Blood Aggregation Research Articles

\u03b2-Dispersion of blood during sedimentation

Aggregation of human red blood cells (RBC) is central to various pathological conditions from bacterial infections to cancer. When left at low shear conditions or at hemostasis, RBCs form aggregates, which resemble stacks of coins, known as ‘rouleaux’. We experimentally examined the interfacial dielectric dispersion of aggregating RBCs. Hetastarch, an RBC aggregation agent, is used to mimic conditions leading to aggregation. Hetastrach concentration is incrementally increased in blood from healthy donors to measure the sensitivity of the technique. Time lapse electrical impedance measurements were conducted as red blood cells form rouleaux and sediment in a PDMS chamber. Theoretical modeling was used for obtaining complex permittivity of an effective single red blood cell aggregate at various concentrations of hetastarch. Time response of red blood cells’ impedance was also studied to parametrize the time evolution of impedance data. Single aggregate permittivity at the onset of aggregation, evolution of interfacial dispersion parameters, and sedimentation kinetics allowed us to distinguish differential aggregation in blood.

Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood.

Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets with C. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected with C. albicans and thereby demonstrate limitations in the translatability of this ex vivo model between hosts.

ИССЛЕДОВАНИЕ ПЛАЗМЕННОГО КОМПОНЕНТА СИСТЕМЫ РЕГУЛЯЦИИ АГРЕГАТНОГО СОСТОЯНИЯ КРОВИ У ИСПЫТАТУЕМЫХ В ЭКСПЕРИМЕНТЕ СО 120-СУТОЧНОЙ ИЗОЛЯЦИЕЙ В ГЕРМООБЪЕМЕ SIRIUS-19

Citrate plasma samples gathered 31 days prior to, on days 37, 63, 120 in and on days 7 and 14 after isolation (project Sirius-19) were analyzed for blood aggregation parameters including fibrinogen (FBG), D-dimer (DD), plasminogen (PG), antithrombin III (АТ3), protein C (PC) and α2-antiplasmin (AP), thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT). DD was lowered in all samples gathered during isolation. The complex of isolation factors combined with physical exercise reduced levels of fibrin formation and fibrinolysis. However, after isolation the procoagulent activity showed an increase manifested by elevated DD and reduced APTT. Appears that in the absence of insertion and reentry effects (redistribution of body fluids in microgravity) and high psychophysiological stresses it is the appropriate use of physical countermeasures that ensures plasma efficiency within the blood aggregation control system, and good body tolerance of the spaceflight factors.

The unfavorable role of titanium particles released from dental implants.

Titanium is considered to be a metal material with the best biological safety. Studies have proved that the titanium implanted in the bone continuously releases titanium particles (Ti particles), significantly increasing the total titanium content in human body. Generally, Ti particles are released slowly without causing a systemic immune response. However, the continuous increased local concentration may result in damage to the intraepithelial homeostasis, aggravation of inflammatory reaction in the surrounding tissues, bone resorption and implant detachment. They also migrate with blood flow and aggregate in the distal organ. The release of Ti particles is affected by the score of the implant surface structure, microenvironment wear and corrosion, medical operation wear, and so on, but the specific mechanism is not clear. Thus, it difficult to prevent the release completely. This paper reviews the causes of the Ti particles formation, the damage to the surrounding tissue, and its mechanism, in particular, methods for reducing the release and toxicity of the Ti particles.

