Preliminary Risk assessment for Acrylamide and Peripheral Neuropathy.
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ABSTRACT:
SUBMITTER: Park RM
PROVIDER: S-EPMC8284192 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity.
| S-EPMC8199319 | biostudies-literature
Project description:Diabetic peripheral neuropathy (DPN), the most common chronic complication of diabetes, has become an important public health crisis worldwide. Given that DPN is extremely difficult to treat, determining its risk factors and controlling it at an early stage is critical to preventing its serious consequences and the burden of social disease. Current studies suggest that the risk factors for diabetic peripheral neuropathy are the duration of diabetes, age, glycosylated hemoglobin A1c (HbA1c), diabetic retinopathy (DR), smoking, and body mass Index (BMI). However, most of the aforementioned studies are cross-sectional, and the sample sizes are very limited, so the strength of causal reasoning is relatively low. The current study systematically evaluated DPN's influencing factors in patients with type 2 diabetes using evidence-based medicine. Overall, 16 included studies (14 cross-sectional studies and 2 case-control studies including 12,116 cases) that conformed to the present criteria were included in the final analysis. The results suggested that the duration of diabetes (MD 2.5, 95% CI 1.71~3.29), age (MD 4.00, 95% CI 3.05~4.95), HbA1c (MD 0.48, 95% CI 0.33~0.64), and DR (OR 2.34, 95% CI 1.74~3.16) are associated with significantly increased risks of DPN among diabetic patients, while BMI, smoking, total triglyceride (TG), and total cholesterol (TC) did not indicate any risks of increasing DPN. The findings provide a scientific basis for a further understanding of the causes of type 2 diabetes complicated with peripheral neuropathy and the improvement of preventive strategies. The next step is to conduct further high-quality prospective cohort studies to validate this paper's findings.
| S-EPMC6382168 | biostudies-literature
Project description:BACKGROUND:Paclitaxel induced peripheral neuropathy (PIPN) is a major debilitating side effect of paclitaxel in patients with breast cancer with no fully known mechanisms. The aim of the study was to find out the possible risk factors for PIPN. METHODS:Eligible patients with node positive breast cancer undergoing chemotherapy with paclitaxel were assessed. They belonged to an initial randomized controlled trial in which the effectiveness of omega-3 fatty acids in preventing and reducing severity of PIPN was evaluated (protocol ID: NCT01049295). Reduced total neuropathy score (r-TNS) was used for measuring PIPN. All analyses were performed adjusting for intervention effect. The association between age, BMI, BSA, pathological grade, molecular biomarkers and PIPN was evaluated. RESULTS:Fifty-seven patients with breast cancer were investigated. Age was significantly associated with risk of PIPN (RR:1.50, P value?=?.024). Body mass index and BSA had significant association with severity of PIPN (B:1.28, P?=?.025; and B: 3.88, P?=?.010 respectively). Also, BSA showed a significant association with the risk of PIPN (RR: 2.28, P?=?.035; B: 3.88, P?=?.035). Incidence and severity of PIPN were much more pronounced in progesterone receptor positive (PR+) patients (RR:1.88, P?=?.015 and B:1.54, P?=?.012). Multivariate analysis showed that age and the status of PR+ were independent risk factor for incidence and the status of PR+ was the only independent risk factor for severity of PIPN. CONCLUSION:Age, BSA and the status of PR+, should be considered as the risk factors for PIPN before commencement of chemotherapy with paclitaxel in patients with breast cancer. Older patients, those with greater BSA and PR+ patients may need closer follow up and more medical attention due to greater incidence and severity of PIPN.
