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Periodic hematological diseases such as cyclical neutropenia or cyclical thrombocytopenia, with their characteristic oscillations of circulating neutrophils or platelets, may pose grave problems for patients. Likewise, periodically administered chemotherapy has the unintended side effect of establishing periodic fluctuations in circulating white cells, red cell precursors and/or platelets. These fluctuations, either spontaneous or induced, often have serious consequences for the patient (e.g. neutropenia, anemia, or thrombocytopenia respectively) which exogenously administered cytokines can partially correct. The question of when and how to administer these drugs is a difficult one for clinicians and not easily answered. In this paper we use a simple model consisting of a delay differential equation with a piecewise linear nonlinearity, that has a periodic solution, to model the effect of a periodic disease or periodic chemotherapy. We then examine the response of this toy model to both single and periodic perturbations, meant to mimic the drug administration, as a function of the drug dose and the duration and frequency of its administration to best determine how to avoid side effects. [ABSTRACT FROM AUTHOR]

Leukemia, also called blood cancer is very common in medical practices. Acute lymphoid leukemia(ALL) and acute myeloid leukemia(AML) are the types of blood cancer that affect the bone, bone marrow, lymphatic system and are major contributors to cancer deaths. ALL is the most common type of leukemia and it is more predominant in children and young adults. As the number of leukemia cases increases, it leads to a delay in early diagnosis and treatment of the disease. The present method for diagnosis includes a manual examination of blood smear by pathologists. Changes in the white blood cells can be an indicator of the nature and severity of the disease. For further classification of the type of leukemia, bone marrow biopsy is done. These manual processes are costly, complex, time-consuming and mostly depends on the operator's ability. Hence, a need for automation arises which will be able to enhance and accelerate the diagnosis process. This paper provides a survey of different types of methodology which can be used to detect leukemia using image processing. These methods differ on the different types of image segmentation and feature extraction process employed by them. The methods are then compared by checking their efficiency and accuracy in differentiating and classifying the different leukemia cells. [ABSTRACT FROM AUTHOR]

Highlights • A microscopic hyperspectral imaging system is used to identify blood cells. • SMACC and ISODATA algorithms are combined to segment leukocytes. • Both spectral and spatial information are used for leukocytes classification. Abstract Observing and identifying blood cells is a direct way for early diagnosis of blood diseases. Traditional blood cell recognition methods are usually time-consuming and laborious tasks for medical staff. This paper proposed an efficient leukocyte recognition method based on microscopic hyperspectral imaging technology. In order to achieve better segmentation performance and further improve the representativeness of features, the sequential maximum angle convex cone algorithm and iterative self-organizing data analysis technique algorithm are combined to segment the leukocytes from microscopic hyperspectral images. In addition, the uniform and rotation invariant local binary pattern is adopted as a textural measurement of the leukocytes. Combined the texture features with shape and spectral features, support vector machine is used to classify the leukocytes into different types. Experimental results show that the proposed method provides higher segmentation and recognition accuracy compared with the existing method. Moreover, the addition of spectral features improves the recognition performance shows the potential diagnosis capacity of microscopic hyperspectral imaging technology. [ABSTRACT FROM AUTHOR]

Blocking cytokine interleukin 10 (IL-10) at the time of immunisation enhances vaccine induced T cell responses and improves control of tumour cell growth in vivo. However, the effect of an IL-10 blockade on the biological function of macrophages has not been explored. In the current paper, a macrophage precursor cell line, U937 cells, was selected to investigate the differential expression of proteins and relevant cell signalling pathway changes, when stimulated with lipopolysaccharide (LPS) in the presence of antibodies to IL-10 or IL-10 receptor. We used a quantitative proteomic strategy to investigate variations in protein profiles of U937 cells following the treatments with LPS, LPS plus human anti-IL10 antibody and anti-IL10R antibody in 24hrs, respectively. The LPS treatment significantly activated actin-related cell matrix formation and immune response pathways. The addition of anti-IL10 and anti-IL10R antibody further promoted the immune response and potentially effect macrophage survival through PI3K/AKT signalling; however, the latter appeared to also upregulated oncogene XRCC5 and Cajal body associated processes. [ABSTRACT FROM AUTHOR]

Aim The aim of this paper is to explore the expression of 6-methyladenine (6mA) DNA and to elucidate its gene regulation role in systemic lupus erythematosus (SLE). Methods Twenty SLE patients and 20 normal control healthy individuals (HCs) were included in this study. Genomic DNA was isolated from peripheral blood mononuclear cells and subsequently underwent 6mA-immunoprecipitation-sequencing (6mA-IP-Seq) after DNA quality control and 6mA precipitation. Bioinformation analysis was applied to the raw data comparing 6mA levels between SLE patients and HCs. Results We identified 5462 hypermethylation and 431 hypomethylation genes in PBMCs of individuals with SLE, which indicated that a high level of 6mA participates in the pathogenesis of SLE. Gene ontology analysis revealed that hypermethylation genes might regulate the inflammatory process, which has been well documented in the pathogenesis of SLE. Conclusion 6mA may be involved in the initial development of SLE, which may lead to its potential use as an early diagnostic marker and therapeutic target. [ABSTRACT FROM AUTHOR]

Lymphomas are a group of malignant blood cell tumors that develop from lymphocytes representing 2.2% of all malignant neoplasms of the head and neck. Two main categories of lymphomas are Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) of which 90% are of the NHL type. Several classification systems have existed for lymphomas, the objectives of which are to help in identification of homogeneous group of well-defined entities and facilitating the recognition of uncommon diseases that require further classification as it affects prognosis and therapeutic implications. Diffuse large B-cell lymphoma (DLBCL) is the most common NHL in the oral cavity involving Waldeyer's ring, base of the tongue, buccal mucosa and hard palate. DLBCL can be divided into germinal center B-cell-like, activated B-cell-like or type 3 gene expression profiles. This paper highlights a case report of DLBCL revisiting the intricacies and difficulties involved in establishing a diagnosis. [ABSTRACT FROM AUTHOR]

