Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection can be fatal in infants <1 year after birth. Morphological findings associated with infant death, however, are insufficient, and screening procedures are problematic. The aim of the present study was to establish a postmortem diagnosis of RSV pathogenicity. Methods: Serial forensic autopsies of 55 infants who suddenly died ≤1 year after birth due to viral pneumonia (n = 18), bacterial pneumonia (n = 12), or other diseases and trauma (n = 25) were assessed. Causes of viral pneumonia determined on immunochemical screening and histological staining of airway effusions consisted of RSV (n = 8) and other viruses (n = 10). Results: Bronchial epithelial and inflammatory cells in the interstitium around bronchioles and alveoli were immunopositive for RSV. Bronchial epithelium was more frequently positive for RSV (5/8, 62.5%) than for bacterial pneumonia and other causes of death (7/47, 14.9%); and intra‐alveolar sites were also more frequently positive for RSV pneumonia (3/8, 37.5%) than for bacterial pneumonia and other causes of death (4/47, 8.5%). Screening immunoassays and immunohistochemical staining for RSV can serve as an index of RSV infection when serum antibody titers, viral identification and polymerase chain reaction (PCR) are not informative. Peribronchiolar interstitial RSV positivity was similar between RSV pneumonia (7/8, 87.5%) and other causes of death (34/47, 72.3%). Conclusions: RSV was the cause of death in only eight infants because RSV infection was difficult to diagnose. Therefore, more deaths associated with RSV need to be investigated. Bronchial epithelium and intra‐alveolar cells that are RSV immunopositive might augment RSV pathogenicity in viral pneumonia. [ABSTRACT FROM AUTHOR]

The present study aimed to determine whether postmortem period, physical constitution, cause of death, and cardiopulmonary resuscitation are associated with positional changes in the postmortem appearance of conjunctival petechiae. We retrospectively investigated serial forensic autopsies from 6 h to 6 days postmortem (n = 442; male, 303; female, 139; median age, 62 years; range, 0-100 years). The causes of death were sharp instrument injury, blunt force trauma, fire, intoxication, asphyxia, drowning, hypothermia, hyperthermia, acute heart failure, and natural causes. Of these, 28 (male, n = 18; female, n = 10) were aged ≤5 years. Palpebral conjunctival petechiae were initially assessed at autopsy in supine bodies, then reassessed in prone bodies after 30 min. Among 414 bodies, 291 (70.2%) and 123 (29.7%) who were aged between 6 and 100 years, and 18 (64.2%) and 10 (35.7%) aged <5 years at the time of death, were discovered in the supine and prone positions, respectively. The amounts of petechiae increased within 1.5 days postmortem, but not in those discovered in the prone position. The rates at which petechiae increased were higher in supine overweight bodies (BMI ≥ 25.0) and in those who were discovered supine and had died of asphyxia or drowning (37.5%). Cardiopulmonary resuscitation for bodies discovered in the supine and prone positions did not statistically affect the occurrence of petechiae. Several postmortem factors can cause hypostatic blood redistribution that manifests as increased amounts of petechiae in the palpebral conjunctivae. [ABSTRACT FROM AUTHOR]

