The document describes a study that tested the ability of the antioxidant resveratrol to protect against noise-induced hearing loss in rats. Ten rats were given either resveratrol or a control treatment for 3 weeks before being exposed to loud noise. The results showed that the rats treated with resveratrol had significantly smaller increases in hearing thresholds after noise exposure compared to the control rats, indicating a protective effect of resveratrol against noise-induced hearing damage.
This study investigated the effects of anti-intercellular adhesion molecule-1 antibody (anti-ICAM-1 Ab) on noise-induced hearing loss in rats. Rats were exposed to loud noise and treated with either anti-ICAM-1 Ab or a saline control. Rats treated with anti-ICAM-1 Ab showed less temporary threshold shifts compared to controls after noise exposure. Both groups recovered some hearing ability 72 hours later. Anti-ICAM-1 Ab may protect against noise-induced hearing loss by blocking reactive oxygen species generation caused by noise-induced cochlear damage and inflammation.
The Topic is Radioprotective Efficacy of RK-IP-006 in mammalian system. Experiments performed were Antioxidant assay, SDS-PAGE, Western Blot to check the effect against radiation of 9Gy.
Environmental enrichment reduces seizure frequency in a rodent model of reflex epilepsy. Long Evans rats were primed to develop audiogenic seizures through repeated exposure to loud tones. One group then received environmental enrichment through interaction with objects and other rats, while a control group did not. Rats receiving enrichment showed less severe seizures, with increased latency to seizures, shorter seizure durations, and a reduced occurrence of seizures, showing that environmental enrichment can counteract the progression of seizure disorders in this model.
This study investigated using high-intensity focused ultrasound (HIFU) to destroy Pseudomonas aeruginosa biofilms grown on implant surfaces in order to provide a noninvasive treatment alternative to surgery. The study exposed P. aeruginosa biofilms grown on graphite disks to ultrasound pulses varying exposure time (5, 15, 30 seconds), pulse period (1, 3, 6, 12 milliseconds), and peak pressures (30 and 13 MPa). It identified thresholds for increased bacterial destruction and complete removal. Results showed 30-second exposure and 6-millisecond pulse period were sufficient to destroy biofilms, but 15-second exposure and 3-millisecond pulse period were optimal considering exposure time, efficacy, and safety as they minimized temperature rise at
In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivat...Georgi Daskalov
This study examined the ability of the nicotinic receptor agonist cytisine and two halogenated derivatives (3-bromocytisine and 5-bromocytisine) to stimulate dopamine release in vivo and protect against dopamine depletion in a rat model of Parkinson's disease. Microdialysis experiments showed that cytisine, 5-bromocytisine, and nicotine were more effective than 3-bromocytisine at inducing striatal dopamine release. Administration of cytisine and 5-bromocytisine before and after an intranigral injection of 6-hydroxydopamine significantly prevented the decrease in striatal dopamine levels, but 3-bromocytisine did not provide protection. These results suggest that the efficacy
This study examined the effects of chronic exposure to nicotine on the function of human α4β2 nicotinic acetylcholine receptors (nAChRs), which play a major role in nicotine addiction. The key findings were:
1) Acetylcholine dose-response curves for human α4β2 nAChRs expressed in human cells were biphasic, consisting of both high- and low-affinity components.
2) Chronic exposure to nicotine or nicotinic antagonists increased the fraction of high-affinity receptors from 25% to around 70% and doubled the acetylcholine-evoked currents.
3) Upregulation of receptor function after chronic nicotine exposure occurred
This study aimed to compare the biomechanical strength of primary nerve repairs versus repairs using a synthetic nerve connector in a rabbit animal model. The researchers repaired nerve segments of varying diameters using either 8-0 sutures for primary repair or the Neurolac nerve connector. The repaired nerve segments were then subjected to tension until failure using a mechanical tester. The results showed that repairs using the nerve connector had a significantly higher maximal load and stress at failure compared to primary repairs. The study concluded that nerve connectors increase the breaking strength of nerve repairs and minimize tension, suggesting potential clinical benefits such as reducing need for nerve grafts and allowing earlier mobilization after repair.
This study investigated the effects of anti-intercellular adhesion molecule-1 antibody (anti-ICAM-1 Ab) on noise-induced hearing loss in rats. Rats were exposed to loud noise and treated with either anti-ICAM-1 Ab or a saline control. Rats treated with anti-ICAM-1 Ab showed less temporary threshold shifts compared to controls after noise exposure. Both groups recovered some hearing ability 72 hours later. Anti-ICAM-1 Ab may protect against noise-induced hearing loss by blocking reactive oxygen species generation caused by noise-induced cochlear damage and inflammation.
The Topic is Radioprotective Efficacy of RK-IP-006 in mammalian system. Experiments performed were Antioxidant assay, SDS-PAGE, Western Blot to check the effect against radiation of 9Gy.
Environmental enrichment reduces seizure frequency in a rodent model of reflex epilepsy. Long Evans rats were primed to develop audiogenic seizures through repeated exposure to loud tones. One group then received environmental enrichment through interaction with objects and other rats, while a control group did not. Rats receiving enrichment showed less severe seizures, with increased latency to seizures, shorter seizure durations, and a reduced occurrence of seizures, showing that environmental enrichment can counteract the progression of seizure disorders in this model.
This study investigated using high-intensity focused ultrasound (HIFU) to destroy Pseudomonas aeruginosa biofilms grown on implant surfaces in order to provide a noninvasive treatment alternative to surgery. The study exposed P. aeruginosa biofilms grown on graphite disks to ultrasound pulses varying exposure time (5, 15, 30 seconds), pulse period (1, 3, 6, 12 milliseconds), and peak pressures (30 and 13 MPa). It identified thresholds for increased bacterial destruction and complete removal. Results showed 30-second exposure and 6-millisecond pulse period were sufficient to destroy biofilms, but 15-second exposure and 3-millisecond pulse period were optimal considering exposure time, efficacy, and safety as they minimized temperature rise at
In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivat...Georgi Daskalov
This study examined the ability of the nicotinic receptor agonist cytisine and two halogenated derivatives (3-bromocytisine and 5-bromocytisine) to stimulate dopamine release in vivo and protect against dopamine depletion in a rat model of Parkinson's disease. Microdialysis experiments showed that cytisine, 5-bromocytisine, and nicotine were more effective than 3-bromocytisine at inducing striatal dopamine release. Administration of cytisine and 5-bromocytisine before and after an intranigral injection of 6-hydroxydopamine significantly prevented the decrease in striatal dopamine levels, but 3-bromocytisine did not provide protection. These results suggest that the efficacy
This study examined the effects of chronic exposure to nicotine on the function of human α4β2 nicotinic acetylcholine receptors (nAChRs), which play a major role in nicotine addiction. The key findings were:
1) Acetylcholine dose-response curves for human α4β2 nAChRs expressed in human cells were biphasic, consisting of both high- and low-affinity components.
2) Chronic exposure to nicotine or nicotinic antagonists increased the fraction of high-affinity receptors from 25% to around 70% and doubled the acetylcholine-evoked currents.
3) Upregulation of receptor function after chronic nicotine exposure occurred
This study aimed to compare the biomechanical strength of primary nerve repairs versus repairs using a synthetic nerve connector in a rabbit animal model. The researchers repaired nerve segments of varying diameters using either 8-0 sutures for primary repair or the Neurolac nerve connector. The repaired nerve segments were then subjected to tension until failure using a mechanical tester. The results showed that repairs using the nerve connector had a significantly higher maximal load and stress at failure compared to primary repairs. The study concluded that nerve connectors increase the breaking strength of nerve repairs and minimize tension, suggesting potential clinical benefits such as reducing need for nerve grafts and allowing earlier mobilization after repair.
