ABSTRACT
BACKGROUND AND PURPOSE: A real-time biomarker in chemotherapy-induced peripheral neurotoxicity (CIPN) would be useful for clinical decision-making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN. METHODS: This single-center prospective observational longitudinal study included patients treated with paclitaxel (TX; n = 34), brentuximab vedotin (BV; n = 29), or oxaliplatin (PT; n = 19). All patients were assessed using the Total Neuropathy Score-clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6-12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa® analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2. RESULTS: Eighty-two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR-CIPN, respectively, without differences among them (p = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents (p < 0.001). CONCLUSIONS: A variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.
Subject(s)
Antineoplastic Agents , Neurofilament Proteins , Neurotoxicity Syndromes , Peripheral Nervous System Diseases , Humans , Female , Male , Middle Aged , Neurofilament Proteins/blood , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/blood , Aged , Adult , Antineoplastic Agents/adverse effects , Longitudinal Studies , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/etiology , Prospective Studies , Biomarkers/blood , Oxaliplatin/adverse effects , Paclitaxel/adverse effectsABSTRACT
ABSTRACT: We present the case of a 65-year-old patient who was treated with high-dose benzylpenicillin for severe invasive pneumococcal pneumonia, complicated by acute renal failure managed with continuous venovenous hemofiltration. After cessation of continuous venovenous hemofiltration, the patient experienced multiple tonic-clonic seizures. Therapeutic drug monitoring revealed high total serum concentrations of benzylpenicillin, identifying it as the likely cause of the neurotoxicity. This case study presents the first documented total serum benzylpenicillin concentration associated with neurotoxicity.
Subject(s)
Anti-Bacterial Agents , Critical Illness , Drug Monitoring , Neurotoxicity Syndromes , Penicillin G , Humans , Aged , Drug Monitoring/methods , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacokinetics , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/blood , Male , Continuous Renal Replacement Therapy/methods , Acute Kidney Injury/therapy , Acute Kidney Injury/chemically induced , Pneumonia, Pneumococcal/drug therapy , Pneumonia, Pneumococcal/complications , Hemofiltration/methodsABSTRACT
Oxaliplatin (L-OHP), a third-generation platinum-based anti-tumor drug, finds widespread application in the first-line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L-OHP-induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high-sensitivity, high-throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra-performance liquid chromatography-high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers.
Subject(s)
Metabolomics , Oxaliplatin , Humans , Male , Female , Middle Aged , Antineoplastic Agents/blood , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/blood , Peripheral Nervous System Diseases/metabolism , Chromatography, High Pressure Liquid , Aged , Biomarkers/blood , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/diagnosisABSTRACT
PURPOSE: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure. METHODS: This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed. RESULTS: A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported. CONCLUSION: Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study.
Subject(s)
Anesthesia, Dental , Anesthesia, General , Biomarkers , Caspase 3 , Feasibility Studies , Neurotoxicity Syndromes , Phosphopyruvate Hydratase , S100 Calcium Binding Protein beta Subunit , Humans , Biomarkers/blood , Prospective Studies , Anesthesia, General/adverse effects , Child , Child, Preschool , Caspase 3/blood , Male , Female , Phosphopyruvate Hydratase/blood , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/diagnosis , Anesthesia, Dental/methods , S100 Calcium Binding Protein beta Subunit/blood , Neurofilament Proteins/bloodABSTRACT
Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits.
Subject(s)
Biomarkers , Erythrocytes , Manganese , Neurotoxicity Syndromes , Animals , Erythrocytes/drug effects , Erythrocytes/metabolism , Manganese/blood , Manganese/toxicity , Manganese/urine , Biomarkers/blood , Biomarkers/urine , Male , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/blood , Rats , Humans , Manganese Poisoning/blood , Rats, Sprague-Dawley , Occupational Exposure/adverse effects , FemaleABSTRACT
Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.
