scholarly journals New Ways to Treat Tuberculosis Using Dendrimers as Nanocarriers

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 105 ◽  
Author(s):  
Serge Mignani ◽  
Rama Tripathi ◽  
Liang Chen ◽  
Anne-Marie Caminade ◽  
Xiangyang Shi ◽  
...  
Keyword(s):  
Polymeric Micelles ◽  
Drug Resistant ◽  
Second Line ◽  
First Line ◽  
Unique Structure ◽  
The Future ◽  
Delivery Vehicles ◽  
Mutagenic Effects

Tuberculosis (TB) is a contagious infection that usually attacks not only the lungs, but also brain and spine. More than twenty drugs have been developed for the treatment of TB, but most of them were developed some years ago. They are used in different combinations. Isoniazid and Rifampicin are examples of the five first line TB drugs, whereas, for instance, Levofloxacin, Kanamycin and Linezolid belong to the second line drugs that are used for the treatment of drug resistant TB. Several new bicyclic nitroimidazoles (e.g., Delamanid) without mutagenic effects were developed. New TB drugs need to provide several main issues such as more effective, less toxic, and less expensive for drug resistant TB. Besides polymeric, metal-based nanoparticles, polymeric micelles and polymers, dendrimer nanostructures represent ideal delivery vehicles and offer high hopes for the future of nanomedicine. In this original review, we present and analyze the development of anti-TB drugs in combination with dendrimers. Few articles have highlighted the encapsulation of anti-TB drugs with dendrimers. Due to their unique structure, dendrimers represent attractive candidates for the encapsulation and conjugation of other anti-TB drugs presenting important drawbacks (e.g., solubility, toxicity, low bioavailability) that hinder their development, including clinic trials.

scholarly journals A Multistrain Mathematical Model To Investigate the Role of Pyrazinamide in the Emergence of Extensively Drug-Resistant Tuberculosis

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Mariam O. Fofana ◽  
Sourya Shrestha ◽  
Gwenan M. Knight ◽  
Ted Cohen ◽  
Richard G. White ◽  
...  
Keyword(s):  
Drug Resistance ◽  
De Novo ◽  
Prolonged Treatment ◽  
Model Parameters ◽  
Drug Resistant ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Content Type ◽  
Extensively Drug Resistant

ABSTRACT Several infectious diseases of global importance—e.g., HIV infection and tuberculosis (TB)—require prolonged treatment with combination antimicrobial regimens typically involving high-potency core agents coupled with additional companion drugs that protect against the de novo emergence of mutations conferring resistance to the core agents. Often, the most effective (or least toxic) companion agents are reused in sequential (first-line, second-line, etc.) regimens. We used a multistrain model of Mycobacterium tuberculosis transmission in Southeast Asia to investigate how this practice might facilitate the emergence of extensive drug resistance, i.e., resistance to multiple core agents. We calibrated this model to regional TB and drug resistance data using an approximate Bayesian computational approach. We report the proportion of data-consistent simulations in which the prevalence of pre-extensively drug-resistant (pre-XDR) TB—defined as resistance to both first-line and second-line core agents (rifampin and fluoroquinolones)—exceeds predefined acceptability thresholds (1 to 2 cases per 100,000 population by 2035). The use of pyrazinamide (the most effective companion agent) in both first-line and second-line regimens increased the proportion of simulations in which the prevalence exceeded the pre-XDR acceptability threshold by 7-fold compared to a scenario in which patients with pyrazinamide-resistant TB received an alternative drug. Model parameters related to the emergence and transmission of pyrazinamide-resistant TB and resistance amplification were among those that were the most strongly correlated with the projected pre-XDR prevalence, indicating that pyrazinamide resistance acquired during first-line treatment subsequently promotes amplification to pre-XDR TB under pyrazinamide-containing second-line treatment. These findings suggest that the appropriate use of companion drugs may be critical to preventing the emergence of strains resistant to multiple core agents.

