induced apoptosis is an important factor for establishing the relationship between cancer genetics and treatment sensitivity. The objective of this study was to develop a non-invasive technique to characterize cancer cells that are undergoing drug-induced apoptosis. We used dielectrophoresis to determine apoptotic cells as early as 2h post drug treatment as compared to 24h with standard flow cytometry method using non-small cell lung cancer (NSCLC) adenocarcinoma cell line (HCC1833) as a study model. Our studies have shown significant differences in apoptotic cells by chromatin condensation, formation of apoptotic bodies and exposure of phosphatidylserine (PS) on the extracellular surface when the cells where treated with a potent Bcl-2 family inhibitor drug (ABT-263). Time lapse dielectrophoretic studies were performed over 24h period after exposure to ABT-263 at clinically relevant concentrations. The dielectrophoretic studies were compared to Annexin-V FITC flow assay for the detection of PS in mid-stage apoptosis using flow cytometry. As a result of physical and biochemical changes, inherent dielectric properties of cells undergoing varying stages of apoptosis showed amplified changes in their cytoplasmic and membrane capacitance. In addition, zeta potential of these fixed isolated cells was measured to obtain direct correlation to biomolecular events. PMID:27262539

  5. Swelling and drug releasing properties of poly(N-isopropylacrylamide) thermo-sensitive copolymer gels

    Institute of Scientific and Technical Information of China (English)

    Chunyue PAN; Qingde LONG; Dian YU; Yanping RAO; Nianqian WU; Xingcui LI

    2008-01-01

    A series of N,isopropylacrylamide (NIPAAm)copolymer gels with different hydrophilicities were prepared from NIPAAm, hydrophilic acrylamide (AAm) and hydrophobic butyl methacrylate (BMA). The swelling and thermo,responsive properties of PNIPAAm P (NIPAm,co,BMA) and P(NIPAm,co,AAm) copolymer hydrogels were investigated. The drug loading and releasing behaviors for two kinds of model drug with different hydrophilicities were studied. The result shows that the copolymer gels present negative thermo,sensitivities. The lower critical solution temperature (LCST), equilibrium swelling degree and the initial swelling rate increase as the hydrophilicity of gels increases when the temperature is below the LCST. With increasing gel hydrophilicity the loading ratio for sodium salicylate increases, while for salicylic acid, the reverse is observed. The initial drug releasing rate of sodium salicylate and salicylic acid also increase with increasing gel hydrophilicity. The initial drug releasing rate of sodium salicylate is significantly higher than that of salicylic acid. For salicylic acid which is less hydrophilic, the equilibrium releasing ratio at high temperature is lower than that at low temperature while for sodium salicylate which is more hydrophilic, the equilibrium releasing ratio at high temperature is almost the same as that at low temperature. Equilibrium releasing ratios of the three gels are significantly different from each other for salicylic acid when the temperature is below LCST while the equilibrium releasing ratios of the three gels are all 100% for sodium salicylate.

  6. Primary mechanisms of erythrocyte photolysis induced by biological sensitizers and phototoxic drugs

    International Nuclear Information System (INIS)

    The elucidation of the molecular mechanism of photosensitized hemolysis of red blood cells may give important clues to the primary events underlying the phototoxic reactions observed in pathological conditions such as porphyria and induced by photosensitizing drugs. Sensitizers effective in photohemolysis are porphyrins, the tryptophan metabolite kynurenic acid, and phototoxic drugs such as chlorpromazine and demethylchlortetracycline. Utilizing the singlet oxygen quenchers, β-carotene and histidine and the large deuterium effect on the lifetime of singlet oxygen previously described, good evidence of the participation of this excited molecular species in the photohemolysis in the presence of kynurenic acid was obtained. Chlorpromazine and demethylchlortetracycline clearly acted by a non-singlet oxygen pathway. The situation observed with haematoporphyrin was less clear and may have represented a mixed Type I-Type II mechanism. (author)

  7. Novel pH-sensitive polyacetal-based block copolymers for controlled drug delivery

    OpenAIRE

    Kim, Jin-Ki; Garripelli, Vivek Kumar; Jeong, Ui-Hyeon; Park, Jeong-Sook; Repka, Michael A.; Jo, Seongbong

    2010-01-01

    The principal aim of this study was to synthesize and characterize pH-sensitive biodegradable triblock copolymers containing a hydrophobic polyacetal segment for controlled drug delivery. Poly(ethylene glycol)-poly(ethyl glyoxylate)-poly(ethylene glycol) (PEG-PEtG-PEG) triblock copolymers with PEG molecular weights 500 (PEtG-PEG500) and 750 (PEtG-PEG750) were synthesized by PEtG end-capping with methoxy PEG via a carbamate linkage. Synthesized amphiphilic PEG-PEtG-PEG was characterized by 1H-...

  8. [A Case of Drug-Induced Thrombocytopenia Resulting from Sensitivity to Oxaliplatin].

    Science.gov (United States)

    Masuda, Taiki; Nagai, Kagami; Sanada, Katsuya

    2015-11-01

    A 67-year-old man was diagnosed with pulmonary metastasis from advanced transverse colon cancer. Thus, a local resection was performed. Adjuvant chemotherapy with mFOLFOX6 was started. Sixteen courses were carried out without problems. However, he complained of chills and chest discomfort 2 hours after beginning the 17th course of chemotherapy. Laboratory data showed remarkable thrombocytopenia, and platelet-associated IgG level was high. After administration of steroids and platelet transfusions, the platelet count improved. Therefore, we diagnosed drug-induced thrombocytopenia resulting from sensitivity to oxaliplatin (L-OHP). Since then, sLV5FU2 therapy was started, and the patient received the whole adjuvant chemotherapy without problems. Thrombocytopenia resulting from sensitivity to L-OHP is a relatively rare side effect. We herein report this case with a review of the relevant literature. PMID:26805296

  9. Inhibition of anaphylactic histamine release from heterologously sensitized mast cells: differential effects of drugs which interfere with calcium influx.

    OpenAIRE

    Kurose, Masao

    1981-01-01

    Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG) were active irrespective of the time interva...

  10. Antimicrobial sensitivity and frequency of DRUG resistance among bacterial strains isolated from cancer patients

    International Nuclear Information System (INIS)

    Blood stream infections (bacteremia) is potentially life threatening. Concomitant with a change in the incidence and epidemiology of infecting organisms, there has been an increase in resistance to many antibiotic compounds. The widespread emergence of resistance among bacterial pathogens has an impact on our ability to treat patients effectively. The changing spectrum of microbial pathogens and widespread emergence of microbial resistance to antibiotic drugs has emphasized the need to monitor the prevalence of resistance in these strains. In the present study frequency of isolation of clinically significant bacteria and their susceptibility and resistance pattern against a wide range of antimicrobial drugs from positive blood cultures collected during 2001-2003 was studied. A total of 102 consecutive isolates were found with 63% gram positive and 44% gram negative strains. The dominating pathogens were Staphylococcus aureus (51%), Streptococci (31%), Pseudomonas (40%), Proteus (13%), Klebsiella (13%). The isolated strains were tested against a wide range of antibiotics belonging to cephalosporins, aminoglycosides and quinolone derivative group by disk diffusion method. It has been observed that isolated strains among gram positive and negative strains showed different level of resistance against aminoglycosides and cephalosporin group of antibiotics with gram positives showing highest number and frequency of resistance against aminoglycosides (40-50%) and cephalosporins.(35-45%) whereas cephalosporins were found to be more effective against gram negatives with low frequency of resistant strains. Cabapenem and quinolone derivative drugs were found to be most effective among other groups in both gram positive and negative strains with 23-41% strains found sensitive to these two drugs. The frequency of sensitive strains against aminoglycoside and cephalosporin in gram negative and gram positive strains were found to be decreasing yearwise with a trend towards an

  11. Morphology and Drug Release of Ph-Sensitive Microspheres Containing Flavonoids

    Science.gov (United States)

    Paola, Scarfato; Elvira, Avallone; Pio, Lannelli; Rita, Aquino; Domenico, Acierno

    2008-08-01

    In this work we developed pH-sensitive microspherical dosage forms for poorly water soluble flavonoids (quercetin and naringenin) by using Eudragit L100 as enteric polymer. The systems were produced by water in oil (w/o) solvent evaporation method, optimizing the formulation and preparation conditions in order to obtain high encapsulation efficiency and production yield. The synthesized microspheres were characterized in terms of particle size distribution, drug loading, morphology and in vitro release properties. The performed analyses evidenced that the microspheres were free- flowing and spherical in shape, both quercetin and naringenin were microencapsulated in the amorphous state and the drug content was near to the theoretical one. Preliminary in vitro dissolution studies, carried out using a pH-change method, showed that the samples exhibit a typical biphasic drug release trend, due to the pH dependent solubility of the enteric polymers used. In particular, the samples have a fairly gastroresistance followed by an about complete release in simulated intestinal fluid.

  12. Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells.

    Directory of Open Access Journals (Sweden)

    Ayako Nakano

    Full Text Available Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2, KG-1 (ABCB1 and HepG2 cells (ABCB1 and ABCG2. Interestingly, although side population (SP cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG-1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells.

  13. A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids

    International Nuclear Information System (INIS)

    We have characterized some of the physiology of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells. Among the parameters studied were oxygen tension distributions within the spheroid. This was achieved using ultramicroelectrodes with tip diameters of 1-5 mu and a perfusion system whereby environmental conditions such as flow, temperature, and chemical makeup of the milieu could be measured and controlled. Plateau pO/sup 2/ values of less than 10 mm Hg were consistently obtained from spheroids under various conditions. We were able to modify these distributions by use of indirect radiation sensitizer drugs such as mechlorethamine HCl (mustargen) at nontoxic doses. We have also made determinations of the inhibitory capacities of several other drugs on the respiration rate of constituent cells of multicellular spheroids in single-cell suspensions. We have concluded that there are indeed hypoxic cells in spheroids whose radioresistance may be modified by essentially nontoxic levels of indirect radiosensitizer drugs and that the system described shows great promise for screening agents which may modify radiation response

  14. Xylan-based temperature/pH sensitive hydrogels for drug controlled release.

    Science.gov (United States)

    Gao, Cundian; Ren, Junli; Zhao, Cui; Kong, Weiqing; Dai, Qingqing; Chen, Qifeng; Liu, Chuanfu; Sun, Runcang

    2016-10-20

    Xylan-based temperature/pH sensitive hydrogels were prepared by the crosslinking copolymerization of xylan with N-isopropylacrylamide (NIPAm) and acrylic acid (AA) using N,Ń-methylenebis-acrylamide (MBA) as a cross-linker and 2,2-dimethoxy-2-phenylacetophenone as a photoinitiator via ultraviolet irradiation. The influence of the NIPAm, AA and MBA amount on properties of xylan-based hydrogels was discussed. The morphology and interactions of hydrogels were characterized by SEM and FTIR. The lower critical solution temperature (LCST) of hydrogels was investigated by DSC. The results indicated that the LCST of hydrogels emerged at around 34°C and increased with increasing the AA content. The drug encapsulation efficiency of as-prepared hydrogels reached to 97.60% and the cumulative release rate of acetylsalicylic acid was 90.12% and 26.35% in the intestinal and gastric fluid, respectively. Xylan-based hydrogels were proved to be biocompatible with NIH3T3 cell by MTT assay and showed the promising application as drug carriers for the intestinal-targeted oral drug delivery. PMID:27474557

  15. Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy.

    Directory of Open Access Journals (Sweden)

    Zai-Fa Hong

    Full Text Available Cholangiocarcinoma (CCA, a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents. The effect of capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by capsaicin compared with either agent alone. In addition, the combination of capsaicin with 5-FU was synergistic, with a combination index (CI < 1, and the combined treatment also suppressed tumor growth in the CCA xenograft to a greater extent than 5-FU alone. Further investigation revealed that the autophagy induced by 5-FU was inhibited by capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by capsaicin, indicating that capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K/protein kinase B (AKT/mammalian target of rapamycin (mTOR pathway in CCA cells. Taken together, these results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

  16. The Effect of MicroRNA-124 Overexpression on Anti-Tumor Drug Sensitivity.

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    Shiau-Mei Chen

    Full Text Available MicroRNAs play critical roles in regulating various physiological processes, including growth and development. Previous studies have shown that microRNA-124 (miR-124 participates not only in regulation of early neurogenesis but also in suppression of tumorigenesis. In the present study, we found that overexpression of miR-124 was associated with reduced DNA repair capacity in cultured cancer cells and increased sensitivity of cells to DNA-damaging anti-tumor drugs, specifically those that cause the formation of DNA strand-breaks (SBs. We then examined which DNA repair-related genes, particularly the genes of SB repair, were regulated by miR-124. Two SB repair-related genes, encoding ATM interactor (ATMIN and poly (ADP-ribose polymerase 1 (PARP1, were strongly affected by miR-124 overexpression, by binding of miR-124 to the 3¢-untranslated region of their mRNAs. As a result, the capacity of cells to repair DNA SBs, such as those resulting from homologous recombination, was significantly reduced upon miR-124 overexpression. A particularly important therapeutic implication of this finding is that overexpression of miR-124 enhanced cell sensitivity to multiple DNA-damaging agents via ATMIN- and PARP1-mediated mechanisms. The translational relevance of this role of miR-124 in anti-tumor drug sensitivity is suggested by the finding that increased miR-124 expression correlates with better breast cancer prognosis, specifically in patients receiving chemotherapy. These findings suggest that miR-124 could potentially be used as a therapeutic agent to improve the efficacy of chemotherapy with DNA-damaging agents.

  17. A sensitive multidimensional method for the detection, characterization, and quantification of trace free drug species in antibody-drug conjugate samples using mass spectral detection.

    Science.gov (United States)

    Birdsall, Robert E; McCarthy, Sean M; Janin-Bussat, Marie Claire; Perez, Michel; Haeuw, Jean-François; Chen, Weibin; Beck, Alain

    2016-01-01

    Conjugation processes and stability studies associated with the production and shelf life of antibody-drug conjugates (ADCs) can result in free (non-conjugated) drug species. These free drug species can increase the risk to patients and reduce the efficacy of the ADC. Despite stringent purification steps, trace levels of free drug species may be present in formulated ADCs, reducing the therapeutic window. The reduction of sample preparation steps through the incorporation of multidimensional techniques has afforded analysts more efficient methods to assess trace drug species. Multidimensional methods coupling size-exclusion and reversed phase liquid chromatography with ultra-violet detection (SEC-RPLC/UV) have been reported, but offer limited sensitivity and can limit method optimization. The current study addresses these challenges with a multidimensional method that is specific, sensitive, and enables method control in both dimensions via coupling of an on-line solid phase extraction column to RPLC with mass spectral detection (SPE-RPLC/MS). The proposed method was evaluated using an antibody-fluorophore conjugate (AFC) as an ADC surrogate to brentuximab vedotin and its associated parent maleimide-val-cit-DSEA payload and the derived N-acetylcysteine adduct formed during the conjugation process. Assay sensitivity was found to be 2 orders more sensitive using MS detection in comparison to UV-based detection with a nominal limit of quantitation of 0.30 ng/mL (1.5 pg on-column). Free-drug species were present in an unadulterated ADC surrogate sample at concentrations below 7 ng/mL, levels not detectable by UV alone. The proposed SPE-RPLC/MS method provides a high degree of specificity and sensitivity in the assessment of trace free drug species and offers improved control over each dimension, enabling straightforward integration into existing or novel workflows. PMID:26651262

  18. Praziquantel sensitivity of Kenyan Schistosoma mansoni isolates and the generation of a laboratory strain with reduced susceptibility to the drug

    OpenAIRE

    Mwangi, Ibrahim N.; Sanchez, Melissa C.; Mkoji, Gerald M.; Lelo E. Agola; Steven M. Runo; Cupit, Pauline M.; Charles Cunningham

    2014-01-01

    Schistosomiasis is a neglected tropical disease caused by blood-dwelling flukes of the genus Schistosoma. While the disease may affect as many as 249 million people, treatment largely relies on a single drug, praziquantel. The near exclusive use of this drug for such a prevalent disease has led to concerns regarding the potential for drug resistance to arise and the effect this would have on affected populations. In this study, we use an in vitro assay of drug sensitivity to test the effect o...

  19. A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Noushin Davoudi

    Full Text Available Leishmaniasis is a major health problem in some endemic areas and yet, no vaccine is available against any form of the disease. Historically, leishmanization (LZ which is an inoculation of individual with live Leishmania, is the most effective control measure at least against cutaneous leishmaniasis (CL. Due to various reasons, LZ is not used today. Several live attenuated Leishmania have been developed but their use is limited. Previously, we developed a transgenic strain of L. major that harbors two suicide genes tk and cd genes (lmtkcd+/+ for use as a challenge strain in vaccine studies. These genes render the parasite susceptible to Ganciclovir (GCV and 5-flurocytosine (5-FC. The dual drug sensitive strain of L. major was developed using gene targeting technology using a modified Herpes Simplex Virus thymidine kinase gene (hsv-tk sensitive to Ganciclovir antibiotic and Saccharomyces cerevisae cytosine deaminase gene (cd sensitive to 5-flurocytosine that were stably introduced into L. major chromosome. BALB/c mice inoculated with lmtkcd+/+ developed lesions which upon treatment with GCV and 5-FC completely healed. In the current study, the transgenic lmtkcd+/+strain was assessed as a live vaccine model to determine the time necessary to develop a protective immune response. C57BL/6 mice were inoculated with the transgenic lmtkcd+/+strain, and treated at the time of inoculation (day 0 or at day 8 after inoculation. Immunized animals were challenged with wild-type L. major, and complete protection was induced in mice that were treated at day 8. The results show that in contrast to leishmanization, in group of mice inoculated with a dual sensitive L. major development and persistence of lesion is not necessary to induce Th1 response and protection.

  20. Sense and sensitivity: physical limits to multicellular sensing and drug response

    CERN Document Server

    Varennes, Julien

    2015-01-01

    Metastasis is a process of cell migration that can be collective and guided by chemical cues. Viewing metastasis in this way, as a physical phenomenon, allows one to draw upon insights from other studies of collective sensing and migration in cell biology. Here we review recent progress in the study of cell sensing and migration as collective phenomena, including in the context of metastatic cells. We describe simple physical models of sensing and migration, and we survey the experimental evidence that cells operate near the purely physical limits to their behavior. We conclude by contrasting cells' sensory abilities with their sensitivity to drugs, and suggesting potential alternatives to cell-death-based cancer therapies.

  1. Highly Sensitive and Validated Spectrophotometric Technique for the Assay of Some Antidepressant Drugs

    Science.gov (United States)

    Deepakumari, H. N.; Prashanth, M. K.; Kumar, B. C. Vasantha; Revanasiddappa, H. D.

    2015-01-01

    The present paper describes a simple, rapid, reproducible, and highly sensitive spectrophotometric method for the determination of the tricyclic antidepressant drugs: amitriptyline hydrochloride (AMT), imipramine hydrochloride (IMH), clomipramine hydrochloride (CPH) and desipramine hydrochloride (DPH) in pure and in pharmaceutical preparations. The method is based on the bromination of the above drugs with known excess of bromine. The unreacted bromine is determined based on its ability to bleach the dye methyl red quantitatively at 520 nm. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration range 0.0-2.5, 0-1.4, 0-1.4, and 0-1.0 μg/ml for AMT, IMH, CPH, and DPH, respectively. The molar absorptivity values were found to be 0.65 × 105, 1.41 × 105, 1.93 × 105, and 2.96 × 105l/mol/cm, with the corresponding Sandell's sensitivity values were 0.0048, 0.0022, 0.0018, and 0.0010 μg/cm2 for AMT, IMH, CPH, and DPH, respectively. The limits of detection (LOD) and quantification (LOQ) are also reported for the developed method. Intra- and inter-day accuracy and precision was established according to the current ICH guidelines. Application of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the proposed method was confirmed by applying the standard addition technique, and the results obtained are in good agreement with those obtained by the official method.

  2. Microflora of conjunctiva in children and its sensitivity and resistance to antibacterial drugs

    Directory of Open Access Journals (Sweden)

    T. N. Vorontsova

    2012-01-01

    Full Text Available Purpose: Investigation of microflora of conjunctiva and its resistance to antibacterial drugs in healthy children and patients with various inflammatory eye diseases.Methods: We examined 402 children (421 eyes in the age from 1 month till 17 years: 62 healthy children (70 eyes and 340 pa- tients with different inflammatory diseases of anterior segment of eye (351 eyes. the smear was done in all children for plating and definition of sensitivity of microflora to antibacterial drugs by method of diffusion to agar.Results: the plating was positive even in 72.9% of healthy children who entered the hospital for the planned surgery. Most often we revealed Staphylococcus epidermidis (44.3%, Staphylococcus aureus (12.8%, Streptococcus faecalis (5.7% and Enterobacter (2.9%. In children with inflammatory diseases Staphylococcus epidermidis and Staphylococcus aureus (62.6% were found fre- quently. the analysis of data showed high level of resistance of all microflora to aminoglycosides (neomycin 37.8% and tobramycin 32.7% and chloramphenicol — 37.1%. the lowest resistance of all microflora was registered to levofloxacin (11.1% and ciprofloxacin (10.5%. In gram-negative microflora we revealed the maximal sensitivity to ciprofloxacin, in gram-positive — to levofloxacin.We detected the maximal resistance of microflora to ampicillin (66.1%, and minimal — to cephalosporines (4.5% among the antibiotics of systemic application.Conclusion: the findings allow us to recommend drops containing levofloxacin (Signicef for clinical practice in pediatric ophthalmology. 

  3. SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets.

    Science.gov (United States)

    Guo, Jing; Liu, Hui; Zheng, Jie

    2016-01-01

    Synthetic lethality (SL) is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. SL reflects the biologically endogenous difference between cancer cells and normal cells, and thus the inhibition of SL partners of genes with cancer-specific mutations could selectively kill cancer cells but spare normal cells. Therefore, SL is emerging as a promising anticancer strategy that could potentially overcome the drawbacks of traditional chemotherapies by reducing severe side effects. Researchers have developed experimental technologies and computational prediction methods to identify SL gene pairs on human and a few model species. However, there has not been a comprehensive database dedicated to collecting SL pairs and related knowledge. In this paper, we propose a comprehensive database, SynLethDB (http://histone.sce.ntu.edu.sg/SynLethDB/), which contains SL pairs collected from biochemical assays, other related databases, computational predictions and text mining results on human and four model species, i.e. mouse, fruit fly, worm and yeast. For each SL pair, a confidence score was calculated by integrating individual scores derived from different evidence sources. We also developed a statistical analysis module to estimate the druggability and sensitivity of cancer cells upon drug treatments targeting human SL partners, based on large-scale genomic data, gene expression profiles and drug sensitivity profiles on more than 1000 cancer cell lines. To help users access and mine the wealth of the data, we developed other practical functionalities, such as search and filtering, orthology search, gene set enrichment analysis. Furthermore, a user-friendly web interface has been implemented to facilitate data analysis and interpretation. With the integrated data sets and analytics functionalities, SynLethDB would

  4. Construction of a novel pH-sensitive drug release system from mesoporous silica tablets coated with Eudragit

    Science.gov (United States)

    Xu, Yingpu; Qu, Fengyu; Wang, Yu; Lin, Huiming; Wu, Xiang; Jin, Yingxue

    2011-03-01

    A novel pH-sensitive drug release system has been established by coating Eudragit (Eud) on drug-loaded mesoporous silica (MS) tablets. The release rate of ibuprofen (IBU) from the MS was retarded by coating with Eudragit S-100, and the higher retardation was due to the increase of coating concentration and the coating layers. The target position of the release depended on the pH of the release medium, which was confirmed by the drug release from IBU/MS/Eud increasing rapidly with the change of medium pH from 1.2 to 7.4. This drug delivery system could prohibit irritant drug from leaking in the stomach and make it only release in the intestine. The loaded and unloaded drug samples were characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectrometer (FTIR), N 2 adsorption/desorption, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

  5. [Sensitivity of clinical strains of facultatively anaerobic bacteria to antimicrobial drugs].

    Science.gov (United States)

    Bazhenov, L G; Iskhakova, Kh I

    1988-02-01

    Six hundred and sixty five samples of clinical materials from patients with various pyoinflammatory diseases were tested for obligatory anaerobes. Anaerobes were detected in 148 samples which amounted to 22.3 per cent of the total number of the samples and to 33.2 per cent of the samples with microbial growth. A total of 171 strains of obligatory anaerobes were isolated. Among them 58.5, 24.5, 16.4 and 0.6 per cent were nonsporulating gramnegative bacilli, grampositive cocci, grampositive bacilli and gramnegative cocci respectively. Sensitivity of the isolated anaerobes was tested with the disk diffusion method. The most active drugs against the tested strains were: nitroxoline, rifampicin, metronidasole, erythromycin, carbenicillin and cefotaxim (4.2, 4.5, 9.3, 10.6, 11.5 and 11.7 per cent of the resistant strains respectively). Gentamicin, polymyxin M, novobiocin and cefazoline were the least active drugs (94.6, 78.9, 65.4 and 50.0 per cent of the resistant strains respectively). Metronidasole, levomycetin, nitroxolin, rifampicin and furazolidone showed the highest activity against bacteroids of the fragilis group (0, 0, 0, 8 and 12.5 per cent of the resistant strains respectively) while gentamicin, polymyxin M, cefazolin, oxacillin, novobiocin and penicillin showed the lowest activity (100, 100, 100, 100, 87.0 and 66.7 per cent of the resistant strains respectively). PMID:3377601

  6. A simple and sensitive spectrofluorimetric method for analysis of some nitrofuran drugs in pharmaceutical preparations.

    Science.gov (United States)

    Belal, Tarek Saied

    2008-09-01

    A simple, rapid, selective and sensitive spectrofluorimetric method was described for the analysis of three nitrofuran drugs, namely, nifuroxazide (NX), nitrofurantoin (NT) and nitrofurazone (NZ). The method involved the alkaline hydrolysis of the studied drugs by warming with 0.1 M sodium hydroxide solution then dilution with distilled water for NX or 2-propanol for NT and NZ. The formed fluorophores were measured at 465 nm (lambda (Ex) 265 nm), 458 nm (lambda (Ex) 245 nm) and 445 nm (lambda (Ex) 245 nm) for NX, NT and NZ, respectively. The reaction pathway was discussed and the structures of the fluorescent products were proposed. The different experimental parameters were studied and optimized. Regression analysis showed good correlation between fluorescence intensity and concentration over the ranges 0.08-1.00, 0.02-0.24 and 0.004-0.050 microg ml(-1) for NX, NT and NZ, respectively. The limits of detection of the method were 8.0, 1.9 and 0.3 ng ml(-1) for NX, NT and NZ, respectively. The proposed method was validated in terms of accuracy, precision and specificity, and it was successfully applied for the assay of the three nitrofurans in their different dosage forms. No interference was observed from common pharmaceutical adjuvants. The results were favorably compared with those obtained by reference spectrophotometric methods. PMID:18246413

  7. Highly sensitive quantitative imaging for monitoring single cancer cell growth kinetics and drug response.

    Directory of Open Access Journals (Sweden)

    Mustafa Mir

    Full Text Available The detection and treatment of cancer has advanced significantly in the past several decades, with important improvements in our understanding of the fundamental molecular and genetic basis of the disease. Despite these advancements, drug-screening methodologies have remained essentially unchanged since the introduction of the in vitro human cell line screen in 1990. Although the existing methods provide information on the overall effects of compounds on cell viability, they are restricted by bulk measurements, large sample sizes, and lack capability to measure proliferation kinetics at the individual cell level. To truly understand the nature of cancer cell proliferation and to develop personalized adjuvant therapies, there is a need for new methodologies that provide quantitative information to monitor the effect of drugs on cell growth as well as morphological and phenotypic changes at the single cell level. Here we show that a quantitative phase imaging modality known as spatial light interference microscopy (SLIM addresses these needs and provides additional advantages over existing proliferation assays. We demonstrate these capabilities through measurements on the effects of the hormone estradiol and the antiestrogen ICI182,780 (Faslodex on the growth of MCF-7 breast cancer cells. Along with providing information on changes in the overall growth, SLIM provides additional biologically relevant information. For example, we find that exposure to estradiol results in rapidly growing cells with lower dry mass than the control population. Subsequently blocking the estrogen receptor with ICI results in slower growing cells, with lower dry masses than the control. This ability to measure changes in growth kinetics in response to environmental conditions provides new insight on growth regulation mechanisms. Our results establish the capabilities of SLIM as an advanced drug screening technology that provides information on changes in proliferation

  8. pH sensitive core-shell magnetic nanoparticles for targeted drug delivery in cancer therapy.

    Science.gov (United States)

    Lungu, Iulia Ioana; Rădulescu, Marius; Mogoşanu, George Dan; Grumezescu, Alexandru Mihai

    2016-01-01

    In the last decade, nanobiotechnology has evolved rapidly with an extensive impact on biomedical area. In order to improve bioavailability and minimize adverse effects, drug delivery systems based on magnetic nanocomposites are under development mainly for cancer imaging and antitumor therapy. In this regard, pH sensitive core-shell magnetic nanoparticles (NPs) with accurate controlled size and shape are synthesized by various modern methods, such as homogeneous precipitation, coprecipitation, microemulsion or polyol approaches, high temperature and hydrothermal reactions, sol-gel reactions, aerosol÷vapor processes and sonolysis. Due to their unique combined physico-chemical and biological properties (such as higher dispensability, chemical and thermal stability, biocompatibility), pH responsive core-shell magnetic NPs are widely investigated for controlled release of cytostatic drugs into the tumor site by means of pH change: magnetite@silicon dioxide (Fe3O4@SiO2), Fe3O4@titanium dioxide (TiO2), β-thiopropionate-polyethylene glycol (PEG)-modified Fe3O4@mSiO2, Fe3O4 NPs core coated with SiO2 with an imidazole group modified PEG-polypeptide (mPEG-poly-L-Asparagine), polyacrylic acid (PAA) and folic acid (FA) coating of the iron oxide NP core, methoxy polyethylene glycol-block-polymethacrylic acid-block-polyglycerol monomethacrylate (MPEG-b-PMAA-b-PGMA) attached by a PGMA block to a Fe3O4 core, PEG-modified polyamidoamine (PAMAM) dendrimer shell with Fe3O4 core and mesoporous silica coated on Fe3O4, mostly coated with an anticancer drug. This review paper highlights the modern research directions currently employed to demonstrate the utility of the pH responsive core-shell magnetic NPs in diagnosis and treatment of oncological diseases. PMID:27151685

  9. In vitro inhibition of drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis by ethnobotanically selected South African plants.

    Science.gov (United States)

    Lall, N; Meyer, J J

    1999-09-01

    Twenty South African medicinal plants used to treat pulmonary diseases were screened for activity against drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis. A preliminary screening of acetone and water plant extracts against a drug-sensitive strain of Mycobacterium tuberculosis, H37Rv, was done by the agar plate method. Fourteen of the 20 acetone extracts showed inhibitory activity at a concentration of 0.5 mg/ml against this strain. Acetone as well as water extracts of Cryptocarya latifolia, Euclea natalensis, Helichrysum melanacme, Nidorella anomala and Thymus vulgaris inhibited the growth of M. tuberculosis. Given the activity of 14 acetone extracts at 0.5 mg/ml against the drug-sensitive strain by the agar plate method, a further study was done employing a rapid radiometric method to confirm the inhibitory activity. These active acetone extracts were screened against the H37Rv strain as well as a strain resistant to the drugs isoniazid and rifampin. The minimal inhibitory concentration of Croton pseudopulchellus, Ekebergia capensis, Euclea natalensis, Nidorella anomala and Polygala myrtifolia was 0.1 mg/ml against the H37Rv strain by the radiometric method. Extracts of Chenopodium ambrosioides, Ekebergia capensis, Euclea natalensis, Helichrysum melanacme, Nidorella anomala and Polygala myrtifolia were active against the resistant strain at 0.1 mg/ml. Eight plants showed activity against both strains at a concentration of 1.0 mg/ml. PMID:10473184

  10. Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Paula I. Moreira

    2009-12-01

    Full Text Available Insulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic and a connection between insulin signaling dysregulation, cognitive decline and dementia has been established. Mitochondria are intracellular organelles that despite playing a critical role in cellular metabolism are also one of the major sources of reactive oxygen species. Mitochondrial dysfunction, oxidative stress and neuroinflammation, hallmarks of neurodegeneration, can result from impaired insulin signaling. Insulin-sensitizing drugs such as the thiazolidinediones are a new class of synthetic compounds that potentiate insulin action in the target tissues and act as specific agonists of the peroxisome proliferator-activated receptor gamma (PPAR-γ. Recently, several PPAR agonists have been proposed as novel and possible therapeutic agents for neurodegenerative disorders. Indeed, the literature shows that these agents are able to protect against mitochondrial dysfunction, oxidative damage, inflammation and apoptosis. This review discusses the role of mitochondria and insulin signaling in normal brain function and in neurodegeneration. Furthermore, the potential protective role of insulin and insulin sensitizers in Alzheimer´s, Parkinson´s and Huntington´s diseases and amyotrophic lateral sclerosis will be also discussed.

  11. Utilização dos registros de dispensação da farmácia como indicador da não-adesão à terapia anti-retroviral em indivíduos infectados pelo HIV Pharmacy records as an indicator of non-adherence to antiretroviral therapy by HIV-infected patients

    Directory of Open Access Journals (Sweden)

    Raquel Regina de Freitas Magalhães Gomes

    2009-03-01

    Full Text Available Este estudo teve como objetivos avaliar os registros de dispensação de anti-retrovirais (ARV por um período de 12 meses após a primeira prescrição e determinar os fatores associados com a retirada irregular ou abandono em dois serviços públicos de referência para AIDS, em Belo Horizonte, Minas Gerais, Brasil. Participaram 323 pacientes infectados pelo HIV, virgens de tratamento, recrutados entre maio de 2001 e maio de 2002. No período, 98 (30,3% pacientes abandonaram a terapia e 187 (57,9% tiveram pelo menos uma retirada irregular. Indivíduos com retirada irregular ou que abandonaram a terapia foram comparados àqueles com retirada regular. Análise multivariada multinomial indicou que morar fora de Belo Horizonte, ter contagem de linfócitos TCD4+ maior que 200 células/mm³ e uso de esquema sem inibidor de protease estavam associados com retirada irregular. Além dessas variáveis, o abandono mostrou associação com não fazer uso de outra medicação e ter registro de não-adesão no prontuário médico. Os registros da farmácia destacaram-se como potencial indicador de não-adesão, devendo ser incorporados à prática clínica. Ações que busquem os pacientes ausentes ou com retirada irregular devem ser priorizadas.The objectives of this study were to evaluate anti-retroviral (ARV prescription pickups during twelve months following the first prescription and to identify factors associated with irregular pickups or permanent dropout in two public HIV/AIDS referral centers in Belo Horizonte, Minas Gerais State, Brazil. Participants (n = 323 were antiretroviral naïve and were recruited from May 2001 to May 2002. A total of 98 (30.3% patients abandoned treatment, and 187 (57.9% had at least one irregular pickup. Patients with irregular pickups and dropouts were compared to those with regular pickups. Multinomial multivariate analysis showed that living outside Belo Horizonte, CD4+ T-lymphocyte count greater than 200/mm³, and

  12. High mobility group A1 protein expression reduces the sensitivity of colon and thyroid cancer cells to antineoplastic drugs

    OpenAIRE

    D’Angelo, Daniela; Mussnich, Paula; De Rosa, Roberta; Bianco, Roberto; Tortora, Giampaolo; Fusco, Alfredo

    2014-01-01

    Background Development of resistance to conventional drugs and novel biological agents often impair long-term chemotherapy. HMGA gene overexpression is often associated with antineoplastic drug resistance and reduced survival. Inhibition of HMGA expression in thyroid cancer cells reduces levels of ATM protein, the main cellular sensor of DNA damage, and enhances cellular sensitivity to DNA-damaging agents. HMGA1 overexpression promotes chemoresistance to gemcitabine in pancreatic adenocarcino...

  13. Novel multifunctional pH-sensitive nanoparticles loaded into microbubbles as drug delivery vehicles for enhanced tumor targeting.

    Science.gov (United States)

    Lv, Yongjiu; Hao, Lan; Hu, Wenjing; Ran, Ya; Bai, Yan; Zhang, Liangke

    2016-01-01

    This study fabricated novel multifunctional pH-sensitive nanoparticles loaded into microbubbles (PNP-MB) with the combined advantages of two excellent drug delivery vehicles, namely, pH-sensitive nanoparticles and microbubbles. As an antitumor drug, resveratrol (RES) was loaded into acetylated β-cyclodextrin nanoparticles (RES-PNP). The drug-loaded nanoparticles were then encapsulated into the internal space of the microbubbles. The characterization and morphology of this vehicle were investigated through dynamic light scattering and confocal laser scanning microscopy, respectively. In vitro drug release was performed to investigate the pH sensitivity of RES-PNP. The antitumor property of RES-loaded PNP-MB (RES-PNP-MB) was also analyzed in vivo to evaluate the antitumor effect of RES-PNP-MB. Results suggested that PNP exhibited pH sensitivity, and was successfully encapsulated into the microbubbles. RES-PNP-MB exhibit effective tumor growth suppressing in vivo. Therefore, such drug delivery vehicle should be of great attention in tumor therapy. PMID:27378018

  14. Haemophilus paragallinarum in chickens in Indonesia: III. Antimicrobial drug sensitivity test ofHaemophilus paragallinarum from chickens suffering of coryza

    OpenAIRE

    Sri Poernomo; Sutarma Sutarma; Sang Ayu Ketut Dewi Silawatri

    1998-01-01

    An agar disc diffusion method was used to examine the sensitivity of 27 Haemophilus paragallinarum (Hpg) isolates consisted of 23 local isolates, 4 standard isolates (serotype A) and Escherichia coli ATCC 24922 as a control to eight antimicrobial drugs (ampicillin, erythromycin, oxytetracycline, doxycycline, neomycin, streptomycin, colistine and sulphanlethoxazole-trimethoprim) . Twenty one out of 23 local isolates of Hpg were sensitive to doxycycline, 19 isolates to ampsllin, 18 isolates to ...

  15. A Genomewide Screen in Schizosaccharomyces pombe for Genes Affecting the Sensitivity of Antifungal Drugs That Target Ergosterol Biosynthesis

    OpenAIRE

    Fang, Yue; Hu, Lingling; Zhou, Xin; Jaiseng, Wurentuya; Zhang, Ben; Takami, Tomonori; Kuno, Takayoshi

    2012-01-01

    We performed a genomewide screen for altered sensitivity to antifungal drugs, including clotrimazole and terbinafine, that target ergosterol biosynthesis using a Schizosaccharomyces pombe gene deletion library consisting of 3,004 nonessential haploid deletion mutants. We identified 109 mutants that were hypersensitive and 11 mutants that were resistant to these antifungals. Proteins whose absence rendered cells sensitive to these antifungals were classified into various functional categories,...

  16. The role of impulsivity in the aetiology of drug dependence: reward sensitivity versus automaticity

    OpenAIRE

    Hogarth, Lee

    2011-01-01

    Rationale Impulsivity has long been known as a risk factor for drug dependence, but the mechanisms underpinning this association are unclear. Impulsivity may confer hypersensitivity to drug reinforcement which establishes higher rates of instrumental drug-seeking and drug-taking behaviour, or may confer a propensity for automatic (non-intentional) control over drug-seeking/taking and thus intransigence to clinical intervention. Method The current study sought to distinguish these two accounts...

  17. Overexpression of Bax induces apoptosis and enhances drug sensitivity of hepatocellular cancer-9204 cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Yong Zheng; Guang-Shun Yang; Wei-Zhong Wang; Jiang Li; Kai-Zong Li; Wen-Xian Guan; Wen-Liang Wang

    2005-01-01

    AIM: To investigate the role of overexpression of Bax in apoptotic pathways and the response of human hepatocellular cancer (HCC)-9204 cells to cell death induced by adriamycin.METHODS: The whole length of Bax cDNA was transfectrd into human HCC-9204 cells by the method of lipofectamine transfection. An inducible MT-Ⅱ regulatory system was constructed, which allowed controlled expression of protein upon addition of ZnSO4 (100 μmol/L) as an external inducer. Stable transfecting inducible expression vector containing Bax gene was performed. Expression of Bax in protein was analyzed by immunohistochemistry and Western blotting. TUNEL and flow cytometry were used to assess the effect of Bax on apoptosis. Colony assay and tetrazolium blue (MTT) assay were used to evaluate the difference in drug sensitivity of HCC-9204 cells after Bax-transfection.RESULTS: Immunohistochemistry and Western blotting demonstrated that the expression of Bax protein markedly increased in Bax-transfected cells 4 h after the addition cytoplasm and perinuclear region of HCC-9404 cells, and there was ectopic expression in cells with marked condensation of chromatin and cytoplasm (apoptotic cells). Apoptotic index significantly increased in Bax-transfected HCC-9204/Bax cells (3.6 vs 27.2, 4.2 vs 32.3, P<0.05).Flow cytometry analysis showed a significant sub-G1 peak and apoptosis in 15.4% HCC-9204/Bax cells 24 h after treatment. Furthermore, colony survival rate decreased from 66% (HCC-9204/pMD) to 45% (HCC-9204/Bax) 2 dafter ADR withdrawal. MTT assay result showed that the effects of Bax on cell viability following ADR exposure were significant as compared to the vehicle-transfected HCC-9204/pMD cells (21% vs 44%, P<0.01).CONCLUSION: Overexpression of Bax not only induces apoptosis, but also sensitizes HCC-9204 cells to cell death induced by adriamycin.

  18. Design and synthesis of pH-sensitive polymeric micelles for oral delivery of poorly water-soluble drugs.

    Science.gov (United States)

    Yang, Xiaolan; Fan, Rongrong; Wang, Wenlong; Wang, Jiexin; Le, Yuan

    2016-09-01

    pH-sensitive polymer poly (polylactide-co-methacrylic acid)-b-poly (acrylic acid) was synthesized using atom transfer radical polymerization and ring-opening polymerization and characterized by gel permeation chromatography and (1)H NMR. The polymers can self-assemble to form micelles in aqueous medium, which respond rapidly to pH change within the gastrointestinal relevant pH range. Critical micelle concentrations and pH response behavior of the polymeric micelle were investigated. Water-insoluble drug nifedipine was loaded and the drug-loading content can be controlled by tuning the composition of the polymers. The in vitro release studies indicate pH sensitivity enabled rapid drug release at the environment of simulated intestinal fluid (pH 7.36), the cumulative released amount of NFD reached more than 80% within 24 h, while only 35% in the simulated gastric fluid (pH 1.35). All the results showed that the pH-sensitive P(PLAMA-co-MAA)-b-PAA micelle may be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior. PMID:27342342

  19. Peroxiredoxin 1 knockdown sensitizes cancer cells to reactive oxygen species-generating drugs - an alternative approach for chemotherapy.

    Science.gov (United States)

    He, Tiantian; Hatem, Elie; Vernis, Laurence; Huang, Meng-Er

    2014-10-01

    Peroxiredoxins have multiple cellular functions as major antioxidants, signaling regulators and tumor suppressors. Peroxiredoxin 1 (PRX1) is the most abundant among the six isoforms of human peroxiredoxins, catalyzing the reduction of peroxides utilizing thioredoxin 1as an electron donor. PRX1 is frequently over-expressed in various cancer cells, which is thought to be associated with carcinogenesis, metastasis and resistance to radiotherapy or chemotherapy. We investigated how modulations of intracellular redox system, especially PRX1, affect cancer cell sensitivity to reactive oxygen species (ROS)-generating drugs. We observed that stable and transient Prx1 knockdown (Prx1-) significantly enhances HeLa cell sensitivity to β-lapachone (β-lap), a potential anticancer agent, and to other ROS-generating molecules. ROS accumulation played a crucial role in drug-enhanced Prx1- cell death. For β-lap, Prx1- cells sensitization is achieved through combined action of accumulation of ROS and enhancement of mitogen-activated protein kinase pathway activation. The effect of other ROS-inducing drugs on Prx1- cell survival will also be presented and discussed. Taken together, our data provide evidence that PRX1 could be an interesting anticancer target and modulation of intracellular redox states through PRX1 inhibition could be an alternative approach to enhance cancer cell sensitivity to ROS-generating drugs. PMID:26461286

  20. Swelling characteristics of hydroxyethylmethacrylate/ methacrylic acid pH -sensitive hydrogel as a drug delivery system

    Directory of Open Access Journals (Sweden)

    M. Falamarzian- J. Varshosaz

    1996-08-01

    Full Text Available Hydroxyethyl methacrylate /methacrylic acid (HEMA/MAA copolymer cross-linked with ethylenglycol dimethacrylate was prepared by a bulk.free radical polymerization method. The results indicate that this polymer is a pH -sensitive hydrogel which is collapsed in the acidic medium but completely swollen in the alkaline and neutral pH . it was determined that a proportion of 40% of MAA, the ionizing monomer of this hydrogel, was the best concentration among the different percentages used which showed a non-Fickian water transport mechanism. Increasing MAA content from 20 to 70% was accompanied with a change in water transport mechanism from Fickian to non-Fickian. However, increasing the percentage of MAA from 40 to 70 didn't improve the swelling capacity of this polymer. Pore size determination by a solute exclusion technique, showed the greatest distribution in the hydrogel with 40% MAA compared to other percentages of this monomer used. About 75% of the pores were less than 16.5 A in diameter in this polymer which is important specially in loading the hydrogel with macromoiecular drugs like proteines.

  1. Functionalized chalcones with basic functionalities have antibacterial activity against drug sensitive Staphylococcus aureus.

