Scutellaria baicalensis: a promising natural source of antiviral compounds for the treatment of viral diseases / 中国天然药物

Viruses, the smallest microorganisms, continue to present an escalating threat to human health, being the leading cause of mortality worldwide. Over the decades, although significant progress has been made in the development of therapies and vaccines against viral diseases, the need for effective antiviral interventions remains urgent. This urgency stems from the lack of effective vaccines, the severe side effects associated with current drugs, and the emergence of drug-resistant viral strains. Natural plants, particularly traditionally-used herbs, are often considered an excellent source of medicinal drugs with potent antiviral efficacy, as well as a substantial safety profile. Scutellaria baicalensis, a traditional Chinese medicine, has garnered considerable attention due to its extensive investigation across diverse therapeutic areas and its demonstrated efficacy in both preclinical and clinical trials. In this review, we mainly focused on the potential antiviral activities of ingredients in Scutellaria baicalensis, shedding light on their underlying mechanisms of action and therapeutic applications in the treatment of viral infections.

Qingre Xiaoyanning inhibits emotional stress-induced reactivation of latent herpes simplex virus type 1 in mice / 药学学报

In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.

Apoptosis of small cell lung cancer cells H1688 and H446 induced by nitidine chloride through PI3K/Akt/Bcl-2/caspase-3/PARP pathway / 中国药理学通报

Aim To explore the apoptosis of small eell lung eancer ( SCLC ) eells HI688 and H446 induced by nitidine chloride and its possible mechanism.Methods The effect of nitidine chloride or cisplatin ( DDP ) on the activity of SCLC cells was detected by j J MTT method; the morphological changes of cells trea¬ted with nitidine chloride or DDP were observed by in- verted fluorescence microscope and HE staining; the effect of nitidine chloride or DDP on apoptosis was de¬tected by flow cytometry; the effect of apoptosis inhibi¬tor Z-VAD-FMK on apoptosis induced by nitidine chlo¬ride or DDP was detected by MTT method.The expres¬sions of Bax , Bcl-2, caspase-3 , PARP, p-PI3K and p- Akt in the cells treated with nitidine chloride or DDP were detected by Western blot.Results MTT results showed that the viability of SCLC cells was significantly reduced after 48 hours of treatment with nitidine chlo¬ ride; compared with DDP, nitidine chloride could in¬hibit SCLC cells with less IC50; inverted fluorescence microscope and HE staining showed that nitidine chlo¬ride could induce apoptosis in SCLC cells, similar to DDP; flow cytometry showed that nitidine chloride J J could induce apoptosis in SCLC cells.The results of MTT assay showed that the inhibitory effect of nitidine chloride on apoptosis of SCLC cells could be partially antagonized by apoptosis inhibitor Z-VAD-FMK.West¬ern blot results showed that, similar to DDP, nitidine chloride could inhibit the expression of PI3K and Akt, increase Bax, inhibit Be 1-2, and promote the cleavage of caspase-3 and PAH P.Conclusion Nitidine chlo¬ride can induce apoptosis of SCLC cells by inhibiting the activation of P13K and Akt.

Qingre Xiaoyanning Capsules alleviate HSV-1 susceptibility induced by emotional stress / 中国中药杂志

In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.

Identification of Key mRNAs and lncRNAs in Neonatal Sepsis by Gene Expression Profiling.

Neonatal sepsis is one of the most prevalent causes of death of the neonates. However, the mechanisms underlying neonatal sepsis remained unclear. The present study identified a total of 1128 upregulated mRNAs and 1008 downregulated mRNAs, 28 upregulated lncRNAs, and 61 downregulated lncRNAs in neonatal sepsis. Then, we constructed PPI networks to identify key regulators in neonatal sepsis, including ITGAM, ITGAX, TLR4, ITGB2, SRC, ELANE, RPLP0, RPS28, RPL26, and RPL27. lncRNA coexpression analysis showed HS.294603, LOC391811, C12ORF47, LOC729021, HS.546375, HNRPA1L-2, LOC158345, and HS.495041 played important roles in the progression of neonatal sepsis. Bioinformatics analysis showed DEGs were involved in the regulation cellular extravasation, acute inflammatory response, macrophage activation of NF-kappa B signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, and ribosome, RNA transport, and spliceosome. lncRNAs were involved in regulating ribosome, T cell receptor signaling pathway, RNA degradation, insulin resistance, ribosome biogenesis in eukaryotes, and hematopoietic cell lineage. We thought this study provided useful information for identifying novel therapeutic markers for neonatal sepsis.

Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1ß and IL-18 in the Septic Response.

Pyroptosis, an inflammatory form of programmed cell death, is the initiating event of sepsis and results in immune imbalance by releasing IL-1ß and IL-18 in the early stages. Studies show that enhancing autophagy via genetic manipulation can inhibit pyroptosis and prolong the survival of a sepsis animal model, indicating a possible therapeutic strategy against sepsis. However, almost no study so far has achieved pyroptosis inhibition via pharmacological autophagy induction in a sepsis disease model. To this end, we established an in vitro sepsis model by stimulating primary human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and analyzed the effect of the autophagy agonist rapamycin (RAPA) on pyroptosis. Phorbol 12-myristate 13-acetate- (PMA-) activated human THP-1 cells were used as the positive control. LPS significantly increased the levels of the pyroptotic protein Gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase 1 (caspase-1), secreted LDH, IL-1ß, and IL-18. RAPA treatment downregulated the above factors and enhanced autophagy in the LPS-stimulated HUVECs and THP-1 cells. This study shows that RAPA abrogates LPS-mediated increase in IL-1ß and IL-18 by inhibiting pyroptosis and enhancing autophagy.

Disturbed Yin-Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1

Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, is able to establish a lifelong latent infection in the human host. Following primary replication in mucosal epithelial cells, the virus can enter sensory neurons innervating peripheral tissues nerve termini. The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny, and thus latency is established in the cell. Yin-Yang balance is an essential concept in traditional Chinese medicine (TCM) theory. Yin represents stable and inhibitory factors, and Yang represents the active and aggressive factors. When the organism is exposed to stress, especially psychological stress caused by emotional stimulation, the Yin-Yang balance is disturbed and the virus can re-engage in productive replication, resulting in recurrent diseases. Therefore, a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1. Here we reviewed the recent advances in the studies of HSV-1 susceptibility, latency and reactivation. We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.

Inhibitory effects of baicalein against herpes simplex virus type 1

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain)

Umbilical Cord Blood Mesenchymal Stem Cells Enhance Lipopolysaccharide-Induced IL-10 and IL-37 Production in THP-1 Cells.

Umbilical cord blood mesenchymal stem cells (UCB-MSCs) have been shown to be a source of stem cells for use in cellular therapies and have immunomodulatory effects on several immune cells in an inflammatory environment. However, whether UCB-MSCs have immunomodulatory effects against lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in macrophages and whether it is involved in phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway remain unclear. After co-culture of UCB-MSCs and phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 cells using a transwell system, it showed that LPS significantly induced increases in the expression levels of interleukin 10 (IL-10), interleukin 37 (IL-37), phospho-PI3K (p-PI3K), and phospho-Akt (p-Akt) in macrophages. UCB-MSCs upregulated the expression of IL-10, IL-37, p-PI3K, and p-Akt, while it had no obvious effect on PI3K and Akt levels. Inhibitors of PI3K (LY294002) significantly suppressed the expression of IL-10, IL-37, p-PI3K, and p-Akt; however, it had no effect on the expression levels of PI3K and Akt. The present study demonstrated that UCB-MSCs increased the LPS-stimulated expression of IL-10 and IL-37 in macrophages through the PI3K/Akt signaling pathway.

Unexpected custodial death due to acute epiglottitis: A rare autopsy case report.