Gene therapy involves inserting normal genes into cells to treat genetic diseases. There are two main methods - using viruses as vectors to deliver genes (viral vectors) or delivering naked DNA. Researchers are studying gene therapy for diseases like cancer, HIV, hemophilia and more. Some successes include treating blindness caused by a genetic defect using a virus to deliver a healthy gene to the eyes. Gene therapy has also reduced Parkinson's disease symptoms by delivering a gene to the brain to increase inhibitory neurotransmitters. While offering hope, gene therapy also faces challenges in terms of safety, cost and ethical issues.
The document discusses approaches to promoting regeneration after spinal cord injury. It describes how secondary injury mechanisms can cause additional damage after the initial injury. Research strategies aim to minimize secondary damage, promote axon regeneration through the injury site, and exploit intact fibers. Potential treatments include neuroprotection, stimulating axon growth by blocking myelin inhibitors, bridging the injury site with cellular grafts, and rehabilitation. Large clinical trials are needed to evaluate safety and efficacy.
Fetal nigral transplantation involves surgically transplanting dopamine-producing neurons from human fetal tissue grafts into the brains of Parkinson's disease patients. This aims to reinnervate the dopamine-depleted striatum and restore motor function. Studies have found the grafts can survive long-term, improve motor symptoms, and allow some patients to reduce their need for dopamine medication. However, fetal tissue transplantation still carries risks of dyskinesia and varying degrees of success, and is unlikely to become a routine therapy for Parkinson's disease.
Synapsin Pharmaceuticals Inc AZ USA Patent US8524741Troy Curtis Stork
This document is a US patent that describes compositions containing piperidine alkaloids from fire ant venom that can be used to treat neurological disorders and enhance cognitive and physical performance. Specifically, it describes solenopsins extracted from fire ant venom that have been shown to inhibit phosphatidylinositol-3-kinase signaling and angiogenesis, and may have applications in treating conditions like Alzheimer's disease. The patent lists the inventors and assignee, provides background on related research, and cites numerous other publications related to fire ant venom components and their neurological effects. It concludes by stating the invention provides piperidine alkaloids and their uses in neurological disorders and physical enhancement.
This document summarizes a study on the effects of particulate contamination during intravenous therapy. The study found that in-line filters can significantly reduce complications in critically ill children. A randomized controlled trial assigned 807 pediatric intensive care patients to either a control non-filter group or an intervention filter group. The filter group showed a significant reduction in overall complication rates, systemic inflammatory response syndrome, organ dysfunction, length of stay, and mortality compared to the non-filter group. The results demonstrate that in-line filtration can effectively reduce harmful particulate contamination and its associated adverse effects during intravenous therapy in critically ill children.
This study implemented a quiet time protocol in a neuro-ICU to reduce noise and light levels twice daily to allow patients to sleep. Noise and light levels were measured before, during, and after quiet time and patients' sleep behaviors were observed. The results showed that noise and light levels were significantly lower during quiet time. Patients were also significantly more likely to be observed sleeping during quiet time periods compared to before and after. The goal of allowing patients rest and sleep during quiet time periods was achieved through reducing environmental stimuli in the ICU.
This study investigates the hypothesis that age-related hearing loss (presbyacusis) is caused by reactive oxygen metabolites (ROM) damaging mitochondrial DNA (mtDNA). The study assigns 130 rats to treatment groups receiving antioxidants, calorie restriction, or placebo. It finds that calorie-restricted rats had the best hearing, fewest mtDNA deletions, and least hair cell loss. Antioxidant-treated rats also had improved hearing and fewer mtDNA deletions than placebo rats. The results support that interventions reducing ROM damage can protect against presbyacusis by reducing mtDNA damage.
This document lists 37 publications by Ravi S. Harapanhalli, Ph.D., including original peer-reviewed articles, manuscripts pending publication, proceedings from meetings, a U.S. patent application, and book chapters. The publications cover a wide range of topics including synthesis of organic compounds, radiopharmaceutical development and testing, radioprotection studies, and modification of antibodies for tumor targeting.
1) The document discusses various potential therapies for human rabies that have been studied experimentally, including ketamine, ribavirin, interferon, and therapeutic coma.
2) Experiments in a mouse model found that ketamine did not provide any benefits such as reduced mortality or viral load, and it has also failed to help in at least 8 reported human rabies cases.
3) Similarly, the "Willoughby protocol" of inducing therapeutic coma has not proven effective and should not be continued without further study, as the risks may outweigh any unproven benefits. More research is needed to identify truly promising treatments.
Concomitant increase in cognitive behavioral deficits and white matter injury...Susan Schwerin
This study investigated cognitive behavioral deficits and white matter injury markers over time in a ferret model of traumatic brain injury (TBI). Ferrets were subjected to controlled cortical impact injury and assessed at various time points post-injury using MRI, histology, and behavioral testing. MRI showed abnormal hyperintensities near the injury site and diffuse changes in white matter diffusivity up to 16 weeks post-injury. Histology revealed chronic reactive gliosis extending from the injury site and elevated injury markers in white matter up to 16 weeks. Behavioral testing showed impaired short-term memory and cognitive flexibility that persisted over time. This gyrencephalic ferret model demonstrated correlations between cognitive impairment and increasing white matter pathology, making it a useful
Repeated nicotine exposure and withdrawal in mice increased acoustic startle response, a measure of stress. Acoustic startle amplitudes increased during the third trial of nicotine exposure and at 24 hours and 120 hours of withdrawal. Administration of the CRF receptor antagonist antalarmin showed a trend of decreasing startle response at 95dB, suggesting CRF mediates increased stress from nicotine exposure and withdrawal. Further studies are needed to examine CRF in the brain during repeated nicotine administration and abstinence periods.
This thesis examines the antioxidant properties of resveratrol, piceatannol, and pterostilbene. It studies their ability to be taken up by Burkitt's Lymphoma cells and protect against DNA damage from oxygen radicals. It also analyzes their role in DNA repair following radical exposure. The ORAC assay measured overall antioxidant capacity, while the Comet assay assessed DNA damage and repair. Pterostilbene was significantly taken up by cells after radical exposure, but not the others. Piceatannol provided protection against hydrogen peroxide DNA damage, while the others increased damage. None affected DNA repair. The study merits further research into these compounds' bioactive roles, including antioxidant capacity
The document discusses various studies on the causes of recurrence after laparoscopic hernioplasty. The main causes identified are technical errors due to incomplete dissection, small mesh size, inadequate mesh fixation, missed hernias, and surgeon inexperience/learning curve. As surgeons gain experience, the recurrence rates due to technical errors decreases from over 10% for surgeons with fewer than 250 cases to under 5% for surgeons with more than 250 cases. Recurrence rates have also decreased as the laparoscopic techniques have evolved with larger and better fixed meshes.
This study examined the effects of AG1478, a Schwann cell inhibitor, on zebrafish caudal fin regeneration. The researchers found that:
1) Zebrafish treated with AG1478 showed significantly reduced caudal fin regrowth compared to controls over 5 days following amputation.
2) Despite decreased regrowth, AG1478-treated zebrafish tended to have more peripheral axons in the new fin tissue than controls.
3) AG1478 treatment did not affect the number of Agr2+ gland cells present in the fin.
This suggests fin regeneration is dependent on a neural factor other than the number of peripheral axons. Future work will examine AG1478's effects on Schw
The document summarizes recent discoveries in spinal cord injury pathophysiology and treatment from The Miami Project to Cure Paralysis. It discusses promising neuroprotective and regenerative treatments currently being studied, including hypothermia, stem cells, and Schwann cell transplantation. It also outlines ongoing clinical trials, such as the ARCTIC trial evaluating hypothermia and a proposed phase 1 trial of autologous Schwann cell transplantation in humans with spinal cord injuries. The overall goal is to translate bench research into new clinical applications and improve outcomes for spinal cord injury patients.
