RESUMEN
BACKGROUND: We previously reported that ethanol-containing liquid diet feeding induces osteonecrosis of the femoral head in male rats. Also, it was reported that a large amount of consumed ethanol and a long-term history of drinking were risk factors for osteonecrosis of the femoral head, and that the frequency of alcohol-induced osteonecrosis of the femoral head in males was much greater than in females. The higher incidence of alcohol-induced osteonecrosis of the femoral head could be due to either higher prevalence of alcohol drinking in males or due to their potential higher sensitivity to alcohol. The aim of the study is to investigate the influence of alcohol consumption and drinking period on the development of osteonecrosis of the femoral head in rats of both sex. METHODS: All the experimental male rats were allocated to the male one-month ethanol drinking group (M1). Female rats were randomly divided into the female one- to five-months ethanol drinking groups (F1-5). All rats were fed a Lieber-DeCarli liquid diet containing 5% ethanol for one to five months. RESULTS: One-month feeding with the ethanol-containing liquid diet resulted in the development of osteonecrosis of the femoral head in seven of twenty in the M1 group, but none in the F1 group, although the mean intake of ethanol per body weight in the M1 group was significantly lower than that in the F1 group. Furthermore, long drinking periods with a large amount of ethanol intake in the F2-5 groups did not induce osteonecrosis of the femoral head. CONCLUSION: The present study shows that lower alcohol consumption over short periods of time that were sufficient to induce osteonecrosis of the femoral head in males had no effect on females. Even with greater alcohol consumption and longer duration, females did not develop osteonecrosis of the femoral head. Therefore, unknown factors related to sex must be responsible for the development of this condition.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Cabeza Femoral , Osteonecrosis/etiología , Caracteres Sexuales , Animales , Femenino , Cabeza Femoral/efectos de los fármacos , Masculino , Ratas , Factores de TiempoRESUMEN
PURPOSE: We retrospectively evaluated the cerebro-spinal fluid (CSF) CT density at the lateral ventricle to compare the postmortem intervals in cadavers. MATERIALS AND METHODS: The number of cadavers enrolled in this study was 189 (male 120, female 69). According to the estimated postmortem time, the cadavers were divided into 13 groups (postmortem day 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 7, 10, 14, 21, 30), and were also re-grouped into 3 groups according to the postmortem time-width: group A (postmortem day 0.5-2.5), group B (day 3-7), and group C (day 10-30). Comparisons between the CSF density and estimated postmortem time were also analyzed. RESULTS: The CSF density was around 20HU up to day 2.5, and it increased gradually after day 3. Day 3 and 4 presented higher CSF density than day 1 and 1.5 (p<0.05). Day 7 presented higher CSF density than day 3 (p<0.05). According to the postmortem time-width, the CSF density increased with postmortem time (p<0.05). The simple linear regression equations presented negative correlation between CSF density and estimated postmortem time, and R(2) was 0.119. CONCLUSION: The CSF density increased, but not linearly, according to the postmortem time, and the 3rd postmortem day was the earliest time allowing the difference to be detected. The CSF density needs further evaluation to enable estimation of the postmortem time.
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Autopsia , Líquido Cefalorraquídeo/fisiología , Cambios Post Mortem , Tomografía Computarizada por Rayos X , Anciano , Cadáver , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: Experimental drowning models were prepared to investigate the time-related course of lung changes using postmortem CT. This study was approved by our institutional animal ethics committee. MATERIALS AND METHODS: Fifteen NZW rabbits (female fifteen, 2.6-4.3 (mean 3.3)kg) were divided into 3 groups: fresh water drowning (FRESH), sea water drowning (SEA), and sea water drowning with anterior chest compression (ACC). All individuals were examined by CT (Aquilion CX, Toshiba, Japan) on postmortem time course. The rabbit's head was submerged in a water bath for a total of 10 min. In ACC, cardiopulmonary resuscitation was performed for 2 min, additionally. The percentage of aerated lung volumes (%ALV=100 (aerated lung volume/total lung volume)) were statistically evaluated and the lung CT image patterns and pleural fluid appearance time were investigated. RESULTS: All lungs had decreased their %ALV within 24h, and there were no statistical differences in and among the 3 groups. After 36 h, %ALV tended to increase in all groups, and only ACC presented a statistical difference between 1h and 36 h (p<0.005). On postmortem lung CT, all lungs presented ground-glass opacity with interstitial thickening spread pattern (100%) and no pattern change during the follow-up period. After presenting pleural space fluid collection, the %ALV tended to increase. CONCLUSION: There were no differences among FRESH, SEA, and ACC in %ALV within 24h. Only ground-glass opacity could be detected on postmortem lung CT, experimentally.