Oral antidiabetics can cause fatal hypoglycemia; although they can be chemically identified and quantified, biochemical investigations are important for assessing the biological consequences of an overdose. Such cases of overdose involving oral antidiabetics may involve other drugs for treating lifestyle-related diseases, particularly antihypertensives. Here, we report a toxicological and biochemical investigation of drugs and biochemical profiles in a fatal overdose involving multiple oral antidiabetics and antihypertensives. A 55-year-old woman died about 2 days after the ingestion of around 110 tablets of antidiabetics and antihypertensives that had been prescribed for her husband. A forensic autopsy and histological analysis demonstrated no evident pathology as the cause of death. A toxicological analysis suggested hypoglycemia and an overdose of antihypertensives as well as the retention of antidiabetics and diuretics in the pericardial fluid. A relatively low pericardial amlodipine concentration was observed, which may have been the result of its long half-life (slower distribution and reduction rate) and/or possible affinity with the myocardium. In addition, a biochemical analysis indicated hypoglycemia, without increased serum insulin and C-peptide, but with increased glucagon levels, as the possible influence of glibenclamide overdose. These observations suggest the usefulness of a combination of toxicological and biochemical analyses in postmortem investigations involving a fatal overdose of such drugs. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) is an illicit stimulant that affects the central nervous system. Cytochrome P450 2D6 (CYP2D6) plays an important role in MA metabolism. Numerous allelic variants confer substantial variation in CYP2D6 activity among individuals. In the present study, we examined the frequencies of CYP2D6 alleles, including CYP2D6*1, *2, *4, *5, *10, *14A, *14B, *18, and *36, and multiplication, in 82 forensic autopsy cases of MA abusers and 567 autopsy cases in which MA was not detected (controls). Ultrarapid metabolizer (UM), extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) phenotypes were predicted from CYP2D6 genotypes. Of MA abusers, 64 subjects were predicted to be EM, 17 were IM, and 1 was UM. No MA abuser had the predicted PM phenotype. No significant differences in CYP2D6 phenotype frequencies were found between MA abusers and controls. MA and amphetamine (AMP) concentrations were measured in the right heart blood, left heart blood, peripheral external iliac blood, urine, pericardial fluid, and bone marrow of MA abusers. MA concentrations in urine and bone marrow were significantly higher in IM than in EM. AMP concentration was not associated with CYP2D6 phenotype in any body fluid. These results suggest that the MA concentration in body fluids is influenced by CYP2D6 phenotypes in the Japanese population. [ABSTRACT FROM AUTHOR]

Background: Recently, the nutritional status of patients has drawn attention in an aging society. Early studies have reported that nutritional status is related to long-term outcomes in patients with acute myocardial infarction (AMI). However, it is not necessarily simple to evaluate the nutritional status of patients with AMI. We hypothesized that appetite before discharge can be a predictor for long-term adverse cardiovascular events in patients with AMI. This retrospective study aimed to investigate whether appetite is related to long-term adverse outcomes in patients with AMI. Methods: This study included 1006 patients with AMI, and divided them into the good appetite group (n = 860) and the poor appetite group (n = 146) according to the percentage of the dietary intake on the day before discharge. Major adverse cardiac events (MACE), which were defined as a composite of all-cause death, non-fatal MI, and re-admission for heart failure, were set as the primary outcome. Results: The median follow-up duration was 996 days, and a total of 243 MACE was observed during the study period. MACE was more frequently observed in the poor appetite group than in the good appetite group (42.5% versus 21.0%, p < 0.001). In the multivariate COX hazard model, poor appetite was significantly associated with MACE (Hazard ratio 1.698, 95% confidence interval 1.243–2.319, p < 0.001) after controlling for multiple confounding factors. Conclusion: Appetite at the time of discharge was significantly associated with long-term clinical outcomes in patients with AMI. Patients with poor appetite should be carefully followed up after discharge from AMI. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to determine and to verify the correlation between the amount of prolactin (PRL) levels in the blood and in the cerebrospinal fluid (CSF) by various causes of death as an indicator for acute hypoxia in autopsy cases. It is to confirm the cause of the change in prolactin level in CSF by in vitro system. Materials and methods: In autopsy materials, the PRL levels in blood from the right heart ventricle and in the CSF were measured by chemiluminescent enzyme immunoassay, and changes in the percentage of PRL-positive cells in the pituitary gland were examined using an immunohistochemical method. Furthermore, an inverted culture method was used as an in vitro model of the blood-CSF barrier using epithelial cells of the human choroid plexus (HIBCPP cell line) and SDR-P-1D5 or MSH-P3 (PRL-secreting cell line derived from miniature swine hypophysis) under normoxic or hypoxic (5% oxygen) conditions, and as an index of cell activity, we used Vascular Endothelial Growth Factor (VEGF). Results and discussion: Serum PRL levels were not significantly different between hypoxia/ischemia cases and other causes of death. However, PRL levels in CSF were three times higher in cases of hypoxia/ischemia than in those of the other causes of death. In the cultured cell under the hypoxia condition, PRL and VEGF showed a high concentration at 10 min. We established a brain-CSF barrier model to clarify the mechanism of PRL transport to CSF from blood, the PRL concentrations from blood to CSF increased under hypoxic conditions from 5 min. These results suggested that PRL moves in CSF through choroidal epithelium from blood within a short time. PRL is hypothesized to protect the hypoxic/ischemic brain, and this may be because of the increased transportation of the choroid plexus epithelial cells. [ABSTRACT FROM AUTHOR]

