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1.
Leg Med (Tokyo) ; 70: 102469, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38870841

RESUMO

Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the MAOA gene has been previously reported. In the present study, we measured serum adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in 90 male and 34 female Japanese autopsy cases in which amphetamines or psychotropic drugs were not detected.We examined the frequencies of MAOA-uVNTR alleles in these cases and investigated the effects of the MAOA-uVNTR polymorphism on serum Adr, Nad, and DA levels. Evaluation indicated no significant association between MAOA-uVNTR polymorphism and serum Adr, Nad, or DA levels in males, although a significant association between MAOA-uVNTR polymorphism and serum Adr and DA levels were observed in females. Females with the 3/3 genotype had higher serum Adr and DA levels than those with a 4-repeat allele (3/4 and 4/4 genotypes) (p = 0.048 and 0.020, respectively). There was no significant association between MAOA-uVNTR polymorphism and serum Nad levels in females. The present study indicates that MAOA-uVNTR polymorphism influences serum Adr and DA levels only in females.

2.
Life (Basel) ; 14(1)2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38276281

RESUMO

The levels and potential role of prolactin (PRL) in the brain under conditions of acute systemic hypoxia were examined, focusing on the accumulation of PRL in cerebrospinal fluid (CSF) and its effects on neuronal activity and injury. The amount of PRL in the brain was investigated using brain tissues from forensic autopsy cases. We counted the number of neurites that formed in human primary neurons (HNs) after the addition of PRL. Furthermore, HNs supplemented with PRL or triiodothyronine (T3) were exposed to hypoxic conditions, and the dead cells were counted. The results showed correlations between brain PRL and CSF PRL levels. Additionally, PRL accumulation in the brain was observed in cases of asphyxia. In vitro experimental findings indicated increased neurite formation in the HNs treated with PRL. Moreover, both PRL and T3 demonstrated neuroprotective effects against hypoxia-induced neuronal cell death, with PRL showing stronger neuroprotective potential than T3. These results suggest that PRL accumulates in the brain during hypoxia, potentially influences neuronal activity, and exhibits neuroprotective properties against hypoxia-induced neuronal injury.

3.
Hum Exp Toxicol ; 42: 9603271231171643, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37072025

RESUMO

The present study aimed to clarify the expressions and roles of clock genes involved in drug metabolism in patients taking benzodiazepines (BZDs), as well as the drug metabolism regulators controlled by clock genes for each BZD type. The relationships between the expressions of the clock genes BMAL1, PER2, and DBP and the drug-metabolizing enzymes CYP3A4 and CYP2C19 were investigated using livers from BZD-detected autopsy cases. In addition, the effect of BZD exposure on various genes was examined in HepG2 human hepatocellular carcinoma cells. The expressions of DBP, CYP3A4, and CYP2C19 in the liver were lower in the diazepam-detected group than in the non-detected group. Furthermore, BMAL1 expression correlated with CYP2C19 expression. Cell culture experiments showed that the expressions of DBP and CYP3A4 decreased, whereas those of BMAL1 and CYP2C19 increased after diazepam and midazolam exposure. The results of the analyses of autopsy samples and cultured cells suggested that DBP regulates CYP3A4 when exposed to BZD. Understanding the relationship between these clock genes and CYPs may help achieve individualized drug therapy.


Assuntos
Benzodiazepinas , Neoplasias Hepáticas , Humanos , Benzodiazepinas/toxicidade , Citocromo P-450 CYP3A/genética , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Citocromo P-450 CYP2C19/genética , Diazepam/farmacologia , Expressão Gênica
4.
Hum Exp Toxicol ; 41: 9603271221124092, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36036424

