ABSTRACT
INTRODUCTION: KMT2B-related dystonia is a childhood-onset movement disorder characterized by focal dystonia of the lower extremities progressing to generalized dystonia with predominant cervical, cranial, and laryngeal involvement. So far, fewer than 100 variants have been reported, the vast majority being de novo mutations. The presenting frame of KMT2B dystonia, with dysmorphology features and other complex neurologic symptoms shows the spectrum of KMT2B dystonia as a probable syndromic disease, rather than an isolated early-onset dystonia, which has been the classic view of the condition. CASE REPORTS: We report three patients who presented regression in their neurodevelopment, focal dystonia of the lower limbs with subsequent generalization, in whom two de novo variants were reported in the KMT2B gene, with a mean age of presentation lower than the average reported worldwide. CONCLUSIONS: We describe the largest local series of patients with KMT2B dystonia in Colombia (to our knowledge), which allows us to expand the genotype-phenotype relationship of this genetic dystonia. Although many affected individuals follow a similar disease course, it is important to determine clinical features that may be associated such as neurodevelopmental regression.
TITLE: Espectro fenotípico y genotípico de la distonía causada por el gen KMT2B. Descripción de tres casos colombianos.Introducción. La distonía relacionada con KMT2B es un trastorno del movimiento hipercinético, de inicio en la infancia, caracterizado inicialmente por distonía focal de las extremidades inferiores que progresa a una distonía generalizada con mayor afectación cervical, craneal y laríngea. Hasta el momento se han descrito aproximadamente 100 variantes causantes de enfermedad, y la mayoría son de novo. La presentación clínica de la distonía con hallazgos fenotípicos comunes en los pacientes, asociada a frecuente afectación del neurodesarrollo, afectación intelectual y otros trastornos del movimiento, hace pensar más en el espectro KMT2B como una condición sindrómica, más que en una distonía aislada de inicio temprano, como clásicamente se ha clasificado. Casos clínicos. Se presenta el caso de tres pacientes con regresión del neurodesarrollo, distonía focal de los miembros inferiores con posterior generalización, en quienes se identificaron tres variantes en el gen KMT2B, en dos de los casos de novo (en una de ellas se desconoce la segregación), y dos de ellas comunicadas por primera vez en la bibliografía. La edad media de presentación fue menor a la edad promedio notificada a nivel mundial. Conclusiones. Describimos una serie de pacientes colombianos con distonía DYT-KMT2B (la más grande en nuestro conocimiento a nivel local), lo que nos permite ampliar la relación genotipo-fenotipo de esta distonía genética. Si bien múltiples individuos afectados siguen un curso de enfermedad similar, es importante determinar las características clínicas que pueden estar asociadas, como la regresión del neurodesarrollo y su potencial clasificación como distonía compleja. Describimos, además, dos nuevas variantes asociadas al fenotipo.
Subject(s)
Dystonic Disorders , Histone-Lysine N-Methyltransferase , Phenotype , Adolescent , Child , Female , Humans , Male , Colombia , Dystonic Disorders/genetics , Genotype , Histone-Lysine N-Methyltransferase/genetics , MutationABSTRACT
Objetivo: El objetivo de este estudio es evaluar los efectos de la vacunación contra el SARS-CoV-2 sobre el patrón convulsivo en pacientes pediátricos con epilepsia que acudieron a nuestro centro terciario en la ciudad de Bogotá, Colombia. Pacientes y métodos: Se pidió a los niños con epilepsia que fueron tratados en nuestro centro y que habían recibido la vacuna contra el SARS-CoV-2 y a sus cuidadores que informaran de su experiencia después de la vacunación. Se documentaron la edad, el sexo, la edad de inicio de la epilepsia, la duración de la epilepsia, el tipo de epilepsia, la frecuencia de las convulsiones, el número de medicamentos, el tiempo transcurrido desde la última crisis, los esquemas de vacunación y las convulsiones dos semanas después de la vacunación. Resultados: Se incluyó a 101 pacientes con epilepsia (58%, hombres; y 42%, mujeres). La edad promedio fue de 11 años, el 73% tenía epilepsia focal, y el 27%, generalizada. Veintiuno cumplían los criterios para la epilepsia refractaria y 11 tenían antecedentes personales de convulsiones febriles. Cuarenta y siete pacientes habían sido vacunados con la vacuna de Sinovac; 41, con Pfizer; 12, con Moderna; y uno, con CoronaVac. Tres pacientes presentaron convulsiones 24 horas después de la aplicación de la vacuna sin una relación clara entre la vacunación y la frecuencia de las convulsiones, y un paciente requirió ingreso en el hospital por una convulsión prolongada. Conclusión: La vacunación contra el SARS-CoV-2 en pacientes pediátricos con epilepsia es segura. Aproximadamente el 3% de los pacientes con epilepsia podría eventualmente tener convulsiones en el período posterior a la vacunación.
