5 research outputs found
Evaluating changes in reactive oxygen species (ROS) as a plausible mechanism underlying the effect of noise on dopamine release
Excessive exposure to noise has been implicated in hearing loss but the mechanism by which this happens remains unknown. Dopamine, an important neurotransmitter involved in learning and reward-related behaviors has also been reported in the central auditory pathways, suggesting its role in auditory processes. For example, dopamine is found in the inferior colliculus, a principal integration center for auditory responses, and is reported to modulate auditory processes. A recent study has shown that loud noise exposure decreases gene expression for tyrosine hydroxylase (a rate-limiting enzyme in the synthesis of dopamine) in the inferior colliculus, implying diminished dopamine levels. On another hand, excessive production of reactive oxygen species (ROS) is a major contributor to noise-induced hearing loss. ROS can also modulate neuronal processes, including synaptic dopamine release. Thus, we hypothesize that loud noise would trigger overproduction of ROS and in turn attenuate dopamine release in the inferior colliculus. The present work evaluates changes in the ROS, hydrogen peroxide (H2O2) as a plausible mechanism underlying the effect of noise on the dopamine system in the inferior colliculus. Following noise exposure (118 dB sound pressure level at 1/3 octave band for four hours) synaptic changes in H2O2 were assessed with fast-scan cyclic voltammetry (FSCV) in brain slices from adult Sprague Dawley rats and compared to their controls (triangular waveform at a carbon-fiber microelectrode surface between +0.2 V and +1.3 V at a scan rate of 400 V/s). Furthermore, intracellular changes in H2O2 was evaluated using H2O2 assay (National Diagnostics) following noise exposure. Overall, the combination of FSCV and H2O2 assay revealed changes that suggest ROS mediates noise induced alterations in the dopamine system in the inferior colliculus
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
EVALUATING CHANGES IN REACTIVE OXYGEN SPECIES (ROS) AS A PLAUSIBLE MECHANISM UNDERLYING THE EFFECT OF NOISE ON THE DOPAMINE SYSTEM IN THE HUB FOR CENTRAL AUDITORY PROCESSES
Excessive exposure to noise leads to hearing loss but the mechanism by which this happens remains unknown. Presently, dopamine, a neurotransmitter widely known for its involvement in learning and reward-based actions, has also been linked to auditory processes in the inferior colliculus, a principal integration center for hearing and related processes. Preliminary data from our research laboratory, has demonstrated that exposure to deafening noise leads to decreased dopamine release in the inferior colliculus, thus implicating the dopamine system in hearing loss. One plausible mechanism underlying this noise-induced alteration in dopamine neurotransmission could be via excessive production of reactive oxygen species (ROS). Reactive oxygen species can also modulate synaptic transmission. Thus, we hypothesize that loud noise would trigger overproduction of ROS, specifically hydrogen peroxide (H2O2) and in turn attenuate dopamine release in the inferior colliculus. Since excessive production of H2O2 could result in the depletion of adenosine triphosphate (ATP), we also evaluate the effect of the noise exposure on ATP levels. In order to determine the effect of deafening noise on proteins that regulate dopamine synthesis, we analyze biometals that act as prosthetic groups and may be involved in protein coordination and neurotransmission. The present work utilizes colorimetric assays and XRF analysis to examine changes in H2O2, ATP and biometal concentrations of Fe, Ca, K and Zn in the inferior colliculus of adult Sprague Dawley rats following exposure to loud noise. Finally, we explore the possibility of minimizing the effect of noise through antioxidant (α-lipoic acid) administration (50 mg/kg -I. P). The results of this study demonstrate that loud noise significantly increases the production of H2O2 (p \u3c 0.0001, n = 10 rats/group). However, the noise exposure had no significant effect on ATP levels (p = 0.5850, 10 rats/group). Furthermore, noise exposure caused a significant increase in Fe, Ca and K levels (n = 5 rats/group). The administration of the antioxidant, α-lipoic acid reduced the concentration of H2O2 in the noise exposed group (p \u3c 0.0001, n = 9 rats/group) and restores biometal concentration for Fe, Ca and K (n = 5 rats/group) to levels comparable with the control but has no effect on ATP. These results expand our understanding on the involvement of dopamine in deafness related changes in the inferior colliculus and open doors to further explore neural mechanisms underlying dopamine’s involvement in hearing