Inhibition of Lassa virus and Ebola virus infection in host cells treated with the kinase inhibitors genistein and tyrphostin

Arenaviruses and filoviruses are capable of causing hemorrhagic fever syndrome in humans. Limited therapeutic and/or prophylactic options are available for humans suffering from viral hemorrhagic fever. In this report, we demonstrate that pre-treatment of host cells with the kinase inhibitors genistein and tyrphostin AG1478 leads to inhibition of infection or transduction in cells infected with Ebola virus, Marburg virus, and Lassa virus. In all, the results demonstrate that a kinase inhibitor cocktail consisting of genistein and tyrphostin AG1478 is a broad-spectrum antiviral that may be used as a therapeutic or prophylactic against arenavirus and filovirus hemorrhagic fever.     

Peripheral photoplethysmography variability analysis of sepsis patients

Sepsis is associated with impairment in autonomic regulatory function. This work investigates the application of heart rate and photoplethysmogram (PPG) waveform variability analysis in differentiating two categories of sepsis, namely systemic inflammatory response syndrome (SIRS) and severe sepsis. Electrocardiogram-derived heart period (RRi) and PPG waveforms, measured from fingertips (Fin-PPG) and earlobes (Ear-PPG), of Emergency Department sepsis patients (n = 28) with different disease severity, were analysed by spectral technique, and were compared to control subjects (n = 10) in supine and 80° head-up tilted positions. Analysis of covariance (ANCOVA) was applied to adjust for the confounding factor of age. Low-frequency (LF, 0.04–0.15 Hz), mid-frequency (MF, 0.09–0.15 Hz) and high-frequency (HF, 0.15–0.60 Hz) powers were computed. The normalised MF power in Ear-PPG (MFnu_Ear) was significantly reduced in severe sepsis patients with hyperlactataemia (lactate > 2 mmol/l), compared to SIRS patients (P < 0.05). Moreover, in a group of normal controls, MFnu_Ear was not altered by head-up tilting (P > 0.05), suggesting that there may be a link between 0.1 Hz ear blood flow oscillation and tissue metabolic changes in sepsis, in addition to autonomic factors. The study highlighted the value of PPG spectral analysis in the non-invasive assessment of peripheral vascular regulation in sepsis patients, with potential implications in monitoring the progression of sepsis.     

Immunogenicity of inactivated polio vaccine with concurrent antiviral V-073 administration in mice

Immunization of mice with inactivated polio vaccine (IPV) with concurrent dosing of poliovirus antiviral V-073 showed no detrimental impact on the elicitation of serum-neutralizing antibodies. A strategy involving coadministration of antiviral V-073 and IPV can be considered for the management of poliovirus incidents.     

Microwave tomography of extremities: 2. Functional fused imaging of flow reduction and simulated compartment syndrome

Medical imaging has recently expanded into the dual- or multi-modality fusion of anatomical and functional imaging modalities. This significantly improves the diagnostic power while simultaneously increasing the cost of already expensive medical devices or investigations and decreasing their mobility. We are introducing a novel imaging concept of four-dimensional (4D) microwave tomographic (MWT) functional imaging: three dimensional (3D) in the spatial domain plus one dimensional (1D) in the time, functional dynamic domain. Instead of a fusion of images obtained by different imaging modalities, 4D MWT fuses absolute anatomical images with dynamic, differential images of the same imaging technology. The approach was successively validated in animal experiments with short-term arterial flow reduction and a simulated compartment syndrome in an initial simplified experimental setting using a dedicated MWT system. The presented fused images are not perfect as MWT is a novel imaging modality at its early stage of the development and ways of reading reconstructed MWT images need to be further studied and understood. However, the reconstructed fused images present clear evidence that microwave tomography is an emerging imaging modality with great potentials for functional imaging.     

Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.     

Mapping Pathways by Which Genetic Risk Influences Adolescent Externalizing Behavior: The Interplay Between Externalizing Polygenic Risk Scores,Parental Knowledge,and Peer Substance Use

Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene–environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent externalizing behavior across two time-points in a high-risk longitudinal sample of 1,200 adolescents (764 European and 436 African ancestry; M_age = 12.99) from the Collaborative Study on the Genetics of Alcoholism. Results from multivariate path analysis indicated that externalizing polygenic scores were directly associated with adolescent externalizing behavior but also indirectly via peer substance use, in the European ancestry sample. No significant polygenic association nor indirect effects of genetic risk were observed in the African ancestry group, likely due to more limited power. Our findings underscore the importance of gene–environment interplay and suggest peer substance use may be a mechanism through which genetic risk influences adolescent externalizing behavior.

