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Results 921 through 940 out of 1136

in category pharmacology and toxicology

 

921: Modulation of Human T-type Calcium Channels by Synthetic Cannabinoid Receptor Agonists in vitro

Chris Bladen, Somayeh Mirlohi et al.

135 downloads (posted 23 Jul 2020)

BACKGROUND AND PURPOSE: Consumption of Synthetic Cannabinoid Receptor agonists (SCRAs) is associated with severe adverse reactions including seizures, arrhythmias and death, but the molecular mechanisms surrounding SCRA toxicity are not yet established. These disease-like symptoms are also synonymous with altered T-type calcium channel activity which controls rhythmicity in the heart and brain. This study examined whether SCRAs alter T-type activity and whether this represents a possible mechanism of toxicity. EXPERIMENTAL APPROACH: Fluorescence-based and electrophysiology assays were used to screen 16 structurally related synthetic cannabinoids for their ability to inhibit human T-type calcium channels expressed in HEK293 cells. The most potent compounds were then further examined using patch clamp electrophysiology. KEY RESULTS: MDMB-CHMICA and AMB-CHMINACA potently blocked CaV3.2 with IC50 values of 1.5 and 0.74 μM respectively. Current inhibition increased from 47 to 80% and 45 to 87% respectively when the channel was in slow-inactivated state. Both SCRAs had little effect on steady state inactivation, however MDMB-CHMICA significantly shifted the half activation potential by -7mV. Neither drug produced frequency dependent block, in contrast to the phytocannabinoid Δ9-THC. CONCLUSIONS and IMPLICATIONS: SCRAs are potent agonists of CB1 receptors and can be extremely toxic, but observed toxicity also resembles symptoms associated with altered CaV3.2 activity. Many SCRAs tested were potent modulators of CaV3.2, raising the possibility that SC toxicity may be due in part to CaV3.2 modulation. This potent T-type channel modulation suggests the possibility of SCRAs as a new drug class with potential to treat diseases associated with altered T-type channel activity. ### Competing Interest Statement The authors have declared no competing interest.

https://rxivist.org/papers/92044
https://doi.org/10.1101/2020.07.22.215434

922: Newly isolated sporopollenin microcages from Cedrus libani and Pinus nigra for controlled delivery of Oxaliplatin

Muhammad Mujtaba, Bahar Akyuz Yılmaz et al.

133 downloads (posted 19 Oct 2020)

Sporopollenin-mediated controlled drug delivery has been studied extensively owing to its physicochemical and biological charachteristics. In the present study, sporopollenin was successfully extracted from pollen grains of C. libani and P. nigra followed by the loading of a commonly known anticancer drug Oxaliplatin. Both the drug loading and physicochemical features were confirmed by using light microscopy, FT-IR, SEM and TGA. For the first time, real-time cell analyzer system, xCELLigence, was employed to record the ...

https://rxivist.org/papers/101380
https://doi.org/10.1101/2020.10.19.345157

923: Evaluating the Immunological cross-reactivity of Indian polyvalent antivenoms towards the venom of Hypnale hypnale (hump-nosed pit viper) from the Western Ghats

Muralidharan Vanuopadath, Dileepkumar Raveendran et al.

133 downloads (posted 03 Aug 2020)

Hypnale hypnale (hump-nosed pit viper) is a venomous pit viper species found in the Western Ghats of India and Sri Lanka. Due to the severe life-threatening envenomation effects induced by its venom components, Hypnale hypnale has been classified under ″category 1″ of medically important snake species by the World Health Organization. Since there are no specific antivenoms available to combat its envenomation in India, the only option available is to administer Indian polyvalent antivenoms. However, the cross-neutraliza...

https://rxivist.org/papers/93340
https://doi.org/10.1101/2020.08.01.232579

924: Glutamic acid promotes hair growth in mice

Carlos P Jara, Beatriz de Andrade Berti et al.