RATIONALE: Acute epiglottitis is a potentially life-threaten disease, which makes it more challenging to save the life for doctors. Unexpected deaths in custody are a primary cause of concern for the forensic community and doctor worldwide. PATIENT CONCERNS: We present a case of a 44-year-old male detainee who was clinically suspected of dying of acute epiglottitis. The man experienced failure of resuscitation and died after admitted to a hospital. DIAGNOSES: The autopsy, toxicological testing, the test of immunoglobulin E and bacterial culture suggested the patient died of acute epiglottitis. INTERVENTIONS: The bacterial culture was performed to imprecisely identify the cause of death. OUTCOMES: The bacterial culture of the patient's heart blood and nasal and throat swabs showed the presence of the pathogenic microorganism Haemophilus influenza type B. LESSONS: We aim to provide a reference to the medical and forensic community and remind the local law enforcement agencies on the problems present within the correctional healthcare system through this case report. Additionally, we also aim to increase the current knowledge and understanding on custodial deaths caused by natural diseases.

The latent infection of HSV-1 and stress-induced reactivation / 中国药理学通报

Herpes simplex virus type Ⅰ(HSV-1) is a common pathogen, and human is the only natural host of it.Following a period of lytic replication in epithelial cells, HSV-1 enters axon terminals of sensory neurons and then travels via retrograde transport to the sensory ganglia where latency can be established.Upon the stimulation of some stressors, the latent virus can reactivate, leading to recurrent diseases.Therefore, to clarify the mechanism of HSV-1 latent infection and stress-induced reactivation will offer new insights into the prevention, treatment and control of HSV-1 infection.In this review, we describes the mechanisms underlying HSV-1 latent infection and stress-induced reactivation.

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.

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.

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.

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.

Fatal extensive bone cement embolism: histological findings confirmed by Fourier transform infrared spectroscopy.

We herein report the first case of fatal extensive bone cement embolism appearing in pulmonary arterioles following surgical vertebral screw augmentation, which histological evidence of bone cement emboli was confirmed by Fourier transform infrared spectroscopy. A 47-year-old woman has accepted multilevel spine fusion and pedicle screw augmentation with totally 4 ml bone cement infusion. She suddenly developed low blood pressure, dyspnoea, and unconsciousness approximately 1 h post anaesthetic recovery, and then she was dead. It was shown both lungs were edematous in autopsy, and bluish emboli were appeared in extensive pulmonary arterioles in H&E stained sections. Negative information was shown in Molybdenum target X-ray imaging, but the emboli were confirmed to be PMMA bone cement by Fourier transform infrared spectroscopy. The present case indicated it might be effective to confirm the dubious trace component in histology by FTIR.

Roles of 3,4-methylenedioxymethamphetamine (MDMA)-induced alteration of connexin43 and intracellular Ca(2+) 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.

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.

Sudden unexpected death in epilepsy: Evaluation of forensic autopsy cases.

Epilepsy is a common chronic neurological disorder characterized by seizures. Mortality is significantly increased in patients with epilepsy. Sudden unexpected death in epilepsy (SUDEP) is the most common seizure-related category of death. A retrospective study of forensic autopsy cases from 2007 to 2009 at the Office of the Chief Medical Examiner (OCME) yielded a total of 104 sudden unexpected deaths directly or indirectly caused by an epilepsy/seizure disorder in the State of Maryland. Of these deaths, 74 cases met a general accepted definition of SUDEP. The age of SUDEP individuals ranged from 14 to 63 with the majority of subjects in the ages between 21 and 50 years (58 cases, 78.4%). Males were slightly more likely than females to die of SUDEP (male:female=1.5:1 based on the rate). The onset age of epilepsy was documented in 47.3% of cases (35/74) based on investigation and medical records. Of the 35 cases, 12 subjects had early onset epilepsy (onset ages 1-15 years) and 20 subjects had duration of epilepsy for more than 10 years. The majority of deaths (61 of the 74 cases, 82.4%) were unwitnessed. Death scene investigation showed that 71 deaths (95.9%) occurred inside their residence with 50 subjects (70.4%) found either in bed or on the bedroom floor near the bed. Forty-three out of 74 cases (58.1%) showed neuropathological lesions. Per history, 50 subjects were reported as being on anti-epileptic drugs (AEDs). However, postmortem toxicological analysis revealed that only 26 subjects (35.1%) had detectable AEDs. Of the 74 cases, seizure disorder or epilepsy was listed as primary cause of death in 66 cases and the term of SUDEP as official cause of death in only 8 cases. This report focuses on the characteristics of death scene investigation and postmortem examination findings of SUDEP cases.

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.