Антикоагулянтное ведение беременных с коронавирусной инфекцией

Введение. Частота распространения новой коронавирусной инфекции COVID-19 (НКИ COVID-19) среди беременных сравнима с общепопуляционными показателями, что требует особого внимания в связи с повышенным риском материнской смертности в результате осложнений инфекционного процесса. Учитывая наличие гиперкоагуляционного статуса во время физиологически протекающей беременности, инфицирование вирусом COVID-19 может способствовать еще большему усилению прокоагулянтных свой ств крови. Патогенетически обоснованным является применение антикоагулянтной терапии во время беременности при условии верифицированной коронавирусной инфекции с целью снижения риска развития тромботических осложнений. Материалы и методы. Представлены 2 клинических случая успешного применения антикоагулянтов (низкомолекулярного гепарина) у беременных с подтвержденным инфицированием COVID-19. Результаты. Ретроспективный анализ лабораторных и клинических данных продемонстрировал эффективность парнапарина натрия в качестве средства профилактики тромботических осложнений у беременных с НКИ COVID-19. Заключение. Применение антикоагулянтной терапии у беременных с НКИ COVID-19 позволяет снизить риск развития тромботических эпизодов и улучшить репродуктивные исходы беременности. Background. The COVID-19 frequency among pregnant women is comparable to general population but it requires specific approach due to increased risk of maternal mortality as a result of infectious complications. The hypercoagulation is during physiological pregnancy, and COVID-19 can enhance further a procoagulant conditions. In such cases the anticoagulant therapy is aimed to reduce the thrombotic risk. Patients / Methods. The article presents 2 clinical cases of successful use of anticoagulants (low molecular weight heparin) in pregnant women with confirmed COVID-19. Results. A retrospective analysis of laboratory and clinical data has demonstrated the effi cacy of parnaparin sodium as a means of preventing thrombotic complications in pregnant women with COVID-19. Conclusions. Anticoagulant therapy in pregnant women with COVID-19 allows to reduce the thrombotic risk and improve the reproductive outcomes of pregnancy.

Характеристика микробиоты и цитокинового профиля спермоплазмы у больных хроническим бактериальным простатитом

BACKGROUND One of the leading causes of the occurrence of chronic bacterial prostatitis (CBP) in men is infection, microecological disorders of the urogenital tract and cytokine-mediated mechanisms of inflammation of the prostate gland, which actualizes a comprehensive study of the clinical and bacteriological features of CBP from the perspective of a symbiotic approach in the framework of a new scientific field - infectious symbiology. OBJECTIVE to study the characteristics of spermogram, microbiota, and the cytokine profile in men with chronic bacterial prostatitis (CBP) and CBP complicated by infertility. MATERIALS AND METHODS A comprehensive study of patients with CBP and CBP complicated by infertility, in comparison with conditionally healthy individuals, was conducted. Species identification of microorganisms was carried out according to biochemical characteristics and the genetic method (sequencing of strains). The biological properties of the microbiota were evaluated: growth properties, biofilm formation, antipeptide activity against the cytokines IL-10, RAIL-1, TNF-, INF- and IL-17 (8 parameters). Immunological parameters of sperm plasma included 13 parameters: the content of cytokines TNF-, INF-, Rail, interleukins (IL) -1, 2, 4, 6, 8, 10, 17, immunoglobulin (Ig) A, lactoferrin and lysozyme. To evaluate sperm plasma, the following quantities were determined: ejaculate volume, pH, sperm plasma liquefaction, total sperm count, sperm count per 1 ml, motility, number of progressively motile, non-progressive motile and motionless spermatozoa, number of round cells, white blood cells, spermatogenesis cells, erythrocytes, erythrocytes, cells, sperm agglutination and aggregation (16 parameters in total). The results are statistically processed. RESULTS Data were obtained on changes in biofilm formation, antipeptide activity of microbiota (especially pronounced in corynebacteria), sperm plasma cytokine profile (increased TNF , IL-2, 6, 17), as well as IgA and lactoferrin, which can be used to build a prognostic model of reproductive pathology tract of men and their fertile activity. CONCLUSION The study of the antipeptide activity of microbiota in combination with the cytokine profile of ejaculate allows us to recommend them as a biotarget for diagnostic, preventive and therapeutic measures for chronic prostatitis in men, which contribute to solving the medical and social problem of preventing male infertility and contributes to the development of health-saving technologies with incorporating elements of personalized medicine.

Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies.