    Science.gov (United States)

    Liu, X L; Xu, Y J; Go, M L

    2008-08-01

    A library of chalcones with basic functionalities were evaluated for antibacterial activity against drug sensitive strains of Staphylococcus aureus and Escherichia coli. The most active compounds were 2-52 and 2-57 (MIC 6.3 microM S. aureus). These compounds had no activity against E. coli (MIC>100 microM). Both compounds were characterized by a ring A that was substituted with 2-hydroxy-4,6-dimethoxy-3-(1-methylpiperidin-4-yl) groups. The phenolic OH and 1-methylpiperidinyl groups were required for activity but the phenolic OH may play a more critical role. While the compounds were comparable to licochalcone A in terms of antibacterial activity, they caused less hemolysis of sheep erythrocytes at high concentrations (100 microM). It was noted that the structural requirements for limiting hemolytic activity were less stringent than those required for antibacterial activity. The present findings suggest that the chalcone framework is an attractive template for optimization to achieve better potency, lower toxicity and a wider spectrum of antibacterial activity. PMID:18031869

  2. Aerosol-Assisted Fast Formulating Uniform Pharmaceutical Polymer Microparticles with Variable Properties toward pH-Sensitive Controlled Drug Release

    Directory of Open Access Journals (Sweden)

    Hong Lei

    2016-05-01

    Full Text Available Microencapsulation is highly attractive for oral drug delivery. Microparticles are a common form of drug carrier for this purpose. There is still a high demand on efficient methods to fabricate microparticles with uniform sizes and well-controlled particle properties. In this paper, uniform hydroxypropyl methylcellulose phthalate (HPMCP-based pharmaceutical microparticles loaded with either hydrophobic or hydrophilic model drugs have been directly formulated by using a unique aerosol technique, i.e., the microfluidic spray drying technology. A series of microparticles of controllable particle sizes, shapes, and structures are fabricated by tuning the solvent composition and drying temperature. It is found that a more volatile solvent and a higher drying temperature can result in fast evaporation rates to form microparticles of larger lateral size, more irregular shape, and denser matrix. The nature of the model drugs also plays an important role in determining particle properties. The drug release behaviors of the pharmaceutical microparticles are dependent on their structural properties and the nature of a specific drug, as well as sensitive to the pH value of the release medium. Most importantly, drugs in the microparticles obtained by using a more volatile solvent or a higher drying temperature can be well protected from degradation in harsh simulated gastric fluids due to the dense structures of the microparticles, while they can be fast-released in simulated intestinal fluids through particle dissolution. These pharmaceutical microparticles are potentially useful for site-specific (enteric delivery of orally-administered drugs.

  3. Imipramine is an orally active drug against both antimony sensitive and resistant Leishmania donovani clinical isolates in experimental infection.

    Directory of Open Access Journals (Sweden)

    Sandip Mukherjee

    Full Text Available BACKGROUND: In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the drug is highly active against antimony sensitive and resistant Leishmania donovani in both promastigotes and intracellular amastigotes and in LD infected hamster model. The drug was found to decrease the mitochondrial transmembrane potential of Leishmania donovani (LD promastigotes and purified amastigotes after 8 h of treatment, whereas miltefosine effected only a marginal change even after 24 h. The drug restores defective antigen presenting ability of the parasitized macrophages. The status of the host protective factors TNF α, IFN γ and iNOS activity increased with the concomitant decrease in IL 10 and TGF β level in imipramine treated infected hamsters and evolution of matured sterile hepatic granuloma. The 10-day therapeutic window as a monotherapy, showing about 90% clearance of organ parasites in infected hamsters regardless of their SSG sensitivity. CONCLUSIONS: This study showed that imipramine possibly qualifies for a new use of an old drug and can be used as an effective orally active drug for the treatment of Kala-azar.

  4. Single-cell analysis of targeted transcriptome predicts drug sensitivity of single cells within human myeloma tumors.

    Science.gov (United States)

    Mitra, A K; Mukherjee, U K; Harding, T; Jang, J S; Stessman, H; Li, Y; Abyzov, A; Jen, J; Kumar, S; Rajkumar, V; Van Ness, B

    2016-05-01

    Multiple myeloma (MM) is characterized by significant genetic diversity at subclonal levels that have a defining role in the heterogeneity of tumor progression, clinical aggressiveness and drug sensitivity. Although genome profiling studies have demonstrated heterogeneity in subclonal architecture that may ultimately lead to relapse, a gene expression-based prediction program that can identify, distinguish and quantify drug response in sub-populations within a bulk population of myeloma cells is lacking. In this study, we performed targeted transcriptome analysis on 528 pre-treatment single cells from 11 myeloma cell lines and 418 single cells from 8 drug-naïve MM patients, followed by intensive bioinformatics and statistical analysis for prediction of proteasome inhibitor sensitivity in individual cells. Using our previously reported drug response gene expression profile signature at the single-cell level, we developed an R Statistical analysis package available at https://github.com/bvnlabSCATTome, SCATTome (single-cell analysis of targeted transcriptome), that restructures the data obtained from Fluidigm single-cell quantitative real-time-PCR analysis run, filters missing data, performs scaling of filtered data, builds classification models and predicts drug response of individual cells based on targeted transcriptome using an assortment of machine learning methods. Application of SCATT should contribute to clinically relevant analysis of intratumor heterogeneity, and better inform drug choices based on subclonal cellular responses. PMID:26710886

  5. Development and Application of Zirconia Coated Paper Substrate for High Sensitivity Analysis of Therapeutic Drugs in Dried Blood Spots.

    Science.gov (United States)

    Zheng, Yajun; Wang, Qian; Wang, Xiaoting; Chen, Ying; Wang, Xuan; Zhang, Xiaoling; Bai, Zongquan; Han, Xiaoxiao; Zhang, Zhiping

    2016-07-19

    Paper spray mass spectrometry has been demonstrated to be promising for direct analysis of therapeutic drugs in dried blood spots (DBS); however, the strong hydrogen bond and van de Waals interactions between paper substrate and analytes containing polar functional groups (e.g., therapeutic drugs) affect greatly the elution behavior and analysis sensitivity of compounds of interest during paper spray. Herein, we developed a one-sided ZrO2 coated paper substrate through a facile vacuum filtration approach using commercial ZrO2 particles as coating material and soluble starch as adhesive agent. Owing to the unique surface properties, as-prepared ZrO2 paper substrate has been shown to have excellent performance for analysis of therapeutic drugs in DBS during paper spray mass spectrometry. In contrast to original cellulose paper substrates, improvements of 43-189-fold in lower limit of quantitation (LLOQ) were obtained for the tested drugs using ZrO2 coated paper for paper spray. In comparing with the previously reported grade SG81 paper and one-sided silica coated paper, the LLOQs of the tested drugs with as-prepared ZrO2 paper decreased 1.5-16.5-fold relative to those from the above two, revealing that ZrO2 coated paper is a good candidate for paper spray in high sensitivity analysis of therapeutic drugs in DBS. PMID:27314839

  6. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    Directory of Open Access Journals (Sweden)

    Taylor David J

    2011-11-01

    Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

  7. New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hui-Kang [DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006 (China)

    2014-08-01

    For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential. - Graphical abstract: New amphiphilic glycopolypeptide conjugate containing the disulfide bond could self-assemble in aqueous solution into reduction-sensitive micelles for triggered release of an anticancer drug (methotrexate, MTX) in the presence of 10 mM 1,4-dithio-DL-threitol (DTT). - Highlights: • Amphiphilic glycopolypeptide conjugate containing disulfide bond was prepared. • Such a conjugate self assembled in aqueous solution into nanosize micelles. • The resultant micelles could encapsulate effectively methotrexate drug. • The drug-loaded micelles showed a reduction-sensitive drug release behavior.

  8. New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release

    International Nuclear Information System (INIS)

    For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential. - Graphical abstract: New amphiphilic glycopolypeptide conjugate containing the disulfide bond could self-assemble in aqueous solution into reduction-sensitive micelles for triggered release of an anticancer drug (methotrexate, MTX) in the presence of 10 mM 1,4-dithio-DL-threitol (DTT). - Highlights: • Amphiphilic glycopolypeptide conjugate containing disulfide bond was prepared. • Such a conjugate self assembled in aqueous solution into nanosize micelles. • The resultant micelles could encapsulate effectively methotrexate drug. • The drug-loaded micelles showed a reduction-sensitive drug release behavior

  9. Anticancer drug sensitivity prediction in cell lines from baseline gene expression through recursive feature selection

    OpenAIRE

    Dong, Zuoli; Zhang, Naiqian; Li, Chun; Wang, Haiyun; Fang, Yun; Wang, Jun; Zheng, Xiaoqi

    2015-01-01

    Background An enduring challenge in personalized medicine is to select right drug for individual patients. Testing drugs on patients in large clinical trials is one way to assess their efficacy and toxicity, but it is impractical to test hundreds of drugs currently under development. Therefore the preclinical prediction model is highly expected as it enables prediction of drug response to hundreds of cell lines in parallel. Methods Recently, two large-scale pharmacogenomic studies screened mu...

  10. Cell-specific intracellular anticancer drug delivery from mesoporous silica nanoparticles with pH sensitivity.

    Science.gov (United States)

    Luo, Zhong; Cai, Kaiyong; Hu, Yan; Zhang, Beilu; Xu, Dawei

    2012-05-01

    A nanoreservoir for efficient intracellular anticancer drug delivery based on mesoporous silica nanoparticles end-capped with lactobionic acid-grafted bovine serum albumin is fabricated. It demonstrates great potential for both cell-specific endocytosis and intracellular pH-responsive controlled release of drugs. A possible endocytosis pathway/mechanism of the smart controlled drug release system is proposed. PMID:23184747

  11. Development of a glucose-sensitive drug delivery device: Microencapsulated liposomes and poly(2-ethylacrylic acid)

    Science.gov (United States)

    Kanokpanont, Sorada

    The current study is the development a self-regulated, glucose responsive drug delivery system, using dioleoylphosphatidylcholine (DOPC) liposomes, a pH sensitive polymer, poly (2-ethylacrylic acid)(PEAA), and the feed back reaction of glucose with glucose oxidase enzyme (GO). The thesis investigates the use of PEAR and liposomes to work inside a microcapsule in response to the glucose level of the environment, by following the release of fluorescence probes, 8-aminonapthalene-1,3,6-trisulfonic acid, disodium salt/p-xylene-bis-pyridimuim bromide (ANTS/DPX) and a model protein, myoglobin. The continuing studies of PEAR and liposome interaction indicated an evidence of the previous hypothesis of two-mode release at different pHs. Differential scanning calorimetric studies of DOPC and PEAA complexes revealed the possibility of polymer adsorption to the liposomes in the pH range 5.5--7.0 and insertion in the liposome bilayer at pH optimal concentration in the capsules. The pH reduction inside the capsule due to GO reaction showed positive results for the use of GO in a non-buffered system. The procedure of liquid-core alginate capsules was modified to facilitate the pH-responsive release of ANTS/DPX and myoglobin. The capsules responded to high blood glucose concentration by releasing myoglobin within 30 minutes. Although more studies are required to improve the response of the system to the normal blood glucose and to control the total protein release from negative controls, the results of in vitro release experiments confirmed the hypothesis that an idealized feedback control insulin delivery system is feasible.

  12. Mammaglobin 1 promotes breast cancer malignancy and confers sensitivity to anticancer drugs.

    Science.gov (United States)

    Picot, Nadia; Guerrette, Roxann; Beauregard, Annie-Pier; Jean, Stéphanie; Michaud, Pascale; Harquail, Jason; Benzina, Sami; Robichaud, Gilles A

    2016-07-01

    Mammaglobin 1 (MGB1), a member of the secretoglobin family, is expressed in mammary epithelial tissues and is overexpressed in most mammary carcinomas. Despite the extensive research correlating MGB1 expression profiles to breast cancer pathogenesis and disease outcome, the biological significance of MGB1 in cancer processes is still unclear. We have thus set out to conduct a functional evaluation of the molecular and cellular roles of MGB1 in breast cancer processes leading to disease progression. Using a series of breast cancer cell models with conditional MGB1 expression, we demonstrate that MGB1 promotes cancer cell malignant features. More specifically, loss of MGB1 expression resulted in a decrease of cell proliferation, soft agar spheroid formation, migration, and invasion capacities of breast cancer cells. Concomitantly, we also observed that MGB1 expression activates signaling pathways mediated by MAPK members (p38, JNK, and ERK), the focal adhesion kinase (FAK), matrix metalloproteinases (MMPs) and NFκB. Moreover, MGB1 regulates epithelial to mesenchymal (EMT) features and modulates Snail, Twist and ZEB1 expression levels. Interestingly, we also observed that expression of MGB1 confers breast cancer cell sensitivity to anticancer drug-induced apoptosis. Together, our results support a role for MGB1 in tumor malignancy in exchange for chemosensitivity. These findings provide one of the first descriptive overview of the molecular and cellular roles of MGB1 in breast cancer processes and may offer new insight to the development of therapeutic and prognostic strategies in breast cancer patients. © 2015 Wiley Periodicals, Inc. PMID:26207726

  13. Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents.

    Directory of Open Access Journals (Sweden)

    Ryan J Mailloux

    Full Text Available Uncoupling protein-2 (UCP2 is known to suppress mitochondrial reactive oxygen species (ROS production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents.

  14. Development of novel polymeric materials for gene therapy and pH-sensitive drug delivery: Modeling, synthesis, characterization, and analysis

    Science.gov (United States)

    Anderson, Brian Curtis

    The aim of this work was to obtain a fundamental understanding of drug release mechanisms from polymers that undergo thermoreversible gelation and to synthesize new polymers based on these that exhibit both pH and temperature sensitivity. Novel block and random copolymers with cationic character have been developed for drug delivery and gene therapy applications. The development of these materials began with a study of the mechanism of drug release from poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) block copolymers. This study revealed the release rates of drugs from water-soluble hydrogels composed of the PEO-PPO-PEO block copolymer PluronicRTM F127 was dictated almost solely by the rate of interfacial dissolution at the water/gel interface. A setup was designed to measure drug release from such soluble systems in order to avoid confounding hydrodynamic effects as a result of shear on the delicate polymer/gel interface. This study was followed by a complementary analysis of the effect ionic salts play in the phase transitions and drug release profiles in aqueous F127 solutions. In an attempt to incorporate pH sensitivity into such drug release systems, several block copolymers of poly(N,N-diethylaminoethyl methacrylate) (PDEAEM), PEO and PPO were synthesized via anionic polymerization. Diblock materials (PEO-b-PDEAEM), either with or without a carboxylic acid endcap, were synthesized and characterized. Tablet dissolution experiments demonstrated pH-sensitivity in their drug release profiles relative to PEO tablets. Pentablock materials (PDEAEM-b-PEO-b-PPO- b-PEO-b-PDEAEM) were synthesized that maintain the thermoreversible gelation and micellization properties of F127 while introducing pH-dependent release from aqueous gels of the copolymer. This is the first example of non-crosslinked materials that exhibit both pH- and temperature-sensitive behavior. Using a similar synthesis route, random copolymers of PDEAEM and poly(poly(ethylene glycol) methyl

  15. Sensitivity Pattern of Second Line Anti-Tuberculosis Drugs against Clinical Isolates of Multidrug Resistant Mycobacterium Tuberculosis

    International Nuclear Information System (INIS)

    Objective:To determine the current sensitivity pattern of second line anti-tuberculosis drugs against clinical isolates of Multidrug Resistant Mycobacterium tuberculosis (MDR-TB). Study Design: A cross-sectional study. Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from November 2011 to April 2013. Methodology: Samples received during the study period were processed on BACTEC MGIT 960 system for Mycobacterium tuberculosis (MTB) culture followed by first line drugs susceptibility testing of culture proven MTB isolates. On the basis of resistance to rifampicin and isoniazid, 100 clinical isolates of MDR-TB were further subjected to susceptibility testing against amikacin (AMK), capreomycin (CAP), ofloxacin (OFL) and ethionamide (ETH) as per standard BACTEC MGIT 960 instructions. Results: Out of 100 MDR-TB isolates, 62% were from male patients and 38% from female patients. 97% were sensitive to AMK, 53% to OFL, 87% to CAP; and 87% were sensitive to ETH. Conclusion: The majority of the MDR-TB isolates showed excellent sensitivity against AMK, CAP and ETH. However, sensitivity of MDR-TB isolates against fluoroquinolones like OFL was not encouraging. (author)

  16. Haemophilus paragallinarum in chickens in Indonesia: III. Antimicrobial drug sensitivity test ofHaemophilus paragallinarum from chickens suffering of coryza

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    Sri Poernomo

    1998-12-01

    Full Text Available An agar disc diffusion method was used to examine the sensitivity of 27 Haemophilus paragallinarum (Hpg isolates consisted of 23 local isolates, 4 standard isolates (serotype A and Escherichia coli ATCC 24922 as a control to eight antimicrobial drugs (ampicillin, erythromycin, oxytetracycline, doxycycline, neomycin, streptomycin, colistine and sulphanlethoxazole-trimethoprim . Twenty one out of 23 local isolates of Hpg were sensitive to doxycycline, 19 isolates to ampsllin, 18 isolates to oxytetracycline, 17 isolates to sulphametoxazole-trimethoprim, 16 isolates to erythromycin, and 13 isolates to neomycin, while 13 isolates were resistance to colistine and 11 isolates were also resistance to streptomycin .

  17. Analysis of drug sensitivity of candida to antifungal drugs in 152 infected patients%152例临床念珠菌感染药敏分析

    Institute of Scientific and Technical Information of China (English)

    奚琳琳; 张群智; 李芳芹

    2011-01-01

    目的 了解医院念珠菌感染药敏情况,为临床合理用药提供实验依据.方法 从临床标本中分离培养念珠菌,进行鉴定和药敏试验.结果 1 538份临床标本中分离出念珠菌152株(9.88%);其中,白色念珠菌111株(73.03%),克柔氏念珠菌31例(20.39%),其他10(6.58%).白色念珠菌时常用抗真菌药物敏感性均较高(伊曲康唑除外),而克柔氏念珠菌则对常用抗真菌药物均有较高的敏感率.结论 白色念珠菌和克柔氏念珠菌对临床一线抗真菌药氟康哇存在耐药株,应重视对高危人群进行微生物学检测和药敏试验.%Aim To investigate drug sensitivity of candida to antibiotics in patients with candida infection.Methods Candida were isolated and cultured from clinical 152 and drug sensitivity of candida to antifungal was conducted and the results were analyzed.Results A total of 152 (9.88%)candida strains were isolated from 1 538 samples,including 111 (73.03%)Candida albicans and 31 (20.39%)Candida krusei.Candida albicans showed higher sensitive rates to conventional antifungal drugs except itraconazole.However,Candida krusei showed higher sensitive rates to antifungal agents.Conclusion Candida albicans and Candida krusei showed resistances to clinical first-line antffuangal drugs such as fluconazole.Thus srug sensitivity tests be carried out to guide clinical treatment of the infections

  18. Trafficking Microenvironmental pHs of Polycationic Gene Vectors in Drug-Sensitive and Multidrug-Resistant MCF7 Breast Cancer Cells

    OpenAIRE

    Kang, Han Chang; Samsonova, Olga; Bae, You Han

    2010-01-01

    While multidrug resistance (MDR) has been a significant issue in cancer chemotherapy, delivery resistance to various anticancer biotherapeutics, including genes, has not been widely recognized as a property of MDR. This study aims to provide a better understanding of the transfection characteristics of drug-sensitive and drug-resistant cells by tracing microenvironmental pHs of two representative polymer vectors: poly(l-lysine) and polyethyleneimine. Drug-sensitive breast MCF7 cells had four-...

  19. Apoptosis-related molecular differences for response to tyrosin kinase inhibitors in drug-sensitive and drug-resistant human bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Jixia Li

    2013-01-01

    Full Text Available Context: The epidermal growth factor receptor (EGFR family is reportedly overexpressed in bladder cancer, and tyrosine kinaseinhibitors (TKIs have been suggested as treatment. Gefitinib is a selective inhibitor of the EGFR and lapatinib is a dual inhibitor of both the EGFR and HER2 (human EGFR type 2 receptor. Both compounds compete with the binding of adenosine triphosphate (ATP to the tyrosine kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical problem. Aims: To compare the apoptosis signaling pathway(s induced by gefitinib and lapatinib, in UM-UC-5 (drug-sensitive and UM-UC-14 (drug-resistant bladder cancer cells and to identify molecular differences that might be useful predictors of their efficacy. Materials and Methods: Cell proliferation, cell cycle and apoptosis assay were used to detect the effect of TKIs on UM-UC-5 and UM-UC-14 cells. Molecular differences for response to TKIs were examined by protein array. Results: TKIs strongly inhibited cell proliferation and induced cell cycle G1 arrest and apoptosis in UM-UC-5 cells. Most notable apoptosis molecular differences included decreased claspin, trail, and survivin by TKIs in the sensitive cells. In contrast, TKIs had no effect on resistant cells. Conclusions: Claspin, trail, and survivin might be used to determine the sensitivity of bladder cancers to TKIs.

  20. Utilização de medicamentos por indivíduos HIV positivos: abordagem qualitativa Utilization of prescribed drugs by HIV infected individuals: qualitative approach

    Directory of Open Access Journals (Sweden)

    Francisco A. Acurcio

    1999-02-01

    Full Text Available OBJETIVO: Analisar, em sua dimensão qualitativa, a utilização de medicamentos por indivíduos infectados pelo HIV, durante o processo de procura e atendimento em serviços de saúde. MÉTODOS: Foram realizadas 52 entrevistas semi-estruturadas com pacientes, trabalhadores da saúde e voluntários de organizações não-governamentais, e revistos 1.079 prontuários médicos para obtenção de informações sobre a utilização de medicamentos por portadores do HIV, cuja primeira visita a um dos serviços públicos de referência estudados ocorreu entre janeiro de 1989 e dezembro de 1992. RESULTADOS: Os problemas relacionados à utilização de anti-retrovirais foram: recusa ao uso, dificuldade de obtenção e de cumprimento da prescrição. Outros problemas foram a auto-medicação, dificuldade de obter medicamentos para patologias associadas e de cumprimento da prescrição de sulfas. CONCLUSÕES: Os resultados permitiram compreender melhor os principais obstáculos e dificuldades vivenciados pelo usuário dos serviços, desde o ato da prescrição até a continuidade do tratamento.OBJECTIVE: The assessment, in its qualitative dimension, of the utilization - by HIV infected individuals - of selected prescribed drugs during the process of the search for and the obtaining of care in public health services in Belo Horizonte, Brazil. METHOD: Fifty two semi-structured interviews with patients, health care workers and non- governamental organizations volunteers were carried out and 1,079 medical records were reviewed. Data were obtained on the utilization of prescribed drugs by HIV infected individuals, whose first visit to one of the public services studied occurred between January 1989 and December 1992. Problems related to the use of anti-retroviral and/or opportunistic infection medication were identified and a qualitative description of their possible causes and consequences was commented on. RESULTS: Refusal to use, difficulty in obtaining and

  1. New oil modified acrylic polymer for pH sensitive drug release: Experimental results and statistical analysis

    OpenAIRE

    Panja, N.; Chattopadhyay, A.K.

    2014-01-01

    We report results of an experimental study, complemented by detailed statistical analysis of the experimental data, on the development of a more effective control method of drug delivery using a pH sensitive acrylic polymer. New copolymers based on acrylic acid and fatty acid are constructed from dodecyl castor oil and a tercopolymer based on methyl methacrylate, acrylic acid and acryl amide were prepared using this new approach. Water swelling characteristics of fatty acid, acrylic acid copo...

  2. Enzyme- and pH-Sensitive Branched Polymer-Doxorubicin Conjugate-Based Nanoscale Drug Delivery System for Cancer Therapy.

    Science.gov (United States)

    Wei, Xiaoli; Luo, Qiang; Sun, Ling; Li, Xue; Zhu, Hongyan; Guan, Pujun; Wu, Min; Luo, Kui; Gong, Qiyong

    2016-05-11

    Owing to their dendritic architectural features, branched copolymers have been investigated as drug delivery systems. In this paper, an enzyme- and pH-sensitive branched poly[N-(2-hydroxypropyl)methacrylamide] (polyHPMA) copolymer-doxorubicin (DOX) conjugate possessing a molecular weight (MW) of 165 kDa was designed and prepared via a one-pot reaction and drug conjugation. This conjugate's potential as a smart, nanoscale drug delivery system (NDDS) is also investigated. The branched conjugate was capable of forming nanoparticles with a negative surface charge. The self-assembled nanoparticles were 102 nm in diameter as measured by dynamic light scattering (DLS) and 95 nm in diameter via scanning electron microscopy, respectively. The nanoparticles were degraded to low-MW products (23∼25 kDa) in the presence of papain or cathepsin B, and the degradation was monitored via DLS and size-exclusion chromatography. The nanoparticles demonstrated pH-sensitive drug release, as the DOX was attached to the branched copolymer via a hydrazone bond. In comparison to free DOX, the conjugate-based nanoparticles exhibited greater accumulation in breast tumors, resulting in enhanced antitumor therapeutic indexes. Furthermore, widespread dissemination of the conjugate among breast tumor cells was confirmed by immunohistochemical assay. Finally, no obvious systemic toxicities were observed in vivo in normal mice. Thus, the branched HPMA copolymer-DOX conjugate may be employed as a safe and efficient pH- and enzyme-responsive NDDS for cancer therapy. PMID:27102364

  3. pH-sensitive nanomicelles for controlled and efficient drug delivery to human colorectal carcinoma LoVo cells.

    Directory of Open Access Journals (Sweden)

    Shi-Ting Feng

    Full Text Available BACKGROUND: The triblock copolymers PEG-P(Asp-DIP-P(Lys-Ca (PEALCa of polyethylene glycol (PEG, poly(N-(N',N'-diisopropylaminoethyl aspartamide (P(Asp-DIP, and poly (lysine-cholic acid (P(Lys-Ca were synthesized as a pH-sensitive drug delivery system. In neutral aqueous environment such as physiological environment, PEALCa can self-assemble into stable vesicles with a size around 50-60 nm, avoid uptake by the reticuloendothelial system (RES, and encase the drug in the core. However, the PEALCa micelles disassemble and release drug rapidly in acidic environment that resembles lysosomal compartments. METHODOLOGY/PRINCIPAL FINDINGS: The anticancer drug Paclitaxel (PTX and hydrophilic superparamagnetic iron oxide (SPIO were encapsulated inside the core of the PEALCa micelles and used for potential cancer therapy. Drug release study revealed that PTX in the micelles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa micelle was effectively internalized by human colon carcinoma cell line (LoVo cells, and PTX could be embedded inside lysosomal compartments. Moreover, the human colorectal carcinoma (CRC LoVo cells delivery effect was verified in vivo by magnetic resonance imaging (MRI and histology analysis. Consequently effective suppression of CRC LoVo cell growth was evaluated. CONCLUSIONS/SIGNIFICANCE: These results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRI-visible drug release system for colorectal cancer therapy.

  4. A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

    International Nuclear Information System (INIS)

    Highlights: ► We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. ► The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. ► In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1IIIB and HIV-1BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1IIIB activity, whereas fusion inhibitors showed both anti-HIV-1IIIB and anti-HIV-1BaL activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, “phenotypic drug evaluation”, may be applicable for the evaluation of various antiviral drugs in vivo.

  5. Cellular HIV type 1 DNA levels are equivalent among drug-sensitive and drug-resistant strains in newly diagnosed and antiretroviral naive patients.

    Science.gov (United States)

    Antoniadou, Zoi-Anna; Hezka, Johana; Kousiappa, Ioanna; Mamais, Ioannis; Skoura, Lemonia; Pilalas, Dimitris; Metallidis, Simeon; Nicolaidis, Pavlos; Malisiovas, Nicolaos; Kostrikis, Leondios G

    2014-03-01

    coreceptor tropism dominance suggests that both drug-resistant and drug-sensitive strains behave similarly in early infection in newly diagnosed patients. PMID:24025041

  6. pH-sensitive, polymer modified, plasma stable niosomes: promising carriers for anti-cancer drugs

    OpenAIRE

    Tila, Dena; Yazdani-Arazi, Seyede Narjes; Ghanbarzadeh, Saeed; Arami, Sanam; Pourmoazzen, Zhaleh

    2015-01-01

    The aim of this study was the design and evaluation of a novel plasma stable, pH-sensitive niosomal formulation of Mitoxantrone by a modified ethanol injection method. Cholesterol hemisuccinate was added instead of cholesterol in order to produce pH-sensitivity property and using PEG-Poly (monomethyl itaconate)-CholC6 (PEG-PMMI-CholC6) copolymer introduced simultaneously pH-sensitivity and plasma stability properties in prepared niosomes. The pH-sensitivity and cytotoxicity of Mitoxantrone ni...

  7. PH-sensitive, polymer modified, plasma stable niosomes: promising carriers for anti-cancer drugs

    OpenAIRE

    Tila, Dena; Yazdani-Arazi, Seyede Narjes; Ghanbarzadeh, Saeed; Arami, Sanam; Pourmoazzen, Zhaleh

    2015-01-01

    The aim of this study was the design and evaluation of a novel plasma stable, pH-sensitive niosomal formulation of Mitoxantrone by a modified ethanol injection method. Cholesterol hemisuccinate was added instead of cholesterol in order to produce pH-sensitivity property and using PEG-Poly (monomethyl itaconate)-CholC6 (PEG-PMMI-CholC6) copolymer introduced simultaneously pH-sensitivity and plasma stability properties in prepared niosomes. The pH-sensitivity and cytotoxicity of Mitoxantrone ni...

  8. Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, enlarge the parasite's food vacuole and alter drug sensitivities.

    Science.gov (United States)

    Pulcini, Serena; Staines, Henry M; Lee, Andrew H; Shafik, Sarah H; Bouyer, Guillaume; Moore, Catherine M; Daley, Daniel A; Hoke, Matthew J; Altenhofen, Lindsey M; Painter, Heather J; Mu, Jianbing; Ferguson, David J P; Llinás, Manuel; Martin, Rowena E; Fidock, David A; Cooper, Roland A; Krishna, Sanjeev

    2015-01-01

    Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction of the C101F or L272F mutation into a chloroquine-resistant variant of PfCRT reduced the ability of this protein to transport chloroquine by approximately 93 and 82%, respectively, when expressed in Xenopus oocytes. These data provide, at least in part, a mechanistic explanation for the increased sensitivity of the mutant parasite lines to chloroquine. Taken together, these findings provide new insights into PfCRT function and PfCRT-mediated drug resistance, as well as the food vacuole, which is an important target of many antimalarial drugs. PMID:26420308

  9. Analysis of Culture and Drug Sensitivity Tests of Mycoplasmas for 387 Patients with Nongonococcal Urethritis (Cervicitis) in Chongqing

    Institute of Scientific and Technical Information of China (English)

    翟志芳; 郝飞; 钟白玉; 黄秀英; 唐书谦; 刁庆春

    2004-01-01

    Objective: To investigate the prevalence of mycoplasma infections and the sensitivity to antibiotics among patients with nongonococcal urethritis or cervicitis (NGU) in Chongqing. Methods: 387 NGU cases with mycoplasma-positive results upon culture were analysed retrospectively. RESULTS: The majority of patients with mycoplasma infections were in the 20-40 year old age group. No significant difference was found between males and females. Ureaplasma urealyticum is the main pathogen of these NGU cases and no clear relationship between its concentration and pathogenic ability was noted. Drug sensitivity was tested against nine antibiotics; the sensitivity rates to josamycin, minocycline and doxycycline were 94.06%, 88.89% and 86.82% respectively, while the resistance rates to lincomycin, ofloxacin, azithromycin and roxthromycin were 74.94%, 42.12%, 41.60% and 40.31% in turn. Conclusions: Josamycin, minocycline and doxycycline could be used as the first choice to treat NGU with mycoplasma infections in Chongqing. It is important to select antibiotics for NGU treatment with mycoplasma infections based on the results of drug sensitivity tests.

  10. Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?

    International Nuclear Information System (INIS)

    Drug resistance is a fundamental problem in the treatment of most common human cancers. Our understanding of the cellular mechanisms underlying death and survival has allowed the development of rational approaches to overcoming drug resistance. The mitogen activated protein kinase family of protein serine/threonine kinases has been implicated in this complex web of signalling, with some members acting to enhance death and other members to prevent it. A recent publication by MacKeigan et al is the first to demonstrate an enhancement of drug-induced cell death by simultaneous blockade of MEK-mediated survival signalling, and offers the potential for targeted adjuvant therapy as a means of overcoming drug resistance

  11. Graphene oxide-enhanced sol-gel transition sensitivity and drug release performance of an amphiphilic copolymer-based nanocomposite

    Science.gov (United States)

    Hu, Huawen; Wang, Xiaowen; Lee, Ka I; Ma, Kaikai; Hu, Hong; Xin, John H.

    2016-01-01

    We report the fabrication of a highly sensitive amphiphilic copolymer-based nanocomposite incorporating with graphene oxide (GO), which exhibited a low-intensity UV light-triggered sol-gel transition. Non-cytotoxicity was observed for the composite gels after the GO incorporation. Of particular interest were the microchannels that were formed spontaneously within the GO-incorporated UV-gel, which expedited sustained drug release. Therefore, the present highly UV-sensitive, non-cytotoxic amphiphilic copolymer-based composites is expected to provide enhanced photothermal therapy and chemotherapy by means of GO’s unique photothermal properties, as well as through efficient passive targeting resulting from the sol-gel transition characteristic of the copolymer-based system with improved sensitivity, which thus promises the enhanced treatment of patients with cancer and other diseases. PMID:27539298

  12. Cross-linked pH sensitive polymer micelles for drug delivery systems

    OpenAIRE

    Cajot, Sébastien; Jérôme, Christine

    2009-01-01

    Over the last decade, polymer micelles attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of tens of nanometers in diameter. In principle, the micelles core is usually constructed with biodegradable hydrophobic polymers such as aliphatic polyesters, e.g. poly(ɛ-caprolactone) (PCL), which serves as a reservoir for the incorpora...

  13. Konjac glucomannan/xanthan gum enzyme sensitive binary mixtures for colonic drug delivery.

    Science.gov (United States)

    Alvarez-Manceñido, Felipe; Landin, Mariana; Martínez-Pacheco, Ramón

    2008-06-01

    The polysaccharide konjac glucomannan (KGM) is degraded in the colon but not the small intestine, which makes it potentially useful as an excipient for colonic drug delivery. With xanthan gum (XG) KGM forms thermoreversible gels with hitherto unexplored biodegradation properties. In this work, rheological measurements of KGM and KGM/XG systems incubated with and without Aspergillus niger beta-mannanase (used to mimic colonic enzymes) showed that KGM was degraded by the enzyme even when interacting with XG. Tablets with KGM/XG/sucrose matrices that varied in accordance with a simplex design and bore diltiazem as a typical highly soluble drug load were prepared by wet granulation, and in most cases were found to possess satisfactory mechanical strength and exhibit slow, nearly zero-order drug release. Drug release from these tablets remained zero-order, but was accelerated (presumably due to degradation of KGM), in the presence of A. niger beta-mannanase at concentrations equivalent to human colonic conditions. However, marked differences between Japanese and American varieties of KGM as regards degree of acetylation and particle size led to significant differences in swelling rate and drug release between formulations prepared with one and the other KGM: whereas a formulation with Japanese KGM released its entire drug load within 24h in the presence of beta-mannanase, only 60% release was achieved under the same conditions by the corresponding formulation with American KGM, suggesting that with this KGM it will be necessary to optimize technological variables such as compression pressure in order to achieve suitable porosity, swelling rate, and drug release. To sum up, the results of this study suggest that sustained release of water-soluble drugs in the colon from orally administered tablets may be achieved using simple, inexpensive formulations based on combinations of KGM and XG that take the variability of KGM characteristics into account. PMID:18294827

  14. Structural Aspects of Drug Resistance and Inhibition of HIV-1 Reverse Transcriptase

    Directory of Open Access Journals (Sweden)

    Stefan G. Sarafianos

    2010-02-01

    Full Text Available HIV-1 Reverse Transcriptase (HIV-1 RT has been the target of numerous approved anti-AIDS drugs that are key components of Highly Active Anti-Retroviral Therapies (HAART. It remains the target of extensive structural studies that continue unabated for almost twenty years. The crystal structures of wild-type or drug-resistant mutant HIV RTs in the unliganded form or in complex with substrates and/or drugs have offered valuable glimpses into the enzyme’s folding and its interactions with DNA and dNTP substrates, as well as with nucleos(tide reverse transcriptase inhibitor (NRTI and non-nucleoside reverse transcriptase inhibitor (NNRTIs drugs. These studies have been used to interpret a large body of biochemical results and have paved the way for innovative biochemical experiments designed to elucidate the mechanisms of catalysis and drug inhibition of polymerase and RNase H functions of RT. In turn, the combined use of structural biology and biochemical approaches has led to the discovery of novel mechanisms of drug resistance and has contributed to the design of new drugs with improved potency and ability to suppress multi-drug resistant strains.

  15. Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A

    Directory of Open Access Journals (Sweden)

    Shinde Ravikumar B

    2012-10-01

    Full Text Available Abstract Background Biofilms formed by Candida albicans are resistant towards most of the available antifungal drugs. Therefore, infections associated with Candida biofilms are considered as a threat to immunocompromised patients. Combinatorial drug therapy may be a good strategy to combat C. albicans biofilms. Methods Combinations of five antifungal drugs- fluconazole (FLC, voriconazole (VOR, caspofungin (CSP, amphotericin B (AmB and nystatin (NYT with cyclosporine A (CSA were tested in vitro against planktonic and biofilm growth of C. albicans. Standard broth micro dilution method was used to study planktonic growth, while biofilms were studied in an in vitro biofilm model. A chequerboard format was used to determine fractional inhibitory concentration indices (FICI of combination effects. Biofilm growth was analyzed using XTT-metabolic assay. Results MICs of various antifungal drugs for planktonic growth of C. albicans were lowered in combination with CSA by 2 to 16 fold. Activity against biofilm development with FIC indices of 0.26, 0.28, 0.31 and 0.25 indicated synergistic interactions between FLC-CSA, VOR-CSA, CSP-CSA and AmB-CSA, respectively. Increase in efficacy of the drugs FLC, VOR and CSP against mature biofilms after addition of 62.5 μg/ml of CSA was evident with FIC indices 0.06, 0.14 and 0.37, respectively. Conclusions The combinations with CSA resulted in increased susceptibility of biofilms to antifungal drugs. Combination of antifungal drugs with CSA would be an effective prophylactic and therapeutic strategy against biofilm associated C. albicans infections.

  16. Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells.

    Science.gov (United States)

    González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; de la Cueva, Ana; Vargas, Teodoro; Santoyo, Susana; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

    2013-06-01

    5-Fluorouracil (5-FU) is the most used chemotherapeutic agent in colorectal cancer. However, resistance to this drug is relatively frequent, and new strategies to overcome it are urgently needed. The aim of this work was to determine the antitumor properties of a supercritical fluid rosemary extract (SFRE), alone and in combination with 5-FU, as a potential adjuvant therapy useful for colon cancer patients. This extract has been recognized as a healthy component by the European Food Safety Authority (EFSA). The effects of SFRE both alone and in combination with 5-FU were evaluated in different human colon cancer cells in terms of cell viability, cytotoxicity, and cell transformation. Additionally, colon cancer cells resistant to 5-FU were used to assay the effects of SFRE on drug resistance. Finally, qRT-PCR was performed to ascertain the mechanism by which SFRE potentiates the effect of 5-FU. Our results show that SFRE displays dose-dependent antitumor activities and exerts a synergistic effect in combination with 5-FU on colon cancer cells. Furthermore, SFRE sensitizes 5-FU-resistant cells to the therapeutic activity of this drug, constituting a beneficial agent against both 5-FU sensitive and resistant tumor cells. Gene expression analysis indicates that the enhancement of the effect of 5-FU by SFRE might be explained by the downregulation of TYMS and TK1, enzymes related to 5-FU resistance. PMID:23557932

  17. Sensitivity to Lovastatin of Saccharomyces cerevisiae Strains Deleted for Pleiotropic Drug Resistance (PDR) Genes

    DEFF Research Database (Denmark)

    Formenti, Luca Riccardo; Kielland-Brandt, Morten

    2011-01-01

    The use of statins is well established in human therapy, and model organisms such as Saccharomyces cerevisiae are commonly used in studies of drug action at molecular and cellular levels. The investigation of the resistance mechanisms towards statins may suggest new approaches to improve therapy...... based on the use of statins. We investigated the susceptibility to lovastatin of S. cerevisiae strains deleted for PDR genes, responsible for exporting hydrophobic and amphi-philic drugs, such as lovastatin. Strains deleted for the genes tested, PDR1, PDR3, PDR5 and SNQ2, exhibited remarkably different...

  18. Development of Nano-Liposomal Formulations of Epidermal Growth Factor Receptor Inhibitors and their Pharmacological Interactions on Drug-Sensitive and Drug-Resistant Cancer Cell Lines

    Science.gov (United States)

    Trummer, Brian J.

    , due to leaky tumor vasculature and the resulting Enhanced Permeability and Retention (EPR) phenomenon. In Chapter 2 we report that both gefitinib and the structurally similar EGFR inhibitor erlotinib display environment-dependent fluorescence properties. Peak excitation was 345 nm, and the emission peak ranged from 365 to 476 nm, depending upon the polarity of the environment and physical state of the drug. The fluorescence was negligible in aqueous solution, but intense in organic solvents or membrane bilayers. The environment-sensitive fluorescence properties of these drugs enabled rapid evaluation of numerous parameters affecting liposomal drug incorporation and performance. Up to 4-6 mol% of gefitinib could be incorporated in the liposome bilayer, based upon hydrophobic interactions with membrane bilayers. In contrast, 40-60 mol% could be loaded into the aqueous core of pre-formed liposomes at high efficiency, using a remote loading procedure. A stable formulation consisting of distearoylphosphatidylcholine: polyethylene glycol-distereoylphosphatidylethanolamine: cholesterol (DSPC:PEGDSPE:Chol, 9:1:5 mol:mol:mol) and containing drug at 50-60 mol% gefitinib (L-GEF) showed minimal leakage in serum-containing medium over 24 h at 37°C, which should be sufficient to improve biodistribution in vivo. Chapter 3 investigated the pharmacological activity of liposome-encapsulated gefitinib, alone and in combination with several prevalent anticancer agents. Experiments with MCF7 breast cancer cell lines demonstrated that liposome encapsulated gefitinib formulation (L-GEF) had a 2-fold higher IC50 (concentration of drug resulting in half-maximal growth inhibition) than free gefitinib. Lower in vitro potency would be consistent with delayed drug release from the carrier. Therapeutic effects were investigated in combination with the cytotoxic agents paclitaxel and doxorubicin. The drug-resistant MCF7R cell line was 23-fold more resistant to paclitaxel than the parental, drug-sensitive

  19. A pH-sensitive binary drug delivery system based on poly(caprolactone)-heparin conjugates.

    Science.gov (United States)

    Ye, Lin; Gao, Zemin; Zhou, Yu; Yin, Xuan; Zhang, Xinpeng; Zhang, Aiying; Feng, Zengguo

    2014-03-01

    PCL-heparin conjugates were synthesized by coupling mono-hydroxyl terminated PCL (Mn = 2000-10000 g/mol) with heparin via EDC/NHS chemistry. The conjugates enabled to self-assemble into the core-shell nanoparticles in around 100 nm diameter to load binary anti-cancer drugs. Lipophilic and neutral paclitaxel (PTX) was first encapsulated in the core, and then hydrophilic and positive charged doxorubicin (DOX) was incorporated into the negative charged shell of PTX loaded nanoparticles via the electrostatic interaction. The in vitro release profiles of the binary-drug loaded nanoparticles revealed that both PTX and DOX were sustainably released from the particles but behaved differently. The release of DOX was pH dependent, ensuring more drug to be released in the tumor cells than in the normal ones. Hence these particles were featured by a sequential controlled drug delivery behavior with a significant cytotoxicity to cervical cancer (Hela cell) and breast cancer (MDA-MB-321) cells. The CLSM observations clearly indicated that both loaded PTX and DOX aggregated in the nucleus of tumor cells to exert their anti-tumor pharmacodynamic effect on the cells. PMID:23554308

  20. Radiation synthesis of pH-sensitive hydrogels from β-cyclodextrin-grafted PEG and acrylic acid for drug delivery

    International Nuclear Information System (INIS)

    A water-soluble macromonomer (PEG-β-CD) was synthesised by reaction of β-cyclodextrin with poly(ethylene glycol) diglycidyl ether. Then, a novel hydrogel with pH-sensitivity was prepared by irradiating the mixture of acrylic acid and PEG-β-CD with electron beam. Compared with the normal PAAc hydrogel, this novel hydrogel had a higher swelling ratio at pH 3-8. 5-Fluorouracil (5-FU) was chosen as a model drug, and the kinetics of 5-FU releasing behavior was studied. Compared with the PAAc hydrogel, the results showed the release time of 5-FU from the cyclodextrin containing hydrogel was prolonged. It may be ascribed to the formation of inclusion complexes between the drug molecules and cyclodextrin groups.

  1. Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Pierangelo eCifelli

    2013-07-01

    Full Text Available The pharmacological treatment of mesial temporal lobe epilepsy (mTLE, the most common epileptic syndrome in adults, is still unsatisfactory, as one third of the patients are or become refractory to antiepileptic agents. Refractoriness may depend upon drug-induced alterations, but the disease per se may also undergo a progressive evolution that affects the sensitivity to drugs. mTLE has been shown to be associated with a dysfunction of the inhibitory signaling mediated by GABAA receptors. In particular, the repetitive activation of GABAA receptors produces a use-dependent decrease (rundown of the evoked currents (IGABA, which is markedly enhanced in the hippocampus and cortex of drug-resistant mTLE patients. This phenomenon has been also observed in the pilocarpine model, where the increased IGABA rundown is observed in the hippocampus at the time of the first spontaneous seizure, then extends to the cortex and remains constant in the chronic phase of the disease. Here, we examined the sensitivity of IGABA to pharmacological modulation. We focused on the antiepileptic agent levetiracetam and on the neurotrophin BDNF, which were previously reported to attenuate mTLE-induced increased rundown in the chronic human tissue. In the pilocarpine model, BDNF displayed a paramount effect, decreasing rundown in the hippocampus at the time of the first seizure, as well as in the hippocampus and cortex in the chronic period. In contrast, levetiracetam did not affect rundown in the hippocampus, but attenuated it in the cortex. Interestingly, this effect of levetiracetam was also observed on the still unaltered rundown observed in the cortex at the time of the first spontaneous seizure. These data suggest that the sensitivity of GABAA receptors to pharmacological interventions undergoes changes during the natural history of mTLE, implicating that the site of seizure initiation and the timing of treatment may highly affect the therapeutic outcome.