In this paper the authors propose a decision support system for automatic blood smear analysis based on microscopic images. The images are pre-processed in order to remove irrelevant elements and to enhance the most important ones - the healthy blood cells (erythrocytes) and the pathologic ones (echinocytes). The separated blood cells are analysed in terms of their most important features by the eigenfaces method. The features are the basis for designing the neural network classifier, learned to distinguish between erythrocytes and echinocytes. As the result, the proposed system is able to analyse the smear blood images in a fully automatic way and to deliver information on the number and statistics of the red blood cells, both healthy and pathologic. The system was examined in two case studies, involving the canine and human blood, and then consulted with the experienced medicine specialists. The accuracy of classification of red blood cells into erythrocytes and echinocytes reaches 96%. [ABSTRACT FROM AUTHOR]

Summary: Background: The incidence of Kaposi sarcoma (KS) has reduced as a result of the introduction of antiretroviral therapy. It is currently considered a rare disease in developed countries, and there has been a paucity of clinical papers on the subject in recent years in Europe. Aim: To analyse the clinical features and evolution of the different clinical forms of KS in the past 30 years. Methods: Patients with cutaneous lesions of KS diagnosed during the period 1987–2016 at Bellvitge Hospital (an 800‐bed university referral centre in Barcelona, Spain) were enrolled. Data recorded included age, sex, ethnicity, involved site, number of lesions, extracutaneous involvement, leg oedema, treatment, blood haemoglobin level, and blood cell (leucocyte, lymphocyte and CD4) counts. Results: Cutaneous lesions of KS were diagnosed in 191 patients (167 men, 24 women, mean ± SD age 51.95 ± 20.16 years). Clinical forms identified were classic KS (n = 53), acquired immunodeficiency syndrome (AIDS)‐associated KS (n = 118), immunosuppression‐associated KS (n = 18), and African endemic KS (n = 2). The number of patients diagnosed annually reached a maximum in the 1990s because of the AIDS epidemic, and has decreased since 2000. However, both classic KS and immunosuppression‐associated KS doubled from the first to the second half of the analysed period. Cutaneous lesions involved the legs in 137 cases, and extracutaneous lesions were detected in 32 patients. In 46 of 118 patients with AIDS, the diagnosis of KS was simultaneous to the detection of human immunodeficiency virus infection. Conclusion: After a decrease in incidence since the middle of the 1990s, AIDS‐associated KS continues to occur in Europe, and the number of annual cases of classic KS and immunosuppression‐associated KS is increasing. [ABSTRACT FROM AUTHOR]

The goal of harmonizing laboratory testing is contributing to improving the quality of patient care and ultimately ameliorating patient outcome. The complete blood and leukocyte differential counts are among the most frequently requested clinical laboratory tests. The morphological assessment of peripheral blood cells (PB) through microscopic examination of properly stained blood smears is still considered a hallmark of laboratory hematology. Nevertheless, a variable inter-observer experience and the different terminology used for characterizing cellular abnormalities both contribute to the current lack of harmonization in blood smear revision. In 2014, the Working Group on Diagnostic Hematology of the Italian Society of Clinical Chemistry and Clinical Molecular Biology (WGDH-SIBioC) conducted a national survey, collecting responses from 78 different Italian laboratories. The results of this survey highlighted a lack of harmonization of interpretative comments in hematology, which prompted the WGDH-SIBioC to develop a project on "Harmonization of interpretative comments in the laboratory hematology report", aimed at identifying appropriate comments and proposing a standardized reporting system. The comments were then revised and updated according to the 2016 revision of the World Health Organization classification of hematologic malignancies. In 2016, the Working Group on Diagnostic Hematology of the Italian Society of Clinical Chemistry and Clinical Molecular Biology (WGDH SIBioC) published its first consensus based recommendation for interpretative comments in laboratory hematology reporting whit the purpose of evaluating comments and the aim to (a) reducing their overall number, (b) standardizing the language, (c) providing information that could be easily comprehended by clinicians and patients, (d) increasing the quality of the clinical information, and (e) suggesting additional diagnostic tests when necessary. This paper represents a review of the recommendations of the former document. [ABSTRACT FROM AUTHOR]

Medical image processing technics has been a great boon to hematologists for the detection and investigation of various disorders which includes leukemia and malarial parasites. Hence image preprocessing and enhancement are done using denoising filers and edge detectors.[4] Edge detection is susceptible to the noise and hence denoising is to be done with Gaussian filter. The idea is to connect the points at which image brightness changes sharply are typically organized into a set of curved line segments termed edges. Canny edge detection algorithm was developed by John F. Canny in 1986 which was a multistage algorithm. In this paper we have implemented few filters on the blood cells to evaluate the best performing edge detector. [ABSTRACT FROM AUTHOR]

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Plasma cell segmentation is the first stage of a computer assisted automated diagnostic tool for multiple myeloma (MM). Owing to large variability in biological cell types, a method for one cell type cannot be applied directly on the other cell types. In this paper, we present PCSeg Tool for plasma cell segmentation from microscopic medical images. These images were captured from bone marrow aspirate slides of patients with MM. PCSeg has a robust pipeline consisting of a pre-processing step, the proposed modified multiphase level set method followed by post-processing steps including the watershed and circular Hough transform to segment clusters of cells of interest and to remove unwanted cells. Our modified level set method utilizes prior information about the probability densities of regions of interest (ROIs) in the color spaces and provides a solution to the minimal-partition problem to segment ROIs in one of the level sets of a two-phase level set formulation. PCSeg tool is tested on a number of microscopic images and provides good segmentation results on single cells as well as efficient segmentation of plasma cell clusters. [ABSTRACT FROM AUTHOR]

Abstract Deep Learning has already shown power in many application fields, and is accepted by more and more people as a better approach than the traditional machine learning models. In particular, the implementation of deep learning algorithms, especially Convolutional Neural Networks (CNN), brings huge benefits to the medical field, where a huge number of images are to be processed and analyzed. This paper aims to develop a deep learning model to address the blood cell classification problem, which is one of the most challenging problems in blood diagnosis. A CNN-based framework is built to automatically classify the blood cell images into subtypes of the cells. Experiments are conducted on a dataset of 13k images of blood cells with their subtypes, and the results show that our proposed model provide better results in terms of evaluation parameters. [ABSTRACT FROM AUTHOR]