BackgroundThe pathogenesis of arterial and venous thrombosis is in large part interlaced. How much platelet phenotype relates to acute venous thromboembolism (VTE) independent of the underlying cardiovascular profile is presently poorly investigated.MethodsPlatelet count and mean platelet volume (MPV), platelet aggregation in whole blood and platelet rich plasma (PRP), platelet-dependent thrombin generation (TG) and platelet surface activation markers were measured under standardized conditions. Machine learning was applied to identify the most relevant characteristics associated with VTE from a large array (N = 58) of clinical and platelet-related variables.FindingsVTE cases (N = 159) presented with lower platelet count and MPV vs controls (N = 140). Whole blood aggregation showed shorter collagen/Epinephrine closure times in cases, particularly within acetylsalicylic acid (ASA) users. Within ASA users, higher PRP aggregation after adenosine diphosphate (ADP), epinephrine, collagen and arachidonic acid was observed in cases vs controls. Within non-ASA and/or subjects on anticoagulants, cases presented with lower aggregation after ADP and collagen vs controls. Lower platelet-dependent TG, higher CD63 on resting and lower PAC-1 expression after collagen/ADP in-vitro stimulated platelets further characterized VTE cases vs controls, independent of therapy. Lasso regression analysis identified 26 variables associated with VTE of which 69% were platelet-related.InterpretationComprehensive phenotyping of platelet function identified a large proportion of low responders to ASA in VTE cases. Lower platelet-dependent TG and lower platelet reactivity after ex-vivo stimulation characterized the “platelet exhausted syndrome” in cases. Finally, from a large array of covariates including clinical risk factors, platelet biomarkers comprised 69% of all selected variables differentiating VTE cases vs controls.FundingGerman Federal Ministry of Education and Research, CTH-Mainz and Bayer AG.

A case study of poly (aryl ether sulfone) hemodialysis membrane interactions with human blood: Molecular dynamics simulation and experimental analyses

Patients with end-stage renal diseases (ESRD) require specific health cares as the accumulation of toxins due to the lack of kidney functionality would affect their lives. However, the mortality rate is still high due to cardiovascular diseases, socks, etc. A majority of patients with chronic kidney disease (CKD) require hemodialysis services. Blood purifying membranes, as the main component of hemodialysis setups, however, still suffer from lack of optimum biocompatibility, which results in morbidity and mortality of hemodialysis service receiving patients. The goal of the present case study is to have an in-depth understanding of the current blood-hemodialysis membrane interactions occurring during hemodialysis sessions using poly (aryl ether sulfone)-poly (vinyl pyrrolidone) (PAES-PVP) membrane. Attenuated total reflectance-Fourier transmission infrared (ATR-FTIR) spectroscopy, Raman spectroscopy, and solid-state nuclear magnetic resonance (SSNMR) spectroscopy were used to assess the initial chemical structure of the PAES-PVP membrane along with the variations after with the infections with human blood. Furthermore, scanning electron microscopy (SEM) and Transition electron microscopy (TEM) were used to visualize the structural variation of the membrane, blood aggregations, and blood clots on the membrane surface. Besides, Molecular dynamics (MD) simulation was used to assess the interaction of PAES-PVP with major human blood proteins, in terms of interaction energy, which is a novel contribution to the area. The macromolecules (human serum albumin (HSA), human serum transferrin (TRF), and human fibrinogen (HFG)) were chosen from the plasma protein component. These protein structures were chosen based on their different molecular size. Three advanced spectroscopy techniques and two advanced visualization techniques were used for the assessment of the membranes. Spectroscopy studies revealed amine related peak displacement and intensity shifts as indices for attachment of biological species to the polymeric membrane surfaces. Raman peaks around 370, 798, and 1299 cm−1, which experienced significant shifts that were related to carbon-nitrogen and sulfur-oxygen bonds due to protein adhesion. Visualization techniques illustrated blood protein fouling patterns and extracellular vesicles’ presence in the pore structures into membranes. The findings highlight the importance of whole structure biocompatibility improvement, rather than only focusing on surface modifications of hemodialysis membranes. Molecular dynamics simulation assessment showed various interaction behaviors for different proteins suggesting molecular weight and active residues of the protein macromolecules play an important role in interacting with polymeric structure. FB had the highest interaction (4,274,749.07 kcal/mol) and binding (10,370.90 kcal/mol) energy with the PAES-PVP structure. TRF owned the lowest interaction energy with respect to its lower molecular weight and fewer active residue count.

