RESUMEN
We report a suicide case of complete decapitation using a self-constructed guillotine. A 45-year-old man, whose body was severely burned, was found dead. The head was completely separated from the middle level of the neck, and a sharp blade with a steel frame was placed between the head and neck. The severance plane passed between the C4 and C5 vertebrae. Vital reactions such as hemorrhage could not be confirmed at the decapitated skin edge because the body was severely burned. Both common carotid arteries were sharply transected. Subendocardial hemorrhage was detected in the left ventricle. Only a little blood, but no soot, was detected in the respiratory tract, including the trachea and bilateral bronchi. Subarachnoid hemorrhage was noted at the edge of the cervical spinal cord. The saturation level of CO-Hb was 5.7% in the left cardiac blood, 5.9% in the right cardiac blood, and 5.8% in the peripheral blood from the femoral vein. Cervical transection was diagnosed as the cause of death. We believe that he was unintentionally burned by spread fire from an automobile after decapitation by a self-constructed guillotine.
Asunto(s)
Quemaduras/patología , Decapitación , Suicidio Completo , Carboxihemoglobina/análisis , Traumatismos de las Arterias Carótidas/patología , Incendios , Ventrículos Cardíacos/patología , Hemorragia/patología , Humanos , Masculino , Persona de Mediana Edad , Sistema Respiratorio/patología , Hemorragia Subaracnoidea/patologíaRESUMEN
This paper presents an unusual complex suicide case that died of nicotine addiction. The deceased was a 40-year-old male who was found lying dead on the floor in his room. In external findings, many incision wounds on his forearms and skin discoloration with epidermolysis on his cervical region could be seen. In the room, a blood-stained scissors and electric cord hanged on the exercise bike were found. Moreover, nine cigarette residues which were only the filter part and empty bottle of coffee were found on his side. At autopsy, we found that those injuries were not serious enough to lead him to the death. Toxicologically, caffeine, nicotine, cotinine, mirtazapine, and olanzapine could be detected, and the concentrations of nicotine were 3.740, 2.140, 3.100, and 451.100 µg/ml in cardiac blood, peripheral blood, urine, and stomach contents, respectively. These concentrations were evaluated as the fatal levels, and the cause of his death was diagnosed as acute nicotine intoxication.
Asunto(s)
Análisis Químico de la Sangre , Toxicología Forense , Contenido Digestivo/química , Nicotina/envenenamiento , Suicidio Completo , Adulto , Autopsia , Cafeína/análisis , Cotinina/análisis , Humanos , Masculino , Mirtazapina/análisis , Olanzapina/análisisRESUMEN
Immunohistochemical investigation of aquaporin (AQP)1 and AQP3 was performed in human skin wounds obtained from forensic autopsy cases. A total of 55 human skin wounds of different postinfliction intervals were collected as follows: group I, 0-3 days (n = 16); II, 4-7 days (n = 11); III, 9-14 days (n = 16); and IV, 17-21 days (n = 12). In uninjured skin samples, AQP1 and AQP3 could be slightly detected in dermal vessels and keratinocytes, respectively. The percentage of AQP1+ vessels and the number of AQP3+ keratinocytes were apparently elevated in accordance with wound ages. The number of AQP3+ keratinocytes was distinctly evident in groups II and III. Morphometrically, both AQP1+ vessel area and AQP3+ cell number were markedly increased in group II, compared with other three groups. With regard to forensic safety, AQP1+ vessel area of over 5% would imply wound ages of 4-12 days. Moreover, the positive area of > 15% would suggest wound age of 7-10 days. Especially, most samples of skin wounds aged 5-10 days except for only one sample (a 10-day-old wound) showed AQP3+ cell number of > 300, and the remaining other samples had that of < 300. Thus, the AQP3+ cell number of > 300 would indicate wound ages of 5-10 days. Collectively, immunohistochemical analyses of AQP1 and AQP3 in human skin wounds would support the objective accuracy of wound age determination.