Subject(s)
Child Behavior Disorders/diagnosis , Environmental Pollutants/adverse effects , Metals, Heavy/adverse effects , Neurotoxicity Syndromes/diagnosis , Child , Child Behavior/drug effects , Child Behavior Disorders/blood , Child Behavior Disorders/chemically induced , Child Behavior Disorders/urine , Cross-Sectional Studies , Environmental Exposure/adverse effects , Environmental Pollutants/analysis , Environmental Pollution/adverse effects , Humans , Italy , Male , Metals, Heavy/analysis , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/urineABSTRACT
People who drink water contaminated with arsenic for a long time develop neuritis, cerebellar symptoms, and deficits in memory and intellectual function. Arsenic induces oxidative stress and promotes apoptosis through multiple signalling pathways in nerve cells. Neuroglobin (Ngb), as a key mediator, is considered to be protective against oxidative stress. In this study, we aimed to study the effects of Ngb knockdown in arsenite-treated rat neurons on levels of apoptosis markers and reactive oxygen species and serum Ngb levels of subjects from arsenic-endemic regions in China. We discovered that arsenic-induced apoptosis and reactive oxygen species production were enhanced in Ngb-knocked-down rat neurons. Silencing of Ngb aggravated the arsenic-induced decrease in the rate of Bcl-2/Bax and the levels of Bcl-2 protein following arsenite treatment. The results also showed that serum Ngb levels were independently negatively correlated with arsenic concentration in drinking water. Furthermore, the serum Ngb levels of four groups (245 individuals) according to different degree exposure to arsenic were 815.18 ± 89.52, 1247.97 ± 117.18, 774.79 ± 91.55, and 482.72 ± 49.30 pg/mL, respectively. Taken together, it can be deduced that Ngb has protective effects against arsenic-induced apoptosis by eliminating reactive oxygen species.
Subject(s)
Arsenic/toxicity , Neuroglobin/blood , Neurons/drug effects , Water Pollutants, Chemical/toxicity , Aged , Animals , Apoptosis/drug effects , Arsenic/analysis , Cells, Cultured , Female , Humans , Male , Middle Aged , Neuroglobin/genetics , Neurons/metabolism , Neurotoxicity Syndromes/blood , Oxidative Stress/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Small Interfering/genetics , Rats , Reactive Oxygen Species/metabolism , Water Pollutants, Chemical/analysisABSTRACT
Cardio- and neurotoxicity of amphetamines play an important role in worsening morbidity, making the initial evaluation of the patient's status a potentially lifesaving action. The current study hypothesized that the S-100ß serum level could predict the severity of acute amphetamine toxicity and the in-hospital outcome. The current study is a prospective cohort study conducted on 77 patients diagnosed with acute amphetamine exposure and referred to Aseer Poison Control Center, Saudi Arabia. The patients admitted to ICU showed significantly higher serum levels of S-100ß in comparison to those not admitted (p < 0.05). Moreover, the S-100ß level was significantly elevated among patients with prolonged QTc intervals. Receiver-operating characteristic curve of S-100ß serum level as an in-hospital outcome predictor showed that at a cutoff value > 0.430 ug/L, the sensitivity of S-100ß serum level as severity predictor was 100%, and the specificity was 74.1%. In conclusion, the current study revealed that the S-100ß serum level could be used as an outcome predictor in hospital admission cases due to toxic amphetamine exposure and offers an idea about the cardiac and neuronal involvement. This can help select patients who will benefit most from ICU admission and early management and assess the severity of cases in settings where GC-MS is not available.
Subject(s)
Amphetamine/adverse effects , Central Nervous System Stimulants/adverse effects , Heart Diseases/blood , Neurotoxicity Syndromes/blood , S100 Calcium Binding Protein beta Subunit/blood , Adolescent , Adult , Biomarkers/blood , Cardiotoxicity , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Gas Chromatography-Mass Spectrometry , Heart Diseases/diagnosis , Heart Diseases/etiology , Heart Diseases/therapy , Hospitalization , Humans , Male , Middle Aged , Neurotoxicity Syndromes/diagnosis , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/therapy , Predictive Value of Tests , Prognosis , Prospective Studies , Saudi Arabia , Up-Regulation , Young AdultSubject(s)
Atropine/therapeutic use , Chlormequat/poisoning , Muscarinic Antagonists/therapeutic use , Neurotoxicity Syndromes/drug therapy , Plant Growth Regulators/poisoning , Poisoning/drug therapy , Accidents , Aged , Chlormequat/pharmacokinetics , Humans , Male , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/diagnosis , Neurotoxicity Syndromes/etiology , Plant Growth Regulators/pharmacokinetics , Poisoning/blood , Poisoning/diagnosis , Recovery of Function , Treatment OutcomeABSTRACT
OBJECTIVE: Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as 'pseudoatrophy', related to reduced inflammation. Treatment-related neurotoxicity may be contributory. We sought objective evidence of post-IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. METHODS: Sera were collected from 22 MS patients pre- and post-IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single-molecule assay. RESULTS: Pre-IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12-month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). INTERPRETATION: There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.
