A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

神经源性声带运动障碍与喉神经电生理

声带运动障碍的病因和临床表现复杂多变，涉及多学科，从病因上分为神经源性和非神经源性。对于神经源性声带运动障碍的诊治，首先通过喉镜等检查明确有无声带运动障碍及严重程度，值得注意的是声带纵向张力变化障碍也属于运动障碍的范畴；然后采用喉肌电图（LEMG）检查进行定性分析，在确诊神经源性损伤后，进一步对神经损伤部位进行定位诊断并查找导致神经损伤的病因；同时根据喉部神经电生理评估结果，判断预后。最后综合上述的评估结果制定相应的治疗策略。     

Nerve ultrasound reference data in children from two to seven years

ObjectiveWe examined selected peripheral and spinal nerves of children aged between two and seven years.MethodHigh resolution ultrasound was performed in 116 children (2–7 years of age) at 19 predefined landmarks of median, ulnar, tibial, fibular, sural and radial nerves, the vagus as well as cervical spinal nerve 5 and 6. Further, side-to-side measuring and grey-scale analysis was done at selected nerve sites.ResultsNerves of children were on average smaller than those of adults. Nerve growth correlates significantly with age in all nerves, the mean values were similar in the age of two to four years and five to seven years. Body mass index (BMI) and gender showed moderate effect at some nerve sites, however not uniformly in all. A side-to-side difference of up to 30% in median, and up to 20% in tibial nerve can occur in healthy individuals. Grey-scale analysis for echointensity has been performed in median, ulnar and tibial nerves.ConclusionNerve size increases with age, BMI and gender have moderate effect. A side-to-side-difference of up to 30% can exist.SignificanceReference values of nerve cross-sectional area, side-to-side-difference and echo intensity are necessary to detect nerve pathology in children as well as in adults.     

Non-viral transfer of BDNF and uPA stimulates peripheral nerve regeneration

Peripheral nerves connect brain and spinal cord with the extremities and inner organs, and nerves injury can lead the disability and social exclusion. Growth factors and other natural stimulators of regeneration processes look very promising as future medicines. In our study, we tested the influence of genetic constructions that contain genes of brain-derived neurotrophic factor and urokinase plasminogen activator on nerve's structure and function after traumatic and ischemic injuries. Injection of pVax1-hBDNF and pVax1-muPA after traumatic injury led to better restoration of nerve's structure and function compared to similar parameters of control group mice. In ischemic injury model pVax1-hBDNF and pVax1-muPA slowed and reduced the damage progression and stimulated nerve regeneration as well. However, the treatment with pVax1-muPA was less effective after the traumatic injury. As we chose a non-viral method of gene delivery during our study the optimal conditions of plasmid intramuscular delivery were also determined.     

Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons

BackgroundProstatic radiation therapy (RT) often causes erectile dysfunction (ED) and the mechanisms governing RT-induced ED are unclear with a lack of therapeutic strategies.AimTo determine the effects of ex vivo RT on major pelvic ganglion (MPG) neuron survival, and neurite growth in whole vs dissociated culture.MethodsMPGs were removed and irradiated (0 or 8 Gy) from male Sprague Dawley rats. For dissociated culture, MPG neurons were digested in collagenase/dispase and cultured on coverslips. Immunofluorescent staining for beta-tubulin III (TUBB3; neuron marker), neuronal nitric oxide synthase (nNOS; nitrergic marker), tyrosine hydroxylase (TH; sympathetic marker), and terminal deoxynucleotidyl transferase dUTP nick end labeling assessed neurite length, branching, autonomic neuron density, and apoptosis. For whole organ culture, MPGs were grown in Matrigel. Gene expression of apoptotic markers (caspase 1, 3), TUBB3, nNOS, TH, and Schwann cells (Sox10, Krox20, glial fibrillary acid protein) was measured in whole organ cultured MPGs by quantitative polymerase chain reaction.OutcomesAfter 72 hours, neurite length, branching, autonomic neuron density, and apoptosis were assessed, and gene expression was measured.ResultsRT increased apoptosis in dissociated neurons measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (P < .001) and whole MPG culture via upregulation of caspase 3 gene expression (P < .05). Nitrergic neurons were markedly decreased in irradiated dissociated culture (P < .05), while nNOS gene expression was upregulated in irradiated whole organ culture (P < .05). The proportion of dissociated sympathetic neurons and whole organ TH gene expression remained unchanged after RT. Interestingly, RT dissociated neurites were 22% shorter than controls, while RT whole organ neurites were 15% longer than controls (P < .01). MPG Schwann cells markers (Sox10, Krox20) were elevated after RT in whole organ culture.Clinical TranslationProstatic RT leads to increased neuronal cell death and less erectogenic nitrergic neurons contributing to ED.Strengths & LimitationsThe advantages of dissociated neuron culture include distinct neurites which are easily measured for apoptosis, length/branching, and specific neuron types. In contrast, whole MPG culture is advantageous as it contains all the supporting cells present in vivo.ConclusionThe 2 different culture methods demonstrated opposing neurite growth after RT indicating the importance of supporting cell network to promote pelvic neuron neuritogenesis and survival following RT.Randolph JT, Pak ES, Koontz BF, et al. Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons. J Sex Med 2020;17:1423–1433.     

皮肤瘙痒神经传导介质的研究进展

瘙痒是皮肤科的一种常见症状,是多因素相互作用的结果,其发生受到中枢和外周机制的双重调控,但具体发生机制尚不十分清楚。近年来随着研究的不断深入,多种物质如组胺、乙酰胆碱、5-羟色胺、蛋白酶和蛋白酶相关受体、细胞因子、阿片样肽等介质在瘙痒产生过程中起重要作用,这些介质通过刺激C类神经纤维或直接与皮肤感觉神经纤维受体相结合来介导瘙痒。本文就将皮肤瘙痒的神经传导及传导介质作一综述。     

Arterial stiffness in women previously with preeclampsia from a semi-rural region of South Africa

Women with pre-eclampsia have an increased risk of cardiovascular disease later in life. The aim of the study was to establish the presence and pattern of arterial stiffness in women previously with pre-eclampsia from a semi-rural region of South Africa. This was a prospective longitudinal study which involved 36 previously pre-eclamptic women and 86 non-pregnant controls (NPC) who had a past history of non-complicated pregnancy. Maternal wave reflection (augmentation index) and carotid-femoral pulse wave velocity were assessed noninvasively, using applanation tonometry with the SphygmoCor device. Endothelial function was assessed by EndoPAT 2000 device; pneumatic probes were fitted to the index fingers; induced flow-mediated reactive hyperemia; the ratio of the readings before and after occlusion was then used to calculate the score, the reactive hyperemia index (RHI) as a measure of endothelial function.

Pulse wave velocity remained significantly higher in previously pre-eclamptic women than non-pregnant controls up to three months after delivery (p < 0.05), then it reduced to nonsignificant values. All blood pressure indices (central and brachial pressures), were higher in previously pre-eclamptic women as compared to nonpregnant controls up to one year postpartum.

Regional (aortic) arterial stiffness, though it persists for some time after delivery, is transitory in previously pre-eclamptic women from the rural Africa setting. However, their increase blood pressure is an indication of compromised arterial compliance in women previously with pre-eclampsia.