Asunto(s)
Acuaporina 1/metabolismo , Acuaporina 3/metabolismo , Piel/lesiones , Piel/metabolismo , Cicatrización de Heridas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células , Niño , Patologia Forense , Humanos , Inmunohistoquímica , Queratinocitos/metabolismo , Persona de Mediana Edad , Piel/citología , Factores de Tiempo , Adulto JovenRESUMEN
Detection of vitality of mechanical wounds in human cadavers is one of the important issues in forensic medicine. In order to explore novel markers for vitality of acute mechanical wounds, we investigated autophagy in mouse and human skin wounds. Western blotting analysis of mouse skin wounds showed marked reduction of LC3-II and reciprocal increase of p62 in wound samples with the postinfliction intervals of ≥0.5 h, compared with the uninjured skin tissues. These observations indicated that autophagy level was reduced in the wound sites. In postmortem wound samples, there were no remarkable changes in LC3-II and p62 levels. Furthermore, the postmortem intervals of 1-4 days have no significant effects on the changes of LC3-II and p62 in the antemortem skin wounds. Like murine wound samples, these alterations of LC3-II and p62 could be detected in human skin wound samples. Collectively, our study using animal and human samples implied that the detection of autophagy-related molecules such as LC3-II and p62 might be useful for forensic practice as markers of wound vitality.
Asunto(s)
Autofagia/fisiología , Cambios Post Mortem , Piel/lesiones , Piel/patología , Heridas y Lesiones/patología , Animales , Biomarcadores/análisis , Humanos , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Endothelial progenitor cells (EPCs), a newly identified cell type, are bone marrow-derived progenitor cells that co-express stem cell markers and vascular endothelial growth factor (VEGF) receptor (Flk-1). In this study, a double-color immunofluorescence analysis was carried out using anti-CD34 and anti-Flk-1 antibodies to examine the time-dependent appearance of EPCs, using 52 human skin wounds with different wound ages (Group I, 0-1 days; Group II, 2-6 days; Group III, 7-14 days; and Group IV, 17-21 days). In wound specimens with an age of less than one day, CD34(+)/Flk-1(+) EPCs were not detected. EPCs were initially observed in wounds aged two days, and their number was increased in lesions with advances in wound age. In morphometrical analysis, the average number of EPCs was the highest in the wounds of Group III. Especially, 20 out of 21 wounds aged 7-12 days had >20 EPCs, and all wound samples with postinfliction intervals of 14-21 days had <15 EPCs. These observations at least showed that >20 EPCs would indicate a wound age of 7-12 days. Taken together, our observations indicate the detection of EPCs would be useful for wound age determination.
Asunto(s)
Células Progenitoras Endoteliales/patología , Piel/lesiones , Piel/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células , Niño , Técnica del Anticuerpo Fluorescente , Patologia Forense , Humanos , Persona de Mediana Edad , Factores de Tiempo , Adulto JovenRESUMEN
Immunohistochemical study combined with morphometry was carried out to examine the expression of cyclooxygenase-2 (COX-2) using 60 human skin wounds of different ages: group I, 0-4 h (n = 11); II, 8 h-2 days (n = 21); III, 3-9 days (n = 14); and IV, 12-21 days (n = 14). In wound specimens aged 2 h to 2 days, anti-myeloperoxidase-positive neutrophils observed at the wound site expressed immunopositive reaction to COX-2. In wound specimens of more than 3 days, CD68-positive macrophages as well as neutrophils were positively immunostained with anti-COX-2. In group II, all 21 wound samples had COX-2-positive ratios of >40 %, and 15 out of them showed >50 %. In group III, only three wound samples with the postinfliction intervals of 3 days showed positive ratios of 40-50 % and the remaining 11 cases less than 40 %. In groups I and IV, all 25 wound specimens had COX-2-positive ratio of <40 %. With regard to the practical applicability with forensic safety, these observations suggested that a COX-2-positive ratio of >40 % indicated a wound age of 8 h to 3 days. Moreover, COX-2-positive ratios, considerably exceeding a ratio of 50 %, indicate a wound age of 8 h to 2 days. Collectively, COX-2 would be a useful marker for the determination of early wound age.