  2. Development of Novel Polymeric Materials for Gene Therapy and pH-Sensitive Drug Delivery: Modeling, Synthesis, Characterization, and Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Brian Curtis Anderson

    2002-08-27

    The underlying theme of this thesis is the use of polymeric materials in bioapplications. Chapters 2-5 either develop a fundamental understanding of current materials used for bioapplications or establish protocols and procedures used in characterizing and synthesizing novel materials. In chapters 6 and 7 these principles and procedures are applied to the development of materials to be used for gene therapy and drug delivery. Chapter one is an introduction to the ideas that will be necessary to understand the subsequent chapters, as well as a literature review of these topics. Chapter two is a paper that has been published in the ''Journal of Controlled Release'' that examines the mechanism of drug release from a polymer gel, as well as experimental design suggestions for the evaluation of water soluble drug delivery systems. Chapter three is a paper that has been published in the ''Journal of Pharmaceutical Sciences'' that discusses the effect ionic salts have on properties of the polymer systems examined in chapter two. Chapter four is a paper published in the Materials Research Society Fall 2000 Symposium Series dealing with the design and synthesis of a pH-sensitive polymeric drug delivery device. Chapter five is a paper that has been published in the journal ''Biomaterials'' proposing a novel polymer/metal composite for use as a biomaterial in hip arthroplasty surgery. Chapter six is a paper that will appear in an upcoming volume of the Journal ''Biomaterials'' dealing with the synthesis of a novel water soluble cationic polymer with possible applications in non-viral gene therapy. Chapter seven is a paper that has been submitted to ''Macromolecules'' discussing several novel block copolymers based on poly(ethylene glycol) and poly(diethylamino ethyl methacrylate) that possess both pH-sensitive and temperature sensitive properties. Chapter eight contains a

  3. pH-sensitive poly(histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery

    OpenAIRE

    Wu, Hong; Zhu, Lin; Torchilin, Vladimir P.

    2012-01-01

    To introduce pH sensitivity into the DSPE-PEG-based micellar system and achieve the quick intracellular drug release in response to the acidity in endosomes, a mixed polymeric micelle was developed based on three grafted copolymers, including 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000(DSPE-PEG2000), antinucleosome antibody (mAb 2C5)-modified DSPE-PEG3400 (DSPE-PEG3400-2C5), and poly(ethylene glycol)-coupled poly(l-histidine) (PHIS-PEG2000). The structure of PHIS-...

  4. One-step synthesis of interpenetrating network hydrogels: Environment sensitivities and drug delivery properties

    OpenAIRE

    Lu, Jingqiong; Li, Yinhui; Hu, Deng; Chen, Xiaoling; Liu, Yongmei; Wang, Liping; Ashraf, Muhammmad Aqeel; Zhao, Yansheng

    2015-01-01

    A novel interpenetrating network hydrogel for drug controlled release, composed of modified poly(aspartic acid) (KPAsp) and carboxymethyl chitosan (CMCTS), was prepared in aqueous system. The surface morphology and composition of hydrogels were characterized by SEM and FTIR. The swelling properties of KPAsp, KPAsp/CMCTS semi-IPN and KPAsp/CMCTS IPN hydrogels were investigated and the swelling dynamics of the hydrogels was analyzed based on the Fickian equation. The pH, temperature and salt se...

  5. Functional genomic analysis of drug sensitivity pathways to guide adjuvant strategies in breast cancer

    DEFF Research Database (Denmark)

    Swanton, Charles; Szallasi, Zoltan Imre; Brenton, James D.;

    2008-01-01

    ) as well as endocrine therapies such as tamoxifen. Given the limited power of microarray signatures to predict therapeutic response in associative studies of small clinical trial cohorts, the use of functional genomic data combined with expression or sequence analysis of genes and microRNAs implicated...... in drug response in human tumours may provide a more robust method to guide adjuvant treatment strategies in breast cancer that are transferable across different expression platforms and patient cohorts....

  6. Mesoscale Simulations and Experimental Studies of pH-Sensitive Micelles for Controlled Drug Delivery.

    Science.gov (United States)

    Wang, Yan; Li, Qiu Yu; Liu, Xu Bo; Zhang, Can Yang; Wu, Zhi Min; Guo, Xin Dong

    2015-11-25

    The microstructures of doxorubicin-loaded micelles prepared from block polymers His(x)Lys10 (x = 0, 5, 10) conjugated with docosahexaenoic acid (DHA) are investigated under different pH conditions, using dissipative particle dynamics (DPD) simulations. The conformation of micelles and the DOX distributions in micelles were obviously influenced by pH values and the length of the histidine segment. At pH >6.0, the micelles self-assembled from the polymers were dense and compact. The drugs were entrapped well within the micellar core. The particle size increases as the histidine length increases. With the decrease of pH value to be lower than 6.0, there was no distinct difference for the micelles self-assembled from the polymer without histidine residues. However, the micelles prepared from the polymers with histidine residues shows a structural transformation from dense to swollen conformation, leading to an increased particle size from 10.3 to 14.5 DPD units for DHD-His10Lys10 micelles. This structural transformation of micelles can accelerate the DOX release from micelles under lower pH conditions. The in vitro drug release from micelles is accelerated by the decrease of pH value from 7.4 (physiological environment) to 5.0 (lysosomal environment). The integration of simulation and experiments might be a valuable method for the optimization and design of biomaterials for drug delivery with desired properties. PMID:26539742

  7. Drug-induced diseases (DIDs: An experience of a tertiary care teaching hospital from India

    Directory of Open Access Journals (Sweden)

    Vishal R Tandon

    2015-01-01

    Full Text Available Background & objectives: Drug-induced diseases (DIDs are well known but least studied. Data on DIDs from India are not available. Hence, this retrospective cross-sectional study was undertaken using suspected adverse drug reaction (ADR data collected form Pharmacovigilance Programme of India (PvPI to evaluate profile of DIDs over two years, in a tertiary care teaching hospital from north India. Methods: The suspected ADRs in the form of DID were evaluated for drug and disease related variables and were classified in terms of causality. Results: DID rate was 38.80 per cent. Mean duration of developing DIDs was 26.05 ± 9.6 days; 25.16 per cent had more than one co-morbid condition. Geriatric population (53.99% accounted for maximum DIDs followed by adult (37.79% and paediatric (8.21%. Maximum events were probable (93.98% followed by possible (6.04%. All DIDs required intervention. Gastritis (7.43%, diarrhoea (5.92%, anaemia (4.79%, hypotension (2.77%, hepatic dysfunction (2.69%, hypertension (1.51%, myalgia (1.05%, and renal dysfunction (1.01% were some of the DIDs. Anti-tubercular treatment (ATT, anti- retroviral treatment (ART, ceftriaxone injection, steroids, non-steroidal anti-inflammatory drugs, antimicrobials and anticancer drugs were found as commonly offending drugs. Interpretation & conclusions: Our findings show that DIDs are a significant health problem in our country, which need more attention.

  8. Inhibition of anaphylactic histamine release from heterologously sensitized mast cells: differential effects of drugs which interfere with calcium influx.

    Directory of Open Access Journals (Sweden)

    Kurose,Masao

    1981-11-01

    Full Text Available Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG were active irrespective of the time interval between antigen and Ca++ addition. Verapamil was more effective when added before or simultaneously with antigen than when added later. When tested in the two-stage experiments, quercetin showed inhibition only in Stage 1 and verapamil was inhibitive primarily in Stage 1, while theophylline and DSCG wee only inhibitive in Stage 2. It seems that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and DSCG selectively inhibit the passage of calcium through open calcium channels.

  9. Dextran hydrogel coated surface plasmon resonance imaging (SPRi) sensor for sensitive and label-free detection of small molecule drugs

    Science.gov (United States)

    Li, Shaopeng; Yang, Mo; Zhou, Wenfei; Johnston, Trevor G.; Wang, Rui; Zhu, Jinsong

    2015-11-01

    The label-free and sensitive detection of small molecule drugs on SPRi is still a challenging task, mainly due to the limited surface immobilization capacity of the sensor. In this research, a dextran hydrogel-coated gold sensor chip for SPRi was successfully fabricated via photo-cross-linking for enhanced surface immobilization capacity. The density of the dextran hydrogel was optimized for protein immobilization and sensitive small molecule detection. The protein immobilization capacity of the hydrogel was 10 times greater than a bare gold surface, and 20 times greater than an 11-mercaptoundecanoic acid (MUA) surface. Such a drastic improvement in immobilization capacity allowed the SPRi sensor to detect adequate response signals when probing small molecule binding events. The binding signal of 4 nM liquid-phase biotin to streptavidin immobilized on the dextran surface reached 435 RU, while no response was observed on bare gold or MUA surfaces. The dextran hydrogel-coated SPRi sensor was also applied in a kinetic study of the binding between an immunosuppressive drug (FK506) and its target protein (FKBP12) in a high-throughput microarray format. The measured binding affinity was shown to be consistent with reported literature values, and a detection limit of 0.5 nM was achieved.

  10. Activator of G-protein Signaling 3: A Gatekeeper of Cocaine Sensitization and Drug-seeking

    OpenAIRE

    Bowers, M.S.; McFarland, K.; Lake, R.W.; Peterson, Y K; Lapish, C.C.; Gregory, M.L.; Lanier, S M; Kalivas, P.W.

    2004-01-01

    Chronic cocaine administration reduces G-protein signaling efficacy. Here we report that the expression of AGS3, which selectively binds to GiαGDP and inhibits GDP dissociation, was upregulated in the prefrontal cortex (PFC) during late withdrawal from repeated cocaine administration. Increased AGS3 was mimicked in the PFC of drug naïve rats by microinjecting a peptide containing the Giα binding domain (GPR) of AGS3 fused to the cell permeability domain of HIV-Tat. Infusion of Tat-GPR mimicke...

  11. Swelling characteristics of hydroxyethylmethacrylate/ methacrylic acid pH -sensitive hydrogel as a drug delivery system

    OpenAIRE

    M. Falamarzian- J. Varshosaz

    1996-01-01

    Hydroxyethyl methacrylate /methacrylic acid (HEMA/MAA) copolymer cross-linked with ethylenglycol dimethacrylate was prepared by a bulk.free radical polymerization method. The results indicate that this polymer is a pH -sensitive hydrogel which is collapsed in the acidic medium but completely swollen in the alkaline and neutral pH . it was determined that a proportion of 40% of MAA, the ionizing monomer of this hydrogel, was the best concentration among the different percentages used which sho...

  12. Evolving Cardiac Conduction Phenotypes in Developing Zebrafish Larvae: Implications to Drug Sensitivity

    OpenAIRE

    Yu, Fei; Huang, Jie; Adlerz, Katrina; Jadvar, Hossein; Hamdan, Mohamed H.; Chi, Neil; Chen, Jau-Nian; Hsiai, Tzung K.

    2010-01-01

    Cardiac arrhythmias include problems with impulse formation and/or conduction abnormalities. Zebrafish (Danio rerio) is an emerging model system for studying the cardiac conduction system. However, real-time recording of the electrocardiogram remains a challenge. In the present study, we assessed the feasibility of recording electrical cardiogram (ECG) signals from the zebrafish larvae using the micropipette electrodes, and demonstrated the dynamic changes in ECG signals and their sensitivity...

  13. Drug Addiction: The Relationship Between Nursing Interventions And Sensitive Outcomes. A Systematic Literature Review

    OpenAIRE

    Seabra, Paulo; Santos, Alexandra; Garcia, Lurdes; Amendoeira, José; Sá, Luís

    2012-01-01

    Background and Significance: The analysis of care contribution provided by different professionals and the results of their interventions is a recommendation that emerges from the practice stems, from costs concerns and to re-structure health services. The need to deepen the nursing contribution, to health outcomes achieved by people, is our challenge. We need to show further evidence that nursing sensitive health outcomes can contribute to health benefits of the people and pronounce today...

  14. Novel pH-sensitive polysialic acid based polymeric micelles for triggered intracellular release of hydrophobic drug.

    Science.gov (United States)

    Zhang, Wuxia; Dong, Dongqi; Li, Peng; Wang, Dongdong; Mu, Haibo; Niu, Hong; Duan, Jinyou

    2016-03-30

    Polysialic acid (PSA), a non-immunogenic and biodegradable natural polymer, is prone to hydrolysis under endo-lysosomal pH conditions. Here, we synthesized an intracellular pH-sensitive polysialic acid-ursolic acid conjugate by a condensation reaction. To further test the drug loading capability, we prepared paclitaxel-loaded polysialic acid-based amphiphilic copolymer micelle (PTX-loaded-PSAU) by a nanoprecipitation method. Results showed PTX-loaded-PSAU exhibited well-defined spherical shape and homogeneous distribution. The drug-loading was 4.5% with an entrapment efficiency of 67.5%. PTX released from PTX-loaded-PSAU was 15% and 42% in 72 h under simulated physiological condition (pH 7.4) and mild acidic conditions (pH 5.0), respectively. In addition, In vitro cytotoxicity assay showed that PTX-loaded-PSAU retained anti-tumor (SGC-7901) activity with a cell viability of 53.8% following 72 h incubation, indicating PTX-loaded-PSAU could efficiently release PTX into the tumor cells. These results indicated that the pH-responsive biodegradable PTX-loaded-PSAU possess superior extracellular stability and intracellular drug release ability. PMID:26794949

  15. Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

    Directory of Open Access Journals (Sweden)

    Tran TH

    2015-08-01

    Full Text Available Tuan Hiep Tran,1 Thiruganesh Ramasamy,1 Ju Yeon Choi,1 Hanh Thuy Nguyen,1 Thanh Tung Pham,1 Jee-Heon Jeong,1 Sae Kwang Ku,2 Han-Gon Choi,3 Chul Soon Yong,1 Jong Oh Kim11College of Pharmacy, Yeungnam University, Dae-Dong, 2College of Korean Medicine, Daegu Haany University, Gyeongsan, 3College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sangnok-gu, Ansan, South KoreaAbstract: The attachment of polyethylene glycol (PEG increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.Keywords: docetaxel, polyaspartic acid, drug delivery systems, antitumor, pH-sensitive

  16. Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs.

    Science.gov (United States)

    Ma, Ming; Zhao, Lianmei; Sun, Guogui; Zhang, Chao; Liu, Lihua; Du, Yanyan; Yang, Xingxiao; Shan, Baoen

    2016-05-01

    Interleukin-24 (IL-24) is a cytokine encoded by a tumor suppressor gene of the IL-10 family, also known as the melanoma differentiation associated gene-7 (Mda-7) and first discovered in human melanoma cells. Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the sensitivity of B cell lymphoma to chemotherapy agents is not yet clear. The present study investigated the effects of Mda-7/IL-24 overexpression on the sensitivity of human B cell lymphoma cells to chemotherapy, as well as its mechanism of action. The sensitivity of stable Mda-7/IL-24 overexpressing Raji and Daudi cells to cis-diamminedichloroplatinum (CDDP), epirubicin and vinblastine (VCR) were assessed by the MTS method, and the IC50 value calculated. Cell apoptosis and the intracellular accumulation of Rhodamine-123 were assayed by flow cytometry. The expression of multidrug resistance gene 1 (MDR1), B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1), topoisomerase II (Topo II) and multidrug resistance-related protein 1 (MRP1) mRNA and protein were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. In addition, western blot analysis was also used to investigate the effect of Mda-7/IL-24 on activity of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells. Growth inhibition and apoptosis rates of Mda-7/IL-24 overexpressing Raji and Daudi cells were higher than those of non-transfected cells and cells transfected with vector alone when treated with CDDP, epirubicin and VCR. The IC50 values of CDDP, epirubicin and VCR were lower for Mda-7/IL-24-overexpressing Raji and Daudi cells than for non-transfected cells and cells transfected with empty vector. Intracellular accumulation of Rhodamine-123 and the expression of Topo II were higher, while the levels of MDR1, BMI and MRP1 mRNA and protein were lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells

  17. Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Vora, Lalit [University under Sect. 3 of UGC Act – 1956, Elite Status and Center of Excellence – Govt. of Maharashtra, Center for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology (India); Tyagi, Monica [Advanced Center for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Gupta Lab, Cancer Research Institute (India); Patel, Ketan [University under Sect. 3 of UGC Act – 1956, Elite Status and Center of Excellence – Govt. of Maharashtra, Center for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology (India); Gupta, Sanjay [Advanced Center for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Gupta Lab, Cancer Research Institute (India); Vavia, Pradeep, E-mail: vaviapradeep@yahoo.com [University under Sect. 3 of UGC Act – 1956, Elite Status and Center of Excellence – Govt. of Maharashtra, Center for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology (India)

    2014-12-15

    The amalgamation of chemotherapy and gene therapy is promising treatment option for cancer. In this study, novel biocompatible self-assembled nanocomplexes (NCs) between carboxylmethylated pullulan t335 (CMP) with polyallylamine (CMP–PAA NCs) were developed for plasmid DNA (pDNA) and pH-sensitive doxorubicin (DOX) delivery. DOX was conjugated to CMP (DOX–CMP) via hydrazone and confirmed by FTIR and {sup 1}H-NMR. In vitro release studies of pH-sensitive DOX–CMP conjugate showed 23 and 85 % release after 48 h at pH 7.4 (physiological pH) and pH 5 (intracellular/tumoral pH), respectively. The CMP–PAA NCs or DOX–CMP–PAA NCs self-assembled into a nanosized (<250 nm) spherical shape as confirmed by DLS and TEM. The hemolysis and cytotoxicity study indicated that the CMP–PAA NCs did not show cytotoxicity in comparison with plain polyallylamine. Gel retardation assay showed complete binding of pDNA with CMP–PAA NCs at 1:2 weight ratio. CMP–PAA NCs/pDNA showed significantly higher transfection in HEK293 cells compared to PAA/pDNA complexes. Confocal imaging demonstrated successful cellular uptake of DOX–CMP–PAA NCs in HEK293 cells. Thus, NCs hold great potential for targeted pDNA and pH-sensitive intratumoral drug delivery.

  18. Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

    International Nuclear Information System (INIS)

    The amalgamation of chemotherapy and gene therapy is promising treatment option for cancer. In this study, novel biocompatible self-assembled nanocomplexes (NCs) between carboxylmethylated pullulan t335 (CMP) with polyallylamine (CMP–PAA NCs) were developed for plasmid DNA (pDNA) and pH-sensitive doxorubicin (DOX) delivery. DOX was conjugated to CMP (DOX–CMP) via hydrazone and confirmed by FTIR and 1H-NMR. In vitro release studies of pH-sensitive DOX–CMP conjugate showed 23 and 85 % release after 48 h at pH 7.4 (physiological pH) and pH 5 (intracellular/tumoral pH), respectively. The CMP–PAA NCs or DOX–CMP–PAA NCs self-assembled into a nanosized (<250 nm) spherical shape as confirmed by DLS and TEM. The hemolysis and cytotoxicity study indicated that the CMP–PAA NCs did not show cytotoxicity in comparison with plain polyallylamine. Gel retardation assay showed complete binding of pDNA with CMP–PAA NCs at 1:2 weight ratio. CMP–PAA NCs/pDNA showed significantly higher transfection in HEK293 cells compared to PAA/pDNA complexes. Confocal imaging demonstrated successful cellular uptake of DOX–CMP–PAA NCs in HEK293 cells. Thus, NCs hold great potential for targeted pDNA and pH-sensitive intratumoral drug delivery

  19. Facile synthesis of glucose-sensitive chitosan-poly(vinyl alcohol) hydrogel: Drug release optimization and swelling properties.

    Science.gov (United States)

    Abureesh, Mosab Ali; Oladipo, Akeem Adeyemi; Gazi, Mustafa

    2016-09-01

    The study describes the development of glucose-sensitive hydrogel and optimization of bovine serum albumin release profile from the hydrogel. To enhance the glucose sensitivity and improve the swelling behaviors of the hydrogel system, boric acid crosslinking, and freeze-thawing cycle techniques were used to prepare chitosan-poly(vinyl alcohol) hydrogel. The structure of the resultant hydrogel was confirmed by scanning electron microscopy and Fourier transform infrared spectroscopy. The experimental results revealed that the swelling of the hydrogel was influenced by the pH of the medium, and the hydrogel displayed explicit glucose-sensitivity under physiological conditions. The values of the diffusion exponent range between 0.34 and 0.44 and the diffusion of water into the gel system are assumed to be pseudo-Fickian in nature. Under optimized conditions, the cumulative Bovine serum albumin (BSA) drug releases ranged between 69.33±1.95% and 86.45±1.16% at 37°C in the presence of glucose and pH 7.4, respectively. PMID:26459171

  20. Approaches of Novel drug delivery systems for Anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Vedha Hari B. N

    2013-12-01

    Full Text Available The Human Immunodeficiency Virus (HIV is a pandemic disease spreading very rapidly all over the world, causing approximately 15,000 or more new infections every day and the community acquiring sexually transmitted infections (STIs is prone to easily acquire this HIV infections. The objective of the current review is to describe the comprehensiveness of the various advanced anti-HIV drug delivery systems and compounds that have been developed for targeting drugs to the macrophages, gastric mucosa and brain. Novel drug delivery system gives an opportunity to bypass the shortcomings related to the anti-retroviral treatment. It helps in addressing towards the complexity of dosage form development such as instability, insolubility and limited entrapment of the drugs. Several optional routes have been identified for the management of the ARV therapy which includes transdermal, mucosal (vaginal, rectal, buccal, etc. and also lymphatic delivery, with the application of novel systems like nanoparticles, vesicular systems (liposomes, niosomes, ethosomes, emulsomes, micellar assemblies, etc. This review spotlights the prospectives of novel drug release systems used in preventing the transmission and treatment of retroviral infections.

  1. Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy.

    Directory of Open Access Journals (Sweden)

    Adam Szulkin

    Full Text Available BACKGROUND: Malignant mesothelioma cells have an epithelioid or sarcomatoid morphology, both of which may be present in the same tumor. The sarcomatoid phenotype is associated with worse prognosis and heterogeneity of mesothelioma cells may contribute to therapy resistance, which is often seen in mesothelioma. This study aimed to investigate differences in sensitivity between mesothelioma cell lines to anti-cancer drugs. We studied two novel drugs, selenite and bortezomib and compared their effect to four conventional drugs. We also investigated the immunoreactivity of potential predictive markers for drug sensitivity; Pgp, MRP-1, ERCC1, RRM1, TS, xCT and proteasome 20S subunit. MATERIALS AND METHODS: We treated six mesothelioma cell lines with selenite, bortezomib, carboplatin, pemetrexed, doxorubicin or gemcitabine as single agents and in combinations. Viability was measured after 24 and 48 hours. Immunocytochemistry was used to detect predictive markers. RESULTS: As a single agent, selenite was effective on four out of six cell lines, and in combination with bortezomib yielded the greatest response in the studied mesothelioma cell lines. Cells with an epithelioid phenotype were generally more sensitive to the different drugs than the sarcomatoid cells. Extensive S-phase arrest was seen in pemetrexed-sensitive cell lines. MRP-1 predicted sensitivity of cell lines to treatment with carboplatin and xCT predicted pemetrexed effect. CONCLUSIONS: The observed heterogeneity in sensitivity of mesothelioma cell lines with different morphology highlights the need for more individualized therapy, requiring development of methods to predict drug sensitivity of individual tumors. Selenite and bortezomib showed a superior effect compared to conventional drugs, motivating clinical testing of these agents as future treatment regime components for patients with malignant mesothelioma.

  2. Genomic diversity among drug sensitive and multidrug resistant isolates of Mycobacterium tuberculosis with identical DNA fingerprints.

    Directory of Open Access Journals (Sweden)

    Stefan Niemann

    Full Text Available BACKGROUND: Mycobacterium tuberculosis complex (MTBC, the causative agent of tuberculosis (TB, is characterized by low sequence diversity making this bacterium one of the classical examples of a genetically monomorphic pathogen. Because of this limited DNA sequence variation, routine genotyping of clinical MTBC isolates for epidemiological purposes relies on highly discriminatory DNA fingerprinting methods based on mobile and repetitive genetic elements. According to the standard view, isolates exhibiting the same fingerprinting pattern are considered direct progeny of the same bacterial clone, and most likely reflect ongoing transmission or disease relapse within individual patients. METHODOLOGY/PRINCIPAL FINDINGS: Here we further investigated this assumption and used massively parallel whole-genome sequencing to compare one drug-susceptible (K-1 and one multidrug resistant (MDR isolate (K-2 of a rapidly spreading M. tuberculosis Beijing genotype clone from a high incidence region (Karakalpakstan, Uzbekistan. Both isolates shared the same IS6110 RFLP pattern and the same allele at 23 out of 24 MIRU-VNTR loci. We generated 23.9 million (K-1 and 33.0 million (K-2 paired 50 bp purity filtered reads corresponding to a mean coverage of 483.5 fold and 656.1 fold respectively. Compared with the laboratory strain H37Rv both Beijing isolates shared 1,209 SNPs. The two Beijing isolates differed by 130 SNPs and one large deletion. The susceptible isolate had 55 specific SNPs, while the MDR variant had 75 specific SNPs, including the five known resistance-conferring mutations. CONCLUSIONS: Our results suggest that M. tuberculosis isolates exhibiting identical DNA fingerprinting patterns can harbour substantial genomic diversity. Because this heterogeneity is not captured by traditional genotyping of MTBC, some aspects of the transmission dynamics of tuberculosis could be missed or misinterpreted. Furthermore, a valid differentiation between disease relapse

  3. PES1 regulates sensitivity of colorectal cancer cells to anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Wei [Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing 100142 (China); Qu, Like, E-mail: qulike@bjcancer.org [Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing 100142 (China); Meng, Lin; Liu, Caiyun; Wu, Jian [Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing 100142 (China); Shou, Chengchao, E-mail: scc@bjcancer.org [Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing 100142 (China)

    2013-02-15

    Highlights: ► PES1 was overexpressed in diverse cancer cell lines. ► PES1-ablation enhances DNA damage response by decreasing DNA repair. ► PES1-ablation increases the sensitivity of HCT116 cells to chemotherapeutic agents. ► PES1-ablation is associated with diminished nuclear entry of RAD51. -- Abstract: PES1 (also known as Pescadillo), a nucleolar protein, was involved in biogenesis of ribosomal RNA. Up-regulation of PES1 has been documented in some human cancers, indicating that PES1 may play some crucial roles in tumorigenesis. In our previous study, it was found that silencing of PES1 resulted in decreased proliferation of colorectal cancer cells. We also noticed that depletion of PES1 altered expression profiles of diverse genes. In the present study, we validated the expression changes of a subset of genotoxic stress-related genes in PES1-silenced HCT116 cells by quantitative RT-PCR. The steady and etoposide-induced phosphorylated H2AX (γ-H2AX) were higher in PES1-silenced cells than in control cells. Besides, etoposide-induced γ-H2AX persisted longer in PES1-silenced cells after removing the etoposide. Next, results of comet assay revealed decreased DNA repair after PES1-ablation. PES1-ablated cells were more sensitive to chemotherapeutic agents, which could be reversed by reconstitution with exogenous PES1. Furthermore, deletion of PES1 diminished steady and DNA damage-induced levels of nuclear RAD51. Our results uncover a potential role of PES1 in chemoresistance by regulating DNA damage response in colorectal cancer cells.

  4. Identification of genes involved in the sensitivity to antitumour drug 17-allylamino,17-demethoxygeldanamycin (17AAG).

    Science.gov (United States)

    Barresi, Vincenza; Fortuna, Cosimo G; Garozzo, Roberta; Musumarra, Giuseppe; Scirè, Salvatore; Condorelli, Daniele F

    2006-05-01

    In the present study we analysed the gene expression database provided by the National Cancer Institute in an attempt to correlate activity profiles of geldanamycin, 17AAG and 11 other analogues in 60 human tumor cell lines with their gene expression profiles determined by the cDNA microarray technique. On the basis of the activity profiles two classes of geldanamycin analogues could be distinguished, having geldanamycin and 17AAG, respectively, as prototype compounds (denominated as gelda-like and 17AAG-like classes). Application of the "soft" statistical methodology of PLS (partial least squares modelling in latent variables or projections to latent structures) allowed us to evaluate the influence of each gene expression target in determining the therapeutical responses. The transcript encoding the translocating chain-associated membrane protein (TRAM) showed a significant statistical correlation with activity profiles of 17AAG. In order to validate the role of TRAM in determining sensitivity to 17AAG we induced a selective knocking-down of this transcript by the RNA interference methodology in H226 non-small cell lung carcinoma cell line. The efficiency of double-stranded RNA oligonucleotides (short-interfering RNAs, siRNAs) was determined by measuring TRAM mRNA levels by quantitative real-time RT-PCR at different times (24-72 hours) after siRNA lipotransfection. A significant increase in chemosensitivity to 17AAG was observed in siRNA-silenced cells. Although a number of factors may affect tumour sensitivity to 17AAG the present methodology allowed us to dissect out a single parameter which may be partly responsible for its activity. PMID:16880941

  5. PES1 regulates sensitivity of colorectal cancer cells to anticancer drugs

    International Nuclear Information System (INIS)

    Highlights: ► PES1 was overexpressed in diverse cancer cell lines. ► PES1-ablation enhances DNA damage response by decreasing DNA repair. ► PES1-ablation increases the sensitivity of HCT116 cells to chemotherapeutic agents. ► PES1-ablation is associated with diminished nuclear entry of RAD51. -- Abstract: PES1 (also known as Pescadillo), a nucleolar protein, was involved in biogenesis of ribosomal RNA. Up-regulation of PES1 has been documented in some human cancers, indicating that PES1 may play some crucial roles in tumorigenesis. In our previous study, it was found that silencing of PES1 resulted in decreased proliferation of colorectal cancer cells. We also noticed that depletion of PES1 altered expression profiles of diverse genes. In the present study, we validated the expression changes of a subset of genotoxic stress-related genes in PES1-silenced HCT116 cells by quantitative RT-PCR. The steady and etoposide-induced phosphorylated H2AX (γ-H2AX) were higher in PES1-silenced cells than in control cells. Besides, etoposide-induced γ-H2AX persisted longer in PES1-silenced cells after removing the etoposide. Next, results of comet assay revealed decreased DNA repair after PES1-ablation. PES1-ablated cells were more sensitive to chemotherapeutic agents, which could be reversed by reconstitution with exogenous PES1. Furthermore, deletion of PES1 diminished steady and DNA damage-induced levels of nuclear RAD51. Our results uncover a potential role of PES1 in chemoresistance by regulating DNA damage response in colorectal cancer cells

  6. Synthesis of new thermo/pH sensitive drug delivery systems based on tragacanth gum polysaccharide.

    Science.gov (United States)

    Hemmati, Khadijeh; Ghaemy, Mousa

    2016-06-01

    In this study, new pH/temperature responsive graft copolymers were synthesized based on natural Tragacanth Gum (TG) carbohydrate and their controlled drug release was investigated. Amphiphilic alkyne terminated terpolymers (mPEG-PCL-PDMAEMA-CCH)s consist of methylated poly(ethyleneglycol) (mPEG), polycaprolactone (PCL), and poly(dimethylaminoethylmethacrylate) (PDMAEMA) were synthesized by using ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP), and then were grafted onto azide-functionalized TG molecules by click chemistry. Different techniques such as FT-IR, (1)H NMR, gel permeation chromatography (GPC), thermo-gravimetrical analysis (TGA) and scanning electron microscopy (SEM) were used to verify the successful synthesis of graft copolymers (TG-g-PDMAEMA-PCL-mPEG)s. The graft copolymers self-assembled to single micelles in aqueous solution and upon pH changes further assembled into micellar aggregates. These micelles were used to prepare quercetin loaded nanocarriers by probe sonication method. Size and morphology of the nanocarriers were studied by dynamic light scattering (DLS) and SEM. The in vitro release behavior of quercetin from these micelles showed pH-dependence. The results showed that release profile of quercetin best followed the first order model. PMID:26955747

  7. Radiation synthesis of temperature-sensitive β-cyclodextrin-grafted PEG/poly (N-isopropylacrylamide) hydrogels for drug delivery

    International Nuclear Information System (INIS)

    In this paper, β-cyclodextrin(β-CD)-based water-soluble macromonomer(PEG-β-CD) was synthesized by reaction of β-CD with poly(ethylene glycol) diglycidyl ether(PEGDE). A novel temperature-sensitive hydrogel composed of PEG-β-CD and poly(N-isopropylacrylamide)(PNIPAAm) was prepared by E-beam irradiation. Compared with the normal PNIPAAm hydrogel, the obtained hydrogel had a high swelling ratio at room temperature and exhibited faster shrinking kinetics at temperature close to the lower critical solution temperature (LCST). 5-fluorouracil (5-FU) was chosen as a model drug loaded into the hydrogels, and the release results showed the β-cyclodextrin-containing hydrogels prolonged the release time. (authors)

  8. Radiological Findings of Extensively Drug-Resistant Pulmonary Tuberculosis in Non-AIDS Adults: Comparisons with Findings of Multidrug-Resistant and Drug-Sensitive Tuberculosis

    International Nuclear Information System (INIS)

    This study was designed to describe the radiological findings of extensively drug-resistant (XDR) pulmonary tuberculosis (TB) and to compare the observed findings with findings of drug-sensitive (DS) and non-XDR multidrug- resistant (MDR) TB in non-AIDS patients. From September 1994 to December 2007, 53 MDR TB patients (M:F = 32:21; mean age, 38 years) and 15 XDR TB non-AIDS patients (M:F = 8:7; mean age, 36 years) were enrolled in the study. All of the MDR TB patients had received no treatment or less than one month of anti-TB treatment. In addition, all XDR TB patients received either no anti-TB treatment or only first-line anti-TB drugs. In addition, 141 consecutive DS TB patients (M:F = 79:62; mean age, 51 years) were also enrolled in the study for comparison. Chest radiograph, CT and demographic findings were reviewed and were compared among the three patient groups. For patients with XDR TB, the most frequent radiographic abnormalities were nodules (15 of 15 patients, 100%), reticulo-nodular densities (11 of 15, 73%), consolidation (9 of 15, 60%) and cavities (7 of 15, 47%) that were located mainly in the upper and middle lung zones. As seen on radiographs, significant differences were found for the frequency of nodules and ground-glass opacity lesions (all p < 0.001) (more frequent in DS TB patients than in MDR and XDR TB patients). For the use of CT, significant differences (more frequent in MDR and XDR TB patients) were found for the frequency of multiple cavities, nodules and bronchial dilatation (p = 0.001 or p < 0.001). Patients with MDR TB and XDR TB were younger as compared to patients with DS TB (p < 0.001). Imaging findings were not different between patients with MDR TB and XDR TB. By observation of multiple cavities, nodules and bronchial dilatation as depicted on CT in young patients with acid-fast bacilli (AFB) positive sputum, the presence of MDR TB or XDR TB rather than DS TB can be suggested. There is no significant difference in imaging

  9. MSH3 mismatch repair protein regulates sensitivity to cytotoxic drugs and a histone deacetylase inhibitor in human colon carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jae Myung Park

    Full Text Available BACKGROUND: MSH3 is a DNA mismatch repair (MMR gene that undergoes frequent somatic mutation in colorectal cancers (CRCs with MMR deficiency. MSH3, together with MSH2, forms the MutSβ heteroduplex that interacts with interstrand cross-links induced by drugs such as cisplatin. To date, the impact of MSH3 on chemosensitivity is unknown. METHODS: We utilized isogenic HCT116 (MLH1-/MSH3- cells where MLH1 is restored by transfer of chromosome 3 (HCT116+ch3 and also MSH3 by chromosome 5 (HCT116+3+5. We generated HCT116+3+5, SW480 (MLH1+/MSH3+ and SW48 (MLH1-/MSH3+ cells with shRNA knockdown of MSH3. Cells were treated with 5-fluorouracil (5-FU, SN-38, oxaliplatin, or the histone deacetylase (HDAC inhibitor PCI-24781 and cell viability, clonogenic survival, DNA damage and apoptosis were analyzed. RESULTS: MSH3-deficient vs proficient CRC cells showed increased sensitivity to the irinotecan metabolite SN-38 and to oxaliplatin, but not 5-FU, as shown in assays for apoptosis and clonogenic survival. In contrast, suppression of MLH1 attenuated the cytotoxic effect of 5-FU, but did not alter sensitivity to SN-38 or oxaliplatin. The impact of MSH3 knockdown on chemosensitivity to SN-38 and oxaliplatin was maintained independent of MLH1 status. In MSH3-deficient vs proficient cells, SN-38 and oxaliplatin induced higher levels of phosphorylated histone H2AX and Chk2, and similar results were found in MLH1-proficient SW480 cells. MSH3-deficient vs proficient cells showed increased 53BP1 nuclear foci after irradiation, suggesting that MSH3 can regulate DNA double strand break (DSB repair. We then utilized PCI-24781 that interferes with homologous recombination (HR indicated by a reduction in Rad51 expression. The addition of PCI-24781 to oxaliplatin enhanced cytotoxicity to a greater extent compared to either drug alone. CONCLUSION: MSH3 status can regulate the DNA damage response and extent of apoptosis induced by chemotherapy. The ability of MSH3 to regulate

  10. An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a Poorly Soluble Drug with a Low Melting Surfactant.

    Science.gov (United States)

    Tatavarti, Aditya; Kesisoglou, Filippos

    2015-11-01

    Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface active agent, known to enhance the bioavailability of lipophilic compounds via wettability, solubility, and in some cases permeability enhancement. MK-0536 is an anti-retroviral drug with poor wettability and solubility and a high dose. Based on pharmacokinetic studies in dogs and humans, use of vitamin E TPGS in oral solid formulations of MK-0536 provides desired PK characteristics. The use of vitamin E TPGS, however, in solid dosage forms is limited because of the processing challenges resulting from its waxy nature and low melting temperature (∼37°C). The current study, for the first time, demonstrates the use of an alternative low pressure extrusion and spheronization approach to enable high loadings of the poorly soluble, poorly compactable drug and relatively high levels of vitamin E TPGS. This approach not only aided in mitigating processing challenges arising from most high energy process steps such as milling, compression, and coating, but also enabled a higher drug load formulation that provided superior bioperformance relative to a conventional high shear wet granulated formulation. An encapsulated dosage form consisting of pellets prepared by extrusion spheronization with 75% (w/w) MK-0536 and 10% (w/w) vitamin E TPGS was developed. PMID:26205160

  11. Effect of differentiating agents (all-trans retinoic acid and phorbol 12-myristate 13-acetate on drug sensitivity of HL60 and NB4 cells in vitro.

    Directory of Open Access Journals (Sweden)

    Jadwiga Mirecka

    2008-12-01

    Full Text Available In vitro studies have shown that human myeloid leukemia cell lines: HL60 and NB4 can be stimulated to differentiation by various agents, for example, all-trans retinoic acid (ATRA and phorbol 12-myristate 13-acetate (PMA. The purpose of this study was to investigate whether differentiation of HL60 and NB4 leukemia cell lines induced by ATRA and PMA alters their drug sensitivity. The differentiation along the neutrophil lineage (upon stimulation with ATRA and along the monocyte/macrophage lineage (upon stimulation with PMA was proved by decreased proliferative potential of cells, changes in their morphology, increased ability for NBT reduction and increased expression of CD11b and CD14 cell surface markers. The effect of drugs: cytosine arabinoside, daunorubicin, mitoxantrone and etoposide was examined by Alamar Blue test (proliferation and survival rates, as well as by evaluation of cell smears stained with Hoechst 33342 (apoptotic index. Differentiation resulted in the change of drug sensitivity in both cell lines: the differentiation along the neutrophil pathway (after stimulation with ATRA increased sensitivity to cytosine arabinoside and mitoxantrone but decreased sensitivity to etoposide; the differentiation along the monocyte/macrophage pathway (induced by PMA resulted in the decreased sensitivity of both cell lines to all drugs tested. In conclusion, we have shown that ATRA- and PMA-mediated differentiation of HL60 and NB4 cell lines results in the changes of their drug sensitivity. Our data may provide a contribution to a strategy aimed at a rational combination of differentiating agents and conventional anticancer drugs.

  12. Time-lapse imaging assay using the BioStation CT: A sensitive drug-screening method for three-dimensional cell culture

    OpenAIRE

    Sakamoto, Ruriko; Rahman, M. Mamunur; SHIMOMURA, MANAMI; Itoh, Manabu; Nakatsura, Tetsuya

    2015-01-01

    Three-dimensional (3D) cell culture is beneficial for physiological studies of tumor cells, due to its potential to deliver a high quantity of cell culture information that is representative of the cancer microenvironment and predictive of drug responses in vivo. Currently, gel-associated or matrix-associated 3D cell culture is comprised of intricate procedures that often result in experimental complexity. Therefore, we developed an innovative anti-cancer drug sensitivity screening technique ...

  13. Controlled release from thermo-sensitive PNVCL-co-MAA electrospun nanofibers: The effects of hydrophilicity/hydrophobicity of a drug.

    Science.gov (United States)

    Liu, Lin; Bai, Shaoqing; Yang, Huiqin; Li, Shubai; Quan, Jing; Zhu, Limin; Nie, Huali

    2016-10-01

    The thermo-sensitive copolymer poly(N-vinylcaprolactam-co-methacrylic acid) (PNVCL-co-MAA) was synthesized by free radical polymerization and the resulting nanofibers were fabricated using an electrospinning process. The molecular weight of the copolymer was adjusted by varying the content of methacrylic acid (MAA) while keeping that of N-vinylcaprolactam (NVCL) constant. Hydrophilic captopril and hydrophobic ketoprofen were used as model drugs, and PNVCL-co-MAA nanofibers were used as the drug carrier to investigate the effects of drug on its release properties from nanofibers at different temperatures. The results showed that slow release over several hours was observed at 40°C (above the lower critical solution temperature (LCST) of PNVCL-co-MAA), while the drugs exhibited a burst release of several seconds at 20°C (below the LCST). Drug release slowed with increasing content of the hydrophobic monomer NVCL. The hydrophilic captopril was released at a higher rate than the hydrophobic ketoprofen. The drug release characteristics were dependent on the temperature, the portion of hydrophilic groups and hydrophobic groups in the copolymer and hydrophilicity/hydrophobicity of drug. Study on the mechanism of release showed that Korsmeyer-Peppas model as a major drug release mechanism. Given these results, the PNVCL-co-MAA copolymers are proposed to have useful applications in intellectual drug delivery systems. PMID:27287157

  14. Evaluation of pH-sensitive poly(2-hydroxyethyl methacrylate-co-2-(diisopropylamino)ethyl methacrylate) copolymers as drug delivery systems for potential applications in ophthalmic therapies/ocular delivery of drugs

    OpenAIRE

    P. A. Faccia; F. M. Pardini; J. I. Amalvy

    2015-01-01

    Smart polymers like pH sensitive systems can improve different pharmacological treatment. In this work the behavior of copolymers containing 2-hydroxyethyl methacrylate (HEMA) with different proportions of 2-(diisopropylamino) ethyl methacrylate (DPA) and different amounts of cross-linker agent, ethylene glycol dimethacrylate (EGDMA) are evaluated as pH-sensitive drug delivery systems for potential application in ophthalmic therapies. A detailed characterization of the pH-responsive behavior ...

  15. miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity.

    Science.gov (United States)

    O'Brien, Keith; Lowry, Michelle C; Corcoran, Claire; Martinez, Vanesa G; Daly, Melissa; Rani, Sweta; Gallagher, William M; Radomski, Marek W; MacLeod, Roderick A F; O'Driscoll, Lorraine

    2015-10-20

    Exosomes (EVs) have relevance in cell-to-cell communication carrying pro-tumorigenic factors that participate in oncogenesis and drug resistance and are proposed to have potential as self-delivery systems. Advancing on our studies of EVs in triple-negative breast cancer, here we more comprehensively analysed isogenic cell line variants and their EV populations, tissues cell line variants and their EV populations, as well as breast tumour and normal tissues. Profiling 384 miRNAs showed EV miRNA content to be highly representative of their cells of origin. miRNAs most substantially down-regulated in aggressive cells and their EVs originated from 14q32. Analysis of miR-134, the most substantially down-regulated miRNA, supported its clinical relevance in breast tumours compared to matched normal breast tissue. Functional studies indicated that miR-134 controls STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection into Hs578Ts(i)8 cells (in which it was greatly down-regulated) reduced STAT5B, Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin-induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti-Hsp90 drugs. While the differing effects achieved by transfection or EV delivery are likely to be, at least partly, due to specific amounts of miR-134 delivered by these routes, these EV-based studies identified miRNA-134 as a potential biomarker and therapeutic for breast cancer. PMID:26416415

  16. ET-66ER-STRESS INDUCING DRUGS SENSITIZES GBM TO TEMOZOLOMIDE THROUGH DOWNREGULATION OF MGMT AND INDUCTION OF REGULATED NECROSIS

    Science.gov (United States)

    Xipell, Enric; Martínez-Velez, Naiara; Vera-Cano, Beatriz; Idoate, Miguel Angel; Garzón, Antonia García; Acanda, Arlet M.; Fueyo, Juan; Gomez-Manzano, Candelaria; Alonso, Marta M

    2014-01-01

    Termozolamide (TMZ) is the standard treatment against GBM, unfortunately its therapeutic effect is limited due to the expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Therefore, approaches that overcome the resistance to TMZ could be feasible therapeutic alternatives for this deadly disease. Endoplasmic reticulum (ER) stress suppresses several DNA damage proteins through the unfolding protein response. In this work we sought to evaluate whether ER-stress inducing drugs were able to downmodulate MGMT and sensitize GBM cells to TMZ treatment. Salinomycin (SLM) is a potassium ionophore that has proven effective against cancer stem cells and a possible candidate to induce ER stress. Our data showed that SLM triggered ER stress that was accompanied by the downregulation of MGMT. We obtained the same results with other ER stress inducing drugs (thapsigergin, tunicamycin) suggesting that this is a general mechanism. Chemical inhibition of ER stress reverted the abrogation of MGMT downregulation. Of importance, SLM induced an aberrant autophagic flux that led to regulated necrosis cell death mediated by the action of AIF protein, which induces DNA damage when localized in the nucleus. Combination of TMZ and SLM displayed a potent antitumor effect in vitro and in vivo in mice bearing a GBM stem cell model. Combination treatment induced a significant increase in DNA damage as shown by H2AX activation and PARP. Moreover, we observed AIF in the nucleus, as a result of the regulated necrosis, furthering favoring the DNA damage. Combination treatment showed an increment of the median survival and of long term survivors. Moreover tissue analysis confirmed a dramatic increase in the level of DNA damage. Altogether our results showed that combination treatment induces a potent antiglioma effect in vitro and in vivo. Our data uncover the possibility to exploit ER stress and regulated necrosis as therapeutic strategies for GBM treatment.

