- Glutamate-based theories of schizophrenia focus on dysfunction of brain glutamate systems, particularly NMDA receptors. These theories originated over 20 years ago and have led to new conceptualizations of schizophrenia and potential assessment and treatment approaches.
- Dopamine dysfunction in schizophrenia may be caused by genetically determined abnormalities or by NMDA receptor dysfunction impairing dopamine system regulation. Disturbances in both glutamate and dopamine systems likely contribute to positive symptoms.
- Glutamate and NMDA receptors are widely distributed in the brain, suggesting schizophrenia involves dysfunction beyond prefrontal and limbic regions, including sensory cortices. Deficits in auditory and visual processing correlate with impaired functioning.
- While past drug trials targeting glut
This document discusses the role of glutamate in psychiatry. It notes that glutamate is the major excitatory neurotransmitter in the brain and is involved in memory, emotions, cognition, and various psychiatric conditions like depression, anxiety, schizophrenia, and drug addiction. It then discusses the specific implications of glutamate for anxiety disorders, mood disorders, addiction disorders, and schizophrenia. Finally, it outlines the future implications of targeting glutamate systems for the treatment of these conditions, noting potential drug candidates and the promise of drugs like ketamine for rapidly treating depression.
1) The study investigated the effects of serotonin receptor agonists on mRNA expression levels of genes related to glutamate and GABA systems in mouse cortical neurons and HT-22 cells.
2) Treatment with the 5-HT1A agonist 8-OH-DPAT decreased mRNA levels of GluR1 and GluR3 while increasing GluR2 mRNA levels in cortical neurons. It also decreased GluR3 and BDNF mRNA levels in HT-22 cells.
3) Treatment with the 5-HT2A/2C agonist DOI increased BDNF mRNA levels in HT-22 cells.
4) The results suggest serotonin receptor agonists can modulate glutamate and BD
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbances in glutamate transmission and NMDA receptor hypofunction are associated with schizophrenia. The NMDA receptor hypofunction hypothesis proposes that reduced NMDA receptor activity leads to increased mesolimbic dopamine activity causing positive symptoms and reduced mesocortical dopamine causing negative and cognitive symptoms. Several clinical studies have explored using NMDA agonists and drugs targeting downstream glutamate release as adjunctive treatments for schizophrenia with some success in improving symptoms. Ongoing research continues to develop new glutamatergic drugs for treating schizophrenia.
Alcohol affects the brain quickly, reaching it within 5 minutes. It impacts many areas of the brain and can cause both short-term and long-term effects. In the short-term, alcohol consumption leads to intoxication and impairment of cognitive and motor functions. Long-term heavy drinking is linked to conditions like Wernicke-Korsakoff syndrome and alcohol use disorder. The neurobiology of alcohol involves its interactions with neurotransmitters like dopamine, GABA, glutamate, opioids and serotonin. Genetic factors also contribute to risk of alcohol dependence. Prenatal alcohol exposure can cause fetal alcohol syndrome and developmental impairments.
The Effect Of Pseudophosphorylated Tau Protein In The Absence Of Fibrillar Be...rob_dorfman
The document summarizes an experiment that examined the role of tau proteins in Alzheimer's disease cell death independently of beta-amyloid plaques. The experiment found that pseudophosphorylated tau vectors, with and without a tau mutation, led to caspase-3 activation and cell death in cells lacking fibrillar beta-amyloid. This suggests that hyperphosphorylated tau can cause Alzheimer's disease cell death characteristics independently of beta-amyloid and may be a potential cause of the disease since tau tangles appear before amyloid plaques in the brain. The results support further research focusing on stopping tau hyperphosphorylation for Alzheimer's treatments.
Hepatic encephalopathy occurs when the liver fails to detoxify toxic substances, such as ammonia, which are then able to pass into the brain. This causes neurological symptoms ranging from mild confusion to coma. Precipitating factors include gastrointestinal bleeding, infections, and certain drugs. Treatment focuses on reducing ammonia production in the gut through lactulose, antibiotics, and low-protein diets. Correcting electrolyte imbalances and removing precipitating medications or infections are also important for management of hepatic encephalopathy.
- Glutamate-based theories of schizophrenia focus on dysfunction of brain glutamate systems, particularly NMDA receptors. These theories originated over 20 years ago and have led to new conceptualizations of schizophrenia and potential assessment and treatment approaches.
- Dopamine dysfunction in schizophrenia may be caused by genetically determined abnormalities or by NMDA receptor dysfunction impairing dopamine system regulation. Disturbances in both glutamate and dopamine systems likely contribute to positive symptoms.
- Glutamate and NMDA receptors are widely distributed in the brain, suggesting schizophrenia involves dysfunction beyond prefrontal and limbic regions, including sensory cortices. Deficits in auditory and visual processing correlate with impaired functioning.
