scholarly journals Targeting the Serine Pathway: A Promising Approach against Tuberculosis?

2019 ◽  
Vol 12 (2) ◽  
pp. 66 ◽  
Author(s):  
Marie Haufroid ◽  
Johan Wouters
Keyword(s):  
Treatment Options ◽  
Infectious Agent ◽  
Selective Inhibition ◽  
Current Treatment ◽  
New Drugs ◽  
Therapeutic Drug ◽  
Regulatory Domains ◽  
Starting Point ◽  
Drug Discovery Program ◽  
Serine Pathway

Tuberculosis is still the leading cause of death by a single infectious agent. Effective chemotherapy has been used and improved since the 1950s, but strains resistant to this therapy and most antibacterial drugs on the market are emerging. Only 10 new drugs are in clinical trials, and two of them have already demonstrated resistance. This paper gives an overview of current treatment options against tuberculosis and points out a promising approach of discovering new effective drugs. The serine production pathway is composed of three enzymes (SerA1, SerC and SerB2), which are considered essential for bacterial growth, and all of them are considered as a therapeutic drug target. Their crystal structure are described and essential regulatory domains pointed out. Sequence alignment with similar enzymes in other host would help to identify key residues to target in order to achieve selective inhibition. Currently, only inhibitors of SerB2 are described in the literature. However, inhibitors of human enzymes are discussed, and could be used as a good starting point for a drug discovery program. The aim of this paper is to give some guidance for the design of new hits for every enzyme in this pathway.

A Tutorial of the Current Treatment Modalities and Voice Management in Laryngeal Cancer

2019 ◽  
Vol 4 (5) ◽  
pp. 805-813
Author(s):  
Kathryn Regan ◽  
Ashwini Joshi
Keyword(s):  
Risk Factors ◽  
Laryngeal Cancer ◽  
Treatment Options ◽  
Current Treatment ◽  
Voice Therapy ◽  
Treatment Modalities ◽  
Cancer Risk Factors ◽  
Starting Point ◽  
Basic Understanding ◽  
The Voice

Purpose The purpose of this tutorial was to provide speech-language pathologists unfamiliar with the rehabilitation of laryngeal cancer a basic understanding of laryngeal cancer and the factors involved in the treatment of the voice. Conclusion This tutorial provides an overview of the types and subsites of laryngeal cancer, risk factors, stages and prognosis, and treatment options at these stages. The readers will gain the foundational knowledge necessary to work with this population and a starting point for further study. More research is needed regarding voice outcomes and the benefits of voice therapy in combination with the available laryngeal cancer treatment modalities so that we may better serve these patients.

scholarly journals New Treatment Options against Carbapenem-ResistantAcinetobacter baumanniiInfections

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Burcu Isler ◽  
Yohei Doi ◽  
Robert A. Bonomo ◽  
David L. Paterson
Keyword(s):  
Treatment Options ◽  
Current Treatment ◽  
New Drugs ◽  
World Health ◽  
Content Type ◽  
Drug Candidates ◽  
Expected Benefits ◽  
New Treatment ◽  
Health Organization ◽  
Available Information

ABSTRACTCarbapenem-resistantAcinetobacter baumannii(CRAB) is a perilous nosocomial pathogen causing substantial morbidity and mortality. Current treatment options for CRAB are limited and suffer from pharmacokinetic limitations, such as high toxicity and low plasma levels. As a result, CRAB is declared as the top priority pathogen by the World Health Organization for the investment in new drugs. This urgent need for new therapies, in combination with faster FDA approval process, accelerated new drug development and placed several drug candidates in the pipeline. This article reviews available information about the new drugs and other therapeutic options focusing on agents in clinical or late-stage preclinical studies for the treatment of CRAB, and it evaluates their expected benefits and potential shortcomings.

