DCA AND Neuropathy

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most common and severe complications of diabetes, with vascular changes, neuropathy, and infections being the primary pathological mechanisms. Glutamine (Gln) metabolism has been found to play a crucial role in diabetes complications. This study aims to identify and validate potential Gln metabolism biomarkers associated with DFU through bioinformatics and machine learning analysis. METHODS: We downloaded two microarray datasets related to DFU patients from the Gene Expression Omnibus (GEO) database, namely GSE134431, GSE68183, and GSE80178...

OBJECTIVE: This study aimed to identify risk factors for diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and construct a nomogram prediction model for DR. METHODS: T2DM patients (n = 520) who underwent funduscopic examinations from June 2020 to June 2022 were included. Of these patients, 220 had DR, yielding a disease rate of 40.38%. Patients were divided into a training set (n = 364) and a validation set (n = 156) at a 7:3 ratio. Feature variables were selected using LASSO regression, random forests, and decision trees...

Paclitaxel leads to peripheral neuropathy (paclitaxel-induced peripheral neuropathy [PIPN]) in approximately 50% of cancer patients. At present, there are no effective treatment strategies for PIPN, the mechanisms of which also remain unclear. In this study, we performed microbiome and metabolome analysis of feces and serum from breast cancer patients with different PIPN grades due to paclitaxel treatment. Our analysis reveals that levels of deoxycholic acid (DCA) are highly increased because of ingrowth of Clostridium species, which is associated with severe neuropathy...

Amphiphysin (AMPH) autoimmunity is associated with a variety of neurological complications, including encephalitis, peripheral neuropathy, myelopathy, and cerebellar syndrome. Its diagnosis is based on clinical neurological deficits and the presence of serum anti-AMPH antibodies. Active immunotherapy, such as intravenous immunoglobulins, steroids, and other immunosuppressive therapies, has been reported to be effective in most patients. However, the extent of recovery varies depending on the case. Herein, we report the case of a 75-year-old woman with semi-rapidly progressive systemic tremors, visual hallucinations, and irritability...

Introduction Diabetic cheiroarthropathy (DCA), also known as the syndrome of limited joint mobility (LJM), is among the most underdiagnosed complications of diabetes mellitus (DM). Although not severe, it can hamper the day-to-day activities of the patient and significantly reduce the quality of life. It is hypothesized to be due to increased glycation of collagen around joints. The objective of our study was to examine the association of diabetic cheiroarthropathy with microvascular complications of type 2 diabetes mellitus...

BACKGROUND: Many diabetic patients develop and progress to diabetic foot ulcers, which seriously affect health and quality of life and cause great economic and psychological stress, especially in elderly diabetic patients who often have various underlying diseases, and the consequences of their progression to diabetic foot ulcers are more serious and seriously affect elderly patients in surgery. Therefore, it is particularly important to analyze the influencing factors related to the progression of elderly diabetic patients to diabetic foot, and the column line graph prediction model is drawn based on regression analysis to derive the influencing factors of the progression of elderly diabetic patients to diabetic foot, and the total score derived from the combination of various influencing factors can visually calculate the probability of the progression of elderly diabetic patients to diabetic foot...

Background: Diabetic peripheral neuropathy (DPN) is a critical clinical disease with high disability and mortality rates. Early identification and treatment of DPN is critical. Our aim was to train and externally validate a prediction nomogram for early prediction of DPN. Methods: 3012 patients with T2DM were retrospectively studied. These patients were hospitalized between 1 January 2017 and 31 December 2020 in the First Affiliated Hospital of Xinjiang Medical University in Xinjiang, China. A total of 901 patients with T2DM from the Suzhou BenQ Hospital in Jiangsu, China who were hospitalized between 1 January 2019 and 31 December 2020 were considered for external validation...

PURPOSE: To analyze the utility of isolated-check visual evoked potential (icVEP) for discriminating between eyes with dysthyroid optic neuropathy (DON) and eyes with thyroid-associated ophthalmopathy (TAO) but not DON. METHODS: Forty-three eyes with TAO but not DON (as non-DON), fifty-three eyes with DON, and sixty healthy eyes (as controls) were included. Comprehensive ophthalmic examinations, including best-corrected visual acuity, refraction, color vision test, intraocular pressure measurement, slit-lamp biomicroscopy, ophthalmoscopy, RAPD, exophthalmometry measurements, pVEP test, icVEP test, standard automated perimetry, and clinical activity score classification of TAO, as well as demographic information, were collected and analyzed...

OBJECTIVE: To develop a nomogram for the risk of diabetic retinopathy (DR) among type 2 diabetes mellitus (T2DM). METHODS: Questionnaires, physical examinations and biochemical tests were performed on 5900 T2DM patients in the Second Hospital of Shijiazhuang. The least absolute shrinkage and selection operator regression was used to optimize feature selection, and the importance of selected features was analyzed by random forest. Logistic regression was performed with selected features, and the nomogram was established based on the results...