The Basic Concepts of the Effect of Rhesus (Rh) Factor on Fetus: A Mini Review

We often hear about cases of incompatibility of the blood of newly married couples, where it results in fears of fetal blood breakdown and others. The same problem generates by transferring blood from a donor to a recipient. This mini-review discusses this problem, outlines the possible reasons for blood aggregation and its negative effects and gives tips to avoid this problem in the future.

What determines blood viscosity at the highest city in the world?

What determines blood viscosity at the highest city in the world?

Effect of differently coated silver nanoparticles on hemostasis

With the emergence of nano-enabled medical devices (MDs) for the use in human medicine, ensuring their safety becomes of crucial importance. Hemocompatibility is one of the major criteria for approval of all MDs in contact with blood (e.g. vascular grafts, stents, or valves). Silver nanoparticles (AgNPs) are among the most used nanomaterials for MDs due to their biocidal activity; however, detailed knowledge on their hemostatic effects is still lacking. This study aimed to evaluate comprehensively AgNPs effects on hemostasis in human blood by exploiting combination of affordable and clinically relevant techniques. Differently stabilized AgNPs were prepared using sodium bis(2-ethylhexyl)sulphosuccinate (AOT), polyvinylpyrrolidone (PVP), poly-L-lysine (PLL), and bovine serum albumin (BSA) as coating agents. They were tested for hemolytic activity, induction of platelet aggregation, plasmatic coagulation, thrombin generation, and hemostasis in whole blood. All AgNPs were found to cause dose-dependent hemolysis. The BSA-, AOT-, and PVP-coated AgNPs delayed plasmatic coagulation, while only PLL-AgNPs inhibited plasmatic coagulation, induced platelet activation, and interfered with hemostasis by delaying clotting time and decreasing clot firmness in whole blood. Obtained results demonstrate that a combination of different techniques should be used for reliable assessment of AgNPs hemostatic effects highlighting the need for a standardized approach in sampling and experimental protocols.

Platelet count and function in umbilical cord blood versus peripheral blood in term neonates

Platelet function in neonates is sparsely investigated. The majority of previous studies investigated platelets in umbilical cord (UC) blood rather than in peripheral blood. We included 20 term neonates and sampled UC blood and peripheral blood within 20 min and 24 h after birth. Platelet count and mean platelet volume (MPV) were measured. Platelet surface glycoproteins (GP) and platelet activation (bound fibrinogen, CD63 and p-selectin) after agonist stimulation were examined by flow cytometry. Platelet aggregation was evaluated by impedance aggregometry. The significance level was set after Bonferroni correction. Platelet count and MPV did not differ between UC and peripheral blood (p-values >0.08). Expression of platelet surface GP was similar in UC and peripheral blood (all p-values >0.02). Platelet activation was lower in UC blood than in peripheral blood for bound fibrinogen (four out of eight p-values <0.001) but did not differ for CD63 (all p-values >0.01) or P-selectin (all p-values >0.01). Platelet aggregation was significantly higher in UC than in peripheral blood (p-values <0.001). In conclusion, platelet count, MPV and expression of platelet surface GP measured in term neonatal UC blood represented that of peripheral blood. Platelet activation and aggregation in UC blood did not reflect that of peripheral blood.