Temporal-Spatial Expressions of Spy1 in Rat Sciatic Nerve After CrushJiao Yang
1. The study examined the expression of the cell cycle protein Spy1 in a rat sciatic nerve crush injury model over time.
2. Spy1 expression was found to gradually increase after injury, peaking at day 3, due to increased expression in both axons and Schwann cells.
3. Spy1 expression correlated with Schwann cell proliferation after injury and Spy1 was found to localize in axons in the injured segment but did not co-localize with the growth protein GAP43.
The document summarizes research studying changes in motor axon excitability in stroke survivors using a technique called TROND. The study had two aims: 1) compare dominant and non-dominant sides in healthy subjects, and 2) compare paretic and non-paretic sides in stroke survivors. The results found no differences between dominant/non-dominant sides in healthy subjects. While membrane potential did not differ between paretic/non-paretic sides in stroke survivors, excitability differences were found, likely due to changes in ionic conductances. The research contributes to understanding mechanisms behind motor deficits post-stroke.
This study examined the effects of dopamine depletion in the basal ganglia region Area X on song behavior in zebra finches. The researchers injected a neurotoxin called 6-OHDA directly into Area X to reduce dopamine levels. They found that 6-OHDA reduced levels of the dopamine marker tyrosine hydroxylase specifically in Area X, but not a nearby region. Vocal variability decreased during undirected singing but not female-directed singing after dopamine depletion. This zebra finch model provides insights into how dopamine loss affects vocal control and variability, as seen in human Parkinson's disease patients.
This study investigated the effects of adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, on noise-induced hearing loss in a rat model. The study demonstrated that ADAC treatment was most effective when administered within the first 24 hours after noise exposure at doses over 50 μg/kg. Pharmacokinetic studies found ADAC had a short half-life in plasma but did not detect degradation products. The results show that ADAC can mitigate noise-induced hearing loss in a dose- and time-dependent manner and warrants further investigation as a potential clinical treatment for noise-induced hearing loss.
This study investigated the pharmacokinetic properties of adenosine amine congener (ADAC) in rat perilymph after systemic intravenous administration using liquid chromatography-tandem mass spectrometry. ADAC was detected in cochlear perilymph within two minutes of administration and remained above its minimally effective concentration for at least two hours. The pharmacokinetic profile of ADAC was altered by noise exposure, suggesting changes in blood-labyrinth barrier permeability or cochlear blood flow. This supports further development of ADAC as a potential clinical treatment for noise-induced hearing loss.
BIO-EFFECTS OF AIRCRAFT NOISE AND ANTIOXIDANT ACTIVITY OF OMEGA3 ON MICE BRAIN ijbesjournal
1) Mice were exposed to recorded aircraft takeoff and landing noise at 100dB for 1, 2, or 3 weeks to study the biological effects of aircraft noise on the brain. Blood glucose, cortisol levels, and brain tissue were analyzed.
2) Exposure to aircraft noise significantly increased blood glucose and cortisol levels compared to unexposed controls. Administration of omega-3 fatty acids significantly improved blood glucose and cortisol levels in mice exposed for 3 weeks.
3) Histological analysis found vesicles, apoptosis, and pyknosis in brain tissue of noise-exposed mice. The effects were most prominent after 3 weeks of exposure. Omega-3 supplementation did not prevent noise-induced brain tissue changes.
Gene therapy involves inserting normal genes into cells to treat genetic diseases. There are two main methods - using viruses as vectors to deliver genes (viral vectors) or delivering naked DNA. Researchers are studying gene therapy for diseases like cancer, HIV, hemophilia and more. Some successes include treating blindness caused by a genetic defect using a virus to deliver a healthy gene to the eyes. Gene therapy has also reduced Parkinson's disease symptoms by delivering a gene to the brain to increase inhibitory neurotransmitters. While offering hope, gene therapy also faces challenges in terms of safety, cost and ethical issues.
The document discusses approaches to promoting regeneration after spinal cord injury. It describes how secondary injury mechanisms can cause additional damage after the initial injury. Research strategies aim to minimize secondary damage, promote axon regeneration through the injury site, and exploit intact fibers. Potential treatments include neuroprotection, stimulating axon growth by blocking myelin inhibitors, bridging the injury site with cellular grafts, and rehabilitation. Large clinical trials are needed to evaluate safety and efficacy.
Fetal nigral transplantation involves surgically transplanting dopamine-producing neurons from human fetal tissue grafts into the brains of Parkinson's disease patients. This aims to reinnervate the dopamine-depleted striatum and restore motor function. Studies have found the grafts can survive long-term, improve motor symptoms, and allow some patients to reduce their need for dopamine medication. However, fetal tissue transplantation still carries risks of dyskinesia and varying degrees of success, and is unlikely to become a routine therapy for Parkinson's disease.
Synapsin Pharmaceuticals Inc AZ USA Patent US8524741Troy Curtis Stork
This document is a US patent that describes compositions containing piperidine alkaloids from fire ant venom that can be used to treat neurological disorders and enhance cognitive and physical performance. Specifically, it describes solenopsins extracted from fire ant venom that have been shown to inhibit phosphatidylinositol-3-kinase signaling and angiogenesis, and may have applications in treating conditions like Alzheimer's disease. The patent lists the inventors and assignee, provides background on related research, and cites numerous other publications related to fire ant venom components and their neurological effects. It concludes by stating the invention provides piperidine alkaloids and their uses in neurological disorders and physical enhancement.
This document summarizes a study on the effects of particulate contamination during intravenous therapy. The study found that in-line filters can significantly reduce complications in critically ill children. A randomized controlled trial assigned 807 pediatric intensive care patients to either a control non-filter group or an intervention filter group. The filter group showed a significant reduction in overall complication rates, systemic inflammatory response syndrome, organ dysfunction, length of stay, and mortality compared to the non-filter group. The results demonstrate that in-line filtration can effectively reduce harmful particulate contamination and its associated adverse effects during intravenous therapy in critically ill children.
This study implemented a quiet time protocol in a neuro-ICU to reduce noise and light levels twice daily to allow patients to sleep. Noise and light levels were measured before, during, and after quiet time and patients' sleep behaviors were observed. The results showed that noise and light levels were significantly lower during quiet time. Patients were also significantly more likely to be observed sleeping during quiet time periods compared to before and after. The goal of allowing patients rest and sleep during quiet time periods was achieved through reducing environmental stimuli in the ICU.
This study investigates the hypothesis that age-related hearing loss (presbyacusis) is caused by reactive oxygen metabolites (ROM) damaging mitochondrial DNA (mtDNA). The study assigns 130 rats to treatment groups receiving antioxidants, calorie restriction, or placebo. It finds that calorie-restricted rats had the best hearing, fewest mtDNA deletions, and least hair cell loss. Antioxidant-treated rats also had improved hearing and fewer mtDNA deletions than placebo rats. The results support that interventions reducing ROM damage can protect against presbyacusis by reducing mtDNA damage.
This document lists 37 publications by Ravi S. Harapanhalli, Ph.D., including original peer-reviewed articles, manuscripts pending publication, proceedings from meetings, a U.S. patent application, and book chapters. The publications cover a wide range of topics including synthesis of organic compounds, radiopharmaceutical development and testing, radioprotection studies, and modification of antibodies for tumor targeting.
1) The document discusses various potential therapies for human rabies that have been studied experimentally, including ketamine, ribavirin, interferon, and therapeutic coma.
2) Experiments in a mouse model found that ketamine did not provide any benefits such as reduced mortality or viral load, and it has also failed to help in at least 8 reported human rabies cases.
3) Similarly, the "Willoughby protocol" of inducing therapeutic coma has not proven effective and should not be continued without further study, as the risks may outweigh any unproven benefits. More research is needed to identify truly promising treatments.