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Ahogamiento , Agua Dulce , Pulmón/diagnóstico por imagen , Pulmón/patología , Agua de Mar , Tomografía Computarizada por Rayos X , Animales , Patologia Forense , Cambios Post Mortem , ConejosRESUMEN
Two 60-year-old males were found at their homes whose bodies had deteriorated due to putrefaction. To prevent worm invasion and minimize deterioration, dry ice was used prior to the autopsy investigation. Prior to autopsy, postmortem CT demonstrated a decreased density in brain parenchyma at the dry-iced side, and autopsy revealed deteriorated brain parenchyma with frozen effect (presented like sherbet). Moreover, the deteriorated cerebral parenchyma maintained their structure and they were evaluated by cutting. When lower CT density presents in postmortem CT, the freezing effect may need to be considered and the physician should evaluate the cadaver's postmortem condition to prevent misdiagnoses.
Asunto(s)
Encéfalo/patología , Patologia Forense/métodos , Congelación , Autopsia , Encéfalo/diagnóstico por imagen , Causas de Muerte , Errores Diagnósticos/prevención & control , Hielo Seco , Humanos , Masculino , Persona de Mediana Edad , Neumotórax/patología , Cambios Post Mortem , Tomografía Computarizada por Rayos X , Imagen de Cuerpo Entero/métodosRESUMEN
We previously reported that a toll-like receptor 4 signaling contributes to the development of osteonecrosis of the femoral head. Also, oxidative stress is suggested to be one of the possible pathogenesis of osteonecrosis of the femoral head. A recent study showed that toll-like receptor 4 signaling leads to oxidative stress. The aim of the present study was to evaluate whether toll-like receptor 4 stimulation and subsequent corticosteroid treatment lead to the development of osteonecrosis of the femoral head in rat, and oxidative stress is associated with it. Male Wistar rats were randomly divided into four treatment groups: Saline + Saline, Saline + Methylprednisolone, Lipopolysaccharide + Saline, Lipopolysaccharide + Methylprednisolone. Osteonecrosis of the femoral head at 14 days after the treatment was observed in 1 of 10 Lipopolysaccharide + Saline, and 5 of 10 Lipopolysaccharide + Methylprednisolone treated rats. However, it was not observed at all in the Saline + Saline and Saline + Methylprednisolone treated groups. Glutathione peroxidase activity in the liver at 1 day after the treatment was significantly increased when treated with lipopolysaccharide. However, methylprednisolone treatment reduced the activity. On the other hand, glutathione peroxidase activity in the femur did not change in any intergroup. In conclusion, the present study showed that toll-like receptor 4 stimulation by lipopolysaccharide administration strengthen incidence of corticosteroid-induced osteonecrosis of the femoral head, however, concomitant oxidative stress via toll-like receptor 4 signaling may not contribute to the development of osteonecrosis of the femoral head in rats.
