Treatment of Darier’s disease with oral magnesium: a case report

Darier’s disease, an autosomal dominant genodermatosis, arises from a mutation in the ATP2A2 gene that codes for sarco/endoplasmic reticulum Ca2+-ATPase in the endoplasmic reticulum and is characterized by greasy keratotic papules commonly found in seborrheic regions. Conventional treatments, including topical corticosteroids, antibiotics, antifungals and retinoids, often have limited efficacy. The present article reports the novel use of oral magnesium chloride supplementation (300 mg daily) in the treatment of Darier disease. After 5 years of limited improvement using conventional therapies, significant improvements in neck lesions were observed within 1 month of starting oral magnesium chloride. This suggests that oral magnesium chloride may be an effective therapeutic option for Darier disease, although further in vitro and clinical trials are necessary to evaluate its clinical efficacy.

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Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666201204162103 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ekta Shirbhate ◽

Preeti Patel ◽

Vijay K Patel ◽

Ravichandran Veerasamy ◽

Prabodh C Sharma ◽

...

Keyword(s):

Therapeutic Option ◽

Antiviral Treatment ◽

The Novel ◽

Clinical Experiences ◽

Synthetic Compounds ◽

Synthetic Drugs ◽

Global Pandemic ◽

The World ◽

Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

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In vitro reconstruction of epidermis from primary Darier's disease keratinocytes replicates the histopathological phenotype

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2013.04.016 ◽

2013 ◽

Vol 71 (2) ◽

pp. 138-140 ◽

Cited By ~ 3

Author(s):

Catherine Lambert de Rouvroit ◽

Céline Charlier ◽

Damien Lederer ◽

Valérie De Glas ◽

Evelyne De Vuyst ◽

...

Keyword(s):

Darier’S Disease ◽

Darier's Disease

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Targeting PI3K and CDKs as effective therapeutic option for PPGLs in vitro and in vivo

Endocrine Abstracts ◽

10.1530/endoabs.73.oc15.3 ◽

2021 ◽

Author(s):

Sebastian Gulde ◽

Daniela De Martino ◽

Hermine Mohr ◽

Swapna Satam ◽

Alessia Foscarini ◽

...

Keyword(s):

Therapeutic Option ◽

Effective Therapeutic Option

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Preclinical Evaluation of Podoplanin-Targeted Alpha-Radioimmunotherapy with the Novel Antibody NZ-16 for Malignant Mesothelioma

Cells ◽

10.3390/cells10102503 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2503

Author(s):

Hitomi Sudo ◽

Atsushi B. Tsuji ◽

Aya Sugyo ◽

Mika K. Kaneko ◽

Yukinari Kato ◽

...

Keyword(s):

Malignant Mesothelioma ◽

Competitive Inhibition ◽

Therapeutic Option ◽

The Novel ◽

Absorbed Doses ◽

Biodistribution Studies ◽

Biodistribution Data ◽

Body Weights ◽

Necrotic Change

The prognosis of advanced mesothelioma is poor. Podoplanin (PDPN) is highly expressed in most malignant mesothelioma. This study aimed to evaluate the potential alpha-radioimmunotherapy (RIT) with a newly developed anti-PDPN antibody, NZ-16, compared with a previous antibody, NZ-12. Methods: The in vitro properties of radiolabeled antibodies were evaluated by cell binding and competitive inhibition assays using PDPN-expressing H226 mesothelioma cells. The biodistribution of 111In-labeled antibodies was studied in tumor-bearing mice. The absorbed doses were estimated based on biodistribution data. Tumor volumes and body weights of mice treated with 90Y- and 225Ac-labeled NZ-16 were measured for 56 days. Histologic analysis was conducted. Results: The radiolabeled NZ-16 specifically bound to H226 cells with higher affinity than NZ-12. The biodistribution studies showed higher tumor uptake of radiolabeled NZ-16 compared with NZ-12, providing higher absorbed doses to tumors. RIT with 225Ac- and 90Y-labeled NZ-16 had a significantly higher antitumor effect than RIT with 90Y-labeled NZ-12. 225Ac-labeled NZ-16 induced a larger amount of necrotic change and showed a tendency to suppress tumor volumes and prolonged survival than 90Y-labeled NZ-16. There is no obvious adverse effect. Conclusions: Alpha-RIT with the newly developed NZ-16 is a promising therapeutic option for malignant mesothelioma.