Aim: The objective of this study is to evaluate effects of SARS-CoV-2 vaccination on seizure pattern in paediatric patients with epilepsy that attended our tertiary center in the city of Bogotá, Colombia. Patients and methods: Children with epilepsy who were treated at our center and have had SARS-CoV-2 vaccination and their caregivers were asked to report their experience following vaccination. We documented age, sex, age at onset of epilepsy, duration of epilepsy, epilepsy type, seizure frequency, number of medications, time from last crisis, vaccination schemes, and seizures two weeks after vaccination. Results: One hundred and one patients with epilepsy were included (58%, male; and 42%, female). The average age was 11 years, 73% had focal epilepsy, and 27%, generalized. Twenty-one fulfilled criteria for refractory epilepsy and 11 had a personal history of febrile seizures. Forty-seven patients had been vaccinated with Sinovacs vaccine; 41 patients, with Pfizers; 12 patients, with Modernas; and one, with CoronaVacs. Three patients presented seizures 24 hours after the application of the vaccine with no clear relation between vaccination and seizure frequency, and one patient required admission to the hospital for a prolonged seizure. Conclusion: Vaccination against SARS-CoV-2 in paediatric patients with epilepsy is safe. Approximately 3% of patients with epilepsy could eventually have seizures in the post-vaccination period.(AU)
Subject(s)
Humans , Male , Female , Child , Severe acute respiratory syndrome-related coronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Pandemics , Epilepsy , Vaccination/adverse effects , Neurology , Nervous System Diseases , Pediatrics , Colombia , Seizures, FebrileABSTRACT
AIM: The objective of this study is to evaluate effects of SARS-CoV-2 vaccination on seizure pattern in paediatric patients with epilepsy that attended our tertiary center in the city of Bogota, Colombia. PATIENTS AND METHODS: Children with epilepsy who were treated at our center and have had SARS-CoV-2 vaccination and their caregivers were asked to report their experience following vaccination. We documented age, sex, age at onset of epilepsy, duration of epilepsy, epilepsy type, seizure frequency, number of medications, time from last crisis, vaccination schemes, and seizures two weeks after vaccination. RESULTS: One hundred and one patients with epilepsy were included (58%, male; and 42%, female). The average age was 11 years, 73% had focal epilepsy, and 27%, generalized. Twenty-one fulfilled criteria for refractory epilepsy and 11 had a personal history of febrile seizures. Forty-seven patients had been vaccinated with Sinovac's vaccine; 41 patients, with Pfizer's; 12 patients, with Moderna's; and one, with CoronaVac's. Three patients presented seizures 24 hours after the application of the vaccine with no clear relation between vaccination and seizure frequency, and one patient required admission to the hospital for a prolonged seizure. CONCLUSION: Vaccination against SARS-CoV-2 in paediatric patients with epilepsy is safe. Approximately 3% of patients with epilepsy could eventually have seizures in the post-vaccination period.