Asunto(s)
Necrosis de la Cabeza Femoral/inducido químicamente , Glucocorticoides/efectos adversos , Glutatión Peroxidasa/metabolismo , Metilprednisolona/efectos adversos , Receptor Toll-Like 4/metabolismo , Animales , Necrosis de la Cabeza Femoral/enzimología , Lipopolisacáridos , Masculino , Distribución Aleatoria , Ratas WistarRESUMEN
OBJECTIVE: Experimental fatal models were prepared to investigate the time-related course of lung changes using postmortem CT (PMCT). This study was approved by our institutional animal ethics committee. MATERIALS AND METHODS: Twenty-four NZW rabbits (female 24, 2.30-4.30 (mean 3.10)kg) were divided into 4 fatal groups; drowning, hypothermia, bag suffocation, and Potassium Chloride intravenous (control) group. All individuals were examined by CT (Aquilion CX, Toshiba, Japan) on postmortem time course until detection of putrefaction air. The percent of aerated lung volume (%ALV=100*(ALV/total lung volume)) was measured and the pleural space fluid was investigated by axial imaging. A paired t-test and Bonferroni/Dunn study were employed for statistical evaluation. RESULTS: In intra-group analysis, the %ALV showed statistically different periods compared with each pre-image: 4-48 h in control, 1-24h in drowning, 5-6h in hypothermia, and 1-4h in bag suffocation. In inter-group comparison (compared with control group), the %ALV increased in suffocation and decreased in drowning within 12h. The %ALV remained significantly high in hypothermia until 24h. The earliest detection times of pleural space fluid collection were different in each group: control (20 h), drowning (18 h), suffocation (36 h), and hypothermia (95 h). CONCLUSION: The lung hypostasis and the appearance of pleural space fluid collection presented differently in individual causes of death and depending on the postmortem time.
Asunto(s)
Patologia Forense/métodos , Pulmón/diagnóstico por imagen , Pulmón/patología , Cambios Post Mortem , Tomografía Computarizada por Rayos X , Animales , Asfixia , Autopsia , Modelos Animales de Enfermedad , Ahogamiento , Femenino , Hipotermia , Cloruro de Potasio/envenenamiento , ConejosRESUMEN
Postmortem CT (PMCT) is increasingly used in forensic practice, and knowledge and classification of typical hemopericardium on PMCT would help to assure correct radiological interpretation. The goal of this study was to evaluate the pericardial and pleural space fluid volumetry, and to evaluate the signs on PMCT pointing to cardiac tamponade as the cause of death, and their pitfalls. Fourteen cadavers (eleven male, three female, 49-87 [mean, 70.9] years) were examined by PMCT. The pericardial volume and pericardial findings with/without pleural space fluid collection were compared with autopsy findings. In addition, the appearance of pericardial lesions on PMCT was documented and compared with the autopsy findings. The respective volumes of pericardial space, and right and left pleural space fluid showed as 172.0-711.0 (mean 368.7) ml, 0-1830.0 (266.1) ml, 0-231.0 (75.2) ml on PMCT, and were 136.0-652.0 (311.1) ml, 0-2100 (299.0) ml, and 0-300.0 (61.3) ml on autopsy. In statistical evaluation, the pericardial space volume was significantly greater on PMCT (p<0.05), but there was no significant difference in pleural space fluid volume. The hemopericardium PMCT showed 3 patterns: double band, single band, and horizontal level, and the former two patterns presented as coagulated blood at autopsy. Single band and horizontal level patterns were thought to result from CPR-related causes and/or postmortem manipulation. In conclusion, double and single band patterns on PMCT were indicative findings of cardiac tamponade. An understanding of the pericardial PMCT appearance and its significance can help to avoid misreading, and is important for making correct radiological interpretation.