RESUMO

This study examined the association between clock gene expression and the effect of methamphetamine (MA) on drug-metabolizing enzymes from the perspective of drug metabolism. The relationship between expression of the clock genes BMAL1 and PER2 and the drug-metabolizing enzymes CYP3A4 and CYP2D6 was investigated using livers from autopsy cases of MA-intoxication deaths. Additionally, the effect of MA exposure on various genes was examined in HepG2 human hepatocellular carcinoma cells. Comparisons of the expression of various genes in MA users according to blood MA concentration revealed that CYP3A4 expression was similar to that of PER2, and CYP2D6 expression was similar to that of BMAL1. In cultured cell experiments, BMAL1 and CYP2D6 expression decreased depending on the time elapsed after MA addition, and PER2 and CYP3A4 expression increased slightly in a concentration-dependent manner. These results were consistent with the findings of autopsy examinations. Expression of CYP3A4 and CYP2D6 under BMAL1 and PER2 suppression, but not CYP2D6 under PER2 suppression alone, was upregulated in response to MA. These results suggest that CYPs are regulated via the clock genes BMAL1 and PER2 during MA metabolism.


Assuntos
Fatores de Transcrição ARNTL , Metanfetamina , Citocromo P-450 CYP3A , Humanos
5.
Hum Cell ; 35(5): 1391-1407, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35737220

RESUMO

Intake of central nervous system (CNS) stimulants causes hypoxia and brain edema, which results in nerve cell death. However, no study has yet investigated the direct and continuous effects on nerve cells of CNS stimulants under hypoxia. Thus, based on autopsy cases, the effects of CNS stimulant drugs on the CNS were examined. The pathological changes in cultured nerve cells when various CNS stimulants were added under a hypoxic condition were also investigated. Five groups (Group A, stimulants; Group B, stimulants with psychiatric drugs; Group C, caffeine; Group D, psychiatric drugs; and Group E, no drugs) according to the detected drugs in autopsy cases were compared, and brain edema was evaluated using morphological findings. Furthermore, the number of dead cultured nerve cells was counted after the addition of drugs (4-aminopyridine (4-AP), caffeine, and ephedrine) under hypoxia (3% O2). Staining with anti-receptor-interacting protein 3 (RIP3) and other associated stains was also performed to investigate the neuronal changes in the brain. Group A showed significantly more brain edema than the other groups. In the culture experiments, the ratio of nerve cell death after the addition of 4-AP was the highest in the hypoxic condition. Groups with stimulants detected were stained more strongly by RIP3 immunostaining than by other staining. Addition of stimulants to cultured nerve cells in a persistent hypoxic condition led to severe cytotoxicity and nerve cell death. These findings suggest that necroptosis is involved in nerve cell death due to the addition of CNS stimulants in the hypoxic condition.


Assuntos
Edema Encefálico , Estimulantes do Sistema Nervoso Central , Edema Encefálico/patologia , Cafeína/efeitos adversos , Morte Celular , Hipóxia Celular/fisiologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Humanos , Hipóxia/patologia , Neurônios/metabolismo
6.
Intern Med ; 61(13): 1999-2006, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35283372

RESUMO

A man in his 30s injected insulin several times into his abdomen and was found dead several hours later. Micropathological findings showed alveolar injury with hemorrhaging and cerebral parietal lobe nerve cell edema. Biochemical examinations showed that the blood insulin level was high, significantly so at the insulin injection sites. The blood glucose and C-peptide levels were low. The insulin level in the kidneys was low. In forensic medicine, a postmortem diagnosis of insulin subcutaneous injection is often difficult. When insulin injection is suspected, particularly high insulin levels can be expected at the insulin injection site, rather than in the blood.