- While past drug trials targeting glut
This document discusses the role of glutamate in psychiatry. It notes that glutamate is the major excitatory neurotransmitter in the brain and is involved in memory, emotions, cognition, and various psychiatric conditions like depression, anxiety, schizophrenia, and drug addiction. It then discusses the specific implications of glutamate for anxiety disorders, mood disorders, addiction disorders, and schizophrenia. Finally, it outlines the future implications of targeting glutamate systems for the treatment of these conditions, noting potential drug candidates and the promise of drugs like ketamine for rapidly treating depression.
1) The study investigated the effects of serotonin receptor agonists on mRNA expression levels of genes related to glutamate and GABA systems in mouse cortical neurons and HT-22 cells.
2) Treatment with the 5-HT1A agonist 8-OH-DPAT decreased mRNA levels of GluR1 and GluR3 while increasing GluR2 mRNA levels in cortical neurons. It also decreased GluR3 and BDNF mRNA levels in HT-22 cells.
3) Treatment with the 5-HT2A/2C agonist DOI increased BDNF mRNA levels in HT-22 cells.
4) The results suggest serotonin receptor agonists can modulate glutamate and BD
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbances in glutamate transmission and NMDA receptor hypofunction are associated with schizophrenia. The NMDA receptor hypofunction hypothesis proposes that reduced NMDA receptor activity leads to increased mesolimbic dopamine activity causing positive symptoms and reduced mesocortical dopamine causing negative and cognitive symptoms. Several clinical studies have explored using NMDA agonists and drugs targeting downstream glutamate release as adjunctive treatments for schizophrenia with some success in improving symptoms. Ongoing research continues to develop new glutamatergic drugs for treating schizophrenia.
Alcohol affects the brain quickly, reaching it within 5 minutes. It impacts many areas of the brain and can cause both short-term and long-term effects. In the short-term, alcohol consumption leads to intoxication and impairment of cognitive and motor functions. Long-term heavy drinking is linked to conditions like Wernicke-Korsakoff syndrome and alcohol use disorder. The neurobiology of alcohol involves its interactions with neurotransmitters like dopamine, GABA, glutamate, opioids and serotonin. Genetic factors also contribute to risk of alcohol dependence. Prenatal alcohol exposure can cause fetal alcohol syndrome and developmental impairments.
The Effect Of Pseudophosphorylated Tau Protein In The Absence Of Fibrillar Be...rob_dorfman
The document summarizes an experiment that examined the role of tau proteins in Alzheimer's disease cell death independently of beta-amyloid plaques. The experiment found that pseudophosphorylated tau vectors, with and without a tau mutation, led to caspase-3 activation and cell death in cells lacking fibrillar beta-amyloid. This suggests that hyperphosphorylated tau can cause Alzheimer's disease cell death characteristics independently of beta-amyloid and may be a potential cause of the disease since tau tangles appear before amyloid plaques in the brain. The results support further research focusing on stopping tau hyperphosphorylation for Alzheimer's treatments.
Hepatic encephalopathy occurs when the liver fails to detoxify toxic substances, such as ammonia, which are then able to pass into the brain. This causes neurological symptoms ranging from mild confusion to coma. Precipitating factors include gastrointestinal bleeding, infections, and certain drugs. Treatment focuses on reducing ammonia production in the gut through lactulose, antibiotics, and low-protein diets. Correcting electrolyte imbalances and removing precipitating medications or infections are also important for management of hepatic encephalopathy.
Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver dysfunction and the buildup of toxins such as ammonia that are normally processed by the liver. Symptoms range from mild confusion to coma and death. Ammonia disrupts the blood-brain barrier and causes cerebral edema, increased intracranial pressure, and reduced brain energy metabolism. Other toxins like manganese, mercaptans, and false neurotransmitters also contribute. Treatment focuses on reducing ammonia production in the gut and increasing ammonia clearance from the blood and brain.
Recently there have been many both open and private courseware repositories appearing on the web. In general however, there has been great commitment to building communities that facilitate the liaison between users/suppliers, but quite a modest employment of sometimes very elementary cataloguing systems. This model tries to go beyond this step.
Hyperammonemia is a condition characterized by elevated levels of ammonia in the blood. Ammonia is normally produced and excreted by the liver through the urea cycle. Primary hyperammonemia is caused by deficiencies in urea cycle enzymes, while secondary hyperammonemia can be caused by other metabolic disorders or liver/kidney dysfunction. Symptoms range from lethargy and vomiting in neonates to intellectual impairment and seizures later in life. Treatment focuses on reducing ammonia levels through dietary changes, medications to increase nitrogen excretion, and in severe cases dialysis or liver transplantation.
Diaporama qui présente dans les grandes lignes l'histoire de l'électromagnétisme : comment deux domaines distincts, électricité et magnétisme, ont été rapprochés en un et unique domaine.
This document provides an overview of hepatic encephalopathy. It defines hepatic encephalopathy as a complex metabolic disorder seen in patients with liver dysfunction, characterized by disturbances in consciousness and behavior. It discusses the pathogenesis, including the ammonia and false neurotransmitter hypotheses. Precipitating factors and clinical manifestations ranging from mild cognitive changes to coma are described. Diagnosis involves ruling out other causes and elevated ammonia levels. Treatment focuses on reducing ammonia through dietary changes, lactulose, antibiotics, and other supportive measures. Prognosis depends on the severity and underlying liver disease.
