Pathologic and molecular studies of enterovirus 71 infection in a fatal case from a recent epidemic in China: A case report.

RATIONALE: Enterovirus 71 (EV71) is identified as the primary cause of hand, foot, and mouth disease (HFMD) and mainly infects the young infants. Though some fatal cases have been reported, the underlying mechanisms of EV71 infection remain elusive and more further pathologic and molecular studies of EV71 infection are needed. PATIENT CONCERNS: A 26-month-old girl with a history of fever and lethargy for 3 days and intermittent seizures for 2 hours associated with rash on 4 limbs was brought to a hospital. DIAGNOSES: The autopsy was performed to identify the cause of death for a medical dispute. The results of histologic examination, immunohistochemistry (IHC), nested reverse transcription polymerase chain reaction (RT-PCR), and viral isolation confirmed that this patient died of EV71 infection. INTERVENTIONS: The patient was transferred to neonatal intensive care unit and was intubated and mechanically ventilated. The other treatment included cardiopulmonary resuscitation and intravenous injection of adrenaline. OUTCOMES: The patient presented persistent coma and intermittent seizures and suddenly developed respiratory arrest and died 16 hours after admission. LESSONS: Our results suggest that EV71 might invade into the central nervous system (CNS) through peripheral nerves which control the digestive tract in the early stage of infection. In addition, we successfully isolated one EV71 strain. Phylogenetic analysis showed that the isolated strain clustered in the C4a of C4 subgenotype. This case also highlights that rapid deterioration in HFMD cases is still a challenge to physicians and they must pay special attention to the infants with HFMD symptoms, particularly in EV71 epidemic areas for early diagnosis and treatment.

Sudden death in a patient with severe mitral annular calcification and end-stage renal disease during hemodialysis: A case report.

RATIONALE: Mitral annular calcification (MAC) is a chronic, degenerative cardiac condition. Although MAC is often considered as an incidental finding in clinical and forensic practice, sudden death due to severe MAC with end-stage renal disease (ESRD) during hemodialysis is uncommon. In addition, spontaneous subepicardial hematoma due to rupture of the subepicardial vein is very rare. PATIENT CONCERNS: A 65-year-old woman had a history of hypertension, diabetes mellitus, and renal failure. DIAGNOSES: Postmortem examination revealed marked MAC with cardiomegaly and ESRD. Spontaneous subepicardial hematoma due to disruption of subepicardial vein was also seen. INTERVENTIONS AND OUTCOMES: The patient became short of breath while on hemodialysis and expired en route to the hospital. LESSONS: In this case, death was attributed to the effects of the calcified mitral valve annulus. This case highlights that MAC must be considered in any patient with ESRD and fatal cardiovascular events should not be overlooked in these patients.

Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity.

Perfluorodecanoic acid (PFDA) is widely used in production of many daily necessities based on their surface properties and stability. It was assigned as a Persistent Organic Pollutant in 2009 and became a public concern partly because of its potential for activation of the peroxisome proliferator-activated receptor alpha (PPARα). In this study, wild-type and Ppara-null mice were administered PFDA (80 mg/kg). Blood and liver tissues were collected and subjected to systemic toxicological and mechanistic analysis. UPLC-ESI-QTOFMS-based metabolomics was used to explore the contributing components of the serum metabolome that led to variation between wild-type and Pparα-null mice. Bile acid homeostasis was disrupted, and slight hepatocyte injury in wild-type mice accompanied by adaptive regulation of bile acid synthesis and transport was observed. The serum metabolome in wild-type clustered differently from that in Pparα-null, featured by sharp increases in bile acid components. Differential toxicokinetic tendency was supported by regulation of UDP-glucuronosyltransferases dependent on PPARα, but it did not contribute to the hepatotoxic responses. Increase in Il-10 and activation of the JNK pathway indicated inflammation was induced by disruption of bile acid homeostasis in wild-type mice. Inhibition of p-p65 dependent on PPARα activation by PFDA stopped the inflammatory cascade, as indicated by negative response of Il-6, Tnf-α, and STAT3 signaling. These data suggest disruptive and protective role of PPARα in hepatic responses induced by PFDA.