Asunto(s)
Autopsia/métodos , Taponamiento Cardíaco/diagnóstico , Derrame Pericárdico/clasificación , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Postmortem CT (PMCT) is increasingly used in forensic practice, and knowledge and classification of typical postmortem imaging findings would facilitate the interpretation of PMCT. The goal of this study was to define the time-related course of postmortem chest findings. Twelve cadavers (eight male, four female, 27-81 [mean, 60.0]years) were examined twice by PMCT within an interval of time (4-164 h [mean, 30.8; median, 17.5]). The pleural-space-fluid volume, pulmonary parenchyma volume, decreased aerated lung volume (DLV), %DLV (=DLV/pulmonary parenchyma volume) and chest cavity volume were compared between the first and second PMCT examinations. To evaluate the volume change rate, the rate of increase in pleural space fluid volume (mL/h) and the DLV rate (mL/h) were plotted according to the postmortem period. On the second PMCT, the volume of pleural space fluid (p=0.0469) and %DLV (p=0.0161) were significantly increased. The increase rate of the pleural space fluid increased at approximately 30 h and the volume continued to increase until approximately 40 h after death. The rate of DLV constantly decreased in the early postmortem period. In conclusion, the pleural-space-fluid collection and the DLV increased over different time-related courses in the postmortem period.
Asunto(s)
Patologia Forense/métodos , Cavidad Pleural/diagnóstico por imagen , Derrame Pleural/diagnóstico por imagen , Cambios Post Mortem , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Non-traumatic osteonecrosis of the femoral head (ONFH) often occurs after corticosteroid therapy in patients with inflammatory diseases. Recent studies suggest that toll-like receptor (TLR) signaling may contribute to the pathogenesis of inflammatory diseases, and that the reason for corticosteroid therapy for inflammatory diseases is related to the anti-inflammatory activities of corticosteroids through the reduction of NF-κB. We hypothesized that the administration of TLR ligands in combination with corticosteroid causes ONFH and that transcription factors may contribute to the pathogenesis of ONFH. The aim of the study was to evaluate (1) the incidence of ONFH in rats after the administration of TLR7 or TLR9 ligands together with methylprednisolone (MPSL) and (2) whether transcription factors contribute to the development of ONFH. Male Wistar rats (n=148) were divided into five groups as follows: Group 1: Saline+MPSL, Group 2: Imiquimod+Saline, Group 3: Imiquimod+MPSL, Group 4: CpG-C+MPSL, Group 5: Imiquimod+BAY11-7082+MPSL. As a result, ONFH was observed in 0 of 12 rats in Group 1, in 1 of 10 in Group 2, in 6 of 12 in Group 3, in 4 of 12 in Group 4, in 0 of 9 in Group 5. MPSL treatment did not significantly affect IRF7 activity, whereas NF-κB activity was significantly repressed in Group 2 and Group 3. Furthermore, the repression in interferon regulatory factor 7 (IRF7) activity by BAY11-7082 interfered with the development of ONFH simultaneously with the MPSL treatment-induced repression in NF-κB activity. In conclusion, in the present study, corticosteroid treatment after the administration of TLR7 or TLR9 ligands caused ONFH. Repression in NF-κB activity by corticosteroid treatment boosted the development of ONFH.
Asunto(s)
Cabeza Femoral/patología , FN-kappa B/metabolismo , Osteonecrosis/fisiopatología , Receptor Toll-Like 7/agonistas , Receptor Toll-Like 9/agonistas , Animales , Secuencia de Bases , Sondas de ADN , Ensayo de Cambio de Movilidad Electroforética , Masculino , Ratas , Ratas WistarRESUMEN
We have developed a technique of CT-guided needle placement in the destructed human body in forensic practice. A sixty-year-old male was found in a burned car and he was also destructed severely. Although blood was needed for the external examination, it was difficult to approach the vessels because of the severely burned condition of the cadaver. Thus, we attempted to obtain a blood sample from a vessel using a CT-guided technique. Postmortem CT demonstrated the presence of blood-containing vessels in the pelvis. Indeed, CT-guided needle placement had no difficulty with surface markers, table location, or depth measurement from the surface. CT-guide needle placement is a feasible and reliable technique, so that when the tissue/blood sample is at risk of being spoiled, CT-guided needle placement could be a substitute for conventional sampling techniques.