This document discusses different types of cerebral edema including cytotoxic, vasogenic, hydrostatic, osmotic, and hydrocephalic edema. It provides details on the causes, mechanisms, and management of each type. The key management strategies for cerebral edema discussed are head elevation, oxygenation, fluid management, seizure prophylaxis, fever control, nutrition, hyperventilation, osmotherapy using mannitol, and other adjunctive therapies.
The document summarizes the urea cycle and protein catabolism. It discusses:
1) Proteins are constantly degraded and resynthesized to remove damaged, unneeded, defective, or old proteins.
2) Amino acids have varying half-lives, and some residues are more stabilizing while others are destabilizing.
3) Amino acids are oxidized or reused. Ammonia produced from amino acid catabolism must be eliminated as it is toxic, especially to the central nervous system.
4) The urea cycle in the liver involves several steps to convert ammonia to less toxic urea for excretion, including transamination to shuttle amino groups to glutamate
Cerebral edema and intracranial hypertension after traumatic brain injury can be managed through various interventions to control increased intracranial pressure. These include cerebral resuscitation, intracranial pressure monitoring, hyperosmolar therapy with mannitol or hypertonic saline, mild hyperventilation, CSF drainage, temperature control, surgical decompression, and in refractory cases high-dose barbiturates or calcium channel blockers. Nutritional support and anti-seizure prophylaxis may also be considered as part of the management approach.
1. Lipids play major roles in cell structure and energy storage. Triacylglycerols are the main form of stored energy in mammals while phospholipids and cholesterol are components of cell membranes.
2. There are two main types of lipids - simple lipids like fats and oils which are esters of fatty acids and alcohols, and compound lipids which also contain phosphate, nitrogenous bases or other groups.
3. Triglycerides from the diet and from adipose tissue are broken down into fatty acids and glycerol. Fatty acids are transported to tissues via the bloodstream bound to albumin or within lipoproteins, then undergo beta-oxidation in the mitochondria to
Portal-systemic encephalopathy is a brain disorder caused by liver dysfunction that allows toxins to reach the brain. It is characterized by alterations in mental status, neurological abnormalities, and distinctive EEG changes. The main underlying mechanism involves increased levels of ammonia in the bloodstream from the gut that are normally processed by the liver. Treatment focuses on reducing ammonia production in the colon through medications like lactulose and restricting protein intake. Prognosis depends on the underlying liver disease and can range from fully treatable acute episodes to chronic and potentially fatal cases.
The urea cycle is a series of chemical reactions that occurs in the liver to convert ammonia into urea. This process involves 5 enzymes and 5 distinct steps. The first two steps occur in the mitochondria and involve the formation of carbamoyl phosphate from ammonia and carbon dioxide. The remaining steps occur in the cytosol. Urea is ultimately synthesized and transported to the kidneys for excretion in urine. Defects in urea cycle enzymes can lead to hyperammonemia, a potentially toxic buildup of ammonia in the blood.
Amino acids from dietary proteins and endogenous protein turnover can be used as an energy source in animals. Carnivores can obtain about 90% of their energy needs from amino acid oxidation after eating. Amino acids are broken down into common intermediate metabolites through transamination and deamination reactions. Excess amino groups are removed as ammonia, which is converted to less toxic urea primarily in the liver and excreted by the kidneys.
Alzheimer's is the most common form of dementia, a general term for memory loss and other intellectual abilities serious enough to interfere with daily life. Alzheimer's disease accounts for 60 to 80 percent of dementia cases.
1) The study investigated whether a catalytically inactive tPA variant (tPA-S481A) could prevent impairment of cerebral autoregulation and histopathology after traumatic brain injury (TBI) in piglets.
2) tPA-S481A prevented pial artery vasoconstriction and blunted dilation impairment during hypotension after TBI.
3) tPA-S481A also prevented neuronal cell loss in the hippocampus that normally occurs after TBI.
Glutamate receptors play an important role in many neurological conditions. They are involved in processes like synaptic plasticity and excitotoxicity. Dysfunctions in glutamate receptors have been linked to conditions like ADHD, autism, ischemia, multiple sclerosis, Parkinson's, schizophrenia, and seizures. Glutamate receptors, especially NMDA and AMPA receptors, are implicated in several neurodegenerative and neuroimmune diseases as well. Targeting glutamate receptors may provide treatment strategies for some of these conditions.
This document discusses hypoxic-ischemic encephalopathy (HIE) and the potential use of therapeutic hypothermia as a treatment. It provides definitions of HIE, describes the pathology and causes. It outlines the evolving nature of brain injury after an hypoxic event and discusses potential mechanisms of hypothermia including modulation of excitotoxicity, free radicals, and apoptosis. It summarizes studies in animal models showing hypothermia initiated within 6 hours and continued for 2-3 days can reduce brain injury. The document concludes that while preliminary human trials are promising, more research is still needed to establish safety and efficacy of hypothermia as a treatment for HIE.