Concomitant increase in cognitive behavioral deficits and white matter injury...Susan Schwerin
This study investigated cognitive behavioral deficits and white matter injury markers over time in a ferret model of traumatic brain injury (TBI). Ferrets were subjected to controlled cortical impact injury and assessed at various time points post-injury using MRI, histology, and behavioral testing. MRI showed abnormal hyperintensities near the injury site and diffuse changes in white matter diffusivity up to 16 weeks post-injury. Histology revealed chronic reactive gliosis extending from the injury site and elevated injury markers in white matter up to 16 weeks. Behavioral testing showed impaired short-term memory and cognitive flexibility that persisted over time. This gyrencephalic ferret model demonstrated correlations between cognitive impairment and increasing white matter pathology, making it a useful
Repeated nicotine exposure and withdrawal in mice increased acoustic startle response, a measure of stress. Acoustic startle amplitudes increased during the third trial of nicotine exposure and at 24 hours and 120 hours of withdrawal. Administration of the CRF receptor antagonist antalarmin showed a trend of decreasing startle response at 95dB, suggesting CRF mediates increased stress from nicotine exposure and withdrawal. Further studies are needed to examine CRF in the brain during repeated nicotine administration and abstinence periods.
This thesis examines the antioxidant properties of resveratrol, piceatannol, and pterostilbene. It studies their ability to be taken up by Burkitt's Lymphoma cells and protect against DNA damage from oxygen radicals. It also analyzes their role in DNA repair following radical exposure. The ORAC assay measured overall antioxidant capacity, while the Comet assay assessed DNA damage and repair. Pterostilbene was significantly taken up by cells after radical exposure, but not the others. Piceatannol provided protection against hydrogen peroxide DNA damage, while the others increased damage. None affected DNA repair. The study merits further research into these compounds' bioactive roles, including antioxidant capacity
The document discusses various studies on the causes of recurrence after laparoscopic hernioplasty. The main causes identified are technical errors due to incomplete dissection, small mesh size, inadequate mesh fixation, missed hernias, and surgeon inexperience/learning curve. As surgeons gain experience, the recurrence rates due to technical errors decreases from over 10% for surgeons with fewer than 250 cases to under 5% for surgeons with more than 250 cases. Recurrence rates have also decreased as the laparoscopic techniques have evolved with larger and better fixed meshes.
This study examined the effects of AG1478, a Schwann cell inhibitor, on zebrafish caudal fin regeneration. The researchers found that:
1) Zebrafish treated with AG1478 showed significantly reduced caudal fin regrowth compared to controls over 5 days following amputation.
2) Despite decreased regrowth, AG1478-treated zebrafish tended to have more peripheral axons in the new fin tissue than controls.
3) AG1478 treatment did not affect the number of Agr2+ gland cells present in the fin.
This suggests fin regeneration is dependent on a neural factor other than the number of peripheral axons. Future work will examine AG1478's effects on Schw
The document summarizes recent discoveries in spinal cord injury pathophysiology and treatment from The Miami Project to Cure Paralysis. It discusses promising neuroprotective and regenerative treatments currently being studied, including hypothermia, stem cells, and Schwann cell transplantation. It also outlines ongoing clinical trials, such as the ARCTIC trial evaluating hypothermia and a proposed phase 1 trial of autologous Schwann cell transplantation in humans with spinal cord injuries. The overall goal is to translate bench research into new clinical applications and improve outcomes for spinal cord injury patients.
Temporal-Spatial Expressions of Spy1 in Rat Sciatic Nerve After CrushJiao Yang
1. The study examined the expression of the cell cycle protein Spy1 in a rat sciatic nerve crush injury model over time.
2. Spy1 expression was found to gradually increase after injury, peaking at day 3, due to increased expression in both axons and Schwann cells.
3. Spy1 expression correlated with Schwann cell proliferation after injury and Spy1 was found to localize in axons in the injured segment but did not co-localize with the growth protein GAP43.
The document summarizes research studying changes in motor axon excitability in stroke survivors using a technique called TROND. The study had two aims: 1) compare dominant and non-dominant sides in healthy subjects, and 2) compare paretic and non-paretic sides in stroke survivors. The results found no differences between dominant/non-dominant sides in healthy subjects. While membrane potential did not differ between paretic/non-paretic sides in stroke survivors, excitability differences were found, likely due to changes in ionic conductances. The research contributes to understanding mechanisms behind motor deficits post-stroke.
This study examined the effects of dopamine depletion in the basal ganglia region Area X on song behavior in zebra finches. The researchers injected a neurotoxin called 6-OHDA directly into Area X to reduce dopamine levels. They found that 6-OHDA reduced levels of the dopamine marker tyrosine hydroxylase specifically in Area X, but not a nearby region. Vocal variability decreased during undirected singing but not female-directed singing after dopamine depletion. This zebra finch model provides insights into how dopamine loss affects vocal control and variability, as seen in human Parkinson's disease patients.
This study investigated the effects of adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, on noise-induced hearing loss in a rat model. The study demonstrated that ADAC treatment was most effective when administered within the first 24 hours after noise exposure at doses over 50 μg/kg. Pharmacokinetic studies found ADAC had a short half-life in plasma but did not detect degradation products. The results show that ADAC can mitigate noise-induced hearing loss in a dose- and time-dependent manner and warrants further investigation as a potential clinical treatment for noise-induced hearing loss.
This study investigated the pharmacokinetic properties of adenosine amine congener (ADAC) in rat perilymph after systemic intravenous administration using liquid chromatography-tandem mass spectrometry. ADAC was detected in cochlear perilymph within two minutes of administration and remained above its minimally effective concentration for at least two hours. The pharmacokinetic profile of ADAC was altered by noise exposure, suggesting changes in blood-labyrinth barrier permeability or cochlear blood flow. This supports further development of ADAC as a potential clinical treatment for noise-induced hearing loss.
BIO-EFFECTS OF AIRCRAFT NOISE AND ANTIOXIDANT ACTIVITY OF OMEGA3 ON MICE BRAIN ijbesjournal
1) Mice were exposed to recorded aircraft takeoff and landing noise at 100dB for 1, 2, or 3 weeks to study the biological effects of aircraft noise on the brain. Blood glucose, cortisol levels, and brain tissue were analyzed.
2) Exposure to aircraft noise significantly increased blood glucose and cortisol levels compared to unexposed controls. Administration of omega-3 fatty acids significantly improved blood glucose and cortisol levels in mice exposed for 3 weeks.
3) Histological analysis found vesicles, apoptosis, and pyknosis in brain tissue of noise-exposed mice. The effects were most prominent after 3 weeks of exposure. Omega-3 supplementation did not prevent noise-induced brain tissue changes.
The document describes a study that investigated the effects of different intensities of noise stress (60, 80, 100, 120, 140 dB) on body weight and adrenal gland weight in male Wistar rats. The rats were exposed to 1 hour of noise per day for 30 days. Food/water intake and body weight were measured on days 1, 15, and 30. Adrenal gland weights were measured on day 30. The results showed that higher noise intensities (120-140 dB) significantly reduced food/water intake and body weight, while lower intensities (60-100 dB) showed recovery. Adrenal gland weights increased with higher noise levels. The study suggests noise stress affects physiology in a intensity-dependent manner.
Effects of Noise Stress on Body Weight and Adrenal Gland Weight of Male Wista...BRNSS Publication Hub
The present study was designed to investigate the effects of varying intensities of noise stress onto the body and adrenal gland weight (absolute) of 17 weeks old (291–296) gram (g) Wistar rat. Animals were exposed to varying intensity of noise, i.e., 60 dB (Decibel), 80 dB, 100 dB, 120 dB, and 140 dB for 1 h (h)/day for 30 days. The dose of different noise intensities was delivered through a special fabricated noise chamber which had provided all daily needs of animal-like oxygen, food, and water. Food and water consumption behavior was recorded on 1st, 14th, and 29th days and body weight change recorded on 1st, 15th, and 30th days after the exposure of noise stress. Absolute adrenal glands weight was recorded on the 30th day. The results of the present study showed that the food, water consumption behavior, and body weight (g) of the experimental group EG1 (60 dB), EG2 (80 dB), EG3 (100 dB), EG4 (120 dB), and EG5 (140 dB) were found to be significantly (P < 0.001) decreased during 1st–14th days and during 15th–30th days a recovery which were observed in food, water consumption, and in body weight of the EG1 (60 dB), EG2 (80 dB), and EG3 (100 dB). A percentage (%) decrease was found, i.e., 0.76, 0.37, 3.87, 25.89, and 30.06% in body weight of EG1 (60 dB), EG2 (80 dB), EG3 (100 dB), EG4 (120 dB), and EG5 (140 dB) experimental groups, respectively.