TITLE: Vacunación contra el SARS-CoV-2 en pacientes pediátricos con epilepsia: experiencia de un centro terciario en Colombia.Objetivo. El objetivo de este estudio es evaluar los efectos de la vacunación contra el SARS-CoV-2 sobre el patrón convulsivo en pacientes pediátricos con epilepsia que acudieron a nuestro centro terciario en la ciudad de Bogotá, Colombia. Pacientes y métodos. Se pidió a los niños con epilepsia que fueron tratados en nuestro centro y que habían recibido la vacuna contra el SARS-CoV-2 y a sus cuidadores que informaran de su experiencia después de la vacunación. Se documentaron la edad, el sexo, la edad de inicio de la epilepsia, la duración de la epilepsia, el tipo de epilepsia, la frecuencia de las convulsiones, el número de medicamentos, el tiempo transcurrido desde la última crisis, los esquemas de vacunación y las convulsiones dos semanas después de la vacunación. Resultados. Se incluyó a 101 pacientes con epilepsia (58%, hombres; y 42%, mujeres). La edad promedio fue de 11 años, el 73% tenía epilepsia focal, y el 27%, generalizada. Veintiuno cumplían los criterios para la epilepsia refractaria y 11 tenían antecedentes personales de convulsiones febriles. Cuarenta y siete pacientes habían sido vacunados con la vacuna de Sinovac; 41, con Pfizer; 12, con Moderna; y uno, con CoronaVac. Tres pacientes presentaron convulsiones 24 horas después de la aplicación de la vacuna sin una relación clara entre la vacunación y la frecuencia de las convulsiones, y un paciente requirió ingreso en el hospital por una convulsión prolongada. Conclusión. La vacunación contra el SARS-CoV-2 en pacientes pediátricos con epilepsia es segura. Aproximadamente el 3% de los pacientes con epilepsia podría eventualmente tener convulsiones en el período posterior a la vacunación.
Subject(s)
COVID-19 , Epilepsy , Status Epilepticus , Child , Humans , Male , Female , Infant, Newborn , COVID-19 Vaccines , Colombia , SARS-CoV-2 , COVID-19/prevention & control , VaccinationABSTRACT
En esta publicación se presentan criterios y fundamentos para la organización del trabajo en la práctica segura de la Radiofarmacia Hospitalaria, a fin de minimizar el riesgo de transmisión viral durante la pandemia de COVID-19, en una instalación de referencia de la Comisión Nacional de Energía Atómica de Argentina, mientras se continúan desempeñando servicios esenciales para el sistema de salud. Con este fin se consultaron como referencia documentos de la Comisión Nacional de Energía Atómica, OIEA, la OMS y otras publicaciones científicas. Estas recomendaciones se encuentran en proceso de revisión constante y son actualizadas de manera permanente. En este marco se propone el presente modelo de organización laboral para esta actividad esencial incluyendo recomendaciones generales, particulares y su fundamento epidemiológico e inmunológico
This publication presents criteria and bases for the work organization in the safe practice of Hospital Radiopharmacy, in order to minimize the risk of viral transmission during the COVID-19 pandemic, in a reference facility of the National Energy Commission Atomic of Argentina, while continuing to perform essential services for the health system. For this purpose, documents from the National Energy Commission Atomic, IAEA, WHO and other scientific publications were consulted as reference. These recommendations are under constant review and are permanently updated. Within this framework, the present model of work organization for this essential activity is proposed, including general and specific recommendations and its epidemiological and immunological basis
Subject(s)
Humans , Severe acute respiratory syndrome-related coronavirus/pathogenicity , Coronavirus Infections/epidemiology , Radiopharmaceuticals/supply & distribution , Pharmaceutical Services/organization & administration , Risk Factors , Coronavirus Infections/prevention & control , Pandemics/statistics & numerical data , Argentina/epidemiology , Disease Transmission, Infectious/prevention & control , Universal Precautions/methods , Good Dispensing PracticesABSTRACT
This publication presents criteria and bases for the work organization in the safe practice of Hospital Radiopharmacy, in order to minimize the risk of viral transmission during the COVID-19 pandemic, in a reference facility of the National Energy Commission Atomic of Argentina, while continuing to perform essential services for the health system. For this purpose, documents from the National Energy Commission Atomic, IAEA, WHO and other scientific publications were consulted as reference. These recommendations are under constant review and are permanently updated. Within this framework, the present model of work organization for this essential activity is proposed, including general and specific recommendations and its epidemiological and immunological basis.