Subject(s)
Glial Fibrillary Acidic Protein/blood , Gray Matter/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Multiple Sclerosis , Neurofilament Proteins/blood , Neurotoxicity Syndromes , Adult , Atrophy/pathology , Clinical Trials, Phase II as Topic , Female , Gray Matter/diagnostic imaging , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/pathology , Multiple Sclerosis/therapy , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/pathology , Treatment Outcome , Young AdultABSTRACT
Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a severe and long-lasting side effect of anticancer therapy, which can severely impair patients' quality of life. It is a sensory and length-dependent neuropathy, which predominantly affects large myelinated fibers. Easy and reliable monitoring of CIPN in patients is still an unmet clinical need. Since increasing clinical evidence supports the potential use of neurofilament light chain (NfL) as a biomarker of axonal injury, in this study we measured serum NfL levels in animals chronically treated with cisplatin (CDDP) and paclitaxel (PTX), two antineoplastic drugs with different neuronal targets. Wistar rats were treated with CDDP (2 mg/kg i.p. twice/week for 4 weeks) or PTX (10 mg/kg i.v. once/week for 4 weeks). Repeated serum NfL quantification was obtained using the Single Molecule Array (Simoa) technology. The onset and progression of peripheral neurotoxicity were evaluated through neurophysiology, morphological assessments and intraepidermal nerve fibers density quantification. Our results showed that serum NfL measurements correlated with the severity of axonal damage. In fact, both treatments induced serum NfL increase, but higher levels were evidenced in PTX-treated animals, compared with CDDP-treated rats, affected by a milder neurotoxicity. Notably, also the timing of the NfL level increase was associated with the severity of morphological and functional alterations of axonal structure. Therefore, NfL could be a useful biomarker for axonal damage in order to follow the onset and severity of axonal degeneration and possibly limit the occurrence of serious PNS disease.
Subject(s)
Antineoplastic Agents , Axons/metabolism , Cisplatin , Neurofilament Proteins/blood , Neurotoxicity Syndromes/blood , Paclitaxel , Peripheral Nerves/metabolism , Peripheral Nervous System Diseases/blood , Animals , Axons/pathology , Biomarkers/blood , Disease Models, Animal , Female , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/pathology , Peripheral Nerves/pathology , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/pathology , Rats, Wistar , Severity of Illness Index , Up-RegulationABSTRACT
RATIONALE: Methylenedioxymethamphetamine (MDMA) and methcathinone (MCAT) are abused psychostimulant drugs that produce adverse effects in human users that include hepatotoxicity and death. Recent work has suggested a connection between hepatotoxicity, elevations in plasma ammonia, and brain glutamate function for methamphetamine (METH)-induced neurotoxicity. OBJECTIVES: These experiments investigated the effect of ambient temperature on the toxicity and lethality produced by MDMA and MCAT in mice, and whether these effects might involve similar mechanisms to those described for METH neurotoxicity. RESULTS: Under low (room temperature) ambient temperature conditions, MDMA induced hepatotoxicity, elevated plasma ammonia levels, and induced lethality. Under the same conditions, even a very high dose of MCAT produced limited toxic or lethal effects. High ambient temperature conditions potentiated the toxic and lethal effects of both MDMA and MCAT. CONCLUSION: These studies suggest that hepatotoxicity, plasma ammonia, and brain glutamate function are involved in MDMA-induced lethality, as has been shown for METH neurotoxicity. The toxicity and lethality of both MDMA and MCAT were potentiated by high ambient temperatures. Although an initial mouse study reported that several cathinones were much less toxic than METH or MDMA, the present results suggest that it will be essential to assess the potential dangers posed by these drugs under high ambient temperatures.