Assuntos
Glicemia , Insulina , Abdome , Humanos , Injeções Subcutâneas , Masculino , Distribuição Tecidual
7.
Int J Mol Sci ; 23(3)2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35163784

RESUMO

Caffeine, a common ingredient in energy drinks, crosses the blood-brain barrier easily, but the kinetics of caffeine across the blood-cerebrospinal fluid barrier (BCSFB) has not been investigated. Therefore, 127 autopsy cases (Group A, 30 patients, stimulant-detected group; and Group B, 97 patients, no stimulant detected group) were examined. In addition, a BCSFB model was constructed using human vascular endothelial cells and human choroid plexus epithelial cells separated by a filter, and the kinetics of caffeine in the BCSFB and the effects of 4-aminopyridine (4-AP), a neuroexcitatory agent, were studied. Caffeine concentrations in right heart blood (Rs) and cerebrospinal fluid (CSF) were compared in the autopsy cases: caffeine concentrations were higher in Rs than CSF in Group A compared to Group B. In the BCSFB model, caffeine and 4-AP were added to the upper layer, and the concentration in the lower layer of choroid plexus epithelial cells was measured. The CSF caffeine concentration was suppressed, depending on the 4-AP concentration. Histomorphological examination suggested that choroid plexus epithelial cells were involved in inhibiting the efflux of caffeine to the CSF. Thus, the simultaneous presence of stimulants and caffeine inhibits caffeine transfer across the BCSFB.


Assuntos
4-Aminopiridina/farmacologia , Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacologia , Líquido Cefalorraquidiano/química , Plexo Corióideo/química , Endotélio Vascular/química , Autopsia , Transporte Biológico , Barreira Hematoencefálica/química , Estudos de Casos e Controles , Células Cultivadas , Plexo Corióideo/citologia , Células Endoteliais/química , Células Endoteliais/citologia , Endotélio Vascular/citologia , Humanos , Modelos Biológicos
8.
Ultramicroscopy ; 233: 113440, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34920279

RESUMO

Ultimate resolution in scanning transmission electron microscopy (STEM) with state-of-the-art aberration correctors requires careful tuning of the experimental parameters. The optimum aperture semi-angle depends on the chosen high tension, the chromatic aberration and the energy width of the source as well as on potentially limiting intrinsic residual aberrations. In this paper we derive simple expressions and criteria for choosing the aperture semi-angle and for counterbalancing the intrinsic sixth-order three-lobe aberration of two-hexapole aberration correctors by means of the fourth-order three-lobe aberration. It is noteworthy that for such an optimally adjusted electron probe the so-called flat area of the Ronchigram is explicitly not maximized. The above considerations are validated by experiments with a CEOS ASCOR in a C-FEG-equipped JEOL NEOARM operated at 60 kV. Sub-Angstrom resolution is demonstrated for a Si[112] single crystal as well as for a single-layered MoS2 crystalline film. Lattice reflections of 73 pm for silicon and 93 pm for molybdenum disulfide are visible in the Fourier transform of the images, respectively. Moreover, single sulfur vacancies can be clearly identified in the MoS2.

9.
Subst Abuse Rehabil ; 12: 89-103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737668

RESUMO

PURPOSE: The purpose of this study was to examine the social and medical background of alcohol dependence and to prevent the abuse of alcohol. METHODS: Alcohol and deaths were retrospectively investigated based on the forensic postmortem data of 1694 decedents ≥20 years of age in 2008-2017. Of these, the 999 cases that could be tested for alcohol within 48 h of death were examined. RESULTS: The alcohol-positive and alcohol-negative groups included 179 (17.9%) and 820 (82.1%) cases, respectively. In terms of medical issues, compared with the alcohol-negative group, men in the positive group were mostly in their 40s to 60s, whereas women's age peaked in the 70s. The causes of death included many blunt injuries in men, though there was no difference in women. Underlying diseases were more frequent in men than women, with many of them having heart or liver disease, and the percentage of cases with mental disorders was 16.8% in the alcohol-positive group. In 15 cases of the alcohol-positive group, phenothiazine and barbituric acids were detected in 53.3% and 46.7% of cases, respectively. The incidence of traffic accidents and homicides was higher in the alcohol-positive group than in the alcohol-negative group. CONCLUSION: Measures to address social issues based on risk factors for alcohol and deaths are required.

