Therapeutic Interventions
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2021 ◽  
Vol 8 ◽  
Helen C. Causton

SARS-CoV2 infection results in a range of symptoms from mild pneumonia to cardiac arrhythmias, hyperactivation of the immune response, systemic organ failure and death. However, the mechanism of action has been hard to establish. Analysis of symptoms associated with COVID-19, the activity of repurposed drugs associated with lower death rates or antiviral activity in vitro and a small number of studies describing interventions, point to the importance of electrolyte, and particularly potassium, homeostasis at both the cellular, and systemic level. Elevated urinary loss of potassium is associated with disease severity, and the response to electrolyte replenishment correlates with progression toward recovery. These findings suggest possible diagnostic opportunities and therapeutic interventions. They provide insights into comorbidities and mechanisms associated with infection by SARS-CoV2 and other RNA viruses that target the ACE2 receptor, and/or activate cytokine-mediated immune responses in a potassium-dependent manner.

2021 ◽  
Vol 12 (11) ◽  
Jiayin Deng ◽  
Ai-Ling Tian ◽  
Hui Pan ◽  
Allan Sauvat ◽  
Marion Leduc ◽  

AbstractColorectal cancers (CRC) can be classified into four consensus molecular subtypes (CMS), among which CMS1 has the best prognosis, contrasting with CMS4 that has the worst outcome. CMS4 CRC is notoriously resistant against therapeutic interventions, as demonstrated by preclinical studies and retrospective clinical observations. Here, we report the finding that two clinically employed agents, everolimus (EVE) and plicamycin (PLI), efficiently target the prototypic CMS4 cell line MDST8. As compared to the prototypic CMS1 cell line LoVo, MDST8 cells treated with EVE or PLI demonstrated stronger cytostatic and cytotoxic effects, increased signs of apoptosis and autophagy, as well as a more pronounced inhibition of DNA-to-RNA transcription and RNA-to-protein translation. Moreover, nontoxic doses of EVE and PLI induced the shrinkage of MDST8 tumors in mice, yet had only minor tumor growth-reducing effects on LoVo tumors. Altogether, these results suggest that EVE and PLI should be evaluated for their clinical activity against CMS4 CRC.

2021 ◽  
Vol 12 ◽  
Kazuhiko Fukushima ◽  
Shinji Kitamura ◽  
Kenji Tsuji ◽  
Jun Wada

Several large clinical trials have shown renal and cardioprotective effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors in diabetes patients, and the protective mechanisms need to be elucidated. There have been accumulating studies which report that SGLT2 inhibitors ameliorate autophagy deficiency of multiple organs. In overnutrition diseases, SGLT2 inhibitors affect the autophagy via various signaling pathways, including mammalian target of rapamycin (mTOR), sirtuin 1 (SIRT1), and hypoxia-inducible factor (HIF) pathways. Recently, it turned out that not only stagnation but also overactivation of autophagy causes cellular damages, indicating that therapeutic interventions which simply enhance or stagnate autophagy activity might be a “double-edged sword” in some situations. A small number of studies suggest that SGLT2 inhibitors not only activate but also suppress the autophagy flux depending on the situation, indicating that SGLT2 inhibitors can “regulate” autophagic activity and help achieve the appropriate autophagy flux in each organ. Considering the complicated control and bilateral characteristics of autophagy, the potential of SGLT2 inhibitors as the regulator of autophagic activity would be beneficial in the treatment of autophagy deficiency.

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1119
Yohei Tomita ◽  
Ayumi Usui-Ouchi ◽  
Anders K. Nilsson ◽  
Jay Yang ◽  
Minji Ko ◽  

Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.

2021 ◽  
Vol 12 ◽  
Micaela K. Roy ◽  
Francesca Cendali ◽  
Gabrielle Ooyama ◽  
Fabia Gamboni ◽  
Holmes Morton ◽  

Background: Pyruvate kinase deficiency (PKD) is the most frequent congenital enzymatic defect of glycolysis, and one of the most common causes of hereditary non spherocytic hemolytic anemia. Therapeutic interventions are limited, in part because of the incomplete understanding of the molecular mechanisms that compensate for the metabolic defect.Methods: Mass spectrometry-based metabolomics analyses were performed on red blood cells (RBCs) from healthy controls (n=10) and PKD patients (n=5).Results: In PKD patients, decreases in late glycolysis were accompanied by accumulation of pentose phosphate pathway (PPP) metabolites, as a function of oxidant stress to purines (increased breakdown and deamination). Markers of oxidant stress included increased levels of sulfur-containing compounds (methionine and taurine), polyamines (spermidine and spermine). Markers of hypoxia such as succinate, sphingosine 1-phosphate (S1P), and hypoxanthine were all elevated in PKD subjects. Membrane lipid oxidation and remodeling was observed in RBCs from PKD patients, as determined by increases in the levels of free (poly-/highly-unsaturated) fatty acids and acyl-carnitines.Conclusion: In conclusion, in the present study, we provide the first overview of RBC metabolism in patients with PKD. Though limited in scope, the study addresses the need for basic science to investigate pathologies targeting underrepresented minorities (Amish population in this study), with the ultimate goal to target treatments to health disparities.