Subject(s)
COVID-19/epidemiology , Nuclear Medicine/organization & administration , Pandemics , Pharmacy Service, Hospital/organization & administration , SARS-CoV-2 , Argentina/epidemiology , COVID-19/diagnosis , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Testing/methods , Humans , Hygiene/standards , Nuclear Medicine/standards , Organizational Objectives , Personnel Staffing and Scheduling/organization & administration , Pharmacy Service, Hospital/standards , Radiopharmaceuticals/standards , SARS-CoV-2/immunology , Workplace/organization & administration , Workplace/standardsABSTRACT
INTRODUCTION: To date, no formal study has been published regarding how Colombian patients with skin disorders could be affected according to their perception of disease. OBJECTIVE: To determine the impact in quality of life of skin diseases in a Colombian population. METHODS: This multicenter study included patients with skin disease from almost the whole country. Individuals >18 years old; of any gender; with any skin disease and who signed informed consent, were included. We applied the Colombian validated version of the Skindex-29 instrument. RESULTS: A total of 1896 questionnaires had sufficient information for the analyses. No significant differences in sociodemographic characteristics of patients who returned the questionnaire incomplete vs. complete, were found. Participants mean age was 41.5 years. There were no statistical differences in men vs. women regarding the global (p = 0.37), symptoms (p = 0.71) and emotions (p = 0.32) domains, whereas statistical differences were found in the function domain (p = 0.04; Mann-Whitney U test). Psoriasis, contact dermatitis, atopic dermatitis, urticaria, hair disorders, Hansen's disease, scars, hyperhidrosis and genital human papillomavirus disease scored the highest. Limitations. Skindex-29 score variability as a result of differences in the location of the skin lesions, their inflammatory or non-inflammatory nature, and the start of therapy. CONCLUSIONS: Even the most localized or asymptomatic skin lesion in our population leads to a disruption at some level of patient's wellness. This study adds well supported scientific data of the burden of skin diseases worldwide
INTRODUCCIÓN: En Colombia se carece de estudios que hayan evaluado formalmente el impacto de las enfermedades dermatológicas en la calidad de vida de los pacientes que las padecen. OBJETIVO: Determinar el impacto en la calidad de vida de las enfermedades cutáneas en una población colombiana. MÉTODOS: Estudio multicéntrico que incluyó a individuos>18 años de edad; de cualquier sexo, con cualquier trastorno cutáneo y que firmaron el consentimiento informado. Se aplicó la versión validada en Colombia del instrumento Skindex-29. RESULTADOS: Un total de 1.896 cuestionarios se incluyeron en el análisis. No se observaron diferencias significativas en las características sociodemográficas entre los que devolvieron el cuestionario incompleto vs. completo. La edad promedio fue de 41,5 años. No hubo diferencias significativas entre hombres y mujeres con respecto al puntaje global del instrumento, ni de los dominios sintomático o emocional, mientras que sí las hubo en el dominio funcional. Entre las enfermedades que más afectaron la calidad de vida se incluyen: psoriasis, dermatitis de contacto, dermatitis atópica, urticaria, trastornos capilares, lepra, cicatrices, hiperhidrosis y las verrugas genitales. Limitaciones. Las puntuaciones del Skindex-29 mostraron una gran variabilidad explicable por diferencias en la localización de las lesiones de la piel, su naturaleza inflamatoria/no inflamatoria, y la iniciación o no del tratamiento. CONCLUSIONES: Cualquier lesión dermatológica por más localizada o asintomática que sea, condujo a una alteración en algún grado de la calidad de vida dermatológica. Este estudio añade soporte científico a la carga de enfermedad que generan los trastornos cutáneos en el mundo