Epilepsy is a chronic neurological disorder characterized by recurrent seizures originating from abnormal neuronal discharge in the brain. It affects people of all ages globally. Seizures occur when there is sudden excessive signaling between brain cells. Epilepsy has various etiologies and can be difficult to diagnose, requiring ruling out other conditions and use of EEG or MRI to identify abnormal electrical activity or structural lesions. While 70% of epilepsy can be treated effectively, many in developing areas do not receive needed treatment. Common anti-epileptic drugs work by enhancing GABA inhibition, blocking sodium or calcium channels, or inhibiting glutamate, with phenytoin a first-line treatment for generalized and partial seizures as well as status epilepticus.
Treatment of schizophrenia current issues and future possibilitiesDr Wasim
The document discusses the evolution of treatments for schizophrenia from early interventions like insulin coma therapy to first-generation antipsychotics like chlorpromazine to newer second-generation drugs. It notes limitations of current antipsychotics in treating negative symptoms and cognitive impairment and side effects like weight gain. The document outlines several new approaches being explored, including modulating the glutamate system by targeting the glycine site on NMDA receptors with drugs like glycine or inhibiting glycine transporters, as well as targeting metabotropic glutamate receptors. Clinical trials are underway to evaluate potential cognitive-enhancing effects of these strategies.
The document discusses the glutamate hypothesis of schizophrenia and glutamate-linked treatments. It proposes that hypofunction of the NMDA glutamate receptor contributes to the symptoms of schizophrenia. Specifically:
1. Antipsychotic drugs and conditions that block NMDA receptors can induce schizophrenia-like symptoms, supporting NMDA hypofunction.
2. Glutamate-linked drugs may improve both positive and negative symptoms by targeting NMDA receptors in the prefrontal cortex, hippocampus, and other brain regions.
3. NMDA hypofunction during neurodevelopment or through excitotoxicity could underlie schizophrenia by disrupting processes like neural migration, pruning, and plasticity.
Glutamate-linked treatments may
Epilepsy is a chronic neurological condition characterized by recurrent seizures. The document discusses the epidemiology, pathophysiology, classification, symptoms, risk factors, diagnosis, and treatment of epilepsy. It also outlines the pharmacist's role in managing epilepsy, including educating patients, ensuring proper adherence and monitoring, and adjusting drug therapy as needed. A case study is then presented of an 11-year old patient experiencing frequent seizures who is prescribed multiple antiepileptic drugs.
Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver dysfunction and the buildup of toxins such as ammonia that are normally processed by the liver. Symptoms range from mild confusion to coma and death. Ammonia disrupts the blood-brain barrier and causes cerebral edema, increased intracranial pressure, and reduced brain energy metabolism. Other toxins like manganese, mercaptans, and false neurotransmitters also contribute. Treatment focuses on reducing ammonia production in the gut and increasing ammonia clearance from the blood and brain.
Recently there have been many both open and private courseware repositories appearing on the web. In general however, there has been great commitment to building communities that facilitate the liaison between users/suppliers, but quite a modest employment of sometimes very elementary cataloguing systems. This model tries to go beyond this step.
Hyperammonemia is a condition characterized by elevated levels of ammonia in the blood. Ammonia is normally produced and excreted by the liver through the urea cycle. Primary hyperammonemia is caused by deficiencies in urea cycle enzymes, while secondary hyperammonemia can be caused by other metabolic disorders or liver/kidney dysfunction. Symptoms range from lethargy and vomiting in neonates to intellectual impairment and seizures later in life. Treatment focuses on reducing ammonia levels through dietary changes, medications to increase nitrogen excretion, and in severe cases dialysis or liver transplantation.
Diaporama qui présente dans les grandes lignes l'histoire de l'électromagnétisme : comment deux domaines distincts, électricité et magnétisme, ont été rapprochés en un et unique domaine.
This document provides an overview of hepatic encephalopathy. It defines hepatic encephalopathy as a complex metabolic disorder seen in patients with liver dysfunction, characterized by disturbances in consciousness and behavior. It discusses the pathogenesis, including the ammonia and false neurotransmitter hypotheses. Precipitating factors and clinical manifestations ranging from mild cognitive changes to coma are described. Diagnosis involves ruling out other causes and elevated ammonia levels. Treatment focuses on reducing ammonia through dietary changes, lactulose, antibiotics, and other supportive measures. Prognosis depends on the severity and underlying liver disease.
This document discusses different types of cerebral edema including cytotoxic, vasogenic, hydrostatic, osmotic, and hydrocephalic edema. It provides details on the causes, mechanisms, and management of each type. The key management strategies for cerebral edema discussed are head elevation, oxygenation, fluid management, seizure prophylaxis, fever control, nutrition, hyperventilation, osmotherapy using mannitol, and other adjunctive therapies.