Asunto(s)
Ciclooxigenasa 2/metabolismo , Piel/lesiones , Piel/metabolismo , Cicatrización de Heridas/fisiología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Patologia Forense , Humanos , Inmunohistoquímica , Macrófagos/inmunología , Macrófagos/metabolismo , Neutrófilos/inmunología , Neutrófilos/metabolismo , Peroxidasa/metabolismo , Factores de TiempoRESUMEN
Here, we report a case of necrotizing fasciitis following intra-articular injection of hyaluronic acid. A 73-year-old female received intra-articular injections of hyaluronic acid due to arthralgia at the left shoulder and knee, and was found dead in her living room at one day. At the forensic autopsy, injection marks with bullae and erythema were found at the left shoulder and knee and liquefactive necrosis of muscle tissues was observed in the left but not right extremities. Histopathological examinations of the left upper arm and thigh revealed severe rhabdomyolysis with lots of bacterial clusters. Bacteriological examinations detected group A Streptococcus from intracardiac blood and affected muscle tissues. Postmortem biochemical analysis of blood showed escalated blood urea nitrogen (133.8 mg/dL), creatinine (4.57 mg/dL) and C-reactive protein (45.0 mg/dL). The cause of her death was diagnosed as streptococcal toxic shock syndrome (STSS). Moreover, it was suggested that the injection was inappropriately conducted and served as a portal of bacterial entry.
Asunto(s)
Fascitis Necrotizante , Infecciones Estreptocócicas , Anciano , Fascitis Necrotizante/etiología , Femenino , Humanos , Enfermedad Iatrogénica , Inyecciones Intraarticulares , Streptococcus pyogenesRESUMEN
Acetaminophen (APAP) induced increases in intrahepatic expression of interleukin (IL)-1 alpha, IL-1 beta, and IL-1 receptor antagonist (IL-1ra), when administered intraperitoneally. These observations prompted us to define the pathophysiological roles of IL-1ra in APAP-induced liver injury. Compared with wild-type (WT) mouse-derived hepatocytes, IL-1ra-deficient (IL-1ra KO)-derived hepatocytes exhibited more resistance against APAP but not APAP-derived major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Moreover, the amounts of a major APAP adduct (selenium-binding protein), an indicator of NAPQI generation from APAP, was significantly lower in IL-1ra KO mice than WT mice with depressed intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, the enzymes crucially involved in NAPQI generation from APAP. These observations would indicate that IL-1ra deficiency impaired APAP metabolism. IL-1 alpha and IL-1 beta were expressed to similar extents in livers of untreated IL-1ra KO and WT mice. By contrast, the intranuclear amount of p65 of NF-kappaB, which can suppress the gene expression of CYP1A2, CYP2E1, and CYP3A11, was higher in untreated IL-1ra KO than WT mice. Moreover, when mice were intraperitoneally administered APAP (200 mg/kg), IL-1ra KO mice exhibited attenuated APAP-induced liver injury as evidenced by reductions in serum alanine transferase levels and histopathological changes such as centrilobular necrosis, hemorrhages, and leukocyte infiltration. Finally, when given 12 h before APAP challenge, IL-1 alpha repressed the intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, eventually reducing APAP-induced liver injury, along with reduction in APAP adducts. Collectively, NF-kappaB was activated without any stimuli by the genetic disruption of IL-1ra, and suppressed cytochrome P450 enzyme expression, thereby reducing APAP-induced liver injury.
