Structure determination of the 2:1 derivatives of copper(I) bromide and iodide with bis(diphenylphosphino)methane. A simple structural scheme for the formation of (CuX)nLm species

The structures of the complexes (CuX)₂DPM (X = Br, I; DMP = bis(diphenylphosphino)methane) were determined from three dimensional X-ray data collected by counter methods. The iodine derivative crystallizes in the space group Pbca with eight units in a cell defined by a = 17.128(9), b = 18.306(9) c, = 16.508 (8) Å. The structure was refined by the least-squares method to a final R factor of 0.054 for 1336 non-zero independent reflections. The bromine derivative crystallizes in the space group P2₁/c with eight units in a cell defined by a = 23.707(1), b = 17.805(9), c = 16.991(1) Å, β = 136.10(5)°. The final least-squares refinement, based on 2489 non-zero independent reflections, gave an R factor of 0.074.Both the compounds have similar structures with a centrosymmetric (CuX)₄ core, in which two copper atoms have a tetrahedral geometry, while the other two are trigonal.The above structures are compared with those already reported for other compounds (CuX)_nL_m and a single scheme is proposed to rationalize the different geometries of the (CuX)_n core on the basis of steric and electronic effects.     

猫脑干上涎核节前神经元电活动的观察

在麻醉的32只猫记录了电刺激颌下腺神经支引起的上涎核平均场电位和单位放电。逆行电刺激颌下腺神经支引起的上涎核平均场电位分布在同侧脑干背面闩部头端5.5—8mm处,与过去的组织学结果大致符合。用微电极在上涎核记录了68个对刺激颌下腺神经支有反应的单位,其中33个单位作了碰撞试验。有9个单位符合逆向反应标准,它们是真正的颌下腺节前神经元,逆行反应的潜伏期为14.4±2.5ms,其轴突传导速度为2.9±0.1m/s。其他不符合逆向反应标准的单位,对刺激颌下腺神经支仍能发生反应,估计多为中间神经元。在一部分单位观察了电刺激舌神经或味觉刺激舌引起的反应。根据这些观察对上涎核内存在复杂神经元回路的可能性作了讨论。     

Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study

The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19.This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020).During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis.In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.     

A mathematical model for the burden of diabetes and its complications

Background  

The incidence and prevalence of diabetes are increasing all over the world. Complications of diabetes constitute a burden for the individuals and the whole society.     

A two-dimensional mathematical model of percutaneous drug absorption

Background  

When a drug is applied on the skin surface, the concentration of the drug accumulated in the skin and the amount of the drug eliminated into the blood vessel depend on the value of a parameter, r. The values of r depend on the amount of diffusion and the normalized skin-capillary clearence. It is defined as the ratio of the steady-state drug concentration at the skin-capillary boundary to that at the skin-surface in one-dimensional models. The present paper studies the effect of the parameter values, when the region of contact of the skin with the drug, is a line segment on the skin surface.     

Cutting edge: a new tool to evaluate human pre-erythrocytic malaria vaccines: rodent parasites bearing a hybrid Plasmodium falciparum circumsporozoite protein

Malaria vaccines containing the Plasmodium falciparum Circumsporozoite protein repeat domain are undergoing human trials. There is no simple method to evaluate the effect of vaccine-induced responses on P. falciparum sporozoite infectivity. Unlike the rodent malaria Plasmodium berghei, P. falciparum sporozoites do not infect common laboratory animals and only develop in vitro in human hepatocyte cultures. We generated a recombinant P. berghei parasite bearing P. falciparum Circumsporozoite protein repeats. These hybrid sporozoites are fully infective in vivo and in vitro. Monoclonal and polyclonal Abs to P. falciparum repeats neutralize hybrid parasite infectivity, and mice immunized with a P. falciparum vaccine are protected against challenge with hybrid sporozoites.     

Targeting of cancer cells with monoclonal antibodies specific for C3b(i)

Purpose: The goal of this research is to determine the feasibility of an immunotherapeutic approach based on the use of monoclonal antibodies (mAb) to target complement activation fragments on opsonized cancer cells. Methods: We investigated whether treatment of LNCaP and C4-2 human prostate cancer cell lines with normal human serum would allow for deposition of sufficient amounts of the complement-activation protein C3b and its fragments [collectively referred to as C3b(i)] such that these proteins could serve as cancer-cell-associated antigens for targeting by mAb. Radioimmunoassays, flow cytometry, and magnetic purging with specific immunomagnetic beads were used for the analyses. Results: In vitro opsonization of human prostate cancer cells with normal human serum resulted in deposition of C3b(i) in sufficient quantity (approx. 100,000 molecules/cell) for the cells to be targeted in a variety of protocols. We found that ⁵¹Cr-labeled and C3b(i)-opsonized cancer cells could be specifically purged at high efficiency (95%–99%) using anti-C3b(i) mAb covalently coupled to magnetic beads. Flow-cytometry experiments indicated that most normal white cells were not removed under similar conditions. Opsonization of cancer cells with sera from men with prostate cancer led to lower levels of cell-associated IgM and, subsequently, lower amounts of C3b(i) deposited than in normal subjects. Prototype experiments suggested that this deficiency could be corrected by addition of IgM from normal donor plasma. Conclusion: mAb directed against complement-activation products may provide new opportunities to deliver diagnostic and therapeutic agents selectively to cancer cells and tumor deposits. These opportunities may include ex vivo purging of C3b(i)-opsonized cancer cells prior to autologous bone marrow or stem cell transplantation. Received: 17 February 2000 / Accepted: 1 August 2000