The effects of p-chloromercuriphenylsulfonic acid on Trypanosoma cruzi infection of mammalian host cells in vitro

Treatment of Trypanosoma cruzi blood trypomastigotes with p-chloromercuriphenylsulfonic acid (PCMS) increased the association of the parasite with either mouse resident peritoneal macrophages or rat heart myoblasts in vitro. The effect was evidenced by elevation of both the percentage of host cells with parasites and the number of flagellates per 100 cells. The effect of PCMS appeared to be largely on the process of parasite penetration rather than surface binding as it was seen at 37 degrees C but not at 4 degrees C. A short pretreatment time, 5 min, was sufficient to elicit the enhancement, suggesting that the primary effect of PCMS might be at the parasite's cell surface. The PCMS effect was reversible as the parasite returned to normal levels of association with the host cells in less than 4 h after removal of excess PCMS. That sulfhydryl groups were involved in the PCMS effect was indicated by the abilities of excess cysteine and glutathione to block it. These results suggest a role for free sulfhydryl groups on the parasite surface in the process of host cell invasion.     

Dextran 70 administration after trauma-hemorrhagic shock does not impair cellular immune functions

: Although the effects of the colloid dextran 70 on induction of anaphylactoid reactions or reticulo-endothelial phagocytosis have been examined previously, its effects on specific cell-mediated immunity after trauma-hemorrhage shock remain unknown.

: Nonheparinized C3H/HeN mice underwent a laparotomy, were bled, and then maintained at a blood pressure of 35 mm Hg for 60 minutes. Then they were resuscitated with either 4 × the shed blood volume as lactated Ringer's solution (LRS) or 2 × LRS + 1 × dextran 70. Control mice underwent all operative protocols but were neither hemorrhaged, nor resuscitated. At 2 or 24 hours posthemorrhage, serum, splenocytes (SPL), and peritoneal macrophages (pMø, splenic Mo (sMø) were obtained. Bioassays were used to determine interleukin-2 (IL-2), IL-3, IL-6, and SPL proliferation.

: Trauma-hemorrhage markedly depressed lymphokine release, splenocyte proliferation, and IL-6 release at 2 hours after the insult. The combination of LRS + dextran did not restore lymphocyte functions, but also did not further suppress them. The release of IL-6 by pMø and sMø at 2 and 24 hours after dextran infusion and serum IL-6 remained at the same level as in LRS-treated animals.

: The combination of LRS and colloid dextran 70 does not adversely affect ex vivo cell-mediated immune functions during the first 24 hours after its administration after trauma-hemorrhage. Thus, from the immunological standpoint, dextran is a safe resuscitation adjunct.     

高血压的时间治疗学

1血压变异性的时间生物学 血压(BP)受很多因素影响,外因如:环境温度(湿度)、躯体活动、情感状况(焦虑,愤怒)、摄入酒精或咖啡因、膳食成分及睡眠(觉醒)作息规律等;内因如:种族、性别、自主神经张力、血管活性激素及血液学和肾脏变化因素,很难清楚地区分外因与内因相互作用对BP昼夜变化的影响[1].     

The RUSH2A Study: Dark-Adapted Visual Fields in Patients With Retinal Degeneration Associated With Biallelic Variants in the USH2A Gene

PurposeTo measure visual fields using two-color dark-adapted chromatic perimetry in a subset of participants in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A), a study of USH2A-mediated syndromic (USH2) and autosomal recessive nonsyndromic retinitis pigmentosa, determine percentage retaining rod function, and explore relationships between dark-adapted visual fields (DAVF) and rod function from ERG and full-field stimulus thresholds (FST).MethodsFull-field rod mean sensitivity, number of rod loci, maximum sensitivity, DAVF full-field hill of vision (DAVF V_TOT), and 30° hill of vision (DAVF V₃₀) were measured in one eye for DAVF ancillary study participants (n = 49). Loci where cyan relative to red sensitivity was more than 5 dB on dark-adapted chromatic perimetry were considered rod mediated. Correlation coefficients between the DAVF measures and standard clinical measures were estimated, as were kappa statistics (κ) for agreement between DAVF and other measures of rod function.ResultsOf 49 participants tested with DAVF, 38 (78%) had evidence of rod function, whereas 15 (31%) had measurable rod ERGs. DAVF maximum sensitivity was highly correlated with FST white thresholds (r = −0.80; P < .001). Although not statistically significant, the number of rod loci and DAVF V_TOT were lower in eyes with longer disease duration by 0.82 (95% confidence interval, −1.76, 0.12) loci/year and 0.59 (95% confidence interval, −1.82, 0.64) dB-steradians/year, respectively.ConclusionsRod-mediated function on FST and DAVF is present in many patients with symptomatic USH2A-related retinal degeneration, including some without measurable rod ERGs. RUSH2A longitudinal data will determine how these measures change with disease progression and whether they are useful for longitudinal studies in inherited retinal degenerations.     

Ewing's Sarcoma with Neuroblastoma-like Features

Four tumors with the clinical and light microscopic features of Ewing's sarcoma contained cells that possessed to varying degrees ultrastructural features suggestive of neuroblastoma. These neoplasms were considered to be Ewing's sarcoma of bone by radiologic examination and on clinical grounds, and light microscopy was consistent with the diagnosis in every case. It is suggested that the ultrastructural morphology of Ewing's sarcoma is broader than had been supposed and that the presence of dendritic processes in a small cell tumor of bone should not exclude the diagnosis of Ewing's sarcoma.     

Apoptotic promoters and inhibitors in Alzheimer's disease: Who wins out?

A spectrum of apoptotic mediators are seen in neurons that are vulnerable in Alzheimer's disease (AD), leading many investigators to suggest that neuronal death in AD is mediated by an apoptotic process. Indeed, the environment of the AD brain is awash with proapoptotic mediators including amyloid-beta, oxidative stress, hydroxynonenal oxidants and metabolic alterations with concomitant energy failures. However, the phenotype that defines the terminal events that are pathogonomic of apoptosis, such as chromatin condensation, apoptotic bodies and membrane blebbing, are not seen in AD. Therefore, we speculated that, although AD presents with a proapoptotic environment, apoptosis does not proceed to completion. In this regard, we found that while the initiator phases of apoptosis were engaged, this does not lead to the activation of the terminal commitment phase necessary for apoptotic cell death. In other words, in AD, there is a lack of effective apoptotic signal propagation to distal effectors. This is a novel phenomenon (which we term abortosis) that represents an inhibition of apoptosis at the postinitiator stage in neurons that survive in AD.