Haem oxygenase protects against thrombocytopaenia and malaria-associated lung injury

BackgroundMalaria-triggered lung injury can occur in both severe and non-severe cases. Platelets may interact with parasitized erythrocytes, leukocytes and endothelium. These interactions can lead to microvessel obstructions and induce release of inflammatory mediators. Induction of the haem oxygenase enzyme is important in the host’s response to free haem and to several other molecules generated by infectious or non-infectious diseases. In addition, an important role for the haem oxygenase-1 isotype has been demonstrated in experimental cerebral malaria and in clinical cases. Therefore, the present work aims to determine the influence of haem oxygenase in thrombocytopaenia and acute pulmonary injury during infection with Plasmodium berghei strain NK65.MethodsC57BL/6 mice were infected with P. berghei and analysed 7-10 days post-infection. For each experiment, Cobalt Protoporphyrin IX/CoPPIX or saline were administered. Bronchoalveolar lavage fluid was used for total and differential leukocyte count and for protein measurement. Lungs were used for histological analyses or for analysis of cytokines and western blotting. The lung permeability was analysed by Evans blue dye concentration. Platelet-leukocyte aggregate formation was assayed using the flow cytometer.ResultsPlasmodium berghei NK65 infection generated an intense lung injury, with increased levels of inflammatory mediators, oedema, and cell migration into the lung. Plasmodium berghei infection was also accompanied by marked thrombocytopaenia and formation of platelet-leukocyte aggregates in peripheral blood. Treatment with the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) modified the inflammatory response but did not affect the evolution of parasitaemia. Animals treated with CoPPIX showed an improvement in lung injury, with decreased inflammatory infiltrate in the lung parenchyma, oedema and reduced thrombocytopaenia.ConclusionData here presented suggest that treatment with CoPPIX inducer leads to less severe pulmonary lung injury and thrombocytopaenia during malaria infection, thus increasing animal survival.

Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia

BackgroundAntiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet therapies is unclear. We therefore investigated the role of sex differences in platelet reactivity in a cohort of outpatients with chest pain, in response to treatment with antiplatelet agents. MethodsPlatelet reactivity was measured in 382 randomly selected patients participating in the Myocardial Ischemia Detection by Circulating Biomarkers (MYOMARKER) study, an observational cohort study of outpatients suspected of myocardial ischemia. In all patients, blood was collected during diagnostic workup, and platelet reactivity was assessed with a flow cytometry–based platelet activation test that quantifies both platelet degranulation (P‐selectin expression) and platelet aggregation (fibrinogen binding to integrin αIIbβ3) in whole blood. ResultsPlatelet reactivity was higher in women compared with men when activated with protease activating receptor 1–activating peptide SFLLRN (PAR1‐AP) and adenosine 5′‐phosphate (ADP), independent of age, basal activation status, estimated glomerular filtration rate < 60, platelet count, statin use, the use of P2Y12 inhibitors, or the use of aspirin. P2Y12 inhibitor use strongly reduced fibrinogen binding after stimulation with PAR1‐AP, but only slightly reduced platelet P‐selectin expression. Calculation of the relative inhibition in P2Y12 users indicated 62% inhibition of the response toward ADP. Stratified analysis showed that women (n = 14) using P2Y12 inhibitors showed less inhibition of fibrinogen binding after PAR1‐AP stimulation than men (n = 38) using P2Y12 inhibitors. ConclusionsThese findings call for further study of differential effects of P2Y12 inhibitors in women with suspected myocardial ischemia.