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Recolección de Muestras de Sangre/métodos , Medicina Legal/métodos , Agujas , Tomografía Computarizada por Rayos X , Anciano , Humanos , MasculinoRESUMEN
An 11-month-old female baby was found dead by her mother. Cranial postmortem CT prior to the forensic autopsy showed dilatation of bilateral extra-axial spaces and ventricles. The autopsy revealed a new linear fracture of the left parietal bone and occipital bone, and a healed linear fracture of the right parietal bone and occipital bone like a mirror image of the left one as well. Intracranially, 230ml of subdural fluid were collected, which was mixed with blood. There was a fresh hemorrhage around a bridging vein of the left parietal lobe and the dura mater. Moreover, the outer side of the cerebrum and the inner side of the dura mater were covered by a thin membrane, which mater might have been previously formed because of being positive for Fe-staining and anti-CD68 antibody. A subdural hematoma might have been developed when the right side of the skull was previously fractured, which was transformed into a subdural hygroma. Subsequently, it is likely that, after the left side fracture of the skull occurred, the subdural hygroma rapidly enlarged due to hemorrhaging from the bridging vein, which resulted in intracranial hypertension, because microbleeding was detected in the brain stem. Accordingly, we diagnosed the cause and manner of death as intracranial hypertension due to subdural hemorrhage in subdural hygroma, and homicide, including child abuse, respectively.
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Maltrato a los Niños , Hematoma Subdural/complicaciones , Efusión Subdural/etiología , Autopsia , Femenino , Humanos , Lactante , Fracturas Craneales/complicaciones , Efusión Subdural/patologíaRESUMEN
Most opioid receptor agonists have abuse potential, and the rewarding effects of opioids can be reduced in the presence of pain. While each of the enantiomers of pentazocine has a differential pharmacologic profile, (±)-pentazocine has been used clinically for the treatment of pain. However, little information is available regarding which components of pentazocine are associated with its rewarding effects, and whether the (±)-pentazocine-induced rewarding effects can be suppressed under pain. Therefore, the present study was performed to investigate the effects of pain on the acquisition of the rewarding effects of (±)-pentazocine, and to examine the mechanism of the rewarding effects of (±)-pentazocine using the conditioned place preference paradigm. (±)-Pentazocine and (-)-pentazocine, but not (+)-pentazocine, produced significant rewarding effects. Even though the rewarding effects induced by (±)-pentazocine were significantly suppressed under pain induced by formalin, accompanied by increase of preprodynorphin mRNA levels in the nucleus accumbens, a high dose of (±)-pentazocine produced significant rewarding effects under pain. In the normal condition, (±)-pentazocine-induced rewarding effects were blocked by a low dose of naloxone, whereas the rewarding effects induced by high doses of pentazocine under pain were suppressed by naltrindole (a δ-opioid receptor antagonist). Interestingly, (±)-pentazocine did not significantly affect dopamine levels in the nucleus accumbens. These findings suggest that the rewarding effects of (-)-pentazocine may contribute to the abuse potential of (±)-pentazocine through µ- as well as δ-opioid receptors, without robust activation of the mesolimbic dopaminergic system. We also found that neural adaptations can reduce the abuse potential of (±)-pentazocine under pain.
Asunto(s)
Analgésicos Opioides/farmacología , Dolor/fisiopatología , Pentazocina/farmacología , Receptores Opioides delta/fisiología , Receptores Opioides mu/fisiología , Recompensa , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/química , Análisis de Varianza , Animales , Condicionamiento Psicológico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Isomerismo , Masculino , Naloxona/farmacología , Naltrexona/análogos & derivados , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Núcleo Accumbens/efectos de los fármacos , Pentazocina/administración & dosificación , Pentazocina/química , Ratas , Receptores Opioides delta/efectos de los fármacos , Receptores Opioides mu/efectos de los fármacosRESUMEN
An 80-year-old female was transferred to the hospital due to a traffic accident. Multiple cranial bone fractures with intracranial hemorrhage and intracranial air were detected. Despite treatment, the patient died after 6h. Twenty-one hours after the patient died, her whole body was scanned by postmortem CT, and a region of high density was detected within the left putamen. The autopsy revealed a cerebral contusion and multiple skull base fractures. Moreover, superabsorbent polymers (SAPs) were found within the left lateral ventricle and adjacent to the putamen, which appeared as a high-density lesion on postmortem CT at the left putamen, where the SAPs were compacted. Both ante- and postmortem conditions should be considered to prevent misdiagnoses based only on postmortem CT.