  17. FORMULATION AND EVALUATION OF GASTRO RETENTIVE DRUG DELIVERY SYSTEM OF STAVUDINE

    Directory of Open Access Journals (Sweden)

    Voleti. Vijaya Kumar

    2011-02-01

    Full Text Available The present study was designed to formulate and evaluate hydro dynamically balanced Floating Drug Delivery Systems as controlled release modules, which prolongs the release rate of the drugs. Stavudine is an anti- retroviral, reverse transcriptase inhibitor (Nucleoside. Stavudine triphosphate inhibits the HIV reverse transcriptase by competing with natural substrate, thymidine triphosphate. It also causes termination of DNA synthesis by incorporating into it. Formulation of Stavudine as gastro retentive drug delivery systems (GRDDS is especially advantageous over other prolonged type drug delivery systems and conventional tablets because the drug is having absorption window in the duodenum and jejunum level and having relatively short half life. Stavudine was taken as the model drug to optimized formulations was prepared. The floating ability of lipoidal fatty polymers Gelucire 13/01, Gelucire 43/ 01 is compared over various polymers like HPMC, HPMC K4M, Ethocel, Sodium carboxy methyl cellulose. The drug: polymer ratios used to prepare the different formulations were 1:0.5 and 1:1. Blend of all the formulations are prepared by melt granulation technique. All the tablets were subjected for dissolution study using USP dissolution apparatus (USP XXIII paddle method and data were analyzed at 265nm. The drug release of Stavudine from all the formulations followed zero order kinetics. According to the dissolution profiles of formulations drug retardation was enhanced in 1:1 Drug: Polymer proportion than 1:0.5 proportions. Of all the formulations in which Gelucire 13/01 is used as a floating polymer, has retarded the drug successfully upto 12 hours.

  18. Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation.

    Science.gov (United States)

    Huang, Amin; Ju, Huai-Qiang; Liu, Kaiyan; Zhan, Guilian; Liu, Daolu; Wen, Shijun; Garcia-Manero, Guillermo; Huang, Peng; Hu, Yumin

    2016-07-28

    Internal tandem duplication (ITD) of the juxtamembrane region of FMS-like tyrosine kinase-3 (FLT3) receptor is a common type of mutation in adult acute myeloid leukemia (AML), and patient response to FLT3 inhibitors appears to be transient due to the emergence of drug resistance. We established two sorafenib-resistant cell lines carrying FLT3/ITD mutations, including the murine BaF3/ITD-R and human MV4-11-R cell lines. Gene expression profile analysis of the resistant and parental cells suggests that the highest ranked molecular and cellular functions of the differentially expressed genes are related to mitochondrial dysfunction. Both murine and human resistant cell lines display a longer doubling time, along with a significant inhibition of mitochondrial respiratory chain activity and substantial upregulation of glycolysis. The sorafenib-resistant cells exhibit increased expression of a majority of glycolytic enzymes, including hexokinase 2, which is also highly expressed in the mitochondrial fraction and is associated with resistance to apoptotic cell death. The sorafenib-resistant cells are collaterally sensitive to a number of glycolytic inhibitors including 2-deoxyglucose and 3-bromopyruvate propylester. Our study reveals a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. PMID:27132990

  19. The REST Gene Signature Predicts Drug Sensitivity in Neuroblastoma Cell Lines and Is Significantly Associated with Neuroblastoma Tumor Stage

    Directory of Open Access Journals (Sweden)

    Jianfeng Liang

    2014-06-01

    Full Text Available Neuroblastoma is the most common and deadly solid tumor in children, and there is currently no effective treatment available for neuroblastoma patients. The repressor element-1 silencing transcription (REST factor has been found to play important roles in the regulation of neural differentiation and tumorigenesis. Recently, a REST signature consisting of downstream targets of REST has been reported to have clinical relevance in both breast cancer and glioblastoma. However it remains unclear how the REST signature works in neuroblastoma. Publicly available datasets were mined and bioinformatic approaches were used to investigate the utility of the REST signature in neuroblastoma with both preclinical and real patient data. The REST signature was found to be associated with drug sensitivity in neuroblastoma cell lines. Further, neuroblastoma patients with enhanced REST activity are significantly associated with higher clinical stages. Loss of heterozygosity on chromosome 11q23, which occurs in a large subset of high-risk neuroblastomas, tends to be correlated with high REST activity, with marginal significance. In conclusion, the REST signature has important implications for targeted therapy, and it is a prognostic factor in neuroblastoma patients.

  20. Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance.

    Science.gov (United States)

    Schneider, E; Horton, J K; Yang, C H; Nakagawa, M; Cowan, K H

    1994-01-01

    A human breast cancer cell line (MCF7/WT) was selected for resistance to etoposide (VP-16) by stepwise exposure to 2-fold increasing concentrations of this agent. The resulting cell line (MCF7/VP) was 28-, 21-, and 9-fold resistant to VP-16, VM-26, and doxorubicin, respectively. MCF7/VP cells also exhibited low-level cross-resistance to 4'-(9-acridinylamino)-methanesulfon-m-anisidide, mitoxantrone, and vincristine and no cross-resistance to genistein and camptothecin. Furthermore, these cells were collaterally sensitive to the alkylating agents melphalan and chlorambucil. DNA topoisomerase II levels were similar in both wild-type MCF7/WT and drug-resistant MCF7/VP cells. In contrast, topoisomerase II from MCF7/VP cells appeared to be 7-fold less sensitive to drug-induced cleavable complex formation in whole cells and 3-fold less sensitive in nuclear extracts than topoisomerase II from MCF7/WT cells. Although this suggested that the resistant cells may contain a qualitatively altered topoisomerase II, no mutations were detected in either the ATP-binding nor the putative breakage/resealing regions of either DNA topoisomerase II alpha or II beta. In addition, the steady-state intracellular VP-16 concentration was reduced by 2-fold in the resistant cells, in the absence of detectable mdr1/P-gp expression and without any change in drug efflux. In contrast, expression of the gene encoding the MRP was increased at least 10-fold in resistant MCF7/VP cells as compared to sensitive MCF7/WT cells. These results suggest that resistance to epipodophyllotoxins in MCF7/VP cells is multifactorial, involving a reduction in intracellular drug concentration, possibly as a consequence of MRP overexpression, and an altered DNA topoisomerase II drug sensitivity. PMID:7903202

  1. 人类免疫缺陷病毒感染者混合感染丙型和乙型肝炎病毒后对高效抗逆转录病毒治疗疗效的影响%The influence of human immunodeficiency virus co-infection with hepatitis C virus and hepatitis B virus on the efficacy of high active anti-retroviral therapy

    Institute of Scientific and Technical Information of China (English)

    李晓菲; 阚全程; 何云; 余祖江; 李志勤; 梁红霞

    2010-01-01

    Objective To evaluate the impact of HIV co-infection with HCV or HBV on the efficacy of highly active anti-retroviral therapy (HARRT). Methods The patients were divided into three groups: HIV + HBV + HCV co-infection group ( 23 patients), HIV + HCV co-infection group ( 166 patients), and HIV-only group (178 patients). HIV RNA, HCV RNA or HBV DNA were detected by real time PCR before treatment and 1,3,6,9 and 12 monthes after treatment, meanwhile the counts of CD4+ T lymphocyte and liver function including ALT, AST and TBil were tested. Results During one-year HAART, HIV RNA of HIV-only group, HIV + HBV + HCV co-infection group and HIV + HCV co-infection group decreased significantly from (6.78 ± 1.08), (6.23 ± 1.34), (6.54 ± 1.23) lg copies/ml to (0.53 ±0.15), (0.67 ±0.16),(0.43 ±0.11 ) lg copies/ml respectively (P<.001 ). And CD4+ T lymphocyte counts of the three groups elevated significantly from ( 197 ± 127), (184 ± 113), (213 ± 143) cells/μl to (382 ±74), (383 ±70),(378 ±76) cells/μl respectively (P <0.001 ). However there were no differences among the three groups in HIV RNA and CD4+ T lymphocyte counts. There were no differences in liver functions including ALT,AST and TBil among the three groups. Conclusiom HIV co-infected with HBV and/or HCV does not impact on the efficacy of HAART. What more, HAART does not impact HCV replication.%目的 观察HIV感染者合并HCV和HBV感染后对高效抗逆转录病毒治疗(HAART)疗效的影响.方法 对某地区HIV、HCV共感染患者166例(HIV+HCV组),HIV、HCV和HBV混合感染患者23例(H1V+HCV+HBV组)及单纯HIV感染者178例,给予1年的HAART治疗,观察3组患者病毒学反应、免疫学反应和肝功能动态变化.以流式细胞仪检测外周血CD4+T淋巴细胞;实时PCR定量检测HCV、HIV和HBV病毒载量.结果 单纯HIV感染组、HIV+HCV+HBV组和HIV+HCV组经HAART 1年后,HIV病毒载量分别由治疗前(6.78±1.08)、(6.23±1.34)、(6.54±1.23)lg拷贝/ml下降至(0

  2. Preparation of pH-sensitive poly(ethylene oxide) hydrogels grafted by γ-ray irradiation and their applications for drug delivery system

    International Nuclear Information System (INIS)

    Hydrogels are three-dimensional networks of hydrophilic polymers held together by crosslinks of covalent bonds or ionic bonds and secondary forces in the form of hydrogen bonds or hydrophobic interactions. Environmentally sensitive hydrogels have an enormous potential for various applications. Either pH-sensitive and/or temperature- sensitive hydrogels can be used for a site-specific controlled drug delivery. Especially, pH-sensitive hydrogels have been most frequently used to develop controlled release formulations for oral administration. All the pH-sensitive hydrogels contain pendent acidic, for example carboxylic and sulfonic acids, or basic, for example ammonium salts, groups that either accept or release protons in response to changes in environmental pH[3-5]. These ionic hydrogels are the swollen polymer networks which show sudden or gradual changes in their dynamic and equilibrium swelling behavior as a result of changing the external pH. In these gels, ionization occurs when the pH of the environment is above the pKa of the ionizable group . As the degree of ionization increases (pH increase in the system), the number of fixed charges increases, resulting in increased electrostatic repulsions between the chains. Irradiation, especially if combined with simultaneous sterilization of the product, is a very convenient tool for the synthesis of hydrogels. Radiation processing has many advantages over other conventional methods. For initiation processes, radiation differs from chemical initiation. In radiation processing, no catalysts or additives are needed to initiate the reaction. The advantages of the radiation methods are that they are relatively simple, and moreover, the degree of crosslinking, which strongly determines the extent of swelling in hydrogels, can be controlled easily by varying the absorbed dose. Therefore, these methods are found to be very useful in preparing hydrogels for medical applications, where even a small contamination is

  3. Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid/Poly(vinyl alcohol IPN Hydrogel and Its Drug Controlled Release

    Directory of Open Access Journals (Sweden)

    Jingqiong Lu

    2015-01-01

    Full Text Available Modified poly(aspartic acid/poly(vinyl alcohol interpenetrating polymer network (KPAsp/PVA IPN hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid grafting 3-aminopropyltriethoxysilane (KH-550 and poly(vinyl alcohol (PVA as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR and scanning electron microscopy (SEM. The thermal stability was analyzed by thermogravimetric analysis (TGA. The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN, and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid and 62.5 wt% at pH = 7.4 (simulated intestinal fluid, respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery.

  4. Stability behaviour of antiretroviral drugs and their combinations. 2: Characterization of interaction products of lamivudine and tenofovir disoproxil fumarate by mass and NMR spectrometry.

    Science.gov (United States)

    Kurmi, Moolchand; Kushwah, Bhoopendra Singh; Sahu, Archana; Narayanam, Mallikarjun; Singh, Saranjit

    2016-06-01

    This study focused on drug-drug interaction behaviour among lamivudine (3TC) and tenofovir disoproxil fumarate (TDF), the two anti-retroviral drugs. Apart from pre-known degradation products of individual drugs, a total of twelve interaction products were detected by high performance liquid chromatography (HPLC) using a C18 column as the stationary phase, and methanol and ammonium formate in gradient mode as the mobile phase. The same HPLC method was employed for liquid chromatography-high resolution mass spectrometry (LC-HRMS) and liquid chromatography-multi stage mass spectrometry (LC-MS(n)). For the characterization of interaction products, stability samples were subjected to LC-HRMS, LC-MS(n) and online hydrogen/deuterium exchange studies. Two isomeric interaction products were isolated and subjected to 1D and 2D nuclear magnetic resonance (NMR) studies. The collated information was utilized for the characterization of all twelve interaction products of the two drugs. Pathway of their formation was also outlined. PMID:27042808

  5. Confocal fluorescence microscopy: An ultra-sensitive tool used to evaluate intracellular antiretroviral nano-drug delivery in HeLa cells

    Science.gov (United States)

    Mandal, Subhra; Zhou, You; Shibata, Annemarie; Destache, Christopher J.

    2015-08-01

    In the last decade, confocal fluorescence microscopy has emerged as an ultra-sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular-level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the world's major health threats by claiming approximately 7,000 new infections daily worldwide. Although combination antiretroviral drugs (cARV) therapy has improved the life-expectancy of HIV-infected patients, routine use of high doses of cARV has serious health consequences and requires complete adherence to the regimen for success. Thus, our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co-glycolic acid) (PLGA) nanoparticles (cARV-NPs) as drug delivery system. However, important aspects of cARV-NPs that require special emphasis are their cellular-uptake, potency, and sustained drug release efficiency over-time. In this article, ultra-sensitive confocal microscopy is been used to evaluate the uptake and sustained drug release kinetics of cARV-NPs in HeLa cells. To evaluate with the above goal, instead of cARV-drug, Rhodamine6G dye (fluorescent dye) loaded NPs (Rho6G NPs) have been formulated. To correlate the Rhodamin6G release kinetics with the ARV release from NPs, a parallel HPLC study was also performed. The results obtained indicate that Rho6G NPs were efficiently taken up at low concentration (delivery with the potential to reduce drug dosage as well as the number of drug administrations per month.

  6. Comparative proteomic analysis of sequential isolates of Mycobacterium tuberculosis from a patient with pulmonary tuberculosis turning from drug sensitive to multidrug resistant

    Directory of Open Access Journals (Sweden)

    Amit Singh

    2015-01-01

    Full Text Available Background & objectives: Tuberculosis is a major health problem in India, and the emergence of multidrug resistant (MDR and extensively drug resistant (XDR strains of Mycobacterium tuberculosis (Mtb has further complicated the situation. Though several studies characterizing drug sensitive and drug resistant strains are available in literature, almost all studies are done on unrelated strains. Therefore, the objective of this study was to compare the proteomic data of four sequential isolates of Mtb from a single patient who developed MDR-TB during the course of anti-tuberculosis therapy (ATT. Methods: In this study, using two-dimensional (2D gel electrophoresis and MALDI-TOF mass spectrometry, we compared and analyzed the cell lysate proteins of Mtb sequential clinical isolates from a patient undergoing anti-TB treatment. The mRNA expression levels of selected identified proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR. Results: The genotypes of all four isolates remained homologous, indicating no re-infection. The initial isolate (before treatment was sensitive to all first-line drugs, but the consecutive isolates were found to be resistant to isoniazid (INH and rifampicin (RIF and developed mutations in the katG, inhA and rpoB. the intensities of 27 protein spots were found to be consistently overexpressed in INH and RIF resistant isolates. The most prominent and overexpressed proteins found during the development of drug resistance were GarA (Rv1827, wag31 (Rv2145c, Rv1437 and Rv2970c. Interpretation & conclusions: This preliminary proteomic study provides an insight about the proteins that are upregulated during drug resistance development. These upregulated proteins, identified here, could prove useful as immunodiagnostic and possibly drug resistant markers in future. However, more studies are required to confirm these findings.

  7. A Mathematical Model for the Transmission and Spread of Drug Sensitive and Resistant Malaria Strains within a Human Population

    OpenAIRE

    Tumwiine, Julius; Hove-Musekwa, Senelani D.; Nyabadza, Farai

    2014-01-01

    Malaria remains by far the world's most important tropical disease, killing more people than any other communicable disease. A number of preventive and control measures have been put in place and most importantly drug treatment. The emergence of drug resistance against the most common and affordable antimalarials is widespread and poses a key obstacle to malaria control. A mathematical model that incorporates evolution of drug resistance and treatment as a preventive strategy is formulated an...

  8. Worry as a window into the lives of people who use injection drugs: a factor analysis approach

    Directory of Open Access Journals (Sweden)

    Cowen Laura

    2009-07-01

    Full Text Available Abstract Background The concept of risk dominates the HIV/AIDS literature pertaining to People Who Use Injection Drugs (PWUID. In contrast the associated concept of worry is infrequently applied, even though it can produce important perspectives of PWUID's lives. This study asked a sample (n = 105 of PWUID enrolled in a Victoria, British Columbia needle exchange program to evaluate their degree of worry about fourteen factors they may encounter in their daily lives. Methods Exploratory factor analysis was used to analyze their responses. Results Factor analysis delineated three factors: 1 overall personal security, 2 injection drug use-specific risks including overdosing and vein collapse and, 3 contracting infectious diseases associated with injection drug use (e.g. HIV/AIDS and hepatitis C. Conclusion PWUID in this study not only worry about HIV/AIDS but also about stressful factors in their daily life which have been linked to both increased HIV/AIDS risk behaviour and decreased anti-retroviral treatment adherence. The importance PWUID give to this broad range of worry/concerns emphasizes the need to place HIV/AIDS intervention, education, and treatment programs within a broader harm-reduction framework that incorporates their perspectives on both worry and risk.

  9. Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening

    Energy Technology Data Exchange (ETDEWEB)

    Jiguet Jiglaire, Carine, E-mail: carine.jiguet-jiglaire@univ-amu.fr [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Baeza-Kallee, Nathalie; Denicolaï, Emilie; Barets, Doriane [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Metellus, Philippe [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); APHM, Timone Hospital, Department of Neurosurgery, 13005 Marseille (France); Timone Hospital, 264 Rue Saint Pierre, 13385 Marseille Cedex 5 (France); and others

    2014-02-15

    Identification of new drugs and predicting drug response are major challenges in oncology, especially for brain tumors, because total surgical resection is difficult and radiation therapy or chemotherapy is often ineffective. With the aim of developing a culture system close to in vivo conditions for testing new drugs, we characterized an ex vivo three-dimensional culture system based on a hyaluronic acid-rich hydrogel and compared it with classical two-dimensional culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of human glioblastomas were subjected to radiation therapy and chemotherapy drugs. It appears that 3D hydrogel preserves the original cancer growth behavior and enables assessment of the sensitivity of malignant gliomas to radiation and drugs with regard to inter-tumoral heterogeneity of therapeutic response. It could be used for preclinical assessment of new therapies. - Highlights: • We have compared primary glioblastoma cell culture in a 2D versus 3D-matrix system. • In 3D morphology, organization and markers better recapitulate the original tumor. • 3D-matrix culture might represent a relevant system for more accurate drug screening.

  10. Drug release behavior of a pH/temperature sensitive calcium alginate/poly(N-acryloylglycine bead with core-shelled structure

    Directory of Open Access Journals (Sweden)

    2010-12-01

    Full Text Available In this study, a novel pH/temperature sensitive hydrogel bead with core-shelled structure, composed of calcium alginate (Ca-alginate and poly((N-acryloylglycine (PAG, was prepared using as a drug delivery system. The equilibrium swelling has indicated the distinct sensitivities of the beads to pH value and temperature. In pH = 7.4 phosphate buffer solution (PBS, the cumulative release amount of indomethacin loaded in the core of the beads was about 83.5% within 650 min, whereas this value only reached 16.6% in pH = 2.1 PBS. In addition, the release rate of indomethacin was much faster at 37°C than that at 24°C. The experimental results have showed that the Ca-alginate/PAG beads have a potential application for the pH/temperature-controlled drug release carrier in the biomedical field.

  11. Comparision of the Cytotoxic Effects of Birch Bark Extract, Betulin and Betulinic Acid Towards Human Gastric Carcinoma and Pancreatic Carcinoma Drug-sensitive and Drug-Resistant Cell Lines

    Directory of Open Access Journals (Sweden)

    Hermann Lage

    2009-04-01

    Full Text Available Betulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicity towards a number of cancer cell lines. These compounds can be found in the bark of the many plants. In this report we have compared the cytotoxic activity of crude birch bark extract and purified betulin and betulinic acid towards human gastric carcinoma (EPG85-257 and human pancreatic carcinoma (EPP85-181 drug-sensitive and drug-resistant (daunorubicin and mitoxantrone cell lines. Our results show significant differences in sensitivity between cell lines depending on the compound used, and suggest that both betulin and betulinic acid can be considered as a promising leads in the treatment of cancer.

  12. A simultaneous determination of related substances by high performance liquid chromatography in a drug product using quality by design approach.

    Science.gov (United States)

    Tol, Trupti; Kadam, Nilesh; Raotole, Nilesh; Desai, Anita; Samanta, Gautam

    2016-02-01

    The combination of Abacavir, Lamivudine and Dolutegravir is an anti-retroviral formulation that displays high efficacy and superiority in comparison to other anti-retroviral combinations. Analysis of related substances in this combination drug product was very challenging due to the presence of nearly thirty peaks including the three active pharmaceutical ingredients (APIs), eleven known impurities and other pharmaceutical excipients. Objective of this study was to develop a single, selective, and robust high performance liquid chromatography method for the efficient separation of all peaks. Initially, one-factor-at-a-time (OFAT) approach was adopted to develop the method. But, it could not resolve all the critical peaks in such complex matrix. This led to the advent of two different HPLC methods for the determination of related substances, one for Abacavir and Lamivudine and the other for Dolutegravir. But, since analysis of a single sample using two methods instead of one is time and resource consuming and thus expensive, an attempt was made to develop a single and robust method by adopting quality by design (QbD) principles. Design of Experiments (DoE) was applied as a tool to achieve the optimum conditions through Response surface methodology with three method variables, pH, temperature, and mobile phase composition. As the study progressed, it was discovered that establishment of the design space was not viable due to the completely distant pH requirements of the two responses, i.e. (i) retention time for Lamivudine carboxylic acid and (ii) resolution between Abacavir impurity B and unknown impurity. Eventually, neglecting one of these two responses each time, two distinguished design spaces have been established and verified. Edge of failures at both design spaces indicate high probability of failure. It therefore, becomes very important to identify the most robust zone or normal operating range (NOR) within the design space with low risk of failure and high

  13. CS/PAA@TPGS/PLGA nanoparticles with intracellular pH-sensitive sequential release for delivering drug to the nucleus of MDR cells.

    Science.gov (United States)

    Wang, Ying-Ying; Zhang, Dan-Dan; Kong, Yan-Yan; Shao, Luan-Luan; Zhang, Fen-Yi; Gao, Yu; Mu, Xu; Wang, Jie; Li, Hao-Fan; Yu, Shu-Qin; Xu, Qian

    2016-09-01

    Development of novel nano-drug delivery systems (NDDS) that can transport anticancer drugs into cell nuclei is still a highly desirable strategy for reversing multi-drug resistance (MDR) in cancer therapy. Herein, we designed and prepared a novel NDDS, designated S@L NPs, in which several smaller nanoparticles are contained within a larger nanoparticle. Our S@L NPs (CS/PAA/VP-16@TPGS/PLGA NPs) possess a structure in which smaller nanoparticles (Chitosan-Poly(acrylic acid) nanoparticles, CS/PAA NPs) containing the drug etoposide (VP-16) are loaded within a larger nanoparticle (Vitamin E d-a-tocopheryl polyethylene glycol 1000 succinate-modified poly(lactic-co-glycolic acid) nanoparticles, TPGS/PLGA NPs). The system utilizes intracellular pH gradients to achieve pH-sensitive sequential release within different intracellular domains of MDR cells. S@L NPs could be triggered to degrade and release CS/PAA/VP-16 NPs in the acid environment of the cytosol, endosomes or lysosomes, and CS/PAA/VP-16 NPs were capable of entering the nucleus through nucleopores. It is significant that CS/PAA/VP-16 NPs exhibit disaggregation in the alkaline environment of the nucleus and thereby release the contained anticancer drug. Further mechanistic studies showed that CS/PAA/VP-16 NPs escaped retention and degradation within lysosomes and protected the drug from P-glycoprotein-induced efflux. Simultaneously, S@L NPs enhanced the anticancer effect of the loaded drug by inducing autophagy and apoptosis of MDR cells. This novel NDDS may provide a promising platform for nuclear drug delivery for reversing MDR. PMID:27289313

  14. 肝癌化疗药敏试验与应用研究%Research and exploratory of chemotherapy drugs sensitivity tests in liver cancer

    Institute of Scientific and Technical Information of China (English)

    傅颖媛; 梅钧; 饶荣生; 张学敏; 徐江霞; 曾小平; 许静

    2008-01-01

    Objective To investigate the feasibility of the drug sensitivity tests of clinical liver cancer in vitro in order to prgvide a significant experimental basis to formulate a reasonable"individualizied"treatment plan.Methods 3H-thymidine incorporation assay(3H-TdR method)and MTS colorimetric assay(MTS method)were used to test the sensitivities of SMMC-7721 and NKM-45 cell lines to nine species of anticancer drugs[Hydroxyeamptothecin(HCPT),vinorelbine(NVB),adriamycin(ADM),5-fluomuracil(5-Fu),cisplatin(DDP),Pingyangmyein(PYM),mitomycin(MMC),Etopeside(VP-16),methotrexate(MTX)],and the other drug sensitivity test was carried on 53 eases of clinical tumor specimen(including 32 eases of liver cancer,13 cases of colorectal cancer,and 8 eases of gastric cancer)by MTS method.Results There Was no significant difference between MTS method and 3H-TdR method for the drug sensitivity tests(P>0.05).The total effective rates of these 9 drugs to 32 cases of clinical fiver ceancer cells samples were significantly different.Of which,the highest one was HCPT (90.63%)and the second NVB(78.10%).The sensitivities of the three species of clinical tumors to 9 drugs were different or partially different.Conclusion Both MTS method and 3H-TdR method are reliable and stable method for the drug sensitivity tests.It is necessary that the drug sensitivity test be carried on the patients before chemotherspy.HCPT and NVB can be priority for liver cancer patients if there is no other choice.%目的 探讨临床肝癌组织细胞体外药敏试验的可行性,为临床制定合理的肿瘤"个体化"治疗方案提供依据.方法 采用MTS比色法和3H-TdR掺入法测定肝癌SMMC-7721及胃癌NKM45细胞株对临床常用9种抗癌药物[羟基喜树碱(HCPT)、盖诺(NVB)、阿霉素(ADM)、5-氟尿嘧啶(5-FU)、顺铂(DDP)、平阳霉素(PYM)、丝裂霉素(MMC)、足叶乙甙(VP-16)、甲氨蝶呤(MTX)]的敏感性,并用MTS比色法对53例临床肿瘤标本(其中肝癌32例、结直肠癌13

  15. Avaliação ultra-sonográfica, ecocardiográfica fetal e resultados perinatais em gestantes portadoras do HIV em uso de terapia anti-retroviral Ultrasound examination, fetal echocardiography and prenatal outcome in HIV-positive pregnant women under antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Marco Antonio Borges Lopes

    2007-10-01

    , with statistic significance (p=0.015 for the cardiac abnormalities. There were eight cases (7.3% of oligohydramnios and 11 cases (10% of polyhydramnios in the Study Group against two cases (1% of oligohydramnios and none of polyhydramnios in the Control Group (p=0.004 and p<0.001. Eleven (10% newborn babies were too small for their gestation age in the Study Group, against three (2.7% in the Control Group (p=0,002. The incidence of preterm delivery was 8.7 and 2.5% in the Study and Control Groups respectively (p=0.041. It was observed six cases (5.5% of fetal death in the Study Group and none in the Control Group (p=0.002. CONCLUSIONS: in the present study, we have observed higher prevalence of amniotic fluid volume and congenital heart abnormalities in the Study Group as compared to the Control Group. Statistical significance was found in both situations. The high fetal death rate found in the Study Group was probably due to fetal malformation, whereas the high prematurity rate and the prevalence of small size for the gestational age of the newborn babies were probably related to antiretroviral therapy, smoking and drug abuse.

  16. Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

    Directory of Open Access Journals (Sweden)

    Karolin Hijazi

    Full Text Available Anti-retroviral (ARV -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on

  17. Mitoxantrone Loaded Superparamagnetic Nanoparticles for Drug Targeting: A Versatile and Sensitive Method for Quantification of Drug Enrichment in Rabbit Tissues Using HPLC-UV

    Directory of Open Access Journals (Sweden)

    Rainer Tietze

    2010-01-01

    Full Text Available In medicine, superparamagnetic nanoparticles bound to chemotherapeutics are currently investigated for their feasibility in local tumor therapy. After intraarterial application, these particles can be accumulated in the targeted area by an external magnetic field to increase the drug concentration in the region of interest (Magnetic-Drug-Targeting. We here present an analytical method (HPLC-UV, to detect pure or ferrofluid-bound mitoxantrone in a complex matrix even in trace amounts in order to perform biodistribution studies. Mitoxantrone could be extracted in high yields from different tissues. Recovery of mitoxantrone in liver tissue (5000 ng/g was 76±2%. The limit of quantification of mitoxantrone standard was 10 ng/mL ±12%. Validation criteria such as linearity, precision, and stability were evaluated in ranges achieving the FDA requirements. As shown for pilot samples, biodistribution studies can easily be performed after application of pure or ferrofluid-bound mitoxantrone.

  18. pH-sensitive micellar systems for controlled drug delivery: synthesis and structural characterization by small-angle neutron scattering

    OpenAIRE

    Joset, Arnaud; Jérôme, Christine; Brulet, Annie; Leyh, Bernard

    2009-01-01

    The aim of the project is the preparation of micellar nanocarriers made of biocompatibles copolymers and their structural analysis by Small Angle Neutron Scattering (SANS). These micelles could be used in drug delivery applications to fight cancer1. The hydrophobic polycaprolactone (PCL) core is intended to incorporate the drug. The corona of hydrophilic polyethylene oxide (PEO) stabilizes the nanocarriers with respect to the plasma proteins. The pH in the neighborhood of the tumoral cells is...

  19. A comprehensive and sensitive method for hair analysis in drug-facilitated crimes and incorporation of zolazepam and tiletamine into hair after a single exposure.

    Science.gov (United States)

    Kim, Jihyun; Yum, Hyesun; Jang, Moonhee; Shin, Ilchung; Yang, Wonkyung; Baeck, Seungkyung; Suh, Joon Hyuk; Lee, Sooyeun; Han, Sang Beom

    2016-01-01

    Hair is a highly relevant specimen that is used to verify drug exposure in victims of drug-facilitated crime (DFC) cases. In the present study, a new analytical method involving ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed for determining the presence of model drugs, including zolazepam and tiletamine and their metabolites in hair specimens from DFCs. The incorporation of zolazepam and tiletamine into hair after a single exposure was investigated in Long-Evans rats with the ratio of the hair concentration to the area under the curve. For rapid and simple sample preparation, methanol extraction and protein precipitation were performed for hair and plasma, respectively. No interference was observed in drug-free hair or plasma, except for hair-derived diphenhydramine in blank hair. The coefficients of variance of the matrix effects were below 12%, and the recoveries of the analytes exceeded 70% in all of the matrices. The precision and accuracy results were satisfactory. The limits of quantification ranged from 20 to 50 pg in 10 mg of hair. The drug incorporation rates were 0.03 ± 0.01% for zolazepam and 2.09 ± 0.51% for tiletamine in pigmented hair. We applied the present method to real hair samples in order to determine the drug that was used in seven cases. These results suggest that this comprehensive and sensitive hair analysis method can successfully verify a drug after a single exposure in crimes and can be applied in forensic and clinical toxicology laboratories. PMID:26454443

  20. Herb-Drug Pharmacokinetic Interactions: Transport and Metabolism of Indinavir in the Presence of Selected Herbal Products

    Directory of Open Access Journals (Sweden)

    Carlemi Calitz

    2015-12-01

    Full Text Available Patients receiving anti-retroviral drug treatment are sometimes simultaneously taking herbal remedies, which may result in pharmacokinetic herb-drug interactions. This study aimed to determine if pharmacokinetic interactions exist between selected commercially available herbal products (i.e., Linctagon Forte®, Viral Choice® and Canova® and indinavir in terms of in vitro transport and metabolism. Bi-directional transport of indinavir was evaluated across Caco-2 cell monolayers in the presence and absence of the selected herbal products and verapamil (positive control. Metabolism of indinavir was determined in LS180 cells in the presence and absence of the selected herbal products as well as ketoconazole (positive control. The secretory transport of indinavir increased in a concentration dependent way in the presence of Linctagon Forte® and Viral Choice® when compared to that of indinavir alone. Canova® only slightly affected the efflux of indinavir compared to that of the control group. There was a pronounced inhibition of the metabolism of indinavir in LS180 cells over the entire concentration range for all the herbal products investigated in this study. These in vitro pharmacokinetic interactions indicate the selected herbal products may affect indinavir’s bioavailability, but the clinical significance needs to be confirmed with in vivo studies before final conclusions can be made.

  1. Herb-Drug Pharmacokinetic Interactions: Transport and Metabolism of Indinavir in the Presence of Selected Herbal Products.

    Science.gov (United States)

    Calitz, Carlemi; Gouws, Chrisna; Viljoen, Joe; Steenekamp, Jan; Wiesner, Lubbe; Abay, Efrem; Hamman, Josias

    2015-01-01

    Patients receiving anti-retroviral drug treatment are sometimes simultaneously taking herbal remedies, which may result in pharmacokinetic herb-drug interactions. This study aimed to determine if pharmacokinetic interactions exist between selected commercially available herbal products (i.e., Linctagon Forte(®), Viral Choice(®) and Canova(®)) and indinavir in terms of in vitro transport and metabolism. Bi-directional transport of indinavir was evaluated across Caco-2 cell monolayers in the presence and absence of the selected herbal products and verapamil (positive control). Metabolism of indinavir was determined in LS180 cells in the presence and absence of the selected herbal products as well as ketoconazole (positive control). The secretory transport of indinavir increased in a concentration dependent way in the presence of Linctagon Forte(®) and Viral Choice(®) when compared to that of indinavir alone. Canova(®) only slightly affected the efflux of indinavir compared to that of the control group. There was a pronounced inhibition of the metabolism of indinavir in LS180 cells over the entire concentration range for all the herbal products investigated in this study. These in vitro pharmacokinetic interactions indicate the selected herbal products may affect indinavir's bioavailability, but the clinical significance needs to be confirmed with in vivo studies before final conclusions can be made. PMID:26690396

  2. Overexpression of miR-34c regulates the sensitivity to doxorubicin in drug-resistant breast cancer cell lines MCF-7/DOX

    Institute of Scientific and Technical Information of China (English)

    Han Li; Tong Li; Li-Hong Zhang

    2016-01-01

    Objective:To study the regulating effect of overexpressing miR-34c on the sensitivity to doxorubicin in drug-resistant breast cancer cell line MCF-7/DOX. Methods:Breast cancer cell lines MCF-7 and drug-resistant breast cancer cell lines MCF-7/DOX were cultured, transfected with miR-34c and negative control fragments and treated with different doses of doxorubicin;treated cells were taken, CCK-8 kits were used to detect cell viability, and RNA detection kits were used to detect mRNA contents of drug resistance-related genes. Results: miR-34a, 34b and 34c expression levels in MCF-7/DOX cell lines were lower than those in MCF-7 cell lines and the reduction of miR-34c expression level was the most significant, and mRNA contents of MDR1, BCRP, UCP2, Twist and c-Src were significantly higher than those in MCF-7 cell lines;after transfection of miR-34c, the inhibitory effect of doxorubicin on the viability of MCF-7/DOX cell lines was stronger than that of MCF-7/DOX cell lines transfected with negative control, and mRNA contents of MDR1, BCRP, UCP2, Twist and c-Src were significantly lower than those in MCF-7 cell lines transfected with negative control. Conclusions:Overexpression of miR-34c in drug-resistant breast cancer cell lines MCF-7/DOX can increase the sensitivity to doxorubicin and inhibit the expression levels of drug resistance-related genes MDR1, BCRP, UCP2, Twist and c-Src .

  3. Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy

    Science.gov (United States)

    Lim, Eun-Kyung; Sajomsang, Warayuth; Choi, Yuna; Jang, Eunji; Lee, Hwunjae; Kang, Byunghoon; Kim, Eunjung; Haam, Seungjoo; Suh, Jin-Suck; Chung, Sang Jeon; Huh, Yong-Min

    2013-11-01

    Smart drug delivery systems that are triggered by environmental conditions have been developed to enhance cancer therapeutic efficacy while limiting unwanted effects. Because cancer exhibits abnormally high local acidities compared to normal tissues (pH 7.4) due to Warburg effects, pH-sensitive systems have been researched for effective cancer therapy. Chitosan-based intelligent theragnosis nanocomposites, N-naphthyl- O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles ( NChitosan-DMNPs), were developed in this study. NChitosan-DMNPs are capable of pH-sensitive drug release with MR-guided images because doxorubicin (DOX) and magnetic nanocrystals (MNCs) are encapsulated into the designed N-naphthyl- O-dimethymaleoyl chitosan ( N-nap- O-MalCS). This system exhibits rapid DOX release as acidity increases, high stability under high pH conditions, and sufficient capacity for diagnosing and monitoring therapeutic responses. These results demonstrate that NChitosan-DMNPs have potential as theragnosis nanocomposites for effective cancer therapy.

  4. An in vitro drug sensitivity test using a higher 3H-TdR incorporation and a modified human tumor stem cell assay

    International Nuclear Information System (INIS)

    An in vitro drug sensitivity test was developed to evaluate the lethal effects of drugs on human pulmonary carcinoma cells (HPCC). This method was a variant and combination of Human Tumor Stem (HTSCA) and a short-term test using 3H-TdR incorporation. It consisted of a cell containing liquid top layer and a soft agar bottom layer in 24-well microplates. The medium was RPMI 1640 supplemented with 20% malignant pleural effusion, which could enhance 3H-TdR incorporation into malignant cells. When 50%, 40%, 30% and 30% of cell survival rate defined as sensitivity-threshold for VCR, MMC, DDP and ADM respectively, in the vitro effectiveness were close to those of clinical single-drug treatment in HPCC by Wright et al. This method was also compared with HTSCA in ten human lung cancer cell lines and four pulmonary carcinoma tissues. The agreement rates were 83% and 100% respectively. Thus we presume this system is more useful for oncological clinics than the others

  5. The Effectiveness and Safety of Fluoroquinolone-Containing Regimen as a First-Line Treatment for Drug-Sensitive Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Lee, Hyun Woo; Lee, Jung Kyu; Kim, Eunyoung; Yim, Jae-Joon; Lee, Chang-Hoon

    2016-01-01

    Background Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis. Methods We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included. Results Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20–1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59–0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46–2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate. Conclusions Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis. PMID:27455053

  6. Collateral Resistance and Sensitivity Modulate Evolution of High-Level Resistance to Drug Combination Treatment in Staphylococcus aureus

    DEFF Research Database (Denmark)

    de Evgrafov, Mari Cristina Rodriguez; Gumpert, Heidi; Munck, Christian;

    2015-01-01

    As drug-resistant pathogens continue to emerge, combination therapy will increasingly be relied upon to treat infections and to help combat further development of multidrug resistance. At present a dichotomy exists between clinical practice, which favors therapeutically synergistic combinations......, and the scientific model emerging from in vitro experimental work, which maintains that this interaction provides greater selective pressure toward resistance development than other interaction types. We sought to extend the current paradigm, based on work below or near minimum inhibitory...... concentration levels, to reflect drug concentrations more likely to be encountered during treatment. We performed a series of adaptive evolution experiments using Staphylococcus aureus. Interestingly, no relationship between drug interaction type and resistance evolution was found as resistance increased...

  7. Affordability, cost and cost-effectiveness of universal anti-retroviral therapy for HIV

    OpenAIRE

    Williams, Brian G; Gouws, Eleanor

    2012-01-01

    If people at risk of HIV infection are tested annually and started on treatment as soon as they are found to be HIV-positive it should be possible to reduce the case reproduction number for HIV to less than one, eliminate transmission and end the epidemic. If this is to be done it is essential to know if it would be affordable, and cost effective. Here we show that in all but eleven countries of the world it is affordable by those countries, that in these eleven countries it is affordable for...

  8. Late Reporting Among Newly Registered Patients for Anti Retroviral Therapy in a Central District Ujjain, India

    Directory of Open Access Journals (Sweden)

    Vidit Khandelwal, Yogesh D Sabde, Riddhi Pradhan, Mehta Chandra Sathsh

    2013-01-01

    Conclusion: Late reporting at the initiation of ART was reported in about one third of the patients which could adversely affect effectiveness of ART. Efforts to investigate lesser representation of women and rural people are indicated. The study raised concerns about the possible routes of transmission need more investigation.

  9. Laboratory Quality Audit in 25 Anti-Retroviral Therapy Facilities in North West of Nigeria

    OpenAIRE

    Feyisayo Ebenezer Jegede; Henry Akwen Mbah; Timothy Nathaniel Yakubu; Oluwasanmi Adedokun; Olubunmi Ruth Negedu-Momoh; Kwasi Torpey

    2014-01-01

    Introduction: A laboratory’s ability to consistently produce high-quality and reliable results hinges on adopting laboratory standards that guide daily practices to ensure steady quality improvement. Although assessment is an extremely rewarding exercise in health care quality improvement processes, it is always considered very time consuming and expensive in developing world settings. A quarterly internal audit was conducted in 25 FHI360 supported Antiretroviral Treatment laboratories in the...

  10. Method development and stability of pheroid-based anti-retroviral formulations / Raadhiya Cassim

    OpenAIRE

    Cassim, Raadhiya

    2007-01-01

    Southern Africa is the worst affected sub region in the world, with South Africa continuing to have the highest number of people living with HIV in the world. It is estimated that 5.3 million people in South Africa were living with HIV at the end of 2003. According to the WHO the total number of people living with HIV in 2004 was 39.4 million. The estimated total for children with HIV under 15 years was 2.2 million. From a total of 3.1 million AIDS deaths in 2004, 510 000 were ...

  11. Anti-retroviral treatment outcomes among older adults in Zomba district, Malawi.

    Directory of Open Access Journals (Sweden)

    Joel Negin

    Full Text Available BACKGROUND: There are approximately 3 million people aged 50 and older in sub-Saharan Africa who are HIV-positive. Despite this, little is known about the characteristics of older adults who are on treatment and their treatment outcomes. METHODS: A retrospective cohort analysis was performed using routinely collected data with Malawi Ministry of Health monitoring tools from facilities providing antiretroviral therapy services in Zomba district. Patients aged 25 years and older initiated on treatment from July 2005 to June 2010 were included. Differences in survival, by age group, were determined using Kaplan-Meier survival plots and Cox proportional hazards regression models. RESULTS: There were 10,888 patients aged 25 and older. Patients aged 50 and older (N = 1419 were more likely to be male (P<0.0001 and located in rural areas (P = 0.003 than those aged 25-49. Crude survival estimates among those aged 50-59 were not statistically different from those aged 25-49 (P = 0.925. However, survival among those aged 60 and older (N = 345 was worse (P = 0.019 than among those 25-59. In the proportional hazards model, after controlling for sex and stage at initiation, survival in those aged 50-59 did not differ significantly from those aged 25-49 (hazard ratio 1.00 (95% CI: 0.79 to 1.27; P = 0.998 but the hazard ratio was 1.46 (95% CI: 1.03 to 2.06; P = 0.032 for those aged 60 and older compared to those aged 25-49. CONCLUSIONS: Treatment outcomes of those aged 50-59 are similar to those aged 25-49. A better understanding of how older adults present for and respond to treatment is critical to improving HIV services.

  12. Impact of hydrogenation on physicochemical and biomedical properties of pH-sensitive PMAA-b-HTPB-b-PMAA triblock copolymer drug carriers.

    Science.gov (United States)

    Xu, Feng; Xu, Jing-Wen; Luo, Yan-Ling

    2016-05-01

    pH-Sensitive poly(methacrylic acid)-block-hydroxyl-terminated polybutadiene-block-poly(methacrylic acid) (PMAA-b-HTPB-b-PMAA) was synthesized and then hydrogenated in this work. The chain structure, phase behavior and thermal properties were characterized by(1)H NMR, FTIR, XRD, DSC, TGA, etc., and the physicochemical and biomedical properties were investigated via fluorescence spectroscopy, TEM, DLS, loading and release of drug and MTT, and so on. The experimental results indicated that the hydrogenation led to the change in the chain aggregate structure of hydrophobic HTPB blocks and the formation of more stable spherical core-shell micelle aggregates, and the critical micelle concentration decreased from 41.8 mg L(-1)before hydrogenation to 4.4 mg L(-1)after hydrogenation. The hydrogenated block copolymer micelle aggregates exhibited pH-triggered response, and could entrap twice as much hydrophobic drug as the unhydrided counterparts and the encapsulation efficiency was significantly improved, which makes them fine to meet the requirements for drug carriers. Therefore, the hydrogenated PMAA-b-HTPB-b-PMAA copolymer micelles as drug target release carriers can be well used in the field of prevention and treatment of cancers. PMID:26939939

  13. Using temperature-sensitive smart polymers to regulate DNA-mediated nanoassembly and encoded nanocarrier drug release.

