Immediate early gene expression and delayed cell death in limbic areas of the rat brain after kainic acid treatment and recovery in the cold

Systemic injection of kainic acid (KA) results in characteristic behaviors and programmed cell death in some regions of the rat brain. We used KA followed by recovery at 4 degrees C to restrict damage to limbic structures and compared patterns of immediate early gene (IEG) expression and associated DNA binding activity in these damaged areas with that in spared brain regions. Male Wistar rats were injected with BA (12 mg/kg, ip) and kept at 4 degrees C for 5 h. This treatment reduced the severity of behaviors and restricted damage (observed by Nissl staining) to the CA1 and CA3 regions of the hippocampus and an area including the entorhinal cortex. DNA laddering, characteristic of apoptosis, was first evident in the hippocampus and the entorhinal cortex 18 and 22 h after RA, respectively. The pattern of IEG mRNA induction fell into three classes: IEGs that were induced in both damaged and spared areas (c-fos, fos B, jun B, and egr-1), IEGs that were induced specifically in the damaged areas (fra-2 and c-jun), and an IEG that was significantly induced by saline injection and/or the cold treatment (jun D). The pattern of immunoreactivity closely followed that of mRNA expression. Binding to the AP-1 and EGR DNA consensus sequences increased in all three regions studied. This study describes a unique modification of the animal model of ICA-induced neurotoxicity which may prove a useful tool for dissecting the molecular cascade that ultimately results in programmed cell death. (C) 1997 Academic Press.

Evaluating Causes of Death in Familial Adenomatous Polyposis

Background Familial adenomatous polyposis is a genetic syndrome associated with an increased risk of colorectal cancer (CRC) and different extracolonic manifestations Goals The goal of this study is to evaluate the frequency of death causes Material and Methods Charts from 97 patients treated from 1977 to 2008 were reviewed Retrieved data and family information allowed us to classify causes of death in those related to CCR to other malignancies or other causes Results There were analyzed data from 46 men (47 4%) and 51 women (52 6%) with an average age of 35 1 years (14 to 82) At diagnosis, 57 patients (58 7%) already had CRC-associated polyposis There were performed 93 colectomies, one internal diversion, and one partial resection Two patients were not operated on Results from 19 deceased patients (19 5%) were analyzed CRC, other tumors (desmoid tumors, lymphoma, and gastric cancer), and other causes (complication of duodenal cancer surgery, complication after ileorectal anastomosis (IRA), and coronary disease) were responsible for 12 (63 1%), four (21 1%), and three (15 8%) of all deaths, respectively Death from CRC occurred in the context of either systemic, rectal, or pouch recurrence Desmoid disease was the second cause of death (10 5% of all causes), leading to a fatal outcome 22% of all patients who developed DT during the study period Upper digestive carcinomas were responsible for other two death cases Conclusions (1) CRC is still the most prevalent cause of death, (2) even after curative resections, CRC can cause death through rectal or pouch malignization, (3) long-term survival was also strongly related to the development of extracolonic neoplasia, especially desmoid tumors and gastroduodenal carcinoma, (4) our results raise the need for local improvement in familiar screening and help us to define follow-up strategies and patient-information standards

Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant hepatitis (Labrea black fever) in the western Brazilian Amazon region

The genotypes of hepatitis B (HBV) and delta (HDV) viruses circulating among fulminant hepatitis cases from the western Amazon Basin of Brazil were characterized in this study. HBV and HDV isolates were obtained from liver samples from 14 patients who developed fulminant hepatitis and died during 1978-1989. HBV DNA and HDV RNA were detected in all samples. Phylogenetic analyses of HDV sequences showed that they all clustered with previously characterized sequences of HDV genotype 3 (HDV-3). HBV genotypes F, A and D were found in 50.0, 28.6 and 21.4% of cases, respectively. These results confirm the predominance of HDV-3 in South America and its association with the severe form of hepatitis, and the finding of the co-infection of HDV-3 with different genotypes of HBV suggests that the association between HDV-3 and HBV-F is not necessarily causally related to a more severe clinical course of infection.