Abstract This paper presents a novel development for a full Eulerian coupling method between a fluid and capsule with hyperelastic membrane to address a cell adhesion process. The capsule motion in the fluid field and their mechanical interactions are expressed in the Eulerian framework, while solving the capsule adhesion process by stochastic events of ligand-receptor bindings in a discrete level, with using Lagrangian markers distributed on the implicit surface of the capsule. In addition to this, numerical improvements of the full Eulerian method for calculating an interface normal vector and dealing with multiple capsules by introducing the temporarily constructed level set function. A numerical validity of the present development is investigated through a comparison with available numerical data in a validation problem, and a capability for the capsule adhesion is shown in a single capsule adhesion and platelet adhesion in a suspension with blood cells. Highlights • Cell adhesion process using the full Eulerian coupling method for suspension flows with multiple capsules. • Combination of Lagrangian and Eulerian frameworks. • Coupling with continuum and stochastic approaches. • Accurate evaluation of the interface normal vector by introducing the level set function. • Numerical treatment for capsule repulsion. [ABSTRACT FROM AUTHOR]

B cells develop high affinity receptors during the course of affinity maturation, a cyclic process of mutation and selection. At the end of affinity maturation, a number of cells sharing the same ancestor (i.e. in the same “clonal family”) are released from the germinal center; their amino acid frequency profile reflects the allowed and disallowed substitutions at each position. These clonal-family-specific frequency profiles, called “substitution profiles”, are useful for studying the course of affinity maturation as well as for antibody engineering purposes. However, most often only a single sequence is recovered from each clonal family in a sequencing experiment, making it impossible to construct a clonal-family-specific substitution profile. Given the public release of many high-quality large B cell receptor datasets, one may ask whether it is possible to use such data in a prediction model for clonal-family-specific substitution profiles. In this paper, we present the method “Substitution Profiles Using Related Families” (SPURF), a penalized tensor regression framework that integrates information from a rich assemblage of datasets to predict the clonal-family-specific substitution profile for any single input sequence. Using this framework, we show that substitution profiles from similar clonal families can be leveraged together with simulated substitution profiles and germline gene sequence information to improve prediction. We fit this model on a large public dataset and validate the robustness of our approach on two external datasets. Furthermore, we provide a command-line tool in an open-source software package () implementing these ideas and providing easy prediction using our pre-fit models. [ABSTRACT FROM AUTHOR]

Knowledge on the immune system of Pomacea canaliculata is becoming increasingly important, because of this gastropod's role as intermediate host and vector of Angiostrongylus cantonensis, the etiologic agent of eosinophilic meningitis in humans and domestic animals. Immune defenses of this gastropod comprise both humoral and cellular components, but they may also involve organs that act as immune barriers to prevent the spread of alien molecules and organisms. Both the kidney and lung are here shown to serve this function, because of (1) their positions in blood circulation, (2) the intricate architecture of their blood spaces, and (3) the proliferative and nodulation reactions of hemocytes to an immune challenge. However, these organs differ in that only the kidney shows permanent hemocyte aggregations. Microcirculation in the kidney was found to flow through an intricate vascular bed containing the permanent aggregations, which occurred either as hemocyte islets anchored by cytoplasmic projections of the renal epithelium or as perivascular accretions. Within 96 h of the injection of yeast cells, hemocyte nodules were formed both in the kidney and lung. Moreover, cell proliferation in renal hemocyte islets was measured by bromodeoxyuridine (BrdU) incorporation. The proportion of BrdU positive nuclei increased 48 h after injection. Signs of nodule regression (apoptotic bodies, lipofuscin-like deposits) and a decrease in the proportion of BrdU positive nuclei were found at 96 h. In addition, the area of renal hemocyte islets was significantly increased 96 h after injection. Nevertheless, the high complexity of the small vascular chambers that constitute the lung's respiratory lamina would also facilitate hemocyte-antigen contacts, required to elicit cellular aggregation, and hence, nodulation. To our knowledge, this paper includes the first quantitative indication of hemocyte proliferation after an immune challenge among Caenogastropoda. [ABSTRACT FROM AUTHOR]

It is well accepted that influenza A virus predisposes individuals to often more severe superinfections with Streptococcus pneumonia. However, the mechanisms that lead to this synergy are not clearly understood. Recent data suggests that competent Th17 immunity is crucial to clearance and protection from invasive pneumococcal disease of the lung. We demonstrate that early influenza infection significantly reduced levels of pneumococcus driven IL-12p70, IL-23 and IL-27 in human monocytes with significant impairment of IL-17A and IFN-γ in HKSP-treated allogeneic mixed lymphocyte cultures. We also provide evidence to suggest that the hemagglutinin component of the virus is at least partially responsible for this downward pressure on IL-17 responses but surprisingly this suppression occurs despite robust IL-23 levels in hemagglutinin-treated monocyte cultures. This study demonstrates that influenza can directly affect the immunological pathways that promote appropriate responses to Streptococcus pneumonia in human immune cells. Importance: Influenza virus is highly contagious and poses substantial public health problems due to its strong association with morbidity and mortality. Approximately 250,000–500,000 deaths are caused by seasonal influenza virus annually, and this figure increases during periods of pandemic infections. Most of these deaths are due to secondary bacterial pneumonia. Influenza-bacterial superinfection can result in hospitalisation and/or death of both patients with pre-existing lung disease or previously healthy individuals. The importance of our research is in determining that influenza and its component haemagglutinin has a direct effect on the classic pneumococcus induced pathways to IL-17A in our human ex vivo model. Our understanding of the mechanism which leaves people exposed to influenza infection during superinfection remain unresolved. This paper demonstrates that early infection of monocytes inhibits an arm of immunity crucial to bacterial clearance. Understanding this mechanism may provide alternative interventions in the case of superinfection with antimicrobial resistant strains of bacteria. [ABSTRACT FROM AUTHOR]

Although there are many independent studies on the detection of white blood cell or classification of white blood cell, few papers have taken them into consideration. This study proposed a method for recognizing five types of leukocytes based on multi-scale regional growth and mean-shift clustering. The key idea of the proposed method is to extract texture features of leukocytes in a visual manner. And it is a non-parametric texture features extracting method different from traditional algorithms. Finally, SVM (Support Vector Machine) is used for classification. Some leukocyte images were used and the overall correct recognition rate reached 97.96%, indicating the feasibility and robustness of the proposed method. [ABSTRACT FROM AUTHOR]

