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Frontiers in Pharmacology 2024Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart...
Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats. Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment. GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects.
PubMed: 38873418
DOI: 10.3389/fphar.2024.1402138 -
Scientific Reports Jun 2024Traumatic brain injury (TBI) is a ubiquitous, common sequela of accidents with an annual prevalence of several million cases worldwide. In forensic pathology, structural...
Traumatic brain injury (TBI) is a ubiquitous, common sequela of accidents with an annual prevalence of several million cases worldwide. In forensic pathology, structural proteins of the cellular compartments of the CNS in serum and cerebrospinal fluid (CSF) have been predominantly used so far as markers of an acute trauma reaction for the biochemical assessment of neuropathological changes after TBI. The analysis of endogenous metabolites offers an innovative approach that has not yet been considered widely in the assessment of causes and circumstances of death, for example after TBI. The present study, therefore, addresses the question whether the detection of metabolites by liquid-chromatography-mass spectrometry (LC/MS) analysis in post mortem CSF is suitable to identify TBI and to distinguish it from acute cardiovascular control fatalities (CVF). Metabolite analysis of 60 CSF samples collected during autopsies was performed using high resolution (HR)-LC/MS. Subsequent statistical and graphical evaluation as well as the calculation of a TBI/CVF quotient yielded promising results: numerous metabolites were identified that showed significant concentration differences in the post mortem CSF for lethal acute TBI (survival times up to 90 min) compared to CVF. For the first time, this forensic study provides an evaluation of a new generation of biomarkers for diagnosing TBI in the differentiation to other causes of death, here CVF, as surrogate markers for the post mortem assessment of complex neuropathological processes in the CNS ("neuroforensomics").
Topics: Humans; Brain Injuries, Traumatic; Biomarkers; Male; Female; Middle Aged; Adult; Aged; Chromatography, Liquid; Metabolomics; Mass Spectrometry; Young Adult; Autopsy; Aged, 80 and over
PubMed: 38871842
DOI: 10.1038/s41598-024-64312-0 -
Scientific Reports Jun 2024Congenital diaphragmatic hernia (CDH) is a birth defect characterized by incomplete closure of the diaphragm, herniation of abdominal organs into the chest, and...
Congenital diaphragmatic hernia (CDH) is a birth defect characterized by incomplete closure of the diaphragm, herniation of abdominal organs into the chest, and compression of the lungs and the heart. Besides complications related to pulmonary hypoplasia, 1 in 4 survivors develop neurodevelopmental impairment, whose etiology remains unclear. Using a fetal rat model of CDH, we demonstrated that the compression exerted by herniated organs on the mediastinal structures results in decreased brain perfusion on ultrafast ultrasound, cerebral hypoxia with compensatory angiogenesis, mature neuron and oligodendrocyte loss, and activated microglia. In CDH fetuses, apoptosis was prominent in the subventricular and subgranular zones, areas that are key for neurogenesis. We validated these findings in the autopsy samples of four human fetuses with CDH compared to age- and sex-matched controls. This study reveals the molecular mechanisms and cellular changes that occur in the brain of fetuses with CDH and creates opportunities for therapeutic targets.
Topics: Animals; Hernias, Diaphragmatic, Congenital; Neurons; Oligodendroglia; Rats; Humans; Brain; Female; Stem Cells; Fetus; Disease Models, Animal; Pregnancy; Male
PubMed: 38871804
DOI: 10.1038/s41598-024-64412-x -
Clinical Practice and Cases in... May 2024Visceral arterial aneurysms and pseudoaneurysms are rare but dangerous pathologies, with reported incidence of 0.01-0.2% of the worldwide population, as found on...
INTRODUCTION
Visceral arterial aneurysms and pseudoaneurysms are rare but dangerous pathologies, with reported incidence of 0.01-0.2% of the worldwide population, as found on autopsy. Pancreaticoduodenal artery pathology accounts for approximately 2% of all visceral aneurysms; it is commonly caused by chronic inflammatory processes, such as pancreatitis or adjacent pseudocysts. Morbidity and mortality commonly result from rupture of the aneurysm itself, leading to life-threatening hemorrhage into the peritoneum or gastrointestinal tract.
