1,720,994 research outputs found
Management of restless legs syndrome in chronic liver disease: a challenge for the correct diagnosis and therapy
Full text linkAIM To investigate the association between restless legs syndrome (RLS) and well-defined chronic liver disease, and the possible therapeutic options. METHODS Two hundred and eleven patients with chronic liver disease, complaining of sleep disturbances, painful leg sensation and daily sleepiness, were included. Patients with persistent alcohol intake, recent worsening of clinical conditions, or hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns Hopkins questionnaire and verified by fulfilling the diagnostic criteria by Allen. All patients were tested, both at baseline and during follow-up, with the Hamilton rating scale for depression, sleep quality assessment (PSQI), Epworth sleepiness scale (ESS), International Restless Legs Syndrome Study Group evaluation, and international RLS severity (IRLS) scoring system. Ironfree level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological examinations and blood test occurred at the beginning of the therapy, after 2 wk, and at the 28th, 75th, 105th, 135th, 165th and 205th day. Regarding therapy, pramipexole or gabapentin were used. RESULTS Patients were moderately depressed, with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep problems and involuntary leg movements had been underestimated, and RLS syndrome had not been considered before the neurological visit. All (211/211) patients fulfilled the RLS diagnostic criteria. Twenty-two patients considered their symptoms as mild, according to IRSL, but 189 found them moderate to very severe. No correlation was found between ammonium level and ESS or PSQI. Augmentation was rather precocious in our patients (135th day), and more frequent (35%) than previous data (8.3%-9.1%). The dosage of dopamine agonists was found to be associated with augmentation and appears in range with the literature. Previous intake of alcohol and lower levels of vitamins have been related to the phenomenon in our study. CONCLUSION RLS is a common disorder, requiring rapid diagnosis and treatment. Further research is therefore fundamental. © 2018 Baishideng Publishing Group Inc
Brain Cytochrome p450 enzymes: a possible Therapeutic Targets for Neurological Diseases
Full text linkNeurological diseases (ND) afflict hundreds of millions of people worldwide and constitute 12% of total deaths of the population all around the world. According to a global study conducted by the World Health Organization, 8 out of 10 disorders in the 3rd highest disability classes are neurologic problems. Commonly they have disabling consequences, compromising severely the quality of the life of affected subjects. Often therapeutic strategies are limited in efficacy. Limitations lie with the enormous fragility of the so complex structure and functions accomplished by the central nervous system, together with the presence of the barrier between the tissue and the blood limiting the penetration of drugs. For these reason new strategies to protect the brain are essential. One way might be the enhancement of local biomolecular mechanisms (metabolizing enzymes, transporters, etc.). However, increasing evidence underline that our knowledge of the brain is still partial, and information cannot simply be derived from other well-known organs such as the liver. This is the case for the brain cytochrome P450 enzymes, showing differential cellular localization, brain regional expression and modulation
Thalamus and language: What do we know from vascular and degenerative pathologies
Full text linkLanguage is a complex cognitive task that is essential in our daily life. For decades, researchers have tried to understand the different role of cortical and subcortical areas in cerebral language representations and language processing. Language-related cortical zones are richly interconnected with other cortical regions (particularly via myelinated fibre tracts), but they also participate in subcortical feedback loops within the basal ganglia (caudate nucleus and putamen) and thalamus. The most relevant thalamic functions are the control and adaptation of cortico-cortical connectivity and bandwidth for information exchange. Despite having the knowledge of thalamic and basal ganglionic involvement in linguistic operations, the specific functions of these subcortical structures remain rather controversial. The aim of this study is to better understand the role of thalamus in language network, exploring the functional configuration of basal network components. The language specificity of subcortical supporting activity and the associated clinical features in thalamic involvement are also highlighted. © 2018 Neurology India, Neurological Society of India
Role of brain Cytochrome P450 mono-oxygenases in bilirubin oxidation - specific induction and activity.