Smoking is an important risk factor for respiratory and cardiovascular diseases. The role of numerous chemical, partly uncharacterised compounds existing in tobacco smoke is not known. (-)-Nicotine, its stereoisomer (+)-nicotine and main metabolite cotinine are biologically active compounds influencing e.g. catecholamine and eicosanoid systems. The precise mechanisms are not well known. The purpose of the present study consisting of a PhD thesis (11) and five original papers was to investigate the in vitro effects of nicotine isomers and cotinine on eicosanoid production in polymorphonuclear leukocytes, platelets and whole blood in vitro, and to clarify the effects of smoking without and with nicotine substitution on eicosanoid production in vivo and ex vivo. It was found that all the tested compounds modulated blood cell eicosanoid synthesis. Nicotine isomers and cotinine increased PGE2 but decreased TXB2, LTB4 and LTE4 synthesis in vitro. Eicosanoid synthesis in vivo and ex vivo was higher in smokers (n = 60) than in non-smoking controls (n = 20). This may contribute to the harmful cardiovascular effects of smoking. Cessation of smoking without, but not with, nicotine substitution reduced eicosanoid synthesis measured ex vivo as whole blood production or in vivo as urinary excretion of eicosanoid metabolites after 3, 7 and 14 days. Thus long-term nicotine substitution diminishes the beneficial effects of smoking cessation.

Current recommendations vary with regard to the frequency of change of a red blood cell (RBC) administration set. A full review was undertaken to evaluate the recommendations for how often a RBC administration set should be changed while a patient is being transfused. Comprehensive searches of Medline, Embase, Cinahl, the Cochrane Library, handsearching of transfusion journals, guidelines and websites and contact with administration set manufacturers identified 32 relevant papers: 11 clinical updates; 11 guidelines; 5 manufacturer data sheets; 3 standards; 1 Department of Health report and 1 expert opinion. Recommendations varied widely across papers. There was no pattern in recommendation by paper type, date or country of origin. Recommendations were based on change of RBC administration set either after a given number of hours or number of RBC units. The recommendations varied widely and ranged from 4 to 48 h and from ‘every unit’ to ‘several units’. The most frequent recommendations were change of RBC administration set after 12 h or 4 units. Methodological quality of the included papers is poor. There is no formal evidence base on which to support current recommendations or challenge the current British Committee for Standards in Haematology guideline. Targeted research aimed at establishing an evidence base may be warranted and would need to document other variables that can impact frequency of change, including type of filter, age of blood and duration of RBC transfusion. [ABSTRACT FROM AUTHOR]

Objectives: In response to increasing numbers of states in the US that test newborn babies for cystic fibrosis (CF), the Newborn Screening Quality Assurance Programme initiated a pilot proficiency testing programme for immunoreactive trypsinogen (IRT), the biomarker for CF. Dried blood spot specimens (DBS) were used to evaluate the performance of laboratories that screen babies for CF. Methods: DBS were prepared from human whole blood enriched with physiologically relevant levels of IRT. Various methods of making IRT-enriched DBS were used to optimize the recovery and stability of the biomarker, including preparation of DBS from either intact or lysed red blood cells, varying the timing of IRT addition to blood before dispensing onto filter paper, adding a protease inhibitor cocktail, and treating serum with charcoal before IRT enrichment. The recovery and stability of IRT in DBS were assessed. Newborn screening laboratories were offered the opportunity to test blind-coded DBS in the pilot PT programme. Results: IRT was stable in the filter paper matrix when stored for one year at either -20°C or 4°C. Fifty percent more IRT was recovered from DBS prepared with lysed red blood cells where the IRT was added to blood just before dispensing; however, protease inhibitors did not improve IRT recovery. Conclusions: IRT in the DBS matrix is stable and can be shipped worldwide under ambient conditions. Optimal IRT recovery was achieved by adjustment of DBS production practices. Laboratories receiving specimens accurately measured IRT by a variety of commercial and in-house methods. [ABSTRACT FROM AUTHOR]

The preset paper deals with the construction and examination of the system used for the red blood cell distribution measurements. Although the state-of-the-art laboratories are equipped with modern, highly automated blood analyzers, the cost of such equipment is very high, especially for Polish conditions. The goal of the paper is the design and measurement quality analysis of system used as an add-on for almost every simple RBC counter. The measurement system is connected to a PC, so the results are presented graphically. [ABSTRACT FROM AUTHOR]

Cardiac resident macrophages play vital roles in heart development, homeostasis, repair, and regeneration. Recent studies documented the hematopoietic potential of cardiac endothelium that supports the generation of cardiac macrophages and peripheral blood cells in mice. However, the conclusion was not strongly supported by previous genetic tracing studies, given the non-specific nature of conventional Cre- loxP tracing tools. Here, we develop an intercellular genetic labeling system that can permanently trace heart-specific endothelial cells based on cell-cell interaction in mice. Results from cell-cell contact-mediated genetic fate mapping demonstrate that cardiac endothelial cells do not exhibit hemogenic potential and do not contribute to cardiac macrophages or other circulating blood cells. This Matters Arising paper is in response to Shigeta et al. (2019), published in Developmental Cell. See also the response by Liu and Nakano (2023), published in this issue. [Display omitted] • Generation of intercellular genetic recording system to label neighboring cells • Genetic tracing of endocardium and coronary endothelial cells by cell-cell contact • Cardiac endothelium does not have hematopoietic potential in development • Cell-cell contact-mediated labeling enhances the specificity of genetic tracing In this Matters Arising article, Liu and Jin et al. re-evaluate the model that the developing endocardium is hemogenic and generates cardiac macrophages and circulating blood cells, which was proposed by Shigeta et al. By using an intercellular genetic tracing system that enables specific labeling of cardiac endothelium, they find that the cardiac endothelium does not have hematopoietic activity during heart development. [ABSTRACT FROM AUTHOR]