Systemic therapy in recurrent ovarian cancer: current treatment options and new drugs

2010 ◽  
Vol 10 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Philipp Harter ◽  
Felix Hilpert ◽  
Sven Mahner ◽  
Florian Heitz ◽  
Jacobus Pfisterer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Systemic Therapy ◽  
Treatment Options ◽  
Recurrent Ovarian Cancer ◽  
Current Treatment ◽  
New Drugs

scholarly journals Selective Inhibition of Prostaglandin E2 Receptors EP2 and EP4 Induces Apoptosis of Human Endometriotic Cells through Suppression of ERK1/2, AKT, NFκB and β-CATENIN Pathways and Activation of Intrinsic Apoptotic Mechanisms

2009 ◽  
Vol 94 (7) ◽  
pp. 2673-2673
Author(s):  
Sakhila K. Banu ◽  
JeHoon Lee ◽  
V. O. Speights ◽  
Anna Starzinski-Powitz ◽  
Joe A. Arosh
Keyword(s):  
Prostaglandin E2 ◽  
Treatment Options ◽  
Uterine Cavity ◽  
Selective Inhibition ◽  
Current Treatment ◽  
Reproductive Age ◽  
Treatment Modalities ◽  
Migration And Invasion ◽  
Antiapoptotic Proteins ◽  
Apoptotic Pathways

Endometriosis is a benign chronic gynecological disease of reproductive age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, reproductive health of women, and fail to prevent reoccurrence of disease. There is a critical need to identify new specific signaling modules for non-estrogen targeted therapies for endometriosis. In our previous study, we reported that selective inhibition of cyclooxygenase-2 prevented survival, migration and invasion of human endometriotic epithelial and stromal cells which was due to decreased PGE2 production. In this study, we determined mechanisms through which prostaglandin E2 (PGE2) promoted survival of human endometriotic cells. Results of the present study indicate that: (i) PGE2 promotes survival of human endometriotic cells through EP2 and EP4 receptors by activating ERK1/2, AKT, NFκB, and β-catenin signaling pathways; (ii) selective inhibition of EP2 and EP4 suppresses these cell survival pathways and augments interactions between proapoptotic proteins (Bax and Bad) and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome C and thus activates caspase-3/PARP-mediated intrinsic apoptotic pathways; and (iii) these PGE2 signaling components are more abundantly expressed in ectopic endometriosis tissues compared to eutopic endometrial tissues during the menstrual cycle in women. These novel findings may provide an important molecular framework for further evaluation of selective inhibition of EP2 and EP4 as potential therapy, including non-estrogen target, to expand the spectrum of currently available treatment options for endometriosis in women.

From Fidgeters, Footerers and Flibbertigibbets to the Medicalisation of Childhood Behaviour

2015 ◽  
Vol 23 (3) ◽  
pp. 548-568
Author(s):  
Maria K. Sheppard
Keyword(s):  
Drug Treatment ◽  
Treatment Options ◽  
Current Treatment ◽  
Best Interests ◽  
School Age Children ◽  
Therapeutic Drug ◽  
Sufficient Information ◽  
School Age ◽  
Ethical Challenges ◽  
Consent To Treatment

This article considers the best interests of young children diagnosed with attention deficit/hyperactivity disorder (adhd). It discusses the situation in the uk where adhd is diagnosed with increasing frequency in school age and pre-school age children. When children are too young to have decision-making capacity, those with parental responsibility may consent to treatment which is in the child’s best interests. The article highlights that such parental decisions are difficult to make when the causes of adhd are unknown and the criteria for the diagnosis of the condition have been changing over time. The risk is that their child may be treated unnecessarily. When parents are asked to consent to treatment, they must be given sufficient information about the treatment options to decide what is in their child’s best interests. The mainstay of treatment for adhd is drugs such as Ritalin. In order for parents to make a decision, they need to weigh up the apparent efficacy of these drugs in treating the symptoms of adhd with the fact that they are controlled substances with the potential to cause considerable adverse reactions. They also need to be informed that these drugs have largely not been tested in clinical trials in children and thus their use is off-label. Current treatment of adhd in a child’s best interests therefore presents legal and ethical challenges. It raises the question as to whether there is a general duty to protect children from harm, sparing them from non-therapeutic drug treatment and, where drug treatment is necessary, to ensure safe and effective treatment which has been researched and tested for its efficacy and safety in children.

scholarly journals The crystal structure of the drug targetMycobacterium tuberculosismethionyl-tRNA synthetase in complex with a catalytic intermediate