Pratik P. Patel ◽  
Priyal M. Raval

The Clozapine is available in the form of 25 Yellow Tablets of 100mg. Clozapine is very famous in now-a-days due to its use of optimisation in transdermal metric basically for experimental process and is used for the improvement of bioavailability. The medications are demonstrated for mitigating the risk of recurrent suicidal behaviour in schizophrenia patients or schizoaffective disorder who really are evaluated to be at persistent risk of convolutional suicidal behaviour in a historical and controlled experimental state. The paper provides a brief analysis of Clozapine drugs Usage, Formulation and Evaluation. The drugs were used upon animals at first to test the effects. There are several side effects of Clozapine that includes High fever and also symptoms like flu, Weakness and dizziness, allergy in skin and red spots, Sometimes itching problems in vaginal, in serious problems it can also create breathing problems and worsening cough. This is known as the Second Generation Antipsychotic that helps in balancing the dopamine and serotonin that improves the cognitive functions like mood, thinking and behaviour of an individual. Clozapine is restricted to use however it is used under one particular condition i.e. when the person suffering from Schizophrenia does not respond to other medications, have suicidal incidents or have positive symptoms. Furthermore, considerable clinical study has proven that clozapine seems to be more efficacious than just about any other antipsychotic drug throughout therapeutic interventions and therefore it clearly outperforms some other antipsychotics with in treatment of recurrent schizoaffective disorder. KEYWORDS: schizophrenia, transdermal, clozapine, antipsychotic

2021 ◽  
pp. 112067212110491
Ali Nouraeinejad

Radiation-induced optic neuropathy (RION) is a late complication of radiation therapy for brain and skull base tumors. RION leads to the devastating total vision loss in one or both eyes. Therefore, the early detection of RION is vital. Since visual symptoms and clinical signs of RION are not present at early stages of the radiation injury, it is essential to apply a diagnostic test to detect RION as early as possible in order to start therapeutic interventions. The author proposes to apply visual evoked potential (VEP) as a diagnostic test in the interval time after radiation therapy.

2021 ◽  
Vol 118 (43) ◽  
pp. e2104925118
Hyoyoung Jeong ◽  
Sung Soo Kwak ◽  
Seokwoo Sohn ◽  
Jong Yoon Lee ◽  
Young Joong Lee ◽  

Early identification of atypical infant movement behaviors consistent with underlying neuromotor pathologies can expedite timely enrollment in therapeutic interventions that exploit inherent neuroplasticity to promote recovery. Traditional neuromotor assessments rely on qualitative evaluations performed by specially trained personnel, mostly available in tertiary medical centers or specialized facilities. Such approaches are high in cost, require geographic proximity to advanced healthcare resources, and yield mostly qualitative insight. This paper introduces a simple, low-cost alternative in the form of a technology customized for quantitatively capturing continuous, full-body kinematics of infants during free living conditions at home or in clinical settings while simultaneously recording essential vital signs data. The system consists of a wireless network of small, flexible inertial sensors placed at strategic locations across the body and operated in a wide-bandwidth and time-synchronized fashion. The data serve as the basis for reconstructing three-dimensional motions in avatar form without the need for video recordings and associated privacy concerns, for remote visual assessments by experts. These quantitative measurements can also be presented in graphical format and analyzed with machine-learning techniques, with potential to automate and systematize traditional motor assessments. Clinical implementations with infants at low and at elevated risks for atypical neuromotor development illustrates application of this system in quantitative and semiquantitative assessments of patterns of gross motor skills, along with body temperature, heart rate, and respiratory rate, from long-term and follow-up measurements over a 3-mo period following birth. The engineering aspects are compatible for scaled deployment, with the potential to improve health outcomes for children worldwide via early, pragmatic detection methods.

2021 ◽  
Vol 101 ◽  
pp. 108204
Saied A. Aboushanab ◽  
Ali H. El-Far ◽  
Venkata Ramireddy Narala ◽  
Rokia F. Ragab ◽  
Elena G. Kovaleva

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