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Quality of Life , Skin Diseases/epidemiology , Skin Diseases/prevention & control , Organ Dysfunction Scores , Psoriasis/epidemiology , Dermatitis, Atopic/epidemiology , Colombia/epidemiology , Surveys and Questionnaires , Data Analysis/methods , Cross-Sectional Studies/methods , Statistics, NonparametricABSTRACT
INTRODUCTION: To date, no formal study has been published regarding how Colombian patients with skin disorders could be affected according to their perception of disease. OBJECTIVE: To determine the impact in quality of life of skin diseases in a Colombian population. METHODS: This multicenter study included patients with skin disease from almost the whole country. Individuals >18 years old; of any gender; with any skin disease and who signed informed consent, were included. We applied the Colombian validated version of the Skindex-29 instrument. RESULTS: A total of 1896 questionnaires had sufficient information for the analyses. No significant differences in sociodemographic characteristics of patients who returned the questionnaire incomplete vs. complete, were found. Participants mean age was 41.5 years. There were no statistical differences in men vs. women regarding the global (p=0.37), symptoms (p=0.71) and emotions (p=0.32) domains, whereas statistical differences were found in the function domain (p=0.04; Mann-Whitney U test). Psoriasis, contact dermatitis, atopic dermatitis, urticaria, hair disorders, Hansen's disease, scars, hyperhidrosis and genital human papillomavirus disease scored the highest. LIMITATIONS: Skindex-29 score variability as a result of differences in the location of the skin lesions, their inflammatory or non-inflammatory nature, and the start of therapy. CONCLUSIONS: Even the most localized or asymptomatic skin lesion in our population leads to a disruption at some level of patient's wellness. This study adds well supported scientific data of the burden of skin diseases worldwide.
Subject(s)
Quality of Life , Skin Diseases , Adolescent , Adult , Cross-Sectional Studies , Diagnostic Self Evaluation , Female , Humans , Male , Middle Aged , Skin Diseases/psychology , Young AdultABSTRACT
Adult female rats, undernourished at perinatal age, were evaluated for anxiolytic action in the plus-maze test after acute and chronic administration of diazepam (DZP) and pentobarbital (PTB). Deprived (D) rats chronically treated with vehicle showed an increased anxiety as compared with control (C) animals. A single intraperitoneal (i.p.) administration of DZP (1 mg/kg) or PTB (7.5 mg/kg) produced similar anticonflict effect in both C and D rats. Tolerance to the anxiolytic effect of DZP and PBT developed in C rats after a 15-day administration schedule, whereas no tolerance was observed in D animals. Drug disposition was not altered after chronic treatment either in C or in D rats. Gamma-aminobutyric acid (GABA)-mediated chloride uptake in microsacs of cerebral cortex of naive D rats was decreased as compared with naive C rats. After chronic DZP administration (1 mg/kg/day i.p. for 15 days), GABA-mediated 36Cl- influx in brain cortex microsacs of C rats did not change; however, GABA efficacy was increased in microsacs of D animals. In addition, chronic DZP treatment induced GABA-benzodiazepine uncoupling in brain cortex of C rats, but not in D animals, as assessed by chloride uptake in microsacs. Chronic PTB treatment (7.5 or 30 mg/kg/day i.p. for 15 days) did not modify GABA stimulation or GABA-PTB interaction in cortical microsacs of C or D rats.