10.
Leg Med (Tokyo) ; 51: 101864, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33798967

RESUMO

This study was designed to examine the pathophysiological differences in interleukin (IL) and structural protein levels between central nervous system (CNS) disorders associated with heat stroke and CNS stimulants. We measured the concentrations of IL-6, IL-8, neuron-specific enolase (NSE), and myelin basic protein (MBP) in blood and cerebrospinal fluid (CSF) from 87 autopsy cases. In addition, to examine changes in each marker, we cultured nerve cells at 40 °C as a heat stroke model and administered 4-aminopyridine and ephedrine in cultured cells as a CNS stimulant model. IL-6 levels in blood and CSF were significantly higher in the stimulant compared with the heat stroke group. IL-8 levels in blood and CSF were relatively high in the stimulant, heat stroke, and psychotropic addiction groups. NSE levels in blood were high in the stimulant and heat stroke groups, while those in CSF were significantly higher in the heat stroke group. MBP levels in blood were markedly higher in the stimulant and heat stroke groups, but no differences were seen in CSF. Compared with the CNS stimulant model, the heat stroke model with cultured human nerve cells showed high values for each marker. The results of the autopsy and laboratory tests in the present cases and those of cultured cell experiments indicated that CNS disorders caused by CNS stimulants such as amphetamines led to changes in IL-6 as an immune response, which suggests that IL-8 may help protect nerve cells in cases involving heat stroke and stimulants.


Assuntos
Doenças do Sistema Nervoso Central , Biomarcadores , Citocinas , Humanos , Fosfopiruvato Hidratase
11.
Hum Cell ; 34(2): 400-418, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33532907

RESUMO

This study aimed to investigate the changes associated with acute systemic hypoxia in the endocrine system, particularly in pancreatic tissues. The investigation was based on macroscopic, pathohistological, biochemical, and molecular biological findings in cell lines and human cadavers. The results showed that cases of death due to asphyxia more frequently showed severe subcapsular/interstitial hemorrhage versus the other causes of death. Histological examination showed that asphyxia cases were associated with severe morphological changes. Although measured insulin levels in the asphyxia were higher compared to other causes of death, no differences were noted for the glucagon and amylase levels with regard to the cause of death. Increased blood insulin levels were not associated with macro- and micromorphological changes, and did not show any association with glucose or cortisol levels. The experiment conducted under hypoxic conditions in cultured cells demonstrated that insulin mRNA expression and insulin protein levels peaked at 10 min after hypoxia exposure. However, there were no changes in either the amylase mRNA or protein levels. Corticosterone level peaked at 120 min after exposure to hypoxic conditions. Overall, acute systemic hypoxic conditions can directly affect the mechanisms involved in pancreatic insulin secretion.


Assuntos
Asfixia/patologia , Hipóxia/patologia , Pâncreas/metabolismo , Pâncreas/patologia , Doença Aguda , Asfixia/metabolismo , Cadáver , Linhagem Celular , Corticosterona/metabolismo , Feminino , Humanos , Hipóxia/metabolismo , Insulina/metabolismo , Masculino
12.
J Forensic Leg Med ; 78: 102089, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33596513

RESUMO

Acute stomach disease in elderly patients often lacks characteristic clinical manifestations. Presentations may differ from those in younger patients and are often complicated by concomitant diseases, delayed presentation, and misdiagnosis. Incorrect diagnosis and treatment can lead to medical-related death claims. We investigated eight cases of elderly fatality due to acute abdominal diseases in forensic autopsy cases. Although most fatalities were unwitnessed, possibly due to the characteristics of elderly individuals, recent social backgrounds, and involvement with health care, some cases of possible misdiagnosis suggested that physicians should carefully consider atypical clinical manifestations and the characteristics of elderly individuals when the managing abdominal symptoms, particularly in primary health care. Our investigation of these forensic autopsy cases indicated the particular importance of peritoneal adhesions as an unexpected cause of acute abdomen in the elderly due to strangulation ileus, even among those with no history of abdominal surgery or trauma. Diagnosis of acute stomach symptoms can be difficult in elderly patients. Pathophysiological examination and autopsy analyses can thus contribute to early-stage diagnosis and prevention of acute stomach symptoms in elderly patient populations.