The document summarizes the urea cycle and protein catabolism. It discusses:
1) Proteins are constantly degraded and resynthesized to remove damaged, unneeded, defective, or old proteins.
2) Amino acids have varying half-lives, and some residues are more stabilizing while others are destabilizing.
3) Amino acids are oxidized or reused. Ammonia produced from amino acid catabolism must be eliminated as it is toxic, especially to the central nervous system.
4) The urea cycle in the liver involves several steps to convert ammonia to less toxic urea for excretion, including transamination to shuttle amino groups to glutamate
Cerebral edema and intracranial hypertension after traumatic brain injury can be managed through various interventions to control increased intracranial pressure. These include cerebral resuscitation, intracranial pressure monitoring, hyperosmolar therapy with mannitol or hypertonic saline, mild hyperventilation, CSF drainage, temperature control, surgical decompression, and in refractory cases high-dose barbiturates or calcium channel blockers. Nutritional support and anti-seizure prophylaxis may also be considered as part of the management approach.
1. Lipids play major roles in cell structure and energy storage. Triacylglycerols are the main form of stored energy in mammals while phospholipids and cholesterol are components of cell membranes.
2. There are two main types of lipids - simple lipids like fats and oils which are esters of fatty acids and alcohols, and compound lipids which also contain phosphate, nitrogenous bases or other groups.
3. Triglycerides from the diet and from adipose tissue are broken down into fatty acids and glycerol. Fatty acids are transported to tissues via the bloodstream bound to albumin or within lipoproteins, then undergo beta-oxidation in the mitochondria to
Portal-systemic encephalopathy is a brain disorder caused by liver dysfunction that allows toxins to reach the brain. It is characterized by alterations in mental status, neurological abnormalities, and distinctive EEG changes. The main underlying mechanism involves increased levels of ammonia in the bloodstream from the gut that are normally processed by the liver. Treatment focuses on reducing ammonia production in the colon through medications like lactulose and restricting protein intake. Prognosis depends on the underlying liver disease and can range from fully treatable acute episodes to chronic and potentially fatal cases.
The urea cycle is a series of chemical reactions that occurs in the liver to convert ammonia into urea. This process involves 5 enzymes and 5 distinct steps. The first two steps occur in the mitochondria and involve the formation of carbamoyl phosphate from ammonia and carbon dioxide. The remaining steps occur in the cytosol. Urea is ultimately synthesized and transported to the kidneys for excretion in urine. Defects in urea cycle enzymes can lead to hyperammonemia, a potentially toxic buildup of ammonia in the blood.
Amino acids from dietary proteins and endogenous protein turnover can be used as an energy source in animals. Carnivores can obtain about 90% of their energy needs from amino acid oxidation after eating. Amino acids are broken down into common intermediate metabolites through transamination and deamination reactions. Excess amino groups are removed as ammonia, which is converted to less toxic urea primarily in the liver and excreted by the kidneys.
Alzheimer's is the most common form of dementia, a general term for memory loss and other intellectual abilities serious enough to interfere with daily life. Alzheimer's disease accounts for 60 to 80 percent of dementia cases.
1) The study investigated whether a catalytically inactive tPA variant (tPA-S481A) could prevent impairment of cerebral autoregulation and histopathology after traumatic brain injury (TBI) in piglets.
2) tPA-S481A prevented pial artery vasoconstriction and blunted dilation impairment during hypotension after TBI.
3) tPA-S481A also prevented neuronal cell loss in the hippocampus that normally occurs after TBI.
Glutamate receptors play an important role in many neurological conditions. They are involved in processes like synaptic plasticity and excitotoxicity. Dysfunctions in glutamate receptors have been linked to conditions like ADHD, autism, ischemia, multiple sclerosis, Parkinson's, schizophrenia, and seizures. Glutamate receptors, especially NMDA and AMPA receptors, are implicated in several neurodegenerative and neuroimmune diseases as well. Targeting glutamate receptors may provide treatment strategies for some of these conditions.
This document discusses hypoxic-ischemic encephalopathy (HIE) and the potential use of therapeutic hypothermia as a treatment. It provides definitions of HIE, describes the pathology and causes. It outlines the evolving nature of brain injury after an hypoxic event and discusses potential mechanisms of hypothermia including modulation of excitotoxicity, free radicals, and apoptosis. It summarizes studies in animal models showing hypothermia initiated within 6 hours and continued for 2-3 days can reduce brain injury. The document concludes that while preliminary human trials are promising, more research is still needed to establish safety and efficacy of hypothermia as a treatment for HIE.
Epilepsy is a chronic neurological disorder characterized by recurrent seizures originating from abnormal neuronal discharge in the brain. It affects people of all ages globally. Seizures occur when there is sudden excessive signaling between brain cells. Epilepsy has various etiologies and can be difficult to diagnose, requiring ruling out other conditions and use of EEG or MRI to identify abnormal electrical activity or structural lesions. While 70% of epilepsy can be treated effectively, many in developing areas do not receive needed treatment. Common anti-epileptic drugs work by enhancing GABA inhibition, blocking sodium or calcium channels, or inhibiting glutamate, with phenytoin a first-line treatment for generalized and partial seizures as well as status epilepticus.