| S-EPMC6173931 | biostudies-literature
Project description:Genetic risk factors for chemotherapy-induced peripheral neuropathy (CIPN), a major dose-limiting side-effect of paclitaxel, are not well understood. We performed a genome-wide association study (GWAS) in 183 paclitaxel-treated patients to identify genetic loci associated with CIPN assessed via comprehensive neuropathy phenotyping tools (patient-reported, clinical and neurological grading scales). Bioinformatic analyses including pathway enrichment and polygenic risk score analysis were used to identify mechanistic pathways of interest. In total, 77% of the cohort were classified with CIPN (n = 139), with moderate/severe neuropathy in 36%. GWAS was undertaken separately for the three measures of CIPN. GWAS of patient-reported CIPN identified 4 chromosomal regions that exceeded genome-wide significance (rs9846958, chromosome 3; rs117158921, chromosome 18; rs4560447, chromosome 4; rs200091415, chromosome 10). rs4560447 is located within a protein-coding gene, LIMCH1, associated with actin and neural development and expressed in the dorsal root ganglia (DRG). There were additional risk loci that exceeded the statistical threshold for suggestive genome-wide association (P < 1 × 10-5) for all measures. A polygenic risk score calculated from the top 46 ranked SNPs was highly correlated with patient-reported CIPN (r2 = 0.53; P = 1.54 × 10-35). Overlap analysis was performed to identify 3338 genes which were in common between the patient-reported CIPN, neurological grading scale and clinical grading scale GWAS. The common gene set was subsequently analysed for enrichment of gene ontology (GO) and Reactome pathways, identifying a number of pathways, including the axon development pathway (GO:0061564; P = 1.78 × 10-6) and neuronal system (R-HSA-112316; adjusted P = 3.33 × 10-7). Our findings highlight the potential role of axon development and regeneration pathways in paclitaxel-induced CIPN.
| S-EPMC9724416 | biostudies-literature
Project description:Chemotherapy is a common treatment for breast cancer (BrCa) and can cause chemotherapy-induced peripheral neuropathy (CIPN). CIPN contributes to falls, and is thus a potential risk factor for nontraumatic fractures (NTFx); yet, the effect of CIPN on NTFx risk has not been examined for BrCa survivors. We therefore investigated the association between CIPN and NTFx in BrCa survivors. Data were extracted from Optum's Deidentified Clinformatics® Data Mart Database years 2010-2015 in this retrospective cohort study. Among women, three groups were derived based on BrCa and CIPN status: BrCa+/CIPN+ (primary group of interest), BrCa+/CIPN- (first comparison group), and BrCa-/CIPN- (second comparison group). After propensity score matching the comparison groups to BrCa+/CIPN+ at a ratio of 1:11 (BrCa:control) for demographics, osteoporosis, glucocorticoid medication, comorbidities, and cancer-related variables for BrCa+/CIPN-, 1-year incidence rate (IR) of NTFx was determined for each group. The incident rate ratio (IRR) determined if the IR for NTFx was different for BrCa+/CIPN+ compared to BrCa+/CIPN- and BrCa-/CIPN-. Cox proportional hazards regression models estimated the hazard ratios (HRs) after adjusting for covariates that were unable to be matched for. The crude IR (95% confidence interval [CI]) of NTFx was 4.54 (2.32-6.77) for BrCa+/CIPN+ (n = 359), 2.53 (2.03-3.04) for BrCa+/CIPN- (n = 3949), and 1.76 (1.35-2.18) for BrCa-/CIPN- (n = 3949). The crude IRR of NTFx was significantly elevated for BrCa+/CIPN+ as compared to BrCa+/CIPN- (IRR = 1.80; 95% CI, 1.06-3.05) and BrCa-/CIPN- (IRR = 2.58; 95% CI, 1.50-4.44). The elevated rate of NTFx for BrCa+/CIPN+ remained unchanged after adjusting for aromatase inhibitors compared to BrCa+/CIPN- (HR = 1.79; 95% CI, 1.06-3.04). Female BrCa survivors have an increased 1-year IR of NTFx after the onset of CIPN, suggesting that CIPN is an additive burden on NTFx risk among BrCa survivors. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
| S-EPMC8328798 | biostudies-literature