The process of texture formation on iron particles was investigated via simple ball milling using graphite particles as milling aid. During milling, the shape of the iron particles changed from granular to platelets owing to repetitive compression and balls rolling in a direction perpendicular to the platelet faces. Simultaneously, a {001} + {111} double-fiber texture was formed, which is characteristic of a metal with a bcc structure deformed under uniaxial compression and multidirectional rolling. Based on these observations, it is concluded that the texture obtained through simple ball milling was induced by uniaxial compression and a multidirectional-rolling-like deformation. Since the main component of the double-fiber texture is {001} and the easy magnetization axes 〈001〉 are oriented toward the in-plane directions with the platelet face in the texture, the iron particles are ideal candidates for use as magnetic cores in motors, inductors, and other electromagnetic parts. [ABSTRACT FROM AUTHOR]

Many studies have reported that the degree of thyroid cartilage ossification correlates with age. However, its use in forensics has been limited by individual variation, tissue fragility, and observer subjectivity. We examined a new method for age estimation from the degree of ossification of thyroid cartilage using postmortem computed tomography (CT) and Bayesian analysis. The scoring of CT density values, ossification rate, and morphological changes was performed in 131 Japanese males (20–80 years old), and an age estimation table was created and verified in 39 other Japanese males. We tried two types of prior probability; one was males undergoing postmortem CT imaging at our institute, and the other was the age composition of the male population in Japan. The differences in percentage in each age group were observed, especially in the ninth decade, but they were not large enough to change the result. Two decedents in their 30s and 80s could not be assigned an age group. Likelihood might have had more significant influence than prior probability. Bayesian approach and new scoring system of thyroid cartilage ossification might be useful as an age estimation method. Although the low posterior probability in decedents the age ≧70 remains a problem, the advantage of Bayesian estimation that it can sequentially update the age estimation table by factoring in exceptional data can solve this problem. In this study, accuracy of age estimation did not dramatically increase, however, Bayesian statistics might become a useful technique for examining any tissue samples subject to age-related calcification. [ABSTRACT FROM AUTHOR]

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)β levels were measured, and histopathological and immunohistochemical examinations were conducted. Furthermore, we cultured human cells and measured IFNβ 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, IFNβ 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 IFNβ after viral stimulation. Conversely, respiratory regional lymph nodes showed enhanced IgA with no marked change in IFNβ. Overproduction of IgA, identified as an aberration of the immune system and resulting from excessive viral infection-induced IFNβ was observed in the intestinal regional lymph nodes, particularly in Peyer's patches. Further, increased IgA without elevated IFNβ in the respiratory system suggested the possibility of a different mechanism from the gastrointestinal system. [ABSTRACT FROM AUTHOR]