Subject(s)
Animals, Newborn/physiology , Anti-Anxiety Agents/administration & dosage , Diazepam/administration & dosage , Nutrition Disorders/physiopathology , Pentobarbital/administration & dosage , Animal Nutritional Physiological Phenomena , Animals , Anti-Anxiety Agents/pharmacokinetics , Anti-Anxiety Agents/pharmacology , Brain/metabolism , Chlorides/pharmacokinetics , Diazepam/pharmacokinetics , Diazepam/pharmacology , Drug Synergism , Drug Tolerance/physiology , Female , Maze Learning/drug effects , Pentobarbital/pharmacokinetics , Pentobarbital/pharmacology , Rats , Rats, Wistar , Time Factors , gamma-Aminobutyric Acid/pharmacologyABSTRACT
Adult female rats, receiving a low protein diet at perinatal age and then recovered with balanced chow (D rats), were evaluated in the Open Field Drink Test (OFDT), after different acute and chronic treatments with benzodiazepines (BZD) ligands, as compared with control (C) female rats. Control and D rats showed similar reactivity to acute administration of diazepam (DZP, 1 mg/kg) and FG 7142 (2.5mg/kg), both BZD ligands with anxiolytic and anxiogenic effects, respectively. After chronic DZP treatment (3mg/kg/day i.p. for 3 weeks), C rats developed tolerance to the anxiolytic effect of DZP as well as withdrawal syndrome upon abrupt interruption of chronic treatment. On the contrary, D animals failed to develop tolerance to the anxiolytic effect of DZP, and did not show an increased anxiety upon withdrawal. The functionality of the GABAA receptor-complex, as measured by (36)Cl(-) uptake in cortical cerebral microsacs, was not altered in the DZP withdrawn rats. The lack of tolerance and withdrawal syndrome may be related to the incapacity of D rats to generate adaptive changes after chronic treatments. For instance, C rats showed a lower anxiety level in the OFDT after chronic vehicle administration, whereas D animals did not evidence such an adaptive response. Furthermore, D rats failed to respond to the anxiolytic effect of DZP after chronic vehicle treatment. These results reassert the deleterious effects of perinatal undernutrition on the capacity to develop adaptive responses to repeated drug administration or adequate stimuli.
ABSTRACT
We have previously reported that recovered adult rats undernourished at perinatal age failed to develop tolerance to the anticonflict effect of ethanol after chronic ethanol administration (1 g/kg/day during 30 days) (4). To further study the extent of this finding, we examined the effect of a similar chronic ethanol treatment on the hypothermic and anticonvulsant effects of ethanol in perinatally deprived rats. Hypoalgesic activity was assessed in ethanol treated rats during 15 days. After chronic ethanol treatment, a similar development of tolerance to the hypothermic effect of ethanol was observed in control and deprived rats. However, tolerance to the anticonvulsant and hypoalgesic effect of ethanol was significantly reduced in deprived as compared with control animals. Thus, early undernutrition differentially affects the development of tolerance elicited by chronic ethanol administration.
Subject(s)
Ethanol/pharmacology , Prenatal Exposure Delayed Effects , Protein-Energy Malnutrition/physiopathology , Animals , Anti-Anxiety Agents/pharmacology , Body Temperature/drug effects , Diet, Protein-Restricted , Drug Tolerance , Ethanol/administration & dosage , Female , Pain Measurement/drug effects , Pregnancy , Rats , Rats, Wistar , Seizures/physiopathologyABSTRACT
Learning ability of adult rats undernourished at perinatal age and nutritionally recovered (D-rats) was assayed in the Morris water maze test as compared with controls (C-rats). D-rats showed longer escape latencies to locate a hidden platform in absence of proximal cues during the acquisition period. Swimming pre-training experience did not improve this shortcoming. Retention scores obtained 1, 3, 10 and 30 days after training showed that spatial information was efficiently consolidated after acquisition since D-rats performed as well as C-rats on retention tests. A cue learning task revealed no significant differences between both groups. These results suggest that perinatal undernutrition induces, even after a long period of nutritional recovery, a deficit in efficient place navigation in adult rats.
Subject(s)
Maze Learning , Protein Deficiency/physiopathology , Analysis of Variance , Animals , Female , Memory , Pregnancy , Rats , Rats, Wistar , Reaction Time , Spatial Behavior , SwimmingABSTRACT
Learning ability of adult rats undernourished at perinatal age and nutritionally recovered (D-rats) was assayed in the Morris water maze test as compared with controls (C-rats). D-rats showed longer escape latencies to locate a hidden platform in absence of proximal cues during the acquisition period. Swimming pre-training experience did not improve this shortcoming. Retention scores obtained 1, 3, 10 and 30 days after training showed that spatial information was efficiently consolidated after acquisition since D-rats performed as well as C-rats on retention tests. A cue learning task revealed no significant differences between both groups. These results suggest that perinatal undernutrition induces, even after a long period of nutritional recovery, a deficit in efficient place navigation in adult rats.