Electrodeposition of copper-organic framework on a carbon nanotube-modified gold wire for non-enzymatic electrochemical sensing of hydrogen peroxide and glucose. [Display omitted] • Developed a dual bio-sensing platform for H 2 O 2 and glucose using swnt-MOF(Cu)@gwe. • The biosensor platform showed wide linear concentrations and low detection limits. • The sensing system was found to be easy, flexible, stable, and free of interference. • The platform was capable of endogenous detection of H 2 O 2 in living cells. • The platform was highly worked in turbid medium of whole blood and milk samples. For clinical research, the precise measurement of hydrogen peroxide (H 2 O 2) and glucose (Glu) is of paramount importance, due to their imbalanced concentrations in blood glucose, and reactive oxygen species (ROS) play a huge role in COVID-19 viral disease. It is critical to construct and develop a simple, rapid, flexible, long-term, and sensitive detection of H 2 O 2 and glucose. In this paper, we have developed a unique morphological structure of MOF(Cu) on a single-walled carbon nanotube-modified gold wire (swnt@gw). Highly designed frameworks with nanotube composites enhance electron rate-transfer behavior while extending conductance and electroactive surface area. The composite sensing system delivers wide linear-range concentrations, low detection limit, and interference-free performance in co-existence with other biomolecules and metal ions. Endogenous quantitative tracking of H 2 O 2 was performed in macrophage live-cells with the help of a strong stimulator lipopolysaccharide. The composite device was effectively utilized for the measurement of H 2 O 2 and glucose in turbid samples of whole blood and milk samples without a pretreatment process. The practical results of biofluids showed favorable voltammetric results and acceptance recovery percentage levels between 97.49 and 98.88%. Finally, a flexible MOF-based hybrid system may provide a suitable detection platform in the construction of electro-biosensors and hold potential promise for clinical-sensory applications. [ABSTRACT FROM AUTHOR]

The application of variable novel drug delivery system has shown a flowering trend in recent years. Among them, the cell-based drug delivery system (DDS) utilizes the unique physiological function of cells to deliver drugs to the lesion area, which is the most complex and intelligent DDS at present. Compared with the traditional DDS, the cell-based DDS has the potential of prolonged circulation in body. Cellular DDS is expected to be the best carrier to realize multifunctional drug delivery. This paper introduces and analyzes common cellular DDSs such as blood cells, immune cells, stem cells, tumor cells and bacteria as well as relevant research examples in recent years. We hope that this review can provide a reference for future research on cell vectors and promote the innovative development and clinical transformation of cell-based DDS. [ABSTRACT FROM AUTHOR]

Cytologic investigations designed to study bone marrow, peripheral blood, spleen, and thymus of albino rats irradiated by an electromagnetic field, 2375, 2450, and 3000 MEGS, revealed structural and functional changes in populations of megakaryocytes, immunocompetent cells as well as of undifferentiated cells, and of other types of cells that are dependent on the intensity of irradiation and permit establishing the probability-threshold levels of exposure taking account of reactions of perception and physiologic adaptation together with compensatory and regenerative processes and the injury sustained. It is shown that changes in bone marrow cells differentiation and reproduction rather than integral shifts in the peripheral blood that acquire the utmost significance. Subjected to a particular scrutiny in the paper are blast cells, which cells' repopulation was noted to be getting increased in low-intensity exposure as were disturbances in their mitosis pattern.

As a result of the activities of the first Soviet plutonium production reactor, large territories of the Southern Urals were exposed to radioactive contamination. Three different incidents occurring between 1948 and 1967 lead to major exposure. A total of 280,000 people residing on the contaminated territories were exposed both to external and internal contamination particularly due to the long-lived radionuclides 137Cs and 90Sr. The highest doses were received by 28,000 people living on the Techa riverside villages. In the present paper 15 presumably exposed children coming from the Muslyumovo village on the Techa river have been analyzed using conventional cytogenetic procedure in order to assess a radiation-induced damage. The data obtained have been compared to a group of matched unexposed controls. The results show a statistical difference between the two cohorts which suggests a possible residual contamination representing a continuous hazard for the new generations., (Copyright 1998 Elsevier Science B.V. All rights reserved.)

We have tested the hypothesis that dense cell formation in sickle cell disease is associated with increased binding of calpromotin to the membrane, an event that occurs during the activation of calcium-dependent potassium transport. By SDS polyacrylamide gel electrophoresis, we found that sickle cell membranes contained more calpromotin than did normal membranes when stained with Coomassie brilliant blue or when transferred to nitrocellulose paper and immunostained with horseradish peroxidase. Also, the membranes from dense sickle cells contained significantly (P = 0.00055) higher levels of calpromotin, 2.62+/-1.59 microg/mg membrane protein, compared to light sickle cells, 1.40+/-0.70 microg/mg membrane protein, when measured by an enzyme-linked immunosorbent assay. The ratio of calpromotin associated with dense cell membranes to light cell membranes was significantly greater than 1.0 (P < 0.00005). Transmission electron micrographs of immunogold-labelled membranes supported the increase in calpromotin binding in dense sickle cell membranes. In addition, the immunogold probe demonstrated clustering, which was not observed in light sickle cell membranes nor in normal membranes. Finally, we incubated HbSS cells in vitro using a repetitive deoxygenation/ reoxygenation procedure to produce dense cells and then measured the levels of calpromotin associated with their membranes. As expected, the levels of calpromotin bound to the membrane doubled during the procedure relative to the basal levels at the beginning of the incubation. The correlation coefficient, calculated between the increase in dense cell formation and the increase in calpromotin associated with the membrane, was statistically significant (P = 0.038). The results demonstrate that an increase in calpromotin binding to the membrane is associated with dense cell formation presumably through the activation of the calcium-dependent potassium channel.

Modern biomedical tasks put forward new requirements to the instrumental base of microscopy. This paper outlines the prospective trends in microscopy which are the most interesting for medicine, on the one hand, and analyzes the probability of meeting the requirements of medicine by modern methods of optic electronics and computer processing of optic information. The authors analyze the following trends: microscopy of three-dimensional objects, super-resolution, microscopic measurements, and automation of microscopes. Progress in optic electronics and computer processing of images permits considering these trends as a priority task of modern microscopy.

Glutathione(GSH) has been implicated as an important factor in the detoxification of many electrophilic xenobiotics, including agents used in cytotoxic chemotherapy. Maintenance of high levels of GSH in normal tissues is believed to be important in the prevention of drug-induced toxicity. Previous studies have indicated that exposure of cells to some toxic electrophiles both in vitro and in vivo can cause a temporary decrease in intracellular levels of GSH. In this paper we report that in a series of 22 children and young adults treated with high dose melphalan (ten courses studied, all 200 mg/m2), cisplatin (eight courses, 80-104 mg/m2) or carboplatin (seven courses, 507-750 mg/m2) there was no significant alteration in the level of plasma, erythrocyte or urine GSH in the period immediately following drug administration. Fluctuations in the level of GSH in mononuclear cells were observed in some patients but did not follow any consistent pattern and were similar to those observed in a series of nine normal adult controls over the same time course. These results suggest that for melphalan, cisplatin and carboplatin, drug-GSH adduct formation is insufficient to cause a measurable decrease in intracellular GSH levels in normal peripheral haematopoietic cells during the course of treatment.