Combination of cyclic nucleotide modulators with P2Y12 receptor antagonists as anti‐platelet therapy

BackgroundEndothelium‐derived prostacyclin and nitric oxide elevate platelet cyclic nucleotide levels and maintain quiescence. We previously demonstrated that a synergistic relationship exists between cyclic nucleotides and P2Y12 receptor inhibition. A number of clinically approved drug classes can modulate cyclic nucleotide tone in platelets including activators of NO‐sensitive guanylyl cyclase (GC) and phosphodiesterase (PDE) inhibitors. However, the doses required to inhibit platelets produce numerous side effects including headache. ObjectiveWe investigated using GC‐activators in combination with P2Y12 receptor antagonists as a way to selectively amplify the anti‐thrombotic effect of both drugs. MethodsIn vitro light transmission aggregation and platelet adhesion under flow were performed on washed platelets and platelet rich plasma. Aggregation in whole blood and a ferric chloride‐induced arterial thrombosis model were also performed. ResultsThe GC‐activator BAY‐70 potentiated the action of the P2Y12 receptor inhibitor prasugrel active metabolite in aggregation and adhesion studies and was associated with raised intra‐platelet cyclic nucleotide levels. Furthermore, mice administered sub‐maximal doses of the GC activator cinaciguat together with the PDE inhibitor dipyridamole and prasugrel, showed significant inhibition of ex vivo platelet aggregation and significantly reduced in vivo arterial thrombosis in response to injury without alteration in basal carotid artery blood flow. ConclusionsUsing in vitro, ex vivo, and in vivo functional studies, we show that low dose GC activators synergize with P2Y12 inhibition to produce powerful anti‐platelet effects without altering blood flow. Therefore, modulation of intra‐platelet cyclic nucleotide levels alongside P2Y12 inhibition can provide a strong, focused anti‐thrombotic regimen while minimizing vasodilator side effects.

Sex differences in platelet reactivity in patients with myocardial infarction treated with triple antiplatelet therapy - results from assessing platelet activity in coronary heart disease (APACHE)

)Several earlier studies have reported increased risk of bleeding in women with myocardial infarction, (MI) compared to men. The reasons for the observed difference are incompletely understood, but one suggested explanation has been excess dosing of antithrombotic drugs in women. The aim of this prospective observational study was to assess sex differences in platelet activity in patients treated with three different platelet inhibitors. We recruited 125 patients (37 women and 88 men) with MI, scheduled for coronary angiography. All patients received clopidogrel and aspirin. A subgroup of patients received glycoprotein (GP) IIb/IIIa-inhibitor. Platelet aggregation in whole blood was assessed at several time points, using impedance aggregometry. Soluble P-selectin was measured 3 days after admission. There were no significant differences between women and men in baseline features or comorbidities except higher frequency of diabetes, lower hemoglobin value, and lower estimated glomerular filtration rate, in women on admission. We observed significantly more in-hospital bleeding events in women compared to men (18.9% vs. 6.8%, p = .04). There were no differences in platelet aggregation using three different agonists, reflecting treatment effect of GPIIb/IIIa-inhibitors, clopidogrel, and aspirin, 6–8 hours, 3 days, 7–9 days, or 6 months after loading dose. Moreover, there was no significant difference in soluble P-selectin. The main finding of this study was a consistent lack of difference between the sexes in platelet aggregation, using three different agonists at several time-points. Our results do not support excess dosing of anti-platelet drugs as a major explanation for increased bleeding risk in women.

The effect of adding lactic acid to canine whole blood on platelet aggregation as measured by impedance aggregometry.

Acidemia in sick dogs often results from the accumulation of lactic acid. The resulting decrease in blood pH can have many physiologic effects, including alteration of platelet function. We aimed to evaluate the effect of hyperlactatemia and subsequent acidemia on platelet aggregation in canine blood using impedance aggregometry. Platelet aggregation was measured in blood from 27 healthy dogs using the Multiplate analyzer at baseline and after in vitro addition of two different volumes of lactic acid to adjust the pH. The area under the curve (AUC), reported by the Multiplate analyzer, was used to assess the extent of platelet aggregation in each sample. A linear mixed effects model was used to test for the association between platelet aggregation and pH. The association of baseline platelet aggregation with HCTs, platelet counts, and WBC counts was assessed using Pearson's correlations. Acidemia was associated with a significant decrease in platelet aggregation. No significant correlations were detected between platelet aggregation and HCT, platelet count, or WBC count. Platelet aggregation measured using the Multiplate analyzer showed substantial individual variation. Worsening acidemia due to the addition of lactic acid caused a mild but significant decrease in platelet aggregation in canine blood. The clinical significance of this change is uncertain but could be important when combined with other abnormalities of hemostasis associated with illness.