ABSTRACT
Adult rats submitted to a protein deprivation schedule at perinatal age (from 14th day of fetal life until 50 days of age) and then recovered on balanced chow (D rats) were assayed in the elevated plus-maze test for anticonflict effects of diazepam and drugs with therapeutic efficacy in panic disorders as compared with controls (C rats). Diazepam and alprazolam showed a similar anticonflict effect in D rats than in C rats. In contrast, buspirone, which was ineffective in C rats at a wide dosage range, showed a significant anticonflict effect on D rats at 0.3 mg/kg. Neither propranolol, desipramine, nor phenelzine treatment (10 mg/kg/day during 3-7 days) induced anticonflict effect in C rats. Conversely, these treatments fostered a significant and selective anxiolytic effect on D rats. Such results underscore long-lasting alterations caused by early undernutrition, namely, changes in reactivity to the drugs assayed. In addition, perinatally deprived rats may represent a useful animal model for studying potential antipanic agents.
Subject(s)
Anti-Anxiety Agents/pharmacology , Anxiety/psychology , Panic Disorder/drug therapy , Protein Deficiency/psychology , Animals , Anti-Anxiety Agents/therapeutic use , Conflict, Psychological , Diazepam/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Exploratory Behavior/drug effects , Female , Pregnancy , Rats , Rats, WistarABSTRACT
The anticonflict effects of ethanol, diazepam and pentobarbital were evaluated in adult rats fed a low protein diet during the perinatal period in the plus-maze test, after single injections and following chronic ethanol administration (1 g.kg-1.d-1 for 30 d). Reactivity to the anticonflict effect of these drugs was similar in control and protein-deprived rats after acute treatment. After chronic ethanol administration, control rats showed tolerance to ethanol and cross-tolerance (i.e., lower reactivity) to the anxiolytic effect of diazepam and pentobarbital. Conversely, protein-deprived rats showed greater reactivity to ethanol and lack of cross-tolerance to diazepam and pentobarbital following chronic ethanol treatment. A significantly greater density of cortical gamma-aminobutyric acid receptors subtype A (GABA-A) was detected in protein-deprived rats after chronic ethanol administration compared with the density after chronic saline treatment, whereas no differences were observed in nourished controls. This suggests that the greater anxiolytic activity detected in protein-deprived rats may correlate with higher GABA-A receptor density.
Subject(s)
Ethanol/pharmacology , Protein Deficiency/metabolism , Animals , Behavior, Animal/drug effects , Diazepam/administration & dosage , Diazepam/pharmacology , Drug Tolerance , Ethanol/administration & dosage , Female , Maternal-Fetal Exchange , Motor Activity/drug effects , Pentobarbital/administration & dosage , Pentobarbital/pharmacology , Pregnancy , Rats , Rats, Inbred Strains , Receptors, GABA-A/drug effects , gamma-Aminobutyric Acid/metabolismABSTRACT
Prenatal alcohol acute contamination of the amniotic fluid and different postnatal manipulations with this drug alter subsequent responsiveness to EtOH's chemosensory cues. In this study, the interaction between prenatal and postnatal alcohol-related experiences was examined. Alcohol administered in the amniotic fluid during gestational Day 21 potentiated subsequent alcohol-odor conditioned preferences resulting from postnatal pairings between the odor and sucrose intraoral infusions. No interaction was attained when examining the impact of the in utero experience with postnatal aversive conditioning defined by alcohol odor-citric acid pairings (Exps. 1a & 1b). In Exp. 2, infantile alcohol aversions derived from a state of acute ethanol intoxication were inhibited by prior alcohol experience in utero. Examination of alcohol levels in fetal trunk blood and the amniotic fluid suggests that the antenatal experience is related to the chemosensory perception of the drug rather than its intoxicating properties (Exp. 3). These results strongly suggest that the alcohol-related memory generated proximal to birth can modulate subsequent learning with the drug.