Autopsy-Proven Determinants of Immediate Fire Death in Lungs

In immediate fire deaths, pulmonary injury may be the main source of mortality, being important to document the histologic findings for the purpose of excluding other modes of death, such as from asphyxia with no gross findings. In this context, a group of morphologic determinants have been targeted with useful makers of pulmonary injury. To facilitate the determination of whether an individual was deceased before the start of a fire and validate the importance of parenchymal alterations in pulmonary injury in fire deaths, we studied lungs in victims of fire (N = 28) and suffocation (N = 40), creating a mathematical model using cluster analysis. For this purpose, a semiquantitative analysis of the distal parenchyma was performed to evaluate the amount of bronchiolar dilatation, overinsufflation (ductal and alveolar), collapse (ductal and alveolar), passive congestion, alveolar edema, and hemorrhage (interstitial and alveolar). These 7 histologic determinants were useful to discriminate fire (bronchiolar dilatation, ductal overinsuflation, alveolar overinsuflation, alveolar hemorrhage) from suffocation lung injuries (alveolar collapse, congestion, and edema). We conclude that these determinants should be included in the routine of forensic pathology.

Immunohistochemical evaluation of macrophage activity and its relationship with apoptotic cell death in the polar forms of leprosy

The objective of the present study was to investigate the correlation between macrophage activity and apoptosis in the polar forms of leprosy because the immunopathological phenomena involved in these forms are still poorly understood For this purpose, 29 skin biopsy samples obtained from patients with the polar forms of leprosy were analyzed. Macrophage activity and apoptosis were evaluated by immunohistochemistry using lysozyme, CD68, iNOS and caspase 3 as markers The nonparametric Mann-Whitney test and Spearman`s linear correlation test were used for statistical analysis The results suggest that the apoptosis rate is under the direct influence of macrophage activity in lesions of patients with the tuberculoid form In contrast, in lepromatous lesions other factors seem to induce programmed cell death, possibly TGF-beta. Further studies are necessary to identify additional factors involved in the immunopathogenesis of leprosy. (C) 2010 Elsevier Ltd. All rights reserved

Myocardial Perfusion Imaging Is a Strong Predictor of Death in Women

OBJECTIVES We sought to assess the prognostic value and risk classification improvement using contemporary single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) to predict all-cause mortality. BACKGROUND Myocardial perfusion is a strong estimator of prognosis. Evidence published to date has not established the added prognostic value of SPECT-MPI nor defined an approach to detect improve classification of risk in women from a developing nation. METHODS A total of 2,225 women referred for SPECT-MPI were followed by a mean period of 3.7 +/- 1.4 years. SPECT-MPI results were classified as abnormal on the presence of any perfusion defect. Abnormal scans were further classified as with mild/moderate reversible, severe reversible, partial reversible, or fixed perfusion defects. Risk estimates for incident mortality were categorized as <1%/year, 1% to 2%/year, and >2%/year using Cox proportional hazard models. Risk-adjusted models incorporated clinical risk factors, left ventricular ejection fraction (LVEF), and perfusion variables. RESULTS All-cause death occurred in 139 patients. SPECT-MPI significantly risk stratified the population; patients with abnormal scans had significantly higher death rates compared with patients with normal scans, 13.1% versus 4.0%, respectively (p < 0.001). Cox analysis demonstrated that after adjusting for clinical risk factors and LVEF, SPECT-MPI improved the model discrimination (integrated discrimination index = 0.009; p = 0.02), added significant incremental prognostic information (global chi-square increased from 87.7 to 127.1; p < 0.0001), and improved risk prediction (net reclassification improvement = 0.12; p = 0.005). CONCLUSIONS SPECT-MPI added significant incremental prognostic information to clinical and left ventricular functional variables while enhancing the ability to classify this Brazilian female population into low-and high-risk categories of all-cause mortality. (J Am Coll Cardiol Img 2011;4:880-8) (C) 2011 by the American College of Cardiology Foundation

Sudden unexpected death in an adolescent with epilepsy: All roads lead to the heart?