Treatment of schizophrenia current issues and future possibilitiesDr Wasim
The document discusses the evolution of treatments for schizophrenia from early interventions like insulin coma therapy to first-generation antipsychotics like chlorpromazine to newer second-generation drugs. It notes limitations of current antipsychotics in treating negative symptoms and cognitive impairment and side effects like weight gain. The document outlines several new approaches being explored, including modulating the glutamate system by targeting the glycine site on NMDA receptors with drugs like glycine or inhibiting glycine transporters, as well as targeting metabotropic glutamate receptors. Clinical trials are underway to evaluate potential cognitive-enhancing effects of these strategies.
The document discusses the glutamate hypothesis of schizophrenia and glutamate-linked treatments. It proposes that hypofunction of the NMDA glutamate receptor contributes to the symptoms of schizophrenia. Specifically:
1. Antipsychotic drugs and conditions that block NMDA receptors can induce schizophrenia-like symptoms, supporting NMDA hypofunction.
2. Glutamate-linked drugs may improve both positive and negative symptoms by targeting NMDA receptors in the prefrontal cortex, hippocampus, and other brain regions.
3. NMDA hypofunction during neurodevelopment or through excitotoxicity could underlie schizophrenia by disrupting processes like neural migration, pruning, and plasticity.
Glutamate-linked treatments may
Epilepsy is a chronic neurological condition characterized by recurrent seizures. The document discusses the epidemiology, pathophysiology, classification, symptoms, risk factors, diagnosis, and treatment of epilepsy. It also outlines the pharmacist's role in managing epilepsy, including educating patients, ensuring proper adherence and monitoring, and adjusting drug therapy as needed. A case study is then presented of an 11-year old patient experiencing frequent seizures who is prescribed multiple antiepileptic drugs.
The document discusses age-related changes to the endocrine system. It covers changes to the hypothalamic-pituitary-adrenal axis, growth hormone, thyroid, adrenal cortex and medulla, pancreas, and hypothalamic-pituitary-testicular axis. Key effects of aging include decreased hormone production and feedback inhibition as well as increased pituitary and adrenal involvement in stress response. Diagnosing endocrine disorders can also be challenging in elderly patients due to nonspecific symptoms and normal age-related endocrine changes.
This document discusses various inborn errors of metabolism that can cause epilepsy. It covers disorders of mitochondrial function, creatine metabolism, GLUT1 deficiency, hypoglycemia, storage disorders, disorders of the urea cycle and amino acid metabolism, organic acid disorders, purine/pyrimidine metabolism, disturbances to neurotransmitter systems, brain malformations, and some vitamin-responsive epilepsies like pyridoxine-dependent epilepsy and pyridox(am)ine phosphate oxygenase deficiency. Specific genetic disorders are discussed in each category along with their associated seizure types, diagnostic testing, treatment approaches, and prognosis.
Nitric oxide (NO) is a highly reactive free radical that functions as a vasodilator and neurotransmitter. It is synthesized from arginine by nitric oxide synthase (NOS) and diffuses to nearby cells to activate guanylate cyclase, increasing cyclic GMP and causing smooth muscle relaxation. There are three isoforms of NOS: neuronal NOS regulates neurotransmitter release, inducible NOS is involved in immune response, and endothelial NOS maintains blood pressure. Glutamate is the major excitatory neurotransmitter, acting on ionotropic AMPA, kainate and NMDA receptors or metabotropic receptors. GABA is the primary inhibitory neurotransmitter, inducing neuronal hyperpolarization through
This document summarizes information about Alzheimer's disease from a student paper, including descriptions of symptoms, causes, pathophysiology and treatment options. It discusses how Alzheimer's is a progressive neurodegenerative disorder causing dementia. Key pathological features are amyloid plaques and neurofibrillary tangles in the brain. Current treatments aim to improve cognitive symptoms and include cholinesterase inhibitors such as donepezil for mild-moderate cases and memantine for moderate-severe cases. Several drug trials are also mentioned.
Movement disorders: A complication of chronic hyperglycemia? A case reportApollo Hospitals
A 77-year-old man presented with bilateral choreic movements that had developed over the past month. He had a history of poorly controlled type 2 diabetes. At admission, he was found to have severe hyperglycemia without ketosis. A CT scan showed hyperdensity in the putamen and lenticular nucleus. Treatment with insulin, haloperidol, and glycemic control led to regression of the choreic movements within 4 days. Chorea secondary to nonketotic hyperglycemia is a rare complication of uncontrolled diabetes that is usually reversible with normalization of blood glucose levels and neuroleptic treatment. The pathophysiology is thought to involve metabolic disturbances from hyperglycemia impairing neurotransmission in basal ganglia structures and
74th ICREA Colloquium "Autoimmunity meets neurodegeneration: different pathwa...ICREA
Studies during the last 10 years have revealed a new category of brain diseases in which crucial neuronal receptors are attacked by autoantibodies. As a result of this attack there is a reduction of the target synaptic proteins leading to alterations in synaptic transmission. The clinical manifestations vary according to the receptor involved, and may resemble many of the symptoms caused by neurodegenerative diseases in which specific receptors are involved, including among others Parkinson, epilepsy, chronically progressive sleep disease, or schizophrenia.
Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency. Thiamine plays a key role in brain energy metabolism. Lack of thiamine can damage brain tissue, especially in regions with high metabolic demand. Common causes include chronic alcoholism, prolonged starvation, pregnancy-related vomiting, and bariatric surgery. Symptoms include confusion, ataxic gait, and eye movement abnormalities. Treatment involves high dose parenteral thiamine supplementation.
Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency. Thiamine plays a key role in brain energy metabolism. Lack of thiamine can damage brain tissue, especially in regions with high metabolic demand. Common causes include chronic alcoholism, prolonged starvation, pregnancy-related vomiting, and bariatric surgery. Symptoms include confusion, ataxic gait, and eye movement abnormalities. Diagnosis involves clinical assessment and testing for thiamine deficiency. Treatment involves high-dose parenteral thiamine supplementation, which can improve symptoms if administered early.
Alzheimer disease , is there any hope for cureOsama Ragab
- Alzheimer's disease affects over 100 million people worldwide and is projected to increase significantly by 2050. While much research has focused on amyloid plaques and tau tangles as potential causes, treatments targeting these pathways have yet to successfully slow or stop the progression of the disease.
- Alternative hypotheses for Alzheimer's causation include neuroinflammation, oxidative stress, metabolic dysfunction, and aging. Strategies targeting these pathways also have not resulted in effective treatments.
- The exact causes and mechanisms of Alzheimer's remain unclear as amyloid and tau are normal brain proteins and their roles are still being understood. Further research is still needed to determine the root causes and identify effective treatments for this devastating disease.
Epilepsy is caused by excessive neuronal discharge in the brain and can cause seizures and abnormal neurological symptoms depending on the site of origin. Seizures are generally classified as partial or generalized based on whether neuronal activity is localized or spreads widely. Anti-seizure medications work by various mechanisms like enhancing GABA inhibition, blocking sodium or calcium channels, and interfering with glutamate transmission to suppress seizure activity. Treatment choice depends on seizure type, patient factors, and drug characteristics and side effects.
Similar to Neurotossicità iperammoniemia martinelli (20)
ASPETTI EMATOLOGICI DELLA MALATTIA DI GAUCHER: DALLA DIAGNOSI AL TRATTAMENTOCentroMalattieRareFVG
Slides presentate dai relatori durante il corso avanzato "Aspetti ematologici della malattia di Gaucher: dalla diagnosi al trattamento", che si è tenuto a Udine nei giorni 25 e 26 ottobre 2017.
Slides presentate dai relatori durante il corso avanzato "Aspetti ematologici della malattia di Gaucher: dalla diagnosi al trattamento", che si è tenuto a Udine nei giorni 25 e 26 ottobre 2017.
Corso avanzato ASPETTI EMATOLOGICI DELLA MALATTIA DI GAUCHER: DALLA DIAGNOSI ...CentroMalattieRareFVG
Slides presentate dai relatori durante il corso avanzato "Aspetti ematologici della malattia di Gaucher: dalla diagnosi al trattamento", che si è tenuto a Udine nei giorni 25 e 26 ottobre 2017.
Slides presentate dai relatori durante il corso avanzato "Aspetti ematologici della malattia di Gaucher: dalla diagnosi al trattamento", che si è tenuto a Udine nei giorni 25 e 26 ottobre 2017.
Slides presentate dai relatori durante il corso avanzato "Aspetti ematologici della malattia di Gaucher: dalla diagnosi al trattamento", che si è tenuto a Udine nei giorni 25 e 26 ottobre 2017.
Presentazione realizzata dal dr Lorenzo Verriello, coordinatore della Rete Regionale delle Malattie Neuromuscolari e della SLA, per illustrare il funzionamento e gli obiettivi della stessa.
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Affettività e sessualità nella disabilità: una sfida per gli operatori
Inquadratura soggettiva:
Affettività e Sessualità attraverso
Lo sguardo dei Protagonisti
Dott. Daniele Ferraresso
Esperto nei processi formativi orientati all’autonomia
Pedagogista Clinico
Udine, 15 Aprile 2015
L’esperienza affettiva-sessuale della persona con disabilità intellettiva in ...CentroMalattieRareFVG
Affettività e sessualità nella disabilità: una sfida per gli operatori
L’esperienza affettiva-sessuale della persona con disabilità intellettiva in un’ottica psico-relazionale
Dott.ssa Orietta Sponchiado
Psicologa-psicoterapeuta
Udine, 15 aprile 2015
Affettività e rischio psicopatologico delle disabilità intellettiveCentroMalattieRareFVG
AFFETTIVITÀ E
RISCHIO
PSICOPATOLOGICO
DELLE DISABILITÀ
INTELLETTIVE
Daniele Fedeli
Professore Associato di
Pedagogia Speciale
Università degli Studi di Udine
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
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These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
The Nervous and Chemical Regulation of Respiration
Neurotossicità iperammoniemia martinelli
1. 1
Disordini del ciclo dell’urea:
la neurotossicità dell'iperammoniemia
Diego Martinelli
Unità Operativa Complessa Patologia Metabolica
diego.martinelli@opbg.net
Napoli 26 - 28 Novembre 2013
2. Pathogenetic Mechanisms of Hyperammonemia
…in general the age of onset, duration and degree of hyperammonemia may predict
prognosis….