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Patologia Forense , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/patología , Tomografía Computarizada por Rayos X , Accidentes de Tránsito , Anciano de 80 o más Años , Autopsia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Traumatismos Craneocerebrales/diagnóstico por imagen , Errores Diagnósticos , Resultado Fatal , Femenino , Humanos , PolímerosRESUMEN
Alcohol-induced osteonecrosis of the femoral head (ONFH) is observed in alcohol abusers and patients with alcoholic fatty liver disease. It has been reported that Toll-like receptor 4 (TLR4) signalling plays a crucial role in the pathogenesis of alcoholic fatty liver disease. We previously reported a corticosteroid-induced ONFH rat model, and suggested that TLR4 signalling contributes to the pathogenesis of ONFH. Thus, it is thought that the pathogenesis of alcohol-induced ONFH is probably similar to that of corticosteroid-induced ONFH. The aim of this study was to develop a new animal model for alcohol-induced ONFH and to evaluate the relationship between the pro-inflammatory response via TLRs and the development of ONFH in rats. Male Wistar rats were fed a Lieber-DeCarli liquid diet containing 5% ethanol (experimental group) or dextran (control group) for 1-24 weeks. Histopathological and biochemical analyses were performed. Feeding the ethanol-containing liquid diet resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction and hyperlipidaemia, whereas feeding the dextran-containing diet did not cause ONFH. However, we could not recognize any relationship between the pro-inflammatory response via TLR4 and the development of alcohol-induced ONFH. Thus in this study we have developed a new rat model for alcohol-induced ONFH based on the feeding of an ethanol liquid diet. ONFH was observed within seven days from the start of feeding with 5% ethanol-containing liquid diet. Although this was linked to hepatic steatosis, a TLR4 association was not a feature of this model.
Asunto(s)
Etanol/efectos adversos , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/fisiopatología , Osteonecrosis/fisiopatología , Animales , Modelos Animales de Enfermedad , Necrosis de la Cabeza Femoral/patología , Masculino , Osteonecrosis/patología , Ratas , Ratas Wistar , Transducción de Señal/fisiología , Receptor Toll-Like 4/fisiologíaRESUMEN
The hip joint is one of the major structures in the human body and the resultant force acting through the hip joint is 300% of body weight. Therefore, weight bearing, as a cause of ischaemia, may contribute to the development of non-traumatic osteonecrosis of the femoral head (ONFH). However, it remains unclear whether weight bearing is related to the development of non-traumatic ONFH. Therefore the aim of this study was to clarify the role of weight bearing in the development of non-traumatic ONFH. Non-weight-bearing (NWB) rats were tail suspended to prevent any weight coming to bear on the hindlimbs from day 1 to the time of sacrifice. The weight-bearing (WB) group rats were also housed individually, although without tail suspension. All rats were injected with lipopolysaccharide and methylprednisolone to promote the development of non-traumatic ONFH. All animals were sacrificed three weeks after the final methylprednisolone injection. Histopathological analysis was performed. Osteonecrosis of the femoral head was observed not only in the NWB but also in the WB rats; however, no osteonecrosis of the humeral head was observed in either group. We confirmed that non-traumatic ONFH developed in NWB rats, suggesting that weight bearing does not contribute to the development of non-traumatic ONFH in rats.
