Fatal diphenidol poisoning: a case report and a retrospective study of 16 cases.

Diphenidol hydrochloride (DPN), a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. However, its toxic or lethal concentration ranges have not yet been determined. We report a case of a 23-year-old female who suffered from DPN poisoning that resulted in death. At autopsy, there were no typical pathological findings, except for cerebral edema with high acetylcholinesterase expression. Postmortem analysis of DPN revealed 45 µg/ml in heart blood, 39 µg/ml in femoral vein blood, 141 µg/g in the liver, and 53 mg in the gastric contents. These concentrations indicated that the cause of death was DPN poisoning. The circumstances indicated that the manner of death was suicide. We also present a retrospective study, in which we review and summarize the literature from 1998 to 2014 and describe 16 cases of poisoning, including information from autopsy reports and postmortem drug concentrations. In forensic practice, drug residues at the scene, patients with convulsions and disturbance of consciousness, and rapidly occurring deaths, should draw attention to the possibility of this drug. Toxicological analysis and the exclusion of other diseases may ultimately be used to confirm DPN poisoning.

Characterization of protein alterations in damaged axons in the brainstem following traumatic brain injury using fourier transform infrared microspectroscopy: a preliminary study.

Axonal injury contributes greatly to neurological dysfunction following traumatic brain injury (TBI), but current histological diagnostic methods are limited in identifying the pathological profiles of injured axons and unable to provide an objective and accurate quantification. Fourier transform infrared microspectroscopy (FTIRM) has the ability to offer macromolecular bioinformatics of the tissues including biochemical composition and structure by calculating band absorption intensity. In this study, axonal injury in the brainstem of rats with traumatic brain injury at 72 h post-trauma, which was confirmed with beta-amyloid precursor protein (ß-APP) immunostaining, was detected with FTIRM technique. The lower intensity of infrared absorbance under the amide I band corresponds strongly to the area of axonal injury, and further analysis of amide I band shows significant differences in protein conformation between injured and normal axons. The findings indicate that using FTIRM technique, the amide I band has potentials to be a infrared spectral marker of axonal injury.

[Advances in Biomarkers of Mild Traumatic Brain Injury in Cerebrospinal Fluid and Blood].

Mild traumatic brain injury (MTBI) is defined as a mild brain trauma resulting in a short loss of consciousness and alteration of mental status. It may also occasionally develop persistent and progressive symptoms. It has been confirmed that MTBI causes changes of anatomic structures in central nervous system and biomarkers in the body fluid. However, there is no sufficient research on relevance among threshold for the brain injury, individual vulnerability and duration of disturbance of consciousness. Furthermore, there are no reliable diagnostic methods to establish whether a blow to the head is sufficient to cause the brain injury. This review provides references for biomarkers in cerebrospinal fluid and blood associated with TBI. It also provides application status and potential prospects for further assessment and diagnosis of MTBI.

Human fatality due to thallium poisoning: autopsy, microscopy, and mass spectrometry assays.

Thallium has been responsible for many intoxications since its discovery; however, toxicological profiles for thallium in human fatalities have not been updated recently. Autopsy, microscopic investigations, and toxicological analyses were performed on a married couple who died from thallium sulfate intended homicidal poisoning. The distribution of thallium was established by inductively coupled plasma mass spectrometry with hair samples showing the highest thallium concentration. Electron microscopy revealed a dystrophic condition of hair with disorganized cuticle and atrophy of the hair bulb. Thallium interacts with cells at different levels, with prominent ultrastructural injuries in the mitochondria and endoplasmic reticulum, and high concentration of electron dense granules observed in the cytoplasm and mitochondria of several organs. Alopecia, toxic encephalopathy, and peripheral neuropathy were diagnosed in the victims and suggested to be crucial implications for thallium poisoning. The analytical procedures used in this case are of considerable forensic importance in the diagnosis of thallium poisoning.

Fatal delayed cardiac tamponade due to rupture of micropseudoaneurysm of left anterior descending coronary artery following stab to the chest.

Traumatic coronary pseudoaneurysm has been described to be mainly associated to iatrogenic lesion of the coronary arteries. However, chest-stab-wound-related coronary pseudoaneurysm caused by isolated partial incision of a coronary artery giving rise to fatal delayed cardiac tamponade is very rare. We describe an autopsy case in which this potentially fatal complication developed 8 days later after a thoracic stab wound. Unfortunately, the imaging examination failed to detect this defect during hospitalization. Postmortem examination revealed that the posterior wall of the left anterior descending coronary artery was intact but that the anterior wall was incised, forming a micropseudoaneurysm which had ruptured. This case highlights that isolated coronary artery injuries must be considered in any patient with a penetrating wound to the thorax, and coronary pseudoaneurysms should not be missed in these patients.

Polyacrylamide hydrogel pulmonary embolism--A fatal consequence of an illegal cosmetic vaginal tightening procedure: A case report.