The document describes a study that investigated the effects of different intensities of noise stress (60, 80, 100, 120, 140 dB) on body weight and adrenal gland weight in male Wistar rats. The rats were exposed to 1 hour of noise per day for 30 days. Food/water intake and body weight were measured on days 1, 15, and 30. Adrenal gland weights were measured on day 30. The results showed that higher noise intensities (120-140 dB) significantly reduced food/water intake and body weight, while lower intensities (60-100 dB) showed recovery. Adrenal gland weights increased with higher noise levels. The study suggests noise stress affects physiology in a intensity-dependent manner.
Michael Festing - MedicReS World Congress 2011MedicReS
The document discusses principles of animal experimentation and summarizes some key points:
- 93% of research involves mice, fish and rats. Animal experiments have led to advances like vaccines, antibiotics, organ transplants, and treatments for diseases.
- Countries have animal welfare laws that encourage humane experimentation and oversight. Experiments use animal models to study effects in humans. Results only apply to the model species.
- The minimum number of animals should be used according to the principles of replacement, refinement and reduction. Statistical quality and design of some published animal studies has room for improvement.
- Using multiple inbred strains in toxicity testing could increase power over using a single outbred stock, with similar or smaller
The document summarizes findings from long-term intrathecal bolus administration studies in cynomolgus monkeys. Transient neurological findings were observed in control animals after intrathecal dosing and anesthesia, including temporarily reduced or absent patellar reflex and absence of the anal reflex lasting up to 8 hours. Single cases of ataxia, leg lameness, or slight tremor lasted up to 4 hours. Background clinical signs observed throughout the studies were similar to those seen with oral or subcutaneous dosing and included injuries, lesions, fractures, swellings, hair loss, diarrhea and others. The document provides details on study designs, housing conditions, dosing procedures, and expected background findings to aid in differentiating treatment effects
Ototoxicity refers to hearing loss or balance problems caused by certain medications or chemicals. Some common ototoxic drugs include aminoglycoside antibiotics, loop diuretics, antimalarial medications, chemotherapy agents like cisplatin, and some analgesics. These drugs can damage inner ear structures like the cochlea and vestibule. Cisplatin in particular commonly causes irreversible, progressive, bilateral high-frequency hearing loss and tinnitus. A study found that 36.83% of patients receiving treatment for multidrug-resistant tuberculosis with injectable antibiotics experienced ototoxicity, usually hearing loss and/or tinnitus. Amikacin was associated with higher risk of ototoxicity than capre
The document provides updates on several studies related to chemotherapy-induced peripheral neuropathy and mucositis pain. It discusses two animal studies looking at chemotherapy-induced peripheral neuropathy and mucositis pain. It also describes an early-stage clinical study examining sensory fiber changes in patients before and after chemotherapy to identify biomarkers of neuropathy. To date, two patients have enrolled in the clinical study with screening of additional patients ongoing.
Cranberry (Vaccinium macrocarpon) protects against doxorubicin-induced cardio...Ahmed Elberry
This document summarizes a research article that studied the protective effects of cranberry extract against doxorubicin-induced cardiotoxicity in rats. The study found that cranberry extract inhibited glutathione depletion and lipid peroxidation caused by doxorubicin in cardiac tissues. It also protected against doxorubicin-induced reductions in the activities of antioxidant enzymes. Cranberry extract alleviated the rise in cardiac injury biomarkers and histopathological changes observed with doxorubicin treatment. The results suggest that cranberry extract has antioxidant properties and can protect against doxorubicin-induced cardiotoxicity in rats.
Evaluation of Radiotherapy Effect on Auditory System in Patients with Head and Neck Tumors by Seyedeh Mahtab Ashja Arvan in Experiments in Rhinology & Otolaryngology
Radiotherapy in patients with head and neck tumors may result in damage of different organs such as eyes and ears. However, there is no consensus regarding the level of damage, especially its effect on hearing threshold. This study has been designed to determine the effect of radiotherapy on auditory system of patients with head and neck tumors.
https://crimsonpublishers.com/ero/fulltext/ERO.000509.php
1. Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the DMD gene that result in lack of dystrophin protein. Current treatments can only manage symptoms but do not cure the underlying issue.
2. Gene therapy and genome editing approaches aim to directly address the genetic cause of DMD. Exon skipping uses oligonucleotides to skip mutated exons and allow production of a truncated but functional dystrophin protein.
3. Studies in 2016 demonstrated that CRISPR-Cas9 genome editing can precisely remove mutated exons in the DMD gene of mouse models, restoring dystrophin expression and improving muscle function. This provides proof-of-concept for a potential
Mobile phone radiation has potential health impacts according to studies. Research shows mobile phone radiation may cause behavioral issues in children, reduce male fertility, and impact the nervous system by altering brain activity and neurotransmitter release. Studies also link mobile phone radiation to oxidative stress, DNA damage, and reduced motility in human sperm. Further research on health effects of mobile phone towers found increased cancer rates and other illnesses like fatigue and sleep problems in people living near towers.
1) Cigarette smoke exposure in rats led to increased airway hyperresponsiveness and lung inflammation, as shown by elevated levels of leukocytes, neutrophils, and macrophages in the bronchoalveolar lavage fluid.
2) Treatment with eucalyptol reduced airway hyperresponsiveness in cigarette smoke-exposed rats, as demonstrated by decreased contractions of tracheal rings and improved lung function.
3) Eucalyptol also reduced cigarette smoke-induced lung inflammation by decreasing the influx of leukocytes, neutrophils, and macrophages into the bronchoalveolar lavage fluid by over 70%.
The document provides an overview of the Human Genome Project (HGP). It describes the HGP's goal of mapping and sequencing the entire human genome. The HGP was an international research effort that worked alongside a private company, Celera Genomics, to complete a rough draft of the human genome by 2000. The completion of the HGP marked a major scientific achievement and has transformed fields like medicine, biotechnology, and genetics by providing a comprehensive map of the human genetic code.
Stereotactic Radiotherapy for the Treatment of Acoustic Neuromas Clinical Whi...Brainlab
Learn more: https://www.brainlab.com/radiosurgery-products/
Acoustic neuromas (AN) have an annual incidence of approximately one per 100,000 people and may account for up to 8% of all new tumors presenting to a neurosurgical referral practice. Acoustic neuromas are benign tumors arising from Schwann cells from the vestibular branch of the eighth cranial nerve. Nevertheless, they can pursue a potentially aggressive course, with uncontrolled local growth resulting in compression of the brainstem and fourth ventricle, cranial nerve and other neurological deficits.
This document summarizes a study examining the role of the nuclear factor erythroid 2-related factor 2 (Nrf2) in protecting against brain injury caused by intracerebral hemorrhage (ICH) in mice. The study found that Nrf2 knockout mice exhibited larger brain injury volumes and greater neurological deficits 24 hours after ICH induction compared to wild-type mice. Additionally, Nrf2 knockout mice showed increased leukocyte infiltration, reactive oxygen species production, DNA damage, and cytochrome c release during the early post-ICH period. These results suggest that Nrf2 provides protection against ICH-induced early brain injury, likely by reducing leukocyte-mediated free radical oxidative damage.