133 downloads (posted 28 Sep 2020)

Glutamic Acid is the main excitatory neurotransmitter in neurons. Abnormal distributions of the glutamic acid receptors have been shown in hyper proliferative models such as psoriasis and skin regeneration. However, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed for the first time that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased expression of genes related to a...

https://rxivist.org/papers/97947
https://doi.org/10.1101/2020.09.27.315523

925: Computationally Guided Design of Novel Selective Serotonin Reuptake Inhibitors

Kavya G Achyutuni, Sambid Adhikari et al.

132 downloads (posted 23 Aug 2020)

Current selective serotonin reuptake inhibitor (SSRI) drugs such as paroxetine, fluoxetine and escitalopram are prescribed for mental health conditions such as anxiety and depression. However, there are still several unpleasant side effects which fuels the need for new designs. In this work, computational studies were conducted to design two novel drug candidates with improved docking scores than paroxetine, an existing SSRI drug. Homology analysis was carried out to determine the suitability of an organism for preclini...

https://rxivist.org/papers/95376
https://doi.org/10.1101/2020.08.21.262006

926: Tocotrienol decreases β-amyloid mediated toxicity in Caenorhabditis elegans model of Alzheimer's disease

Chee Wah Yuen, Mardani Abdul Halim et al.

132 downloads (posted 14 Apr 2020)

Alzheimers disease (AD) is a neurological disease caused by the accumulation of extracellular senile plaques consisting of beta-amyloid peptide (AB) in the brain. A transgenic Caenorhabditis elegans which demonstrated paralysis due to the expression of human beta amyloid AB42 gene was used to study the anti-paralysis effect of mixed tocotrienols. The content of the mixed tocotrienols were 12.1% alpha-, 2.7% beta-, 18.6% gamma-, and 8.1% delta-tocotrienols. Mixed tocotrienols significantly delayed the AB-induced paralysi...

https://rxivist.org/papers/79861
https://doi.org/10.1101/2020.04.13.040105

927: Total mercury concentrations in invasive lionfish (Pterois volitans/miles) from the Atlantic coast of Florida

Eric G. Johnson, Angelina Dichiera et al.

131 downloads (posted 29 May 2020)

Invasive lionfish ( Pterois volitans/miles ) pose a serious threat to marine ecosystems throughout the western Atlantic Ocean and Caribbean Sea. The development of a fishery for lionfish has been proposed as a strategy for controlling populations; however, there is concern about consumption of this species by humans due to its high trophic position and potential for bioaccumulation of mercury. We analyzed total mercury (THg) in tissues of lionfish from two locations on the east coast of Florida. THg in lionfish increase...

https://rxivist.org/papers/85272
https://doi.org/10.1101/2020.05.29.123117

928: A novel RyR1 inhibitor prevents and rescues sudden death in a mouse model of malignant hyperthermia and heat stroke

Toshiko Yamazawa, Takuya Kobayashi et al.

130 downloads (posted 02 Jul 2020)

Mutations in the type 1 ryanodine receptor (RyR1), a Ca2+ release channel in skeletal muscle, hyperactivate the channel to cause malignant hyperthermia (MH) and are implicated in severe heat stroke. Dantrolene, the only approved drug for MH, has the disadvantages of having very poor water solubility and long plasma half-life. We show here that a novel RyR1-selective inhibitor, 6,7-(methylenedioxy)-1-octyl-4-quinolone-3-carboxylic acid (Compound 1, Cpd1), effectively prevents and treats MH and heat stroke in several mous...

https://rxivist.org/papers/89780
https://doi.org/10.1101/2020.07.02.185520

929: Development of nano-emulsions based on Ayapana triplinervis for the control of Aedes aegypti larvae

Alex Bruno Lobato Rodrigues, Rosany Martins Lopes et al.

130 downloads (posted 09 Jul 2020)

Ayapana triplinervis is a plant species used in traditional medicine and in mystical-religious rituals by traditional communities in the Amazon. The aim of this study is to evaluate the larvicidal activity against A. aegypti of nano-emulsions containing essential oils from A. triplinervis morphotypes, and acute oral toxicity in non-target organism. Essential oils were identified and nano-emulsions were prepared using the low energy method. The mortality test of A. aegypti larvae was performed according to the protocol r...

https://rxivist.org/papers/90511
https://doi.org/10.1101/2020.07.09.194985

930: Drug Screening Platform Using Human Induced Pluripotent Stem Cell-Derived Atrial Cardiomyocytes and Optical Mapping

Marvin G. Gunawan, Sarabjit S. Sangha et al.