     

Biopharmaceutical study of nanosystems containing betulin for inhalation administration

Betulin, a triterpenoid present in birch bark, possesses a broad spectrum of biological activity. Its bioavailability is limited by low solubility in water whereas the shape and size of particles are not suited for administration via inhalation. One of the main drawbacks of inhalation preparations is low bioavailability because of the sedimentation of particles in the mouth. The present work was aimed at a biopharmaceutical study of nanosystems with betulin for administration via inhalation. Nanosystems were characterized by photon-correlation spectroscopy, differential scanning calorimetry, and x-ray powder diffraction. In addition, their dissolution profile was obtained by the Dissolution test. It is established that the obtained nanosystems with betulin exhibit high bioavailability, have optimal physicochemical properties for inhalation administration, and ensure deposition of betulin in the lower part of the respiratory tract.     

Isolation,production, and characterization of a new single chain anti-idiotypic antibody against benzo[a]pyrene

Polycyclic aromatic hydrocarbons are chemical carcinogens which could induce the development of human cancers. Anti-idiotypic antibodies against benzo[a]pyrene (BP) are perspective for human cancer immunoprophylaxis and tumor immunodiagnostic techniques. The purpose of this study was to isolate anti-idiotypic antibodies against BP from human lymphocytes naïve phage library. The anti-idiotypic antibody, named B5, was selected. Analysis of the nucleotide and amino acid sequences B5 showed no similarity to known protein databases antibodies. B5 bound idiotypic antibodies against BP in direct and competitive ELISA. It was suggested that the B5 carried an immunological image of BP and bound the idiotypic antibodies against BP.

Abbreviations: scFv: single-chain variable fragment; Ab1: idiotypic antibodies; Ab2: anti-idiotypic antibodies; CBD: cellulose binding domain; BSA: bovine serum albumin; PBS: phosphate buffer; BP-BSA: benzo[a]pyrene-BSA conjugate; Cr-BSA: chrysene-BSA conjugate; Py-BSA: pyrene-BSA conjugate; Ac-BSA: anthracene-BSA conjugate; Ba-BSA: benz[a]anthracene-BSA conjugate; PAH: polycyclic aromatic hydrocarbons; pSh: mouse idiotypic single-chain variable fragment against benzo[a]pyrene; T72: human idiotypic single-chain variable fragment against benzo[a]pyrene.     

Short-term memory processes in delayed visual differentiation in rhesus macaques after bilateral removal of field 7 of the parietal cortex

Monkeys (Macaca mulatta) with preliminary removal of field 7 of the lower parietal cortex and previously trained to differentiate images differing in shape, color, size, orientation, and spatial relationships were used to study the processes involved in short-term storage of different types of information required for a delayed (by 0–8 sec) visual differentiation task and the effects on these processes of the antioxidant Oxymetacil. Significant differences were found in comparison with intact animals. Removal of field 7 sharply worsened short-term storage processes during visual differentiation of different types of images, including those differing in terms of properties such as color, geometrical shape, and the spatial relationships between image elements. There were significant reductions in the level of correct responses for all delay periods with significant increases in the motor reaction time, indicating a sharp reduction in the duration of short-term information storage, which suggests that the monkeys' short-term memory mechanisms were disrupted. Oxymetacil had a correcting effect only in relation to stimuli differing in terms of color and shape, but had no effect at all on the short-term storage of spatial information. It is suggested that these data suggest that field 7 has at least two functions. These are, firstly, a role in processes underlying the evaluation, differentiation, and storage of spatial information depending on visual-vestibular interactions, and secondly, a role in the mechanisms underlying the attention system, which is disrupted by removal of field 7 and restored by treatment with the antioxidant when there is no need to differentiate spatial information, a process which depends on assessment of the body image and egocentric orientation based on visual-vestibular interactions. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 84, No. 5–6, pp. 480–489, May–June, 1998.