The combination of chronic amiodarone treatment and acute ranolazine administration has synergistic electrophysiological effects in canine atrial preparations that lead to potent prevention of atrial fibrillation induction. Specifically, ranolazine caused greater reductions in sodium channel current-dependent parameters like maximum upstroke velocity and increases in diastolic threshold and effective refractory period in atria from amiodarone-treated dogs compared to untreated dogs. This drug combination effectively suppressed triggered activity in pulmonary vein sleeves but had relatively small effects on these parameters in ventricular preparations. The authors conclude the combination produces use-dependent depression of sodium current in atria, preventing atrial fibrillation.
- The axolotl was tested to characterize its baseline hearing sensitivity from 0.1-6 kHz and determine if it could recover hearing after sound exposure.
- Baseline audiograms found peaks in sensitivity at 0.6 and 3 kHz.
- After 48 hours of 150 Hz sound at 170 dB, axolotls experienced temporary threshold shifts (TTS) of 6-12 dB greatest near 150 Hz.
- Hearing recovered to baseline levels within 8 days post-sound exposure, indicating the axolotl can regenerate inner ear hair cells like other amphibians.
Resveratrol induces apoptotic death in human glioma U251 cells through multiple signaling pathways. Resveratrol treatment leads to dose- and time-dependent cell death, as measured by lactate dehydrogenase release and DNA fragmentation assays. It activates caspase-3 and increases cleavage of poly(ADP-ribose) polymerase. Resveratrol also induces cytochrome c release from mitochondria, caspase-9 activation, Bax expression/translocation, and G0/G1 cell cycle arrest. These findings suggest resveratrol may be an attractive anticancer agent for treating gliomas.
This study examined the effects of two mitochondrial metabolites, acetyl-L-carnitine and alpha-lipoic acid, on age-related hearing loss in rats. Twenty-one aged rats were divided into three groups receiving one of the metabolites or a placebo daily for 6 weeks. Hearing was tested before and after, and tissue samples were analyzed. The control group showed expected age-related hearing decline, while treated groups experienced reduced progression. Acetyl-L-carnitine significantly improved hearing thresholds. Both metabolites reduced mitochondrial DNA damage associated with aging and hearing loss. The results suggest these compounds can delay age-related declines by protecting mitochondrial function.
This document summarizes research on age-related hearing loss (presbyacusis) and its association with reactive oxygen species and mitochondrial DNA damage. It discusses several theories of aging and applies them to presbyacusis. Several animal models of presbyacusis are described that have helped illuminate the molecular mechanisms, including mitochondrial dysfunction and hair cell loss. Presbyacusis is characterized by a progressive, high-frequency hearing loss that affects a significant portion of older populations. Understanding its molecular underpinnings may help address its socioeconomic impacts and identify methods for mitigating age-related hearing impairment.
1) The document discusses research on the role of antioxidants in attenuating various types of hearing loss, including age-related and noise-induced hearing loss.
2) It suggests that reactive oxygen species (ROS) produced during mitochondrial respiration and other processes may play an important role in these types of hearing loss by damaging cellular structures.
3) Recent studies further support the notion that antioxidant therapy can help treat hearing loss by scavenging ROS and reducing oxidative damage in the auditory system.
1) The study investigated the effects of two mitochondrial metabolites, alpha-lipoic acid and acetyl-L-carnitine, on age-related hearing loss in rats.
2) 21 aged rats were divided into groups receiving one of the metabolites or a control, and hearing was tested before and after.
3) The treated groups experienced less progression of hearing loss compared to controls. Acetyl-L-carnitine significantly improved auditory thresholds.
This study investigated the effects of resveratrol on noise-induced hearing loss in rats. [1] Ten rats were divided into two groups, with one group receiving resveratrol treatment and the other receiving a control treatment. [2] Both groups were exposed to loud noise, and auditory brainstem response tests were conducted over time to measure hearing thresholds. [3] The resveratrol group showed significantly less threshold shifts compared to the control group, indicating resveratrol protected against noise-induced hearing loss.
The ViSalus Sciences BMW Program provides monthly bonus payments to distributors who achieve and maintain the rank of Regional Director or above. To qualify, distributors must acquire a black BMW and meet certain volume requirements. The program offers a $600 monthly bonus for those with a BMW or $300 monthly bonus for those without a BMW. Distributors are responsible for BMW purchase or lease agreements and ViSalus only provides the monthly bonuses if all requirements are continuously met. The program runs through December 2010.
1) ViSalus is launching a community challenge to donate 1,000,000 shake meal donations to children in need through donations made by customers.
2) Donors can donate 30 shake meals for $24, and ViSalus will match with an additional 30 meals. This feeds a child for less than 50 cents per meal.
3) Donations will help shape communities across the world by providing nutrition to children who otherwise would not have access to meals.
The National Director Experience provides an opportunity for ViSalus' new and emerging leaders to spend time with company founders and leaders. During the experience, National Directors will build relationships, visit ViSalus offices, receive specialized training, and create plans to become Ambassadors. They will also enjoy a night out in Hollywood. The experience marks an important step for National Directors as future company Ambassadors.
The document describes the Body by Vi 90-Day Challenge, which includes three different kits at various price points to support weight loss, fitness, and health goals. The Balance kit costs $49 and provides basic nutrition and support. The Shape kit costs $99 and adds additional supplements and flavors. The Transformation kit costs $249 and contains the full range of ViSalus products and online tools for maximum results. The challenge involves using the products daily for 30 days, tracking progress online, and potentially earning a free kit by recruiting others.
Body by Vi is a 90-day nutrition and fitness program offered by ViSalus Sciences that provides meal plans, recipes, exercise videos and an online community for support. The program includes nutritional shakes, supplements and health flavors designed to help people lose weight, tone up or build muscle through balanced nutrition and lifestyle changes. Customers can choose from various kits that bundle the products at discounted prices and provide different options depending on weight loss or general health and wellness goals.
This document is a registration form for a ViSalus event taking place from July 16-18, 2010 in Orlando, Florida. It provides information on event location, pricing, and policies. Attendees can register by filling out their name, distributor ID, contact details, and credit card information. Rooms at the host hotel Wyndham Orlando Resort start at $89 per night when booked through the provided number and mentioning "VISALUS".
This document announces regional success tour events in September and October 2010 across five US cities. Each event will feature presentations from top earning Visalus distributors and ambassadors. The events will include general sessions as well as separate trainings just for directors. Attendees can learn success tips, stories of 90 day transformations, and how to earn $100,000+ annually from home. BMWs will be raffled at some events. Pre-registration is required and costs $25 for individuals or $40 for couples.
The Body by ViTM Challenge is hosting a concert on March 1st at the Denver International Airport Convention Center to benefit the Food Bank of the Rockies. The concert will feature a band recreating authentic U2 concerts. The event aims to provide healthy nutrition for children in need throughout the Denver community. Suggested donation is $20 and proceeds will provide over 60 meals for children.
The document summarizes the compensation plan for ViSalus distributors. There are 8 ways to earn income, including direct sales commissions, bonuses for enrolling new distributors, team commissions based on sales throughout the distributor's organization, and leadership bonuses. To remain active and qualify for earnings, a distributor must maintain a minimum monthly sales volume through personal or customer sales. The compensation plan is designed to incentivize customer acquisition, new distributor enrollment, organizational development, and long-term leadership development.