129 downloads (posted 15 Jul 2020)

Current drug development efforts for the treatment of atrial fibrillation (AF) are hampered by the fact that many preclinical models have been unsuccessful in reproducing human cardiac atrial physiology and its response to medications. In this study, we demonstrated an approach using human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes (hiPSC-aCMs and hiPSC-vCMs, respectively) coupled with a sophisticated optical mapping system for drug screening of atrial-selective compounds in vitro. We op...

https://rxivist.org/papers/91084
https://doi.org/10.1101/2020.07.14.203232

931: In vivo Evaluation and in silico Prediction of the Toxicity of Drepanoalpha Hard capsules

Benjamin Gbolo Zoawe, Jean-Paul Ngbolua Koto-te-Nyiwa et al.

129 downloads (posted 04 Dec 2020)

Drepanoalpha(R) hard capsules, a dry ethanolic extract (drug-extract ratio, 100/11) of a mixture of Justicia secunda Vahl and Moringa oleifera Lam dried leaves (1: 1, w/w) are used for the management of sickle cell disease in the Democratic Republic of Congo. Aim of the study: This phytomedicine safety was investigated by acute and sub-acute administration in Guinea pigs. Materials and methods: Healthy, male and nulliparous and non-pregnant female Guinea pigs were obtained from Laboratory of Animal Experimentation and T...

https://rxivist.org/papers/120264
https://doi.org/10.1101/2020.12.03.411124

932: Fluoxetine treatment prevents cardiovascular changes in baroreflex and chemoreflex in rats subjected to chronic stress

Egidi Mayara Silva Firmino, Luciana Bärg Kuntze et al.

128 downloads (posted 05 Mar 2020)

Stress may influence the autonomic regulation, pathogenesis of cardiovascular disease and play an important role in animal behavior as depression. Depression is evidenced as a significant risk factor for cardiovascular changes. This is of great importance as some studies show an association between symptoms of depression and increased risk of cardiovascular disease (CVD) morbidity. Additionality, those alterations can be alleviated by use of antidepressants such as fluoxetine, which is a selective serotonin reuptake inh...

https://rxivist.org/papers/75840
https://doi.org/10.1101/2020.03.04.977033

933: Antioxidant enriched fraction from Pueraria tuberosa alleviates ovariectomized-induced osteoporosis in rats, and inhibits growth of breast and ovarian cancer cell lines in vitro

Swaha Satpathy, Arjun Patra et al.

128 downloads (posted 21 Sep 2020)

Pueraria tuberosa ( P. tuberosa ), known as Indian Kudzu belongs to family Fabaceae and it is solicited as “Rasayana” drugs in Ayurveda. In the present study, we analyzed the efficacy an antioxidant enriched fraction (AEF) from the tuber extract of P. tuberosa against menopausal osteoporosis and breast and ovarian cancer cell lines. The AEF from P. tuberosa was identified by determining phenolic composition (total phenolic and flavonoid amount). Antioxidant property ( in vitro assays) was also carried out followed by an...

https://rxivist.org/papers/98601
https://doi.org/10.1101/2020.09.21.305953

934: Gene Deletion Studies Reveal A Critical Role For Prostamide/Prostaglandin F2α Synthase In Prostamide F2α Formation

Jacques A Bertrand, David F. Woodward et al.

128 downloads (posted 04 Apr 2020)

Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide and prostaglandin F2α. The importance of this enzyme, relative to the aldoketoreductase (AKR) series, in providing functional tissue prostamide F2α levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (fam213b) was accomplished by a two exon disruption. Prostamide F2α levels in WT and PM/PGFS KO mice were determined by...

https://rxivist.org/papers/78802
https://doi.org/10.1101/2020.04.01.020768

935: Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington’s Like Disorder in Preclinical Model

Aniruddha Adhikari, Susmita Mondal et al.