Asunto(s)
Acetaminofén , Analgésicos no Narcóticos , Enfermedad Hepática Inducida por Sustancias y Drogas , Proteína Antagonista del Receptor de Interleucina 1/deficiencia , Hepatopatías/prevención & control , Acetaminofén/farmacología , Acetaminofén/envenenamiento , Analgésicos no Narcóticos/farmacología , Analgésicos no Narcóticos/envenenamiento , Animales , Células Cultivadas , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Resistencia a Medicamentos , Expresión Génica/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Interleucina-1alfa/farmacología , Hígado/enzimología , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , FN-kappa B/metabolismo , Factor de Transcripción ReIA/metabolismoRESUMEN
Fibrocytes, a newly identified cell type, are bone marrow-derived mesenchymal progenitors that coexpress hematopoietic cell antigens and fibroblast products. In this study, a double-color immunofluorescence analysis was carried out using anti-CD45 and anti-collagen type I antibodies to examine the time-dependent appearance of fibrocytes, using 53 human skin wounds with different wound ages (group I, 0-3 days; group II, 4-7 days; group III, 9-14 days; and group IV, 17-21 days). In wound specimens with an age of less than 3 days, CD45+/collagen type I+ fibrocytes were not detected. The fibrocytes were initially observed in wounds aged 4 days, and their number increased in lesions with advances in wound age. In a semiquantitative morphometrical analysis, the average number of fibrocytes was highest in the wounds of group III. These findings imply that human skin wounds containing fibrocytes are at least 4 days old. Moreover, a fibrocyte number of over 10 indicates a wound age between 9 and 14 days (i.e., group III). Based on the average number of fibrocytes in each group, a fibrocyte number of over 15 more strongly suggests a wound age of 9-14 days. Together, our observations indicate the participation of fibrocytes in wound healing of human skin inducing the accumulation of extracellular matrix components, and therefore, detection of fibrocytes could be a useful marker for wound age determination.
Asunto(s)
Células Madre Mesenquimatosas/metabolismo , Piel/lesiones , Piel/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Niño , Colágeno Tipo I/metabolismo , Humanos , Antígenos Comunes de Leucocito/metabolismo , Microscopía Fluorescente , Persona de Mediana Edad , Piel/patología , Factores de TiempoRESUMEN
We herein report an intoxication case caused by the ingestion of the pesticide Ortoran®, which consists of 50% acephate aqueous solution. A man in his 60 s was found dead in his car with a 100-mL bottle containing approximately 50 mL of Ortoran®. In a gas chromatography - mass spectrometry (GC-MS) screening test, acephate and its metabolite methamidophos were qualitatively detected in his stomach contents. The amounts of acephate and methamidophos (µg/g) in the extract of each body fluid or organ tissue were measured using GC-MS and were as follows: 35.8, 2.84 (heart blood); 44.0, 2.26 (peripheral blood); 2,240, 2.79 (urine); 53.1, 8.91 (brain occipital lobe); 43.7, 2.95 (liver); 102.3, 8.02 (right kidney); and 5450, 22.9 (stomach contents). Based on these results and autopsy findings, the cause of death was concluded to be acute fatal intoxication caused by the pesticide containing acephate and its active metabolite, methamidophos. Concentration ratios between acephate and methamidophos in each body fluid and organ tissue showed higher relative concentrations of brain methamidophos to acephate than those of other organ tissues. A high relative concentration of brain methamidophos may contribute to the intoxication of acephate in humans.
Asunto(s)
Insecticidas/farmacocinética , Compuestos Organotiofosforados/farmacocinética , Fosforamidas/farmacocinética , Química Encefálica , Cromatografía de Gases y Espectrometría de Masas , Contenido Digestivo/química , Humanos , Insecticidas/envenenamiento , Riñón/química , Hígado/química , Pulmón/química , Masculino , Persona de Mediana Edad , Compuestos Organotiofosforados/envenenamiento , Fosforamidas/envenenamiento , Distribución TisularRESUMEN
We report a fatal intoxication case by the ingestion of an herbicide, 2-methyl-4-chlorophenoxyacetic acid (MCPA). A 23-year-old male was found dead in his car. The forensic autopsy revealed no remarkable morphological changes. However, in a toxicological screening test, MCPA was qualitatively detected from the extracts of stomach contents. Then MCPA in the extract of each body fluid and organ tissue was determined by gas chromatography-mass spectrometry with trimethylsilyl-derivatization as follows (microg/g): 888.3 in the heart blood, 578.1 in the peripheral blood, 52.2 in the urine, 770.9 in the brain, 1362 in the right lung, 1135 in the liver, 755.5 in the right kidney, and 10,200 in the stomach contents. These data strongly suggested that the male orally ingested MCPA. Moreover, p-chloro-o-cresol (4-chloro-2-methylphenol) was also determined in the body fluids and organ tissues, suggesting a metabolite of MCPA. From these toxicological data, together with autopsy findings, the cause of his death was diagnosed as acute MCPA poisoning.