Subject(s)
Amniotic Fluid/chemistry , Animals, Newborn/physiology , Conditioning, Psychological/drug effects , Embryonic and Fetal Development , Ethanol/administration & dosage , Maternal-Fetal Exchange , Smell/drug effects , Animals , Avoidance Learning/drug effects , Ethanol/pharmacology , Female , Humans , Infant, Newborn , Pregnancy , Rats , Rats, Inbred Strains , Reinforcement, Psychology , SucroseABSTRACT
Adult female rats submitted to a protein deprivation schedule at perinatal age (from 14th day of fetal life until 50 days of age) were tested for alcohol intake in a preference test. When compared with control animals, experimental rats exhibited higher overall fluid intake. Nevertheless, in terms of ethanol preference these subjects evidenced lower preference to this drug. A test for assessing ethanol olfactory preference did not show any differences between control and experimental rats in basal conditions. However, after repeated exposure to alcohol, deprived rats showed an aversion to ethanol odor, while controls evidenced the opposite effect, i.e., heightened preference. Possible differences to the aversive effects of ethanol between control and experimental animals were assayed by means of two taste aversion tests, by associating alcohol to sucrose or NaCl. No differences were detected between both groups of rats. These results demonstrate that early undernutrition reduces ethanol preference in a free choice situation. Such an effect could be due, at least partially, to odor aversion developed by repeated exposure.
Subject(s)
Alcohol Drinking/physiology , Avoidance Learning/physiology , Food Deprivation/physiology , Taste/physiology , Animals , Body Weight/physiology , Brain/physiology , Conditioning, Classical/physiology , Dietary Proteins/administration & dosage , Female , Neurotransmitter Agents/physiology , Pregnancy , Rats , Rats, Inbred Strains , Social EnvironmentABSTRACT
Different effects of ethanol were assayed in adult rats submitted to a protein deprivation schedule at perinatal age. Hypothermic and hypnotic responses were higher than normal in experimental rats, while the anticonflict effect of ethanol was lower in deprived animals. No differences were detected in the ethanol clearance rate between control and undernourished rats. These results stressed that the deleterious effects of early undernutrition persist in adult recovered animals and induce an altered reactivity to different pharmacological treatments.
Subject(s)
Avoidance Learning/drug effects , Ethanol/pharmacology , Hypothermia/physiopathology , Protein-Energy Malnutrition/physiopathology , Sleep/drug effects , Animals , Female , Male , Pregnancy , Protein-Energy Malnutrition/diet therapy , Rats , Rats, Inbred StrainsABSTRACT
Ganglioside pretreatment enhanced the anti-immobility effect induced in the forced swim test after a chronic treatment with desipramine, mianserin, clomipramine, nialamide or repeated electroconvulsive shock in mice. Gangliosides, which had no effect per se, showed a clear dose-response relationship in enhancing the anti-immobility effect of desipramine. These results suggest that, regardless of their mechanisms of action, gangliosides facilitate the behavioral response of several antidepressant treatments.
Subject(s)
Antidepressive Agents/pharmacology , Gangliosides/pharmacology , Motor Activity/drug effects , Animals , Clomipramine/pharmacology , Desipramine/pharmacology , Dose-Response Relationship, Drug , Electroshock , Halothane/pharmacology , Male , Mianserin/pharmacology , Mice , Nialamide/pharmacologyABSTRACT
Different effects of ethanol were assayed in adult rats submitted to a protein deprivation schedule at perinatal age. Hypothermic and hypnotic responses were higher than normal in experimental rats, while the anticonflict effect of ethanol was lower in deprived animals. No differences were detected in the ethanol clearance rate between control and undernourished rats. These results stressed that the deleterious effects of early undernutrition persist in adult recovered animals and induce an altered reactivity to different pharmacological treatments.
ABSTRACT
Offspring of rats were submitted to a protein deprivation dietary treatment from the third week of gestation until 50 days of age, and later nutritionally rehabilitated for at least 90 days. In the punished lever-pressing conflict test, undernourished animals exhibited a decreased reactivity to the anticonflict effect of a 3 mg/kg dose of diazepam as compared to control animals. This decreased reactivity to diazepam in a shock-induced conflict test indicates that functional alterations in the GABAergic transmission might contribute to the state of hypersensitivity to stressful or aversive situations present in undernourished animals.