CASE REPORT
Here we present the case of a 64-year-old male patient with previous history of alcohol use disorder leading to chronic pancreatitis and prior embolization of an inferior pancreaticoduodenal pseudoaneurysm, who presented to the emergency department (ED) with abdominal pain, nausea, and vomiting, and was found to have a large recurrent inferior pancreaticoduodenal pseudoaneurysm with associated obstructive cholangitis and pancreatitis via contrast-enhanced computed tomography (CT) of the abdomen and pelvis. The patient was managed emergently by interventional radiology angiography with embolic coiling and percutaneous biliary catheter placement, and he subsequently underwent biliary duct stenting with gastroenterology. The patient was successfully discharged after a brief hospitalization after resolution of his pancreatitis and associated hyperbilirubinemia.
CONCLUSION
Pancreaticoduodenal artery aneurysms and pseudoaneurysms are rare and dangerous visceral pathologies. Patients can be diagnosed rapidly in the ED with CT imaging and need urgent endovascular management to prevent morbidity and mortality.
PubMed: 38869334
DOI: 10.5811/cpcem.1598 -
Clinical Case Reports Jun 2024Pleomorphic lung cancer is a very rare type of cancer and very few cases have been reported in the literature. We present a case of pleomorphic lung cancer in a patient...
Pleomorphic lung cancer is a very rare type of cancer and very few cases have been reported in the literature. We present a case of pleomorphic lung cancer in a patient with history of IgA nephropathy on hemodialysis.
PubMed: 38868109
DOI: 10.1002/ccr3.9057 -
Europace : European Pacing,... Jun 2024
Topics: Humans; Autopsy; Epilepsy; Adolescent; Death, Sudden, Cardiac; Cause of Death; Sudden Unexpected Death in Epilepsy; Young Adult; Child
PubMed: 38867571
DOI: 10.1093/europace/euae163 -
BMJ Open Jun 2024Stillbirth is a fundamental component of childhood mortality, but its causes are still insufficiently understood. This study aims to explore stillbirth risk factors by...
Stillbirth is a fundamental component of childhood mortality, but its causes are still insufficiently understood. This study aims to explore stillbirth risk factors by using a multidisciplinary approach to stimulate public policies and protocols to prevent stillbirth, improve maternal care and support bereaved families. METHODS AND ANALYSIS: In this case-control study with stillbirths and live births in 14 public hospitals in São Paulo, mothers are interviewed at hospitals after delivery, and hospital records and prenatal care registries are reviewed. Maternal and umbilical cord blood samples and placentas are collected to analyse angiogenesis and infection biomarkers, and the placenta's anatomopathological exam. Air pollutant exposure is estimated through the participant's residence and work addresses. Traditional and non-invasive autopsies by image-guided histopathology are conducted in a subset of stillbirths. Subsample mothers of cases are interviewed at home 2 months after delivery on how they were dealing with grief. Information contained in the official prenatal care registries of cases and controls is being compiled. Hospital managers are interviewed about the care offered to stillbirth mothers. Data analysis will identify the main risk factors for stillbirth, investigate their interrelations, and evaluate health services care and support for bereaved families. We hope this project will contribute to the understanding of stillbirth's risk factors and related health services in Brazil, providing new knowledge about this central public health problem, contributing to the improvement of public policies and prenatal and puerperal care, helping to prevent stillbirths and improve the healthcare and support for bereaved families. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Municipal Health Secretary (process no 16509319.0.3012.5551) and of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (process no 16509319.0.0000.0068). Results will be communicated to the study participants, policy-makers and the scientific community.
Topics: Humans; Stillbirth; Brazil; Case-Control Studies; Female; Pregnancy; Risk Factors; Prenatal Care; Research Design; Risk Assessment; Placenta
PubMed: 38866578
DOI: 10.1136/bmjopen-2023-079261 -
International Journal of Legal Medicine Jun 2024The authors present the case of a 58-year-old man found hanging from a radiator by his shoelaces. The time of death was approximately 6 h before the body was...