Asunto(s)
Ácido 2-Metil-4-clorofenoxiacético/envenenamiento , Causas de Muerte , Herbicidas/envenenamiento , Suicidio , Ácido 2-Metil-4-clorofenoxiacético/análisis , Ácido 2-Metil-4-clorofenoxiacético/metabolismo , Adulto , Cresoles/análisis , Cresoles/metabolismo , Toxicología Forense , Cromatografía de Gases y Espectrometría de Masas , Contenido Digestivo/química , Herbicidas/análisis , Herbicidas/metabolismo , Humanos , Masculino , Reproducibilidad de los Resultados , Detección de Abuso de SustanciasRESUMEN
A fatal case of acute nifedipine intoxication in a two-year-old boy is presented. The boy accidentally orally ingested an unknown amount of his grandfather's nifedipine (40mg/tablet), mistaking it for a ramune confectionery. Despite intensive medical treatment, his death was confirmed at 31h after the accidental ingestion. The forensic autopsy revealed that there were neither pathological alterations or injuries in all of the organs. Toxicologically, nifedipine could be detected at the concentrations of 0.463, 0.669 and 13.0µg/g in cardiac blood, peripheral blood and stomach contents, respectively. These concentrations were evaluated as fatal levels, and the cause of death was diagnosed as acute nifedipine intoxication. Recently, the number of infants and children who accidentally ingest drugs in the home is increasing. This case report prompts forensic pathologists and toxicologists to emphasize that children are always exposed to the risk of accidental drug ingestion in daily life.
Asunto(s)
Accidentes Domésticos , Toxicología Forense , Nifedipino/envenenamiento , Autopsia , Preescolar , Contenido Digestivo , Humanos , Japón , MasculinoRESUMEN
We herein report a fatal intoxication case caused by the ingestion of the insecticides chlorpyrifos-methyl (CPFM) and fenitrothion (MEP). A 70-year-old man was found dead in his house and a cup containing a small amount of agricultural chemicals was on the table near his body. External and internal examinations revealed no injuries. In a gas chromatography-mass spectrometry (GC-MS) screening test, CPFM, MEP, and their metabolites, 3,5,6-trichloro-2-pyridinol (TCPY) and 3-methyl-4-nitrophenol (3MNP), respectively, were qualitatively detected in his stomach contents. The concentrations (µg/g) of CPFM, TCPY, MEP, and 3MNP in the extracts of each body fluid and organ tissue were assessed by GC-MS and were as follows: 27.8, 56.2, 17.2, and 2.82 (heart blood); 6.60, 42.9, 1.80, and 2.59 (peripheral blood); 0.0821, 45.9, 2,09, and 102 (urine); 21.4, 26.6, 76.2, and 3.83 (brain (frontal portion)); 16.1, 101, 9.67, and 1.26 (liver); 7.45, 101, 21.4, and 26.1 (right kidney); and 73,500, 9750, 232,000, and 1880 (stomach contents), respectively. Based on these results and autopsy findings, the cause of death was acute fatal intoxication by CPFM and MEP.
