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Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD.

In dry age-related macular degeneration (AMD), LCN2 (lipocalin 2) is upregulated. Whereas LCN2 has been implicated in AMD pathogenesis, the … sosomal organelles complex 1 subunit 1; C57BL/6J: C57 black 6J; CGAS: cyclic GMP-AMP synthase; ChQ: chloroquine; cKO: conditional knockout; Cys74: cysteine 74; Dab2: DAB adaptor protein 2; Def: deferoxamine; DHE: dihydroethidium; DMSO: dimethyl sulfoxide; ERG: electroretinography; FAC: ferric ammonium citrate; Fe2+: ferrous; FTH1: ferritin heavy chain 1; GPX: …

Factors associated with the spatial heterogeneity of the first wave of COVID-19 in France: a nationwide geo-epidemiological study.

BACKGROUND: The objective of this study was to better understand the factors associated with the heterogeneity of in-hospital COVID-19 morbi … cture, baseline intensive care capacities, baseline population health and health-care services, new chloroquine and hydroxychloroquine dispensations, economic indicators, degree of urbanisation, and climate profile) and in-hospital COVID-19 incidence, mortality, and case fatality rates. Incidence rate was defined as the cumulative number of in-hospital COVID- …

Unusual Case of Granuloma Annulare Associated with Diabetes Mellitus.

Dear Editor, Granuloma annulare (GA) is an asymptomatic, chronic, and relatively common granulomatous skin condition which presents with ann … costeroids are the most common localized treatments (8). Systemic therapy includes corticosteroids, chloroquine, dapsone, and isotretinoin (1,9). Cryotherapy and UV-therapy can also be used, although with limited efficacy (10). GA is a common idiopathic disorder of the dermis and subcutaneous tissue that can be associated with a variety of underlying conditio …

Tafenoquine for preventing relapse in people with Plasmodium vivax malaria.

BACKGROUND: Plasmodium vivax malaria is widespread, and the persistent liver stage causes relapse of the disease which contributes to contin … lusion criteria, with the asexual infection in both the tafenoquine and comparator arm treated with chloroquine, and in all trials G6PD deficiency patients were excluded. Tafenoquine dose comparisonsThree of the included trials compared eight different dosing regimens. Tafenoquine doses of 300 mg and above resulted in fewer relapses than no hypnozoite treatme …

Extracorporeal membrane oxygenation in the treatment of poisoned patients.

CONTEXT: Although extracorporeal membrane oxygenation (ECMO) was used in many patients following its introduction in 1972, most hospitals ha … les include poisoning due to calcium channel antagonists, beta-blockers, tricyclic antidepressants, chloroquine and colchicine. ETHICS OF ECMO USE: It is only ethical to use such a costly intervention (£19,252 and US$ 31,000 per quality-adjusted life year) if the treatment has a real purpose such as a 'bridge to recovery', a 'bridge to transplant', or a 'brid …

Cardiovascular manifestations and treatment considerations in COVID-19.

Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, COVID-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of COVID-19 have similarities to that of severe acute respiratory syndrome, Mid

Degradation of radioiodinated B cell monoclonal antibodies: inhibition via a FCgamma-receptor-II-mediated mechanism and by drugs.

Our aim is to treat patients with B cell malignancies with radioimmunotherapy using monoclonal antibodies (mAb) such as CD19, CD20 and CD22. In this study we investigated the rate of internalization and catabolism of these mAb. After 24 h at 37 degrees C, 20%-25% of initially cell-bound (125)I-CD19 mAb and (125)I-CD22 mAb was degraded in B cells, whereas almost no degredation occurred after binding of (125)I-CD20 mAb. For B cells expressing Fcgamma receptor II (FcgammaRII), isotype-dependent degradation was noted as the CD19 IgGl mAb showed an enhanced degradation rate compared to the switch v

Existing highly accumulating lysosomotropic drugs with potential for repurposing to target COVID-19.

Given the speed of viral infection spread, repurposing of existing drugs has been given the highest priority in combating the ongoing COVID-19 pandemic. Only drugs that are already registered or close to registration, and therefore have passed lengthy safety assessments, have a chance to be tested in clinical trials and reach patients quickly enough to help in the current disease outbreak. Here, we have reviewed available evidence and possible ways forward to identify already existing pharmaceuticals displaying modest broad-spectrum antiviral activity which is likely linked to their high accum

Malaria Surveillance - United States, 2017.

PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the … ciated with resistance to pyrimethamine were found in 108 (97.3%), to sulfadoxine in 77 (69.4%), to chloroquine in 38 (33.3%), to mefloquine in three (2.7%), and to atovaquone in three (2.7%); no specimens tested contained a marker for artemisinin resistance. The data completeness of key variables (species, country of acquisition, and resident status) was low …

A Survey-based Estimate of COVID-19 Incidence and Outcomes among Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension and Impact on the Process of Care.

Rationale: Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) typically undergo frequent clinical evaluation. The incidence and outcomes of coronavirus disease (COVID-19) and its impact on routine management for patients with pulmonary vascular disease is currently unknown.Objectives: To assess the cumulative incidence and outcomes of recognized COVID-19 for patients with PAH/CTEPH followed at accredited pulmonary hypertension centers, and to evaluate the pandemic's impact on clinic operations at these centers.Methods: A survey was e-m

COVID-19 and neuromuscular disorders.

