The Microvascular Architecture of the Vestibule and the Endolymphatic Duct and Sac of the Rat in Vascular Corrosion Casts

The blood vessels of the vestibule and the endolymphatic duct and sac (ES) of the rat were reproduced with methacrylate casting medium and observed under a scanning electron microscope. Dense capillary networks of the macula utriculi and the macula sacculi were observed. The collecting venules from the vestibule emptied into the vein of the vestibular aqueduct (VVAQ). The plexus of the vessels in the ES was triangular in shape and had anastomoses with vessels of the bone and dura and drained into the VVAQ. The posterior meningeal artery (PMA) gave off two branches to the ES. These findings supported the similarity of the vascularization of the vestibule and the ES between the human and the rat

Simplified Analysis of Toxic Gaseous Substance in Forensic Practice: Experiences from Japan

Toxicological examination in forensic practice is important for the proper diagnosis of acute poisoning. We have discussed the properties and features of poisoning incidents due to gaseous substances and elaborated on the simplified analytical techniques and apparatus used for their identification and quantitation for forensic purposes. Briefly, we have explained the simplified analysis of toxic gaseous substances such as carbon monoxide, hydrogen cyanide, hydrogen sulfide, and helium in blood. The techniques used include color testing, gas chromatography, detector tube, oximeter, and spectrophotometric method. In doing so, we have shared our experiences and highlighted the fact that the analysis of gaseous substances can be performed using readily available laboratory tools and equipment. We have emphasized the need and usefulness of the reference data tables for guiding forensic diagnosis. We hope that the above overview will assist other colleagues to implement such simplified techniques for the advancement of forensic medicine practice

Application of CO-oximeter for Forensic Samples

CO-oximeter is routinely used in clinical practice, and it has been applied in the field of forensic medicine. It is a simultaneous and nondestructive technique for the analysis of total hemoglobin (Hb) and various Hb species, such as oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, and methemoglobin. It automatically measures the proportion of each species of Hb and oxygen contents. This is an easy, rapid, and convenient way as the laboratory test. Since there are many advantages such as no necessity of sample preparation, easy handling, and portability, it may provide valuable information for forensic diagnosis. In the present paper, we discuss about the diagnostic application of CO-oximeter in the field of forensic medicine

Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms

Impairment of peripheral neurons by anti-cancer agents, including taxanes and platinum derivatives, has been considered to be a major cause of chemotherapy-induced peripheral neuropathy (CIPN), however, the precise underlying mechanisms are not fully understood. Here, we examined the direct effects of anti-cancer agents on Schwann cells. Exposure of primary cultured rat Schwann cells to paclitaxel (0.01 μM), cisplatin (1 μM), or oxaliplatin (3 μM) for 48 h induced cytotoxicity and reduced myelin basic protein expression at concentrations lower than those required to induce neurotoxicity in cultured rat dorsal root ganglion (DRG) neurons. Similarly, these anti-cancer drugs disrupted myelin formation in Schwann cell/DRG neuron co-cultures without affecting nerve axons. Cisplatin and oxaliplatin, but not paclitaxel, caused mitochondrial dysfunction in cultured Schwann cells. By contrast, paclitaxel led to dedifferentiation of Schwann cells into an immature state, characterized by increased expression of p75 and galectin-3. Consistent with in vitro findings, repeated injection of paclitaxel increased expression of p75 and galectin-3 in Schwann cells within the mouse sciatic nerve. These results suggest that taxanes and platinum derivatives impair Schwan cells by inducing dedifferentiation and mitochondrial dysfunction, respectively, which may be important in the development of CIPN in conjunction with their direct impairment in peripheral neurons

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target