Current Alzheimer Research

Editor-in-Chief:

Debomoy K. Lahiri  
Department of Psychiatry
Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202
USA

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Current Organic Chemistry

Editor-in-Chief:

György Keglevich
Budapest University of Technology and Economics
Budapest
Hungary

 

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‘New/Designer Benzodiazepines’: an analysis of the literature and psychonauts’ trip reports

(E-pub Abstract Ahead of Print)

Author(s): Laura Orsolini*, John M. Corkery, Stefania Chiappini, Amira Guirguis, Alessandro Vento, Domenico De Berardis, Duccio Papanti, Fabrizio Schifano.

Journal Name: Current Neuropharmacology

Abstract:

Background: NPS belonging to the benzodiazepine (BZD) class, e.g., ‘legal/designer BZDs’/‘research chemicals’, have recently emerged on the drug (mainly online/virtual) market.

Objective: Whilst certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians’/public health knowledge/awareness, to incentive harm reduction strategies.

Method: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the ‘new BZDs’ so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/toxicological data, including psychonauts’ online trip reports.

Results: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds.

Conclusions: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.

Keywords: New benzodiazepines, NPS, Novel psychoactive substances, Benzodiazepines, Designer benzodiazepines, Synthetic benzodiazepines

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(E-pub Abstract Ahead of Print)
DOI: 10.2174/1570159X18666200110121333
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Focusing on DNA Repair and Damage Tolerance mechanisms in Mycobacterium tuberculosis: an Emerging Therapeutic Theme

(E-pub Abstract Ahead of Print)

Author(s): Pooja Mittal, Rajesh Sinha, Amit Kumar, Pooja Singh, Archana Singh, Moses Rinchui Ngasainao, Indrakant K. Singh*.

Journal Name: Current Topics in Medicinal Chemistry

Abstract:

Tuberculosis (TB) is one such disease that has become a nuisance in world scenario and one of the most deadly diseases of current times. The etiological agent of tuberculosis, Mycobacterium tuberculosis (Mtb) kills millions of people each year. Not only 1.7 million people worldwide are estimated to harbor Mtb in latent form but 5 to 15 percent of which are expected to acquire an infection during lifetime. Though curable, long duration of drug regimen and expense leads to low patient adherence. Emergence of multi-, extensive- and total- drug resistant strains of Mtb further complicates the situation. Owing to high TB burden, scientists worldwide are trying to design novel therapeutics to combat this disease. Therefore, to identify new drug targets, there is a growing interest in targeting DNA repair pathways to fight this infection. Thus, this review aims to explore DNA repair and damage tolerance as an efficient target for drug development by understanding Mtb DNA repair and tolerance machinery and its regulation, its role in pathogenesis and survival, mutagenesis, and consequently in development of drug resistance.

Keywords: DNA repair, tuberculosis, drug resistance, damage tolerance, drug targets, pathogenesis, mutation rate

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(E-pub Abstract Ahead of Print)
DOI: 10.2174/1568026620666200110114322
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Oxidative Medicine in Brain Injury

Author(s): Matilde Otero-Losada, Francisco ` Capani.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 45 , 2019

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VOLUME: 25
ISSUE: 45
Year: 2019
Page: [4735 - 4736]
Pages: 2
DOI: 10.2174/138161282545200110113639

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Current Pharmaceutical Design

Editor-in-Chief:

William A. Banks  
Seattle VA Puget Sound Health Care System
Room 810C, Building 1
1660 S. Columbian Way
Seattle, WA 98108
USA

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Clinical relevance of Alternative lengthening of telomeres in cancer

(E-pub Abstract Ahead of Print)

Author(s): Guilherme G da Silva, Karollyne S Morais, Daniel S Arcanjo, Diêgo M de Oliveira*.

Journal Name: Current Topics in Medicinal Chemistry

Abstract:

The alternative lengthening of telomere (ALT) is a pathway responsible for cell immortalization in some kinds of tumors. Since the first description of ALT is relatively recent in the oncology field, its mechanism remains elusive, but recent works address ALT-related proteins or cellular structures as potential druggable targets for more specific and efficient antitumor therapies. Also, some new generation compounds for antitelomerase therapy in cancer were able to provoke acquisition of ALT phenotype in treated tumors, enhancing the importance of studies on this alternative lengthening of telomere. However, ALT has been implicated in different – sometimes opposite – outcomes, according to tumor type studied. Then, in order to design and to develop new drugs for ALT+ cancer in an effective way, it is crucial to understand its clinical implications. In this review, we gathered works published in the last two decades to highlight the clinical relevance of ALT on oncology.

Keywords: ALT, cancer, telomeres, telomerase, cell immortalization, oncology

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DOI: 10.2174/1568026620666200110112854
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A Single Medical Marker for Diagnosis of Methamphetamine Addiction - DNA Methylation of SHATI/NAT8L Promoter Sites from Patient Blood

(E-pub Ahead of Print)

Author(s): Yuka Kusui, Daisuke Nishizawa, Junko Hasegawa, Kyosuke Uno, Hajime Miyanishi, Hiroshi Ujike, Norio Ozaki, Toshiya Inada, Nakao Iwata, Ichiro Sora, Masaomi Iyo, Mitsuhiko Yamada, Naoki Kondo, Moo-Jun Won, Nobuya Naruse, Kumi Uehara-Aoyama, Kazutaka Ikeda, Atsumi Nitta*.

Journal Name: Current Pharmaceutical Design

Abstract:

Background: Methamphetamine (METH) is one of the most widely distributed psychostimulants in worldwide. Despite active Countermeasures taken by different countries, neither the overall usage of METH nor the frequency of repeat users has reduced over the past decade. METH induces abuse and dependence as it acts on the central nervous system and temporarily stimulates the brain. The recidivism rate for abuse of stimulants in Japan is very high and therefore prevention of repeated usage is paramount. However, we lack information about the relationship between METH-users and genomic changes in humans in Japan, which would provide important information to aid such efforts.

Objective: Shati/Nat8l is a METH-inducible molecule and its overexpression has protective effects on the brain upon METH usage. Here we investigated the effect of METH usage on DNA methylation rates at the promoter site of SHATI/NAT8L. We used DNA samples from human METH users, who are usually difficult to recruit in Japan.

Methods: We measured DNA methylation at SHATI/NAT8L promoter sites by pyrosequencing method using 193 samples of METH users and 60 samples of healthy subjects. In this method, DNA methylation is measured by utilizing the property that only non-methylated cytosine changes to urasil after bisulfite conversion.

Results: We found that the rate of DNA methylation at six CpG islands of SHATI/NAT8L promoter sites is significantly higher in METH users when compared to healthy subjects.

Conclusion: These results suggest that the DNA methylation rate of SHATI/NAT8L promotor regions offers a new diagnostic method for METH usage.

Keywords: Words, methamphetamine (METH), addiction, epigenetics, DNA methylation, SHATI/NAT8L, diagnosis

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DOI: 10.2174/1381612826666200110111703
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Acknowledgements to Reviewers

Author(s): .

Journal Name: Adolescent Psychiatry

Volume 9 , Issue 3 , 2019

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VOLUME: 9
ISSUE: 3
Year: 2019
Page: [244 - 244]
Pages: 1
DOI: 10.2174/221067660903200110104159

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Adolescent Psychiatry

Editor-in-Chief:

Lois T. Flaherty
Harvard University Medical School
Cambridge, MA
USA

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