Luo Zhuo

Involvement of oxidative stress in the mechanism of triptolide-induced acute nephrotoxicity in rats

Triptolide is one of the most widely used and one of the most potent Chinese traditional herbal medicines. However, side effects, especially nephrotoxicity, limit the use of triptolide. It has been reported that oxidative stress is involved in drug-induced nephrotoxicity. In the present study, we focused on observing triptolide-induced acute nephrotoxicity in rats and investigating whether or not oxidative stress is involved in the pathogenesis of this process. The results showed that a single large dose peritoneal injection of triptolide caused severe oxidative stress characterized by significant decreases of renal SOD and GSH-Px activities, as well as significant increase of renal MDA content and also led to severe impairment of renal structure and function characterized by injury of renal tubules observed in HE-stained and TUNEL-stained slides and increases of Cre and BUN concentrations in a short time. However, pretreatment with the antioxidant vitamin C significantly ameliorated triptolide-induced depletion in renal SOD and GSH-Px activities, caused marked normalization of renal MDA content and also blunt the impairment of renal tubules and renal function. These results suggest that triptolide induces oxidative stress via impairing the antioxidant system, and oxidative stress contributes, at least in part, to the mechanism of triptolide-induced acute nephrotoxicity.

Poisoning deaths in China: Type and prevalence detected at the Tongji Forensic Medical Center in Hubei

The records of 218 poisoning deaths from a Department of Forensic Medicine in a University of China, Tongji Center for Medicolegal Expertise in Hubei (TCMEH), from 1999 to 2008 were retrospectively reviewed. The majority (69.7%) of fatalities was between the ages of 20 and 49 years, and there was a male preponderance (male:female=1.7:1). The most common classes of substances involved in fatalities were rodenticide (19.7%), insecticide and herbicide (17.9%), carbon monoxide (16.5%), drugs (13.8%) and alcohols (12.4%). Ingestion was the predominant route of exposure (65.1%), followed in frequency by inhalation, injection and dermal. In vast majority (64.7%), the manner of death was accidental; suicidal intent was present in 25.2% of cases, homicide in 3.7%, and undetermined 6.4%. When compared to the former reports from the same institution, one for 1956-1984 and another for 1983-1999, an increase was found in the proportion of deaths due to rodenticides, CO, alcohols and drugs, as well as in accidental poisoning deaths. Poisoning deaths due to pesticides remain the major public health problem in China. Further regulatory enforcement should be carried out by government to restrict and manage the use of pesticides and rodenticides which are most toxic to humans.

Interpolation function estimates post mortem interval under ambient temperature correlating with blood ATP level.

OBJECTIVE We developed a mathematical model using interpolation function, to characterize the correlation between blood ATP levels in the right ventricle of rabbit and post mortem interval (PMI) at different ambient temperatures. METHODS Forty-eight healthy rabbits were randomly divided into 6 groups of 8 each. The sacrificed rabbits were maintained in calorstats at 10°C, 15°C, 20°C, 25°C, 30°C and 35°C, respectively. Blood from the right ventricle was sampled every 4h until 72h after death. At different time points, ATP concentrations in the blood samples were measured using an ATP fluorescence rapid detector, and then displayed on the detector screen in the form of relative light units (RLU). Relationship between PMI and ATP degradation levels was investigated statistically by SPSS 17.0 and MATLAB 10.0 software. RESULTS We obtained six regression equations (Ra(2)=0.887-0.929) with RLU values at PMIs of 72h (10°C), 60h (15°C), 56h (20°C), 52h (25°C), 40h (30°C) and 32h (35°C), and an interpolation function (Ra(2)=0.930) was established with PMI as the dependent variable (z), RLU value as independent variable (x) and temperature as independent variable (y). CONCLUSION Interpolation function is an appropriate choice for PMI estimation by weakening influence of ambient temperature.

Role of neuropeptide Y and peroxisome proliferator-activated receptor γ coactivator-1α in stress cardiomyopathy.

Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage electric foot shock for about 1 h at 10 s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress cardiomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.SummaryDeath following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage electric foot shock for about 1 h at 10 s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress cardiomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.

Lessons learned from poisoning cases caused by 2 illegal rodenticides: Tetramine and fluoroacetamide.

Background: Tetramine (tetramethylene disulphotetramine, TETS) and fluoroacetamide (FAA) are known as illegal rodenticides with high toxicity to animal species and human beings, which could lead to severe clinical features, including reduction of consciousness, convulsions, coma, and even death. Methods and Results: We presented 2 cases that involved rodenticides poisoning. Even though the patients showed severe manifestations, they were initially misdiagnosed, resulting in 2 persons finally died from TETS and FAA poisoning in homicide cases. Conclusion: From the clinical and forensic experience of these 2 cases, we suggest that physicians should consider TETS and FAA poisoning when patients present generalized seizures, especially in some cases without clear cause and diagnosis of disease. Early diagnosis and treatment are essential for positive management and criminal investigation in intentional poisoning cases. Moreover, clinical toxicology education should be reinforced.