127 downloads (posted 25 Sep 2020)

The potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu , and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, we have shown that citrate functionalized manganese-based biocompatible nanoscale materi...

https://rxivist.org/papers/98248
https://doi.org/10.1101/2020.09.23.310995

936: Rearing medium dictates variability across replicates in untreated and arsenic challenged zebrafish larvae

Anjana Ramdas Nair, Patrice Delaney et al.

127 downloads (posted 23 Aug 2020)

Reproducibility and consistency are hallmarks of scientific integrity. Biological systems are inherently noisy, posing a challenge to reproducibility. This is particularly relevant to the field of environmental toxicology, where many unaccounted experimental parameters can have a marked influence on the biological response to exposure. Here, we extend the use of zebrafish as a robust toxicological model for studying the effects of inorganic arsenic (iAs) on liver biology. We observed that iAs toxicity in this system is ...

https://rxivist.org/papers/95373
https://doi.org/10.1101/2020.08.23.263202

937: Mutations associated with pyrethroid resistance in Varroa mites, a parasite of honey bees, are widespread across the USA

Anabel Millán-Leiva, Óscar Marín et al.

127 downloads (posted 28 Nov 2020)

BACKGROUND: Managed honey bees are key pollinators of many crops and play an essential role in the United States food production. For more than 10 years, beekeepers in the US have been reporting high rate of colony losses. One of the drivers of this colony loss is the parasitic mite Varroa destructor. Preserving healthy honey bee colonies in the US is dependent on a successful control of this mite. The pyrethroid tau-fluvalinate (Apistan(R)) was among the first synthetic varroacide registered in the US. With over 20 yea...

https://rxivist.org/papers/119288
https://doi.org/10.1101/2020.11.27.401927

938: Application of Generalized Concentration Addition to Predict Mixture Effects of Glucocorticoid Receptor Ligands

Rosemarie de la Rosa, JJ Schlezinger et al.

126 downloads (posted 26 May 2020)

Environmental exposures often occur in complex mixtures and at low concentrations. Generalized concentration addition (GCA) is a method used to estimate the joint effect of receptor ligands that vary in efficacy. GCA models have been successfully applied to mixtures of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPARγ) ligands, each of which can be modeled as a receptor with a single binding site. Here, we evaluated whether GCA could be applied to homodimer nuclear receptors, wh...

https://rxivist.org/papers/84812
https://doi.org/10.1101/2020.05.21.109439

939: Membrane-tethered peptides derived from intracellular loops 2 and 3 of the urotensin II receptor act as allosteric biased ligands

Hassan Nassour, Tuan Anh Hoang et al.

126 downloads (posted 24 Nov 2020)

Over the last decade, the urotensinergic system has garnered significant attention as a promising new target for the treatment of various cardiovascular diseases and also cancer. Significant investment toward the development of clinically relevant UT ligands for therapeutic intervention has been made but have met little to no success to date. The UT system, which has yet to be effectively targeted, therefore remains to be therapeutically exploited. The discovery of allosteric sites that allow modulation of receptor acti...

https://rxivist.org/papers/104996
https://doi.org/10.1101/2020.11.23.394270

940: Antimicrobial efficacy of neem and liquorice with chlorhexidine on Streptococcus sanguis, Streptococcus mutans, Lactobacillus and Actinomyces naeslundii – An In Vitro Study

Saad M Alqahtani

126 downloads (posted 26 Sep 2020)

The study was to formulate 2% neem and 2% liquorice mouthwashes and to compare the antimicrobial efficacy of these mouthwashes with the standard 0.2% chlorhexidine mouthwash. Alcoholic solution was prepared and added to neem mixture and liquorice mixture separately and made up to a volume of 16000 ml with purified water. Nine dilutions of each drug were done with Brain heart infusion broth (BHI) for MIC. Culture suspension was added in each serially diluted tube of 200 μl. The tubes were incubated for 24 hours and obser...

https://rxivist.org/papers/98093
https://doi.org/10.1101/2020.09.23.311019