Using appropriate standards immune flow cytometry permits quantitative analysis of the expression levels of cellular antigens. This information can be gained on an absolute basis and reported in terms of numbers of molecules per cell. This offers clues for reaching time-to-time and lab-to-lab comparability of immuno-fluorescence data. After briefly reminding the characteristics of available standards this paper provides an overview of the main relevant candidate molecules for flow cytometric quantitation on hemopoietic cells and reviews the major fields of application in immuno-hematology.

The paper describes processing of peripheral blood screening based on methods of mathematical statistics and partially ordered sets theory. This allows global assay of individual and populational blood, assessment of borderline conditions by introduction of global criterion. The above methodology was tried to analyze data obtained at screening of peripheral blood from children living in radionuclide-contaminated regions. The most considerable contribution to region-specific populational differences belongs to red cells, monocytes, band neutrophils, eosinophils. Hemogram deterioration in children and adolescents seems to result rather from chemical pollution and social factors than radiation effect (in doses not high than 2.2 rem a year).

The damage to disk microcirculation in glaucoma and ocular hypertension is correlated with the damage to the neuronal tissue. However, it is not clear whether the primary damage is vascular or neurogenic. We have developed a new method which allows in vivo observation of the retinal capillary blood cell flow and the plasma flow, separately. The method was used to examine the blood cell flow in the optic disks of cats' eyes. The intraocular pressure was controlled by extra-fine intraocular canula at the anterior chamber. It was found that blood cell flow became stagnant in a few capillaries at the optic disk with an intraocular pressure of 30-45% of the systemic mean blood pressure. When an induced IOP increase to 45% of systemic mean blood pressure was sustained for 30 minutes, microcirculatory blood flow recovery was complete two hours later. When this pressure was sustained for 120 minutes, the recovery was incomplete two hours later. This work represents a new tool in the research of retinal and disk hemodynamics and microvascular pathologies. The results presented in this paper support the hypothesis that early ischemic microdamage might be the basis of the pathogenesis of the chronic glaucomas.

Blood cell transplantation (BCT) is the procedure of choice for autologous bone marrow transplantation. In this paper we review the current status of BCT with emphasis on important recent advances. These include increasing knowledge of the biologic nature of mobilized blood cells and important evidence showing that very primitive cells are present in blood cells. An increasing understanding of mechanisms of mobilization is likely to result in the design of more rational mobilization strategies. Current mobilization methods are discussed including justification of combined chemotherapy and cytokine mobilization as the method of choice for cancer patients. Single-apheresis BCT may be possible in the future. Recent data show variable malignant contamination of blood cell harvests, but whether this contributes to relapse is unknown. Clinical applications and the efficacy of high-dose therapy are discussed. BCT may allow novel approaches to increase both total dose and dose intensity of therapy as well as application to allogeneic transplantation.

Interactions between blood cells in the form of cellular aggregates or adhesion are observed in a variety of normal and pathological conditions. Aggregation of erythrocytes or platelets, adhesion of platelets and leucocytes and immune agglutination of RBC are examples of interactions involving blood cells. Cell adhesion and aggregation are modulated by specific interactions (antigen-antibodies reactions, adhesive macromolecules interactions...) or non-specific (van der Waals forces, electrostatic interactions, molecular bridgings...). These interactions may result in morphological and structural changes, or polarization phenomena. At the dynamic level, cellular adhesion (or aggregation) can divided in 4 main steps: transport, cellular activation (endogenous or exogenous), morphological, physical or steric rearrangements, contact (intercellular or on an artificial surfaces). It will be the nature of the interactions involved in these steps that will determine the binding cohesion and kinetic. In this paper, different types of interactions and the regulation mechanisms of adhesion and aggregation phenomena involved in blood hemodynamics will be summarized and some examples (RBC or platelets aggregation; platelets or leucocytes adhesion) will illustrate the importance of these phenomena in clinical hemorheology.

The final diagnosis of sickle cell disease (SCD) is established by haemoglobin (Hb) electrophoresis. The test, however, is expensive and absent in most hospitals in Kenya. We studied sensitivity, specificity and cost-effectiveness of the peripheral blood film (PBF) in diagnosing sickle cell anaemia (SCA), the most common type of sickle cell disease (SCD) in Kenya. The PBF can be done even in dispensaries. The study was performed in SCA endemic western Kenya in 767 subjects during 12 months. Hb level, WBC count, PBF, sickle cell test (SCT) and cellulose acetate paper electrophoresis (CAPE) were performed. In the PBF, presence of sickle cells was pathognomonic for SCA. SCA was found in 21, sickle cell trait in 120, and normal genotype in 616 subjects. Sensitivity of the PBF versus SCT and CAPE to detect SCA was 76% with a specificity of 99.7%. The PBF was cheaper than both methods by 31.1%.

The following corrections have been made to the paper: In section "Lectin staining of hemocytes by LEL and WGA", the sentence "After washing twice, hemocytes were analyzed by flow cytometry and observed under a fluorescence microscope" was changed to read: "After washing twice, stained hemocytes were analyzed by flow cytometry and observed under a fluorescence microscope. Dot plot analysis of WGADim hemocytes (c), WGAStrong hemocytes (d), LELDim hemocytes (e), LELStrong hemocytes (f) and unstained hemocytes (g). x-axis Forward-scatter filter (FSC), y-axis side-scatter filter (SSC) In the Figs. Unstained and unseparated hemocytes (total hemocytes) were also analyzed by flow cytometry as negative control". [Extracted from the article]