Assuntos
Abdome Agudo/etiologia , Dor Abdominal/etiologia , Idoso Fragilizado , Gastropatias/diagnóstico , Abdome/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Autopsia , Causas de Morte , Feminino , Humanos , Íleus/fisiopatologia , Pulmão/diagnóstico por imagem , Masculino , Peritonite/fisiopatologia
13.
Int J Mol Sci ; 23(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35008744

RESUMO

Viral infections increase the risk of developing allergies in childhood, and disruption of mucosal homeostasis is presumed to be involved. However, no study has reported a role for viral infections in such disruption. In this study, we clarified the mechanism of immunoglobulin A (IgA) overproduction in viral infections. Autopsies were performed on 33 pediatric cases, IgA and interferon (IFN)ß levels were measured, and histopathological and immunohistochemical examinations were conducted. Furthermore, we cultured human cells and measured IFNß and IgA levels to examine the effect of viral infections on IgA production. Blood IgA levels in viral infections were higher than in bacterial infections. Moreover, IFNß levels in most viral cases were below the detection limit. Cell culture revealed increased IgA in gastrointestinal lymph nodes, especially in Peyer's patches, due to enhanced IFNß after viral stimulation. Conversely, respiratory regional lymph nodes showed enhanced IgA with no marked change in IFNß. Overproduction of IgA, identified as an aberration of the immune system and resulting from excessive viral infection-induced IFNß was observed in the intestinal regional lymph nodes, particularly in Peyer's patches. Further, increased IgA without elevated IFNß in the respiratory system suggested the possibility of a different mechanism from the gastrointestinal system.


Assuntos
Imunidade , Intestinos/imunologia , Linfonodos/imunologia , Viroses/imunologia , Autopsia , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Criança , Feminino , Humanos , Imunoglobulina A/sangue , Lactente , Recém-Nascido , Interferon beta/sangue , Intestinos/patologia , Linfonodos/patologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Nódulos Linfáticos Agregados/efeitos dos fármacos , Nódulos Linfáticos Agregados/imunologia , Poli I-C/farmacologia , Valores de Referência , Viroses/sangue
14.
J Forensic Leg Med ; 74: 102001, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33012316

RESUMO

There have been few studies of the death of children secondary to child abuse-related abdominal compression, and the detailed pathophysiology of such deaths is therefore unknown. The autopsy findings of a 3-year-old boy who died of hemorrhagic shock due to non-accidental severe blunt abdominal trauma were compared to those of children who died of other non-accidental abdominal injuries. Old and acute subcutaneous hemorrhages, abrasions, and scars were present all over the subject's body. No superficial injuries were found on the ventral midline, but a minor hemorrhage was found in the subcutaneous fat tissue, as well as in the rectus abdominis muscle. The intraperitoneal space contained 450 mL of blood, including coagulated blood. There was a tear in the transverse mesocolon and a crush injury in the small bowel mesentery. The inferior mesenteric artery was transected 0.5 cm from the aortic root. The transverse colon was necrotic, with hemorrhages in the mucosa. Since various organs were ischemic, the cause of death was determined to be blood loss from the inferior mesenteric artery injuries. Blunt abdominal trauma in children usually causes organ damage and intestinal injury, but because it is caused on the posterior surface of the mesentery, vascular injury should also be considered, and an autopsy should be performed. In the case of child abuse-related deaths, damage to the skin surface may not always be present; therefore, imaging tests, histopathological examinations, and biochemical tests should be performed with a focus on the gross anatomy to determine the cause of death and pathology.