The authors present the case of a 58-year-old man found hanging from a radiator by his shoelaces. The time of death was approximately 6 h before the body was discovered. An autopsy was performed approximately 24 h after the body was found, which revealed hemorrhages in the thoracic aorta at the junctions of the posterior intercostal arteries. Before autopsy, a routine whole-body CT scan was performed. Histologic examination of the aorta and the posterior intercostal arteries revealed a fresh hemorrhage into the tunica adventitia of the aorta. To our knowledge, there is no case description of such findings in hanged persons in the literature. Conclusion: Hemorrhages into the tunica adventitia of the junction of the posterior costal arteries may occur in association with suicidal hanging. The significance of these hemorrhages as a sign of vitality may be debated.
PubMed: 38861166
DOI: 10.1007/s00414-024-03261-9 -
Journal of Arthropod-borne Diseases Sep 2023It is possible to identify drugs and poisons present in cadavers by analyzing blowfly larvae and pupae collected during forensic autopsies. The main purpose of this...
BACKGROUND
It is possible to identify drugs and poisons present in cadavers by analyzing blowfly larvae and pupae collected during forensic autopsies. The main purpose of this study was to use larvae and pupae to identify drugs and poisons present in human cadavers.
METHODS
In an investigation, immature fed meat treated with methamphetamine (MA) at various concentrations (45, 90, and 180 ng/mg) were analyzed to detect MA. Acetylation derivatization and liquid-liquid extraction (LLE) were used as sample preparation methods prior to gas chromatography-mass spectrometry (GC-MS) analytical instrumentation to find MA.
RESULTS
According to this study, can be used in toxicological testing to identify MA in a host body. All larval stages, particularly the third stage larva, pupa and empty pupa tested were positive for MA. Larvae in their first instar produced weak peaks. The post-feeding instar following the 45 ng/mg treatment showed the highest MA concentration. For the first time, derivatization using the acetylation approach was used to prepare samples, and successfully, excellent results were obtained.
CONCLUSION
Low quantities of MA can be easily found in immature fly samples using GC-MS. It is important to analyze all samples including human tissues and insect samples, for postmortem drug testing. They can be utilized to find entire MA before they are excreted in excretory samples such as urine. Also, third instar larvae are a great and reliable sample for toxicological study.
PubMed: 38860200
DOI: 10.18502/jad.v17i3.14984 -
Cureus May 2024Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by photosensitivity, rashes on the nose and cheeks, short stature, and a predisposition...
Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by photosensitivity, rashes on the nose and cheeks, short stature, and a predisposition to develop cancers. In this report, we discuss the diagnosis and management of a 34-year-old Canadian male BS patient, originally from Honduras, who developed B-cell lymphoma and a subsequent non-small cell lung carcinoma (NSCLC). Given the radiosensitivity of the patient due to his BS diagnosis and the early stage of the low-grade B-cell lymphoma, we relied on surveillance as the clinical approach to his management. The treatment for NSCLC was initiated in stage III of the disease and was palliative in intent. Chemotherapy (12 rounds of paclitaxel, with the dosage gradually increasing from 48 mg to 58 mg and finally to 72 mg) was employed to shrink the left upper lobe (LUL) lung mass. Subsequently, radiotherapy (3000 cGY in 20 fractions) was administered to improve symptoms further. The radiotherapy dose schedule was modified given the patient's BS diagnosis to avoid excessive toxicity. The palliative treatment course was well tolerated by the patient and resulted in symptom relief. However, his cancer progressed over the course of the treatment, ultimately resulting in his death 18 months after the initial diagnosis of NSCLC; no autopsy was performed. We believe this report will spur clinicians to engage in fruitful discussions about tailoring chemotherapy and radiation therapy regimens for treating cancer in BS patients.
PubMed: 38860091
DOI: 10.7759/cureus.60107