Asunto(s)
Necrosis de la Cabeza Femoral/patología , Cabeza Femoral/patología , Suspensión Trasera/fisiología , Articulación de la Cadera/fisiología , Animales , Modelos Animales de Enfermedad , Quimioterapia Combinada , Cabeza Femoral/efectos de los fármacos , Necrosis de la Cabeza Femoral/inducido químicamente , Lipopolisacáridos/toxicidad , Masculino , Metilprednisolona/toxicidad , Ratas , Ratas Wistar , Soporte de Peso/fisiologíaRESUMEN
Withdrawal from chronic alcohol cause the persistent molecular alteration, such as changes in the release of neurotransmitter and gene expression. The alterations are thought to increase in the risk of relapse. Recent studies suggest that the gene expression regulated by histone acetylation may play an important role in the dependence of abused drugs, including of ethanol. Furthermore, miRNA, another regulator of gene expression, are also important molecules for the dependence. However, changes in the molecules under ethanol withdrawal and its relationship are poorly understood. In the present study, we investigated the expression of acetylated histone H3 and miR-124 in mouse brain at 3 days after ethanol withdrawal. 6-Week ages of C57BL/6J mice were treated with liquid diet containing ethanol for 10 days. Using the escalating ethanol dosage schedule, the mice were fed the ethanol diet as follows: 1st day: 1 w/v%: 2nd and 3rd day: 3 w/v%; 4th and 5th day: 4 w/v% and from the 6th to 10th day: 5 w/v% ethanol diet, respectively. The pair-fed control mice were given the same volume of ethanol-free liquid diet with glucose substituted in isocaloric quantities for ethanol. After feeding alcohol liquid diet, the mice showed severe withdrawal signs. The expression of acetylated histone H3 was significantly decreased in limbic forebrain at 3 days after withdrawal. We found that miR-124 also decreased in the limbic forebrain. It has been reported that Cdc42 regulates neuronal development as a target of miR-124. We found that Cdc42 protein markedly increased in both brain regions at 3 days after withdrawal. Our findings suggest that changes in the expression of miR-124 via histone acetylation leads to change the Cdc42 expression under ethanol withdrawal.
Asunto(s)
Epigénesis Genética , Etanol/farmacología , MicroARNs/metabolismo , Síndrome de Abstinencia a Sustancias/metabolismo , Acetilación/efectos de los fármacos , Alcoholismo/genética , Alcoholismo/metabolismo , Animales , Histonas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Síndrome de Abstinencia a Sustancias/genética , Proteína de Unión al GTP cdc42/metabolismoRESUMEN
Alcohol consumption augments brain edema by expression of brain aquaporin-4 after traumatic brain injury. However, how ethanol induces brain aquaporin-4 expression remains unclear. Aquaporin-4 can operate with some of ion channels and transporters. Therefore, we hypothesized that ethanol may affect electrolytes through regulating ion channels, leading to express aquaporin-4. To clarify the hypothesis, we examined role of AQP4 expression in ethanol-induced brain edema and changes of electrolyte levels after traumatic brain injury in the rat. In the rat traumatic brain injury model, ethanol administration reduced sodium ion concentration in blood significantly 24 hr after injury. An aquaporin-4 inhibitor recovered sodium ion concentration in blood to normal. We observed low sodium ion concentration in blood and the increase of brain aquaporin-4 in cadaver with traumatic brain injury. Therefore, ethanol increases brain edema by the increase of aquaporin-4 expression with hyponatremia after traumatic brain injury.