Vaginal tightening is a kind of esthetic surgery aimed at enhancing sexual satisfaction during intercourse. Although the injective vaginal tightening procedure is informal, there are already some reports of its application. But pulmonary embolism is a really rare therapeutic complication of this procedure. We report a case of death due to the non-thrombotic pulmonary embolism as a consequence of illegal cosmetic vaginal-tightening procedure using polyacrylamide hydrogel. A 34-year-old woman was hospitalized with paroxysmal abdominal cramps and diarrhea as initial symptoms, while she concealed the genital cosmetic surgery history. Respiratory distress presented only 1.5h before she died. The result of autopsy revealed the cause of death as pulmonary embolism due to the hydrogel which was injected into her vaginal wall. The emboli were confirmed as polyacrylamide hydrogel by Alcian-blue stain and the Fourier transform infrared scanning. It is suggested that pulmonary embolism should not be discarded in the expertise of deaths following cosmetic implant surgeries. It broadens our understanding about death associated with esthetic genital procedures and informs clinicians and medical examiners of the potential death of this type. And detailed investigations of previous medical and surgical history will always play a critical role in the certification of cause of death.

Temporal profiles of axonal injury following impact acceleration traumatic brain injury in rats--a comparative study with diffusion tensor imaging and morphological analysis.

Traumatic axonal injury (TAI) plays a major role in the development of neurological impairments after traumatic brain injury (TBI), but it is commonly difficult to evaluate it precisely and early with conventional histological biomarkers, especially when the patients experience short-term survival after TBI. Diffusion tensor imaging (DTI) has shown some promise in detecting TAI, but longitudinal studies on the compromised white matter with DTI at early time points (≤72 h) following impact acceleration TBI are still absent. In the present study, rats were subjected to the Marmarou model and imaged with DTI at 3, 12, 24, and 72 h (n = 5 each) post-injury. Using a region-of-interest-based approach, the regions of interest including the corpus callosum, bilateral external capsule, internal capsule, and pyramidal tract were studied. Two DTI parameters, fraction anisotropy and axial diffusivity, were significantly reduced from 3 to 72 h in each region after trauma, corresponding to the gradient of axonal damage demonstrated by immunohistochemical staining of ß-amyloid precursor protein and neurofilament light chain. Remarkably, DTI changes predicted the approximate time in the acute phase following TBI. These results indicate that the temporal profiles of diffusion parameters in DTI may be able to provide a tool for early diagnosis of TAI following impact acceleration TBI.

[Magnetic resonance diffusion tensor imaging for diagnosis of pyramidal tract damage in rats].

OBJECTIVE: To explore the applicability of magnetic resonance diffusion tensor imaging (DTI) for diagnosis of pyramidal tract damage in rats. METHODS: Marmarou's model was set up, followed by DTI scanning at 3, 12, 24 and 72 h post trauma to acquire the dispersion parameter of bilateral pyramidal tracts. Moreover, axonal varicosities per square millimeter and the percentage of positive area of axons demonstrated by beta-amyloid precursor protein (beta-APP) immunostaining were obtained, as well as the mean density and sum density of neurofilament (NF) 68 immunostaining. RESULTS: Axial diffusivity (AD), fraction anisotropy (FA) and relative anisotropy (RA) in the pyramidal tract were significantly and continuously reduced and reached to the bottom at 72h post trauma (P < 0.05) in accord with the gradient of axonal damage verified by beta-APP and NF68 immunostaining. Furthermore, the changes of AD, FA and RA showed a significant negative correlation with the beta-APP immunohistochemical results. CONCLUSION: DTI has important value for early diagnosis in pyramidal tract damage.

Sudden death due to cerebral leukemic hemorrhage occurring after acupuncture treatment for gingival bleeding.

A 45-year-old woman who experienced stomalgia and gingival bleeding for several days died unexpectedly after acupuncture treatment. At autopsy, trivial injuries on the liver and the stomach and mild hemoperitoneum due to improper acupuncture were found. Also,acute lymphoblastic leukemia and hyperleukocytosis were diagnosed by postmortem examinations. Intracranial hemorrhage due to undiagnosed acute lymphoblastic leukemia was identified as the cause of death.Moreover, the relationship between therapeutic misadventure and death was also determined. We suggest that undiagnosed leukemia should be considered as a differential diagnosis when sudden death occurs owing to intracranial hemorrhage. If therapeutic misadventure was involved,it is also of great importance to assess the relationship between that and death in forensic expertise.

[Advance in animal models of traumatic brain injury].

Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Animal models of TBI are used to elucidate primary and secondary injury mechanisms and pathophysiological changes and to provide the diagnostic and therapeutical basis for TBI. The choices of animal models depend upon the research objectives. However, various animal models have limitations. The models only can duplicate the pivotal injury mechanisms or a certain important pathophysiological course. The characteristics of human TBI can not fully be reflected by using these models. In the review, animal models of traumatic brain injury are classified as dynamic direct brain injury, indirect dynamic brain injury and combined neuro-traumatic models. Several common models are described for consideration.

Role of reactive oxygen species in triptolide-induced apoptosis of renal tubular cells and renal injury in rats.