    Science.gov (United States)

    Hamner, Kristen L; Alexander, Colleen M; Coopersmith, Kaitlin; Reishofer, David; Provenza, Christina; Maye, Mathew M

    2013-08-27

    In this paper we describe the use of a temperature-responsive polymer to regulate DNA interactions in both a DNA-mediated assembly system and a DNA-encoded drug delivery system. A thermoresponsive pNIPAAm-co-pAAm polymer, with a transition temperature (TC) of 51 °C, was synthesized with thiol modification and grafted onto gold nanoparticles (Au NPs) also containing single-stranded oligonucleotides (ssDNA). The thermoresponsive behavior of the polymer regulated the accessibility of the sequence-specific hybridization between complementary DNA-functionalized Au NPs. At T TC, the polymer shell undergoes a hydrophilic to -phobic phase transition and collapses, shrinking below the outer ssDNA, allowing for the sequence-specific hybridization to occur. The potential application of this dynamic interface for drug delivery is shown, in which the chemotherapy drug doxorubicin (DOX) is bound to double-stranded DNA (dsDNA)-functionalized Au NPs whose sequences are known to be high-affinity intercalation points for it. The presence of the polymer capping is shown to decrease drug release kinetics and equilibrium at T TC, thus improving the cytotoxicity of the encoded nanocarrier design. PMID:23899347

  14. Evaluation of pH-sensitive poly(2-hydroxyethyl methacrylate-co-2-(diisopropylaminoethyl methacrylate copolymers as drug delivery systems for potential applications in ophthalmic therapies/ocular delivery of drugs

    Directory of Open Access Journals (Sweden)

    P. A. Faccia

    2015-06-01

    Full Text Available Smart polymers like pH sensitive systems can improve different pharmacological treatment. In this work the behavior of copolymers containing 2-hydroxyethyl methacrylate (HEMA with different proportions of 2-(diisopropylamino ethyl methacrylate (DPA and different amounts of cross-linker agent, ethylene glycol dimethacrylate (EGDMA are evaluated as pH-sensitive drug delivery systems for potential application in ophthalmic therapies. A detailed characterization of the pH-responsive behavior was performed by swelling studies and scanning electron microscopy (SEM analysis. Drug loading and release studies at different pH values were evaluated using Rhodamine 6G (Rh6G as a model drug. The interaction between Rh6G and hydrogels was studied by Fourier Transform Infrared (FTIR spectroscopy and scanning electron microscopy (SEM. The results show that the presence of DPA in the copolymers confers pH-responsive properties to the polymer, as noted in swelling and SEM studies, when the pH decreases below 7.40 the swelling degree increases and a porous morphology is observed. The apparent pKa of copolymers was estimated between 6.80 and 7.17 depending on the composition. The amount of Rh6G loaded depends mainly on the medium pH and the interaction between the drug and the copolymers, observed by SEM and FTIR spectrum. The release of Rh6G of copolymers p(HEMA/DPA show a normal Fickian or anomalous diffusion behavior at different pH values, depending on the HEMA/DPA ratio.

  15. An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

    Directory of Open Access Journals (Sweden)

    Ding Y

    2015-10-01

    Full Text Available Yuan Ding,1,* Dan Sun,1,* Gui-Ling Wang,1 Hong-Ge Yang,1 Hai-Feng Xu,1 Jian-Hua Chen,2 Ying Xie,1,3 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Medicine, Jianghan University, Wuhan, 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: Cell-penetrating peptides (CPPs as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into

  16. Effect of anticancer drugs on breast cancer cells sensitive and resistant to doxorubicin: expression of mRNAs of TGF-β and its receptors

    OpenAIRE

    Chorna I. V.; Fedorenko O. V.; Stoika R. S.

    2014-01-01

    Aim. Comparative study of the effect of chemotherapeutic drugs (doxorubicin, methotrexate and cisplatin) and TGF-β on the human breast carcinoma MCF-7 cells, sensitive (wt) and resistant (DOX/R) to the doxorubicin action. Methods. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the estimation of expression of mRNAs coding for the TGF-β isoforms (TGF-β1 and TGF-β2) and the TGF-β type I and II receptors (TRI and TRII). Trypan blue exclusion method was use...

  17. An analysis on drug sensitivity of 279 clinical Candida isolates%279株临床标本念珠菌药物敏感的分析

    Institute of Scientific and Technical Information of China (English)

    林建鹏; 龙淑珍; 潘莉明

    2011-01-01

    目的 分析279株临床念珠菌的药物敏感性,以指导临床合理用药治疗真菌感染.方法 沙保弱培养基培养标本,用APIAUX20C真菌板条进行鉴定分型,用ATB药敏板条进行药敏实验.结果 分离的菌株对两性霉素B敏感率100%、其次是5-氟胞嘧啶除了白色念珠菌敏感率88.2%,其它念珠菌在100%.依曲康唑,氟康唑,依立康唑敏感率很低,都在32%以上.结论 两性霉素B、5-氟胞嘧啶为治疗念珠菌感染的首选用药.%Objective To instruct reasonable use of medications for fungal infections by analyzing the drug sensitivity of 279 clinical Candida isolates. Methods The Candida isolates were cultured with Sobouraud's bouillon and were then typed with the API AUX 20C fungi ID panel. Susceptibility testing was performed with ATB strips. Results The sensitivity of all the isolates to amphotericin B was 100%, and that of all the isolates except Candida albicans to 5-fluorocytosine was 100%; 88.2% of Candida albicans isolates were sensitive to 5-fluorocytosine. The sensitivity to itraconazole, fluconazole, or uniconazole was very low ( approximately 32% ). Conclusions Amphotericin B and 5-fluorocytosine are the first drug of choice for treating Candida infections.

  18. Prenatal stress alters progestogens to mediate susceptibility to sex-typical, stress-sensitive disorders, such as drug abuse: a review

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2011-10-01

    Full Text Available Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to prenatal stress and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, prenatal stress, with consequences for neurodevelopmental-, neuropsychiatric- and/or neurodegenerative- relevant processes, such as addiction.

  19. Progress in drug therapies for HIV infection.

    OpenAIRE

    Broder, S; Fauci, A S

    1988-01-01

    The discovery of effective therapies for HIV requires a fundamental knowledge of retroviral infections. Research by the Public Health Service and collaborating organizations on oncogenic viruses, including retroviruses, has provided much of the basic understanding of retroviruses in general and anti-retroviral therapeutic strategies in particular. Early work by the Viral Cancer and Developmental Therapeutic Programs of the National Cancer Institute and the Intramural Research Program of the N...

  20. Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells

    International Nuclear Information System (INIS)

    Dielectrophoresis (DEP)-the motion of particles in non-uniform AC fields-has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K+ and Ca2+ levels were extremely similar between sensitive and resistant lines, levels of Cl- were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function. (note)

  1. NOTE: Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells

    Science.gov (United States)

    Duncan, L.; Shelmerdine, H.; Hughes, M. P.; Coley, H. M.; Hübner, Y.; Labeed, F. H.

    2008-01-01

    Dielectrophoresis (DEP)—the motion of particles in non-uniform AC fields—has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K+ and Ca2+ levels were extremely similar between sensitive and resistant lines, levels of Cl- were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function.

  2. Dielectrophoretic analysis of changes in cytoplasmic ion levels due to ion channel blocker action reveals underlying differences between drug-sensitive and multidrug-resistant leukaemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, L [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Shelmerdine, H [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Hughes, M P [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Coley, H M [Postgraduate Medical School, University of Surrey, Guildford GU27XH (United Kingdom); Huebner, Y [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom); Labeed, F H [Centre for Biomedical Engineering, School of Engineering (H5), University of Surrey, Guildford GU27XH (United Kingdom)

    2008-01-21

    Dielectrophoresis (DEP)-the motion of particles in non-uniform AC fields-has been used in the investigation of cell electrophysiology. The technique offers the advantages of rapid determination of the conductance and capacitance of membrane and cytoplasm. However, it is unable to directly determine the ionic strengths of individual cytoplasmic ions, which has potentially limited its application in assessing cell composition. In this paper, we demonstrate how dielectrophoresis can be used to investigate the cytoplasmic ion composition by using ion channel blocking agents. By blocking key ion transporters individually, it is possible to determine their overall contribution to the free ions in the cytoplasm. We use this technique to evaluate the relative contributions of chloride, potassium and calcium ions to the cytoplasmic conductivities of drug sensitive and resistant myelogenous leukaemic (K562) cells in order to determine the contributions of individual ion channel activity in mediating multi-drug resistance in cancer. Results indicate that whilst K{sup +} and Ca{sup 2+} levels were extremely similar between sensitive and resistant lines, levels of Cl{sup -} were elevated by three times to that in the resistant line, implying increased chloride channel activity. This result is in line with current theories of MDR, and validates the use of ion channel blockers with DEP to investigate ion channel function. (note)

  3. Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment

    Directory of Open Access Journals (Sweden)

    Kristin A. Gabor

    2014-11-01

    Full Text Available Seasonal influenza virus infections cause annual epidemics and sporadic pandemics. These present a global health concern, resulting in substantial morbidity, mortality and economic burdens. Prevention and treatment of influenza illness is difficult due to the high mutation rate of the virus, the emergence of new virus strains and increasing antiviral resistance. Animal models of influenza infection are crucial to our gaining a better understanding of the pathogenesis of and host response to influenza infection, and for screening antiviral compounds. However, the current animal models used for influenza research are not amenable to visualization of host-pathogen interactions or high-throughput drug screening. The zebrafish is widely recognized as a valuable model system for infectious disease research and therapeutic drug testing. Here, we describe a zebrafish model for human influenza A virus (IAV infection and show that zebrafish embryos are susceptible to challenge with both influenza A strains APR8 and X-31 (Aichi. Influenza-infected zebrafish show an increase in viral burden and mortality over time. The expression of innate antiviral genes, the gross pathology and the histopathology in infected zebrafish recapitulate clinical symptoms of influenza infections in humans. This is the first time that zebrafish embryos have been infected with a fluorescent IAV in order to visualize infection in a live vertebrate host, revealing a pattern of vascular endothelial infection. Treatment of infected zebrafish with a known anti-influenza compound, Zanamivir, reduced mortality and the expression of a fluorescent viral gene product, demonstrating the validity of this model to screen for potential antiviral drugs. The zebrafish model system has provided invaluable insights into host-pathogen interactions for a range of infectious diseases. Here, we demonstrate a novel use of this species for IAV research. This model has great potential to advance our

  4. Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment.

    Science.gov (United States)

    Gabor, Kristin A; Goody, Michelle F; Mowel, Walter K; Breitbach, Meghan E; Gratacap, Remi L; Witten, P Eckhard; Kim, Carol H

    2014-11-01

    Seasonal influenza virus infections cause annual epidemics and sporadic pandemics. These present a global health concern, resulting in substantial morbidity, mortality and economic burdens. Prevention and treatment of influenza illness is difficult due to the high mutation rate of the virus, the emergence of new virus strains and increasing antiviral resistance. Animal models of influenza infection are crucial to our gaining a better understanding of the pathogenesis of and host response to influenza infection, and for screening antiviral compounds. However, the current animal models used for influenza research are not amenable to visualization of host-pathogen interactions or high-throughput drug screening. The zebrafish is widely recognized as a valuable model system for infectious disease research and therapeutic drug testing. Here, we describe a zebrafish model for human influenza A virus (IAV) infection and show that zebrafish embryos are susceptible to challenge with both influenza A strains APR8 and X-31 (Aichi). Influenza-infected zebrafish show an increase in viral burden and mortality over time. The expression of innate antiviral genes, the gross pathology and the histopathology in infected zebrafish recapitulate clinical symptoms of influenza infections in humans. This is the first time that zebrafish embryos have been infected with a fluorescent IAV in order to visualize infection in a live vertebrate host, revealing a pattern of vascular endothelial infection. Treatment of infected zebrafish with a known anti-influenza compound, Zanamivir, reduced mortality and the expression of a fluorescent viral gene product, demonstrating the validity of this model to screen for potential antiviral drugs. The zebrafish model system has provided invaluable insights into host-pathogen interactions for a range of infectious diseases. Here, we demonstrate a novel use of this species for IAV research. This model has great potential to advance our understanding of

  5. Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

    OpenAIRE

    Kim, Jong Oh

    2015-01-01

    Tuan Hiep Tran,1 Thiruganesh Ramasamy,1 Ju Yeon Choi,1 Hanh Thuy Nguyen,1 Thanh Tung Pham,1 Jee-Heon Jeong,1 Sae Kwang Ku,2 Han-Gon Choi,3 Chul Soon Yong,1 Jong Oh Kim11College of Pharmacy, Yeungnam University, Dae-Dong, 2College of Korean Medicine, Daegu Haany University, Gyeongsan, 3College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sangnok-gu, Ansan, South KoreaAbstract: The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparti...

  6. Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells

    OpenAIRE

    Tran TH; Ramasamy T; Choi JY; Nguyen HT; Pham TT; Jeong JH; SK Ku; Choi HG; Yong CS; Kim JO

    2015-01-01

    Tuan Hiep Tran,1 Thiruganesh Ramasamy,1 Ju Yeon Choi,1 Hanh Thuy Nguyen,1 Thanh Tung Pham,1 Jee-Heon Jeong,1 Sae Kwang Ku,2 Han-Gon Choi,3 Chul Soon Yong,1 Jong Oh Kim11College of Pharmacy, Yeungnam University, Dae-Dong, 2College of Korean Medicine, Daegu Haany University, Gyeongsan, 3College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sangnok-gu, Ansan, South KoreaAbstract: The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles...

  7. ZEB1 knockdown mediated using polypeptide cationic micelles inhibits metastasis and effects sensitization to a chemotherapeutic drug for cancer therapy

    Science.gov (United States)

    Fang, Shengtao; Wu, Lei; Li, Mingxing; Yi, Huqiang; Gao, Guanhui; Sheng, Zonghai; Gong, Ping; Ma, Yifan; Cai, Lintao

    2014-08-01

    Metastasis and drug resistance are the main causes for the failure in clinical cancer therapy. Emerging evidence suggests an intricate role of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) in metastasis and drug resistance. The EMT-activator ZEB1 is crucial in malignant tumor progression by linking EMT-activation and stemness-maintenance. Here, we used multifunctional polypeptide micelle nanoparticles (NP) as nanocarriers for the delivery of ZEB1 siRNA and doxorubicin (DOX). The nanocarriers could effectively deliver siRNA to the cytoplasm and knockdown the target gene in H460 cells and H460 xenograft tumors, leading to reduced EMT and repressed CSC properties in vitro and in vivo. The complex micelle nanoparticles with ZEB1 siRNA (siRNA-NP) significantly reduced metastasis in the lung. When DOX and siRNA were co-delivered by the nanocarriers (siRNA-DOX-NP), a synergistic therapeutic effect was observed, resulting in dramatic inhibition of tumor growth in a H460 xenograft model. These results demonstrated that the siRNA-NP or siRNA-DOX-NP complex targeting ZEB1 could be developed into a new therapeutic approach for non-small cell lung cancer (NSCLC) treatment.Metastasis and drug resistance are the main causes for the failure in clinical cancer therapy. Emerging evidence suggests an intricate role of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) in metastasis and drug resistance. The EMT-activator ZEB1 is crucial in malignant tumor progression by linking EMT-activation and stemness-maintenance. Here, we used multifunctional polypeptide micelle nanoparticles (NP) as nanocarriers for the delivery of ZEB1 siRNA and doxorubicin (DOX). The nanocarriers could effectively deliver siRNA to the cytoplasm and knockdown the target gene in H460 cells and H460 xenograft tumors, leading to reduced EMT and repressed CSC properties in vitro and in vivo. The complex micelle nanoparticles with ZEB1 siRNA (siRNA-NP) significantly reduced

  8. Novel pH-sensitive nano-containers based on EUDRAGIT/Brij98 mixture for oral drug delivery

    Czech Academy of Sciences Publication Activity Database

    Kaberov, Leonid; Hrubý, Martin; Bogomolova, Anna; Pánek, Jiří; Štěpánek, Petr; Filippov, Sergey K.

    Dresden: Leibniz-Institut für Polymerforschung Dresden e.V. (IPF), 2015. 254 /SOFT-P-032/. ISBN 978-3-936028-89-8. [European Polymer Federation Congress 2015. 21.06.2015-26.06.2015, Dresden] R&D Projects: GA MŠk(CZ) LH14292; GA ČR(CZ) GC15-10527J Grant ostatní: AV ČR(CZ) M200501201 Institutional support: RVO:61389013 Keywords : eudragit * drug delivery Subject RIV: CD - Macromolecular Chemistry

  9. Cytotoxicity of Elaoephorbia drupifera and other Cameroonian medicinal plants against drug sensitive and multidrug resistant cancer cells

    OpenAIRE

    Kuete, Victor; Voukeng, Igor K; Tsobou, Roger; Mbaveng, Armelle T; Wiench, Benjamin; Beng, Veronique P; Efferth, Thomas

    2013-01-01

    Background Multidrug resistance (MDR) is a major hurdle for cancer treatment worldwide and accounts for chemotherapy failure in over 90% of patients with metastatic cancer. Evidence of the cytotoxicity of Cameroonian plants against cancer cell lines including MDR phenotypes is been intensively and progressively provided. The present work was therefore designed to evaluate the cytotoxicity of the methanol extracts of twenty-two Cameroonian medicinal plants against sensitive and MDR cancer cell...

  10. Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

    International Nuclear Information System (INIS)

    Highlights: → We found a novel inhibitor of Nrf2 known as a chemoresistance factor. → Overexpressed Nrf2 in lung cancer cells was suppressed by Cinnamomi Cortex extract. → Cytotoxic action of anticancer drugs in cells treated with the extract was enhanced. → Procyanidin tetramers and pentamers were active components in suppressing Nrf2. -- Abstract: Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2.

  11. Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

    Energy Technology Data Exchange (ETDEWEB)

    Ohnuma, Tomokazu; Matsumoto, Takashi; Itoi, Ayano; Kawana, Ayako; Nishiyama, Takahito; Ogura, Kenichiro [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan); Hiratsuka, Akira, E-mail: hiratuka@toyaku.ac.jp [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan)

    2011-10-07

    Highlights: {yields} We found a novel inhibitor of Nrf2 known as a chemoresistance factor. {yields} Overexpressed Nrf2 in lung cancer cells was suppressed by Cinnamomi Cortex extract. {yields} Cytotoxic action of anticancer drugs in cells treated with the extract was enhanced. {yields} Procyanidin tetramers and pentamers were active components in suppressing Nrf2. -- Abstract: Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2.

  12. Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery

    Directory of Open Access Journals (Sweden)

    Zhang CY

    2014-10-01

    Full Text Available Can Yang Zhang, Di Xiong, Yao Sun, Bin Zhao, Wen Jing Lin, Li Juan Zhang School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong Province, People’s Republic of China Abstract: A novel amphiphilic triblock pH-sensitive poly(ß-amino ester-g-poly(ethylene glycol methyl ether-cholesterol (PAE-g-MPEG-Chol was designed and synthesized via the Michael-type step polymerization and esterification condensation method. The synthesized copolymer was determined with proton nuclear magnetic resonance and gel permeation chromatography. The grafting percentages of MPEG and cholesterol were determined as 10.93% and 62.02%, calculated from the area of the characteristic peaks, respectively. The amphiphilic copolymer was confirmed to self-assemble into core/shell micelles in aqueous solution at low concentrations. The critical micelle concentrations were 6.92 and 15.14 mg/L at pH of 7.4 and 6.0, respectively, obviously influenced by the changes of pH values. The solubility of pH-responsive PAE segment could be transformed depending on the different values of pH because of protonation–deprotonation of the amino groups, resulting in pH sensitivity of the copolymer. The average particle size of micelles increased from 125 nm to 165 nm with the pH decreasing, and the zeta potential was also significantly changed. Doxorubicin (DOX was entrapped into the polymeric micelles with a high drug loading level. The in vitro DOX release from the micelles was distinctly enhanced with the pH decreasing from 7.4 to 6.0. Toxicity testing proved that the DOX-loaded micelles exhibited high cytotoxicity in HepG2 cells, whereas the copolymer showed low toxicity. The results demonstrated how pH-sensitive PAE-g-MPEG-Chol micelles were proved to be a potential vector in hydrophobic drug delivery for tumor therapy. Keywords: micelle, pH-sensitive, cholesterol, poly(ß-amino ester, drug delivery

  13. Preparation, characterization, and in vitro drug release behavior of glutathione-sensitive long-circulation micelles based on polyethylene glycol prodrug.

    Science.gov (United States)

    Shi, Liyan; Ding, Kaikai; Sun, Xin; Zhang, Ling; Zeng, Tian; Yin, Yihua; Zheng, Hua

    2016-04-01

    In this paper, a kind of glutathione-sensitive polymeric micelles was prepared through assembling in aqueous solution of an amphiphilic polymeric prodrug which was synthesized by linkage of 6-mercaptopurine (6-MP) and polyethylene glycol monomethyl ether using propiolic acid as a connecting arm. The glutathione (GSH)-sensitive strategy is based on a Michael addition-elimination reaction, that is the amphiphilic polymeric prodrug which contains α, β-unsaturated carbonyl group acts as a Michael acceptor to receive the attack of nucleophile - glutathione, and undergoes elimination reaction to release the original drug. Transmission electron microscope observation showed that the polymeric micelles (PMs) had a spherical-like morphology with a mean diameter of 28 ± 3.2 nm. The dynamic light scattering investigation data exhibited that the size and distribution changes of PMs are negligible after being placed for 15 days. In vitro drug release study indicated that only less than 13% of 6-MP was released from the micelles under GSH stimulation at micromolar level, while 34.5, 53.7, and 77.8% accumulative release rates were achieved under GSH stimulation at millimolar level (1, 2 and 10 mM), respectively. The cell inhibition rate of PM solution against HL-60 cells carried out by MTT method reached 85%. The cellular uptake and the intracellular drug release of PMs in HL-60 cells were observed through determining the intracellular 6-MP content by UV-vis spectrophotometer. In vitro macrophage uptake study showed a low phagocytosis rate, indicating the long-circulation ability of the PMs. PMID:26764973

  14. In vitro Plasmodium falciparum drug sensitivity assay: inhibition of parasite growth by incorporation of stomatocytogenic amphiphiles into the erythrocyte membrane.

    Science.gov (United States)

    Ziegler, Hanne L; Staerk, Dan; Christensen, Jette; Hviid, Lars; Hägerstrand, Henry; Jaroszewski, Jerzy W

    2002-05-01

    Lupeol, which shows in vitro inhibitory activity against Plasmodium falciparum 3D7 strain with a 50% inhibitory concentration (IC50) of 27.7 +/- 0.5 microM, was shown to cause a transformation of the human erythrocyte shape toward that of stomatocytes. Good correlation between the IC50 value and the membrane curvature changes caused by lupeol was observed. Preincubation of erythrocytes with lupeol, followed by extensive washing, made the cells unsuitable for parasite growth, suggesting that the compound incorporates into erythrocyte membrane irreversibly. On the other hand, lupeol-treated parasite culture continued to grow well in untreated erythrocytes. Thus, the antiplasmodial activity of lupeol appears to be indirect, being due to stomatocytic transformation of the host cell membrane and not to toxic effects via action on a drug target within the parasite. A number of amphiphiles that cause stomatocyte formation, but not those causing echinocyte formation, were shown to inhibit growth of the parasites, apparently via a mechanism similar to that of lupeol. Since antiplasmodial agents that inhibit parasite growth through erythrocyte membrane modifications must be regarded as unsuitable as leads for development of new antimalarial drugs, care must be exercised in the interpretation of results of screening of plant extracts and natural product libraries by an in vitro Plasmodium toxicity assay. PMID:11959580

  15. Yolk-shell hybrid nanoparticles with magnetic and pH-sensitive properties for controlled anticancer drug delivery

    Science.gov (United States)

    Li, Shunxing; Zheng, Jianzhong; Chen, Dejian; Wu, Yijin; Zhang, Wuxiang; Zheng, Fengying; Cao, Jing; Ma, Heran; Liu, Yaling

    2013-11-01

    A facile and effective way for the preparation of nano-sized Fe3O4@graphene yolk-shell nanoparticles via a hydrothermal method is developed. Moreover, the targeting properties of the materials for anticancer drug (doxorubicin hydrochloride) delivery are investigated. Excitingly, these hybrid materials possess favorable dispersibility, good superparamagnetism (the magnetic saturation value is 45.740 emu g-1), high saturated loading capacity (2.65 mg mg-1), and effective loading (88.3%). More importantly, the composites exhibit strong pH-triggered drug release response (at the pH value of 5.6 and 7.4, the release rate was 24.86% and 10.28%, respectively) and good biocompatibility over a broad concentration range of 0.25-100 μg mL-1 (the cell viability was 98.52% even at a high concentration of 100 μg mL-1) which sheds light on their potentially bright future for bio-related applications.

  16. Radiation sensitizers

    International Nuclear Information System (INIS)

    The following classes of radiosensitizers are discussed: electron affinic compounds, pyrimidine analogs, and antibiotics. Metronidazole and nitroimidazole are discussed as examples of electron-affinic compounds. Studies on the enhancement ratio for sensitization of x-irradiated hamster cells showed that these drugs sensitize at concentrations much lower than the toxic concentrations. Criteria for a clinically useful hypoxic cell sensitizer are listed and mechanisms of electron-affinic sensitizers are discussed. The radiosensitizing effects of the pyrimidine analogs, BUDR, BCDR, IUDR, CUDR, and FUDR, are examined and the enhancement of radiation effects by the chemotherapeutic agent, 5-fluorouracil, is discussed. Other agents discussed are methotrexate, actinomycin D, bleomycin, and adriamycin

  17. Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery.

    Science.gov (United States)

    Zhang, Can Yang; Xiong, Di; Sun, Yao; Zhao, Bin; Lin, Wen Jing; Zhang, Li Juan

    2014-01-01

    A novel amphiphilic triblock pH-sensitive poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol) was designed and synthesized via the Michael-type step polymerization and esterification condensation method. The synthesized copolymer was determined with proton nuclear magnetic resonance and gel permeation chromatography. The grafting percentages of MPEG and cholesterol were determined as 10.93% and 62.02%, calculated from the area of the characteristic peaks, respectively. The amphiphilic copolymer was confirmed to self-assemble into core/shell micelles in aqueous solution at low concentrations. The critical micelle concentrations were 6.92 and 15.14 mg/L at pH of 7.4 and 6.0, respectively, obviously influenced by the changes of pH values. The solubility of pH-responsive PAE segment could be transformed depending on the different values of pH because of protonation-deprotonation of the amino groups, resulting in pH sensitivity of the copolymer. The average particle size of micelles increased from 125 nm to 165 nm with the pH decreasing, and the zeta potential was also significantly changed. Doxorubicin (DOX) was entrapped into the polymeric micelles with a high drug loading level. The in vitro DOX release from the micelles was distinctly enhanced with the pH decreasing from 7.4 to 6.0. Toxicity testing proved that the DOX-loaded micelles exhibited high cytotoxicity in HepG2 cells, whereas the copolymer showed low toxicity. The results demonstrated how pH-sensitive PAE-g-MPEG-Chol micelles were proved to be a potential vector in hydrophobic drug delivery for tumor therapy. PMID:25364250

  18. Quantitative evaluation of cellular uptake, DNA incorporation and adduct formation in cisplatin sensitive and resistant cell lines: Comparison of different Pt-containing drugs.

    Science.gov (United States)

    Corte-Rodríguez, M; Espina, M; Sierra, L M; Blanco, E; Ames, T; Montes-Bayón, M; Sanz-Medel, A

    2015-11-01

    The use of Pt-containing compounds as chemotherapeutic agents facilitates drug monitoring by using highly sensitive elemental techniques like inductively coupled plasma mass spectrometry (ICP-MS). However, methodological problems arise when trying to compare different experiments due to the high variability of biological parameters. In this work we have attempted to identify and correct such variations in order to compare the biological behavior of cisplatin, oxaliplatin and pyrodach-2 (a novel platinum-containing agent). A detailed study to address differential cellular uptake has been conducted in three different cell lines: lung adenocarcinoma (A549); cisplatin-sensitive ovarian carcinoma (A2780); and cisplatin-resistant ovarian carcinoma (A2780cis). The normalization of Pt results to cell mass, after freeze-drying, has been used to minimize the errors associated with cell counting. Similarly, Pt accumulation in DNA has been evaluated by referencing the Pt results to the DNA concentration, as measured by (31)P monitoring using flow-injection and ICP-MS detection. These strategies have permitted to address significantly lower Pt levels in the resistant cells when treated with cisplatin or oxaliplatin as well as an independent behaviour from the cell type (sensitive or resistant) for pyrodach-2. Similarly, different levels of incorporation in DNA have been found for the three drugs depending on the cell model revealing a different behavior regarding cell cisplatin resistance. Further speciation experiments (by using complementary HPLC-ICP-MS and HPLC-ESI-Q-TOF MS) have shown that the main target in DNA is still the N7 of the guanine but with different kinetics of the ligand exchange mechanism for each of the compounds under evaluation. PMID:26352094

  19. Monitoring the drug-sensitivity of Plasmodium falciparum in coastal towns in Madagascar by use of in vitro chemosensitivity and mutation detection tests

    Directory of Open Access Journals (Sweden)

    Rason M.A.

    2002-09-01

    Full Text Available The dissemination of mutant and resistant strains of Plasmodium falciparum makes a considerable contribution to the spread of drug-resistant malaria. Populations around harbours and airports could be particularly exposed to Plasmodium isolates introduced with imported cases of malaria. The use of chloroquine as well as the use of and sulfadoxine/pyrimethamine is currently an effective method for treating uncomplicated cases of malaria in Madagascar. As part of a monitoring programme, in vitro methods were used to assess the sensitivity of P. falciparum isolates in two coastal towns in Madagascar: Mahajanga on the west coast and Toamasina on the east coast. All of the isolates from both sites were sensitive to amodiaquine, quinine, pyrimethamine and cycloguanil. All of the isolates from Mahajanga were sensitive to chloroquine (n = 25; mean IC50 = 22.6 nM, 95 % confidence interval: 16.8-28.7 nM, whereas three of the isolates from Toamasina were resistant to chloroquine (n = 18; mean IC50 = 66.3 nM; 95 % confidence interval : 42.6-90 nM, The frequency of the Pfcrt Thr-76 and the dhfr Asn- 108 mutations was estimated by PCR/RFLP. The 43 P. falciparum isolates examined, including the three in vitro chloroquine-resistant isolates from Toamasina were all wild-type (Lys-76. Phenotyping and genotyping studies suggested that the prevalence of chloroquine- and pyrimethamine-resistant isolates and of mutant strains of P. falciparum is very low. These results showed that in vitro test and genotyping of resistance markers approaches could be successfully used to monitor the emergence of drug-resistant malaria and to try to alleviate the lack of medical teams able to carry out in vivo test. The possible hazard/risk associated with imported cases of malaria is discussed.

  20. TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

    DEFF Research Database (Denmark)

    Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik Axel;

    2013-01-01

    affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab and...... lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level of...

  1. Preparation of pH-sensitive zwitterionic nano micelles and drug controlled release for enhancing cellular uptake.

    Science.gov (United States)

    Wu, Luyan; Ni, Caihua; Zhang, Liping; Shi, Gang

    2016-05-01

    Zwitterionic copolymers have exhibited high resistance to nonspecific protein adsorption and have wide applications in drug delivery systems. Herein, a pH-responsive poly(Lysine-alt-N,N'-bis(acryloyl) diaminohexane) was synthesized through the Michael addition polymerization between N, N'-bis(acryloyl) diaminohexane and lysine. Subsequently, nano micelles (NMs) were formed by self-assembly of the copolymer in an aqueous solution. The NMs showed a slightly negative charge in blood environment, but a positively charged surface in extracellular pH of tumor. This feature could be used to enhance permeability and retention effect, and reinforce tumor cell uptake. Vitro release studies revealed that the release of DOX from the DOX-loaded NMs was evidently faster at pH 5.0 than at pH 7.4. MTT assays revealed that NMs were nontoxic. Thus, these smart NMs were feasible candidates and could be potentially used in cancer chemotherapy. PMID:26813767

  2. 肉鸡沙门氏菌的分离鉴定及药敏试验%Isolation, Identification and Drug Sensitive Assay of Salmonella From Broiler

    Institute of Scientific and Technical Information of China (English)

    王傲雪; 张凌云; 张桉潮; 李昆鹏; 张秀丽; 梁晚枫; 张林波

    2013-01-01

    为了解吉林省某地鸡源性沙门氏菌的感染及耐药情况,对该地7个肉鸡场150份病鸡组织样品进行细菌分离,并进行了血凝试验、致病性试验和药敏试验.分离得到26株沙门氏菌,经血凝鉴定有19株呈阳性,其中5株呈强阳性并均能使雏鸡致死.药敏试验结果显示,该5株沙门氏菌对头孢噻肟较为敏感;对氨苄西林、替米考星、林可霉素、阿奇霉素和头孢拉定表现出极高的耐药性,耐药率高达100%;诺氟沙星、恩诺沙星、环丙沙星、强力霉素和氯霉素5种临床用药与痢菌净不具有协同或累加作用.试验结果表明,沙门氏菌是危害该地肉鸡养殖场的主要病原菌之一,且耐药性十分严重.%To find out the situations about infection of Salmonella and its drug resistance somewhere in Jilin province,the bacteria were isolated from 150 tissue samples of sick broiler of 7 farms in this city,and hemagglutinin test,pathogenity test and drug sensitive test were carried out.26 strains were isolated,and 19 strains were identified positive by the HA,of which five were strongly positive and killed broiler,drug sensitive test results showed that the 5 strains of Salmonella were more sensitive to cefotaxime,and very high resistance to ampicillin,tilmicosin,lincomycin,azithromycin and cephradine,resistance rates as high as 100 %.Norfloxacin,enrofloxacin,ciprofloxacin,doxycycline and chloramphenicol didn't have synergistic or additive effect with mequindox which was used in clinical.These results suggested that Salmonella was one of the main pathogens harmful to the broiler of farms,and resistance was very serious.

  3. Sensitive spectrophotometric determination of ascorbic acid in drugs and foods using surface plasmon resonance band of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Kobra Zarei

    2015-12-01

    Full Text Available A simple and sensitive procedure was proposed for spectrophotometric determination of ascorbic acid. It was found that the reduction of Ag+ to silver nanoparticles (Ag-NPs by ascorbic acid in the presence of polyvinylpyrrolidone (PVP as a stabilizing agent produce very intense surface plasmon resonance peak of Ag-NPs. The plasmon absorbance of the Ag-NPs at λ = 440 nm allows the quantitative spectrophotometric detection of the ascorbic acid. The calibration curve was linear with concentration of ascorbic acid in the range of 0.5–60 μM. The detection limit was obtained as 0.08 μM. The influence of potential interfering substances on the determination of ascorbic acid was studied. The proposed method was successfully applied for the determination of ascorbic acid in some powdered drink mixtures, commercial orange juice, natural orange juice, vitamin C injection, effervescent tablet, and multivitamin tablet.

  4. Behavioral Sensitization and Underlying Mechanism in Drug Addiction%成瘾药物行为敏化及机制

    Institute of Scientific and Technical Information of China (English)

    刘胜; 周文华; 杨国栋

    2004-01-01

    反复、间断给予依赖性药物(如吗啡、苯丙胺、可卡因、尼古丁、酒精等)后,能增强实验动物的自发性活动反应(locomotor response),这种伴随着反复给药而出现的行为反应增强被称为行为敏化(behavioral sensitization)。行为敏化的形成和表达与药物成瘾有着重要的关系,目前已经证明成瘾药物诱导的行为敏化对觅药行为和复吸的发生和维持有着重要的影响。

  5. Evaluation of adverse drug reactions in HIV positive patients in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Anshu Kumar Jha

    2015-01-01

    Full Text Available Context: The advancement and development of new drugs and treatment strategies increase the risk of unusual Adverse Events (AEs in HIV patients. Aims: The objective of our study was to assess the incidence, types and nature of AEs in HIV positive subjects. Settings and Design: Patients with WHO stage IV disease irrespective of the CD4 cell count, or WHO stage III disease with a CD4 cell count <350 cell/cu. Mm, or, WHO stage I or II disease with a CD4 cell count of <200 cells/cu. mm, and on prior anti-retroviral therapy for not more than six months preceding the observation date, were included in the study. After initiation of therapy, the patients were examined for the occurrence any adverse events including the type and severity, or any other abnormal laboratory findings. Causality assessment of the adverse events was done using the Naranjo′s scale. Results: Out of 327 patients studied prospectively, 43 patients developed AEs. Out of these, 23 (53.5% were males and 20 (46.5% were females. A total of 53 (16.21% AEs were reported. Antitubercular drugs caused the maximum AEs (28.3% followed by zidovudine (20.7%, nevirapine (15.0% and efavirenz (5.6%. Stavudine, ethambutol, sulfamethoxazole and trimethoprim, and atazanavir were also responsible for 3.7% of AEs individually. Causality assessment done according to the Naranjo′s scale revealed that 66.04% AEs were ′probable′ and 33.96% were ′possible′. Conclusions: Anemia, hepatitis and dermatological adverse effects are the most common AEs. Antitubercular drugs contributed significantly for the incidence of AEs in these patients. Frequency of AEs was slightly more in males compared to females.

  6. Hiv-1 Drug Resistance Among Newly Hiv-1 Infected Individuals Attending Tertiary Referral Center in Chennai, India

    Directory of Open Access Journals (Sweden)

    Hussain Syed Iqbal

    2011-01-01

    Full Text Available Context: In the era of free HAART, accessibility and availability of ARV has been dramatically increased in India. However, rates of treatment literacy and adherence appear to be sub-optimal. Therefore, it is essential to monitor the extent of primary drug resistance in such settings. Materials and Methods: Between July and October 2006, 18 anti-retroviral-naοve individuals were identified as recent infected by the BED-Capture enzyme immunoassay in a VCTC clinic in Chennai. Specimens from these individuals were subjected to genotypic drug resistance testing. Phylogenetic trees were generated using MEGA for Windows version 4.0 using neighbor-joining method. The significant differences in polymorphic mutation frequencies between the study specimens and established subtype C-specific polymorphisms were examined using the Chi-square test. Results: Amino acid substitution (K103N and V106MV at drug resistance positions occurred in two (11% isolates, conferring high-level resistance to the non-nucleoside reverse-transcriptase inhibitors nevirapine (NVP, efavirenz (EFV, delavirdine (DLV and notably extensive genetic variations were observed. K122E (94.4% and K49R/KR (11.1% polymorphisms identified in this study have not been previously described in established subtype-C specific polymorphisms. The rate of polymorphisms showed marked difference at the locations V60, D121, V35, and D123 (P < 0.0001. All the sequences showed maximum homology with Indian HIV-1 subtype C reference strain C.IN.95IN21068. Conclusions: The finding of resistance to NNRTIs is of public health importance. There is an urgent need to establish surveillance for primary drug resistance in large scale. Further studies are required to determine the phenotype impact of newer polymorphic mutations in relation to drug resistance and viral fitness.

  7. The reliability of sensitive information provided by injecting drug users in a clinical setting: clinician-administered versus audio computer-assisted self-interviewing (ACASI).

    Science.gov (United States)

    Islam, M Mofizul; Topp, Libby; Conigrave, Katherine M; van Beek, Ingrid; Maher, Lisa; White, Ann; Rodgers, Craig; Day, Carolyn A

    2012-01-01

    Research with injecting drug users (IDUs) suggests greater willingness to report sensitive and stigmatised behaviour via audio computer-assisted self-interviewing (ACASI) methods than during face-to-face interviews (FFIs); however, previous studies were limited in verifying this within the same individuals at the same time point. This study examines the relative willingness of IDUs to report sensitive information via ACASI and during a face-to-face clinical assessment administered in health services for IDUs. During recruitment for a randomised controlled trial undertaken at two IDU-targeted health services, assessments were undertaken as per clinical protocols, followed by referral of eligible clients to the trial, in which baseline self-report data were collected via ACASI. Five questions about sensitive injecting and sexual risk behaviours were administered to participants during both clinical interviews and baseline research data collection. "Percentage agreement" determined the magnitude of concordance/discordance in responses across interview methods, while tests appropriate to data format assessed the statistical significance of this variation. Results for all five variables suggest that, relative to ACASI, FFI elicited responses that may be perceived as more socially desirable. Discordance was statistically significant for four of the five variables examined. Participants who reported a history of sex work were more likely to provide discordant responses to at least one socially sensitive item. In health services for IDUs, information collection via ACASI may elicit more reliable and valid responses than FFI. Adoption of a universal precautionary approach to complement individually tailored assessment of and advice regarding health risk behaviours for IDUs may address this issue. PMID:22452446

  8. A novel application of maleimide for advanced drug delivery: in vitro and in vivo evaluation of maleimide-modified pH-sensitive liposomes

    Directory of Open Access Journals (Sweden)

    Li T

    2013-10-01

    Full Text Available Tianshu Li, Shinji TakeokaDepartment of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns, Shinjuku-ku, Tokyo, JapanAbstract: Maleimide is a stable and easy-to-handle moiety that rapidly and covalently conjugates thiol groups of cysteine residues in proteins or peptides. Herein, we use maleimide to modify the surface of liposomes in order to obtain an advanced drug delivery system. Employing a small amount (0.3 mol% of maleimide-polyethylene glycol (PEG to modify the surface of the liposomes M-GGLG-liposomes, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG/cholesterol/poly(ethylene glycol 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG5000-DSPE/maleimide-PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03, drug delivery efficiency was remarkably improved both in vitro and in vivo compared to unmodified liposomes (GGLG-liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03. Moreover, this modification did not elicit any detectable increase in cytotoxicity. The maleimide-modification did not alter the physical characteristics of the liposomes such as size, zeta potential, pH sensitivity, dispersibility and drug encapsulation efficiency. However, M-GGLG-liposomes were more rapidly (≥2-fold internalized into HeLa, HCC1954, and MDA-MB-468 cells compared to GGLG-liposomes. In vivo, M-GGLG-liposomes encapsulating doxorubicin (M-GGLG-DOX-liposomes also showed a more potent antitumor effect than GGLG-DOX-liposomes and the widely used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC-DOX-liposomes after two subcutaneous injections around breast cancer tissue in mice. The biodistribution of liposomes in this model was observed using an in vivo imaging system, which showed that M-GGLG-liposomes were present for significantly longer at the injection site compared to GGLG-liposomes. The outstanding biological functions of

  9. pH-sensitive interpenetrating polymer network microspheres of poly(vinyl alcohol) and carboxymethyl cellulose for controlled release of the nonsteroidal anti-inflammatory drug ketorolac tromethamine.

    Science.gov (United States)

    Kondolot Solak, Ebru; Er, Akın

    2016-05-01

    In this study, we aimed to produce pH-sensitive microspheres for the controlled release of the nonsteroidal anti-inflammatory drug, ketorolac tromethamine (KT). For this purpose, an interpenetrating polymer network (IPN) of microspheres of poly(vinyl alcohol) (PVA)/sodium carboxymethyl cellulose (NaCMC) were prepared, based on different formulations using glutaraldehyde (GA) (0.66 M) and hydrochloric acid (HCl) (3%, v/v). The preparation conditions of the microspheres were optimized by considering the percentage of entrapment efficiency and swelling capacity of the microspheres, and their release data. The effects of PVA and NaCMC ratio on the release of KT for over a period of 6 h, at three pH values (1.2, 6.8, and 7.4), have been discussed. PMID:25619756

  10. In vitro study of drug sensitivity of Plasmodium falciparum: assessment of semi-microtest by /sup 3/H-hypoxanthine incorporation

    Energy Technology Data Exchange (ETDEWEB)

    Le Bras, J.; Andrieu, B.; Hatin, I.; Savel, J.; Coulaud, J.P. (Hopital Claude-Bernard, 75 - Paris (France))

    1984-05-01

    Recent advances in cultivation methods and knowledge of in vitro response of Plasmodium falciparum to antimalarials have led to improved chemosensitivity tests. The semi-microtest is a useful tool for screening presumptive antimalarials, and also for the testing sensitivity of strains recovered from patients in hospital and field studies to currently used drugs. Microscopic parasite counts on thin blood films can be replaced by measurement of /sup 3/H-hypoxanthine by the uptake parasite. Conditions which ensure optimal parasite growth and high radioisotope incorporation are described. Wells containing less than 3.10/sup 4/ asexualparasites can be studied with this method. Results of the semi-microtest are closely correlated with those of microscopic parasite count. Advantages of both methods are discussed.

  11. Optimization of a low cost and broadly sensitive genotyping assay for HIV-1 drug resistance surveillance and monitoring in resource-limited settings.