Full text linkIn the Crigler–Najjar type I syndrome, the genetic absence of efficient hepatic glucuronidation of unconjugated bilirubin (UCB) by the uridine 5′-diphospho-glucuronosyltransferase1A1 (UGT1A1) enzyme produces the rise of UCB level in blood. Its entry to central nervous system could generate toxicity and neurological damage, and even death. In the past years, a compensatory mechanism to liver glucuronidation has been indicated in the hepatic cytochromes P450 enzymes (Cyps) which are able to oxidize bilirubin. Cyps are expressed also in the central nervous system, the target of bilirubin toxicity, thus making them theoretically important to confer a protective activity toward bilirubin accumulation and neurotoxicity. We therefore investigated the functional induction (mRNA, EROD/MROD) and the ability to oxidize bilirubin of Cyp1A1, 1A2, and 2A3 in primary astrocytes cultures obtained from two rat brain region (cortex: Cx and cerebellum: Cll). We observed that Cyp1A1 was the Cyp isoform more easily induced by beta-naphtoflavone (βNF) in both Cx and Cll astrocytes, but oxidized bilirubin only after uncoupling by 3, 4,3′,4′-tetrachlorobiphenyl (TCB). On the contrary, Cyp1A2 was the most active Cyp in bilirubin clearance without uncoupling, but its induction was confined only in Cx cells. Brain Cyp2A3 was not inducible. In conclusion, the exposure of astrocytes to βNF plus TCB significantly enhanced Cyp1A1 mediating bilirubin clearance, improving cell viability in both regions. These results may be a relevant groundwork for the manipulation of brain Cyps as a therapeutic approach in reducing bilirubin-induced neurological damage
Wernicke Korsakoff Encephalopathy
No full textConsideration for Wernicke encephalopathy should be given to patients with any evidence of long-term alco- hol abuse or malnutrition and any of the following: acute confusion, decreased conscious level, ataxia, ophthalmo- plegia, memory disturbance, hypothermia with hypoten- sion, and delirium tremens. Wernicke encephalopathy should be considered when any patient with long-term malnutrition presents with confusion or altered metal sta- tus. Signi cant overlap exists between Wernicke enceph- alopathy and Korsako psychosis, in which patients ex- perience delayed and potentially irreversible anterograde and retrograde amnesia. For this reason, the two entities have been described together as Wernicke-Korsako syn- drome. Bariatric surgery, human immunode ciency virus, hyperemesis gravidarum, and other disorders associated with grossly impaired nutritional status have been asso- ciated with Wernicke-Korsako syndrome. Additionally, infantile thiamine de ciency with manifestations of Wer- nicke syndrome has been reported in infants fed formula that was de cient in thiamine.
Implementation therapy, with thiamine is a fun- damental approach for the treatment of WE: it must be avoided the administration of ev glucose, which may cause a precipitation of thiamine defects. No therapy has been validated for the treatment of Korsako amnestic syndrome. erefore, the clinicians should avoid any po- tential precipitating factor in speci c patients, more at risk to develop Wernicke-Korsako syndrome
Bilirubin and inflammation in neurodegenerative and other neurological diseases
Full text linkInflammation links neurodegenerative, neuropsychiatric and other neurological diseases (NDs) with acute brain events. It is responsible for the alteration of neurotransmission and circuity, brain architecture, and cell fate, affecting mood and personality (anxiety, depression and schizophrenia) and behavior (decline in cognitive, motor and speech abilities, altered sleep, fatigue, pain sensitivity and dementia). Inflammation is also a key component in systemic chronic diseases (cardiovascular disease, cancer, diabetes, and metabolic syndrome), in which bilirubin has been demonstrated to improve the diseases by acting as a multi-target antiinflammatory molecule, and where the evaluation of pharmacological modulation of the pigment level as a therapeutic approach has already started. While altered serum bilirubin levels have been reported in ND patients, the potential activity of bilirubin in the brain is vague. This review summarizes the available fragmentary information on the interplay of bilirubin with neuroinflammation, aiming to elucidate the pigment’s role in the central nervous system environment
Basal ganglia: Their role in complex cognitive procedures in experimental models and in clinical practice
Full text linkApart from the well known role of the basal ganglia (BG) in motor control, their important role in regulating the cognitive functions is emerging. This article traces the scientific work that explores this role of BG in reinforcement learning, perceptual decision making, and other nonmotor pathways (speech fluency, cognition, attention and behaviour). It also highlights the important role played by the BG networks in determining the development of a child's brain. It retraces the various pathways and connections of the BG with the cerebral cortex, cerebellum and other regions that may be utilized in the establishment of complex cognitive procedures. Various diseases that may be the direct result of disruption of these basal ganglionic networks and interconnections are also recounted
Homocysteine in neurology: From endothelium to Neurodegeneration
No full textVitamin B12 and folate are supplied via two major pathways, the conversion of homocysteine to methionine and the conversion of methyl malonyl coenzyme A to succinyl coenzyme A. Therefore, the defect in both the vitamins results in an increase in both serum homocysteine and methylmalonic acid. Hence, homocysteine, vitamin B12, and folate are closely linked together in the so-called one-carbon cycle, making vitamin B12 the necessary co-enzyme for the methyl donation from 5-methyl-tetra-hydrofolate in tetra-hydro-folate, necessary for methionine synthetase. Folate is a cofactor in one-carbon metabolism, and it promotes the remethylation of homocysteine, which can cause DNA strand breakage, oxidative stress and apoptosis. Vitamin B12 and folate are involved in nucleic acid synthesis and in the methylation reactions, and their deficit causes the inhibition of S-adenosylmethionine mediated methylation reactions, and through the related toxic effects of homocysteine, a possible direct alteration of the vascular endothelium and inhibition of N-methyl-D-Aspartate receptors take place. We discussed the possible and still controversial role of homocysteine accumulation in cerebral pathologies, starting from vascular events to neurodegeneration and to endothelium damage mechanism
Neonatal hyperbilirubinemia
No full textUnconjugated hyperbilirubinemia is a common condition in the first week of postnatal life. Low levels of bilirubin exert antioxidant effects, but some neonates may develop very high levels of unconjugated bilirubin (UCB), with an increase of the unbound free fraction (Bf), able to diffuse through the blood brain barrier.