Asunto(s)
Líquidos Corporales/química , Cloropirifos/análogos & derivados , Fenitrotión/análisis , Fenitrotión/metabolismo , Insecticidas/análisis , Insecticidas/metabolismo , Anciano , Autopsia/métodos , Cloropirifos/efectos adversos , Cloropirifos/análisis , Cloropirifos/metabolismo , Fenitrotión/efectos adversos , Cromatografía de Gases y Espectrometría de Masas , Contenido Digestivo/química , Humanos , Insecticidas/efectos adversos , MasculinoRESUMEN
It is well known that the intake of paraquat (PQ), an herbicide, causes severe lung injury at chronic phases. We examined the intrapulmonary gene expression of cytokines and growth factors after PQ administration. To induce lung injury, C57BL/6 mice were intraperitoneally injected twice a week with 20 mg/kg of PQ. Histopathologically, at the early phase, lots of alveolar spaces contained edematous fluid. At 3 weeks after PQ challenge, a marked thickening of the alveolar walls with the accumulation of macrophages and T cells was found. Azan staining revealed the patchy distribution of collagen accumulation, indicating pulmonary fibrosis. Consistently, intrapulmonary hydroxyproline contents were significantly elevated, compared with the controls. Semi-quantitative RT-PCR analysis demonstrated that the gene expression of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly increased at 3 weeks after PQ challenge compared with the controls. The mRNA expression of macrophage inflammatory protein (MIP)-1alpha and MIP-2 was significantly enhanced at 1 and 2 weeks after PQ treatment, respectively. Moreover, PQ-treated mice showed enhanced gene expression of fibrogenic growth factors such as transforming growth factor-beta, platelet-derived growth factor-A, acidic fibroblast growth factor, and hepatoctyte growth factor at 2 and/or 3 weeks after PQ challenge. The synergistic effects of these molecules are presumed to cause pulmonary fibrosis due to PQ challenge.
Asunto(s)
Citocinas/genética , Sustancias de Crecimiento/genética , Herbicidas/farmacología , Pulmón/metabolismo , Paraquat/farmacología , Animales , Colágeno/metabolismo , Citocinas/metabolismo , Técnica del Anticuerpo Fluorescente , Patologia Forense , Expresión Génica , Sustancias de Crecimiento/metabolismo , Hidroxiprolina/metabolismo , Inmunohistoquímica , Pulmón/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/metabolismoRESUMEN
Gender is one of the essential factors in the development of various diseases and poisoning. Therefore, we herein examined gender differences in sodium arsenite (NaAsO2)-induced acute renal dysfunction. When male and female BALB/c mice were subcutaneously injected with NaAsO2 (12.5mg/kg), serum and urinary markers for proximal tubular injury were significantly higher in female mice than in male ones. NaAsO2-induced histopathological alterations were consistently more evident in females than in males. Ovariectomy, but not orchiectomy significantly attenuated NaAsO2-induced renal injury. These results imply that the hypersusceptibility of female mice is attributed to estrogen signals. NaAsO2 suppressed the autophagic flux in tubular cells through the activation of ERK. Enhancements in the activation of ERK were significantly greater in females than in males, with the eventual accumulation of LC3-II and P62 in the kidneys, implying that the autophagic flux is impaired in females. The IL-6/STAT3 signaling pathway had protective roles in NaAsO2-induced nephrotoxicity through the suppression of ERK activation. Despite the absence of differences in intrarenal IL-6 expression between male and female mice, STAT3 was less activated with enhanced SOCS3 expression in females than in males. An in vitro study using mProx24 cells revealed that the estrogen treatment induced SOCS3 expression, and eventually suppressed the autophagic flux, as evidenced by greater increases in the accumulation of LC3-II and p62 with ERK activation, which was canceled by the knockdown of Socs3. Collectively, these results indicate that estrogen has a negative impact on the development of NaAsO2 nephrotoxicity through its suppression of the autophagic flux.
Asunto(s)
Arsenitos/toxicidad , Autofagia/efectos de los fármacos , Estrógenos/fisiología , Enfermedades Renales/patología , Compuestos de Sodio/toxicidad , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Femenino , Proteínas de Choque Térmico/biosíntesis , Proteínas de Choque Térmico/genética , Inyecciones Subcutáneas , Interleucina-6/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Enfermedades Renales/inducido químicamente , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metales Pesados/farmacología , Ratones , Ratones Endogámicos BALB C , Proteínas Asociadas a Microtúbulos/biosíntesis , Proteínas Asociadas a Microtúbulos/genética , Ovariectomía , Factor de Transcripción STAT3/efectos de los fármacos , Proteína Sequestosoma-1 , Caracteres Sexuales , Transducción de Señal/efectos de los fármacos , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/biosíntesis , Proteínas Supresoras de la Señalización de Citocinas/genéticaRESUMEN
To clarify interleukin (IL)-6 roles in wound healing, we prepared skin excisions in wild-type (WT) and IL-6-deficient BALB/c [knockout (KO)] mice. In WT mice, the wound area was reduced to 50% of original size at 6 days after injury. Microscopically, leukocyte infiltration was evident at wound sites. Furthermore, the re-epithelialization rate was approximately 80% at 6 days after injury with increases in angiogenesis and hydroxyproline contents. The gene expression of IL-1, chemokines, adhesion molecules, transforming growth factor-beta1, and vascular endothelial growth factor was enhanced at the wound sites. In contrast, the enhanced expression of these genes was significantly reduced in KO mice. Moreover, in KO mice, the reduction of wound area was delayed with attenuated leukocyte infiltration, re-epithelialization, angiogenesis, and collagen accumulation. Finally, the administration of a neutralizing anti-IL-6 monoclonal antibody significantly delayed wound closure in WT mice. These observations suggest that IL-6 has crucial roles in wound healing, probably by regulating leukocyte infiltration, angiogenesis, and collagen accumulation.