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Abstract P233: Inhibition Of Aldosterone Synthesis In Non-human Primates By PB6440, The Novel Highly Selective And Potent CYP11B2 Inhibitor

Hypertension ◽

10.1161/hyp.76.suppl_1.p233 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Bertram Pitt ◽

Deepak L Bhatt ◽

Karen Morris ◽

J. David Becherer ◽

William Hoekstra ◽

...

Keyword(s):

Oral Bioavailability ◽

Multiple Dose ◽

Therapeutic Option ◽

Dependent Manner ◽

The Novel ◽

Aldosterone Synthase ◽

Acth Challenge ◽

High Doses ◽

Synthase Inhibitor

Aldosterone is an important mineralocorticoid responsible for fluid and electrolyte homeostasis produced by aldosterone synthase (CYP11B2). An aldosterone synthase inhibitor (ASI) may be a therapeutic option for primary aldosteronism-related conditions such as resistant hypertension. An ASI with sufficient selectivity for CYP11B2 versus the similar cortisol-producing enzyme CYP11B1 has remained elusive. PB6440 is a novel ASI that is potent and highly selective for CYP11B2. In vitro studies demonstrated 200-300-fold selectivity of PB6440 for human CYP11B2 compared to human CYP11B1. In single and multiple dose cynomolgus monkey studies of orally administered PB6440, dose-and concentration-dependent reduction of plasma aldosterone after ACTH challenge was observed with >90% reduction at higher doses. Consistent with its high selectivity, PB6440 had little effect on the CYP11B1 cortisol pathway. Plasma levels of cortisol, 11-deoxycortisol, and deoxycorticosterone, remained unchanged even at high doses of PB6440. Systolic and diastolic blood pressure was reduced in a dose-dependent manner. Circulating half-life of PB6440 was approximately 17 hours with high oral bioavailability. In summary, PB6440 is a highly selective ASI that demonstrated sustained aldosterone suppression for 14 days with no effect on the CYP11B1 pathway in non-human primates. In single and multiple dose studies, PB6440 appeared well tolerated, demonstrating good oral bioavailability, and a PK profile supportive of once daily dosing. These results suggest that PB6440 may be useful in humans as a novel therapeutic for treating hypertension or other conditions caused by excess aldosterone.

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Role of Double-Carbapenem Regimen in the Treatment of Infections due to Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae: A Single-Center, Observational Study

BioMed Research International ◽

10.1155/2018/2785696 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

F. Cancelli ◽

A. Oliva ◽

M. De Angelis ◽

M. T. Mascellino ◽

C. M. Mastroianni ◽

...

Keyword(s):

Observational Study ◽

Therapeutic Option ◽

Clinical Effectiveness ◽

Synergistic Activity ◽

Single Center ◽

Minimal Inhibitory Concentrations ◽

Carbapenem Resistant ◽

Effective Therapeutic Option ◽

Bacteremic Infection

Purpose. (i) To compare infections caused by carbapenem-susceptible (CS) and carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE); (ii) to evaluate the clinical effectiveness of the double-carbapenem (DC) regimen in comparison with the best available treatment (BAT) in infections caused by CP-CRE; and (iii) to determine the exact minimal inhibitory concentrations (MICs) of meropenem/ertapenem (MEM/ETP) and the degree of in vitro ETP+MEM synergism in subjects receiving the DC. Methodology. Over a 3-year period (2014-2017), patients with infections due to Enterobacteriaceae were included in a single-center, retrospective, observational study. According to the susceptibility to carbapenems, subjects were divided into CSE and CP-CRE groups. CP-CRE group was further divided into subjects receiving the DC regimen and those treated with other regimens (BAT group). Clinical characteristics and the presence of 5th-day response and 60-day outcome were evaluated for DC and BAT groups. The determination of MEM and ETP actual MICs and the MEM+ETP synergistic activity were performed on strains obtained from subjects receiving the DC regimen. Results. A total of 128 patients were included in the study: 55/128 (43%) with infections due to CP-CRE and 73/128 (57%) with infections due to CSE. Among CP-CRE (n=55), 21 subjects (39%) were treated with the DC regimen whereas 34 (61%) received BAT. No differences in terms of severity of infection, presence/absence of concomitant bacteremia, type of infection, and resolution of infection were found; in contrast, DC group tended to have a higher rate of sepsis or septic shock at the onset of infection and a higher rate of 5th-day response. MICs 50/90 were 256/512 and 256/256 μg/mL for MEM and ETP, respectively. Overall, complete in vitro synergism was found in 6/20 strains (30%). Conclusion. The DC regimen is a valid and effective therapeutic option in patients with infections due to KPC producing CRE, including those with bacteremic infection and more severe clinical conditions. The clinical effectiveness is maintained even in the presence of extremely high MEM MICs.

