查看更多>>摘要：Background: Mood stabilizers with disparate chemical structures are approved for treating bipolar disorder， but their mechanisms of action are not agreed on。 However， when administered to unanesthetized rats at clinically relevant doses， they modulate neurotransmission involving arachidonic acid and brain activity of COX-2， which oxidizes arachidonic acid within the arachidonic acid metabolic cascade。 Hypothesis: Inhibiting COX-2 directly might enhance mood stabilizer effects in bipolar disorder patients。 Observations: This paper reviews randomized controlled trials that showed that celecoxib， a selective COX-2 inhibitor， or low-dose aspirin， which inhibits COX-1 and inhibits/acetylates COX-2， reduced bipolar symptoms in patients on mood stabilizers。 More convincing are two population based pharmacoepidemiological studies that each demonstrated that chronic low dose aspirin reduced bipolar severity markers in patients on mood stabilizers。 Conclusions: This clinical evidence is consistent with the hypothesis that low-dose chronic aspirin and celecoxib， which can inhibit COX-2 and enter brain， can be repurposed in bipolar disorder to enhance mood stabilizer effects on arachidonic acid metabolism and neurotransmission。
查看更多>>摘要：Amyotrophic Lateral Sclerosis (ALS) remains a terminal disease without an established etiology for the majority of patients。 The dominant theory of ALS before the 1970?s was the presence of a poison。 One of the primary means of treating patients with a toxic exposure has been plasma exchange， but plasma exchange of ALS patients failed to alter the clinical course。 The failure of plasma exchange assumes the patient is no longer exposed to the poison。 If the exposure to poison continued， then plasma exchange alone would fail。 I found laboratory evidence of a poisoning in every patient with ALS examined。 A search for specific poisons found evidence of mycotoxins。 Treatment with antifungal agents corrected the laboratory findings。 All of the ALS patients had evidence of immune suppression。 There is mounting evidence that many mycotoxins cause both neurotoxicity and immune suppression。 These mycotoxins may be able to explain the full spectrum of pathology in ALS without a secondaryevent。
Chukwunyere, UgochukwuSehirli, Ahmet OzerAbacioglu, Nurettin
4页
查看更多>>摘要：The COVID-19 pandemic has become a burden to the global healthcare community。 Despite the severity of the complications associated with COVID-19， no antiviral agent is yet available for the treatment of this disease。 Several studies have reported arrhythmias as one of the numerous manifestations associated with COVID-19 infection。 Clinicians use different therapeutic agents in the management of COVID-19 patients with arrhythmias， apart from ranolazine; however， some of these drugs are administered with caution because of their significant side effects。 In this study， we reviewed the potential antiarrhythmic effects of ranolazine in the management of cardiac arrhythmias associated with COVID-19。 Ranolazine is a second-line drug approved for the treatment of chronic stable angina pectoris。 Previous studies have shown that ranolazine produces its beneficial cardiac effects without any significant impact on the body?s hemodynamics; hence， blood pressure is not altered。 Due to its reduced side effects， ranolazine may be more effective than other drugs in producing the desired relief from COVID-19 related arrhythmias， since it produces its antiarrhythmic effect by modulating sodium， potassium and calcium channels， and suppressing cytokine expression。
Brown, Gregory M.Karthikeyan, RamanujamPandi-Perumal, Seithikurippu R.Cardinali, Daniel P....