The incidence of sudden unexpected death in epilepsy (SUDEP) has been estimated from 0.5-1.4/1,000 person-years in people with treated epilepsy, and 9/1,000 person-years in candidates for epilepsy surgery. Potential risk factors for SUDEP include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure type and winter temperatures. The arrythmogenic side-effect of antiepileptic drugs and seizures may increase the risk of SUDEP. In this report, we describe a patient with prolonged post-ictal tachycardia in EEG video recordings with a typical case of SUDEP: a 16-year-old boy with medically intractable complex partial seizures. Magnetic resonance imaging revealed left mesial temporal sclerosis. During non-invasive video-EEG monitoring, the patient presented a post-ictal heart rate increased for five hours. Two months after video-EEG, he died from SUDEP during a tonic-clonic secondary generalized seizure. The possibility of cardiac involvement in the pathogenesis of SUDEP has been suggested by many studies. Evaluation of this patient with EEG-video monitoring, including measurement of heart rate, contributed to an identification of ictal tachycardia that may have played a role in the SUDEP. Premature mortality seems to be increased in patients with epilepsy, and cardiac abnormalities may be a possible cause of SUDEP. (Cardiol J 2011; 18, 2: 194-196)

Subclinical hyperthyroidism and sudden unexpected death in epilepsy

Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. In parallel, several studies have shown a link between hormones and epilepsy. However, exact knowledge regarding the association of thyroid hormones and epilepsy is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease, we propose in this paper that SUDEP, at least in some cases, could be related with subclinical thyroid dysfunction. (C) 2009 Elsevier Ltd. All rights reserved.

Benefits of sunlight: Vitamin D deficiency might increase the risk of sudden unexpected death in epilepsy

Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. In parallel, studies have shown a link between vitamin D dysfunction and epilepsy. Moreover, several evidences in the literature suggest an association between low vitamin D and seizures, indicating the possibility of anticonvulsant properties of this hormone. Quite interesting, a growing body of data suggests that low vitamin D levels may adversely affect cardiovascular health, directly associated with death from heart failure and sudden cardiac death. In view of the above findings, our research group focused in this review article that SUDEP, at least in some cases, could be related with low vitamin D levels. (C) 2009 Elsevier Ltd. All rights reserved.

Does the lunar phase have an effect on sudden unexpected death in epilepsy?

The incidence of sudden unexpected death in epilepsy (SUDEP) in Our epilepsy unit over an 8-year period was analyzed to determine a possible association between phase of the moon and SUDEP. Analysis revealed that the number of SUDEPs was highest in full moon (70%), followed by waxing moon (20%) and new moon (10%). No SUDEPs Occurred during the waning cycle. These preliminary findings suggest that the full moon appears to correlate with SUDEP. (C) 2008 Elsevier Inc. All rights reserved.

Precise Temporal Regulation of roughest is Required for Correct Salivary Gland Autophagic Cell Death in Drosophila

The Drosophila roughest (rst) locus encodes an immunoglobulin superfamily transmembrane glycoprotein implicated in a variety of embryonic and postembryonic developmental processes. Here we demonstrate a previously unnoticed role for this gene in the autophagic elimination of larval salivary glands during early pupal stages by showing that overexpression of the Rst protein ectodomain in early pupa leads to persistence of salivary glands up to at least 12 hours after head eversion, although with variable penetrance. The same phenotype is observed in individuals carrying the dominant regulatory allele rst(D), but not in loss of function alleles. Analysis of persistent glands at the ultrastructural level showed that programmed cell death starts at the right time but is arrested at an early stage of the process. Finally we describe the expression pattern and intracellular distribution of Rst in wild type and rstD mutants, showing that its downregulation in salivary glands at the beginning of pupal stage is an important factor in the correct implementation of the autophagic program of this tissue in space and time. genesis 47:492-504, 2009. (C) 2009 Wiley-Liss, Inc.

Thyroid gland and cerebella lesions: New risk factors for sudden cardiac death in schizophrenia?