AIMS: The aim of the study was to construct and validate a risk nomogram for clinically significant macular edema (CSME) prediction in diabetes mellitus (DM) patients using systemic variables. METHODS: In this retrospective study, DM inpatients who underwent routine diabetic retinopathy screening were recruited and divided into training and validation sets according to their admission date. Ninety-three demographic and systemic variables were collected. The least absolute shrinkage and selection operator was used to select the predictive variables from the training set...

Purpose: To develop a nomogram model that predicts the risk of diabetic nephropathy (DN) incidence in type 2 diabetes mellitus (T2DM) patients. Methods: We collect information from electronic medical record systems. The data were split into a training set (n=521) containing 73.8% of patients and a validation set (n=185) holding the remaining 26.2% of patients based on the date of data collection. Stepwise and multivariable logistic regression analyses were used to screen out DN risk factors...

BACKGROUND: Peripheral neuropathy (PN) is the damage and dysfunction of neurons of the peripheral nervous system. The present study was conducted to estimate the effectiveness of low-power laser therapy (LPLT) in the management of PN in a rats' model. METHODS: PN was induced by giving dichloroacetate (DCA) (250 mg/kg/day) for up to 12 weeks. Four groups of rats were used: control group, PN group, PN group treated with gabapentin and PN group treated with LPLT...

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most serious complications of type 2 diabetes mellitus (T2DM). DPN increases the risk of ulcers, foot infections, and noninvasive amputations, ultimately leading to long-term disability. METHODS: Seven hundred patients with T2DM were investigated from 2013 to 2017 in the Sanlin community by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 681 patients (19 missing) were investigated using a questionnaire, physical examination, biochemical index test, and follow-up Toronto clinical scoring system (TCSS) test...

BACKGROUND: Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it. METHODS: Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum...

OBJECTIVE: To determine the diagnostic ability of isolated-check visual evoked potential (icVEP), pattern visual evoked potential (pVEP), and standard automated perimetry (SAP) between dysthyroid optic neuropathy (DON) and thyroid-associated ophthalmopathy (TAO) without DON (non-DON). METHODS: This is a case-control study, 49 bilateral patients (26 DON and 23 non-DON) were included. icVEP, pVEP, and SAP were conducted in all the subjects, icVEP parameters compared were signal-to-noise ratios (SNRs) under 8, 16, and 32% depth of modulation (DOM)...

Glutathione transferase zeta 1 (GSTZ1), expressed in liver and several extrahepatic tissues, catalyzes dechlorination of dichloroacetate (DCA) to glyoxylate. DCA inactivates GSTZ1, leading to autoinhibition of its metabolism. DCA is an investigational drug for treating several congenital and acquired disorders of mitochondrial energy metabolism, including cancer. The main adverse effect of DCA, reversible peripheral neuropathy, is more common in adults treated long-term than in children, who metabolize DCA more quickly after multiple doses...

Dichloroacetate is an investigational drug that is used in the treatment of various congenital and acquired disorders of energy metabolism. Although DCA is generally well-tolerated, some patients experience peripheral neuropathy, a side effect more common in adults than children. Repetitive DCA dosing causes downregulation of its metabolizing enzyme, GSTZ1, which is also critical in the detoxification of maleylacetoacetate and maleylacetone. GSTZ1 (-/-) knockout mice show upregulation of GSTs and antioxidant enzymes as well as an increase in GSSG:GSH, suggesting GSTZ1 deficiency causes oxidative stress...

Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK). It is metabolized by GSTZ1, which has common polymorphisms altering enzyme or promoter activity. GSTZ1 is also irreversibly inactivated by DCA. In the first clinical trial of DCA in a hematological malignancy, DiCAM (DiChloroAcetate in Myeloma), we have examined the relationship between DCA concentrations, GSTZ1 genotype, side effects, and patient response. DiCAM recruited seven myeloma patients in partial remission...

Dichloroacetate (DCA) has been the focus of research by both environmental toxicologists and biomedical scientists for over 50 years. As a product of water chlorination and a metabolite of certain industrial chemicals, DCA is ubiquitous in our biosphere at low μg/kg body weight daily exposure levels without obvious adverse effects in humans. As an investigational drug for numerous congenital and acquired diseases, DCA is administered orally or parenterally, usually at doses of 10-50mg/kg per day. As a therapeutic, its principal mechanism of action is to inhibit pyruvate dehydrogenase kinase (PDK)...

The dorsal cricoarytenoid (DCA) muscles, are a fundamental component of the athletic horse's respiratory system: as the sole abductors of the airways, they maintain the size of the rima glottis which is essential for enabling maximal air intake during intense exercise. Dysfunction of the DCA muscle leads to arytenoid collapse during exercise, resulting in poor performance. An electrodiagnostic study including electromyography of the dorsal cricoarytenoid muscles and conduction velocity testing of the innervating recurrent laryngeal nerves (RLn) was conducted in horses with normal laryngeal function...