Sudden death in custody due to pituitary apoplexy during long restriction in a sitting position: A case report and review of the literature

Pituitary apoplexy is an uncommon clinical emergency arising from hemorrhage into or infarction of a pituitary adenoma. The most common presentation is sudden headache, visual field defects and signs of hypopituitarism. It usually occurs in the age group from 20 to 50 years and affects more male than female. Sudden death due to pituitary apoplexy without common symptoms is rarely reported. Here, we described a scarcely-reported case of sudden death in custody caused by pituitary apoplexy resulting from stress-induced hemorrhage of gonadotroph adenoma, a kind of pituitary adenoma, without common clinical symptoms. In this case, a 49-year-old man was restrained in a sitting position for 4 days and died unexpectedly. At autopsy, external examination showed free of trauma. Destruction of bony structure and a circumscribed pituitary tumor were observed in sella turcica. Immunohistochemically, the tumor cells were particular positive for follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thus clarifying the presence of a pituitary gonadotroph adenoma. We provide the case description and a short review of pituitary apoplexy and pituitary adenoma as a rare cause of sudden death.

Roles of 3,4-methylenedioxymethamphetamine (MDMA)-induced alteration of connexin43 and intracellular Ca2+ oscillation in its cardiotoxicity

UNLABELLED Although it is well known that 3,4-methylenedioxymethamphetamine (MDMA) can cause various cardiovascular abnormalities and even sudden death from cardiac arrhythmia, whether it has any effect on myocardial gap junctions, which might be one of the targets mediating MDMA-induced cardiotoxicity, remains unclear. OBJECTIVE To test the hypothesis that MDMA may affect the myocardial gap junction protein connexin43 (Cx43) and induce cardiac dysrhythmia. METHOD (1) In vivo study: adult rats were treated with a single dose MDMA administration (20mg/kg, i.p.). Electrocardiogram detection and immunohistochemical analysis were performed to evaluate cardiac function and expression of Cx43, respectively; (2) in vitro study: cultured ventricular myocytes of neonatal rats were treated with MDMA (10, 100, 1000μmol/L) for 1h. Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to investigate the total Cx43 mRNA expression. Immunofluorescent analysis was used to evaluate the amount of junctional Cx43. The phosphorylation status of Cx43 at site Ser368 and intracellular Ca(2+) oscillation were also studied. RESULTS Obvious changes in electrocardiographic patterns were found in rats following MDMA administration. They were characterized by prolonged QRS duration associated with increased amplitude of QRS complex. The heart rates in treated rats were significantly decreased compared to the rats in the control group. The immunohistochemical findings revealed a significant decrease in Cx43 expression. The in vitro study also showed a marked decline in total Cx43 protein associated with reduction of Cx43 mRNA, whereas the phosphorylated Cx43 at Ser368 was increased. Decrease of junctional Cx43 was found correlated with reduction in N-cadherin induced by high concentration of MDMA. Additionally, confocal microscopy findings revealed alteration of intracellular calcium oscillation patterns characterized by high frequency and increasing influx Ca(2+). CONCLUSIONS MDMA reduces expression of cardiac gap junction protein Cx43. The increase of phosphorylation status of Cx43 at Ser368 induced by MDMA is attributed, at least in part, to the Ca(2+)-dependent regulation of protein kinase C (PKC) activity. Our findings provide first evidence of MDMA-mediated changes in those cardiac gap junctions that may underlie MDMA-induced cardiac arrhythmia.

Death from bilateral pulmonary congenital cystic adenomatoid malformation: a rare case report.

Congenital cystic adenomatoid malformation is one of rare pulmonary hypoplastic diseases. It has been subdivided into 3 types (I-III). Respiratory distress and hydrops are usually diagnosed pre- or postnatally by ultrasonography or radiography. The pathogenesis of CCAM has not been clarified yet. Here, we present an unusual case of bilateral CCAM (type III) of a 2-month-old infant who died suddenly. Concomitant lung malformation and fatty degeneration in hepatic cells make this case unique since such malformation is seldom found in type III CCAM.

Child homicide or natural death? A case report of unexpected death of unusual asymptomatic acute laryngotracheobronchitis

Cases involving the unexpected deaths of children are always a concern for the police and medical examiners alike. In particular, unexpected deaths due to asphyxia without obvious injuries sometimes make decisions regarding the manner of death more difficult. In the present case, a 2-year-old boy was found dead at home, and his mother was initially believed to have killed him. A complete autopsy and forensic investigation were performed, and no injuries were found on the body; however, marked laryngeal edema was observed. Histology showed extensive inflammatory infiltration of the mucosa and submucosa of the larynx, trachea, and bronchi. The cause of death was given as respiratory failure due to acute laryngotracheobronchitis; thus, the manner of death was natural. This case helps to remind the forensic community to keep an open mind and consider a broad differential diagnosis when approaching a case rather than jumping to a conclusion based solely on a preliminary investigation.