People with schizophrenia show a two to threefold increased risk to die prematurely than those without schizophrenia. Patients` life style, suicide, premature development of cardiovascular disease, high prevalence of metabolic syndrome and sudden cardiac death are well-known causes of the excess mortality. The exact pathophysiological cause of sudden death in schizophrenia is unknown, but it is likely that cardiac arrhythmia and respiratory abnormalities play potential role. Some antipsychotics may be associated with cardiovascular adverse events (e.g., QT interval prolongation) and lesions in specific brain regions, such as cerebella may be associated with respiratory abnormalities, suggesting that metabolic and brain dysfunction could lead to sudden cardiac death in patients with schizophrenia. However, exact knowledge regarding the association of these findings and schizophrenia is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease and cerebella progressive atrophy has been observed in patients with schizophrenia, we propose in this paper that subclinical thyroid dysfunction and cerebella volume loss could be considered as new risk factor for sudden cardiac death in schizophrenia. (C) 2010 Elsevier Ltd. All rights reserved.

Could sudden death syndrome (SDS) in chickens (Gallus gallus) be a valid animal model for sudden unexpected death in epilepsy (SUDEP)?

Epilepsy is the most common serious neurological disorder and approximately 1% of the population worldwide has epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning fisk factors for SUDEP is conflicting, but potential risk factors include: young age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Similarly, sudden death syndrome (SDS) is a disease characterized by an acute death of well-nourished and seeming healthy Gallus gallus after abrupt and brief flapping of their wings and incidence of SDS these animals has recently increased worldwide. Moreover, the exactly cause of SDS in Gallus gallus is unknown, but is very probable that cardiac abnormalities play a potential role. Due the similarities between SUDEP and SDS and as Gallus gallus behavioral manifestation during SDS phenomenon is close of a tonic-clonic seizure, in this paper we suggest that epilepsy could be a new possible causal factor for SDS. (C) 2009 Elsevier Ltd. All rights reserved.

Insulin Affects Tissue Organization and the Kinetics of Epithelial Cell Death in the Rat Ventral Prostate After Castration

Prostate growth and physiology are regulated by steroid hormones and modulated by multiple endocrine factors We investigated the action of insulin on the tissue organization and kinetics of epithelial cells in the rat ventral prostate (VP) in response to castration up to 120 hours after surgery by using an acute protocol of alloxan induced diabetes Diabetes caused a reduction in volume density (Vv(o)/) and volume of the epithelium The effects of castration on the epithelium were accelerated in the diabetic animals as determined by changes in V(o)/, and volume The smooth muscle cells became atrophic and apparently relaxed in response to castration in contrast to the spinous aspect observed in nondiabetic castrated rats Counting of apoptotic nuclei in the epithelium showed the classical apoptosis peak at 72 hours in nondiabetic rats and an advance of the apoptosis peak to 48 hours after castration in diabetic rats Insulin restored the time of the peak to 72 hours These results were confirmed after immunostaining for cleaved caspase 3 and suggest a survival and antiapoptotic effect on VP epithelial cells in both the presence and absence of androgen stimulation This idea is supported by the observation that insulin also reduced the overall rate of apoptosis at all experimental points analyzed before and after castration

Activation of the peroxisome proliferator-activated receptor-alpha enhances cell death in cultured cerebellar granule cells

Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is a member of the steroid hormone receptor superfamily. In rodents, PPAR alpha. alters genes involved in cell cycle regulation in hepatocytes. Some of these genes are implicated in neuronal cell death. Therefore, in this study, we examined the toxicological consequence of PPAR alpha activation in rat primary cultures of cerebellar granule neurons. Our studies demonstrated the presence of PPAR alpha mRNA in cultures by reverse transcriptase-polymerase chain reaction. After 10 days in vitro, cerebellar granule neuron cultures were incubated with the selective PPAR alpha activator 4-chloro-6-(2,3-xylidino)2-pyrimidinylthioacetic acid (Wy-14,643). The inherent toxicity of Wy-14,643 and the effect of PPAR alpha activation following toxic stimuli were assessed. In these studies, neurotoxicity was induced through reduction of extracellular [KCl] from 25 mM to 5.36 mM. We observed no inherent toxicity of Wy-1 4,643 (24 hr) in cultured cerebellar granule cells. However, after reduction of [KCl], cerebellar granule cell cultures incubated with Wy-14,643 showed significantly greater toxicity than controls. These results suggest a posssible role for PPAR(x in augmentation of cerebellar granule neuronal death after toxic stimuli. (C) 2001 Wiley-Liss, Inc.