“Good Will Toward Men” (Luke 2 14)

1917 ◽  
Vol 10 (1) ◽  
pp. 52-56 ◽  
Author(s):  
James Hardy Ropes
Keyword(s):  
Human Nature ◽  
Textual Criticism ◽  
Greek Text ◽  
Second Line ◽  
First Line ◽  
Rare Word ◽  
The Past ◽  
Berlin Academy ◽  
The Future ◽  
Good Will

Professor Adolf von Harnack in the Sitzungsberichte of the Berlin Academy for December 9, 1915 (pages 854–875) has discussed afresh in his characteristically interesting and instructive fashion the textual criticism and meaning of the angels' song in Luke 2 14. After a full exposition of the evidence and an investigation of the rare word εὐδοκία, he decides for the following text:Δόξα ἐν ὑΨίστοις ϑεῷ καὶ ἐπὶ γῆςΕἰρήνη ἀνϑρώποις εὐδοκίας,which he translates:“Glory in the highest to God and on earthPeace to men of (His) gracious will.”This form of the Greek text is in the second line substantially that on which the English Revised Version rests (“men in whom he is well pleased”); but Harnack, following Origen, connects εὐδοκίας not with ἀνϑρώποις but, by a somewhat harsh hyperbaton, with εἰρήνη, and interprets: “Peace is now given to men—no ordinary peace but the peace of His gracious will.”Harnack's argument, which contains much valuable discussion on various aspects of the verse, need not be here repeated. But two of the points which he makes, and in regard to which his reasoning is convincing, deserve notice; for although at first sight they might appear to occupy but a modest place among his results, in reality they seem to offer the key to the serious textual problem of the passage, and so lead to a translation and interpretation quite different from Harnack's. They may be stated thus:(1) With the reading εὐδοκίας, the song is a distich, of which the first line must be taken to include the words ἐπὶ γῆς and the second to begin with εἰρήνη.(2) ἀνϑρώποις εὐδοκίας is a phrase wholly unexampled and in itself full of difficulty. For εὐδοκία means “God's gracious will.” It refers to His purpose, His choice, not to His approval or satisfaction with man's performance; and it looks to the future, to grace, to the hope of a needy world, not to the past, to man's merit, or even to the inherent worth of human nature.

scholarly journals Scaling Up Molecular Diagnostic Tests for Drug-Resistant Tuberculosis in Uzbekistan from 2012–2019: Are We on the Right Track?

2021 ◽  
Vol 18 (9) ◽  
pp. 4685
Author(s):  
Sharofiddin Yuldashev ◽  
Nargiza Parpieva ◽  
Salikhdjan Alimov ◽  
Laziz Turaev ◽  
Khasan Safaev ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
Scale Up ◽  
Multidrug Resistant ◽  
Molecular Diagnostic ◽  
Drug Resistant ◽  
Second Line ◽  
First Line ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Uzbekistan has a large burden of drug-resistant tuberculosis (TB). To deal with this public health threat, the National TB Program introduced rapid molecular diagnostic tests such as Xpert MTB/RIF (Xpert) and line probe assays (LPAs) for first-line and second-line drugs. We documented the scale-up of Xpert and LPAs from 2012–2019 and assessed whether this led to an increase in patients with laboratory-confirmed multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) and extensively drug-resistant TB (XDR-TB). This was a descriptive study using secondary program data. The numbers of GeneXpert instruments cumulatively increased from six to sixty-seven, resulting in annual assays increasing from 5574 to 107,330. A broader use of the technology resulted in a lower proportion of tests detecting Mycobacterium tuberculosis with half of the positive results showing rifampicin resistance. LPA instruments cumulatively increased from two to thirteen; the annual first-line assays for MDR-TB increased from 2582 to 6607 while second-line assays increased from 1435 in 2016 to 6815 in 2019 with about one quarter to one third of diagnosed patients showing second-line drug resistance. Patient numbers with laboratory-confirmed MDR-TB remained stable (from 1728 to 2060) but there was a large increase in patients with laboratory-confirmed XDR-TB (from 31 to 696). Programmatic implications and ways forward are discussed.

scholarly journals Is Rapid Molecular Testing Enough In Screening Drug-Resistant Tuberculosis In Community?

2021 ◽  
Author(s):  
Ashok Dhaker ◽  
Ashish Bahal ◽  
Vishal Mangal ◽  
Arun K Yadav ◽  
Anuj Singhal ◽  
...  
Keyword(s):  
Sputum Sample ◽  
Nucleic Acid Amplification ◽  
Smear Microscopy ◽  
Molecular Testing ◽  
Drug Resistant ◽  
Second Line ◽  
First Line ◽  
Sensitivity Testing ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis

Background: The study aimed to compare the sensitivity and specificity of cartridge-based nucleic acid amplification test (CBNAAT) for diagnosis of Drug-Resistant Tuberculosis (DRTB) with culture sensitivity assays. Methods: Patients with cough symptoms for more than two weeks with any one symptom such as night sweats, fever, and unintentional weight loss were enrolled. Cases where Mycobacterium Tuberculosis was detected on sputum CBNAAT, were included in the study. Demographic variables, clinical features, and chest radiographs were collected. Each sputum sample was divided into three aliquots: smear microscopy, culture, and genotypic drug sensitivity testing (DST). Results of all three diagnostic modalities were compared with CBNAAT. Results: Out of 236 patients with sputum positive CBNAAT, 49.4 % (117/236) were rifampicin-resistant while 50. 6 % (119/236) were Rifampicin sensitive. The genotypic DST assays carried out on all enrolled patients showed that 76. 3 % (181/236) patients were resistant to one or more first-line or second-line antitubercular (ATT) drugs, while 23.7 % (55/236) patients were sensitive to all ATT drugs. On concordant analysis of CB NAAT with DST assays, we found that among 119 CB NAAT rifampicin sensitive patients, 66 patients were resistant to first-line or second-line antitubercular drugs. Conclusion: This study found that the screening of DRTB with CBNAAT at the community level is suboptimal compared to the gold standard. Although CBNAAT's sensitivity in detecting DRTB is significantly higher, the specificity is lower in that population who have received ATT earlier.

Social Representations and Commitment

2018 ◽  
Vol 23 (3) ◽  
pp. 233-249 ◽  
Author(s):  
Eric Bonetto ◽  
Fabien Girandola ◽  
Grégory Lo Monaco
Keyword(s):  
Social Representations ◽  
Social Representation ◽  
Second Line ◽  
Review Of The Literature ◽  
First Line ◽  
Research Perspectives ◽  
The Social ◽  
Bibliographic Search ◽  
English Articles

Abstract. This contribution consists of a critical review of the literature about the articulation of two traditionally separated theoretical fields: social representations and commitment. Besides consulting various works and communications, a bibliographic search was carried out (between February and December, 2016) on various databases using the keywords “commitment” and “social representation,” in the singular and in the plural, in French and in English. Articles published in English or in French, that explicitly made reference to both terms, were included. The relations between commitment and social representations are approached according to two approaches or complementary lines. The first line follows the role of commitment in the representational dynamics: how can commitment transform the representations? This articulation gathers most of the work on the topic. The second line envisages the social representations as determinants of commitment procedures: how can these representations influence the effects of commitment procedures? This literature review will identify unexploited tracks, as well as research perspectives for both areas of research.

mCRPC: Cabazitaxel zukünftige Second-line-Option nach Docetaxel?

2010 ◽  
Vol 01 (06) ◽  
pp. 282-282
Author(s):  
Birgit-Kristin Pohlmann
Keyword(s):  
Second Line ◽  
First Line

Bislang steht für Patienten mit metastasiertem kastrationsresistentem Prostatakarzinom (mCRPC), die auf die Standard-First-line-Chemotherapie mit Docetaxel nicht mehr adäquat ansprechen, keine Evidenz-basierte Therapieoption zur Verfügung. Große Hoffnungen verbinden sich daher mit Cabazitaxel, einer neuen Substanz, die diesen Patienten noch einmal die Chance auf eine Überlebenszeitverlängerung bietet. In den USA ist Cabazitaxel bereits für die Second-line-Behandlung beim mCRPC nach Docetaxel-Versagen zugelassen. In Europa ist die Zulassung für diese Indikation bean-tragt.

A Rational Sequencing of Anti-Angiogenic Agents as Second-Line Treatment Choice for mCRC Patients Progressing After a Bevacizumab-Based First Line

2020 ◽  
pp. 14-19
Author(s):  
Sara De Dosso
Keyword(s):  
Acquired Resistance ◽  
Predictive Biomarker ◽  
Cancer Therapies ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Vegf Pathway ◽  
Effective Choice ◽  
Endothelial Growth Factor

A large proportion of patients with metastatic colorectal cancer (mCRC) experience disease progression after first-line treatment with chemotherapy and bevacizumab, an anti-angiogenic agent, as a result of acquired resistance. However, blocking angiogenesis by targeted therapy towards the vascular endothelial growth factor (VEGF) pathway still forms an essential part of the second-line treatment strategy. Although three approved evidence-based choices for angiogenic agents (continuing treatment with bevacizumab, ramucirumab and aflibercept) are currently available in the second line, making the most effective choice is challenging due to the lack of studies directly comparing these agents. Moreover, despite huge investigational efforts, no predictive biomarker for anti-angiogenic cancer therapies could be identified so far.

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