[Effect of triptolide on iNOS and SP expressions in spinal dorsal horn and dorsal root ganglion of rats with adjuvant arthritis].

OBJECTIVE: To observe the analgesic effect of triptolide (TP) of high, middle and low doses on rats with adjuvant arthritis (AA), and the expressions of inducible nitric oxide synthase (iNOS) and substance P (SP) in spinal dorsal horn and dorsal root ganglion (DRG) of corresponding sections, in order to discuss the possible mechanism for the analgesic effect of TP on rats with adjuvant arthritis. METHOD: Fifty SD rats were selected and randomly divided into the normal group (group A), the model group (group B), and TP low (group C), middle (group D), high (group E) dose groups. Except for the group A, all of the remaining groups were injected with 0.1 mL of Freund's complete adjuvant through their right rear toes to establish the model. At 14 d after the model establishment, rats in C, D and E groups were intraperitoneally injected with different doses of TP (0.1 mg x kg(-1) for the group C, 0.2 mg x kg(-1) for the group D, 0.4 mg x kg(-1) for the group E) once a day for 9 days. Then the 50% mechanical withdraw threshold (MWT) was determined. And the expressions of iNOS and SP in lumbar5 (L5) spinal dorsal horn and DRG were detected with the immunohistochemical method. RESULT: The 50% MWT of rats in the group B was significantly lower than that of the group A (P < 0.01). After being treated with TP, the Thermal withdrawal latencies of groups C, D and E were significantly higher than that of the group B (P < 0.01). TP could notably increase the MWT of AA rats, with a certain dose-effect relationship. The immunohistochemical results indicated that the iNOS and SP expressions significantly increased in the group B (P < 0.01), while the positive expression levels of iNOS and SP in groups C, D and E were significantly lower than that of the group B (P < 0.01), with a certain dose-effect relationship. CONCLUSION: TP shows a good analgesic effect on AA, and could inhibit the iNOS and SP expressions in spinal dorsal horn and DRG in rats with adjuvant arthritis, which may be one of action mechanisms for the analgesic effect of TP.

[Effect of Triptolide on expression of NMDAR1 and BSI-B4 binding sites in spinal dorsal horn and dorsal root ganglion in rats with adjuvant arthritis].

OBJECTIVE: To study the analgesic effect of Triptolide(TP) in rats with adjuvant and the possible mechanism. METHODS: Fifty healthy SD rats were randomly divided into normal control group (group A), model group (group B), and low(group C), middle (group D) and high(group E) dose TP treatment groups. Except the group A, each group of rats were reared by toe intradermal injection of 0. 1 mL Freund's complete adjuvant. After 14 days,rats in the C, D and E groups were taken different doses (0. 1 mg/kg group C, 0. 2mg/kg group D, and 0. 4 mg/kg group E) by intraperitoneal injection of TP for 9 days, and then thermal withdrawal latency and the expression of NMDAR1 and BSI-B4 binding sites in lumbar5 (L5) spinal dorsal horn and DRG were detected. RESULTS: Thermal withdrawal latency of rats in group B was significantly lower than that of group A (P <0. 01), while those in group C, D and E were significantly higher than those in group B (P <0. 05 or P <0. 01). TP increased the thermal pain threshold by a quantity-effect relationship; NMDAR-1 and BSI-B4 binding sites expression levels were significantly increased in group B than those in group A (P <0. 01), while those in group C, D and E were lower than those in group B. CONCLUSION: Analgesic effect of TP is related to reducing levels of expression of NMDAR1 and BSI-B4 binding sites in spinal dorsal horn and DRG in rats with adjuvant arthritis.

Sudden unexpected death due to Graves' disease during physical altercation.