Project description:Poly(N-isopropyl acrylamide) (pNIPAM) is one of the most popular stimulus-responsive polymers for research. It is especially of great interest in the field of tissue engineering. While it is known that the NIPAM monomer is toxic, there is little conclusive research on the cytotoxicity of the polymer. In this work, the relative biocompatibility of the NIPAM monomer, pNIPAM, and pNIPAM-coated substrates prepared using different polymerization (free radical and plasma polymerization) and deposition (spin coating and plasma polymerization) techniques was evaluated using appropriate cytotoxicity tests (MTS, Live/Dead, plating efficiency). Four different mammalian cell types (endothelial, epithelial, smooth muscle, and fibroblasts) were used for the cytotoxicity testing. The pNIPAM-coated surfaces were evaluated for their thermoresponse and surface chemistry using X-ray photoelectron spectroscopy and goniometry. We found that while cell viability on pNIPAM surfaces decreases when compared to controls, the viability also seems to be deposition type dependent, with sol-gel based pNIPAM surfaces being the least biocompatible. Long term experiments proved that all pNIPAM-coated surfaces were not cytotoxic to the four cell types evaluated in a direct contact test. Plating efficiency experiments did not show cytotoxicity. Cellular sensitivity to pNIPAM and to the NIPAM monomer varied depending on cell type. Endothelial cells consistently showed decreased viability after 48 hours of exposure to pNIPAM extracts and were more sensitive than the other cell lines to impurities in the polymer.
| S-EPMC3979476 | biostudies-literature
Project description:Background: Pain secondary to chemotherapy-induced peripheral neuropathy (CIPN) can limit the administration of chemotherapy, cancer-treatment outcomes, and the quality of life of patients. Oxidative stress and inflammation are some of the key mechanisms involved in CIPN. Successful treatments for CIPN are limited. This report shows our preliminary experience using ozone treatment as a modulator of oxidative stress in chronic pain secondary to CIPN. Methods: Ozone treatment, by rectal insufflation, was administered in seven patients suffering from pain secondary to grade II or III CIPN. Pain was assessed by the visual analog scale (VAS). Results: All patients, except one, showed clinically relevant pain improvement. Median pain score according to the VAS was 7 (range: 5-8) before ozone treatment, 4 (range: 2-6) at the end of ozone treatment (p = 0.004), 5.5 (range: 1.8-6.3) 3 months after the end of ozone treatment (p = 0.008), and 6 (range: 2.6-6.6) 6 months after the end of ozone treatment (p = 0.008). The toxicity grade, according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0), improved in half of the patients. Conclusion: This report shows that most patients obtained clinically relevant and long-lasting improvement in chronic pain secondary to CIPN after treatment with ozone. These observed effects merit further research and support our ongoing randomized clinical trial (NCT04299893).
| S-EPMC9468657 | biostudies-literature
Project description:BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect that worsens quality of life and increases the risk of falls in cancer survivors. Evidence of yoga's safety and efficacy in treating CIPN is lacking.MethodsIn a randomized controlled study, we assigned breast and gynecological cancer survivors with persistent moderate-to-severe CIPN pain, numbness, or tingling with a score of 4 or greater (0-10 numeric rating scale [NRS]) for at least 3 months after chemotherapy to 8 weeks of usual care or yoga focused on breathwork and musculoskeletal conditioning. Primary endpoint was treatment arm differences for NRS, and secondary endpoints were Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx), and Functional Reach Test after week 8. We tested treatment arm differences for each outcome measure using linear mixed models with treatment-by-time interactions. All statistical tests were two-sided.ResultsWe randomly assigned 41 participants into yoga (n = 21) or usual care (n = 20). At week 8, mean NRS pain decreased by 1.95 points (95% confidence interval [CI] = -3.20 to -0.70) in yoga vs 0.65 (95% CI = -1.81 to 0.51) in usual care (P = .14). FACT/GOG-Ntx improved by 4.25 (95% CI = 2.29 to 6.20) in yoga vs 1.36 (95% CI = -0.47 to 3.19) in usual care (P = .035). Functional reach, an objective functional measure predicting the risk of falls, improved by 7.14 cm (95% CI = 3.68 to 10.59) in yoga and decreased by 1.65 cm (95% CI = -5.00 to 1.72) in usual care (P = .001). Four grade 1 adverse events were observed in the yoga arm.ConclusionAmong breast and gynecological cancer survivors with moderate-to-severe CIPN, yoga was safe and showed promising efficacy in improving CIPN symptoms.