Asunto(s)
Interleucina-6/fisiología , Fenómenos Fisiológicos de la Piel , Cicatrización de Heridas , Proteínas de Fase Aguda/análisis , Animales , Moléculas de Adhesión Celular/biosíntesis , Moléculas de Adhesión Celular/genética , Movimiento Celular , Quimiocinas/biosíntesis , Quimiocinas/genética , Citocinas/biosíntesis , Citocinas/genética , Epidermis/anatomía & histología , Epidermis/fisiología , Femenino , Sustancias de Crecimiento/biosíntesis , Sustancias de Crecimiento/genética , Hidroxiprolina/análisis , Cinética , Leucocitos/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Neovascularización Fisiológica , Recuento de Plaquetas , Piel/anatomía & histología , Piel/química , Piel/metabolismo , Transcripción GenéticaRESUMEN
Acetaminophen (APAP) causes a massive production of intrahepatic tumor necrosis factor alpha (TNF-alpha). However, it still remains elusive regarding the roles of TNF-alpha in APAP-induced liver injury. Hence, we examined pathogenic roles of the TNF-alpha-TNF receptor with a molecular weight of 55 kDa (TNF-Rp55) axis in APAP-induced hepatotoxicity using TNF-Rp55-deficient [TNF-Rp55-knockout (KO)] mice. When wild-type (WT) BALB/c and TNF-Rp55-KO mice were intraperitoneally injected with a lethal dose of APAP (750 mg/kg), the mortality of TNF-Rp55-KO mice was marginally but significantly reduced compared with WT mice. Upon treatment with a nonlethal dose (600 mg/kg), WT mice exhibited an increase in serum transaminase levels. Histopathologically, centrilobular hepatic necrosis with leukocyte infiltration was evident at 10 and 24 h after APAP challenge. Moreover, mRNA expression of adhesion molecules, several chemokines, interferon-gamma (IFN-gamma), and inducible nitric oxide synthase (iNOS) was enhanced in the liver. On the contrary, serum transaminase elevation and histopathological changes were attenuated in TNF-Rp55-KO mice injected with APAP (600 mg/kg). The gene expression of all molecules except for IFN-gamma and iNOS was significantly attenuated in TNF-Rp55-KO mice. Moreover, anti-TNF-alpha neutralizing antibodies alleviated liver injury when administered at 2 or 8 h after but not at 1 h before APAP challenge to WT mice. Collectively, the TNF-alpha-TNF-Rp55 axis has pathogenic roles in APAP-induced liver failure.