A man in his 40s was found unconscious on a sofa in a communal residence for people with various disabilities. He appeared to have drunk 800 ml of undiluted citric acid from a commercial plastic bottle. The instructions on the label of the beverage specified that the beverage be diluted 20- to 30-fold before consumption. The patient was admitted to an emergency hospital with severe metabolic acidosis (pH, 6.70; HCO 3 − , 3.6 mEq/L) and a low ionized calcium level (0.73 mmol/L). Although ionized calcium and catecholamines were continuously administered intravenously to correct the acidosis, the state of acidemia and low blood pressure did not improve, and he died 20 h later. Citric acid concentrations in the patient’s serum drawn shortly after treatment in the hospital and from the heart at autopsy were 80.6 mg/ml and 39.8 mg/dl, respectively (normal range: 1.3–2.6 mg/dl). Autopsy revealed black discoloration of the mucosal surface of the esophagus. Microscopically, degenerated epithelium and neutrophilic infiltration in the muscle layer were observed. In daily life, drinking a large amount of concentrated citric acid beverage is rare as a cause of lethal poisoning. However, persons with mental disorders such as dementia may mistakenly drink detergent or concentrated fluids, as in our case. Family members or facility staff in the home or nursing facility must bear in mind that they should not leave such bottles in places where they are easily accessible to mentally handicapped persons. [ABSTRACT FROM AUTHOR]

• In stimulant cases, IL-6 and IL-8 levels in blood and CSF were high. • In heat stroke cases, IL-6 was decreased in blood, while IL-8 was elevated. • Blood NSE was elevated in stimulant and heat stroke. • MBP in blood was elevated in stimulant, while CSF was elevated in heat stroke. • In a culture experiment, marker was elevated under a high-temperature environment. 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. [ABSTRACT FROM AUTHOR]

Highlights • Catecholamine levels were measured in cerebrospinal fluid (CSF) from autopsy cases. • MAOA-uVNTR polymorphism was associated with CSF adrenaline and dopamine levels in females. • MAOA-uVNTR polymorphism was not associated with CSF noradrenaline levels in females. • MAOA-uVNTR polymorphism was not associated with CSF catecholamine levels in males. Abstract Monoamine oxidase A (MAOA) plays important roles in the metabolism of catecholamines and modulates adrenergic, noradrenergic, and dopaminergic signaling. A polymorphic promoter variable number tandem repeat (VNTR) locus (MAOA-uVNTR) is located approximately 1.2 kb upstream from MAOA exon 1. Functional studies revealed that MAOA-uVNTR affects gene expression. In the present study, we examined the frequencies of MAOA-uVNTR alleles in Japanese autopsy cases, in which amphetamines or psychotropic drugs were not detected. In total, 87 males and 35 females were evaluated and investigated for the possible effect of MAOA-uVNTR polymorphisms on cerebrospinal fluid (CSF) catecholamine concentrations. In males, there was no significant association between MAOA-uVNTR polymorphisms and CSF adrenaline (Adr), noradrenaline (Nad), or dopamine (DA) levels. In contrast, females who were homozygous for the 3-repeat allele (i.e., 3/3 genotype carriers) had higher CSF levels of Adr (p = 0.024) and DA (p = 0.035) than individuals who were heterozygous or homozygous for the 4-repeat allele (3/4 and 4/4, respectively). We found no significant association between MAOA-uVNTR polymorphisms and CSF Nad levels in females. Thus, the results of the present study indicated that MAOA-uVNTR polymorphism influences CSF Adr and DA levels in females. [ABSTRACT FROM AUTHOR]

Dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 ( DRD2/ANKK1 ) gene polymorphisms have been associated with responses to psychotropic drugs and addiction. We analyzed two DRD2/ANKK1 polymorphisms, Taq1A and –141C Ins/Del, in 37 fatal methamphetamine (MA) intoxication cases and 235 control cases in which MA and psychotropic drugs were not detected. The association among polymorphism, cause of death, and cerebrospinal fluid (CSF) dopamine concentration was evaluated. The Taq1A polymorphism distribution in the fatal MA intoxication cases differed from in the controls ( P  = 0.030) with a significantly high A1/A1 + A1/A2 genotype frequency. No significant associations were observed between –141C Ins/Del polymorphisms and MA intoxication cases or between DRD2/ANKK1 polymorphisms and CSF dopamine concentrations. Our findings suggest that the DRD2/ANKK1 Taq1A polymorphism is associated with susceptibility to fatal MA intoxication. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It has been suggested that store-operated Ca2+ entry (SOC) facilitates catecholamine secretion and synthesis in bovine adrenal medullary (AM) cells. However, there has been no experimental result clearly showing that cation channel activity is enhanced by store Ca2+ depletion. Thus the present experiments were undertaken to address the issue of whether rat AM cells have SOC channels. Inhibition of the sarco(endo)plasmic reticulum Ca2+ (SERCA) pump resulted in a sustained increase in intracellular Ca2+ concentration ([Ca2+]i) in rat AM cells. This increase was completely suppressed by 2 mM Ni2+ but not by 100 μM D600. A bath application of Ni2+ but not D600, produced an outward current at -60 mV in rat AM cells, whereas exposure to a SERCA pump inhibitor did not affect either the whole cell current level or the Ni2+-induced outward current. The refilling of intracellular store sites was suppressed by the addition of Ni2+ to the perfusate. RT-PCR revealed that transcripts for transient receptor potential channels 1 (TRPC1) and 5 (TRPC5) were present in rat adrenal medullas. Immunocytochemistry showed that TRPC1 channels, which have been implicated in SOC in certain types of cells, were mainly localized in the endoplasmic reticulum (ER) and not in the plasma membrane, and that STIM1, a Ca2+ sensor in the ER, was not expressed in rat AM cells. On the basis of these results, we conclude that rat AM cells lack the SOC mechanism. [ABSTRACT FROM AUTHOR]

Purpose: A procedure is needed for bodies with disfiguring injuries to the face and the use of their portrait for visual identification. Method: We present the application of a simple image processing procedure, otherwise known as "bubbling," which is based on the concept of "perceptual filling-in," to images for visual identification in the forensic context. The method is straight forward and can be performed using readily available software and hardware.. Results: The method is demonstrated and examples are shown. The visual recognition of known persons using "bubbled" images was successfully tested. Conclusion: The "bubbling" procedure for visual identification enhancement is quick and straightforward and may be attempted before escalating to more involved identification methods and procedures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Femicide is a murder due to the failure to recognize the victim's right to self-determination. • There is a need for homogeneous methodology for the study of female homicides. • Male and female homicides can be considered as two distinct victimological phenomena. • Injuries and circumstantial patterns in femicides could represent evidence of a specific murder, deserving a specific regulatory framework. • More studies with a standardized data collection are needed to corroborate the theory of this paper. In a previous work, authors have proposed a medico-legal definition of femicide as the murder due to the failure to recognize the right of self-determination of women. The aim of this paper was to apply the proposed definition to a cohort of cases to characterise femicides and female homicides and assess whether femicides can be considered a distinct entity or not. A comparison between female and male homicides was performed to assess common and distinctive features. Femicides were identified and compared to the cohort of non-femicide female murder. Results were compared to those reported in published forensic studies. Significant associations between female and male homicides were found for sex and partner/ex-partner offender, sex and indoor homicide and sex and asphyxia as dynamic of death emerged. A higher prevalence of indoor homicides and asphyxiation and of partner relationships were documented in female homicides. Gunshot, blunt injuries and cut wounds are well represented in both types of homicides. Most affected sites are back and chest in male homicides, and head, breasts, pubis, and limbs in female homicides. When comparing femicides and female homicides, a positive association between strangulation as harmful mean and a negative one between femicides and indoor homicides were found. Male and female homicides can be considered as two distinct victimological phenomena. Focusing on femicide allows to establish injuries and circumstantial patterns, that could represent evidence of a specific murder. More studies with a standardized data collection are needed to corroborate the theory of this paper. [ABSTRACT FROM AUTHOR]

This report describes the case of a man who developed fatal sigmoid volvulus that was identified on postmortem radiography before forensic autopsy. Postmortem radiography is useful for visualizing the body prior to autopsy. We discuss postmortem multidetector computed tomography that was tailored for optimum image quality to allow reconstruction of the fatal findings in multiple axes and in three dimensions, helping to pinpoint the anatomical sites of interest. This involves techniques such as manipulation of the scanning beam pitch and overlapping CT section acquisition. These techniques are best performed by personnel with CT technology training. [ABSTRACT FROM AUTHOR]