    Directory of Open Access Journals (Sweden)

    Zhiyong Zhou

    Full Text Available Commercially available HIV-1 drug resistance (HIVDR genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS. This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR and reverse transcriptase (RT regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N = 96. Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N = 87, P<0.001 and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N = 230, all 72 (100% plasma and 69 (95.8% of the matched dried blood spots (DBS in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL ≥ and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N = 46 and 78.6% (N = 14 genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06_CPX, CRF07_BC and CRF09_CPX.The optimized in-house assay is broadly sensitive in genotyping HIV-1 group M viral strains and more sensitive than the original in-house, TRUGENE® and ViroSeq® in detecting mixed viral populations. The broad sensitivity and substantial reagent cost saving make this assay more accessible

  12. Changes in sensitivity of reward and motor behavior to dopaminergic, glutamatergic, and cholinergic drugs in a mouse model of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    Eric W Fish

    Full Text Available Fragile X syndrome (FXS is a leading cause of intellectual disability. FXS is caused by loss of function of the FMR1 gene, and mice in which Fmr1 has been inactivated have been used extensively as a preclinical model for FXS. We investigated the behavioral pharmacology of drugs acting through dopaminergic, glutamatergic, and cholinergic systems in fragile X (Fmr1 (-/Y mice with intracranial self-stimulation (ICSS and locomotor activity measurements. We also measured brain expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in dopamine biosynthesis. Fmr1 (-/Y mice were more sensitive than wild type mice to the rewarding effects of cocaine, but less sensitive to its locomotor stimulating effects. Anhedonic but not motor depressant effects of the atypical neuroleptic, aripiprazole, were reduced in Fmr1 (-/Y mice. The mGluR5-selective antagonist, 6-methyl-2-(phenylethynylpyridine (MPEP, was more rewarding and the preferential M1 antagonist, trihexyphenidyl, was less rewarding in Fmr1 (-/Y than wild type mice. Motor stimulation by MPEP was unchanged, but stimulation by trihexyphenidyl was markedly increased, in Fmr1 (-/Y mice. Numbers of midbrain TH+ neurons in the ventral tegmental area were unchanged, but were lower in the substantia nigra of Fmr1 (-/Y mice, although no changes in TH levels were found in their forebrain targets. The data are discussed in the context of known changes in the synaptic physiology and pharmacology of limbic motor systems in the Fmr1 (-/Y mouse model. Preclinical findings suggest that drugs acting through multiple neurotransmitter systems may be necessary to fully address abnormal behaviors in individuals with FXS.

  13. Effect of anticancer drugs on breast cancer cells sensitive and resistant to doxorubicin: expression of mRNAs of TGF-β and its receptors

    Directory of Open Access Journals (Sweden)

    Chorna I. V.

    2014-01-01

    Full Text Available Aim. Comparative study of the effect of chemotherapeutic drugs (doxorubicin, methotrexate and cisplatin and TGF-β on the human breast carcinoma MCF-7 cells, sensitive (wt and resistant (DOX/R to the doxorubicin action. Methods. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR was used for the estimation of expression of mRNAs coding for the TGF-β isoforms (TGF-β1 and TGF-β2 and the TGF-β type I and II receptors (TRI and TRII. Trypan blue exclusion method was used for measuring cell number and cell viability. Results. The MCF-7(DOX/R cells were more refractory to the TGF1-dependent growth inhibition than the MCF-7(wt cells. The level of mRNAs coding for TGF and its receptors was higher in the untreated MCF-7 (DOX/R cells comparing to the MCF-7(wt cells. The expression of mRNA coding for TRII was decreased in both cell lines treated with doxorubicin, methotrexate and cisplatin, while the down-regulation of mRNA coding for TRI was revealed only in the MCF-7(DOX/R cells upon the treatment with doxorubicin and methotrexate. Conclusions. The differential effects of studied anticancer drugs and TGF-β on the doxorubicin-sensitive and -resistant cells have been demonstrated. The elucidation of the molecular mechanisms of escape of the MCF-7 (DOX/R cells from the growth inhibition by TGF-β requires further investigation.

  14. Role of MRP Transporters in Regulating Antimicrobial Drug Inefficacy and Oxidative Stress-induced Pathogenesis during HIV-1 and TB Infections

    Directory of Open Access Journals (Sweden)

    Upal eRoy

    2015-09-01

    Full Text Available Multi-Drug Resistance Proteins (MRPs are members of the ATP binding cassette (ABC drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV used in highly active antiretroviral therapy (HAART and antibacterial agents used in Tuberculus Bacilli (TB therapy. Due to their role in efflux of glutathione (GSH conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9 have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

  15. Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer.

    Science.gov (United States)

    Park, Hansoo; Cho, Sung-Yup; Kim, Hyerim; Na, Deukchae; Han, Jee Yun; Chae, Jeesoo; Park, Changho; Park, Ok-Kyoung; Min, Seoyeon; Kang, Jinjoo; Choi, Boram; Min, Jimin; Kwon, Jee Young; Suh, Yun-Suhk; Kong, Seong-Ho; Lee, Hyuk-Joon; Liu, Edison T; Kim, Jong-Il; Kim, Sunghoon; Yang, Han-Kwang; Lee, Charles

    2015-10-01

    Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Recent high-throughput analyses of genomic alterations revealed several driver genes and altered pathways in GC. However, therapeutic applications from genomic data are limited, largely as a result of the lack of druggable molecular targets and preclinical models for drug selection. To identify new therapeutic targets for GC, we performed array comparative genomic hybridization (aCGH) of DNA from 103 patients with GC for copy number alteration (CNA) analysis, and whole-exome sequencing from 55 GCs from the same patients for mutation profiling. Pathway analysis showed recurrent alterations in the Wnt signaling [APC, CTNNB1, and DLC1 (deleted in liver cancer 1)], ErbB signaling (ERBB2, PIK3CA, and KRAS), and p53 signaling/apoptosis [TP53 and BCL2L1 (BCL2-like 1)] pathways. In 18.4% of GC cases (19/103), amplification of the antiapoptotic gene BCL2L1 was observed, and subsequently a BCL2L1 inhibitor was shown to markedly decrease cell viability in BCL2L1-amplified cell lines and in similarly altered patient-derived GC xenografts, especially when combined with other chemotherapeutic agents. In 10.9% of cases (6/55), mutations in DLC1 were found and were also shown to confer a growth advantage for these cells via activation of Rho-ROCK signaling, rendering these cells more susceptible to a ROCK inhibitor. Taken together, our study implicates BCL2L1 and DLC1 as potential druggable targets for specific subsets of GC cases. PMID:26401016

  16. The molecular epidemiological study of colistin-only-sensitive strains in multi-drug resistant Acinetobacter baumannii

    Institute of Scientific and Technical Information of China (English)

    YANG Li; HAN Lizhong; SUN Jingyong; YU Yunsong; NI Yuxing

    2007-01-01

    This paper reported the epidemiology of the colistin-only-sensitive Acinetobacter baumannii(COS-AB)in a tertiary teaching hospital in China.We analyzed the clinical data of 136 COS-AB isolates from June 2004 to May 2005 and collected 66 A.baumannii isolates in which 33 strains were COS-AB,and the rest were non-COS-AB.Random amplified polymorphic DNA(RAPD)analysis (primer ERIC2 and 272)showed that all COS-AB were identical,while pulsed-field gel electrophotesis(PFGE)analysis showed two separate genotypes of these COS-ABwhich were distinctly different from that of non-COS-AB.The COS-AB from burn wards showed the identical PFGE pattern which was distinguished from the genotype of COS-AB in other departments,mainly surgical systems.The cross-infection was severe and strict methods of disinfection and sterilization should be implemented.Meanwhile,the epidemiology of COS-AB in environment and patients should be closely monitored.The PFGE analysis is a reliable method of A.baumannii typing.

  17. pH-sensitive micelles based on acid-labile pluronic F68-curcumin conjugates for improved tumor intracellular drug delivery.

    Science.gov (United States)

    Fang, Xiao-Bin; Zhang, Jin-Ming; Xie, Xi; Liu, Di; He, Cheng-Wei; Wan, Jian-Bo; Chen, Mei-Wan

    2016-04-11

    Curcumin (Cur) is a highly pleiotropic anticancer agent that inhibits cell proliferation and induces apoptosis in cancer cells. A variety of nano-systems constituted by polymer-drug conjugates have been designed to overcome its shortages on water solubility, chemical instability, and poor bioavailability. However, most of them suffer from ineffective release of Cur in cancer cells in vivo. This work developed a novel flexible acid-responsive micelle formulation by covalently conjugating Cur on the hydrophilic terminals of pluronic F68 chains via cis-aconitic anhydride linkers. The synthesized F68-Cis-Cur conjugates can readily precipitate to form homogeneous micelles with average size about 100nm in aqueous solution. In acid environments, F68-Cis-Cur conjugates would break down and subsequently release Cur rapidly, for the reason of pH-sensitive cleavage of cis-aconitic anhydride linkers. In vitro anticancer activity tests demonstrated that F68-Cis-Cur micelles induced higher cytotoxicity against both A2780 and SMMC 7721 cells than free Cur. It provided a larger decrease of mitochondrion membrane potential and induced cellular apoptosis. F68-Cis-Cur micelles remarkably increased cellular uptake of Cur than free Cur through caveolae-mediated endocytosis in an energy-dependent manner. This study demonstrates F68-Cis-Cur conjugation as a promising tool for improving intracellular drug delivery in cancer therapy. PMID:26784981

  18. Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1

    Directory of Open Access Journals (Sweden)

    Zantl Niko

    2010-06-01

    Full Text Available Abstract Background Human renal cell carcinoma (RCC is very resistant to chemotherapy. ABT-737 is a novel inhibitor of anti-apoptotic proteins of the Bcl-2 family that has shown promise in various preclinical tumour models. Results We here report a strong over-additive pro-apoptotic effect of ABT-737 and etoposide, vinblastine or paclitaxel but not 5-fluorouracil in cell lines from human RCC. ABT-737 showed very little activity as a single agent but killed RCC cells potently when anti-apoptotic Mcl-1 or, unexpectedly, A1 was targeted by RNAi. This potent augmentation required endogenous Noxa protein since RNAi directed against Noxa but not against Bim or Puma reduced apoptosis induction by the combination of ABT-737 and etoposide or vinblastine. At the level of mitochondria, etoposide-treatment had a similar sensitizing activity and allowed for ABT-737-induced release of cytochrome c. Conclusions Chemotherapeutic drugs can overcome protection afforded by Mcl-1 and A1 through endogenous Noxa protein in RCC cells, and the combination of such drugs with ABT-737 may be a promising strategy in RCC. Strikingly, A1 emerged in RCC cell lines as a protein of similar importance as the well-established Mcl-1 in protection against apoptosis in these cells.

  19. A new double-antibody sandwich ELISA targeting Plasmodium falciparum aldolase to evaluate anti-malarial drug sensitivity

    Directory of Open Access Journals (Sweden)

    Brun Reto

    2009-10-01

    Full Text Available Abstract Background The standard in vitro test to assess anti-malarial activity of chemical compounds is the [3H]hypoxanthine incorporation assay. It is a radioactivity-based method to measure DNA replication of Plasmodium in red blood cells. The method is highly reproducible, however, the handling of radioactive material is costly, hazardous and requires the availability of appropriate technology and trained staff. Several other ways to evaluate in vitro anti-malarial activity do exist, all with their own assets and limitations. Methods The newly developed double-antibody sandwich ELISA described here is based on the properties of a non-overlapping pair of monoclonal antibodies directed against Plasmodium falciparum aldolase. This glycolytic enzyme possesses some unique nucleotide sequences compared to the human isoenzymes and has been highly conserved through evolution. Out of twenty possibilities, the most sensitive antibody pair was selected and used to quantitatively detect parasite aldolase in infected blood lysates. Results A total of 34 compounds with anti-malarial activity were tested side-by-side by ELISA and the [3H]hypoxanthine incorporation assay. The novel ELISA provided IC50s closely paralleling those from the radioactivity-based assay (R = 0.99, p Conclusion The newly developed ELISA presents several advantages over the comparative method, the [3H]hypoxanthine incorporation assay. The assay is highly reproducible, less hazardous (involves no radioactivity and requires little and cheap technical equipment. Relatively unskilled personnel can conduct this user-friendly assay. All this makes it attractive to be employed in resource-poor laboratories.

  20. Drug mules” as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

    International Nuclear Information System (INIS)

    Purpose: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox®) in the detection of internal cocaine containers. Methods: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. Results: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. Conclusions: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage

  1. Drug mules” as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Patricia M., E-mail: patricia.flach@irm.uzh.ch [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Department of Neuroradiology, Inselspital Bern, University of Bern, 3010 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Department of Radiology, University Hospital USZ, University of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Ross, Steffen G. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Ampanozi, Garyfalia; Ebert, Lars [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Germerott, Tanja; Hatch, Gary M. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Thali, Michael J. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Patak, Michael A. [Department of Radiology, Inselspital Bern, University of Bern, 3010 Bern (Switzerland); Department of Radiology, University Hospital USZ, University of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

    2012-10-15

    Purpose: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox{sup ®}) in the detection of internal cocaine containers. Methods: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. Results: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. Conclusions: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.

  2. EXPERIMENTAL RESEARCH OF EFFECTIVENESS OF siRNA-Her-2/neu ON DRUG SENSITIVITY OF Her-2/neu-OVER-EXPRESSING LUNG ADENOCARCINOMA CELL LINE

    Institute of Scientific and Technical Information of China (English)

    REN Shu-hua; WANG Jing-wei; QU Ping; LIU Yi; ZHANG Wei; ZHANG Lin

    2006-01-01

    Objective: Her-2/neu protein overexpression has been demonstrated in lung adenocarcinoma. Its overexpression often indicates a poor prognosis and resistance to chemotherapeutic agents. The objectives of this paper is to explore the effectiveness of double-stranded short inhibitory RNAs (siRNA) targeting Her-2/neu oncogene on the drug sensitivity of Her-2/neu-overexpressing lung adenocarcinoma cells. Methods: Lung adenocarcinoma cell line calu-3 was transfected with siRNAs formulated LipofectAMINE 2000, and Her-2/neu protein and P-gp were determined by flow cytometry (FCM). The chemosensitivity of transfected cells to cisplatin (CDDP) was measured by MTT. Cell apoptosis detection kit (Annexin V method) was used to examine the drug induced apoptosis rate. Results: siRNA targeting Her-2/neu greatly reduced the cell surface expression of Her-2/neu protein and had no effect on P-gp. Consequently the inhibitory rate of CDDP in combination with siRNA targeting Her-2/neu was (67.1(2.3)%, while the inhibitory rates were (48.1(3.5)%, (46.3(5.9)% and (50.2(2.9)% in untreated control, empty vector and unrelated siRNA groups, respectively. The FCM results showed that the apoptosis rate of cells treated with CDDP combined with siRNAs-Her-2/neu was elevated when compared with unrelated siRNA group and empty vector group. Conclusion: Sequence specific siRNA targeting Her-2/neu was capable of enhancing the chemosensitivity of calu-3 cell to cisplatin.

  3. Isolation, Identification and Drug-Sensitivity Test of P.aeruginosa%雏鸡绿脓杆菌的分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    靳双星; 陈理盾; 段继永

    2011-01-01

    对河南省中牟县某养殖户送检的病鸡进行病理剖检及细菌分离鉴定,根据发病临床症状,病理变化及病原分离鉴定,确诊为绿脓杆菌感染.药敏试验结果显示,所分离的绿脓杆菌对庆大霉素、氧氟沙星高度敏感;对丁胺卡那、多黏菌素中度敏感;对阿莫西林、氨苄西林及强力霉素耐药.%Diseased chicken collected in the Zhongmu country chicken house were examined. The investigation showed that P. Aeruginosa was main reason that caused chicken to death. P. Aeruginosa was isolated from diseased chickens. The result of drug-sensitivity suggested that isolated P. Aeruginosa was highly susceptible to Gentamicin,Ofloxacin. The isolated P. Aeruginosa was susceptible to Amikacin,Colistin. The isolated P. Aeruginosa showed resistance to Amoxicillin, Ampicillin.Doxycyc-line.

  4. Drug-sensitive tuberculosis, multidrug-resistant tuberculosis, and nontuberculous mycobacterial pulmonary disease in nonAIDS adults: comparisons of thin-section CT findings

    International Nuclear Information System (INIS)

    The aim of this work was to compare thin-section CT (TSCT) findings of drug-sensitive (DS) tuberculosis (TB), multidrug-resistant (MDR) TB, and nontuberculous mycobacterial (NTM) pulmonary disease in nonAIDS adults. During 2003, 216 (113 DS TB, 35 MDR TB, and 68 NTM) patients with smear-positive sputum for acid-fast bacilli (AFB), and who were subsequently confirmed to have mycobacterial pulmonary disease, underwent thoracic TSCT. The frequency of lung lesion patterns on TSCT and patients' demographic data were compared. The commonest TSCT findings were tree-in-bud opacities and nodules. On a per-person basis, significant differences were found in the frequency of multiple cavities and bronchiectasis (P<0.001, chi-square test and multiple logistic regression analysis). Multiple cavities were more frequent in MDR TB than in the other two groups and extensive bronchiectasis in NTM disease (multiple logistic regression analysis). Patients with MDR TB were younger than those with DS TB or NTM disease (P<0.001, multiple logistic regression analysis). Previous tuberculosis treatment history was significantly more frequent in patients with MDR TB or NTM disease (P<0.001, chi-square test and multiple logistic regression analysis). In patients with positive sputum AFB, multiple cavities, young age, and previous tuberculosis treatment history imply MDR TB, whereas extensive bronchiectasis, old age, and previous tuberculosis treatment history NTM disease. (orig.)

  5. 三种不同方法检测结核分枝杆菌药物敏感性分析%Analyse of drug sensitivity of mycobacterium tuberculosis using three different methods

    Institute of Scientific and Technical Information of China (English)

    蔡杏珊; 张院良; 谭耀驹

    2010-01-01

    Objective To discuss the accordance of mycobacterium tuberculosis drug sensitivity test result with equipment liquid proportion method and L-J proportion method.Methods Detecting the four anti-mycobacterium drugs ( INH、 SM、 RFP, EMB ) susceptibility of 107 strains mycobacterium with BacT/ALERT 3D rapid drug sensitivity test 、MGIT 960 rapid drug sensitivity test and L-J proportion method. Results ( 1 ) The four drug ( INH、 SM、 RFP, EMB ) sensitivity ratio was 93%、 90%、 95% 、 90% respectively with BacT/ALERT 3D rapid drug sensitivity test、 MGIT 960 rapid drug sensitivity test and L-J proportion method.( 2 ) The resistance rate of INH、 SM、 RFP, EMB using BacT/ALERT 3D、 MGIT 960 and L-J proportion method was 27%、 28%、 24%; 12%、 13%、19%; 25%、 25%、 22%; 7%、 6%、 9% respectively.There was no significant difference among the drug resistance rate detected by the three methods.( 3 )The average drug sensitivity test time using BacT/ALERT 3D、 MGIT 960 and L-J proportion method was 10.5 days、 7.7 days、 28 days. There was significant difference through statistical analysis ( P < 0.001 ) Conclusions The four drug ( INH、 SM、 RFP,EMB )sensitivity test using BacT/ALEBT 3D、MGIT 960 and L-J proportion method had high comparability.The drug sensitivity test time was shortest using MGIT 960 method.%目的 探讨仪器液体比例法(BacT/ALERT 3D与MGIT 960系统)与L-J比例法测试结核分枝杆菌药物敏感性结果 的一致性.方法 用BacT/ALERT 3D快速药敏法、MGIT 960快速药敏法、L-J比例法同时对107株结核分枝杆菌进行INH、SM、RFP及EMB四种抗结核药物的耐药性测定.结果 (1)INH、SM、RFP及EMB用BacT/ALERT 3D法、MGIT960法、L-J比例法药敏测试结果 一致率分别为:93%、90%、95%、90%.(2)BacT/ALERT 3D法、MGIT 960法、L-J比例法对INH、SM、RFP、EMB的耐药率分别是:27%、28%、24%;12%、13%、19%;25%、25%、22%;7%、6%、9%.三种方法 四种药物的耐

  6. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection

    DEFF Research Database (Denmark)

    Kuller, Lewis H; Tracy, Russell; Belloso, Waldo;

    2008-01-01

    HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis. METHODS AND FINDINGS: Stored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and......BACKGROUND: In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]).We hypothesized that increased...

  7. Opiate Drug Use and the Pathophysiology of NeuroAIDS

    OpenAIRE

    Hauser, Kurt F.; Fitting, Sylvia; Dever, Seth M; PODHAIZER, Elizabeth M.; Knapp, Pamela E.

    2012-01-01

    Opiate abuse and HIV-1 have been described as interrelated epidemics, and even in the advent of combined anti-retroviral therapy, the additional abuse of opiates appears to result in greater neurologic and cognitive deficits. The central nervous system (CNS) is particularly vulnerable to interactive opiate-HIV-1 effects, in part because of the unique responses of microglia and astroglia. Although neurons are principally responsible for behavior and cognition, HIV-1 infection and replication i...

  8. Fasciola hepatica: Histology of the Reproductive Organs and Differential Effects of Triclabendazole on Drug-Sensitive and Drug-Resistant Fluke Isolates and on Flukes from Selected Field Cases

    Directory of Open Access Journals (Sweden)

    Robert Hanna

    2015-06-01

    Full Text Available This review summarises the findings of a series of studies in which the histological changes, induced in the reproductive system of Fasciola hepatica following treatment of the ovine host with the anthelmintic triclabendazole (TCBZ, were examined. A detailed description of the normal macroscopic arrangement and histological features of the testes, ovary, vitelline tissue, Mehlis’ gland and uterus is provided to aid recognition of the drug-induced lesions, and to provide a basic model to inform similar toxicological studies on F. hepatica in the future. The production of spermatozoa and egg components represents the main energy consuming activity of the adult fluke. Thus the reproductive organs, with their high turnover of cells and secretory products, are uniquely sensitive to metabolic inhibition and sub-cellular disorganisation induced by extraneous toxic compounds. The flukes chosen for study were derived from TCBZ-sensitive (TCBZ-S and TCBZ-resistant (TCBZ-R isolates, the status of which had previously been proven in controlled clinical trials. For comparison, flukes collected from flocks where TCBZ resistance had been diagnosed by coprological methods, and from a dairy farm with no history of TCBZ use, were also examined. The macroscopic arrangement of the reproductive system in flukes was studied using catechol/carmine stained whole mounts, and the histology of the main organs was examined using conventional haematoxylin-eosin stained sections. Validation of apoptosis in the fluke sections was carried out using an in situ hybridisation method designed to label endonuclease-induced DNA strand breaks. In TCBZ-S flukes exposed to TCBZ metabolites for 24–96 h in vivo, but not in TCBZ-R flukes, those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles, were found to display progressive loss of cell content. This was due to apparent failure of cell division to keep pace with expulsion of the mature or

  9. Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis.

    Science.gov (United States)

    Zhang, Ruiguang; Li, Yan; Wang, Zhongliang; Chen, Lingjuan; Dong, Xiaorong; Nie, Xiu

    2015-11-01

    Non-small cell lung cancer is commonly seen with higher morbidity and mortality. High-mobility group protein 1 (HMGB1) is a highly conserved nuclear protein, which is involved in multiple human diseases including cancers. However, the mechanisms of HMGB1 in non-small cell lung cancer remain unclear. The goal of the present study is to identify the relationship between HMGB1 and the progresssion of non-small cell lung cancer and investigate the molecular mechanism of HMGB1 in non-small lung cancer cell lines. Firstly, we detected the expression levels of HMGB1 by by real-time PCR and western blotting analysis, and the results demonstrated that HMGB1 was much higher expressed in non-small cell lung cancer cell lines, including A549, SPC-1-1, NCI-2170, SK-MES-1, and NCI-H1299, compared with that of WI-38. Next, 5 μM of adriamycin (AMD), 20 μM of cisplatin (DDP), and 50 μM of methotrexate (MTX) were used to treat A549 cells and SPC-A-1 cells for 48 h. The results showed that treatment with chemotherapy drugs significantly increased the levels of HMGB1 in A549 cells and SPC-A-1 cells. Moreover, the expression levels of HMGB1 increased in a time-dependent manner being treated with DDP. Then, the endogenous HMGB1 expression was successfully interferred with shRNA specific to HMGB1 in A549 and SPC-A-1 cells, which was detected by western blotting analysis. Then, the cisplatin-sensitive A549 cells and cisplatin-resistant A549/DDP cells were treated with increasing concentrations of cisplatin for 24, 48, and 72 h; cell viability were analyzed by MTT assay; and IC50 values were calculated. The results demonstrated that the expression level of HMGB1 in A549/DDP cells was much higher than that of A549 cells; moreover, transfection with HMGB1 shRNA in A549/DDP cells decreased the IC50 value of cisplatin in A549/DDP cells. The expression levels of autophagy-related proteins beclin-1 and LC3-II were significantly higher in A549/DDP cells or the A549 cells treated with

  10. In vivo evaluation of pH-sensitive polymeric microparticles for site specific drug delivery to the small intestine and colon

    OpenAIRE

    Kendall, R. A.; Murdan, S.; Basit, A. W.

    2006-01-01

    A novel emulsification/solvent evaporation process was developed to formulate prednisolone-loaded Eudragit L and S microparticles as drug delivery vehicles to target different regions of the gastrointestinal tract. Microparticles were characterised in vitro and in vivo. This is the first report of drug absorption form orally administered Eudragit L and S microparticles.

  11. Analysis of pathogens and drug sensitivity on 87 cases of chronic suppurative osteomyelitis%87例慢性化脓性骨髓炎病原菌构成及药敏分析

    Institute of Scientific and Technical Information of China (English)

    陈爱宝; 龚琦; 宋建辉; 曾国庆

    2012-01-01

    Objective To analyse constitutes strains of pathogenic bacteria and drug sensitivity test of 87 cases of chronic suppurative osteomyelitis. Methods Bacteria culture and drug sensitive test were performed by taking sinus secretions or tissue in deep focus of infection from patients with chronic suppurative osteomyelitis. Results A total of 120 strains of pathogenic bacteria were isolated. From high to low infection rate the top 3 bacteria as Staphylococcus aureus ( 30% ), Pseudomonas aeruginosa (25% ), Escherichia coli ( 14.2% ). Vancomycin, imipenem were the highest rate of sensitive drug. Conclusion The main pathogens of chronic suppurative osteomyelitis were composed with Staphylococcus aureus, Pseudomonas aeruginosa. Drug sensitive test is the important basis for selection of antibiotics.%目的 分析87 例慢性化脓性骨髓炎的病原菌菌种构成、药敏实验结果.方法 取慢性化脓性骨髓炎患者窦道深部分泌物或病灶组织做细菌培养及药敏试验.结果 共培养出病原菌120 株,感染率由高到低前三位菌为金黄色葡萄球菌(占30%)、铜绿假单胞菌(占25%)、大肠埃希菌(占14.2%).万古霉素、亚胺培南是敏感率最高药物.结论 慢性化脓性骨髓炎的病原菌构成以金黄色葡萄球菌、铜绿假单胞菌为主,药敏试验是选用抗菌药物的重要依据.

  12. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Atrayee Banerjee

    Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  13. IN VITRO EFFECT OF VITAMIN C ON THE LABORATORY ISOLATES OF MYCOBACTERIUM TUBERCULOSIS WITH KNOWN SENSITIVITY AND RESISTANCE TO THE FIRST LINE ANTI TUBERCULAR DRUGS: AN EXPERIMENTAL PILOT STUDY

    Directory of Open Access Journals (Sweden)

    Talaulikar Nikita.S , Dsouza Delia.B , Rodrigues Savio , Kulkarni MS

    2015-04-01

    Full Text Available Background and Objectives: Globally, 3.5% of new cases of Tuberculosis (TB and 20.5% of previously treated cases are estimated to have multidrug- resistant tuberculosis, the corresponding estimates for India are 2.2%, and 15% respectively. Progress has been made in research and development of new drugs for TB over the last decade, thus fuelling the need for more innovative options. Recent in-vitro studies that claim Vitamin C to have an inhibitory effect on Mycobacterium tuberculosis could possibly prove to be a major breakthrough in Medicine. Hence this experimental study was conducted on a pilot basis with the objective of studying the in -vitro effect of the active ingredient of vitamin C on the laboratory isolates of Mycobacterium tuberculosis that were known to be sensitive and resistant to the first line anti tubercular drugs (Isoniazid, Rifampicin, Pyrazinamide and Ethambutol and to compare the dose related response of both sensitive and resistant strains of Mycobacterium tuberculosis to varying concentrations of Vitamin C. Materials and Methods: Using a Completely Randomized Design, a total of 17 viable Mycobacterium tuberculosis strains, 10 of which were sensitive to all first line anti-TB drugs (Isoniazid, Rifampicin, Pyrazinamide and Ethambutol and seven strains resistant to all first line Anti-TB drugs were experimented upon. Proportion method was used to determine drug susceptibility of Mycobacterium tuberculosis to Ascorbic acid. Data is presented in a summary table. Results: With 1mM (millimole concentration of Ascorbic acid, growth of Mycobacterium tuberculosis was observed on both drug containing as well as control media, but with higher concentration of Ascorbic acid (10 mM and 100mM, no growth was observed on Ascorbic acid containing Lowenstein Jenson media. Conclusion: Although the findings of this pilot study add to the supportive evidence of an in- vitro susceptibility of Mycobacterium tuberculosis to Vitamin C, the authors

  14. Pectin-HPMC E15LV Vs pH sensitive polymer coating films for delayed drug delivery to colon: a comparison of two dissolution models to assess colonic targeting performance in-vitro

    Directory of Open Access Journals (Sweden)

    A. Maria John Newton

    2012-08-01

    Full Text Available Summary.The study was designed to evaluate the in vitro dissolution characteristics comparatively between pH sensitive polymer coated tablets and natural polymer coated tablets in a various simulated fluids (pH values 1.2, 6, 6.8, 7.2, 5. The fabricated Mesalamine tablets were coated with pectin-HPMC(Hydroxy propyl methyl cellulose E15LV (FC1-FC5 in combination and with Eudragit L100 ( FC6-FC10separately. Different buffer conditions were chosen to mimic the pH changes of the terminal part of the ileum as well as the colon.  Two in vitro studies were conducted separately in all the formulations. The impact of the pH changes on the coated tablets in normal pH condition and reduced pH condition (which occurs during inflammation in the colon were compared. The results showed that the impact of pH changes on the release profile of Eudragit L100  coated tablets was significant in reduced pH condition. In pH sensitive polymer coated tablets, drug release characteristics and the rate were affected when compared to the pectin coated tablets.  This study indicates that poly methacrylate polymers could not release the drug in predetermined rate in a variety of pH conditions. The present treatment methods of inflammatory bowel disease (IBD mostly depend on pH sensitive polymers. These pH sensitive polymers based colonic devices may not serve the patient need successfully because the influence of colonic pH on pH sensitive polymers plays an important role in drug release. The lowered pH condition in diseased state could not trigger the drug release, as it was not the threshold pH of the particular coated polymer. Therefore, in such diseased conditions natural polymer (pectinbased devices serve better for the objective of the therapy. The study on the effect of pH changes on the drug release profile of natural polymer-based colonic devices revealed that there was no impact by pH changes on the devices since they release the drug by the effect of colonic

  15. Occurrence of intestinal parasites amongst persons on highly active antiretroviral drug therapy in Calabar, Cross River State, Nigeria

    Directory of Open Access Journals (Sweden)

    Paul C. Inyang-Etoh

    2015-02-01

    Full Text Available Opportunistic and intestinal parasite infections are common health problem among HIV/AIDS patients. Early detection and treatment of these parasites are important to improve the quality of life of this category of patients. The occurrence of intestinal parasites among 400 patients on highly active anti-retroviral drug therapy (HAART aged 11-60 years was investigated. Standard parasitological techniques like direct microscopy, formol ether concentration and modified Ziehl- Neelsen staining techniques were used to analyze the stool samples. Intestinal parasite infections were positive in 116 (29% of the subjects on HAART while control subjects had 12 (12% and the difference was statistically significant (P<0.05. Subjects in the age group 21-30 years had the highest infection rate 54 (35.1%. There was no statistically significant difference in infection according to age (P>0.05. Females 76 (32.5% had a higher prevalence rate than males 40 (24.1%. But there was no statistically significant difference in infection according to gender (P<0.05. Patients with CD4 count of less than 200 cells/mm3 were observed to be more infected than those with CD4 count of more than 200 cells/mm3. There was a strong positive correlation (r=0.94 between CD4 count and the occurrence of intestinal parasite infection. Protozoan parasites 84 (21.0% accounted for a higher prevalence rate than helminthic parasites 32 (8.0%. These findings has revealed a high prevalence of intestinal parasite infection among patients on HAART thus the routine screening of stool samples from these category of patients for intestinal parasites is advocated for effective management of the disease.

  16. METHYLPHENIDATE ENHANCES THE ABUSE-RELATED BEHAVIORAL EFFECTS OF NICOTINE IN RATS: INTRAVENOUS SELF-ADMINISTRATION, DRUG DISCRIMINATION AND LOCOMOTOR CROSS-SENSITIZATION

    OpenAIRE

    Wooters, Thomas E.; Neugebauer, Nichole M.; Rush, Craig R.; Bardo, Michael T.

    2007-01-01

    Stimulant drugs, including d-amphetamine, cocaine and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination and locomotor cross-se...

  17. Ex vivo drug sensitivity profiles of Plasmodium falciparum field isolates from Cambodia and Thailand, 2005 to 2010, determined by a histidine-rich protein-2 assay

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    Tyner Stuart D

    2012-06-01

    Full Text Available Abstract Background In vitro drug susceptibility assay of Plasmodium falciparum field isolates processed “immediate ex vivo” (IEV, without culture adaption, and tested using histidine-rich protein-2 (HRP-2 detection as an assay, is an expedient way to track drug resistance. Methods From 2005 to 2010, a HRP-2 in vitro assay assessed 451 P. falciparum field isolates obtained from subjects with malaria in western and northern Cambodia, and eastern Thailand, processed IEV, for 50% inhibitory concentrations (IC50 against seven anti-malarial drugs, including artesunate (AS, dihydroartemisinin (DHA, and piperaquine. Results In western Cambodia, from 2006 to 2010, geometric mean (GM IC50 values for chloroquine, mefloquine, quinine, AS, DHA, and lumefantrine increased. In northern Cambodia, from 2009–2010, GM IC50 values for most drugs approximated the highest western Cambodia GM IC50 values in 2009 or 2010. Conclusions Western Cambodia is associated with sustained reductions in anti-malarial drug susceptibility, including the artemisinins, with possible emergence, or spread, to northern Cambodia. This potential public health crisis supports continued in vitro drug IC50 monitoring of P. falciparum isolates at key locations in the region.

  18. Mangiferin enhances the sensitivity of human multiple myeloma cells to anticancer drugs through suppression of the nuclear factor κB pathway.

    Science.gov (United States)

    Takeda, Tomoya; Tsubaki, Masanobu; Kino, Toshiki; Kawamura, Ayako; Isoyama, Shota; Itoh, Tatsuki; Imano, Motohiro; Tanabe, Genzoh; Muraoka, Osamu; Matsuda, Hideaki; Satou, Takao; Nishida, Shozo

    2016-06-01

    Multiple myeloma (MM) is still an incurable hematological malignancy with a 5-year survival rate of ~35%, despite the use of various treatment options. The nuclear factor κB (NF-κB) pathway plays a crucial role in the pathogenesis of MM. Thus, inhibition of the NF-κB pathway is a potential target for the treatment of MM. In a previous study, we showed that mangiferin suppressed the nuclear translocation of NF-κB. However, the treatment of MM involves a combination of two or three drugs. In this study, we examined the effect of the combination of mangiferin and conventional anticancer drugs in an MM cell line. We showed that the combination of mangiferin and an anticancer drug decreased the viability of MM cell lines in comparison with each drug used separately. The decrease in the combination of mangiferin and an anticancer drug induced cell viability was attributed to increase the expression of p53 and Noxa and decreases the expression of XIAP, survivin, and Bcl-xL proteins via inhibition of NF-κB pathway. In addition, the combination treatment caused the induction of apoptosis, activation of caspase-3 and the accumulation of the cells in the sub-G1 phase of the cell cycle. Our findings suggest that the combination of mangiferin and an anticancer drug could be used as a new regime for the treatment of MM. PMID:27035859

  19. Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: Application of PET to drug pharmacokinetic study

    International Nuclear Information System (INIS)

    Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [11C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [11C]MAP using positron emission tomography (PET). A significant increase of [11C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization

  20. A profile of patients attending an Anti Retroviral Therapy (ART) centre at a tertiary care hospital in South India

    OpenAIRE

    Sanjeev Badiger

    2010-01-01

    In 2004, the Indian government began providing free antiretroviral therapy (ART) through established ART centers. Despite the fact that ART is provided free by the government, there are a large number of sero positive people who do not come forward to receive treatment. Non-adherence is further confounds efforts to offer effective treatment. This study reports the profile of patients who attend an ART centres in southern India.

  1. Effect of micronutrient and probiotic fortified yogurt on immune-function of anti-retroviral therapy naive HIV patients

    NARCIS (Netherlands)

    R.B.S. Hummelen (Ruben); J. Hemsworth (Jaimie); J. Changalucha (John); N.L. Butamanya (Nicodemus); S. Hekmat (Sharareh); J.D.F. Habbema (Dik); G. Reid (Gregor)

    2011-01-01

    textabstractBackground: Micronutrient supplementation has been shown to reduce the progression of HIV but does not have an effect on the intestinal barrier or the intestinal microbiota of HIV patients. Studies have suggested that probiotics could potentially complement micronutrients in preserving t

  2. Incubation periods under various anti-retroviral therapies in homogeneous mixing and age-structured dynamical models: A theoretical approach

    CERN Document Server

    Rao, Arni S R Srinivasa

    2008-01-01

    Abstract. We consider previously well-known models in epidemiology where the parameter for incubation period is used as one of the important components to explain the dynamics of the variables. Such models are extended here to explain the dynamics with respect to a given therapy that prolongs the incubation period. A deconvolution method is demonstrated for estimation of parameters in the situations when no-therapy and multiple therapies are given to the infected population. The models and deconvolution method are extended in order to study the impact of therapy in age-structured populations. A generalisation for a situation when n-types of therapies are available is given.

  3. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study

    DEFF Research Database (Denmark)

    Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd; Gordin, Fred M; Grund, Birgit; Lundgren, Jens D; Neaton, James D; Pett, Sarah L; Phillips, Andrew; Touloumi, Giota; Vjechaj, Michael J

    Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an incr...

  4. Terapia antirretroviral directamente observada en mujeres privadas de libertad Directly observed anti-retroviral therapy amongst female inmates

    Directory of Open Access Journals (Sweden)

    L. De Carolis

    2009-02-01

    Full Text Available Objetivos: La adherencia al tratamiento antirretroviral de alta eficacia (TARV se considera el gold standard para el éxito del mismo. Para mejorar la adherencia en persona privadas de libertad viviendo con VIH-Sida, se propuso la utilización del tratamiento directamente observado tomando el modelo para el tratamiento de la tuberculosis. Material y métodos: se incluyeron las mujeres VIH positivas con criterios de TARV que voluntariamente decidieron participar. Los datos principales a evaluar fueron control inicial y final de CD4 y carga viral para VIH. Resultados: estudiamos 52 mujeres, edad promedio 34 años, entre 1 y 20 años de infección VIH. CD4 menor a 100 cél/ml inicial en 16 pacientes (30.7% y final en 4 pacientes (7.6%. Carga viral indetectable inicial en ninguna paciente y final en 33 pacientes (63.4% 21 % con infecciones oportunistas, principal tuberculosis. 17% coinfectadas con HCV. El esquema de TARV más utilizado fue 2 INTR más 1 INNTR. Conclusiones: La estrategia DOT aplicada al TARV fue efectiva en nuestras pacientes, evidenciado por el aumento de los CD4 y el mayor número de pacientes con disminución de la carga viral hasta permanecer indetectables. Si bien es difícil de implementar en tratamientos crónicos consideramos que es una herramienta útil para personas privadas de libertad.Objectives: It is considered that the gold standard for success in HAART is adherence. To improve adherence amongst inmates with HIV-AIDS, the use of directly observed treatment (DOT is proposed using the tuberculosis treatment model. Material and methods: HIV positive female patients with ARVT criteria who voluntarily participated were used for the study. The initial and final CD4 cell count and HIV viral load were the principal data used for assessment purposes. Results: 52 women with an average age of 34 years were studied, with an average HIV infection time span of between 1 and 20 years. Initial CD4 cell count of <100 copies/mL in 16 patients (30.7% and an equivalent final count in 4 patients (7.6% were found. Initial undetectable viral loads were not found in any patient, while final undetectable viral loads were found in 33 (63.4%. 21% of patients had opportunistic infections. The most important of these was tuberculosis, followed by HCV co-infection. The most frequently used ARVT schedule was two NRTI with one NNTRI. Conclusions: The application of DOT strategy to ARVT was effective amongst our patients, as shown by the increase in CD4 counts and the increased number of patients with reductions in viral loads to undetectable levels. While it is a tool that is not easy to use for cases of chronic treatment, we do consider it to be useful for prison inmates.

  5. Cognitive and psychosocial development of HIV pediatric patients receiving highly active anti-retroviral therapy: a case-control study

    Directory of Open Access Journals (Sweden)

    Theodoridou Maria

    2010-12-01

    Full Text Available Abstract Background The psychosocial development of pediatric HIV patients has not been extensively evaluated. The study objectives were to evaluate whether emotional and social functions are differentially associated with HIV-related complications. Methods A matched case-control study design was conducted. The case group (n = 20 consisted of vertically infected children with HIV (aged 3-18 years receiving HAART in Greece. Each case was matched with two randomly selected healthy controls from a school-based population. CNS imaging and clinical findings were used to identify patients with HIV-related neuroimaging abnormalities. The Wechsler Intelligence Scale III and Griffiths Mental Abilities Scales were applied to assess cognitive abilities. The age specific Strengths and Difficulties Questionnaire was used to evaluate emotional adjustment and social skills. The Fisher's exact test, student's t-test, and Wilcoxon rank sum test were used to compare categorical, continuous, and ordinal scores, respectively, of the above scales between groups. Results HIV patients without neuroimaging abnormalities did not differ from patients with neuroimaging abnormalities with respect to either age at HAART initiation (p = 0.306 or months of HAART treatment (p = 0.964. While HIV patients without neuroimaging abnormalities had similar cognitive development with their healthy peers, patients with neuroimaging abnormalities had lower mean General (p = 0.027 and Practical (p = 0.042 Intelligence Quotient scores. HIV patients without neuroimaging abnormalities had an increased likelihood of both Abnormal Emotional Symptoms (p = 0.047 and Hyperactivity scores (p = 0.0009. In contrast, HIV patients with neuroimaging abnormalities had an increased likelihood of presenting with Abnormal Peer Problems (p = 0.033. Conclusions HIV patients without neuroimaging abnormalities are more likely to experience maladjustment with respect to their emotional and activity spheres, while HIV patients with neuroimaging abnormalities are more likely to present with compromised social skills. Due to the limited sample size and age distribution of the study population, further studies should investigate the psychosocial development of pediatric HIV patients following the disclosure of their condition.

  6. The factors that influence adherence of pregnant women with HIV/AIDS to anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Valéria Lima de Barros

    2011-12-01

    Full Text Available Objective: To learn the experiences of pregnant women with HIV/AIDS in relation to adherence to antiretroviral therapy in two public hospitals of reference for HIV/AIDS in Fortaleza-CE, Brazil. Methods: A descriptive study conducted with 24 pregnant women who were in prenatal care and use of antiretroviral therapy. Sociodemographic and obstetric data and information regarding the experience with antiretroviral therapy adherence were collected from July to September 2009, through a semi-structured interview. Results: Womenhad a mean age of 29, low income, low education and a stable partner. It was found that some factors affect pregnant women adherence to antiretroviral therapy. Among these, stand out not accepting the diagnosis and the absence of signs and symptoms of AIDS. However,the fear of transmitting the virus to the baby acted as a stimulus for pregnant women adhere to treatment. Conclusion: The non-acceptance of diagnosis and the absence of signs and symptoms of AIDS negatively affect pregnant women adherence to antiretroviral treatment. On the other hand, the fear that the child be born with the virus and the desire to continue to live are stimuli to adherence.

  7. Clinical presentation and outcome of Tuberculosis in Human Immunodeficiency Virus infected children on anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Walters Lourens O

    2008-01-01

    Full Text Available Abstract Background The tuberculosis (TB and human immunodeficiency virus (HIV epidemics are poorly controlled in sub-Saharan Africa, where highly active antiretroviral treatment (HAART has become more freely available. Little is known about the clinical presentation and outcome of TB in HIV-infected children on HAART. Methods We performed a comprehensive file review of all children who commenced HAART at Tygerberg Children's Hospital from January 2003 through December 2005. Results Data from 290 children were analyzed; 137 TB episodes were recorded in 136 children; 116 episodes occurred before and 21 after HAART initiation; 10 episodes were probably related to immune reconstitution inflammatory syndrome (IRIS. The number of TB cases per 100 patient years were 53.3 during the 9 months prior to HAART initiation, and 6.4 during post HAART follow-up [odds ratio (OR 16.6; 95% confidence interval (CI 12.5–22.4]. A positive outcome was achieved in 97/137 (71% episodes, 6 (4% cases experienced no improvement, 16 (12% died and the outcome could not be established in 18 (13%. Mortality was less in children on HAART (1/21; 4.8% compared to those not on HAART (15/116; 12.9%. Conclusion We recorded an extremely high incidence of TB among HIV-infected children, especially prior to HAART initiation. Starting HAART at an earlier stage is likely to reduce morbidity and mortality related to TB, particularly in TB-endemic areas. Management frequently deviated from standard guidelines, but outcomes in general were good.

  8. Who has access to counseling and testing and anti-retroviral therapy in Malawi – an equity analysis

    Directory of Open Access Journals (Sweden)

    Banda Talumba

    2009-05-01

    Full Text Available Abstract Background The HIV and AIDS epidemic in Malawi poses multiple challenges from an equity perspective. It is estimated that 12% of Malawians are living with HIV or AIDS among the 15-49 age group. This paper synthesises available information to bring an equity lens on Counselling and Testing (CT and Antiretroviral Therapy (ART policy, practice and provision in Malawi. Methods A synthesis of a wide range of published and unpublished reports and studies using a variety of methodological approaches was undertaken. The analysis and recommendations were developed, through consultation with key stakeholders in Malawi. Findings At the policy level Malawi is unique in having an equity in access to ART policy, and equity considerations are also included in key CT documents. The number of people accessing CT has increased considerably from 149,540 in 2002 to 482,364 in 2005. There is urban bias in provision of CT and more women than men access CT. ART has been provided free since June 2004 and scale up of ART provision is gathering pace. By end December 2006, there were 85,168 patients who had ever started on ART in both the public and private health sector, 39% of the patients were male while 61% were female. The majority of patients were adults, and 7% were children, aged 14 years or below. Despite free ART services, patients, especially poor rural patients face significant barriers in access and adherence to services. There are missed opportunities in strengthening integration between CT and ART and TB, Sexually Transmitted Infections (STI and maternal health services. Conclusion To promote equitable access for CT and ART in Malawi there is need to further invest in human resources for health, and seize opportunities to integrate CT and ART services with tuberculosis, sexually transmitted infections and maternal health services. This should not only promote access to services but also ensure that resources available for CT and ART strengthen rather than undermine the provision of the essential health package in Malawi. Ongoing equity analysis of services is important in analyzing which groups are unrepresented in services and developing initiatives to address these. Creative models of decentralization, whilst maintaining quality of services are needed to further enhance access of poor rural women, men, girls and boys.