Subject(s)
Central Nervous System Stimulants/toxicity , Hot Temperature , N-Methyl-3,4-methylenedioxyamphetamine/toxicity , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/mortality , Propiophenones/toxicity , Ammonia/blood , Animals , Brain/drug effects , Brain/metabolism , Disease Models, Animal , Female , Glutamic Acid/metabolism , Male , Methamphetamine/toxicity , Mice , Mice, Inbred C57BL , Neurotoxicity Syndromes/blood , Signal Transduction/drug effects , Substance-Related Disorders/mortalityABSTRACT
Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholinesterase activity and hematological and biochemical alterations in agriculture workers. In continuation with that, the present study aimed to investigate the pesticide-induced neurochemical imbalance and its association with behavior alterations in agricultural workers. A significant increase in depressive symptoms, assessed by the Beck Depression Inventory-II was observed in pesticide exposed workers as compared to the unexposed. A decrease in the level of dopamine in plasma and levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acids, norepinephrine, serotonin, and hydroxyindoleacetic acid in urine was also observed. An increase in the levels of MAO-A and MAO-B has also been observed in these individuals. The decreased levels of neurotransmitters in the blood and urine have been linked with increased levels of MAO and pesticide residues in plasma and urine. Furthermore, these changes were associated with a higher incidence of depression in agricultural workers.
Subject(s)
Depression/chemically induced , Farmers , Neurotoxicity Syndromes/etiology , Occupational Exposure , Pesticide Residues/toxicity , Adolescent , Adult , Aged , Biomarkers/blood , Biomarkers/urine , Depression/blood , Depression/epidemiology , Depression/urine , Dopamine/blood , Dopamine/urine , Female , Humans , Incidence , India/epidemiology , Male , Middle Aged , Monoamine Oxidase/blood , Monoamine Oxidase/urine , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/epidemiology , Neurotoxicity Syndromes/urine , Neurotransmitter Agents/blood , Neurotransmitter Agents/urine , Pesticide Residues/blood , Pesticide Residues/urine , Young AdultABSTRACT
PURPOSE: The aim of this study was to investigate the demographic and clinical characteristics and treatment modalities of elderly patients with carbon monoxide (CO) intoxication. The secondary aim was to evaluate the importance of plasma lactate values in the diagnosis of acute CO intoxication in geriatric patients. METHODS: Data on geriatric patients who were admitted to the emergency department of Atatürk University Medical Faculty between January 2013 and April 2016 were analyzed retrospectively. RESULTS: Of the 197 cases included in the study, 97 were in the intoxication group and 100 were in the control group; 82.5% of the intoxication cases had mild neurological symptoms and 17.5% had severe neurological symptoms. Carboxyhemoglobin levels were significantly higher in patients with severe neurological symptoms (p = 0.031). All patients with severe neurological symptoms received hyperbaric-oxygen therapy (p < 0.001). In the intoxication group, lactate levels were significantly higher than in the control group (p = 0.001). The specificity for lactate 4 mmol/L and above was found as 98.0% with a positive predictive value and negative predictive value of 84.5% and 53.3%, respectively. CONCLUSION: High initial lactate levels may be a guide for cases with nonspecific symptoms in geriatric patients with suspected CO intoxication.
Subject(s)
Carbon Monoxide Poisoning/blood , Carboxyhemoglobin/analysis , Lactic Acid/blood , Neurotoxicity Syndromes/blood , Aged , Aged, 80 and over , Carbon Monoxide Poisoning/diagnosis , Emergency Service, Hospital , Female , Hospitalization , Humans , MaleABSTRACT
We aimed to explore the possible neurotoxicity and infertility mechanisms of prolonged metronidazole (MTZ) use and the effects of antioxidant grapefruit (GP) co-therapy on MTZ-induced complications. Sixty male albino Wistar rats were divided into four groups (n = 15 each). Group I (control group) received 1% dimethyl sulfoxide (27 ml/ kg/day), group II (MTZ group) received MTZ (400 mg/kg/day), group III (MTZ + GP) received MTZ (400 mg/kg/ day) plus GP juice (27 ml/kg/ day) and group IV (GP group) received GP juice (27 ml/kg) for 60 days. Semen analyses were performed. Free testosterone, gonadotrophin (follicle-stimulating hormone (FSH) and luteinizing hormone) and thiamine levels were measured. Samples of cerebellar, testicular and epididymal tissues were used for both colorimetric assays of oxidative stress markers and histopathological examinations. Significant decreases in the sperm count, percent total sperm motility, serum thiamine levels, free testosterone levels and FSH levels were observed in the MTZ and MTZ + GP groups (p < 0.05 for all parameters). Significantly higher oxidative stress levels (p < 0.05) were observed in the cerebellar and testicular tissue homogenates of these groups than in those of the control group, and associated disruptions in the cerebellar, testicular and epididymal structures were apparent compared to those of the control group. Although the GP group showed a significantly higher sperm count and significantly lower oxidative stress than the control group (p < 0.05), with histological similarity to the control group, the GP group exhibited significantly higher prolactin levels and lower free testosterone and FSH levels than the control group (p < 0.05). Oxidative stress and decreased thiamine levels could explain the MTZ-induced neurotoxicity and infertility side effects that aggravated by GP co-administration.
