scholarly journals Quantitative Evaluation of Various Preparations and Extracts of the Male Contraceptive Justicia gendarussa and Identification of a New Aminobenzyl Derivative

2018 ◽  
Vol 5 (01) ◽  
pp. e30-e38
Author(s):  
Mariam Mnatsakanyan ◽  
Emerson Queiroz ◽  
Laurence Marcourt ◽  
Bambang Prajogo ◽  
Jean-Luc Wolfender
Keyword(s):  
Clinical Trials ◽  
Ethanolic Extract ◽  
The Novel ◽  
Chemical Profile ◽  
Main Compound ◽  
Male Contraceptive ◽  
Quantitative Studies ◽  
Medium Pressure Liquid Chromatography ◽  
Safety Precaution ◽  
Contraceptive Activity

Abstract Justicia gendarussa is a medicinal plant found in different regions of Indonesia and used in decoctions by Papuan tribes to reduce male fertility. An enriched ethanolic extract of this plant has been used in the frame of clinical trials in Indonesia to evaluate its male contraceptive activity. Previous studies have indicated that the flavonoid gendarusin A may have a role in the male contraception properties of this plant. In addition, the level of aminobenzyl derivatives was lowered as a safety precaution. In order to obtain a comprehensive chemical profile of the methanolic plant extract, it was analysed by HPLC-PDA-ESI-MS and UHPLC-TOF-HRMS. The same method was also applied to profile extracts of the same plant material from different Indonesian regions, a water decoction used traditionally, and the enriched extract used in clinical trials. This allowed for the dereplication of all previously known flavonoids and newly reported amides, and permitted highlighting the presence of the potentially new aminobenzyl derivative. Targeted isolation of this new amide was performed using medium-pressure liquid chromatography. NMR and HRMS allowed for the establishment of the identity of the novel compound. The same procedure was used to obtain pure standards for quantitative studies. Quantitation of the major compounds was performed for different extracts using HPLC-UV. Significant differences were observed between the samples. Although gendarusin A was the main compound in all samples, it occurred in different amounts in the batches of dried material obtained from different Indonesian regions. The enriched extract contained mainly gendarusin A, as did the traditional decoction, but the level of the aminobenzyl derivatives was significantly lower.

scholarly journals Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1103
Author(s):  
Philipp von Hundelshausen ◽  
Wolfgang Siess
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Kinase Inhibitors ◽  
Phase 1 ◽  
The Novel ◽  
B Cell Malignancies ◽  
Bruton Tyrosine Kinase ◽  
Dermatological Disorders ◽  
Reversible Covalent

Bruton tyrosine kinase (Btk) is expressed in B-lymphocytes, myeloid cells and platelets, and Btk-inhibitors (BTKi) are used to treat patients with B-cell malignancies, developed against autoimmune diseases, have been proposed as novel antithrombotic drugs, and been tested in patients with severe COVID-19. However, mild bleeding is frequent in patients with B-cell malignancies treated with the irreversible BTKi ibrutinib and the recently approved 2nd generation BTKi acalabrutinib, zanubrutinib and tirabrutinib, and also in volunteers receiving in a phase-1 study the novel irreversible BTKi BI-705564. In contrast, no bleeding has been reported in clinical trials of other BTKi. These include the brain-penetrant irreversible tolebrutinib and evobrutinib (against multiple sclerosis), the irreversible branebrutinib, the reversible BMS-986142 and fenebrutinib (targeting rheumatoid arthritis and lupus erythematodes), and the reversible covalent rilzabrutinib (against pemphigus and immune thrombocytopenia). Remibrutinib, a novel highly selective covalent BTKi, is currently in clinical studies of autoimmune dermatological disorders. This review describes twelve BTKi approved or in clinical trials. By focusing on their pharmacological properties, targeted disease, bleeding side effects and actions on platelets it attempts to clarify the mechanisms underlying bleeding. Specific platelet function tests in blood might help to estimate the probability of bleeding of newly developed BTKi.