  9. Impact of Hiv-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

    Science.gov (United States)

    Marshall, Catherine S.; Curtis, Andrea J.; Spelman, Tim; O’Brien, Daniel P.; Greig, Jane; Shanks, Leslie; du Cros, Philipp; Casas, Esther C.; da Fonseca, Marcio Silveira; Athan, Eugene; Elliott, Julian H.

    2013-01-01

    Objectives To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). Design, Setting Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010. Subjects, Participants 36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55–2.27). Outcome Measures Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation. Results There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21–5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with increased mortality (HR: 2.21; 95% CI: 1.97–2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74–4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), non-tuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80–3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80–3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary tuberculosis, Kaposi’s sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates. Conclusions A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for diagnostics, therapeutic interventions and research. PMID:23935870

  10. Impact of HIV-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

    OpenAIRE

    Marshall, Catherine S; Curtis, Andrea J.; Spelman, Tim; O'Brien, Daniel P.; Greig, Jane; Shanks, Leslie; du Cros, Philipp; Casas, Esther C; da Fonseca, Marcio Silveira; Athan, Eugene; Elliott, Julian H

    2013-01-01

    Objectives To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). Design, Setting Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010. Subjects, Participants 36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55–2.27). Outcome Measures Using a proportional hazards model we identified factors...

  11. Dual fluorescent HPMA copolymers for passive tumor targeting with pH-sensitive drug release II: impact of release rate on biodistribution

    Czech Academy of Sciences Publication Activity Database

    Chytil, Petr; Hoffmann, S.; Schindler, Lucie; Kostka, Libor; Ulbrich, Karel; Caysa, H.; Mueller, T.; Mäder, K.; Etrych, Tomáš

    2013-01-01

    Roč. 172, č. 2 (2013), s. 504-512. ISSN 0168-3659. [International Symposium on Recent Advances in Drug Delivery Systems /16./. Salt Lake City, 03.02.2013-06.02.2013] R&D Projects: GA ČR GCP207/12/J030; GA MŠk EE2.3.30.0029 Institutional support: RVO:61389013 Keywords : HPMA copolymers * pH-responsive drug release * tumor accumulation Subject RIV: CD - Macromolecular Chemistry Impact factor: 7.261, year: 2013

  12. Inhibition of GSK-3β activity can result in drug and hormonal resistance and alter sensitivity to targeted therapy in MCF-7 breast cancer cells

    OpenAIRE

    Sokolosky, Melissa; Chappell, William H.; Stadelman, Kristin; Abrams, Stephen L.; Davis, Nicole M.; Steelman, Linda S.; McCubrey, James A.

    2014-01-01

    The PI3K/Akt/mTORC1 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance, and metastasis. One molecule regulated by this pathway is GSK-3β. GSK-3β is phosphorylated by Akt on S9, which leads to its inactivation; however, GSK-3β also can regulate the activity of the PI3K/Akt/mTORC1 pathway by phosphorylating molecules such as PTEN, TSC2, p70S6K, and 4E-BP1. To further elucidate the roles of GSK-3β in chemotherapeutic drug and hormonal resistance o...

  13. Drug sensitivity analysis of type 2 diabetes complicated with urinary tract infection in Handan City%邯郸市2型糖尿病伴尿路感染的药敏分析

    Institute of Scientific and Technical Information of China (English)

    高玉梅; 韩永霞; 冯采兰

    2013-01-01

    目的 分析2型糖尿病伴尿路感染病例药敏试验结果,以指导临床合理选择抗生素.方法 取糖尿病伴尿路感染患者的清洁中段尿进行培养,采用配套的药敏卡进行药敏试验;按糖尿病伴尿路感染和非糖尿病伴尿路感染分组进行分析.结果 糖尿病伴尿路感染组患者感染的菌种存在多样性,糖尿病伴尿路感染组比非糖尿病伴尿路感染组对亚胺培南(敏感率91.49%)、阿米卡星(敏感率53.19%)敏感率高,且两组比较,差异有统计学意义(P<0.05).两组对头孢哌酮/舒巴坦、哌拉西林/他唑巴坦敏感率均>60%,所有菌株均对亚胺培南、阿米卡星敏感;糖尿病伴尿路感染阳性组有4例合并肠球菌感染.结论 糖尿病伴尿路感染患者应根据药敏试验结果合理使用抗生素,亚胺培南、阿米卡星、头孢哌酮/舒巴坦、哌拉西林/他唑巴坦为敏感药物.%[Objective] To analyze the results of drug sensitive test of type 2 diabetes complicated with urinary tract infection cases, guide reasonable choice of antibiotics in clinic. [ Methods] The samples of clean midstream urine from patients with diabetes and u-rinary tract infection were cultured, and the drug sensitive test was conducted with targeted drug sensitivity cards. Two groups, which included the diabetes with urinary tract infection group and the non-diabetes with urinary tract infection group, were analyzed. [ Results] The patients in the diabetes with urinary tract infection group were infected with a variety of bacteria. The sensitivity to imipenem (91.49% ) and amikacin (53.19% ) of the diabetes with urinary tract infection group was higher than that of the non-diabetes with urinary tract infection group, and the differences were significant (P < 0. 05). The sensitivity to cefoperazone/ sulbactam and piperacillin/tazobactam of both two groups were higher than 60% , while all strains were sensitive to imipenem and amikacin. 4 cases were

  14. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental ...

  15. On the absorption and emission properties of three new non-steroidal anti-inflammatory drugs-β-cyclodextrin host-guest inclusion complexes: differentiated sensitivity to the microenvironment upon light excitation

    OpenAIRE

    MONTI S; Salemi, M. G.; S. Giuffrida; De Fazio, S; Guidi, G.; Sortino, S.

    1999-01-01

    The effects of β-cyclodextrin (β-CD) complexation on the absorption and emission properties of the non-steroidal anti-inflammatory drugs tolmetin (TM), diflunisal (DF), and fenbufen (FB) have been investigated. The absorption spectra of all these compounds are only slightly affected by the addition of ��-CD. In contrast, the emission properties were markedly influenced by CD complexation and in a different manner for the three compounds due to a differentiated sensitivity of the exci...

  16. 生牛乳中金黄色葡萄球菌的分离鉴定与药物敏感性分析%Analysis on Isolation,Identification and Drug Sensitivity of Staphylococcus aureus in Raw Cow Milk

    Institute of Scientific and Technical Information of China (English)

    王文博; 谷晓红; 苑学霞; 李瑞菊; 梁京芸; 李鸳鸯

    2015-01-01

    采用金黄色葡萄球菌(Staphylococcus aureus)测试片快速筛选的方法,对采集于陕西省西安市和渭南市20份样品中 S.aureus 进行分离鉴定及药物敏感性研究,以了解此地区生牛乳中 S.aureus 的污染情况及对药物敏感性。结果表明:S.aureus 测试片可用于大量生牛乳样品中 S.aureus 的初筛工作,方便且省力;S.aureus 的检出率为10%;检出的两株 S.aureus 对青霉素都为耐药,其中一株对磺胺异恶唑也表现为耐药,两株 S.aureus 对复方新诺明、红霉素、万古霉素、氧氟沙星、克林霉素都表现为敏感。牛场应根据药物敏感性实时调整抗感染药物的使用方案。%With 20 samples from Xi’an and Weinan City,Shaanxi Province,as materials,the isolation, identification and drug sensitivity of Staphylococcus aureus in raw cow milk were studied using S.aureus detec-tive slips to know the pollution situation and drug sensitivity of S.aures in this area.The results showed that S. aureus detective slips could be used to screen the S.aureus preliminarily from a large number of raw cow milk samples.The method was convenient and labor -saving.The detection rate of S.aureus was 1 0%.Both the detected S.aureus isolates were resistant to penicillin,but sensitive to trimethoprim -sulfamethoxazole,eryth-romycin,vancomycin,ofloxacin and clindamycin.One of the isolates was resistant to sulfisoxazole.Cow farms should adjust their anti -infection drugs timely according to the drug sensitivity of pathogen.

  17. Drug Facts

    Medline Plus

    Full Text Available ... Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts ... and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free Talking to Kids ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What To Say if You Were ...

  19. The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study

    Directory of Open Access Journals (Sweden)

    Tom D. Bunney

    2015-03-01

    Full Text Available Fibroblast growth factor receptors (FGFRs are recognized therapeutic targets in cancer. We here describe insights underpinning the impact of mutations on FGFR1 and FGFR3 kinase activity and drug efficacy, using a combination of computational calculations and experimental approaches including cellular studies, X-ray crystallography and biophysical and biochemical measurements. Our findings reveal that some of the tested compounds, in particular TKI258, could provide therapeutic opportunity not only for patients with primary alterations in FGFR but also for acquired resistance due to the gatekeeper mutation. The accuracy of the computational methodologies applied here shows a potential for their wider application in studies of drug binding and in assessments of functional and mechanistic impacts of mutations, thus assisting efforts in precision medicine.

  20. In vitro Plasmodium falciparum drug sensitivity assay: inhibition of parasite growth by incorporation of stomatocytogenic amphiphiles into the erythrocyte membrane

    DEFF Research Database (Denmark)

    Ziegler, Hanne L; Staerk, Dan; Christensen, Jette;

    2002-01-01

    -treated parasite culture continued to grow well in untreated erythrocytes. Thus, the antiplasmodial activity of lupeol appears to be indirect, being due to stomatocytic transformation of the host cell membrane and not to toxic effects via action on a drug target within the parasite. A number of amphiphiles that...... cause stomatocyte formation, but not those causing echinocyte formation, were shown to inhibit growth of the parasites, apparently via a mechanism similar to that of lupeol. Since antiplasmodial agents that inhibit parasite growth through erythrocyte membrane modifications must be regarded as unsuitable...... as leads for development of new antimalarial drugs, care must be exercised in the interpretation of results of screening of plant extracts and natural product libraries by an in vitro Plasmodium toxicity assay....

  1. Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier.

    Science.gov (United States)

    Lv, Ouyang; Tao, Yongxin; Qin, Yong; Chen, Chuanxiang; Pan, Yan; Deng, Linhong; Liu, Li; Kong, Yong

    2016-10-01

    Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the -NH2 groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel. PMID:27287145

  2. Alteration of Drug Sensitivity in Human Colon Cancer Cells after Exposure to Heat: Implications for Liver Metastasis Therapy using RFA and Chemotherapy

    OpenAIRE

    Makizumi, Ryouji; Yang, Weng-Lang; Owen, Randall P.; Sharma, Rohit R.; Ravikumar, T S

    2008-01-01

    Radiofrequency ablation (RFA) is gaining popularity for treating colorectal liver metastases by inducing image guided tumor hyperthermia. In order to reduce tumor recurrence, adjuvant therapies have been administered post-RFA. We hypothesized that tumor cells escaping RFA cytotoxicity by being in the sublethal zones of tumor might develop differential behavior toward cytotoxic drugs. Here, we used cultured human colorectal cancer cells to evaluate the interaction between heat treatment and ch...

  3. Downregulation of δ opioid receptor by RNA interference enhances the sensitivity of BEL/FU drug-resistant human hepatocellular carcinoma cells to 5-FU

    OpenAIRE

    Tang, Bo; Hu, Zhigao; Li, Yang; YUAN, SHENGGUANG; Wang, Zhenran; Yu, Shuiping; He, Songqing

    2015-01-01

    δ opioid receptor (DOR) was the first opioid receptor of the G protein-coupled receptor family to be cloned. Our previous studies demonstrated that DOR is involved in regulating the development and progression of human hepatocellular carcinoma (HCC), and is involved in the regulation of the processes of invasion and metastasis of HCC cells. However, whether DOR is involved in the development and progression of drug resistance in HCC has not been reported and requires further elucidation. The ...

  4. A sensitive and semi-quantitative method for determination of multi-drug residues in animal body fluids using multiplex dipstick immunoassay.

    Science.gov (United States)

    Han, Shuaijuan; Zhou, Tianjiao; Yin, Bingjie; He, Pingli

    2016-07-13

    The objective of this research was to develop a multiplex dipstick immunoassay method for the simultaneous determination of multi-veterinary drug residues, such as β-agonists, sulfonamides, and tetracyclines in milk, urine, and serum. The multiplex dipstick assay format was based on an indirect competitive approach: Three test lines (different antigens) and one control line (goat anti-mouse IgG) were located on the strip membrane. Labeled antibodies were freeze-dried in microwells. Samples did not require pretreatment and could be directly analyzed within 10 min. Threshold levels in different sample matrices were visually estimated at 0.3-0.45 ng mL(-1) for clenbuterol; 3-4 ng mL(-1) for sulfadiazine; and 4.5-6 ng mL(-1) for tetracycline, respectively. The linear relationship between the concentrations of veterinary drug residues and the Au nanoparticles plasmon absorbance allowed quantitative determination of these veterinary drug residues. The recoveries of clenbuterol, sulfadiazine and tetracycline in spiked samples ranged from 78.4% to 112.6%, and the relative standard deviations were below 11.2%. Analysis of animal samples suggested that the proposed multiplex dipstick assay method was consistent with the LC-MS/MS method. The percentage of false results was less than or equal to 5%. Thus, the proposed multiplex dipstick assay is inexpensive, easy-to-use, and suitable for the purposes of rapid and comprehensive screening of 3 families of β-agonists, sulfonamides and tetracyclines including 26 drugs in animal body fluids. PMID:27237838

  5. Analysis on drug sensitivity of ESBL-producing Escherichia coli%产超广谱β-内酰胺酶大肠埃希菌药敏情况分析

    Institute of Scientific and Technical Information of China (English)

    孙午; 熊莺

    2013-01-01

    目的 分析产ESBLs大肠埃希菌的临床分离和药敏情况,并与不产酶的大肠埃希菌的情况进行比较.方法 回顾性分析198株产ESBLs大肠埃希菌和287株不产ESBLs大肠埃希菌的耐药情况,采用x2检验分析耐药株和敏感株的来源差异和对常用抗菌药物的敏感性差异.结果 药敏实验证实产ESBLs大肠埃希菌和不产ESBLs大肠埃希菌除对亚胺培南、美洛培南和阿米卡星的敏感性差异无统计学意义外(P>0.05),对其他抗菌药物的敏感性差异都有统计学意义(P<0.05),产ESBLs大肠埃希菌对这些抗菌药物的耐药率相对于不产ESBLs大肠埃希菌都有不同程度的提高.结论 由于产ESBLs大肠埃希菌耐药机制的多样性和存在多重耐药情况,在临床确诊产ESBLs大肠埃希菌株感染时应根据药敏结果合理使用抗菌药物,同时应该珍惜使用对产ESBLs大肠埃希菌和不产ESBLs大肠埃希菌治疗无显著差异的碳青霉烯类以及阿米卡星等抗菌药物.%OBJECTIVE To analyze drug sensitivity of ESBL-producing Escherichia coli and compare with non-ESBL-produc-ing Escherichia coli. METHODS We got 198 ESBL-producing Escherichia coli and 287 non-ESBL-producing Escherichia coli. The results of ESBL-producing Escherichia coli and non-ESBL-producing Escherichia coli were analysed by χ2 test. RESULTS There were no significant differences in drug sensitivity of ESBL-producing Escherichia coli and Non-ESBL-producing Escherichia coli to imipenem, meropenem and amikacin (P> 0.05). Drug sensitive test discovered that there were significant differences in drug sensitivity of ESBL-producing Escherichia coli and non-ESBL-producing Escherichia coli to other antibiotics (P> 0.05), and drug sensitivity of ESBL-producing Escherichia coli was higher than non-ESBL-producing Escherichia coli. CONCLUSION We should use drug to treat patients in time and reasonably when the patient is diagnosed as infection by ESBL

  6. HIV quasispecies dynamics during pro-active treatment switching: impact on multi-drug resistance and resistance archiving in latent reservoirs.

    Directory of Open Access Journals (Sweden)

    Max von Kleist

    Full Text Available The human immunodeficiency virus (HIV can be suppressed by highly active anti-retroviral therapy (HAART in the majority of infected patients. Nevertheless, treatment interruptions inevitably result in viral rebounds from persistent, latently infected cells, necessitating lifelong treatment. Virological failure due to resistance development is a frequent event and the major threat to treatment success. Currently, it is recommended to change treatment after the confirmation of virological failure. However, at the moment virological failure is detected, drug resistant mutants already replicate in great numbers. They infect numerous cells, many of which will turn into latently infected cells. This pool of cells represents an archive of resistance, which has the potential of limiting future treatment options. The objective of this study was to design a treatment strategy for treatment-naive patients that decreases the likelihood of early treatment failure and preserves future treatment options. We propose to apply a single, pro-active treatment switch, following a period of treatment with an induction regimen. The main goal of the induction regimen is to decrease the abundance of randomly generated mutants that confer resistance to the maintenance regimen, thereby increasing subsequent treatment success. Treatment is switched before the overgrowth and archiving of mutant strains that carry resistance against the induction regimen and would limit its future re-use. In silico modelling shows that an optimal trade-off is achieved by switching treatment at days after the initiation of antiviral therapy. Evaluation of the proposed treatment strategy demonstrated significant improvements in terms of resistance archiving and virological response, as compared to conventional HAART. While continuous pro-active treatment alternation improved the clinical outcome in a randomized trial, our results indicate that a similar improvement might also be reached after

  7. 儿童假丝酵母感染状况分析及药物敏感性研究%Analysis on the infection status of Candida in children and the drug sensitive test

    Institute of Scientific and Technical Information of China (English)

    王长嘉; 孙晓红; 贺丹; 李广泉; 高磊; 高嵩; 王丽

    2012-01-01

    目的:探讨儿童假丝酵母的感染情况,分析其对常用抗真菌药物的敏感性,为真菌感染的治疗和预防提供依据.方法:收集临床假丝酵母感染患儿标本77例,进行菌株的分离、鉴定.并从患儿年龄、基础疾病及标本来源、检出病原菌种类、菌株药物敏感性等方面进行分析.结果:真菌感染患儿的平均年龄为6岁.标本主要来源于咽拭子,白假丝酵母的分离率最高(63.6%),其次为光滑假丝酵母、热带假丝酵母、克柔假丝酵母和其他假丝酵母.药物敏感性实验结果表明,假丝酵母对两性霉素B (AmB)、5-氟胞嘧啶(5- FC)的敏感性较高.其中,白假丝酵母对AmB、5- FC、氟康唑(FCZ)及伊曲康唑(ICZ)的敏感率依次为100.0%、91.9%、83.7%、69.4%;对ICZ、FCZ、5- FC的耐药率依次为4.1%、2.0%、2.0%.结论:儿童真菌感染以白假丝酵母最多见,分离菌株对FCZ和ICZ的耐药性较高,临床医生应高度重视,并根据药物敏感性实验结果进行治疗和预防.%Objective: To explore the infection status of Candida in children, analyze its sensitivity to antibiotics commonly used in clinic, provide a basis for the treatment and prevention of fungal infection. Methods; A total of 77 specimens of clinical infection of Candida in children were collected, then isolation and identification of bacterial strains were conducted, then the results were analyzed from the aspects of age, basic diseases, source of specimens, types of pathogens detected , and drug sensitivity of bacterial strains. Results -. The average age of the children with fungal infection was six years. The specimens were mainly from nasopharyngeal swabs. The isolation rate of Candida albicans was the highest (63. 6% ) , followed by Candida glabrata, Candida tropicalis, Candida krusei, and other Candida. The results of drug sensitive test showed that the sensitivities of Candida to amphoteriein B and 5 - fluorouracil were high. The

  8. 4-IBP, a σ1 Receptor Agonist, Decreases the Migration of Human Cancer Cells, Including Glioblastoma Cells, In Vitro and Sensitizes Them In Vitro and In Vivo to Cytotoxic Insults of Proapoptotic and Proautophagic Drugs

    Directory of Open Access Journals (Sweden)

    Veronique Mégalizzi

    2007-05-01

    Full Text Available Although the molecular function of cr receptors has not been fully defined and the natural ligand(s is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-tibenzylpiperidin-4-yl-4iodobenzamide (4-IBP, a selective σ1, agonist, has been used to investigate whether this compound is able to modify: 1 in vitro the migration and proliferation of human cancer cells; 2 in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3 in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC models the survival of mice coadministered cytotoxic agents. 4-IBP has revealed weak anti proliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

  9. Self-assembly of BODIPY based pH-sensitive near-infrared polymeric micelles for drug controlled delivery and fluorescence imaging applications

    Science.gov (United States)

    Liu, Xiaodong; Chen, Bizheng; Li, Xiaojun; Zhang, Lifen; Xu, Yujie; Liu, Zhuang; Cheng, Zhenping; Zhu, Xiulin

    2015-10-01

    Responsive block copolymer micelles emerging as promising imaging and drug delivery systems show high stability and on-demand drug release activities. Herein, we developed self-assembled pH-responsive NIR emission micelles entrapped with doxorubicin (DOX) within the cores by the electrostatic interactions for fluorescence imaging and chemotherapy applications. The block copolymer, poly(methacrylic acid)-block-poly[(poly(ethylene glycol) methyl ether methacrylate)-co-boron dipyrromethene derivatives] (PMAA-b-P(PEGMA-co-BODIPY)), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the molecular weight distribution of this copolymer was narrow (Mw/Mn = 1.31). The NIR fluorescence enhancement induced by the phenol/phenolate interconversion equilibrium works as a switch in response to the intracellular pH fluctuations. DOX-loaded PMAA-b-P(PEGMA-co-BODIPY) micelles can detect the physiological pH fluctuations with a pKa near physiological conditions (~7.52), and showed pH-responsive collapse and an obvious acid promoted anticancer drug release behavior (over 58.8-62.8% in 10 h). Real-time imaging of intracellular pH variations was performed and a significant chemotherapy effect was demonstrated against HeLa cells.Responsive block copolymer micelles emerging as promising imaging and drug delivery systems show high stability and on-demand drug release activities. Herein, we developed self-assembled pH-responsive NIR emission micelles entrapped with doxorubicin (DOX) within the cores by the electrostatic interactions for fluorescence imaging and chemotherapy applications. The block copolymer, poly(methacrylic acid)-block-poly[(poly(ethylene glycol) methyl ether methacrylate)-co-boron dipyrromethene derivatives] (PMAA-b-P(PEGMA-co-BODIPY)), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the molecular weight distribution of this copolymer was narrow (Mw/Mn = 1.31). The NIR

  10. TRAIL sensitize MDR cells to MDR-related drugs by down-regulation of P-glycoprotein through inhibition of DNA-PKcs/Akt/GSK-3β pathway and activation of caspases

    Directory of Open Access Journals (Sweden)

    Kim Dong-Wan

    2010-07-01

    Full Text Available Abstract Background The development of new modulator possessing high efficacy, low toxicity and high selectivity is a pivotal approach to overcome P-glycoprotein (P-gp mediated multidrug resistance (MDR in cancer treatment. In this study, we suggest a new molecular mechanism that TRAIL (tumor necrosis factor-related apoptosis-inducing ligand down-regulates P-glycoprotein (P-gp through inhibition of DNA-PKcs/Akt/GSK-3β pathway and activation of caspases and thereby sensitize MDR cells to MDR-related drugs. Results MDR variants, CEM/VLB10-2, CEM/VLB55-8 and CEM/VLB100 cells, with gradually increased levels of P-gp derived from human lymphoblastic leukemia CEM cells, were gradually more susceptible to TRAIL-induced apoptosis and cytotoxicity than parental CEM cells. The P-gp level of MDR variants was positively correlated with the levels of DNA-PKcs, pAkt, pGSK-3β and c-Myc as well as DR5 and negatively correlated with the level of c-FLIPs. Hypersensitivity of CEM/VLB100 cells to TRAIL was accompanied by the activation of mitochondrial apoptotic pathway as well as the activation of initiator caspases. In addition, TRAIL-induced down-regulation of DNA-PKcs/Akt/GSK-3β pathway and c-FLIP and up-regulation of cell surface expression of death receptors were associated with the increased susceptibility to TRAIL of MDR cells. Moreover, TRAIL inhibited P-gp efflux function via caspase-3-dependent degradation of P-gp as well as DNA-PKcs and subsequently sensitized MDR cells to MDR-related drugs such as vinblastine and doxorubicin. We also found that suppression of DNA-PKcs by siRNA enhanced the susceptibility of MDR cells to vincristine as well as TRAIL via down-regulation of c-FLIP and P-gp expression and up-regulation of DR5. Conclusion This study showed for the first time that the MDR variant of CEM cells was hypersensitive to TRAIL due to up-regulation of DR5 and concomitant down-regulation of c-FLIP, and degradation of P-gp and DNA-PKcs by

  11. Effect of Skin Sensitizers on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Skin Dendritic Cells: Role of Different Immunosuppressive Drugs

    OpenAIRE

    Cruz, M. T.; Neves, B. M.; Gonçalo, M; Figueiredo, A; C. B. Duarte; Lopes, M C

    2007-01-01

    Nitric oxide (NO) is involved in the pathogenesis of acute and chronic inflammatory conditions, namely in allergic contact dermatitis (ACD). However, the mechanism by which NO acts in ACD remains elusive. The present study focuses on the effects of different contact sensitizers (2,4-dinitrofluorbenzene, 1,4-phenylenediamine, nickel sulfate), the inactive analogue of DNFB, 2,4-dichloronitrobenzene, and two irritants (sodium dodecyl sulphate and benzalkonium chloride) on the expression of the i...

  12. Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery

    OpenAIRE

    Zhang, LIJUAN; Zhang, Can Yang; Xiong, Di; Sun, Yao; Zhao, Bin; Lin, Wen Jing

    2014-01-01

    Can Yang Zhang, Di Xiong, Yao Sun, Bin Zhao, Wen Jing Lin, Li Juan Zhang School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong Province, People’s Republic of China Abstract: A novel amphiphilic triblock pH-sensitive poly(ß-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol) was designed and synthesized via the Michael-type step polymerization and esterification condensation method. The synthe...

  13. Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery

    OpenAIRE

    Zhang CY; Xiong D; Sun Y; Zhao B; Lin WJ; Zhang LJ

    2014-01-01

    Can Yang Zhang, Di Xiong, Yao Sun, Bin Zhao, Wen Jing Lin, Li Juan Zhang School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong Province, People’s Republic of China Abstract: A novel amphiphilic triblock pH-sensitive poly(ß-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol) was designed and synthesized via the Michael-type step polymerization and esterification condensation method. The synthesized co...

  14. Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review

    OpenAIRE

    Frye, Cheryl A.; Paris, Jason J.; Osborne, Danielle M.; Campbell, Joannalee C.; Kippin, Tod E.

    2011-01-01

    Maternal–offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well underst...

  15. Prenatal stress alters progestogens to mediate susceptibility to sex-typical, stress-sensitive disorders, such as drug abuse: a review

    OpenAIRE

    Frye, Cheryl A.; Paris, Jason J.; Danielle eOsborne; Joanna eCampbell; Tod eKippin

    2011-01-01

    Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well unders...

  16. Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer.

    Science.gov (United States)

    Li, Wei-Ming; Chiang, Chih-Sheng; Huang, Wei-Chen; Su, Chia-Wei; Chiang, Min-Yu; Chen, Jian-Yi; Chen, San-Yuan

    2015-12-28

    We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers. PMID:26478017

  17. Acupoint-Specific, Frequency-Dependent, and Improved Insulin Sensitivity Hypoglycemic Effect of Electroacupuncture Applied to Drug-Combined Therapy Studied by a Randomized Control Clinical Trial

    Directory of Open Access Journals (Sweden)

    Rong-Tsung Lin

    2014-01-01

    Full Text Available The application of electroacupuncture (EA to specific acupoints can induce a hypoglycemic effect in streptozotocin-induced rats, normal rats, and rats with steroid-induced insulin resistance. EA combined with the oral insulin sensitizer rosiglitazone improved insulin sensitivity in rats and humans with type II diabetes mellitus (DM. There are different hypoglycemic mechanisms between Zhongwan and Zusanli acupoints by EA stimulation. On low-frequency (2 Hz stimulation at bilateral Zusanli acupoints, serotonin was involved in the hypoglycemic effect in normal rats. Moreover, after 15 Hz EA stimulation at the bilateral Zusanli acupoints, although enhanced insulin activity mainly acts on the insulin-sensitive target organs, the muscles must be considered. In addition, 15 Hz EA stimulation at the bilateral Zusanli acupoints has the combined effect of enhancing cholinergic nerve activity and increasing nitric oxide synthase (NOS activity to enhance insulin activity. Despite the well-documented effect of pain control by EA in many systemic diseases, there are few high-quality long-term clinical trials on the hypoglycemic effect of EA in DM. Combination treatment with EA and other medications seems to be an alternative treatment to achieve better therapeutic goals that merit future investigation.

  18. 暹罗斗鱼致病性嗜水气单胞菌的分离·鉴定及药敏试验%Isolation, Identification and Drug Sensitivity Test of Pathogenic Aeromonas hydrophila from Betta splendens Regan

    Institute of Scientific and Technical Information of China (English)

    杨宁; 黄海; 张希; 魏赟; 巫火连

    2012-01-01

    [Objective] The research aimed to discuss the disease cause of Betta splcnders Regan and the prevention and control methods of its diseases and pests. [Method] The pathogenic bacteria of B, splenders were isolated and identified by determining die physiological and biochemical indices and 16 S rDNA sequencing. And the drug sensitivity test was made. [Result] Strain DY001 was the pathogenic bacteria that caused Aeromonas hydrophila disease of B. splenders. Strain DY001 was identified as Aeromonas hydrophila. The median lethal dose (LD50) of this pathogeny to B. splenders was 0. 04 × 106 CFU/g. The results of drug sensitivity test showed that this pathogenic bacteria was sensitive to azithromycin, ofloxacin, norfloxacin, compound sinomin, ceftriaxone, trimethoprim, chloramphenicol and other antibiotics. [Conclusion] Aeromonas hydropkila was the pathogenic bacteria that caused the disease incidence of B. splenders. The results of drug sensitivity test could provide references for the disease prevention and control of B. splenders.%[目的]探讨暹罗斗鱼的发病原因和病害防治方法.[方法]对暹罗斗鱼的病原菌进行分离,并通过生理生化指标测定和16S rDNA测序对其鉴定,同时进行药敏试验.[结果]菌株DY001为暹罗斗鱼嗜水气单胞菌病的病原菌.经鉴定,确定菌株DY001为嗜水气单胞菌(Aeromonas hydrophila).该病原菌对暹罗斗鱼的半致死量(LD50)为0.04×106 CFU/g.药敏试验结果表明,病原菌对阿奇霉素、奥复星、氟哌酸、复方新诺明、菌必治、甲氧苄啶和氯霉素等抗生素敏感.[结论]嗜水气单胞菌是引起此次暹罗斗鱼发病的病原菌,而药敏试验结果将为其防治提供参考.

  19. Guías para el manejo de la tuberculosis resistente: OMS 2011 WHO guidelines for the management of drug-resistant tuberculosis: 2011 update

    Directory of Open Access Journals (Sweden)

    Juan Carlos Rodríguez D

    2012-06-01

    multidrug-resistant tuberculosis (MDR-TB. However, most of them are based on expert opinion, without good evidence. The new guidelines are the following: I. Rapid sensitivity testing of isoniazid and rifampicin or of rifampicin alone is recommended over conventional testing or no testing at the time of diagnosis of tuberculosis, subject to available resources. II. The use of sputum smear microscopy and culture rather than sputum smear microscopy alone is recommended for the monitoring of patients with MDR-TB during treatment. III. In the treatment of patients with MDR-TB the following rules are given: 1 a fluoroquinolone should be used; 2 a later-generation fluoroquinolone rather than an earlier-generation fluoroquinolone should be used; 3 ethionamide (or prothionamide should be used; 4 four second-line anti-TB drugs likely to be effective (including a parenteral agent from among the second-line injectables kanamycin, amika-cin or capreomycin, as well as pyrazinamide, should be included in the intensive phase of treatment; 5 regimens should include at least pyrazinamide, a fluoroquinolone, a parenteral agent (kanamycin, amikacin or capreomycin, ethionamide (or prothionamide, and either cycloserine or p-aminosalicylic acid (PAS if cycloserine cannot be used; 6 an intensive phase of 8 months' duration is recommended. 7 a total treatment duration of 20 months is recommended in patients without any previous MDR-TB treatment. IV.- Anti-retroviral treatment is recommended for all patients with HIV and drug-resistant TB requiring second-line anti-TB drugs, irrespective of CD4 cell count, as early as possible (within the first 8 weeks following initiation of anti-TB treatment. V.-Patients with MDR-TB should be treated using mainly ambulatory care rather than models of care based principally on hospitalization.

  20. CCR5 antibodies HGS004 and HGS101 preferentially inhibit drug-bound CCR5 infection and restore drug sensitivity of Maraviroc-resistant HIV-1 in primary cells

    International Nuclear Information System (INIS)

    R5 HIV-1 strains resistant to the CCR5 antagonist Maraviroc (MVC) can use drug-bound CCR5. We demonstrate that MVC-resistant HIV-1 exhibits delayed kinetics of coreceptor engagement and fusion during drug-bound versus free CCR5 infection of cell lines. Antibodies directed against the second extracellular loop (ECL2) of CCR5 had greater antiviral activity against MVC-bound compared to MVC-free CCR5 infection. However, in PBMCs, only ECL2 CCR5 antibodies HGS004 and HGS101, but not 2D7, inhibited infection by MVC resistant HIV-1 more potently with MVC-bound than with free CCR5. In addition, HGS004 and HGS101, but not 2D7, restored the antiviral activity of MVC against resistant virus in PBMCs. In flow cytometric studies, CCR5 binding by the HGS mAbs, but not by 2D7, was increased when PBMCs were treated with MVC, suggesting MVC increases exposure of the relevant epitope. Thus, HGS004 and HGS101 have antiviral mechanisms distinct from 2D7 and could help overcome MVC resistance.

  1. 比较盐敏感性与非盐敏感性高血压的联合药物治疗%Comparison of Combined Drug Salt Sensitivity and Non Salt Sensitive Hypertension Treatment

    Institute of Scientific and Technical Information of China (English)

    姚萍; 朱江红

    2014-01-01

    Objective To explore the value of transabdominal and transvaginal ultrasonography in diagnosis of pregnancy. Methods 120 cases in hospitalized patients with mild to moderate hypertension, after the salt load test tests to determine the 60 cases of salt-sensitive hypertension group (SS), another 60 patients as a non-salt-sensitive hypertension group (NSS) , and then the two groups were in groups of 30 cases were randomly divided into two groups, each with felodipine tablets combined perindopril and indapamide sustained release tablets tablets combined perindopril tablets for 12 weeks, measuring treatment change after 24 h of each index. Results SS group compared with the NSS group, dif erent levels of FPG and Cr were statistical y significant ( <0.01), the difference FINS, LVMI, MAU, BMI, HOMA-IR are also statistically significant ( <0.05 ); SS group of patients is the use of joint training indapamide perindopril treatment, and the detection of indicators are within the normal range, the difference was statistical y significant ( <0.05); NSS group of patients is the use of felodipine combined perindopril treatment, and its detection indicators are located within the normal range, the dif erence was statistical y significant ( <0.05).Conclusion Salt-sensitive hypertension obvious target organ damage, for indapamide and perindopril combination therapy, rather than salt-sensitive patients for felodipine combination therapy with perindopril.%目的探讨盐敏感性与非盐敏感性高血压对靶器官的损害和联合药物治疗的差异。方法在住院的轻中度高血压患者中选取120例,经过盐负荷试验测试,确定60例为盐敏感性高血压组(SS),另选择60例作为非盐敏感性高血压组(NSS),再将这两组分别以每组30例随机分为两小组,分别用非洛地平片联合培哚普利片和吲达帕胺缓释片联合培哚普利片治疗12w,测量治疗前后24 h各指标的变化。结果 SS组与NSS组相比,FPG和Cr水

  2. Silencing of the transcription factor STAT3 sensitizes lung cancer cells to DNA damaging drugs, but not to TNFα- and NK cytotoxicity

    International Nuclear Information System (INIS)

    Transcription factor STAT3 (Signal Transducers and Activators of Transcription 3) is persistently active in human tumors and may contribute to tumor progression. Inhibition of STAT3 expression/activity could be a good strategy to modulate tumor cell survival and responses to cancer chemotherapeutics or immune cytotoxicity. We silenced STAT3 expression in human A549 lung cancer cells to elucidate its role in cell survival and resistance to chemotherapeutics, TNFα and natural killer (NK)-mediated cytotoxicity. We demonstrate that STAT3 is not essential for basal survival and proliferation of A549 cancer cells. Stable silencing of STAT3 expression sensitized A549 cells to DNA damaging chemotherapeutics doxorubicin and cisplatin in a p53-independent manner. Sensitization to DNA damage-inducing chemotherapeutics could be due to down-regulation of the Bcl-xL expression in STAT3 depleted cells. In contrast, knockdown of STAT3 in cancer cells did not modulate responses to TNFα and NK-mediated cytotoxicity. We found that STAT3 depletion increased the NFκB activity likely providing the compensatory, pro-survival signal. The treatment with TNFα, but not doxorubicin, enhanced this effect. We conclude that STAT3 is not crucial for the control of basal cell proliferation and survival of lung carcinoma cells but modulates susceptibility to DNA damaging chemotherapeutics by regulation of intrinsic pro-survival pathways. - Highlights: ► STAT3 silencing is negligent for basal lung cancer cell viability and proliferation. ► STAT3 depletion sensitizes lung cancer cells to DNA damaging chemotherapeutics. ► STAT3 depletion has no effect on susceptibility to extrinsic apoptosis inducers. ► Increased pro-survival NFκB activity may compensate for STAT3 depletion

  3. Silencing of the transcription factor STAT3 sensitizes lung cancer cells to DNA damaging drugs, but not to TNFα- and NK cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kulesza, Dorota W. [Laboratory of Transcription Regulation, Department of Cell Biology, The Nencki Institute of Experimental Biology, Warsaw (Poland); Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw (Poland); Carré, Thibault; Chouaib, Salem [Unité INSERM U753, Institut de Cancérologie Gustave Roussy, Villejuif Cedex (France); Kaminska, Bozena, E-mail: bozenakk@nencki.gov.pl [Laboratory of Transcription Regulation, Department of Cell Biology, The Nencki Institute of Experimental Biology, Warsaw (Poland)

    2013-02-15

    Transcription factor STAT3 (Signal Transducers and Activators of Transcription 3) is persistently active in human tumors and may contribute to tumor progression. Inhibition of STAT3 expression/activity could be a good strategy to modulate tumor cell survival and responses to cancer chemotherapeutics or immune cytotoxicity. We silenced STAT3 expression in human A549 lung cancer cells to elucidate its role in cell survival and resistance to chemotherapeutics, TNFα and natural killer (NK)-mediated cytotoxicity. We demonstrate that STAT3 is not essential for basal survival and proliferation of A549 cancer cells. Stable silencing of STAT3 expression sensitized A549 cells to DNA damaging chemotherapeutics doxorubicin and cisplatin in a p53-independent manner. Sensitization to DNA damage-inducing chemotherapeutics could be due to down-regulation of the Bcl-xL expression in STAT3 depleted cells. In contrast, knockdown of STAT3 in cancer cells did not modulate responses to TNFα and NK-mediated cytotoxicity. We found that STAT3 depletion increased the NFκB activity likely providing the compensatory, pro-survival signal. The treatment with TNFα, but not doxorubicin, enhanced this effect. We conclude that STAT3 is not crucial for the control of basal cell proliferation and survival of lung carcinoma cells but modulates susceptibility to DNA damaging chemotherapeutics by regulation of intrinsic pro-survival pathways. - Highlights: ► STAT3 silencing is negligent for basal lung cancer cell viability and proliferation. ► STAT3 depletion sensitizes lung cancer cells to DNA damaging chemotherapeutics. ► STAT3 depletion has no effect on susceptibility to extrinsic apoptosis inducers. ► Increased pro-survival NFκB activity may compensate for STAT3 depletion.

  4. A STUDY ON AETIOLOGICAL AGENTS OF LRTI WITH SPECIAL EMPHASIS ON DRUG SENSITIVITY PATTERN OF ISOLATED BACTERIA AND INCIDENCE OF PNEUMOCYSTIS CARINII PNEUMONIA

    Directory of Open Access Journals (Sweden)

    Manab Kumar

    2015-12-01

    Full Text Available Lower Respiratory Tract Infections (LRTIs are important causes of morbidity and mortality for all age groups both in the hospital as well as in the community. Though international guidelines are available for treating bacterial LRTI they have not been validated very much in the Indian scenario. Scarce local information is available regarding aetiological agents of LRTI and their antibiotic sensitivity pattern. Pneumocystis carinii (Jiroveci is a common pathogen in LRTI in immuno-compromised patients. It is rarely documented in our country. MATERIALS AND METHODS Two hundred adults suffering from LRTI of less than 2 weeks duration from both inpatient and outpatient departments in a Tertiary Care Hospital at Kolkata were included in the study after taking valid informed consent. Study period was one year (2014- 15. Sputum samples were collected as per criteria of Murray et al. 1975. After performing routine culture, diagnosis was made based on colony character and biochemical reactions. Antimicrobial sensitivity testing was then done according to CLSI guidelines. RESULTS This study reveals that, LRTI was common in all age groups, in both Human Immunodeficiency Virus Non-Reactive (HIVNR and Human Immunodeficiency Virus Reactive (HIVR groups. In both the groups, 75% showed growth of single organism in sputum. But in the HIVR group, a considerable number showed growth of multiple organisms. Both the groups (HIVNR and HIVR showed predominance of Gram positive bacteria. Antibiotic sensitivity was unremarkable, but one E.coli isolate was an Extended Spectrum Beta-Lactamase producer (ESBL. Pneumocystis Carinii (PC was found in Giemsa stained smear of induced sputum in one HIVR case, who developed Pneumo-mediastinum and surgical emphysema, but recovered due to early initiation of treatment, suggesting that Pneumocystis Carinii (Jiroveci pneumonia was not uncommon in HIVR patients and early diagnosis and treatment can save the life of the patient

  5. Hormone Resistance in Two MCF-7 Breast Cancer Cell Lines is Associated with Reduced mTOR Signaling, Decreased Glycolysis, and Increased Sensitivity to Cytotoxic Drugs

    OpenAIRE

    Leung, Euphemia Yee; Kim, Ji Eun; Askarian-Amiri, Marjan; Joseph, Wayne R.; McKeage, Mark J; Baguley, Bruce C.

    2014-01-01

    The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume, and resistance to mTOR inhibition. Here, we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, d...

  6. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    OpenAIRE

    Euphemia Yee Leung; Ji Eun eKim; Marjan eAskarian-Amiri; Joseph, Wayne R.; McKeage, Mark J; Bruce Charles Baguley

    2014-01-01

    The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, doc...

  7. The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Clausen, Mathias Porsmose; Bennetzen, Martin;

    2009-01-01

    interacts strongly with lipid bilayers of different composition leading to increased permeability. This implies that chlorpromazine can change influx properties of membranes hence suggesting that chlorpromazine may be a promising chemosensitizing compound for enhancing the cytotoxic effect of tamoxifen...... compound is now also recognized as a multitargeting drug with diverse potential applications, for example, it has antiproliferative properties and it can reverse resistance toward antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug resistance caused by overexpression of P......-glycoprotein in cancer cells. In this study, we have investigated the effect of chlorpromazine on tamoxifen response of human breast cancer cells. We found that chlorpromazine worked synergistically together with tamoxifen with respect to reduction of cell growth and metabolic activity, both in the antiestrogen...

  8. Drug Facts

    Medline Plus

    Full Text Available ... Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between Drug ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn ...

  10. Evaluation of zwitterionic polymersomes spontaneously formed by pH-sensitive and biocompatible PEG based random copolymers as drug delivery systems.

    Science.gov (United States)

    Laskar, Partha; Dey, Joykrishna; Ghosh, Sudip kumar

    2016-03-01

    The development of stimuli-responsive biocompatible polymersomes is important for the improvement of drug delivery systems. Herein, we report the spontaneous formation of polymersomes by three random copolymers, l-cys-graft-poly[GMA-co-mPEG300], containing different ratios of l-cysteine (Cys) and methoxy poly(ethylene glycol) (mPEG) covalently linked to the polymer backbone. Cysteine was conjugated to the polymeric backbone through metal free thiol-epoxy 'click' chemistry at final step. The copolymers, without having any typical hydrophobe in the backbone, are sufficiently surface active. The self-assembly formation of the copolymers was studied in aqueous solution by steady-state fluorescence probe technique. Spontaneous polymersomes formation, without any help of stimuli and organic solvent, above a relatively low critical aggregation concentration was confirmed by dynamic light scattering and microscopic techniques. Polymersomes were shown to be able to encapsulate not only hydrophilic dye in their aqueous core but also hydrophobic guest molecules in the bilayer membrane constituted by the mPEG chains. The polymersomes are sufficiently stable under physiological condition. These nano-sized polymersomes exhibit pH-triggered release of encapsulated guest under acidic pH. All three copolymers were found to be completely cell viable and hemocompatible up to very high concentration. Their ability to cross cell membrane was demonstrated by use of a fluorescent dye-tagged polymer. Further, these copolymers did not show any denaturising effect on the secondary structure of the human serum albumin, a transport protein in the blood. Based on the results of this study it is concluded that these spontaneously formed stable and biocompatible polymersomes can have potential use as drug delivery systems. PMID:26704991

  11. The putative ABC transporter encoded by the orf19.4531 plays a role in the sensitivity of Candida albicans cells to azole antifungal drugs.

