Four peptidyl inhibitors of the small-conductance Ca2+-activated K' channels (SK,,) have been isolated from the venom of the Chinese scorpion Buthus martensi. These peptides were identified by screening C,, HPLC fractions of the crude venom by means of mass analysis by matrix-assisted-laser-desorption/ ionization time-of-flight mass spectrometry, and toxicological tests in mice. Edman degradation analysis of the purified peptides showed sequences of 28-31 amino acids including 6 cysteine residues. Three of the sequences were similar to the PO1 peptides from Androctonus scorpions, showing 76% sequence similarity for the most closely related, named BmPO1, and 46% for the other two, named BmP02 and BmP03. Like the PO1 peptides, these molecules showed a low toxic activity in mice after intracerebroventricular injection, and competed (K,,, > 1 pM) with iodinated apamin for binding to its receptor site from rat brain, which has been proved to be the SK,, channels. The fourth toxin was structurally related to the POS/leiurotoxin I toxin family, with 90% similarity, and was named BmPO5. This toxin exhibited a high toxic activity with lethal effects in mice. Due to its small representation in the venom [less than 0.01% (by mass)], its biological properties have been assessed on the synthetic analogue of BmPOS, which was assembled on a solid phase by means of Fmoc methodology. The synthetic peptide was physicochemically identical to the natural peptide, as shown by comparison of their molecular masses and amino acid compositions, and by their coelution after coinjection on capillary electrophoresis. These results confirmed the primary structure of BmPO5 including an amidated C-terminus. Similarly to natural BmPO5, synthetic BmPO5 produced toxic and lethal effects after intracerebroventricular injection in mice (LD,,, = 37 ng), and was able to compete with iodinated apamin for binding to its receptor in rat brain
Three novel toxins belonging to the scorpion K+ channel-inhibitor family were purified to homogeneity from the venom of the Chinese scorpion Buthus martensi. They have been identified according to their molecular mass (3800-4300 Da) and their neurotoxicity in mice and characterized as 37-amino acid peptides. One of them shows 81-87% sequence identity with members of the kaliotoxin group (named BmKTX), whereas the other two, named BmTX1 and BmTX2, show 65-70% identity with toxins of the charybdotoxin group. Their chemical synthesis by the Fmoc methodology allowed us to show that BmKTX, unlike BmTX1 and BmTX2, possesses an amidated C-terminal extremity. Toxicity assays in vivo established that they are lethal neurotoxic agents in mice (LD50s of 40-95 ng per mouse). Those toxins proved to be potent inhibitors of the voltage-gated K+ channels, as they were able to compete with [125I]kaliotoxin for its binding to rat brain synaptosomes (IC50s of 0.05-1 nM) and to block the cloned voltage-gated K+ channel Kv1.3 from rat brain, expressed in Xenopus oocytes (IC50s of 0.6-1.6 nM). BmTX1 and BmTX2 were also shown to compete with [125I]charybdotoxin for its binding to the high-conductance Ca2+-activated K+ channels present on bovine aorta sarcolemmal membranes (IC50s of 0.3-0.6 nM). These new sequences show multipoint mutations when compared to the other related scorpion K+ channel toxins and should prove to be useful probes for studying the diverse family of K+ channels.
Background and Purpose— We aimed to systematically investigate the characteristics of cervicocranial artery dissection (CCAD) on high-resolution magnetic resonance imaging that are associated with acute ischemic stroke. Methods— Patients with CCAD were recruited and divided into stroke and nonstroke groups. The lesion location, the presence of a double lumen, intimal flap, intramural hematoma, pseudoaneurysm, irregular surface, intraluminal thrombus, and other quantitative parameters of each dissected segment were reviewed. Multiple logistic regression was used to examine the association between imaging features of CCAD and ischemic stroke. Results— A total of 145 affected vessels from 118 patients with CCAD were analyzed. Anterior circulation, intramural hematoma, irregular surface, intraluminal thrombus, and severe stenosis (>70%) on high-resolution magnetic resonance imaging were more prevalent in CCAD patient with stroke (54.4% versus 36.4%; P =0.030, 96.2% versus 84.8%; P =0.017, 74.7% versus 37.9%; P <0.001, 44.3% versus 4.5%; P <0.001, and 54.4% versus 31.8%; P =0.008, respectively). In multivariable logistic regression analysis, the presence of irregular surface and intraluminal thrombus on imaging were independently associated with acute ischemic stroke in CCAD with odds ratios of 4.29 (95% CI, 1.61–11.46, P =0.004) and 7.48 (95% CI, 1.64–34.07, P =0.009). Conclusions— The current findings supported that the presence of irregular surface and intraluminal thrombus were related to stroke occurrence in patients with CCAD. High-resolution magnetic resonance imaging might give insights into pathogenesis of ischemic stroke in CCAD. It may be useful for individual prediction of ischemic stroke early in CCAD.