scholarly journals WEE1 Inhibitor: Clinical Development

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Anthony Kong ◽  
Hisham Mehanna
Keyword(s):  
Clinical Trials ◽  
Tp53 Mutation ◽  
Predictive Biomarker ◽  
Concurrent Chemotherapy ◽  
Clinical Development ◽  
Novel Agents ◽  
The Novel ◽  
Grade 3 ◽  
Chemotherapy Agents

Abstract Purpose of Review WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents. Recent Findings Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. Summary There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

Robot-Aided Neuro-Rehabilitation in Stroke: Neuro-Recovery for Thalamic Lesion

1999 ◽  
Author(s):  
Hermano I. Krebs ◽  
Neville Hogan ◽  
Bruce Volpe ◽  
Mindy Aisen ◽  
Lisa Edelstein ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Information Technology ◽  
Clinical Trials ◽  
Video Games ◽  
Thalamic Lesion ◽  
The Novel ◽  
New Class ◽  
Rehabilitation Hospital ◽  
Thalamic Lesions ◽  
Interactive User

Abstract We are applying robotics and information technology to assist, enhance, and quantify neuro-rehabilitation. Our goal is a new class of interactive, user-affectionate clinical devices designed not only for evaluating patients, but also for delivering meaningful therapy via engaging “video games.” Notably, the novel robot MIT-MANUS has been designed and programmed for clinical neurological applications, and has undergone extensive clinical trials for more than four years at Burke Rehabilitation Hospital – White Plains, NY. This paper will review the main result of the pilot clinical trial of the 20 patients focusing on the consequences of thalamic lesions.

scholarly journals Emerging Therapeutic Modalities against COVID-19

2020 ◽  
Vol 13 (8) ◽  
pp. 188 ◽  
Author(s):  
Shipra Malik ◽  
Anisha Gupta ◽  
Xiaobo Zhong ◽  
Theodore P. Rasmussen ◽  
Jose E. Manautou ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Small Molecules ◽  
Therapeutic Interventions ◽  
Pharmaceutical Companies ◽  
The Novel ◽  
Comprehensive Overview ◽  
Therapeutic Modalities ◽  
Academic Researchers ◽  
Approved Drugs ◽  
Fda Approved Drugs

The novel SARS-CoV-2 virus has quickly spread worldwide, bringing the whole world as well as the economy to a standstill. As the world is struggling to minimize the transmission of this devastating disease, several strategies are being actively deployed to develop therapeutic interventions. Pharmaceutical companies and academic researchers are relentlessly working to investigate experimental, repurposed or FDA-approved drugs on a compassionate basis and novel biologics for SARS-CoV-2 prophylaxis and treatment. Presently, a tremendous surge of COVID-19 clinical trials are advancing through different stages. Among currently registered clinical efforts, ~86% are centered on testing small molecules or antibodies either alone or in combination with immunomodulators. The rest ~14% of clinical efforts are aimed at evaluating vaccines and convalescent plasma-based therapies to mitigate the disease's symptoms. This review provides a comprehensive overview of current therapeutic modalities being evaluated against SARS-CoV-2 virus in clinical trials.

scholarly journals Antiproliferative Activity and Antioxidant Potential of Extracts of Garcinia gardneriana

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3201
Author(s):  
Simone da Cunha Demenciano ◽  
Magalli Costa Barbosa Lima e Silva ◽  
Caroline Almeida Farias Alexandrino ◽  
Wilson Hino Kato Junior ◽  
Patrícia de Oliveira Figueiredo ◽  
...  
Keyword(s):  
Vitamin C ◽  
Antiproliferative Activity ◽  
High Performance ◽  
Ethanolic Extract ◽  
Antioxidant Potential ◽  
Array Detector ◽  
Chloroform Fraction ◽  
Chemical Profile ◽  
Polycarboxylic Acids