……….the underlying mechanisms of hyperammonemic encephalopathy are not
completely understood………
Gropman A, Summar M, Leonard JV
JIMD 2007;30:865-79
...although several theories exist, it is
not well understood how
hyperammonemia
disrupts brain function…..
Gropman A
MGM 2010;100:S20-S30
6. PROGNOSIS DEPENDS ON COMA DURATION
Msall et al. NEJM 1984;310:1500-5
Picca et al. Pediatr Nephrol 2001;16:862-7
Good 2y
22.210.1
2210*
pre-treatment
Bad 2y
4711*
*p<0.02
48.811.2
4911
7813
7. • PERI-INSULAR
• FRONTAL
• PARIETAL
• OCCIPITAL
ADC map
ADC map
• THALAMIC RESTRICTED DIFFUSION (unusual in UCDs)
…suggesting that brain MRI may assist in determining prognosis & helping
clinicians with subsequent treatment decisions
12. The concentration changes of the nitrogen scavenger
glutamine have to be interpreted in the light of NH4 levels.
In contrast to other hyperammonemic syndromes, in PA
plasma glutamine do not increase in hyperammonemia,
whereas CSF glutamine concentrations are elevated.
2010
13. depletion of oxaloacetate (>methylcitrate production)
reduced supply of succinyl-CoA
alfa-ketoglutarate
glutamate > glutamine
14. Glutamine synthesis the principal means of NH4 detoxification?
The osmotic action of glutamine
CEREBRAL EDEMA
NEURON
ASTROCYTE
SWELLING
ASTROCYTE
SWELLING
NH4
NH4
Glutamate
Glutamine
GS
Alzheimer type II
astrocytosis
Glutamine
Alzheimer type II
astrocytosis
Glutamate
25. The role of energy failure
NH4+ exposure
generates
secondary Cr
deficiency in
brain cell
cultures
Braissant 2010
• altered oxidative
phosphorylation
• cessation of ATP
synthesis
• production of
ROS and cell
death
26. Pathogenesis of brain damage in HA: others
Astrocyte swelling can cause a secondary release of Glu into the intercellular space
KGM neurotoxic ?
**
*
↑↑
«Trojan horse» hypothesis
SNAT5
Modified from Braissant; J Inherit Metab Dis (2013) 36:595–612
*KMG : α-ketoglutaramate; AKGM are increased in UCDs
ROS ↑↑
MPT open
↓↓ SNAT5. Trapping GLn
Altered Neurotrasnsmitter
system
**Imp:, brain NO metabolism is affected in a number of ways by NH4 + exposure. Effects vary
depending on whether the exposure is acute or chronic, on brain cell type, and whether Arg
supply is normal or decreased
Braissant; J Inherit Metab Dis (2013) 36:595–612;Albrecht; Hepatolgoy . 2006 Oct;44(4):788-94; Halámková; Talanta. 2012 Oct 15;100:7-11;
Vergara F et al; Science 1974;183:81-83; P. Desjardins et al. / Neurochemistry International 60 (2012) 690–696
27. Pathogenesis underlying brain dysfunction. Acute and chronic
hyperammonemia
Conclusions
•
How HA can lead to severe consequences in the central nervous system (CNS) remains unclear.
•
The rise in ammonia levels, the elevations of glutamine, and the effect of glutamine on the brain are
proposed to account for the different effects of acute (vs chronic) hyperammonemia on the brain.
•
In acute hyperammonemia the excessive NMDA receptors activation could be inducing neuronal death
•
In chronic hyperammonemia the impaired function of the glutamate-nitric oxide-cGMP pathway,
associated to NMDA receptors could be inducing cognitive impairment.
•
N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA) receptors are fundamental for
learning because they are the major modulators of the long-term potentiation, the electrophysiologic
mechanism for learning.
Braissant; J Inherit Metab Dis (2013) 36:595–612;Albrecht; Hepatolgoy . 2006 Oct;44(4):788-94; Halámková; Talanta. 2012 Oct 15;100:7-11;
Vergara F et al; Science 1974;183:81-83; P. Desjardins et al. / Neurochemistry International 60 (2012) 690–696;
Cauli O et al Metab Brain Disease ; 2009 Mar;24(1):69-80; Alison S. Et al ; Chest Chest 2007;132;1368-1378