Microglia, the resident macrophages of the central nervous system (CNS), can be distinguished from most other cells of the myelomonocytic lineage by a distinct pattern of membrane currents. In the accompanying paper we have shown that the characteristic morphological feature of microglia, ramification, develops both in microglia and other myelomonocytic cells when they are cocultured with astrocytes. We therefore propose that the electrophysiological properties of microglia also develop under the influence of astrocytes, and, moreover, that these properties can also be induced in other cells of the myelomonocytic lineage. Microglia cultured on poly-d-lysine or on a monolayer of fibroblasts possess an inwardly rectifying K(+)-current only, which is of composite nature. In single-channel recordings two types of K(+)-channels are found: i) a noninactivating channel with a conductance of 43pS, and ii) an inactivating channel with 32pS. Microglia cultured on a monolayer of astrocytes additionally develop an outward K(+)-current and a Na(+)-current. The electric parameters of activation and inactivation of the microglial Na(+)-current are identical to those of the neuronal Na(+)-current. Monocytes from peripheral blood and macrophages from spleen exhibit no inward currents. However, when these cells are cocultured with astrocytes they develop microglia-like membrane currents, including the inward and outward K(+)-rectifyer and the Na(+)-current. By contrast, on fibroblasts they retain their macrophage current profile. The expression of the microglia-like membrane currents in the mononuclear phagocytes is induced by a diffusible factor released from the astrocytes into the culture medium, since monocytes and microglia develop the mature microglial current profile, when cultured in astrocyte conditioned medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of zinc concentrations in white blood cells has been used to establish zinc deficiency. During pathological conditions changes in zinc concentrations in these blood cells were observed. However, these investigations were hampered by the low amount of zinc in this form per mL blood. Earlier we demonstrated that, in the case of zinc deficiency, the uptake of zinc was increased, using the in vitro exchange of zinc by the various blood cells with extracellular zinc labeled with 65Zn in fairly physiologic conditions. In case of inflammation, no increase in zinc uptake by erythrocytes was seen, indicating that this method probably can be used to differentiate real from apparent zinc deficiency. Only during the first days of the inflammatory process, probably representing the redistribution phase during which zinc moves from the serum to the liver, a small increase in in vitro zinc uptake was seen in mononuclear cells (MNC) and polymorphonuclear cells (PMNC). Earlier papers raised some questions; e.g., is the uptake part of an exchange process and can the efflux of zinc by the cells be measured by the same method; what is the influence of time on the process of zinc uptake; what is the magnitude of the uptake of zinc by the cells compared to the zinc concentration in the cells; and, what is the influence of temperature on the uptake of zinc? In the present study, the influence of incubation time and temperature on the uptake of zinc by human and rat blood cells and on the release of zinc by rat blood cells was studied. At least three phases of uptake of zinc in the various cells were found by varying the incubation time--a fast phase during the first half hour, probably caused by an aspecific binding of zinc on or in the cell membrane; a second fast uptake between 60-330 min, probably caused by an influx of zinc in the cell as part of the exchange process of zinc; and a slow third phase after 5.5 h, in which probably the in- and efflux of the rapidly exchangeable intracellular pool is more or less equilibrated. For mononuclear cells, polymorphonuclear cells, and erythrocytes of rats, the rapidly exchangeable intracellular pool is 40%, 53%, and 10%, respectively, of the total zinc content of the cells. This study is also performed in human cells; in human cells the exchangeable pool of mononuclear cells and erythrocytes is 17 and 3.5% of the total zinc content of the cells, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Cryoultramicrotomy applying immunogold staining (immunocryoultramicrotomy) is a useful method to demonstrate the localization of antigens in biological specimens. Recently, we have developed a modified method for immunocryoultramicrotomy using gelatin as an embedding medium (gelatin embedding method). In this study, we compared the results obtained by the gelatin embedding method with those obtained by a conventional method applying polyvinyl alcohol embedding (PVA embedding method). Both methods were easy to perform, and yielded fairly satisfactory results in terms of detecting antigens and preserving ultrastructures. According to the gelatin embedding method, membranes enclosing organelles revealed a negatively stained image, and organelles were clearly delineated by an electron-lucent layer. In contrast, a positively stained image was obtained by the PVA embedding method; however, the delineation of organelles was somewhat inferior to that of the gelatin embedding method. Although these methods were useful to detect various biological antigens, they had some limitations in sensitivity. Prior glutaraldehyde fixation was requisite for cryosectioning and preserving ultrastructures, but it caused the loss of antigenicity to some extent. This should be taken into account when evaluating the results obtained by immunocryoultramicrotomy. In this paper, we present the detailed procedures of the gelatin embedding method, as well as the PVA embedding method, and demonstrate the localization of myeloperoxidase, lysozyme and CD3 molecules in human blood cells using both methods.

Background/Aim. Measles is a contagious disease with a good prognosis; however, severe complications may sometimes develop. C-reactive protein (CRP) and blood cells count-derived inflammatory indices – granulocyte-lymphocyte ratio (GLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean plate-let volume (MPV)/platelet count ratio (MPR), red blood cell distribution width (RDW), and MPV are the indicators related to the clinical outcome in various inflammatory diseases. The aim of the study was to analyze the values of CRP, blood cell count, GLR, PLR, MLR, MPR, RDW, and MPV in measles-affected children compared to healthy controls and between measles-affected children with complicated and severely complicated measles form. A particular aim of the paper was to assess the suitability of inflammatory-derived markers for predicting the severity of the disease. Methods. The study included 55 measles-affected children who developed complications (examination group), while the control group included 30 healthy children. The first peripheral blood count, obtained on the first hospitalization day (before treatment), was used for further analyses. Results. The white blood cells, lymphocytes, monocytes, and platelets count were significantly lower, while GLR, PLR, MPR, and CRP were significantly higher in measles-affected children (p ˂ 0.05). In severely complicated measles form, significantly higher values of granulocytes, CRP, GLR, and PLR were documented, including lower lymphocytes (p ˂ 0.05). A linear regression analysis showed that CRP was the only indicator with predictive significance for the severity of the course of measles. Conclusion. The blood cell count-derived inflammatory indices should not be crucial in assessing the severity of measles in children. CRP was the most valuable predictive factor for the development of the severe course of measles in measles-affected children.

1. This paper describes and illustrates the dangers of sub-optimal mixtures of EDTA anticoagulant:blood during the preparation of avian blood smears. 2. Excessive concentrations of EDTA lead to variable staining and make cellular differentiation more difficult. 3. It is recommended, for the use of a 2.5 ml graded blood tube containing 3.75 mg EDTA, that no less than 1.0 ml of blood be mixed.