The aim of this study was to evaluate the antiproliferative activity, the antioxidant potential, and the chemical profile obtained from the whole fruit and from leaves of Garcinia gardneriana, a fruit tree from Brazilian Cerrado. To determine in vitro antiproliferative activity, the following neoplastic cell lines were considered, along with an immortalized nontumor cell line. The antioxidant potential was determined, and the evaluation of antiradical air activity was performed. The levels of vitamin C and carotenoids were determined. The chemical profile was analyzed by high-performance liquid chromatography coupled to a diode array detector and a mass spectrometer using electrospray ionization interface. The chloroform fraction of the leaf showed antioxidant activity. The vitamin C content had lower values in fruits and higher in leaves. The content of carotenoids for fruits and leaves was expressive. The ethanolic extract and the hexane and chloroform fractions of fruits were active in all neoplastic lines tested. The leaves showed cytotoxic activity in the hexane fraction in the breast carcinoma line. The analysis of data obtained verified the presence of dimers, monomers, and tetramers of hexoses, polycarboxylic acids, xanthones, flavonoids, biflavonoids, and benzophenones.

A 96-well Microfiltration Assay for Measurement of Total Clottable Fibrinogen

1999 ◽  
Vol 81 (02) ◽  
pp. 264-267 ◽  
Author(s):  
A. Keller ◽  
S. Argirion ◽  
D. L. Heene ◽  
C. E. Dempfle
Keyword(s):  
Clinical Trials ◽  
Protein Concentration ◽  
The Novel ◽  
Plasma Samples ◽  
Clotting Time ◽  
Buffer Solution ◽  
Clinical Routine ◽  
Vacuum Suction ◽  
Time Determination ◽  
Method R

SummaryIn clinical routine use, fibrinogen is measured by clotting-time methods, or by clot turbidity in photometric prothrombin time determination. For calibration of these assays measurement of total thrombinclottable protein has been recommended. We have now developed a microfiltration assay for total thrombin-clottable protein. Plasma samples were mixed with thrombin in a 96-well microfiltration device. After clot formation, the fluid was extracted by vacuum suction, and fibrin adherent to the filter membranes washed with buffer. Membrane segments with adherent fibrin were recovered from the 96-well manifold with a punch and transferred to tubes containing denaturing buffer solution. After dissolution of fibrin, protein concentration was determined by optical absorption at 280 nm. The microfiltration assay displayed a high correlation with the total clottable protein method (R = 0.95), and fibrinogen antigen (r = 0.96). Correlation with clotting time assays, and PT-derived fibrinogen in 150 clinical plasma samples was in the range of r = 0.84 to r = 0.97. Intraassay and day-to-day variability of the assay was comparable to the conventional total clottable fibrinogen assay. The novel microfiltration assay appears to be well suited for measurement of large series of samples for calibration, screening purposes, and clinical trials.

scholarly journals POTENTIAL THERAPIES FOR TREATMENT OF COVID-19

2020 ◽  
Vol 7 (1) ◽  
pp. 062-071
Author(s):  
Beatriz Gasser ◽  
Ricardo Andres Ramirez Uscategui
Keyword(s):  
Clinical Trials ◽  
Distress Syndrome ◽  
Multiple Organ ◽  
The Novel ◽  
Controlled Clinical Trials ◽  
Interferon Β ◽  
The World ◽  
Novel Coronavirus ◽  
Time Point

Since discovery of the novel coronavirus (SARS-CoV-2) in December of 2019, this viral pneumonia originated in Wuhan, China quickly spread around the world. This new disease, called COVID-19 can cause Acute Respiratory Distress Syndrome (ARDS) due to an uncontrolled inflammatory response like sepsis, that leads to multiple organ failure and even death. Several pharmacotherapeutics alternatives are being tested over the world, looking for most diverse drugs that might be able to fight the infection. The objective of this paper is to review the main pharmacotherapeutics techniques development, as remdesivir, chloroquine/hydroxychloroquine, lopinavir plus ritonavir, interferon-β, ivermectin, anticoagulants, convalescent plasma and vaccine, currently undergoing clinical trials in order to evaluate its effectiveness and safety to combat the COVID-19, presenting their characteristics, possible adverse effects and main scientific findings of its potential action. In conclusion, some therapies presented promising in-vitro results or in the treatment of some patients, nonetheless, multicentric blinded placebo controlled clinical trials are necessary to determine their effectiveness, safety, dosage, and best time point of treatment.

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