Assuntos
Traumatismos Abdominais/patologia , Maus-Tratos Infantis/diagnóstico , Lacerações/patologia , Artéria Mesentérica Inferior/lesões , Ferimentos não Penetrantes/patologia , Traumatismos Abdominais/complicações , Pré-Escolar , Cicatriz/patologia , Colo/patologia , Hemorragia/patologia , Humanos , Lacerações/etiologia , Pulmão/diagnóstico por imagem , Masculino , Artéria Mesentérica Inferior/patologia , Mesocolo/lesões , Mesocolo/patologia , Necrose , Radiografia Abdominal , Gordura Subcutânea/patologia , Tela Subcutânea/patologia , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/complicações
15.
Hum Cell ; 33(3): 545-558, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32146707

RESUMO

This study aimed to investigate the usefulness of the thyroid-related hormones as markers of acute systemic hypoxia/ischemia to identify deaths caused by asphyxiation due to neck compression in human autopsy cases. The following deaths from pathophysiological conditions were examined: mechanical asphyxia and acute/subacute blunt head injury; acute/subacute non-head blunt injury; sharp instrument injury as the hemorrhagic shock condition; drowning as alveolar injury; burn; and death due to cardiac dysfunction. Blood samples were collected from the left and right cardiac chambers and iliac veins, and serum triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), and thyroid-stimulating hormone (TSH) levels were measured using electrochemiluminescence immunoassays. Two types of thyroid cell lines were used to confirm independent thyroid function under the condition of hypoxia (3% O2). The human thyroid carcinoma cell line (HOTHC) cell line derived from human anaplastic thyroid carcinoma and the UD-PTC (sample of the second resection papillary thyroid carcinoma) cell line derived from human thyroid papillary adenoma, which forms Tg retention follicles, were used to examine the secretion levels of T3, T4, and Tg hormones. The results showed a strong correlation between T3 and T4 levels in all blood sampling sites, while the TSH and Tg levels were not correlated with the other markers. Serum T3 and T4 levels were higher in cases of mechanical asphyxia and acute/subacute blunt head injury, representing hypoxic and ischemic conditions of the brain as compared to those in other causes of death. In the thyroid gland cell line, T4, T3, and Tg levels were stimulated after exposure to hypoxia for 10-30 min. These findings suggest that systemic advanced hypoxia/ischemia may cause a rapid and TSH-independent release of T3 and T4 thyroid hormones in autopsy cases. These findings demonstrate that increased thyroid-related hormone (T3 and T4) levels in the pathophysiological field may indicate systemic hypoxia/ischemia.


Assuntos
Asfixia/diagnóstico , Hipóxia/diagnóstico , Isquemia/diagnóstico , Tireoglobulina/sangue , Tireotropina/sangue , Tri-Iodotironina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biomarcadores/sangue , Feminino , Traumatismos Cranianos Fechados , Humanos , Masculino , Pessoa de Meia-Idade , Tiroxina
16.
PLoS One ; 15(2): e0218910, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069307

RESUMO

We previously showed that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, and specifically cortisol, responds to hypothermia. Human samples: Autopsies on 205 subjects (147 men and 58 women; age 15-98 years, median 60 years) were performed within 3 days of death. Cause of death was classified as either hypothermia (cold exposure, n = 14) or non-cold exposure (controls; n = 191). Cortisol levels were determined in blood samples obtained from the left and right cardiac chambers and common iliac veins using a chemiluminescent enzyme immunoassay. Adrenal gland tissues samples were stained for cortisol using a rabbit anti-human polyclonal antibody. Cell culture: AtT20, a mouse ACTH secretory cell line, and Y-1, a corticosterone secretory cell line derived from a mouse adrenal tumor, were analyzed in mono-and co-culture, and times courses of ACTH (in AtT20) and corticosterone (in Y-1) secretion were assessed after low temperature exposure mimicking hypothermia and compared with data for samples collected postmortem for other cases of death. However, no correlation between ACTH concentration and cortisol levels was observed in hypothermia cases. Immunohistologic analyses of samples from hypothermia cases showed that cortisol staining was localized primarily to the nucleus rather than the cytoplasm of cells in the zona fasciculata of the adrenal gland. During both mono-culture and co-culture, AtT20 cells secreted high levels of ACTH after 10-15 minutes of cold exposure, whereas corticosterone secretion by Y-1 cells increased slowly during the first 15-20 minutes of cold exposure. Similar to autopsy results, no correlation was detected between ACTH levels and corticosterone secretion, either in mono-culture or co-culture experiments. These results suggested that ACTH-independent cortisol secretion may function as a stress response during cold exposure.