Amount and duration of hyperbilirubinemia and the neurodevelopmental age (preterm neonates) at the time of insult exposition is supposed to influence the location of selective brain damage, as well as the severity of consequences [1]. The clinical manifestations range from the less severe Bilirubin-Induced Neurological Damage (BIND) to a more severe chronic kernicterus, while the regional selectivity of damage may elicit to motor disorders and athetosis (basal ganglia and cerebellum), auditory dysfunction (inferior colliculus), memory and learning impairment (hippocampus) [2].
To avoid neurological consequences, the Clinical Practice Guideline of the American Academy of Pediatrics recommend total bilirubin determination (TSB) on every jaundice infant, both during hospital stay and post discharge follow-up. To this goal, Bilistik [3], a new minimally invasive method for measuring TSB, may improve substantially the triage of jaundice newborns with potential risk of brain damage and kernicterus to be addressed to phototherapy. Moreover, recent studies have raised concerns about the potential toxicity of intensive phototherapy in preterm neonates, and no information about its effectiveness in quickly reducing brain bilirubin concentration are yet available [4].
Early neuronal accumulation of bilirubin in damaged regions and its brain metabolism may have a role in the marked regional differences observed in kernicterus impairment. This hypothesis is supported by the role of brain cytochrome P-450 (Cyp), known to oxidize UCB. In the brain of Gunn rats, an early upregulation of Cyp mRNAs was observed in the unaffected brain regions, cortex and superior colliculus, in contrast to the delayed and slight upregulation observed in the affected regions, inferior colliculus and cerebellum [6], where UCB alters the cell cycle inducing apoptosis [7].
Clarification of pathophysiology of UCB neurotoxicity, that continues to be an important risk among newborns worldwide, may open new perspectives for therapeutic approaches, focused in protecting directly the brain, the final target of bilirubin toxicity. To this aim the development of new research models, appear of particular relevance. Among them the organotypic brain cultures, living slices of the CSN that can be cultured in vitro and challenged with bilirubin in controlled (concentration/timing) manner, strictly modelling different histopathological aspects of neurological conditions
Evaluation of region selective bilirubin-induced brain damage as a basis for a pharmacological treatment
No full textThe neurologic manifestations of neonatal hyperbilirubinemia in the central nervous system (CNS) exhibit high variations in the severity and appearance of motor, auditory and cognitive symptoms, which is suggestive of a still unexplained selective topography of bilirubin-induced damage. By applying the organotypic brain culture (OBC: preserving in vitro the cellular complexity, connection and architecture of the in vivo brain) technique to study hyperbilirubinemia, we mapped the regional target of bilirubin-induced damage, demonstrated a multifactorial toxic action of bilirubin, and used this information to evaluate the efficacy of drugs applicable to newborns to protect the brain. OBCs from 8-day-old rat pups showed a 2-13 fold higher sensitivity to bilirubin damage than 2-day-old preparations. The hippocampus, inferior colliculus and cerebral cortex were the only brain regions affected, presenting a mixed inflammatory-oxidative mechanism. Glutamate excitotoxicity was appreciable in only the hippocampus and inferior colliculus. Single drug treatment (indomethacin, curcumin, MgCl2) significantly improved cell viability in all regions, while the combined (cocktail) administration of the three drugs almost completely prevented damage in the most affected area (hippocampus). Our data may supports an innovative (complementary to phototherapy) approach for directly protecting the newborn brain from bilirubin neurotoxicity
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