scholarly journals Intracellular Localization of the ABCC Proteins of Leishmania and Their Role in Resistance to Antimonials

2009 ◽  
Vol 53 (6) ◽  
pp. 2646-2649 ◽  
Author(s):  
Philippe Leprohon ◽  
Danielle Légaré ◽  
Marc Ouellette
Keyword(s):  
Intracellular Localization ◽  
First Line ◽  
Line Drug

ABSTRACT The ABCC subfamily of proteins is composed of nine members in Leishmania. We report that all of these proteins have an intracellular localization and that the overexpression of at least four members, ABCC3, ABCC4, ABCC5, and ABCC7, can confer resistance to antimonials, the first-line drug against Leishmania.

scholarly journals New InhA Inhibitors Based on Expanded Triclosan and Di-Triclosan Analogues to Develop a New Treatment for Tuberculosis

2021 ◽  
Vol 14 (4) ◽  
pp. 361
Author(s):  
Sarentha Chetty ◽  
Tom Armstrong ◽  
Shalu Sharma Kharkwal ◽  
William C. Drewe ◽  
Cristina I. De Matteis ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Protein Crystal ◽  
First Line ◽  
Isoniazid Resistance ◽  
Structure Based Drug Design ◽  
Extensively Drug Resistant ◽  
New Treatment ◽  
Flexible Ligands ◽  
Line Drug

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has reinforced the need for the development of new anti-TB drugs. The first line drug isoniazid inhibits InhA. This is a prodrug requiring activation by the enzyme KatG. Mutations in KatG have largely contributed to clinical isoniazid resistance. We aimed to design new ‘direct’ InhA inhibitors that obviate the need for activation by KatG, circumventing pre-existing resistance. In silico molecular modelling was used as part of a rational structure-based drug-design approach involving inspection of protein crystal structures of InhA:inhibitor complexes, including the broad spectrum antibiotic triclosan (TCS). One crystal structure exhibited the unusual presence of two triclosan molecules within the Mycobacterium tuberculosis InhA binding site. This became the basis of a strategy for the synthesis of novel inhibitors. A series of new, flexible ligands were designed and synthesised, expanding on the triclosan structure. Low Minimum Inhibitory Concentrations (MICs) were obtained for benzylphenyl compounds (12, 43 and 44) and di-triclosan derivative (39), against Mycobacterium bovis BCG although these may also be inhibiting other enzymes. The ether linked di-triclosan derivative (38) displayed excellent in vitro isolated enzyme inhibition results comparable with triclosan, but at a higher MIC (125 µg mL−1). These compounds offer good opportunities as leads for further optimisation.

Sedação Paliativa, Perspetiva de Um Clínico

2018 ◽  
Vol 26 (52) ◽  
pp. 127-138
Author(s):  
Madalena Feio ◽  
Keyword(s):  
Double Effect ◽  
Palliative Sedation ◽  
Ethical Principles ◽  
First Line ◽  
Scientific Societies ◽  
Refractory Symptoms ◽  
Medical Associations ◽  
Line Drug

Palliative sedation does not have a universally accepted definition. It is used as a measure of last resort for the control of refractory symptoms in the last days of life. The ethical principles invoked in its use are those of double effect and proportionality. Its prevalence varies according to the place of care, type of study and country. The most frequent indications for its use are the control of dyspnea, delirium and pain. The recommended first line drug is midazolam. The studies performed do not diminish the survival of the patient. It is important that fami­ly support is maintained throughout the process. Several scientific societies and medical associations have defined guidelines that regulate their implementation.

scholarly journals Methotrexate Toxicity: Molecular Mechanisms and Management

2021 ◽  
pp. 204-217
Author(s):  
Riyadh S. Almalki ◽  
Hala Eweis ◽  
Fatemah Kamal ◽  
Dina Kutbi
Keyword(s):  
Side Effects ◽  
Cancer Chemotherapy ◽  
Pulmonary Toxicity ◽  
Molecular Mechanisms ◽  
Hematological Toxicity ◽  
Comprehensive Understanding ◽  
First Line ◽  
Cutaneous Toxicity ◽  
Gi Toxicity ◽  
Line Drug