Assuntos
Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Hidrocortisona/metabolismo , Hipotermia/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade
17.
Int J Legal Med ; 134(1): 243-249, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30955048

RESUMO

We reported the first comprehensive autopsy case of death due to intravenous injection of nicotine. We examined the distribution of nicotine in the body tissues and fluid and exposed the pathophysiology of nicotine poisoning. A 19-year-old woman was rushed to the hospital in cardiorespiratory arrest and was confirmed dead upon arrival. Liquid nicotine, hydrogen peroxide water, and a syringe were found in the hotel room where she stayed. On autopsy, nicotine concentration was the highest (15,023 µg/mg) in the tissue around the injection mark on the right upper arm. Among the body fluids, the intraperitoneal fluid had the highest, whereas the pericardial fluid had the lowest (0.736 µg/mL) nicotine concentration. Among the organs, the brain had the highest (11.637 µg/mg), whereas the fat tissue had the lowest (1.307 µg/mg) nicotine concentration. The concentration of cotinine, which is the metabolite of nicotine, was the highest in the tissue around the injection mark on the right arm (5.495 µg/mg) and was almost the same among the other body fluids and organs. The respective concentrations of nicotine and cotinine were 1.529 µg/mL and 0.019 µg/mL in the left heart blood and 3.157 µg/mL and 0.002 µg/mL in right heart blood. In this case, the nicotine concentrations in blood reached the lethal level. The distributions of nicotine and cotinine, as indicated by the intravenous injection, were related to the distribution of organs that metabolize nicotine and the distribution of nicotinic acetylcholine receptors.


Assuntos
Parada Cardíaca/etiologia , Injeções Intravenosas , Nicotina/intoxicação , Autopsia , Cotinina/metabolismo , Evolução Fatal , Feminino , Humanos , Líquido Pericárdico/metabolismo , Absorção Peritoneal , Distribuição Tecidual , Adulto Jovem
18.
J Clin Res Pediatr Endocrinol ; 12(2): 160-167, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31514489

RESUMO

Objective: To determine the time relationships of soluble receptor for glycation end-products (sRAGE), [a decoy of the advanced glycation end-products (AGE)-RAGE axis] and D-lactate, (a metabolite of methylglyoxal) in the inflammatory response to diabetic ketoacidosis (DKA). Methods: Sixteen children and adolescents with type 1 diabetes (T1D) had blood samples obtained, 6-12 hours into treatment, at three weeks and three months post start of treatment. sRAGE and D-lactate concentrations at three months were considered baseline. Expression of RAGE was investigated in the myocardium of a newly diagnosed and untreated young person with fatal T1D/DKA. Results: sRAGE 6-12 hours after the start of treatment was 39% lower than the values at two weeks (p=0.0036) and at three months (p=0.0023) post treatment. D-lactate was higher during treatment than at three weeks (p=0.04) and at three months (p=0.035). Conclusion: sRAGE concentration was decreased during treatment, compared to concentrations at two weeks and three months after treatment. The increased D-lactate during treatment was in keeping with the known increase in dicarbonyls at this time. The finding of RAGE expression in a young myocardium prior to DKA treatment suggested cardiovascular inflammation pre-treatment and at a young age.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/sangue , Cetoacidose Diabética/tratamento farmacológico , Produtos Finais de Glicação Avançada/sangue , Hipoglicemiantes/farmacologia , Inflamação/sangue , Ácido Láctico/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Adolescente , Criança , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/etiologia , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Estudos Longitudinais , Masculino , Miocardite/sangue , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Am J Forensic Med Pathol ; 41(1): 67-69, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31789819