2018 ◽  
Vol 74 (4) ◽  
pp. 245-254 ◽  
Author(s):  
Ximena Barros-Álvarez ◽  
Stewart Turley ◽  
Ranae M. Ranade ◽  
J. Robert Gillespie ◽  
Nicole A. Duster ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Protein Biosynthesis ◽  
Treatment Options ◽  
Infectious Agent ◽  
Current Treatment ◽  
Trna Synthetase ◽  
Mitochondrial Enzyme ◽  
Amino Acid Sequence Level ◽  
Adenine Ring

Mycobacterium tuberculosisis a pathogenic bacterial infectious agent that is responsible for approximately 1.5 million human deaths annually. Current treatment requires the long-term administration of multiple medicines with substantial side effects. Lack of compliance, together with other factors, has resulted in a worrisome increase in resistance. New treatment options are therefore urgently needed. Here, the crystal structure of methionyl-tRNA synthetase (MetRS), an enzyme critical for protein biosynthesis and therefore a drug target, in complex with its catalytic intermediate methionyl adenylate is reported. Phenylalanine 292 of theM. tuberculosisenzyme is in an `out' conformation and barely contacts the adenine ring, in contrast to other MetRS structures where ring stacking occurs between the adenine and a protein side-chain ring in the `in' conformation. A comparison with human cytosolic MetRS reveals substantial differences in the active site as well as regarding the position of the connective peptide subdomain 1 (CP1) near the active site, which bodes well for arriving at selective inhibitors. Comparison with the human mitochondrial enzyme at the amino-acid sequence level suggests that arriving at inhibitors with higher affinity for the mycobacterial enzyme than for the mitochondrial enzyme might be achievable.

scholarly journals The Future Perspectives of Drug Repurposing and Treatment for the Drug Resistant Breast Cancer: A Review

2021 ◽  
Author(s):  
Panneerselvam Theivendren ◽  
Selvaraj Kunjiappan ◽  
Yashoda Mariappa Hegde ◽  
Kaveena Ravi ◽  
Sivakumar Vellaichamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Survival Rates ◽  
Drug Repurposing ◽  
Current Treatment ◽  
New Drugs ◽  
Health Concern ◽  
Drug Resistant ◽  
The Future ◽  
New Treatment

Breast cancer is a major health concern as it is the second leading cause of death from cancer. There are several well-known risk factors that contribute to breast cancer. Despite the various treatment options available, complete cure is still difficult due to heterogenicity of BC subtypes. As a result, identifying BC subtypes is critical for determining the optimal treatment approach. Over the last several years, new drugs targeting particular therapeutic targets have resulted in significant advances in the treatment of breast cancer. Nonetheless, resistance to treatment is the “major” issue, and a significant increase in survival rates has been the main focus for researchers. The purpose of this review article is to provide a broad overview of the molecular basis of drug resistance in breast cancer, as well as a detailed assessment of current treatment options, potential new treatment methods for drug-resistant breast cancer and repurposed drugs used for treatment. The possibility of non-cancer drugs being studied for breast cancer in the future, as well as the obstacles and bottlenecks of drug repurposing, is also highlighted. Finally, we go through present problems and future prospects in drug-resistant breast cancer therapy.

scholarly journals Neuroprotective Strategies Using Vegetal Compounds in the Treatment of Alzheimer’s Disease

2015 ◽  
Vol 45 ◽  
pp. 56-62
Author(s):  
Loredana Sandu ◽  
Alin Ciobica ◽  
Radu Lefter ◽  
Daniel Timofte ◽  
Emil Anton
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Research Effort ◽  
Treatment Options ◽  
Therapeutic Strategies ◽  
New Drugs ◽  
Simultaneous Application ◽  
Starting Point ◽  
Neuroprotective Strategies ◽  
Therapy Strategies