| S-EPMC7666827 | biostudies-literature
Project description:ObjectiveDiabetic large-nerve fiber dysfunction, as measured by vibration perception threshold (VPT), predicts foot ulceration, amputation, and mortality. Thus, determination of modifiable risk factors is of great clinical importance.Research design and methodsWe assessed 1,407 patients with type 1 diabetes and a normal VPT participating in the EURODIAB Prospective Complications Study, at baseline mean +/- SD age of 32.7 +/- 10.2 years with diabetes duration of 14.7 +/- 9.3 years and follow-up of 7.3 +/- 0.6 years. VPT was measured using biothesiometry on the right big toe and medial malleolus. An abnormal result was defined as >2 SD from the predicted mean for the patient s age.ResultsAn abnormal VPT was associated with an increased incidence of gangrene, amputation, foot ulceration, leg bypass or angioplasty, and mortality (P < OR = 0.02). The incidence of abnormal VPT was 24% over the 7.3-year follow-up. Duration of diabetes and A1C significantly influenced the incidence of abnormal VPT (P < 0.0001). After correction for these, established risk factors for cardiovascular disease (CVD), including male sex (P = 0.0004), hypertension (P < 0.0001), total cholesterol (P = 0.002), LDL cholesterol (P = 0.01), smoking (P < 0.0001), weight (P < 0.0001), and diabetes complications (retinopathy [P = 0.0001], nephropathy [P = 0.01], and autonomic neuropathy [P = 0.001]), were all found to be significant risk factors. A previous history of CVD doubled the incidence of abnormal VPT.ConclusionsThis prospective study indicates that cardiovascular risk factors predict development of large-fiber dysfunction, which may account for the high mortality rate in patients with an abnormal VPT, and emphasizes the importance of early determination of VPT to detect subclinical neuropathy and to address cardiovascular risk factors.
| S-EPMC2752908 | biostudies-literature
Project description:Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with chemotherapy, but researchers rarely study its risk factors, fall risk, and prevalence in long-term breast cancer survivors. We aimed to determine CIPN prevalence, risk factors, and association with psychological distress and falls among long-term breast cancer survivors. We conducted Cross-sectional analyses among postmenopausal women with a history of stage I-III breast cancer who received taxane-based chemotherapy. Participants reported neuropathic symptoms of tingling/numbness in hands and/or feet on a 0-10 numerical rating scale. We conducted multivariate logistic regression analyses to evaluate risk factors associated with the presence of CIPN and the relationship between CIPN and anxiety, depression, insomnia, and patient-reported falls. Among 296 participants, 173 (58.4 %) reported CIPN symptoms, 91 (30.7 %) rated their symptoms as mild, and 82 (27.7 %) rated them moderate to severe. Compared with women of normal weight, being obese was associated with increased risk of CIPN (adjusted OR 1.94, 95 % CI: 1.03-3.65). Patients with CIPN reported greater insomnia severity, anxiety, and depression than those without (all p < 0.05). Severity of CIPN was associated with higher rates of falls, with 23.8, 31.9, and 41.5 % in the "no CIPN," "mild," and "moderate-to-severe" groups, respectively, experiencing falls (p = 0.028). The majority of long-term breast cancer survivors who received taxane-based chemotherapy reported CIPN symptoms; obesity was a significant risk factor. Those with CIPN also reported increased psychological distress and falls. Interventions need to target CIPN and comorbid psychological symptoms, and incorporate fall prevention strategies for aging breast cancer survivors.
| S-EPMC5509538 | biostudies-literature