3页
查看更多>>摘要：Patients with Autism Spectrum Disorder (ASD) may be particularly prone to develop COVID-19。 An unusual extended course of COVID-19 disease illness has been reported in one ASD patient and a group of patients have COVID-19 disease in a neurodevelopmental facility。 It has been widely reported that many of those with ASD have substantial sleep disorders with low levels of melatonin and various genetic alterations related to melatonin production have been found。 Several lines of evidence point to a substantial role of melatonin in the body?s innate defense system including acting as a scavenger， an antioxidant and modulating the immune system。 We therefore hypothesize that melatonin deficiency may predispose those ASD patients who have low melatonin output to COVID-19 disease。 Potential implications for treatment are discussed。
查看更多>>摘要：Diabetic foot ulcer (DFU) has become a major medical， social and economic concern worldwide。 It is highly desirable to develop promising new solutions to effectively and appropriately treat DFU。 In recent years， investigators have used an innovative technology called proximal tibial cortex transverse distraction (PTCTD) to treat DFU and have achieved satisfactory results in terms of improved wound healing and circumvention of amputation as a consequence of enhanced neovascularization and perfusion of the ulcerated feet after the operation， but the underlying mechanism has not been explored。 Previous studies have suggested that in addition to stimulating osteogenesis， bone distraction also facilitates neovascularization， which may be associated with the chemokine stromal cell-derived factor-1 (SDF-1)。 As an important member of the chemokine family， SDF-1 is primarily responsible for the homing and migration of endothelial progenitor cells (EPCs) or bone marrowderived mesenchymal stem cells (BMSCs)， and plays a central role in the process of neovascularization。 In vivo or in vitro experiments show that bone distraction can induce the expression of SDF-1 and increase its plasma concentration。 Moreover， some researchers have found that an insufficient level of SDF-1 in the circulation and wounds of patients with DFU can lead to impaired neovascularization。 Therefore， we believe that SDF1 plays an important role in promoting neovascularization of DFU as a result of bone distraction。 We summarize the currently relevant literature to put forward an undisclosed but meaningful mechanism of bone distraction in the treatment of DFU。
查看更多>>摘要：Hidradenitis Suppurativa (HS) is a chronic， recurrent， debilitating skin disease of the hair follicle that usually presents after puberty with painful， deep-seated， inflamed lesions in the apocrine gland bearing areas of the body， most commonly the axillae， inguinal and anogenital regions。 The pathophysiology of the disease remains elusive， with newer therapies targeting various aspects of the dysregulated immune system。
查看更多>>摘要：It's since December 2019 that Corona virus disease (COVID-19) has emerged to be the global issue of concern。 A "pandemic"; this is what WHO has declared about the COVID-19 outbreak on March 3rd， 2020。 Vitamin D and its deficiency have recently been claimed to be one of the potential factors affecting COVID-19 risks and outcomes [1]。 As Selberstein et al。， has recently discussed the effect of vitamin D deficiency， and the role of vitamin D supplementation in COVID-19 patients [2]， I'd believe that vitamin D binding protein (DBP) is maybe also involved。 A closer look on DBP and its action on regulating the circulatory vitamin D levels， its polymorphisms and their impact on COVID-19 prevalence and mortality， will be briefly discussed。
查看更多>>摘要：As the COVID-19 pandemic continues， researchers seek to identify efficacious treatments。 Current approaches to COVID-19 therapeutics focus on antiviral agents， convalescent plasma， monoclonal antibodies， immunomodulators and more traditional therapies such as steroids [1-6]。 Reversing disturbances in coagulation has also been identified as a priority area for candidate therapies， such as through the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 adaptive clinical trial (ACTIV-4) which is currently evaluating aspirin， heparins and apixaban [7]。 Since there is a clear relationship between mechanisms of coagulation and the immune response， it is possible that reversing disturbances in coagulation may diminish the dysregulated immune response observed in COVID-19。 The basis for this hypothesis is described below and is followed by discussion of a proposed candidate therapy - activated protein C。 By treating COVID-19 patients using a novel approach， which does not focus on immune-based or antiviral treatments， but instead which addresses both the anti-thrombotic and inflammatory consequences of infection， the hope is that new therapeutic targets can be considered and new candidate therapies， such as activated protein C， may be evaluated。
查看更多>>摘要：Hypoparathyroidism is one of the most common postoperative complications of thyroid surgery， and organoid transplantation is a frontier field expected to treat hypoparathyroidism。 Organoids are three-dimensional cell aggregates derived from embryonic stem cells， pluripotent stem cells， or tissue precursor cells， possessing similar structures and functions to organs。 Thus they can replace diseased organs to play a role。 Adipose-derived stem cells (ASCs) are a population of postnatal stem cells residing in the fat tissue， capable of differentiating into parathyroid-like cells with parathyroid hormone secretion function。 Additionally， we have prepared cartilaginous organoids by intelligent porous hydrogel and differentiated ASCs via ?bottom-up? strategy in vitro。 Therefore， we speculate that parathyroid organoids can be achieved by the biomaterial-assisted assembly of differentiated adipose stem cells and it is a promising treatment for hypoparathyroidism。
NSTL
Elsevier