RESUMO

The patient was a 5-year-old boy who was found in a state of cardiorespiratory arrest in the tub of a washing machine without water with the door closed. The autopsy findings included severe facial congestion and petechiae of the facial skin and palpebral conjunctiva. Several organs exhibited congestion. Hemorrhagic spots were seen on the serous membranes of various organs, with particularly marked hemorrhagic spots seen on the lungs. The heart contained fluid blood without soft clots. There were no findings indicative of marked trauma, intoxication, or hyperthermia. The examination results suggested that asphyxia had occurred in this case. However, there were no findings indicative of cervical compression, oronasal obstruction, or the presence of a foreign body in the respiratory tract. Image analysis showed the child could make postural changes inside the washing machine tub. Consequently, impaired thoracic movement and postural asphyxia were considered unlikely to have occurred. The results of blood gas analysis showed no evidence of marked hypercapnia. We, therefore, concluded that the cause of the child's death was asphyxia due to hypoxia caused by being in a closed space, that is, a washing machine tub.


Assuntos
Asfixia/etiologia , Espaços Confinados , Hipóxia/etiologia , Lavanderia/instrumentação , Parada Cardíaca Extra-Hospitalar/etiologia , Acidentes Domésticos , Pré-Escolar , Humanos , Hipóxia/complicações , Deficiência Intelectual , Masculino
20.
J Forensic Leg Med ; 65: 48-54, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31103923

RESUMO

The water contents of individual organs are maintained in a narrow range, but altered in morbidity owing to a disturbance of water equilibrium. The present study investigated the tissue water contents of major organs with regard to the cause of death in serial autopsy cases within 3 days postmortem (n = 329; 223 males, 106 females; age range, 1-100 years). Individual tissue water contents differed markedly across organs, but no significant postmortem or survival-period dependence, gender-related difference, or age dependence was observed. However, the lung water contents were higher in drowning cases, especially in saltwater cases (p < 0.05), and in strangulation among the acute mechanical asphyxiation cases. The brain water contents were higher in hypothermia cases (cold exposure) and tended to be higher in hyperthermia cases (heatstroke). The kidney water contents were higher in drowning and acute cardiac cases than in fatal intoxication and fire fatality cases, but tended to be higher in fresh- and bathwater drowning cases than in saltwater cases (p > 0.05). The spleen water contents were higher in bathwater drowning than in saltwater and freshwater cases, but did not differ among other the causes of death. These findings suggest that the postmortem tissue water content of individual organs, especially the lungs and/or kidney, depends on the cause of death and particularly contributes to differentiation between saltwater and freshwater drowning, respectively. This work therefore provides insight into the investigation of varied tissue water imbalances during the death process. In conclusion, we recommend the measurement of tissue water content because it is easy to perform and appears to be useful for evaluating the pathophysiology of systemic circulatory failure.


Assuntos
Água Corporal/metabolismo , Encéfalo/metabolismo , Rim/metabolismo , Pulmão/metabolismo , Mudanças Depois da Morte , Baço/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Asfixia/metabolismo , Doenças Cardiovasculares/metabolismo , Causas de Morte , Criança , Pré-Escolar , Afogamento/metabolismo , Feminino , Febre/metabolismo , Patologia Legal , Água Doce , Hematócrito , Humanos , Hipotermia/metabolismo , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Água do Mar , Fatores Sexuais , Adulto Jovem
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