The coronavirus 2019 (COVID-19) pandemic has potential to disproportionately and severely affect patients with neuromuscular disorders. In a short period of time, it has already caused reorganization of neuromuscular clinical care delivery and education, which will likely have lasting effects on the field. This article reviews (1) potential neuromuscular complications of COVID-19, (2) assessment and mitigation of COVID-19-related risk for patients with preexisting neuromuscular disease, (3) guidance for management of immunosuppressive and immunomodulatory therapies, (4) practical guidance rega

Potential of Flavonoid-Inspired Phytomedicines against COVID-19.

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show p

Differential ERK activation during autophagy induced by europium hydroxide nanorods and trehalose: Maximum clearance of huntingtin aggregates through combined treatment.

Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy process induced by europium hydroxide nanorods [EHNs: Eu(III)(OH)3], but the underlying molecular mechanism of EHNs mediated autophagy was unclear. The present report reveals that EHNs induced autophagy does not follow the classical AKT-mTOR and AMPK signaling pathways. The inhibition of ERK1/2 phosp

Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells.

Imatinib mesylate (IM), a potent inhibitor of the BCR/ABL tyrosine kinase, has become standard first-line therapy for patients with chronic myeloid leukemia (CML), but the frequency of resistance increases in advancing stages of disease. Elimination of BCR/ABL-dependent intracellular signals triggers apoptosis, but it is unclear whether this activates additional cell survival and/or death pathways. We have shown here that IM induces autophagy in CML blast crisis cell lines, CML primary cells, and p210BCR/ABL-expressing myeloid precursor cells. IM-induced autophagy did not involve c-Abl or Bcl-

Natural and semisynthetic candidate molecules for COVID-19 prophylaxis and treatment.

Coronaviruses (CoVs) represent a family of viruses that have numerous animal hosts, and they cause severe respiratory, as well as systemic and enteric infections, in humans. Currently, there are limited antiviral strategies for treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The lack of specific antiviral medicines and SARS-CoV-2 vaccines continues to aggravate the situation. Natural product-based antiviral drugs have been used in the two previous CoV outbreaks: Middle East respiratory syndrome coronavirus (MERS-CoV) and the first SARS-CoV. This re

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… ⧉ Efficacy and safety of chloroquines for COVID-19 treatment Chloroquines In Germany, the well-known Bayer drug manufacturer synthesized CQ, an amine form of quinine, for the first time in 1934. … Review of side effects and toxicity of chloroquine; pp. 2–18. 76. White NJ, Watson JA, Hoglund RM, Chan XHS, Cheah PY, Tarning J. COVID-19 prevention and treatment: a critical analysis of chloroquine and hydroxychloroquine clinical pharmacology. …

Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality.

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively,

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… | 148 (89) | 157 (94) Azithromycin | 91 (54) | 115 (69) Antiretrovirals | 103 (62) | 103 (62) Antiviral combination therapy | | None | 11 (7) | 5 (3) (Hydroxy)chloroquine only | 16 (10) | 14 (8) (Hydroxy)chloroquine and retroviral | 47 (28) | 31 (19) (Hydroxy)chloroquine and azithromycin | 34 (20) … | | | None | 11 (6) | 6 (55) | 5 (45) (Hydroxy)chloroquine only | 16 (10) | 11 (69) | 5 (31) (Hydroxy)chloroquine and retrovirals | 47 (28) | 30 (64) | 17 (36) (Hydroxy)chloroquine and azithromycin | 34 (20) | 27 (79) | 7 (21) (Hydroxy)chloroquine, azithromycin, and retrovirals | 51 (31) | 33 (65) …

COVID-19 Therapeutic Options Under Investigation.

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexame

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… Chloroquine Phosphate and Hydroxychloroquine Chloroquine phosphate (CQ), a 4-aminoquinoline compound, is approved for the treatment of malaria and extraintestinal amebiasis ( Food and Drug Administration, 2009a ). … Hydroxychloroquine (HCQ), a chloroquine phosphate derivative, is also an FDA-approved antimalarial and immunomodulatory agent. …

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consiste

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… Antidiabetics Glitazones | Diabetes mellitus | PPARγ | PPARγ | Metformin | Diabetes mellitus | AMPK | AMPK | | | | | Antiobesity Orlistat | Obesity | Fatty-Acid Synthase | Fatty-Acid Synthase | | | | | Cholesterol lowering agents Statins | Cholesterolemia | HMGC | HMGC | | | | | Antimalarial Chloroquine …

Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma.

Haematopoiesis is a tightly orchestrated process where a pool of hematopoietic stem and progenitor cells (HSPCs) with high self-renewal potential can give rise to both lymphoid and myeloid lineages. The HSPCs pool is reduced with ageing resulting in few HSPC clones maintaining haematopoiesis thereby reducing blood cell diversity, a phenomenon called clonal haematopoiesis. Clonal expansion of HSPCs carrying specific genetic mutations leads to increased risk for haematological malignancies. Therefore, it comes as no surprise that hematopoietic tumours develop in higher frequency in elderly peopl

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… The resistance can be overcome by the use of Chloroquine. … Furthermore, recently a study on Chloroquine demonstrated that unlike Bafilomycin A1, Chloroquine and Hydroxychloroquine leads to an accumulation of autophagosomes [ 334 ]. Additionally, Chloroquine alters the Golgi organization and causes the vacuolization of lysosomes. …