Although anopheline mosquitoes will ingest plasma without blood cells, Culex spp. and Aedes spp. require the phagostimulatory effect of blood cells; this effect can be duplicated by the addition of adenine-nucleotides to plasma. Because activation of platelets released ADP and ATP into the plasma, they were suspected as the major source of the phagostimulant. This paper describes quantitatively the role of platelets in ingestion by Aedes aegypti (L.) and Culex univittatus Theobald. We found that about 10(6)/mm3 inactivated platelets are required to induce engorgement by 80-90% of the mosquitoes of both species. Thrombin activation of the platelets reduced the effective dose to < 2 x 10(4)/mm3. Other blood fractions also were tested as possible sources of stimulation. A series of washed red blood cells (RBC) dilutions was tested; 5 x 10(5) RBC/mm3 were required to induce 90% engorgement. Several types of leukocytes derived from blood by standard methods also induced engorgement at their physiological concentrations. Macrophages and cultured lymphocytes that do not contain any platelets induced gorging in Cx. univittatus, but not in Ae. aegypti. Because RBC and leukocytes do not release nucleotides unless broken, we suggest that their phagostimulatory effect is due to platelet contamination, which invariably occurs during standard methods of blood fractionation.

This paper present hematological data obtained during space flights of the third and the fourth prime crew flights (EO-3 and EO-4). In the EO-3 flight, RBCs, WBCs and blood formed elements were counted by the cosmonaut-researcher. In the EO-4 flight, blood was drawn by the cosmonaut-researcher and analyzed on the ground; also, blood smears treated in the Microview unit and videotaped were used. Blood parameters in EO-3 and EO-4 crewmembers were close or equal to the normal. However there were cases with changes in bends, myelocytes, neutrophils, lymphocytes; also anisocytosis, hypochromia, target-like erythrocytes, and single acanthocytes were seen. Comparison of blood smears on unstained and stained glass slides revealed significant differences in the amount of target-like erythrocytes in the same cosmonaut at the same time (on the prestained glass slide only 4 erythrocytes and no aggregates in single fields of vision were detected while on the unstained glass slide aggregates in single fields of vision were seen). Pre- and postflight examinations of bone marrow revealed polymorphocellular marrow and mature hemopoietic cells.

This paper presents the results of evaluating blood morphology (counts of red blood cells, hemoglobin, reticulocytes, platelets, leukocytes and their forms), hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin content and concentration, and erythrocyte sedimentation rate (ESR) in 9 test subjects during a 370-day head-down tilt study. It was demonstrated that blood morphology variations in 9 test subjects remained within normal variations throughout the entire period of observation, including the baseline, head-down tilt, and rehabilitation periods. There were the following exceptions. In the baseline period, a single episode of MCV increase and MCH decrease was recorded. In the course of head-down tilt, monocytosis, lymphocytosis, thrombocytopenia, basophilia, and lowered MCH were occasionally observed. MCV was slightly increased during several measurements. As compared to the norm, hematocrit increased or decreased. After exposure, there was a single episode of a decrease of erythrocyte count and hemoglobin, hematocrit, an increase of MCV and basophil count, and three episodes of monocytosis. These blood changes during 370-day head-down tilt should be viewed as a result of a combined effect of adverse factors accompanying hypokinesia, particularly reduced infection resistance.

Although image data are almost universally acquired on rectangular sampling lattices, the regular hexagonal lattice offers important theoretical advantages for tessellation of images, particularly when subsequent processing involves operations on local image neighborhoods. The few systems capable of processing hexagonally tessellated images have approximated this tessellation by using image data acquired on a rectangular sampling lattice, from which six of the eight image samples were selected from each local neighborhood. This paper describes a simple method of directly acquiring image data in hexagonal image tessellations; the method is used to compare at constant sampling density the most common of these approximating image tessellations with both a nonregular and a regular hexagonal image tessellation. The test objects were human blood cells, from which features describing cellular geometry were extracted for each image tessellation. Compared to the approximating tessellation, the nonregular tessellation tended to decrease feature means and increase feature variances. In contrast, the regular tessellation tended to increase feature means and decrease feature variances. Consequently, the extracted features showed subtle but consistent differences, with decreasing anisotropic effects and data dispersion for the regular tessellation. In addition, cells contacting others near the 45 degree diagonals were more readily segmented when the image was tessellated on the regular lattice. Expected to be general, these trends recommend use of the regular tessellation, especially when classification accuracy may depend on small differences in several similar geometric features.

The enzyme thymidine phosphorylase (TP) is important for activation of capecitabine and 5-fluorouracil. Assessment of TP phenotype might be suitable for identification of patients at risk of fluoropyrimidine-induced toxicity. In this paper, we describe the development and validation an assay for TP activity in peripheral blood mononuclear cells (PBMCs). The assay was based on ex vivo conversion of the TP substrate thymidine to thymine. The amount of thymine formed was determined by high-performance liquid chromatography - ultraviolet detection (HPLC-UV) with 5-bromouracil as internal standard. Lymphocytes and monocytes were purified from isolated PBMCs to examine cell-specific TP activity. TP activity in PBMCs demonstrated Michaelis-Menten kinetics. The lower limit of quantification was 2.3 µg PBMC protein and assay linearity was demonstrated up to 22.7 µg PBMC protein. Within-day and between-day precisions were ≤9.2% and ≤6.0%, respectively. Adequate stability TP activity was demonstrated after long-term storage of PBMC dry pellets and lysates at −80 °C. In monocytes, TP activity was approximately 3 times higher than in lymphocytes. Clinical applicability was demonstrated in samples that were collected from five cancer patients. A simple, precise and sensitive HPLC-UV assay for quantification of TP activity in PBMCs was developed that can be applied for clinical research. [ABSTRACT FROM AUTHOR]

Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p<0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p<0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug. [ABSTRACT FROM AUTHOR]

This paper analysed Sickle cell anaemia literature on Nigeria listed in PubMed to understand the research performance of medical researchers on sickle cell anaemia literature on Nigeria. Data covering the period of 2006-2016 were collected from the PubMed, a citation database developed by the National Centre for Biotechnology Information (NCBI).The search strategy used was ((sickle cell anaemia) OR (sickle cell anemia)) AND Nigeria AND (("2006/01/01"[PDat] : "2016/12/31"[PDat])), bearing in mind variance in spelling (anaemia and anemia), which retrieved 326 sickle cell literature on Nigeria between 2006 and 2016. Article productivity increased between 2006 and 2010. However, there was a drastic drop in article publication between 2010 and 2011 as well as between 2013 and 2015. The degree of collaboration ranged between 0.85 and 1. University of Nigeria Teaching Hospital, Enugu, Nigeria, had the highest number of contributing authors. Authors published more in journals located in Nigeria, with Nigeria Journal of Clinical Practice being the most prolific publication outlet for authors publishing sickle cell anaemia literature on Nigeria. [ABSTRACT FROM AUTHOR]