Methotrexate (MTX) is the most widely used drug in cancer chemotherapy and is considered to be the first-line drug for the treatment of a number of rheumatic and non-rheumatic disorders. The pulmonary toxicity, hepatotoxicity of MTX are two of its major side effects. Other toxicities such as endocrinological toxicity, GI toxicity, cutaneous toxicity, hematological toxicity, fatal malfunction or loss, and malignancy can also occur, but at a significantly lower rate of prevalence. This review aims to provide a comprehensive understanding of the molecular mechanisms of methotrexate toxic effects and Lastly, we discussed the management of this toxicity.

scholarly journals SUBFERTILE PATIENTS; EFFICACY OF LETROZOLE AS A FIRST LINE DRUG IN IN TERM OF PREGNANCY RATE

2016 ◽  
Vol 23 (02) ◽  
pp. 152-155
Author(s):  
Dr. Shazia Abbass ◽  
Dr. Ejaz Ahmed ◽  
Dr. Iram Shabbir
Keyword(s):  
Pregnancy Rate ◽  
First Line ◽  
Line Drug

Gabapentin Is a First Line Drug for the Treatment of Neuropathic Pain in Spinal Cord Injury

Spine ◽  
2004 ◽  
Vol 29 (7) ◽  
pp. 743-751 ◽  
Author(s):  
Funda Levendoğlu ◽  
Cemile Ö. Öğün ◽  
Önder Özerbil ◽  
Tunç C. Öğün ◽  
Hatice Uğurlu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
First Line ◽  
Cord Injury ◽  
Line Drug

Letters to the Editor

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 615-616
Author(s):  
David D. Berry ◽  
Ben H. Brouhard ◽  
Quellin T. Box
Keyword(s):  
Patient Population ◽  
Pseudomembranous Colitis ◽  
First Line ◽  
Letters To The Editor ◽  
True Incidence ◽  
Line Drug

We appreciate Dr Liner's interest in our paper. We agree, as we stated in the paper, that lincomycin is not a first line drug and should be reserved for the patient population described in his letter.1 Furthermore, we certainly concur that the incidence of pseudomembranous colitis (PMC) following parenteral lincomycin is lese than 2%, in fact much less. If indeed the true incidence is 2%, then the probability of observing one or more cases of PMC in our series of 265 is 0.995, and thus the probability of observing no cases is 0.005.

Brain metastasis from gallbladder neuroendocrine carcinoma

2020 ◽  
Vol 13 (11) ◽  
pp. e238114
Author(s):  
Hanako Sasaki ◽  
Takayoshi Goto ◽  
Motohiro Hirao ◽  
Yasunori Fujimoto
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Peritoneal Metastases ◽  
Pathological Examination ◽  
Tubular Adenocarcinoma ◽  
First Line ◽  
Pathological Analysis ◽  
Metastatic Lesions ◽  
Significant Regression ◽  
Line Drug ◽  
Line Chemotherapy

A 52-year-old woman was diagnosed with unresectable gallbladder neuroendocrine carcinoma (GB-NEC) exhibiting lymph node and peritoneal metastases, and received eight courses of chemotherapy with irinotecan plus cisplatin. Radiological examinations revealed significant regression of the GB tumour and disappearance of metastatic lesions, so the patient underwent laparoscopic cholecystectomy. However, the patient presented with multiple haemorrhagic brain metastases (BMs) and died 13 months after the initial diagnosis despite neurosurgical interventions. Pathological examination of the resected gallbladder demonstrated an extensive fibrous scar along with tubular adenocarcinoma components, which may indicate that the chemotherapy eliminated a pre-existing neuroendocrine carcinoma (NEC) component. Furthermore, pathological analysis confirmed that the BMs comprised NEC. In patients with advanced GB-NEC, conversion surgery may be a reasonable option if a first-line chemotherapy leads to downstaging of the tumour. Second-line drug therapy and systemic screening might also be considered in cases with BMs.

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