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to affect acoustic damage. Some interventions that mg/kg and 15 mg/kg, respectively) given subcu-
reduce acoustic damage include lowering the body taneously.
temperature, stimulating the efferent olivocochlear Auditory stimuli were generated using a D/A
bundle, treating with various pharmacological converter (Model DA3-2; Tucker-Davis Technol-
compounds or endogenous factors, and increasing ogies (TDT), Gainesville, FL, USA) with a sam-
oxygenation with carbogen or oxygen.2,3 Studies pling frequency of 100 kHz. The output of the D/A
from our laboratory and others have achieved sim- converter was connected to a programmable at-
ilar partial protection from noise damage by inter- tenuator (Model PA4; TDT), a weighted summer
fering with the activity of reactive oxygen species. (Model SM3; TDT), a headphone buffer (Model
Resveratrol, found mainly in the skin of grapes, is HB6; TDT), and an earphone (Model DT-48;
noted for its antioxidant and anti-inflammatory Beyer Dynamic, Heilbronn, Germany), which was
properties, as well as its potential to prevent can- placed within 1 to 2 mm from the tympanic mem-
cer and heart disease. Epidemiological evidence brane of the animal. The stimuli consisted of tone
has shown that moderate consumption of red wine bursts with a rise/fall time of 1 ms, a duration of
is inversely correlated with the incidence of de- 15 ms, and a period of 100 ms. A series of stimuli
mentia and ischemic heart disease.4 Direct neuro- were produced at 3, 6, 9, 12 and 18 kHz test
protective effects of resveratrol against oxidative frequencies with intensities ranging from 5 to 100
stress have been demonstrated in PC12 cells.5 dB SPL in 5 dB increments. The system was
Resveratrol stimulates a key enzyme in the brain calibrated at the tympanic membrane using a
known as Map-kinase, which is involved in nerve probe microphone (Model ER-7C; Etymotic Re-
regeneration and neural protection from the dam- search, Elk Grove Village, IL), which was con-
age caused by systemic injection of the excito- nected to an A/D converter (Model AD2, TDT)
toxin kainic acid.6 Our study will assess the pos- and a computer. Automated calibrating routines
sible protective effects of resveratrol on noise were used for online calibration.
damage by evaluating noise-induced temporary Auditory brainstem responses were collected
threshold shifts (TTS), permanent threshold shifts using subcutaneous electrodes (Model E2; Grass
(PTS), and inner ear histologic changes. Instruments, Quincy, MA, USA) placed at the
vertex and under both pinnae of each animal. This
MATERIAL AND METHODS output was channeled into a biologic amplifier
Subjects (Model P5 Series; Grass Instruments) with a gain
of 100,000X. The response was filtered between
Ten healthy male Fischer rats (130 to 175 gm)
0.3 and 3.0 kHz, and then the output was sent to an
were used to study noise-induced TTS and PTS as A/D converter (Model AD2; TDT). Custom-de-
determined by auditory brainstem response (ABR) signed software allowed these responses to be
measurements. These animals were randomly as- displayed with a sampling rate of 50 kHz in real
signed to either the resveratrol treatment group (n time on a computer monitor. For each recording, a
5) or the control group (n 5). The use of 20-ms neural response was averaged 1,024 times.
experimental animals for this study was approved For each of the 5 test frequencies, auditory thresh-
by the Care for Experimental Animals Committee olds were determined by identifying the smallest
at Henry Ford Health System. Additionally, all intensity (in dB SPL) at which ABR waveforms
procedures were conducted in strict compliance became consistently evident at 1 mV responses.
with the National Institutes of Health guidelines This was determined objectively by the computer
for experimental animal subjects. and confirmed by direct observation of the wave-
form.
Auditory Brainstem Response (ABR) After baseline ABR testing, treatment group
Baseline ABR measurements were obtained animals (n 5) received 3 weeks of trans-resvera-
from these 10 healthy male Fischer rats at initial trol (430/ug/kg/day) treatment by gavage feeding.
entry into the study. Animals were anesthetized Trans-resveratrol was purchased from Sigma (St
with a mixture of ketamine and xylazine (100 Louis, MO) and was dissolved in 100% ethanol
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Fig 1. Baseline auditory brainstem response thresholds. Mean auditory threshold levels of treatment group (dark line) and
control group (light line) at 5 test frequencies. Measurements were obtained before treatment with resveratrol. (Bars
represent Standard Error of the mean.)
(10 mg/ml), stocked at –20°C, and diluted with aortic perfusion. The bullae were rapidly removed
0.9% NaCl to final ethanol concentration of 2.5% and the cochleae were perfused in vitro with a
vol/vol as necessary. The control group (n 5) 2.5% glutaraldehyde solution in veronal acetate
was gavaged with an equivalent volume of 0.9% buffer (pH 7.4) through the oval and round
NaCl. The animals were then placed in an acous- windows. The tissues were fixed in the same so-
tically insulated noise booth (Industrial Acoustics, lution at 4°oC for 48 hours. The cochleae were
New York, NY) and exposed to 105 dB SPL at perfused with 1% osmium tetroxide in veronal
4500 to 9000 Hz narrow band noise for 24 con- acetate buffer (pH 7.4) through the oval and
tinuous hours. After the completion of the noise round windows for 30 minutes. The cochleae were
exposure, experimental group animals received dehydrated using ethanol of ascending strength
another 4 weeks of resveratrol (430/ug/kg/day) by from 30% through 50% to 70% and decalcified
gavage, and the control group was gavaged with overnight in 0.35 M ethylenediaminetetracetic
an equivalent volume of 0.9% NaCl. Although acid (EDTA) in veronal acetate buffer (pH 7.4).
caging was designed to be acoustically transpar- The organ of Corti was then dissected in 70%
ent, calibration measurements throughout the cage
ethanol. Each cochlear turn was mounted with
revealed a variance of 2 to 3 dB from the front of
99% glycerol and examined under an optical mi-
the cage to the back. To determine temporary
croscope. The hair cells were counted at 400
threshold shifts (TTS) and permanent threshold
using a differential interference contrast micro-
shifts (PTS), ABR measurements were recorded at
various times: immediately, 3 days, 7 days, and 4 scope (Carl Zeiss GFL, Goettingen, Germany).
weeks after the completion of the noise exposure. These data were then used to generate a cytoco-
chleogram as a frequency-position map based on
Cochlear Histology the following mathematical derivation: f (kHz)
At the end of the 7-week study period, 8 of the 3.109 * (10 (100-d)*0.0142) - 0.7719), where d is the
animals involved in the auditory sensitivity studies percent distance from the cochlear base.7
were sacrificed; 4 from the resveratrol treatment Outer and inner hair cell loss was evaluated
group and 4 from the control group. One animal in for each animal as a percent hair cell loss and
each group had expired before the cochleae was plotted against basilar membrane distance (cal-
able to be harvested. The cochleae were perfused culated from the cochlear apex). The basilar
in vivo with a 2.5% glutaraldehyde solution in membrane length was also matched for frequen-
veronal acetate buffer (pH 7.4) via transcardiac cy-position. The pattern of hair cell loss was
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466 SEIDMAN et al November 2003
Fig 2. Auditory treshold shifts. Mean auditory shifts measured immediately (A), 3 days (B), 7 days (D), and 4 weeks (D) after
high-level noise exposure. Dark lines represent resveratrol treatment group and light lines represent control group at 5 test
frequencies (3, 6, 9, 12, and 18 kHz). (Standard Error bars are plotted for each condition.)
compared between the treatment and control and 4 weeks after noise exposure (SigmaStat Soft-
groups. ware). Significant differences in audiologic data
between the 2 groups were assessed using Stu-
RESULTS dent’s t test.