    Science.gov (United States)

    Jiang, Linghuo; Xu, Dayong; Chen, Zhen; Cao, Yongbing; Gao, Pinghui; Jiang, Yuanying

    2016-05-01

    ATP-binding cassette (ABC) transporters constitute a large superfamily of integral membrane proteins in prokaryotic and eukaryotic cells. In the human fungal pathogenCandida albicans, there are 28 genes encoding ABC transporters and many of them have not been characterized so far. The orf19.4531 (also known as IPF7530) encodes a putative ABC transporter. In this study, we have demonstrated that disruption of orf19.4531 causesC. albicanscells to become tolerant to azoles, but not to polyene antifungals and terbinafine. Therefore, the protein encoded by orf19.4531 is involved in azole sensitivity and we name it asROA1, the regulator of azole sensitivity 1 gene. Consistently, we show that the expression ofROA1is responsive to treatment of either fluconazole or ketoconazole inC. albicans In addition, through a GFP tagging approach, Roa1 is localized in a small punctuate compartment adjacent to the vacuolar membrane. However,ROA1is not essential for thein vitrofilamentation ofC. albicanscells. PMID:26975389

  12. 金鱼嗜水气单胞菌的分离鉴定及药敏试验%Identification and Drug Sensitivity Test of Pathogenic Aeromonas hydrophila from Goldfish Carassius auratus

    Institute of Scientific and Technical Information of China (English)

    周毅; 张培培; 徐晔; 曹洁; 孟学平; 段宏安

    2014-01-01

    自病死金鱼肝脏中分离到一株优势菌,对其进行感染试验、培养特性观察、生化特性鉴定及16S rRNA序列分析。试验结果表明,该分离菌株为嗜水气单胞菌,与已报道的嗜水气单胞菌的16S rRNA序列同源性>99.3%。用纸片扩散法进行药敏试验,试验结果显示,该分离株对四环素类、喹诺酮类、磺胺类、头孢呋新、头孢他啶、头孢吡肟等21种药物敏感,对青霉素G、氨苄西林、阿莫西林、头孢氨苄、林可霉素、麦迪霉素耐药。本次金鱼发病是由嗜水气单胞菌感染引起,可选用强力霉素、麦迪霉素、复方新诺明、磺胺甲基异恶唑、阿奇霉素、恩诺沙星、诺氟沙星等多种药物进行防治。%Aeromonas hydrophila is one of the main pathogen of freshwater fish bacterial septicemia .The bacterium was isolated and identified from dead gold fish and drug sensitive tests were performed in order to provide references for the bacterial disease prevention and control in ornamental fish .A dominant bacteria strain was isolated from hepatopancreas of dead Carassius auratus and identified by artificial infection experiment ,cultural characteristics ,physical and chemical characters ,and 16S rRNA sequence analysis .The results showed that the strain was A .hydrophila .Homology of 16S rRNA of the isolated strain and other several A .hydrophila was more than 99 .3% .Drug sensitive test revealed that the isolated strain was highly sensitive to 21 kinds of drugs , including tetracyclines ,quinolones , sulfonamides , cefuroxime ,ceftazidimeand cefepime ,and resistant to penicillin G ,ampicillin ,amoxicillin ,cefalexin , lincomycin and medemycin . Results in this study showed that many antibiotics (such as doxycycline , midecamycin ,co‐trimoxazole ,sulfamethoxazole ,azithromycin ,enrofloxacin ,and norfloxaci) can be used to control and prevent bacterial disease caused by A .hydrophila in gold fish .

  13. 368例宫颈分泌物支原体检测及药敏研究%368 cases of mycoplasma detection and drug sensitivity of cervical secretion

    Institute of Scientific and Technical Information of China (English)

    蔡晓红

    2015-01-01

    目的:结合临床资料研究女性宫颈分泌物支原体检测及药敏情况。方法:选择某院2013-2014年收治的368例女性患者为研究对象,提取其宫颈分泌物做支原体检测与药敏试验,对比解脲、人型支原体单项阳性率,以及具体的药敏检测结果,总结结论。结果:368例患者中,支原体感染178例,解脲、人型支原体单项阳性率分别为32.22%,11.3%,敏感率最高的是交沙霉素和强力霉素,比例为97.44%,86.19%。结论:女性宫颈分泌物出现支原体感染的几率很高,在做支原体检测和药敏测试时,需选择有效的抗菌药物,方能避免感染。%Objective: Combined with clinical data to investigate cervical secretions mycoplasma detection and drug susceptibility. Methods To choose a hospital treated 368 cases of female patients in 2013-2014 as the research object, and extract its cervical secretions do mycoplasma detection and drug sensitive test, comparison of ureaplasma, one type of single positive rate of mycoplasma, and drug susceptibility test of concrete results, summarizes the conclusion. Results 368 cases of patients, mycoplasma infection of 178 cases of ureaplasma, humanoid mycoplasma single positive rate were 32.22%, 11.3%, and the sensitive rate is the highest josamycin and doxycycline, the proportion is 97.44%, 86.19%. Conclusion Women cervical secretions in the mycoplasma infection is very high, doing mycoplasma detection and drug susceptibility test, need to select effective antimicrobial agents, in order to avoid infection.

  14. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  15. Radiation sensitivity of microorganisms adhering to the crude drug ''Bezoar Bovis'' and stability of its main components for γ-ray irradiation

    International Nuclear Information System (INIS)

    The sterilization dose (SD) of γ rays required for the microbial-contaminated crude drug ''Bezoar Bovis'' and the residual rates of its characteristic and effective components, bilirubin and some kinds of cholic acid, were studied experimentally. Samples of Bezoar Bovis made in America were used. The contamination level of the samples was 2.2 x 108 cells of bacteria and 6.0 x 105 spores of fungi per g specimen. The survival rate of these microorganisms showed nearly an exponential dependence on radiation dose. The decimal reduction doses (D10) for the bacteria and fungi were found to be 1.5 kGy and 1.1 kGy respectively. From these values, the dose required for attaining the contamination level provided by the administrative guidance (Bacteria, 3 cells/g; Fungi, 2 spores/g) were estimated to be 7.5 kGy and 4.3 kGy, respectively. The G-values for bilirubin, cholic acid and deoxycholic acid were calculated to be 13, 6 and 8, respectively. If the sterilization treatment is carried out with a dose less than 10 kGy on the specimen in a dry powder state, the reduction of the main components such as bilirubin and cholic acids by γ-ray irradiation is considered to be negligible. (author)

  16. Condition of mycoplasma infection of genitourinary tract and drug sensitive tests%泌尿生殖道支原体感染情况及药敏分析

    Institute of Scientific and Technical Information of China (English)

    刘宏; 李静; 王艳新; 张欣

    2011-01-01

    目的 了解本地区支原体在人类泌尿生殖系统的感染及药敏情况,指导临床合理用药.方法 采用支原体培养及药敏试剂盒对420例泌尿生殖道感染患者进行支原体培养和鉴定,并进行了12种常用抗生素的药敏试验.结果 420例泌尿生殖道感染患者中,支原体阳性205例,阳性率为48.8%,其中女性感染率(66.5%)高于男性感染率(30.2%)(P<0.05).解脲支原体(Uu)、人型支原体(Mh)、混合(Uu+Mh)感染率分别为29.8%、0.7%、18.3%;药敏结果显示支原体对美满霉素和强力霉素敏感性较高.结论 美满霉素和强力霉素可作为目前本地区治疗泌尿生殖道感染的首选药物.%Objective To understand the conditions of genitourinary system mycoplasma infection and drug sensitivity and provide rational administration for clinical practice. Methods The mycoplasma was cultured and identified by mycoplasma culture and identification kits in 420 cases with urinary genital tract mycoplasma infection and the sensitivity of mycoplasma to 12 antibacterials were tested. Results In 420 suspected cases,positive rate of mycoplasma was 48. 8% (205 cases) ,and the female infection rate(66. 5% ) was significantly higher than that of male(30.2% )(P<0.05). The Ureaplasma urealytic-um( Uu) ,Mycoplasma homins( Mh) and Uu + Mh infection rates were 29. 8% ,0. 7% , 18. 3% respectively. The sensitive tests showed that the mycoplasma had higher sensitivity to minocycline and deoxycycline. Conclusion The minocycline and deoxycycline can be used as the first choice drug for treatment genitourinary tract mycoplasma infection.

  17. Drug Facts

    Medline Plus

    Full Text Available ... Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between Drug Abuse and HIV/AIDS Recovery & Treatment Drug Treatment Facts Does Drug Treatment Work? Types of Drug Treatment What Is a Relapse? ...

  18. Highly sensitive isotope-dilution liquid-chromatography-electrospray ionization-tandem-mass spectrometry approach to study the drug-mediated modulation of dopamine and serotonin levels in Caenorhabditis elegans.

    Science.gov (United States)

    Schumacher, Fabian; Chakraborty, Sudipta; Kleuser, Burkhard; Gulbins, Erich; Schwerdtle, Tanja; Aschner, Michael; Bornhorst, Julia

    2015-11-01

    Dopamine (DA) and serotonin (SRT) are monoamine neurotransmitters that play a key role in regulating the central and peripheral nervous system. Their impaired metabolism has been implicated in several neurological disorders, such as Parkinson's disease and depression. Consequently, it is imperative to monitor changes in levels of these low-abundant neurotransmitters and their role in mediating disease. For the first time, a rapid, specific and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DA and SRT in the nematode Caenorhabditis elegans (C. elegans). This model organism offers a unique approach for studying the effect of various drugs and environmental conditions on neurotransmitter levels, given by the conserved DA and SRT biology, including synaptic release, trafficking and formation. We introduce a novel sample preparation protocol incorporating the usage of sodium thiosulfate in perchloric acid as extraction medium that assures high recovery of the relatively unstable neurotransmitters monitored. Moreover, the use of both deuterated internal standards and the multiple reaction monitoring (MRM) technique allows for unequivocal quantification. Thereby, to the best of our knowledge, we achieve a detection sensitivity that clearly exceeds those of published DA and SRT quantification methods in various matrices. We are the first to show that exposure of C. elegans to the monoamine oxidase B (MAO-B) inhibitor selegiline or the catechol-O-methyltransferase (COMT) inhibitor tolcapone, in order to block DA and SRT degradation, resulted in accumulation of the respective neurotransmitter. Assessment of a behavioral output of the dopaminergic system (basal slowing response) corroborated the analytical LC-MS/MS data. Thus, utilization of the C. elegans model system in conjunction with our analytical method is well-suited to investigate drug-mediated modulation of the DA and

  19. 泌尿生殖道支原体属感染及药敏结果分析%Urogenital tract infection caused by Mycoplasma and analysis of drug sensitivity

    Institute of Scientific and Technical Information of China (English)

    刘家芹; 储新民; 马筱玲; 蒋法兴

    2014-01-01

    OBJECTIVE To analyze the infection status and antimicrobial susceptibility of Ureaplsma urealyticum (Uu) and Mycoplasma hominis (Mh) in urogenital tract ,and provide a basis for clinical rational selection of drugs .METHODS Using culture ,identification ,drug sensitivity integration kit ,Mycoplasma culture and anti‐microbial susceptibility test were performed on the urogenital tract specimens of 5 972 patients with suspected My‐coplasma infection ,statistical analysis was performed with SPSS10 .0 statistical software .RESULTS In the total of 5972 inspected specimens ,1641 cases were positive with a positive rate of 27 .5% .The positive rate of Uu ,and Mh was 78 .3% ,and 1 .7% respectively and the positive rate of Uu and Mh mixed infection was 20 .0% .The results of drug sensitive tests showed the drug resistances of Uu ,Uu+ Mh ,Mh infections were different for 13 kinds of antibacterials .The Uu was most resistant to lincocin (98 .0% ) ,then ciprofloxacin (81 .2% ) and norflox‐acin (70 .6% ) .Drug resistance rates of Uu + Mh to lincomycin ,ciprofloxacin ,norfloxacin ,azithromycin ,rox‐ithromycin ,clarithromycin ,and sparfloxacin were all over 70 .0% .CONCLUSION Mycoplasma infection in uro‐genital tract is mainly caused by Uu with a serious drug resistance ,and rational clinical medication should be used based on antimicrobial susceptibility test results .%目的:分析解脲脲支原体(Uu)和人支原体(Mh)在泌尿生殖道的感染状况及药物敏感性,为临床合理选用抗菌药物提供依据。方法采用支原体属培养、鉴定、药敏一体化试剂盒对5972例临床疑似患者送检的泌尿生殖道标本进行支原体属计数培养、鉴定及药物敏感试验,采用SPSS10.0进行统计分析。结果5972份标本中支原体属培养阳性1641例,阳性率27.5%,Uu、Mh、Uu+Mh的分布分别占78.3%、1.7%、20.0%;Uu、Mh、Uu+M h三类感染对13种抗菌药物的耐药性不同,U u

  20. Low-cost, high-sensitivity SERS nano-bio-chip for kinase profiling, drug monitoring and environmental detection: a translational platform technology

    Science.gov (United States)

    Chen, Yi; Liu, Logan

    2014-03-01

    The interaction of biomolecules and solid-state nanomaterials at the nano-bio interfaces is a long-lasting research topic in nanotechnology. Historically, fundamental problems, such as the electron transfer, energy transfer, and plasmonic interaction at the bio-nano interfaces, have been intensively studied, and revolutionary technologies, such as molecular electronics, peptide chips, nanoplasmonic sensors, have been created. With the combined effort of molecular dynamics simulation and surface-enhanced Raman spectroscopy, we studied the external electric field-induced conformation changes of dodecapeptide probes tethered to a nanostructured metallic surface. Through this study, we demonstrated a reversible manipulation of the biomolecule conformations as well as an in situ eletro-optical detection of the subnanometer conformational changes at the bio-nano interfaces. Based on the proof-of-concept established in this study, we further propose a novel nanophotonic peptide phosphorylation sensor for high-sensitive peptide kinase profiling. We have also demonstrated the same SERS nano-bio-chip can be used for environmental monitoring applications, such as detection of contaminants in drinking water at ultralow concentrates. The fabrication of this nanosensor is based on a single step, lithography-less nanomanufacturing process, which can produce hundreds of these chips in several minutes with nearly 100% yield and uniformity. Therefore, the demonstrated research can be readily translated into industrial mass productions.

  1. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... vomiting to life-threatening anaphylaxis . A true drug allergy is caused by a series of chemical steps ...

  2. NOVEL DELIVERY SYSTEM ENHANCES EFFICACY OF ANTIRETROVIRAL THERAPY IN ANIMAL MODEL FOR HIV-1 ENCEPHALITIS (HIVE)

    OpenAIRE

    Spitzenberger, Timothy J.; Heilman, David; Diekmann, Casey; Batrakova, Elena; Kabanov, Alexander; Gendelman, Howard E.; Elmquist, William F.; Persidsky, Yuri

    2006-01-01

    Most potent anti-retroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier. Brain distribution can be limited by the efflux transporter, P-glycoprotein (P-gp). The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of anti-retroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). SCID mice inoculated with HIV-1 infected human monocyt...

  3. A nucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosylcytosine (TAS106, sensitizes cells to radiation by suppressing BRCA2 expression

    Directory of Open Access Journals (Sweden)

    Fukushima Masakazu

    2011-07-01

    Full Text Available Abstract Background A novel anticancer drug 1-(3-C-ethynyl-β-D-ribo-pentofuranosylcytosine (ECyd, TAS106 has been shown to radiosensitize tumor cells and to improve the therapeutic efficiency of X-irradiation. However, the effect of TAS106 on cellular DNA repair capacity has not been elucidated. Our aim in this study was to examine whether TAS106 modified the repair capacity of DNA double-strand breaks (DSBs in tumor cells. Methods Various cultured cell lines treated with TAS106 were irradiated and then survival fraction was examined by the clonogenic survival assays. Repair of sublethal damage (SLD, which indicates DSBs repair capacity, was measured as an increase of surviving cells after split dose irradiation with an interval of incubation. To assess the effect of TAS106 on the DSBs repair activity, the time courses of γ-H2AX and 53BP1 foci formation were examined by using immunocytochemistry. The expression of DNA-repair-related proteins was also examined by Western blot analysis and semi-quantitative RT-PCR analysis. Results In clonogenic survival assays, pretreatment of TAS106 showed radiosensitizing effects in various cell lines. TAS106 inhibited SLD repair and delayed the disappearance of γ-H2AX and 53BP1 foci, suggesting that DSB repair occurred in A549 cells. Western blot analysis demonstrated that TAS106 down-regulated the expression of BRCA2 and Rad51, which are known as keys among DNA repair proteins in the homologous recombination (HR pathway. Although a significant radiosensitizing effect of TAS106 was observed in the parental V79 cells, pretreatment with TAS106 did not induce any radiosensitizing effects in BRCA2-deficient V-C8 cells. Conclusions Our results indicate that TAS106 induces the down-regulation of BRCA2 and the subsequent abrogation of the HR pathway, leading to a radiosensitizing effect. Therefore, this study suggests that inhibition of the HR pathway may be useful to improve the therapeutic efficiency of

  4. Isolation and Identification of Swine Streptococcus suis Pathogeny and Its Drug Sensitive Test%猪链球菌病病原的分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    范国英; 杨雪峰; 刘俊伟; 陈俊杰

    2012-01-01

    Based on the clinical samples of suspected streptococcic pigs from a pig farm of Xinxiang, the pathogens were I-dentified after isolation and culture, and then were used to do biochemistry identification, animal test and drug sensitive test. The results showed that the isolated pathogens were a -hemolytic Streptococcus suis. And it was hypersensitive to Bawangjinzhen, rifampicin and saratiofur, and high sensitive to tilmicosin, cefazolin sodium, ampicillin sodium, zhu kang-II.%采集疑似猪链球菌病的病猪病料,经病原分离培养、生化鉴定、动物试验和药教试验,结果表明所分离的细菌为α溶血链球菌(α-hemolytic streptococci.),该菌对霸王金针、利福平、沙拉噻呋极敏,对替米考星、头孢唑啉钠、氨苄西林钠、猪康2号为高敏.

  5. Mycoplasma infection among patients with abnormal pregnancy and drug sensitivity analysis%不良妊娠患者支原体感染及药敏的分析

    Institute of Scientific and Technical Information of China (English)

    赵秋彦; 盘宗敏; 梁国泉; 陈笑娟

    2015-01-01

    Objective To analyze the infection of mycoplasma hominis (Mh) and ureaplasma urealytium (Uu) and drug sensitivity of abnormal pregnant patients from Nansha district in Guangzhou city, so as to offer reference for clinical rational drug use. Methods During January 2011 to December 2013, 750 cases, including 245 cases of sterility, 266 cases of habitual abortion and 239 cases of premature, were randomized sampling into case group. Another 750 normal pregnant women were pair matched into control group according to age, occupation, cultural degree and nutrition condition. Mh and Uu culture and drug sensitivity test were done among 526 samples. Results The detection rates of Uu, Mh and Uu+Mh were 58. 40%, 3. 07% and 3. 87% respectively in observation group, which were higher than those of the control group (χ2 value was 358. 66,7. 411 and 7. 247, respectively, all P0. 05), but that of Uu was higher in cases of sterility, habitual abortion and premature than the control group (χ2 value was 231. 856, 224. 418 and 227. 530, respectively, all P0.05),其中观察组中不孕、习惯性流产者、早产Uu的检出率均高于对照组(χ2值分别为231.856、224.418、227.530,均P<0.05);观察组中不孕、习惯性流产者 Mh和 Uu+Mh检出率均高于对照组(χ2值分别为5.642、8.181;2.849、8.841;均P<0.05)。 Uu对甲砜霉素、美满霉素和交沙霉素都具有较高的敏感性(85.71%~77.71%),Mh对强力霉素、交沙霉素和美满霉素高度敏感(90.32%~100.00%);Uu+Mh对交沙霉素、强力霉素、美满霉素均具有较高的敏感性(80.49%~87.80%)。结论生殖道支原体感染能引起不孕症、习惯性流产及早产等;监测其药敏变迁对合理用药非常重要。

  6. Distribution and drug sensitivity results analysis of femal reproductive tract infection my coplasma genus%女性生殖道感染支原体属的分布及药敏结果分析

    Institute of Scientific and Technical Information of China (English)

    唐婷婷

    2014-01-01

    Objective:To explore the region female reproductive tract mycoplasma infection and drug sensitivities. Methods:Use mycoplasma culture and drug susceptibility test kit 1435 cases of female genital tract Ureaplasma urealyticum, and 10 kinds of antibiotics susceptibility test analysis.Results:698 cases detected Mycoplasma positive rate was 48.6%among Ureaplasma urealyticum infection in 578 cases , accounting for 82.8 percent is the highest. Ureaplasma urealyticum on doxycycline, josamycin, clarithromycin sensitive . The Mycoplasma fluoroquinolone antibiotics resistance rate is high, so the region should not be optional. Conclusions:The region in the female genital tract infection mycoplasma infection rate was 48.6%. Doxycycline , josamycin , clarithromycin is the region of the female genital tract mycoplasma infection drug of choice.%目的:探讨本地区女性生殖道支原体感染及对药物的敏感情况。方法:使用支原体培养及药敏试剂盒检测1435例女性生殖道的解脲支原体,并对10种抗生素的药敏试验进行分析。结果:698例检测出支原体属,阳性率为48.6%其中解脲脲支原体感染578例,占82.8%为最高。解脲脲支原体对多西环素、交沙霉素、克拉霉素较为敏感。而支原体属对氟喹诺酮类抗菌药物耐药率均高,因此本地区不宜选用。结论:本地区女性生殖道感染中支原体感染率为48.6%。多西环素、交沙霉素、克拉霉素是本地区女性生殖道支原体感染的首选药物。

  7. Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation.

    Science.gov (United States)

    Zhang, Xiaoyan; Wang, Xiaofei; Zhong, Weitong; Ren, Xiaoqing; Sha, Xianyi; Fang, Xiaoling

    2016-01-01

    Since elevated expression of matrix metalloproteinase (MMP)-2 and MMP-9 is commonly observed in several malignant tumors, MMPs have been widely reported as key factors in the design of drug delivery systems. Several strategies have been proposed to develop MMPs-responsive nanoparticles to deliver chemotherapeutics to malignant solid tumors. A stimuli-responsive drug delivery system, which could be cleaved by MMPs, was proposed in this study. By inserting an MMP-2/9 cleavable oligopeptide GPVGLIGK-NH2 (GK8) as spacer between α-tocopherol succinate (α-TOS) and methoxy-polyethylene glycol molecular weight (MW 2000 Da) activated by N-hydroxysuccinimide (mPEG2K-NHS), mPEG2K-GK8-α-TOS (TGK) was synthesized as the primary ingredient for MMP-2/9-sensitive micelles composed of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and TGK (n:n =40:60, TGK micelles). mPEG2K-α-TOS (T2K) was similarly synthesized as nonsensitive control. The TGK micelles showed better stability than nonsensitive micelles composed of TPGS and T2K (n:n =40:60, T2K micelles) owing to the inserted peptide. Fluorescence resonance energy transfer results indicated that TGK micelles could be successfully cleaved by MMP-2/9. Effective drug release was demonstrated in the presence of collagenase type IV, a mixture of MMP-2 and MMP-9. Compared with nonsensitive micelles, docetaxel (DTX)-loaded TGK micelles showed a fold higher cellular uptake in HT1080 cells. While the half-maximal inhibitory concentration (IC50) of TGK and T2K micelles were similar (P>0.05) in MCF-7 cells (MMP-2/9 underexpression), the IC50 values of the aforementioned micelles were 0.064±0.006 and 0.122±0.009 μg/mL, respectively, in HT1080 cells (MMP-2/9 overexpression). The MMP-2/9-sensitive micelles also demonstrated desired tumor targeting and accumulation ability in vivo. The results of in vivo antitumor effect evaluation indicate that TGK micelles are potent against solid tumors while maintaining minimum systemic

  8. 泵抑制剂提高肺炎克雷伯菌对环丙沙星的敏感性%Efflux pump Inhibitors improve the sensitivity of ciprofloxacin in drug-resistance Klebsiella pneumoniae

    Institute of Scientific and Technical Information of China (English)

    王若伦; 叶晓光

    2007-01-01

    目的 研究泵抑制剂利血平和羰基氰氯苯腙(CCCP)能否提高肺炎克雷伯菌对环丙沙星的敏感性.方法 收集临床分离对环丙沙星敏感的肺炎克雷伯菌20株,随机抽取10株,应用不同浓度梯度环丙沙星逐级诱导为高耐药株.用琼脂稀释法测定应用泵抑制剂前后,分离的临床敏感株和诱导耐药株的最小抑菌浓度(MIC).结果 应用泵抑制剂利血平和CCCP后,分别有6株(60%)和8株(80%)诱导耐药株的MIC值有所下降,泵阳性株分别有4株和7株.结论 起始低浓度后梯度环丙沙星可以人工诱导出肺炎克雷伯菌高度耐药株.泵抑制剂利血平和CCCP能提高耐药肺炎克雷伯菌对环丙沙星的敏感性.%Objective To explore whether efflux pump inhibitors can improve the sensitivity of ciprofloxacin in drug-resislance Klebsilla pneumoniae. Methods Twenty sensitive strains of Klebsiella pneumoniae were isolated from patients. Ten strains were induced by concentration gradient ciprofloxacin and changed into ciprofloxacin-high resistant Klebsiella pneumoniae. The MICs of ciprofloxacin in the absence or presence of reserpine or carbonyl cyanide m-chlorophenyl hydrazone(CCCP) were detected by agar dilution method. Results After treated with efflux pump inhibitor, the MICs of most induced-resistant bacteria to ciprofloxacin were decreased:6 strains (60%) and 8 strains (80%) in the presence of reserpine and CCCP respectively. The positive efflux pump Klebsiella prveumoniae strains in the presence of reserpine and CCCP were 4(40%) and 6(60%) respectively. Conclusions The high drug-resistance Klebsiella pneumoniae can be artificialy induced with concentration gradient of ciprofloxaein. The efflux pump inhibitors can obviously improve the antibacterial activities of ciprofloxacin in drug-resistance Klebsiella pneumoaiae.

  9. Drug Facts

    Science.gov (United States)

    ... text to you. This web site talks about drug abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol ... of the drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different ...

  10. Generic Drugs

    Science.gov (United States)

    ... name drug. A brand- name drug has a patent. When the patent runs out— usually after 10 to 14 years— ... if you do not have drug coverage. Condition Diabetes Heart failure High cholesterol Migraine Brand-name drug ...

  11. Microwave Assisted Drug Delivery

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór; Zhurbenko, Vitaliy; Johansen, Tom Keinicke

    2014-01-01

    In this work, the microwave radiation is adopted for remote activation of pharmaceutical drug capsules inside the human body in order to release drugs at a pre-determined time and location. An array of controllable transmitting sources is used to produce a constructive interference at a certain...... focus point inside the body, where the drugs are then released from the specially designed capsules. An experimental setup for microwave activation has been developed and tested on a body phantom that emulates the human torso. A design of sensitive receiving structures for integration with a drug...

  12. Study of sensitivity test to neisseria gonorrhoeae antibiotic drug in NanTong district%南通地区2006~2008年淋球菌耐药性分析

    Institute of Scientific and Technical Information of China (English)

    孙亚军; 袁建芬; 喻海忠

    2009-01-01

    Objective To explore the sensitivity of Neisseria Gonorrhoea in Nantong to antibiotic remedy.Methods To select and identify 147 cases of Neisseria Gonorrhoeae specimens.Then drug sensitivity test was carried out through making five sorts of antibiotics.Results Of all the 3 antibiotic agents,the higher resistances to Neisseria Gonorrhoeae were penicillin,acheomycin, ciprofloxacin in turn,the percentages of resistance were 72.10%,68.08% and 8.85% respectively.On the other hand,the higher susceptibilities to Neisseria Gonorrhoeae were ceftriaxone and spectinomycin the percentages of susceptibility were 100% and 94.56% respectively.Conclusion Ceftriaxone and spectinomycin can still be used as primary agents to cure the disease like Neisseria Gonorrhoeae specimens in Nantong,but clinical doctors need to pay more attention to the fact that resistant strains to spectinomycin have come into existence.The result suggests that these antibiotics may be used under guidance of drug sensitivity test in clinic .%目的 探讨南通地区淋病奈瑟菌(NG) 对抗菌药物的敏感性.方法 选择147株NG标本进行菌株鉴定和5种抗菌药物的敏感试验.结果 NG对青霉素、四环素及环丙沙星的耐药率分别为72.10%、68.08%和8.85%,NG对菌必治(头孢三嗪)、壮观霉素的敏感率为100.00%、94.56%.结论 菌必治(头孢三嗪)和壮观霉素仍可作为南通地区淋病治疗的首选药物,但淋球菌对壮观霉素已出现耐药株,应引起临床医生的高度警惕;建议临床应在药敏试验的指导下用药.

  13. 677 cases of urogenital-tract mycoplasma infection and drug sensitivity%677例泌尿生殖道支原体感染情况及药物敏感性

    Institute of Scientific and Technical Information of China (English)

    杨泽

    2014-01-01

    目的:了解该地泌尿生殖道解脲支原体(Uu)和人型支原体(Mh)的感染及药敏试验情况,为临床医生治疗泌尿生殖道支原体的感染提供参考依据。方法对677例疑为泌尿生殖道支原体感染患者的标本采用梅里埃支原体试剂盒进行培养、鉴定及药敏试验。结果677例患者以U u单一感染为主,检出率为49.3%(334/677),U u、M h混合感染的检出率为13.9%(94/677),M h单一感染的检出率为1.1%(8/677)。男性和女性患者的总检出率分别为22.2%和65.6%。药敏试验显示支原体对原始霉素、交沙霉素、多西环素、四环素、红霉素的总敏感率分别为97.4%、91.7%、81.9%、73.4%、65.1%。结论泌尿生殖道支原体感染以Uu单一感染为主,女性的检出率高于男性,对该地区Uu感染者进行治疗的一线药物可以是原始霉素、交沙霉素、多西环素、四环素、红霉素。%Objective To investigate the situation of urogenital Ureaplasma urealyticum (Uu) and Mycoplasma hominis(Mh) in-fection and the drug sensitivity of the mycoplasmas ,and provide references for clinic treatment of urogenital-tract mycoplasmas in-fection .Methods Culture ,identification and drug-sensitivity test of mycoplasmas were performed on 677 specimens collected from suspected mycoplasma-infection patients by using Biomerieux mycoplasma kit .Results In the 677 patients ,the detection rates of Uu single infection was 49 .3% (334/677) ,Uu and Mh double infection was 13 .9% (94/677) ,Mh single infection was 1 .1% (8/677) .The detection rate in men and women were 22 .2% and 65 .6% respectively .The sensitivity tests indicated that the total sensi-tive rates of mycoplasmas to pristinamycin ,josamycin ,doxycycline ,tetracycline ,and erythromycin were 97 .4% ,91 .7% ,81 .9% , 73 .4% ,65 .1% ,respectively .Conclusion The incidence of urogenital mycoplasma infection in women is higher than

  14. Drug Facts

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    Full Text Available ... Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children ... a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free ...

  15. Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

    International Nuclear Information System (INIS)

    Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance in vitro occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters. To address these issues, MCF-7 cells were selected for survival in increasing concentrations of doxorubicin (MCF-7DOX-2), epirubicin (MCF-7EPI), paclitaxel (MCF-7TAX-2), or docetaxel (MCF-7TXT). During selection cells were assessed for drug sensitivity, drug uptake, and the expression of various drug transporters. In all cases, resistance was only achieved when selection reached a specific threshold dose, which was well within the clinical range. A reduction in drug uptake was temporally correlated with the acquisition of drug resistance for all cell lines, but further increases in drug resistance at doses above threshold were unrelated to changes in cellular drug uptake. Elevated expression of one or more drug transporters was seen at or above the threshold dose, but the identity, number, and temporal pattern of drug transporter induction varied with the drug used as selection agent. The pan drug transporter inhibitor cyclosporin A was able to partially or completely restore drug accumulation in the drug-resistant cell lines, but had only partial to no effect on drug sensitivity. The inability of cyclosporin A to restore drug sensitivity suggests the presence of additional mechanisms of drug resistance. This study indicates that drug resistance is achieved in breast tumour cells only upon exposure to concentrations of drug at or above a specific selection dose. While changes in drug accumulation and the expression of drug transporters does occur at the threshold dose, the magnitude of resistance

  16. Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

    Directory of Open Access Journals (Sweden)

    Veitch Zachary

    2008-11-01

    Full Text Available Abstract Background Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance in vitro occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters. To address these issues, MCF-7 cells were selected for survival in increasing concentrations of doxorubicin (MCF-7DOX-2, epirubicin (MCF-7EPI, paclitaxel (MCF-7TAX-2, or docetaxel (MCF-7TXT. During selection cells were assessed for drug sensitivity, drug uptake, and the expression of various drug transporters. Results In all cases, resistance was only achieved when selection reached a specific threshold dose, which was well within the clinical range. A reduction in drug uptake was temporally correlated with the acquisition of drug resistance for all cell lines, but further increases in drug resistance at doses above threshold were unrelated to changes in cellular drug uptake. Elevated expression of one or more drug transporters was seen at or above the threshold dose, but the identity, number, and temporal pattern of drug transporter induction varied with the drug used as selection agent. The pan drug transporter inhibitor cyclosporin A was able to partially or completely restore drug accumulation in the drug-resistant cell lines, but had only partial to no effect on drug sensitivity. The inability of cyclosporin A to restore drug sensitivity suggests the presence of additional mechanisms of drug resistance. Conclusion This study indicates that drug resistance is achieved in breast tumour cells only upon exposure to concentrations of drug at or above a specific selection dose. While changes in drug accumulation and the expression of drug transporters does

  17. 医院分离病原菌分布及药物敏感性分析%Distributions of pathogens isolated from hospital and analysis of drug sensitivity

    Institute of Scientific and Technical Information of China (English)

    董春雷; 朱长太

    2011-01-01

    目的 分析临床分离的病原菌分布及不同细菌的药物敏感性,了解细菌耐药的特点,为临床合理使用抗菌药物及有效控制医院感染提供参考.方法 细菌培养鉴定及药敏试验采用AMSVITEK仪器分析并结合手工法.药敏试验结果判定按2008年美国临床实验室标准化协会(CLSI)标准进行.利用WHONET软件对临床分离出的388株病原菌分布及其药敏结果进行回顾性分析.结果 革兰阳性菌占31.2%,革兰阴性菌占68.8%.分离率较高的依次为为:大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、肺炎克雷伯菌、奇异变形杆菌、鲍曼不动杆菌、粪肠球菌、阴沟肠杆菌、表皮葡萄球菌、溶血葡萄球菌等.多重耐药菌菌种分布较为广泛,但主要集中于鲍曼不动杆菌、大肠埃希菌、葡萄球菌属、阴沟肠杆菌、铜绿假单胞菌等.结论 对临床有较大威胁的主要病原菌是多重耐药鲍曼不动杆菌、产超广谱β-内酰胺酶(ESBL)大肠埃希菌、耐甲氧西林金黄色葡萄球菌、多重耐药阴沟肠杆菌.了解临床分离细菌的分布及耐药情况有助于指导临床合理使用抗菌药物及控制医院感染.%Objective To analyze the distribution of pathogens isolated from Changzhou Cancer Hospital and the drug sensitivity of different bacteria, and understand the characteristics of bacterial resistance to antibiotics and provide a reference for clinical rational use of antibiotics and effective control of nosocomial infections. Methods The identification of bacterial culture and the sensitivity test were used AMSVITEK auto micro-biological system analysis combined with manual method. According to 2008 Clinical and Laboratory Standards Institute (CLSI) standards, the results of drug sensitivity test were judged. The distribution and drug sensitivity results of 388 pathogenic bacteria isolated from the clinical samples were analyzed retrospectively by WHONET software. Results

  18. 20例感染性心内膜炎病原菌及耐药性分析%Pathogenic Bacteria Distribution in 20 Cases with Infective Endocarditis and their Drug Sensitivity Test Results

    Institute of Scientific and Technical Information of China (English)

    熊祝嘉; 岳志刚; 李小瑛

    2013-01-01

    目的 通过对20例感染性心内膜炎患者的培养结果进行回顾性研究,为临床合理使用抗生素提供依据.方法 回顾性分析煤炭总医院2010年20例感染性心内膜炎病原菌的分布及其对抗生素的敏感性.结果 革兰阳性球菌19株,占到95%,其中链球菌9株(占45%),主要为化脓性链球菌;葡萄球菌7株(占35%),主要为金黄色葡萄球菌;肠球菌3株(占15%),均为屎肠球菌.此外大肠埃希菌检出1株(占5%).不同的病原菌有其自身的耐药特点,金黄色葡萄球菌的耐药较严重,所有阳性菌对万古霉素敏感.结论 感染性心内膜炎病原菌以链球菌为主.不同的病原菌有其自身的耐药特点,对感染性心内膜炎患者应及早进行细菌培养和耐药检测,以指导临床正确用药,防止耐药株的出现.%Objective To detect the distribution of pathogenic bacteria in 20 cases with infective endocarditis and their resistance to antimicrobial drugs, and to provide the reference for selecting antimicrobial drugs rationally in clinical treatment. Methods To analysis the pathogenic bacteria distribution and their sensitivity to antibiotics from 20 cases with infective endocarditis conformed by bacterial culture. Results The proportion of Gram-positive cocco bacterium was 95% (Streptococcus account for 45% ,the most was Streptococcus pyogenes; Staphylococcus account for 35% ,the most was Staphylococcus aureus; Enterococ-cus account for 15% ,all was Enterococcus faecium) ;the proportion of Gram-necgative bacillus was 5% ( Escherichia coli). Different pathogens had its own characteristics of resistance, and the drug resistance of staphylococcus aureus was serious. The Gram-positive cocco bacterium were found to be all sensitive to vancomycin. Conclusion Streptococcus is still the primary pathogen among patients with Infective Endocarditis. Different pathogens had its own characteristics of resistance, and we should carry out cultivation

  19. Analysis of Mycoplasma Culture and Drug Sensitivity for Huangshi Male Patients with Infertility%黄石地区男性不育症患者支原体培养及药敏分析

    Institute of Scientific and Technical Information of China (English)

    汤瑾; 张晓宏

    2013-01-01

    Objective: to understand the status of male infertility patients with urogenital mycoplasma infection and its drug resistance .Method: separation mycoplasma culture identification and drug susceptibility test kit are adopted for male infertility patients′sperm separation for mycoplasma culture identification and drug sus-ceptibility test .Results:of the 108 cases of male infertility patients ,there are 42 mycoplasma culture positive cases,accounting for 38.9%,32 ureaplasma mycoplasma ( uu) positive cases accounting for 29.6%,and 7 mixed type mycoplasma cases,accounting for 6.5%.The person type mycoplasma ( mh) was found in 3 pa-tients with a positive rate 2.8%.Among the 48 control group cases,there are 3 cases of ureaplasma mycoplas-ma,positive rate 6.2%.After statistics processing x2 =17.25,P<0.01,significant differences are observed. Conclusion:Thedrug sensitivity of mycoplasma are josamycin,doxycycline and minocycline.Meanwhile,it has the highest rate of resistance to ciprofloxacin ,ofloxacin and erythromycin .In conclusion mycoplasma infection is an important factor in male infertility .In the process of diagnosisand treatment ,the epidemiological charac-teristics of the region and drug sensitive test must be taken into account comprehensively ,so as to make a rea-sonable choice of antibiotics .%  为了解黄石地区男性不育症患者泌尿生殖系统支原体感染状况及其耐药性,采用支原体分离培养鉴定与药敏试验试剂盒,对男性不育患者精液进行支原体分离培养鉴定及药敏试验。结果为:108例男性不育患者支原体培养阳性42例,阳性率为38.9%,其中解脲支原体( uu)阳性32例,阳性率为29.6%;混合型支原体7例,阳性率为6.5%;人型支原体(mh)3例,阳性率为2.8%。对照组48例,其中解脲支原体3例,阳性率为6.2%,经统计学处理,x2=17.25,P <0.01,有显著性差异。支原体对药物敏感的为交

  20. Preliminary study of the relationship between drug sensitivity and molecular typing of of acinetobacter baumannii%鲍曼不动杆菌耐药性与分子分型相关性研究

    Institute of Scientific and Technical Information of China (English)

    尤涛; 辛那; 井发红; 康炜

    2012-01-01

    目的 初步研究11株鲍曼不动杆菌临床分离株药敏试验结果与脉冲场电泳分子分型结果之间的相关性.方法 利用常规方法对从临床标本中分离的鲍曼不动杆菌进行培养鉴定后进行药敏实验,利用脉冲场电泳方法进行分子分型,并比较二者结果.结果 4株对所有抗菌药物均敏感的菌株带型数为10~13条,而1株对所有抗菌药物全耐药为19条带型,其余6株带型在二者之间.结论 分子分型结果初步可以显示耐药情况,相同的分子分型菌株药敏试验结果一致性较高.%Objective To study the; correlation between the antimicrobial susceptibility and pulsed-field gel electrophoresis molecular classification of 11 strains of acinetobacter baumannii .Methods 11 strains of acinetobacter baumannii were isolated from clinical samples .Conventional methods were used for culturing and drug sensitivity testing .Pulsed-field gel electrophoresis method was performed for molecular typing .The two results were compared by using statistical methods .Results 4 strains that sensitive to all antibiotics had 10-13 electrophoresis strips,and 1 strain that resistance to all antibiotics had 19 electrophoresis strips .The rest strains were with electrophoresis strip between the two results mentioned above .Conclusion Molecular typing results could pre-liminaryly show drug resistance,and molecular typing of the same results,higher consistency of antibiotic susceptibility .

  1. Isolation, Identification and Drug Sensitive Test of Aeromonas jandaei from Tilapia (Tilapia nilotica)%罗非鱼(Tilapia nilotica)简达气单胞菌病的病原分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    杨宁; 姜芳燕; 黄海; 焦健

    2015-01-01

    Tilapia is a very important freshwater aquacultural species in China; however, bacterial disease caused huge economic losses in recent years with the continous expansion of tilapia aquaculture. The aim of this research was to isolate, identify, and test drug sensitivity of bacteria pathogen found in diseased Tilapia nilotica. Six bacteria were isolated from diseased T. nilotica as suspected pathogenic bacteria. The bacteria (NL05) isolated from intestine of diseased T. nilotica was determined as pathogenic bacteria by infection experiment. The LD50 was 1×103 CFU/g. Bacteria NL05 was identified as Aeromonas jandaei. Morphology observation indicated that NL05 was gram-negative, rod-shaped. Thirteen physiological and biochemical indexes were positive including maltose, mannitol, glucose, salicin, and hydrogen sulfide. Ten indexes were negative including saccharum, arabinose, xylose, inositol, and dulcitol. There was 1442 bp in the sequence of 16S rRNA, which was submitted into GenBank (Accession number: KC916744). The phylogenetic tree based on 16S rRNA showed that NL05 was A. jandaei. Drug sensitivity test indicated that NL05 was sensitive to 13 antibiotics including ofloxacin, ciprofloxacin, amikacin, polymyxin B, norfloxacin, rifampicin, and lincomycin, and intermediate sensitive to 5 antibiotics including azithromycin, ceftriaxone, kanamycin, streptomycin and minocycline, and resistant to 13 antibiotics including ampicillin, amoxicillin, enrofloxacin, sulfamethoxazole, and trimethoprim. The results will provide references for the prevention and treatment of diseases caused by T. nilotica.%从患病罗非鱼(Tilapia nilotica)体内分离得到细菌 NL05,通过回归感染试验确定 NL05为致病菌,并测出 NL05对罗非鱼的半致死量(LD50)为1×103 CFU/g。结合细菌形态学特征、生理生化指标和16S rRNA 基因同源分析,鉴定 NL05为简达气单胞菌(Aeromonas jandaei)。形态学观察发现, NL05为革兰氏阴性、短杆状;

  2. Prescription Drugs

    Science.gov (United States)

    ... Us Search Search close Teens Teachers Parents Drugs & Health Blog NDAFW Enter Search Term(s): Teens / Drug Facts / Prescription Drugs Prescription Drugs Print What Is Prescription Drug Abuse? Also known as: Opioids: Hillbilly heroin, oxy, OC, oxycotton, percs, happy pills, vikes Depressants: ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Work? Types of Drug Treatment What Is a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What To Say if You Were Once Addicted Drug Abuse Prevention Phone ... English ...

  4. Isolation, Identification and Drug Sensitivity Test of Pathogenic E. coil in Meat Pigeon%肉鸽致病性大肠杆菌的分离鉴定及药敏试验

    Institute of Scientific and Technical Information of China (English)

    周佰祥

    2011-01-01

    对吉林省某珍禽养殖场患病肉鸽进行了临诊检查、病理剖检,并结合病原分离、生化培养、动物试验等方法,确诊为大肠杆菌病.最后对分离细菌进行了药敏试验。结果表明,该致病性大肠杆菌对卡那霉素、阿米卡星和氟苯尼考敏感。%The diseased meat pigeons from a rare bird breeding farm in Jilin Province were examined by epidemiological and clinical symptoms, pathological changes. Using the pathogen isolation, biochemical culture, animal test and other methods, it was confirmed as colibacillosis. Finally, the drug sensitivity test was made on the isolated bacteria. The results suggested that the pathogenic E. coli was susceptible to kanamycin, amikacin and florfenicol.

  5. Club Drugs

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    ... Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can cause serious health problems and sometimes death. ...

  6. Drug Facts

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    Full Text Available ... Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  7. Club Drugs

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    ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... Learn more Statistics and Trends Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  8. Drug Facts

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    Full Text Available ... Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What ... About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800- ...

  9. Drug Facts

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    Full Text Available ... Drugs That People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800-662- ...

  10. Drug Reactions

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    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as gingko and blood thinners ...

  11. Drug Resistance

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    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  12. Sensitivity analysis

    Science.gov (United States)

    </