Subject(s)
Anti-Infective Agents/toxicity , Citrus paradisi , Food-Drug Interactions , Fruit and Vegetable Juices , Infertility/chemically induced , Metronidazole/toxicity , Neurotoxicity Syndromes , Thiamine Deficiency/chemically induced , Animals , Cerebellum/drug effects , Cerebellum/pathology , Epididymis/drug effects , Epididymis/pathology , Hormones/blood , Infertility/blood , Infertility/pathology , Male , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/pathology , Oxidative Stress/drug effects , Rats, Wistar , Sperm Count , Spermatozoa/drug effects , Testis/drug effects , Testis/pathology , Thiamine Deficiency/blood , Thiamine Deficiency/pathologyABSTRACT
BACKGROUND: Delayed neurological sequels (DNS) have been described after carbon monoxide (CO) poisoning. There is a need to find a new prognostic marker to guide the use of hyperbaric oxygen (HBO) therapy. AIM: To evaluate serum S-100ß level in patients presenting with acute CO poisoning as an indicator of poisoning severity and predictor of DNS occurrence and HBO need in those patients. METHODS: This prospective cohort study included patients with acute CO poisoning. On admission, carboxyhemoglobin (COHb) and S-100ß levels were measured. Patients were followed up for 6 months for signs of DNS. RESULTS: Out of 50 patients, 6 only developed DNS. The mean of S-100ß levels was significantly higher in patients with severe poisoning and those with DNS. Receiver operating characteristic curve analysis revealed that S-100ß had an area under the curve 0. 871; at a cutoff value ≥ 0.67 µg/L, its sensitivity and specificity were 100% and 77.3%, respectively. The sensitivity of S-100ß was significantly higher than that of COHb, while its specificity and overall accuracy were significantly higher than those of HBO criteria. CONCLUSION: Serum S-100ß level on admission could be a marker of poisoning severity and a predictor of CO-induced DNS development that guides the use of HBO therapy.
Subject(s)
Carbon Monoxide Poisoning/blood , Carbon Monoxide Poisoning/therapy , Hyperbaric Oxygenation , Neurotoxicity Syndromes/blood , S100 Calcium Binding Protein beta Subunit/blood , Adolescent , Adult , Biomarkers/blood , Carboxyhemoglobin/analysis , Female , Humans , Male , Middle Aged , ROC Curve , Severity of Illness Index , Young AdultABSTRACT
The pancreatic enzymes lipase and amylase serve important functions in digestion/absorption of fats and polysaccharides. Measurement of these enzymes is often used in the emergency department to rule out acute pancreatitis in patients with nonspecific abdominal pain. In acute pancreatitis, serial measurements of plasma lipase and amylase typically follow a predictable temporal pattern of rise-and-fall kinetics: lipase levels rise within 4 to 8 hours, crest at 2× to 50× the upper reference limit at 24 hours, and decline to normal concentrations in 7 to 14 days. In situations in which the duration and magnitude of pancreatic enzyme elevation are more transient, clinicians should consider alternative causes for enzyme elevation. In this case report, incidental discovery of elevated lipase in an African American baby girl who ingested oxycodone resulted in additional laboratory and radiological work-up. Stronger awareness of exogenous influences on gastrointestinal motility may have prevented the need for further testing in this patient.