Asunto(s)
Acuaporina 4/análisis , Lesiones Encefálicas/complicaciones , Etanol/farmacología , Hiponatremia/inducido químicamente , Animales , Edema Encefálico/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
Osteonecrosis of the femoral head (ONFH), the pathogenesis of which remains unclear, has been observed in autoimmune disease patients treated with corticosteroids. Recently, it has been shown that anti-tripartite motif-containing 21 (TRIM21) autoantibodies, which are often present in patients with systemic lupus erythematosis and Sjögren's syndrome, inhibit the E3 ligase activity of TRIM21. TRIM21 negatively regulates nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs) 3 and 7, three downstream transcription factors, via toll-like receptor 4 signaling. The aim of this study was to clarify the role of TRIM21 in the pathogenesis of ONFH using an animal model. Male Wistar rats were injected with lipopolysaccharide (LPS) twice and with methylprednisolone (MPSL) or saline three times. N-acetyl cysteine (NAC) was administered either concurrently with MPSL or once daily for the 3 days following the last MPSL injection. The incidence of ONFH in the MPSL group was 23.5%. Co-treatment of NAC and MPSL increased the incidence of ONFH to 55.6%. MPSL treatment decreased the activity of NF-κB in the liver and significantly increased the activity of both IRF3 and IRF7. No significant differences were observed in the activity of any of these three transcription factors between the MPSL and the co-treatment groups. In the femoral head, co-treatment with NAC and MPSL significantly decreased the expression of TRIM21 at 3 h and significantly increased the expression of interferon (IFN)-α at 24 h when compared with the MPSL group. IFN-α is known to induce cell death. These findings suggest that the suppression of TRIM21 in the femoral head causes an accumulation of IFN-α, which in turn leads to the development of ONFH. In conclusion, the suppression of TRIM21 resulting from altered NF-κB and IRF homeostasis accelerates the ONFH in rats treated with corticosteroids following LPS administration.
Asunto(s)
Necrosis de la Cabeza Femoral/fisiopatología , Interferón-alfa/metabolismo , Ubiquitina-Proteína Ligasas/fisiología , Animales , Ensayo de Cambio de Movilidad Electroforética , Necrosis de la Cabeza Femoral/metabolismo , Inmunohistoquímica , Masculino , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas de Motivos TripartitosRESUMEN
We previously reported that ethanol consumption affects morbidity and mortality after traumatic brain injury (TBI) by accelerating brain edema via oxidative stress after TBI. Aquaporin-4 (AQP4), a water channel, is involved in brain edema formation. In this study, we found that acute ethanol administration increased AQP4 expression after TBI, leading to severe brain edema in rats. Rats were pretreated with ethanol (3 g/kg) or dl-buthionine-(S,R)-sulfoximine (BSO; 100 mg/kg), an oxidative stressor, before TBI. Acetazolamide, an AQP4 inhibitor, was administered to ethanol-pretreated rats 3 or 12 hours after TBI. Brain edema was increased 24 hours after TBI in both the ethanol- and BSO-pretreated groups. Ethanol pretreatment induced lipid peroxidation 24 hours after TBI. Transcription factors, NF-κB and hypoxia-inducible factor-1α, were activated 3 and 24 hours after TBI in the BSO- and ethanol-pretreated groups, respectively. In the ethanol-pretreated group, AQP4 was accumulated, particularly in astrocyte end feet, 24 hours after TBI. Acetazolamide treatment improved the survival rate to 100% and decreased brain edema and AQP4 in ethanol-pretreated rats. These findings suggest that ethanol induces up-regulation of AQP4, leading to brain edema. The accumulation of AQP4 may play an important role in the augmentation of brain edema after TBI under ethanol consumption.
Asunto(s)
Acuaporina 4/metabolismo , Edema Encefálico/inducido químicamente , Lesiones Encefálicas/inducido químicamente , Etanol/toxicidad , Solventes/toxicidad , Acetazolamida/farmacología , Animales , Acuaporina 4/antagonistas & inhibidores , Edema Encefálico/metabolismo , Lesiones Encefálicas/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Imagen por Resonancia Magnética , Masculino , FN-kappa B/metabolismo , Ratas , Ratas WistarRESUMEN
Titanium dioxide (TiO(2)) nanoparticles are widely used in cosmetics, sunscreen and as a photocatalyst. However, little is known about the biological effect of TiO(2) nanoparticles in humans and other animals. Here, we investigated whether prenatal exposure to TiO(2) nanoparticles impacted the central nervous system in mice. We measured the levels of dopamine (DA) and its metabolites in several regions of the brain in mice using high performance liquid chromatography (HPLC). HPLC analysis showed that DA and its metabolites were increased in the prefrontal cortex and the neostriatum following prenatal exposure to TiO(2) nanoparticles. The present study highlights the possibility that maternal exposure to TiO(2) nanoparticles might influence the development of the central dopaminergic system in offspring.