Centella asiatica herbs have been prescribed as a traditional medicine for wound healing in China and Southeast Asia for a long time. They contain many kinds of triterpenoid compounds, mainly including glycosides (asiaticoside and madecassoside) and corresponding aglycones (asiatic acid and madecassic acid). To identify which is the major active constituent, a comprehensive and comparative study of these compounds was performed. In vitro, primary human skin fibroblasts, originating from healthy human foreskin samples, were treated with various concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid, respectively. Cell proliferation, collagen synthesis, MMP-1/TIMP-1 balance, and TGF-β/Smad signaling pathway were investigated. In vivo, mice were orally administered with the four compounds mentioned above for two weeks after burn injury. The speed and quality of wound healing, as well as TGF-β 1 levels in skin tissues, were examined. Interestingly, in contrast to prevalent postulations, asiaticoside and madecassoside themselves, rather than their corresponding metabolites asiatic acid and madecassic acid, are recognized as the main active constituents of C. asiatica herbs responsible for burn wound healing. Furthermore, madecassoside is more effective than asiaticoside (P = 0.0446 for procollagen type III synthesis in vitro, P = 0.0057 for wound healing speed, and P = 0.0491 for wound healing pattern in vivo, correspondingly).
A-to-A embolic infarction has distinct vulnerable plaque characteristics compared with non-A-to-A embolic infarction. HIP and plaque surface irregularity may predict A-to-A embolic infarction.
BackgroundIntracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole‐brain vessel wall imaging, we sought to study the differences in plaque features among various types of plaques in patients with a recent unilateral anterior circulation ischemic stroke.Methods and ResultsSixty‐one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole‐brain vessel wall imaging (before and after contrast) within 1 month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque‐wall contrast ratio, high signal on T1‐weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole‐brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1‐weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9–44.1; P=0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8–164.9; P=0.013), and type 2 (≥50% cross‐sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3–82.2; P=0.030) were independently associated with culprit lesions.ConclusionsHigh signal on T1‐weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification.
Background To investigate the impact of protective measures and isolation on respiratory tract infections in children during the COVID-19 outbreak. Methods We extracted data on outpatient visits and respiratory infection visits, and tests of respiratory viruses (adenovirus (ADV), influenza A (FluA), influenza B (FluB) and respiratory syncytial virus (RSV)) from electronic healthcare records in Children’s Hospital, Zhejiang University School of Medicine during the COVID-19 outbreak (January–April, 2020), compared with those in 2018 and 2019 during the same periods. Results We found that outpatient visits in January, 2020 was comparable with those in 2018 and 2019, but decreased by 59.9% (288,003 vs. 717,983) and 57.4% (288,003 vs. 676,704), respectively during the period of February-April, 2020, as compared with the same periods in 2018 and 2019. The total number of respiratory tract infections from January to April 2020 decreased by 65.7% (119,532 vs.348,762) and 59.0% (119,532 vs.291,557), respectively compared with the same periods in 2018 and 2019. The proportion of respiratory tract infections during the outbreak also dropped compared with the same periods in 2018 and 2019 (P<0.001). We also found significantly decreased number of completed tests for respiratory viruses and positive cases of ADV, FluA, FluB, and RSV during February-April, 2020. Conclusions In this study, we found that outpatient visits and respiratory tract infections in children significantly decreased during COVID-19 outbreak. Adequate protective measures and isolation in children may help to prevent respiratory virus infections in children.
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