This study investigated the role of reactive oxygen species (ROS) in the pathogenesis of triptolide-induced renal injury in vivo. Rats were randomly divided into 4 groups (n=5 in each): triptolide group in which the rats were intraperitoneally injected with triptolide solution at a dose of 1 mg/kg of body weight on day 8; control group in which the rats received a single intraperitoneal injection of 0.9% physiological saline on day 8; vitamin C group in which the rats were pretreated with vitamin C by gavage at a dose of 250 mg/kg of body weight per day for 7 days before the same treatment as the control group on day 8; triptolide+vitamin C group in which the rats were first subjected to an oral administration of vitamin C at a dose of 250 mg/kg of body weight per day for 7 days, and then to the same treatment as the triptolide group on day 8. All the rats were sacrificed on day 10. Blood samples were collected for detection of plasma creatinine (Pcr) and plasma urea nitrogen (PUN) concentrations. Both kidneys were removed. The histological changes were measured by haematoxylin-eosin (HE) staining. The production of ROS was determined by detecting the fluorescent intensity of the oxidation-sensitive probe rhodamine 123 in renal tissue. Renal malondialdehyde (MDA) content was measured to evaluate lipid peroxidation level in renal tissue. TUNEL staining was performed to assess apoptosis of renal tubular cells. Renal expression of apoptosis-related proteins Bcl-2, Bax, Bid, Bad, Fas and FasL, as well as corresponding encoding genes were assessed by Western Blotting and real-time PCR. The results showed that triptolide treatment promoted the generation of a great amount of ROS, up-regulated the expression of Bax, Bid, Bad, Fas and FasL at both protein and mRNA levels, as well as the ratio of Bax to Bcl-2, and caused the apoptosis of renal tubular cells and renal injury. However, pretreatment with an antioxidant, vitamin C, significantly reduced the generation of ROS and effectively inhibited the triptolide-induced apoptosis of renal tubular cells and renal injury. It was concluded that ROS plays a critical role in triptolide-induced apoptosis of renal tubular cells and renal injury. The protective administration of vitamin C may help alleviate triptolide-induced renal injury and nephrotoxicity.

Role of Reactive Oxygen Species in Triptolide-induced Apoptosis of Renal Tubular Cells and Renal Injury in Rats / 华中科技大学学报（医学）（英德文版）

This study investigated the role of reactive oxygen species (ROS) in the pathogenesis of triptolide-induced renal injury in vivo.Rats were randomly divided into 4 groups (n=5 in each):triptolide group in which the rats were intraperitoneally injected with triptolide solution at a dose of 1 mg/kg of body weight on day 8; control group in which the rats received a single intraperitoneal injection of 0.9％ physiological saline on day 8; vitamin C group in which the rats were pretreated with vitamin C by gavage at a dose of 250 mg/kg of body weight per day for 7 days before the same treatment as the control group on day 8; triptolide+vitamin C group in which the rats were first subjected to an oral administration of vitamin C at a dose of 250 mg/kg of body weight per day for 7 days,and then to the same treatment as the triptolide group on day 8.All the rats were sacrificed on day 10.Blood samples were collected for detection of plasma creatinine (Pcr) and plasma urea nitrogen (PUN) concentrations.Both kidneys were removed.The histological changes were measured by haematoxylin-eosin (HE)staining.The production of ROS was determined by detecting the fluorescent intensity of the oxidation-sensitive probe rhodamine 123 in renal tissue.Renal malondialdehyde (MDA) content was measured to evaluate lipid peroxidation level in renal tissue.TUNEL staining was performed to assess apoptosis of renal tubular cells.Renal expression of apoptosis-related proteins Bcl-2,Bax,Bid,Bad,Fas and FasL,as well as corresponding encoding genes were assessed by Western Blotting and real-time PCR.The results showed that triptolide treatment promoted the generation of a great amount of ROS,up-regulated the expression of Bax,Bid,Bad,Fas and FasL at both protein and mRNA levels,as well as the ratio of Bax to Bcl-2,and caused the apoptosis of renal tubular cells and renal injury.However,pretreatment with an antioxidant,vitamin C,significantly reduced the generation of ROS and effectively inhibited the triptolide-induced apoptosis of renal tubular cells and renal injury.It was concluded that ROS plays a critical role in triptolide-induced apoptosis of renal tubular cells and renal injury.The protective administration of vitamin C may help alleviate triptolide-induced renal injury and nephrotoxicity.

[Study on electrical current mark with environmental scanning electron microscopy and energy dispersive X-ray microanalyser].

OBJECTIVE: To provide objective proof on diagnosis of electrical current mark in electrocution, the environmental scanning electron microscopy and energy dispersive X-ray microanalyser (ESEM-EDX) were adopted to study the microscopic morphological characteristics and elemental composition of electrical current mark. METHODS: Morphological characteristics of electrical current marks, the elemental composition and morphology of metal particles were studied with ESEM-EDX. RESULTS: The electroporation and metal melted beads could be found in the electrical current marks and skin around them. The metal melted beads mainly composed of common metal such as iron, copper, aluminum and some uncommon metal including gold, titanium and barium. CONCLUSION: ESEM-EDX can be applied in forensic diagnosis of electrocution.