We report a case of a 30-year-old woman who suddenly collapsed after having a physical altercation with her husband. Despite immediate resuscitation, she died on arrival at the hospital. The victim's parents requested an autopsy because they believed that their daughter was killed by her husband. Postmortem examination revealed that the victim had a diffusely enlarged thyroid gland and cardiomegaly with left ventricular hypertrophy. There was no evidence of significant trauma on the body. Further postmortem thyroid function tests and review of her medical history indicated that her death was due to Graves' disease. To the best of our knowledge, this is the first case reported of sudden death due to cardiac arrhythmia from Graves' disease induced by physical and emotional stress associated with the criminal activity of another person. The autopsy findings are described. In addition, the literature is reviewed and the significance of postmortem evaluation of thyroid hormones in the cases of sudden death is discussed.

Causes of sudden death in patients with obstructive sleep apnea.

There are few autopsy studies of patients dying suddenly with obstructive sleep apnea (OSA). Twenty-five forensic autopsies of unexpected sudden death in individuals with OSA were reviewed. The causes of death were as follows: cardiomyopathy (n = 11); sudden unexpected death without morphologic findings (SUDNA, n = 6); and other cardiovascular diseases not related to OSA (n = 8). The cardiomyopathy group comprised five hearts with concentric left ventricular hypertrophy without dilatation and six with left ventricular diameter >4 cm (dilated cardiomyopathy). Four of six hearts in the SUDNA group showed right ventricular dilatation compared with seven of 11 showed cardiomyopathy and one of eight miscellaneous. The degree of obesity was greatest in the dilated cardiomyopathy group (10 of 11 obese) followed by the SUDNA group (four of six obese). The cardiac findings in patients dying suddenly and unexpectedly with OSA include nonspecific cardiomyopathy, other cardiac conditions, and hearts without a morphologic cause of death, which show frequent right ventricular dilatation as the only finding.

Triptolide inhibits CC chemokines expressed in rat adjuvant-induced arthritis.

Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F (TWHF), has been proven to have potent immunosuppressive and anti-inflammatory activities. It has been clinically used to treat patients with rheumatoid arthritis (RA), in which chemokines play an important role in immune and inflammatory responses. To investigate the effect of triptolide on MCP-1, MIP-1alpha and RANTES, we used complete Freund's adjuvant to induce adjuvant-induced arthritis (AA) in rats. AA in rat is a useful experimental model of human RA. Our data show that the thickness of arthritic ankle decreases with administration of triptolide. Both mRNA and protein levels of MCP-1, MIP-1alpha and RANTES in synovial tissue of rats with AA are significantly higher than those in normal rats. mRNA levels of MIP-1alpha and RANTES increase in peripheral blood mononuclear cells of rats with AA in comparison with those in normal rats, whereas no MCP-1 mRNA can be detected. Triptolide can significantly inhibit rat AA induced over-expression of MCP-1, MIP-1alpha and RANTES at both mRNA and protein levels in a dose-dependent manner. These results may contribute to the therapeutic effects of triptolide in rheumatoid arthritis.

[Influence of triptolide on neuronal apoptosis in rat with cerebral injury after focal ischemia reperfusion].

OBJECTIVE: To study effect of triptolide (TL) on neuronal apoptosis in cerebral tissue of rat after ischemia-reperfusion. METHOD: Triptolide at dose 0.2 or 0.4 mg x kg(-1) was intraperitoneally injected once a day for 4 d. The focal cerebral ischemia-reperfusion model was established with thread embolism in middle artery before triptolide injection on the fourth day. Neurological deficit score of rats was evaluated; and immunohistochemical techniques were used to count positive cells of express of MPO and TUNEL in cerebraltissue. RESULT: Compared with the control group, the deficit of neural function was significantly improved, and the number of infiltrate of neutrophil and neuronal apoptosis in cerebral tissue was remarkably reduced in two TL-treated groups. CONCLUSION: The results suggested that TL can inhibit infiltration of neutrophil and decrease the degree of neuronal apoptosis in cerebral tissue.