Subject(s)
Analgesics, Opioid/poisoning , Lethargy/diagnosis , Lipase/blood , Neurotoxicity Syndromes/diagnosis , Oxycodone/poisoning , Amylases/blood , Amylases/urine , Female , Humans , Infant , Lethargy/blood , Lipase/urine , Neurotoxicity Syndromes/bloodSubject(s)
Aluminum/toxicity , Neurotoxicity Syndromes , Occupational Diseases , Spinal Cord Diseases , Adult , Aluminum/blood , Humans , Male , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/diagnosis , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/physiopathology , Occupational Diseases/blood , Occupational Diseases/chemically induced , Occupational Diseases/diagnosis , Occupational Diseases/physiopathology , Occupational Exposure , Spinal Cord Diseases/blood , Spinal Cord Diseases/chemically induced , Spinal Cord Diseases/diagnosis , Spinal Cord Diseases/physiopathologyABSTRACT
This study aimed to assess the feasibility of using the plasma neutrophil gelatinase-associated lipocalin (NGAL) level at the time of presentation in the emergency department (ED) to predict acute kidney injury (AKI) and the long-term neurological outcomes of acute charcoal-burning carbon monoxide (CO) poisoning. This retrospective study included 260 patients who suffered acute charcoal-burning CO poisoning. The median plasma NGAL concentration at the time of presentation in the ED after acute charcoal-burning CO poisoning was 78 (54-115) ng/ml. The NGAL level was an independent predictor of AKI development and could be used to stratify the severity of AKI. However, the area under the receiver operating characteristic curve (AUC) of the predictive model for AKI that included both the plasma NGAL level and clinical parameters was comparable to that of the predictive model including only the clinical parameters. The plasma NGAL level at the time of presentation in the ED was an independent factor predicting long-term neurological outcomes in patients who did not develop AKI. In these patients, the plasma NGAL level significantly improved the predictive accuracy of the model when used in combination with clinical parameters. In contrast, the plasma NGAL level was not associated with long-term neurological outcomes in patients who developed AKI. Measurement of the plasma NGAL level at the time ED presentation might improve the prediction of long-term neurological outcomes in patients who do not develop AKI after acute charcoal-burning CO poisoning. However, it might not offer additional benefit for AKI prediction compared to previously used markers.
Subject(s)
Acute Kidney Injury/blood , Carbon Monoxide Poisoning/blood , Lipocalin-2/blood , Neurotoxicity Syndromes/blood , Academic Medical Centers , Adult , Aged , Charcoal , Emergency Service, Hospital , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Tertiary Care CentersABSTRACT
INTRODUCTION: A fixed-dose association of bismuth subcitrate, metronidazole and tetracycline (BMT) (Pylera®, Allergan, NJ, USA) was made available in France in 2013 for the eradication of Helicobacter pylori. Due to a historical issue of bismuth encephalopathy, the French Health Authorities requested a study of blood and plasma bismuth concentrations with BMT in daily practice. AIMS: The aim of the study was to measure eventual bismuth accumulation and neurological toxicity in patients prescribed BMT. METHODS: Patients initiating BMT for H. pylori between March 2014 and December 2015 were included. A blood sample was taken before first BMT intake and 24 h after the last intake, for assay of bismuth. A concentration > 50 µg/L was considered abnormal. Neurological complaints were assessed at inclusion, at the end of the 10-day treatment course, and 28 days later. RESULTS: 202 patients were included, of whom 190 took at least one dose of BMT, and 167 provided both required blood samples. Mean blood bismuth concentrations after the BMT course were 16.9 µg/L (95% confidence interval 15.6-18.3). Concentrations were > 50 µg/L (56.0 µg/L and 50.9 µg/L) in two elderly patients, one of whom presented mild, transient memory impairment during treatment. Non-serious neurological symptoms occurred in 20% of all patients and treatment failure was documented in 5% of patients. CONCLUSIONS: In this study measuring blood bismuth concentrations in real-life practice, in < 1% of patients the BMT course resulted in blood bismuth concentrations > 50 µg/L. No serious neurological adverse events were observed. STUDY REGISTRATION: EU-PAS register EUPAS3142 at www.encepp.eu ; ENCePP study seal.