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Expression of the sarco/endoplasmic reticulum calcium ATPase type 2 and 3 isoforms in normal skin and Darier's disease

British Journal of Dermatology ◽

10.1111/j.1365-2133.2004.06130.x ◽

2004 ◽

Vol 151 (2) ◽

pp. 440-445 ◽

Cited By ~ 21

Author(s):

S. Tavadia ◽

K.S. Authi ◽

M.B. Hodgins ◽

C.S. Munro

Keyword(s):

Endoplasmic Reticulum ◽

Normal Skin ◽

Calcium Atpase ◽

Endoplasmic Reticulum Calcium ◽

Darier’S Disease ◽

Darier's Disease

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RNAi-mediated silencing of CD40 prevents leukocyte adhesion on CD154-activated endothelial cells

Blood ◽

10.1182/blood-2004-03-0817 ◽

2004 ◽

Vol 104 (12) ◽

pp. 3642-3646 ◽

Cited By ~ 34

Author(s):

Raquel Pluvinet ◽

Jordi Pétriz ◽

Joan Torras ◽

Inmaculada Herrero-Fresneda ◽

Josep M. Cruzado ◽

...

Keyword(s):

Endothelial Cells ◽

Leukocyte Adhesion ◽

Therapeutic Option ◽

Surface Expression ◽

Costimulatory Receptor ◽

Inflammatory Conditions ◽

Effective Therapeutic Option ◽

Inflammatory Processes ◽

Interfering Rna

The CD40-CD154 dyad has a central role in the development of immune-inflammatory processes. Therefore, disruption of CD40 signaling has the potential to be therapeutically useful in a number of disease indications, including autoimmune syndromes, atherosclerosis, and allograft rejection. Blocking antibodies to CD154 have been successfully employed in experimental animal models, and recently in clinical trials, to prevent or treat these immunologically induced diseases. However, the thrombotic events observed in some of these studies raise important issues regarding future use of anti-CD154 antibodies in humans. In this study, we demonstrate that a small interfering RNA (siRNA) can effectively reduce the surface expression of the human CD40 costimulatory receptor. Moreover, by rendering endothelial cells unresponsive to CD154+ Jurkat cell–mediated activation through RNA interference, induction of endothelial cell-adhesion molecule expression and leukocyte adhesion is prevented in vitro. Thus, anti-CD40 siRNA may become a safe and effective therapeutic option for interfering with CD40-CD154–mediated acute or chronic immune-inflammatory conditions.

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Repurposing Potential of Riluzole as an ITAF Inhibitor in mTOR Therapy Resistant Glioblastoma

International Journal of Molecular Sciences ◽

10.3390/ijms21010344 ◽

2020 ◽

Vol 21 (1) ◽

pp. 344 ◽

Cited By ~ 2

Author(s):

Angelica Benavides-Serrato ◽

Jacquelyn T. Saunders ◽

Brent Holmes ◽

Robert N. Nishimura ◽

Alan Lichtenstein ◽

...

Keyword(s):

Rna Binding ◽

Therapeutic Option ◽

Mtor Inhibitors ◽

Hnrnp A1 ◽

Entry Site ◽

Internal Ribosome Entry ◽

Docking Analysis ◽

In Silico Docking ◽

Effective Therapeutic Option

Internal ribosome entry site (IRES)-mediated protein synthesis has been demonstrated to play an important role in resistance to mechanistic target of rapamycin (mTOR) targeted therapies. Previously, we have demonstrated that the IRES trans-acting factor (ITAF), hnRNP A1 is required to promote IRES activity and small molecule inhibitors which bind specifically to this ITAF and curtail IRES activity, leading to mTOR inhibitor sensitivity. Here we report the identification of riluzole (Rilutek®), an FDA-approved drug for amyotrophic lateral sclerosis (ALS), via an in silico docking analysis of FDA-approved compounds, as an inhibitor of hnRNP A1. In a riluzole-bead coupled binding assay and in surface plasmon resonance imaging analyses, riluzole was found to directly bind to hnRNP A1 and inhibited IRES activity via effects on ITAF/RNA-binding. Riluzole also demonstrated synergistic anti-glioblastoma (GBM) affects with mTOR inhibitors in vitro and in GBM xenografts in mice. These data suggest that repurposing riluzole, used in conjunction with mTOR inhibitors, may serve as an effective therapeutic option in glioblastoma.

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