Asunto(s)
Acetaminofén/toxicidad , Antígenos CD/fisiología , Hígado/patología , Receptores del Factor de Necrosis Tumoral/fisiología , Alanina Transaminasa/sangre , Animales , Antígenos CD/genética , Moléculas de Adhesión Celular/genética , Cartilla de ADN , Regulación de la Expresión Génica/efectos de los fármacos , Interleucinas/genética , Leucocitos/fisiología , Hígado/efectos de los fármacos , Hígado/fisiopatología , Masculino , Ratones , Ratones Endogámicos BALB C , Receptores del Factor de Necrosis Tumoral/genética , Receptores Tipo I de Factores de Necrosis Tumoral , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción GenéticaRESUMEN
Toxicological analyses of medicines and chemicals in formaldehyde-treated specimens are a component of forensic toxicology. This review involves two parts: (i) reactions of formaldehyde with substances in tissues fixed with formalin (aqueous formaldehyde solution) and (ii) the stability of substances in formalin-treated tissues and formalin solutions. Because it was well known that formaldehyde reacts with amines to form Schiff bases, it was additionally suggested in 1998 that formaldehyde reacts with primary and secondary amines together with formic acid to form N-methyl substances via the Eschweiler-Clarke conversion, which proceeds at room temperature. The reaction increases with pH and the concentration of formaldehyde. In addition, this report includes both experimental studies and practical cases involving embalmed bodies.
Asunto(s)
Fijadores/química , Formaldehído/química , Preparaciones Farmacéuticas/análisis , Fijación del Tejido , Aminas/química , Animales , Embalsamiento , Medicina Legal , Humanos , Drogas Ilícitas/análisis , Reproducibilidad de los ResultadosRESUMEN
We report a case of fatal intoxication caused by the ingestion of an organophosphate pesticide, methidathion (DMTP). An 80-year-old male was found dead in his bed. Forensic autopsy revealed no remarkable morphological changes. However, in a toxicological screening test, methidathion was qualitatively detected in extracts of stomach contents. Concentrations of methidathion (µg/g) in body fluids and organ tissues, determined by gas chromatography-mass spectrometry, were as follows; 66.2 in heart blood, 8.33 in peripheral blood, 8.80 in urine, 2000 in the brain (frontal lobe), 4800 in the left lung, 810 in the liver, 150 in the left kidney, and 64,000 in the stomach contents (total 1.9 g). These results strongly suggested that the victim orally ingested methidathion. Additionally, xylene was determined in body fluids and organ tissues. From the toxicological data together with autopsy findings, the cause of his death was diagnosed as acute poisoning by an emulsion of methidathion.
Asunto(s)
Líquidos Corporales/química , Toxicología Forense , Insecticidas/envenenamiento , Compuestos Organotiofosforados/envenenamiento , Xilenos/envenenamiento , Anciano de 80 o más Años , Autopsia , Causas de Muerte , Ingestión de Alimentos , Contenido Digestivo/química , Humanos , Insecticidas/análisis , Insecticidas/metabolismo , Masculino , Compuestos Organotiofosforados/análisis , Compuestos Organotiofosforados/metabolismo , Xilenos/análisisRESUMEN
Neutrophils and macrophages infiltrate after acetaminophen (APAP)-induced liver injury starts to develop. However, their precise roles still remain elusive. In untreated and control IgG-treated wild-type (WT) mice, intraperitoneal APAP administration (750 mg/kg) caused liver injury including centrilobular hepatic necrosis and infiltration of neutrophils and macrophages, with about 50% mortality within 48 h after the injection. APAP injection markedly augmented intrahepatic gene expression of inducible nitric oxide synthase (iNOS) and heme oxygenase (HO)-1. Moreover, neutrophils expressed iNOS, which is presumed to be an aggravating molecule for APAP-induced liver injury, while HO-1 was mainly expressed by macrophages. All anti-granulocyte antibody-treated neutropenic WT and most CXC chemokine receptor 2 (CXCR2)-deficient mice survived the same dose of APAP, with reduced neutrophil infiltration and iNOS expression, indicating the pathogenic roles of neutrophils in APAP-induced liver injury. However, APAP caused more exaggerated liver injury in CXCR2-deficient mice with reduced macrophage infiltration and HO-1 gene expression, compared with neutropenic WT mice. An HO-1 inhibitor, tin-protoporphyrin-IX, significantly increased APAP-induced mortality, implicating HO-1 as a protective molecule for APAP-induced liver injury. Thus, CXCR2 may regulate the infiltration of both iNOS-expressing neutrophils and HO-1-expressing macrophages, and the balance between these two molecules may determine the outcome of APAP-induced liver injury.