Lately, different therapy strategies for treating or slowing the progression of Alzheimer's disease are being analyzed. Moreover, the last two decades have seen a considerable research effort directed towards discovering the causes of Alzheimer's disease with the ultimate hope of developing safe and effective pharmacological treatments. In addition to the therapeutic strategies based on targeted drugs, the regimens will require the simultaneous application of neuroprotective drugs. Therefore, although there is currently no "cure" for Alzheimer's disease, a large number of potential therapeutic strategies emerged lately. In this small mini-review we will selectively describe some of the compounds derived from plants that could have a great potential in the treatment of various diseases, including Alzheimer's disease. In this way, there are many plant species that have been traditionally used for memory disorders. The differentiated results and powerful activity of these extracts are making these neuroprotective strategies to be somehow plausible for the treatment of Alzheimer's disease. In addition, these plants can be examined in order to isolate and identify their active ingredients and this can serve as a starting point to find safer and more effective agents for therapeutic use. On thing is certain: as the effective treatment options are limited, there is a demand for new drugs. Thus, plant extracts or vegetal compounds could represent an important part in this equation.

Two isoprenylated flavonoids from Dorstenia psilurus activate AMPK, stimulate glucose uptake, inhibit glucose production and lower glycemia

2019 ◽  
Vol 476 (24) ◽  
pp. 3687-3704 ◽  
Author(s):  
Aphrodite T. Choumessi ◽  
Manuel Johanns ◽  
Claire Beaufay ◽  
Marie-France Herent ◽  
Vincent Stroobant ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Human Cancer ◽  
Glucose Production ◽  
Liver Mitochondria ◽  
New Drugs ◽  
Structural Isomer ◽  
Rat Liver Mitochondria ◽  
Ionization Mass ◽  
Ampk Activation ◽  
Starting Point

Root extracts of a Cameroon medicinal plant, Dorstenia psilurus, were purified by screening for AMP-activated protein kinase (AMPK) activation in incubated mouse embryo fibroblasts (MEFs). Two isoprenylated flavones that activated AMPK were isolated. Compound 1 was identified as artelasticin by high-resolution electrospray ionization mass spectrometry and 2D-NMR while its structural isomer, compound 2, was isolated for the first time and differed only by the position of one double bond on one isoprenyl substituent. Treatment of MEFs with purified compound 1 or compound 2 led to rapid and robust AMPK activation at low micromolar concentrations and increased the intracellular AMP:ATP ratio. In oxygen consumption experiments on isolated rat liver mitochondria, compound 1 and compound 2 inhibited complex II of the electron transport chain and in freeze–thawed mitochondria succinate dehydrogenase was inhibited. In incubated rat skeletal muscles, both compounds activated AMPK and stimulated glucose uptake. Moreover, these effects were lost in muscles pre-incubated with AMPK inhibitor SBI-0206965, suggesting AMPK dependency. Incubation of mouse hepatocytes with compound 1 or compound 2 led to AMPK activation, but glucose production was decreased in hepatocytes from both wild-type and AMPKβ1−/− mice, suggesting that this effect was not AMPK-dependent. However, when administered intraperitoneally to high-fat diet-induced insulin-resistant mice, compound 1 and compound 2 had blood glucose-lowering effects. In addition, compound 1 and compound 2 reduced the viability of several human cancer cells in culture. The flavonoids we have identified could be a starting point for the development of new drugs to treat type 2 diabetes.

An Overview of Dementias

2012 ◽  
Vol 21 (3) ◽  
pp. 75-84
Author(s):  
Venkata Vijaya K. Dalai ◽  
Jason E. Childress ◽  
Paul E Schulz
Keyword(s):  
Clinical Presentation ◽  
Treatment Options ◽  
Current Treatment ◽  
Great Variability ◽  
Health Concern ◽  
Public Health Concern ◽  
Life Threatening ◽  
The Common ◽  
Neurodegenerative Dementias ◽  
Made In

Dementia is a major public health concern that afflicts an estimated 24.3 million people worldwide. Great strides are being made in order to better diagnose, prevent, and treat these disorders. Dementia is associated with multiple complications, some of which can be life-threatening, such as dysphagia. There is great variability between dementias in terms of when dysphagia and other swallowing disorders occur. In order to prepare the reader for the other articles in this publication discussing swallowing issues in depth, the authors of this article will provide a brief overview of the prevalence, risk factors, pathogenesis, clinical presentation, diagnosis, current treatment options, and implications for eating for the common forms of neurodegenerative dementias.

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