Auditory Brainstem Response (ABR) Also reductions were noted in threshold shifts at
ABR thresholds were recorded at 5 test frequen- 12 kHz in the immediate and 7 day time points.
cies (3, 6, 9, 12, and 18 kHz) and 5 time points
(baseline, 0, 3, 7 days, and 4 weeks after noise Cochlear Histology
exposure) as described previously. ABR measure- Figure 3 displays surface preparations of the
ments obtained before resveratrol treatment indi- organ of Corti from a control ear and a resveratrol
cated that there were no significant differences in treated ear from representative animals. All of the
mean auditory thresholds between the treatment selected animals showed outer hair cell loss, but
and control groups at baseline (Fig 1). Subsequent the loss was significantly less in the resveratrol
mean auditory threshold shifts from baseline were treated group. Figure 4 depicts a mean cytoco-
also graphed (Fig 2). Statistically significant re- chleogram for both the control and resveratrol
ductions in auditory threshold shifts were noted treatment groups. Outer hair cell (OHC) loss was
when comparing the resveratrol treatment group to determined over 0.24 mm intervals along the co-
the control group at 2 test frequencies (6 kHz and chlea from apex to base. The mean basilar mem-
9 kHz) at all 4 times: immediately, 3 days, 7 days, brane length in the control group was 8.9 mm. The
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Volume 129 Number 5 SEIDMAN et al 467
Fig 3. Cochlear histology. Photomicrographs ( 40) of surface mount preparation of the organ of Corti from a control ear
(A) and resveratrol-treated ear (B). (Three outer hair cell rows are labeled 1, 2, and 3; I, single hair cell row; arrowhead
points to outer hair cells loss.)
mean basilar membrane length in the resveratrol inner hair cells was not detected in either group of
treatment group was 8.97 mm. The mean OHC animals.
loss was 1.3% in the control group. OHC loss in
the resveratrol treatment group was 0.48%. In the DISCUSSION
control group, peak outer hair cell loss was 5.2%, The current study shows that treatment with
corresponding to 7 to 9 kHz. In the resveratrol resveratrol prevents significant noise-induced
group, peak outer hair cell loss was 2.7%, corre- hearing loss based on auditory brainstem response
sponding to 7 to 8 kHz. A significant change of the testing and histologic examination. Statistically
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468 SEIDMAN et al November 2003
Fig 4. Cochlear histology. Mean cytocochleograms of control (dark line) and rseveratrol-treated group (light line) show
percentage of hair cell loss as a function of frequency position on basilar lamina.
significant reductions in auditory threshold shifts Hypoperfusion and ischemia to the cochlea is a
were noted when comparing the resveratrol treat- possible mechanism of damage associated with
ment group to the control group at 2 test frequen- noise-induced hearing loss. Ischemia, which is
cies (6 and 9 kHz) at all 4 time points: immedi- known to cause injury to the cochlea, results in
ately, 3 days, 7 days, and 4 weeks after noise oxidative stress that stimulates the generation and
exposure. The traumatic noise exposure consisted release of reactive oxygen species (ROS).8 These
of frequencies between 4500 and 9000 Hz, thus ROS affect energy production and ultimately re-
accounting for the threshold shift at 6 and 9 KHz duce outer hair cell function. This damage is evi-
and the protective effects of resveratrol at these dent in the auditory system in the form of thresh-
frequencies as well. Additionally, a greater loss of old shifts. Many studies have shown signs of
hair cells was found in the control group compared vascular insufficiency following noise expo-
with the resveratrol treated group. This demon- sure.9-11 Our in vivo studies have shown hypoper-
strates a protective effect of resveratrol on the fusion and ischemia in the cochlear microcircula-
cochlea. Although unlikely this effect may have tion during noise exposure.12 Reductions in
been influenced by the use of ethanol as the dis- cochlear blood flow, such as occurs with noise
solving agent for resveratrol. Ongoing studies are exposure, have long been known to decrease au-
investigating the role of ethanol causing a protec- ditory sensitivity.13 Indeed, recent evidence sug-
tive role. gests an increase in ROS following noise expo-
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Volume 129 Number 5 SEIDMAN et al 469
sure.14 Several studies from our laboratories have tection; and neuroprotection.24-28 Bertelli et al29
shown ROS scavenger treatment in the auditory investigated the absorption, the concentration in
system reduces these threshold shifts following different organs, and the excretion of natural trans-
experimentally induced cochlear ischemia.15,16 and cis-Resveratrol after red wine oral administra-
ROS are also implicated in other ototoxic insults tion to rats. Their results show that prolonged
such as cisplatin, trimethyltin, and aminoglyco- administration of red wine in the diet could lead to
sides.5,9,17,18 Studies have also demonstrated that an increased resveratrol concentration in different
a reduction of ROS attenuates noise-induced hear- tissues even though the amount of resveratrol in
ing loss.19,20 In summary, noise results in isch- these different tissues was lower than that required
emia, a condition known to affect auditory thresh- for pharmacological activity. This may explain its
olds. This ischemia results in the generation of beneficial role against coronary heart disease.
ROS and the damaging effects of these radicals Oxidative stress in the central nervous system
can be attenuated with scavengers and inhibitors may cause oxidation of lipoprotein particles. The
in the auditory system. oxidized lipoproteins may damage cellular and
Resveratrol is found in over 70 fruits and plants, subcellular membranes, leading to tissue injury
many of which are edible, such as mulberries, and cell death. Draczynska-Lusiak et al30 have
peanuts, and grapes. It is thought that this chem- shown that antioxidants, such as vitamins E or C,
ical is produced in response to environmental or resveratrol, protect neuronal cell damage from
stress or attack by pathogens including mold. oxidative stress in vitro. Results indicated that
Grapes contain particularly high concentrations of oxidized lipoproteins may serve as an oxidative
resveratrol in the skin. Trans-resveratrol was first stressor, which may initiate the neuronal cell death
detected in grapevines in 1976 by Langcake and leading to the manifestation of Alzheimer disease.
Pryce,21 who found that the compound was syn- Zini et al31 studied the possible effects of resvera-
thesized by leaf tissues in response to fungal in- trol on the mitochondrial respiratory chain in rat
fection or exposure to ultraviolet light.5 Resvera- brains. Resveratrol was found to decrease complex
trol was brought to the public attention when its III activity in rat brain by competition with coen-
presence in wine was reported in 1992 by Siemann zyme Q. This property is especially interesting as
and Creasy.22 The authors suggested that this this complex is the site where reactive oxygen
compound might be the biologically active ingre- substances (ROS) are generated. By decreasing
dient of red wine.23 The consumption of red wine the activity of complex III, resveratrol not only
is becoming increasingly popular due to the in- opposes the production of ROS but also scavenges
trigue created by the French Paradox. Despite the them.31 Virgili and Contestabile14 report that
high fat diet and smoking tendencies of the pop- chronic administration of resveratrol to young
ulation in Southern France, there is an astonishing adult rats, significantly protects from the damage
42% lower incidence of heart disease than that caused by systemic injection of the excitotoxin
found in Americans.4 The effect known as the kainic acid in the olfactory cortex and the hip-
French Paradox has been attributed to the con- pocampus.
sumption of red wine. World Health Organization Several studies have demonstrated that antioxi-
data indicate that resveratrol may be one of the dants can attenuate hearing loss in various condi-
active ingredients in the wine that reduces the risk tions, such as noise-induced hearing loss, ototox-
of coronary heart disease by up to 40% in red wine icity, ischemia, and presbycusis.2,16,32-33
drinkers.1
Resveratrol has many important biologic activ- CONCLUSION
ities including: inhibition of lipid peroxidation; Considering the importance of the biological
chelation of copper; free-radical scavenging; alter- activities of resveratrol, along with previous stud-
ation of eicosanoid synthesis; inhibition of platelet ies from our laboratory showing the protective
aggregation; anti-inflammatory activity; vasore- effects of antioxidants and dietary restriction on
laxing activity; modulation of lipid metabolism; noise-induced and age-induced hearing loss, the
anticancer activity; estrogenic activity; cardiopro- current study demonstrates similar effects with
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470 SEIDMAN et al November 2003
resveratrol. Thus, resveratrol appears to protect 18. Hester T, Jones R, Clerici W. Protection against aminogly-
the cochlea from acoustic trauma and ongoing coside otic drop-induced ototoxicity by a spin trap. I. acute
effects. Otolaryngol Head Neck Surg 1998;119:581-7.
studies are being done to evaluate the efficacy of 19. Kopke R, Liu W, Gabazadeh R, et al. Use of organotypic
resveratrol on age-related hearing loss. cultures of Corti’s organ to study the protective effects of
antioxidant molecules on cisplatin-induced damage of
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