The Biochemical and Histological Effect of Cadmium Chloride on the Pancreas of Adult Albino Rats and the Possible Protective Effect of Nigella Sativa Seeds

Aim: The current study evaluates the important role of Nigella Sativa against cadmium (Cd) induced toxic changes in pancreasof rats.Materials and Methods: Eighteen adult Wistar albino rats were divided into three equal groups. Control group, cadmiumtreated group that received 5 mg CdCl2/kg BW/day dissolved in water orally for three months, and cadmium with Nigellasativa (NS) group received a mixture of 1g/kg/day of aqueous suspension of Nigella sativa seeds powder and 5 mgCdCl2/kg BW/day dissolved in water for three consecutive months. Hormonal assay of insulin was done. Pancreatic tissueswere prepared for both Hematoxylin and Eosin and toluidine blue. Electron microscopic study of pancreatic tissues was alsodone.Results: The present study showed that the administration of CdCl2 induced evident decrease in insulin serum level. Thebiochemical results were confirmed by histological investigations where degenerative changes of pancreatic acini with lossof normal lobular architecture, distorted pancreatic acini, degenerated and widely separated cells in the islets of Langerhans,blood vessels congestion and aggregation of perivascular cellular infiltrates were detected in pancreatic tissues stained withH&E. Toluidine blue-stained sections showed few deeply stained apical zymogen granules in some acini, whereas other acinishowed absence of these granules.Administration of NS with CdCl2 showed a significant improvement in the measured serum insulin level and histologicalpictures.Conclusion: CdCl2 induced several toxic changes in the exocrine and endocrine parts of pancreas of rats. NS could protect thepancreas against these alterations.

Identification of physicochemical properties that modulate nanoparticle aggregation in blood.

Inorganic materials are receiving significant interest in medicine given their usefulness for therapeutic applications such as targeted drug delivery, active pharmaceutical carriers and medical imaging. However, poor knowledge of the side effects related to their use is an obstacle to clinical translation. For the development of molecular drugs, the concept of safe-by-design has become an efficient pharmaceutical strategy with the aim of reducing costs, which can also accelerate the translation into the market. In the case of materials, the application these approaches is hampered by poor knowledge of how the physical and chemical properties of the material trigger the biological response. Hemocompatibility is a crucial aspect to take into consideration for those materials that are intended for medical applications. The formation of nanoparticle agglomerates can cause severe side effects that may induce occlusion of blood vessels and thrombotic events. Additionally, nanoparticles can interfere with the coagulation cascade causing both pro- and anti-coagulant properties. There is contrasting evidence on how the physicochemical properties of the material modulate these effects. In this work, we developed two sets of tailored carbon and silica nanoparticles with three different diameters in the 100–500 nm range with the purpose of investigating the role of surface curvature and chemistry on platelet aggregation, activation and adhesion. Substantial differences were found in the composition of the protein corona depending on the chemical nature of the nanoparticles, while the surface curvature was found to play a minor role. On the other hand, large carbon nanoparticles (but not small carbon nanoparticles or silica nanoparticles) have a clear tendency to form aggregates both in plasma and blood. This effect was observed both in the presence or absence of platelets and was independent of platelet activation. Overall, the results presented herein suggest the existence of independent modes of action that are differently affected by the physicochemical properties of the materials, potentially leading to vessel occlusion and/or formation of thrombi in vivo.

Platelet Mapping by Thromboelastography and Whole Blood Aggregometry in Adult Patients Supported by Mechanical Circulatory Support Device on Aspirin Therapy

Patients on mechanical circulatory support (MCS) devices are placed on aspirin and may require platelet function testing (PFT) to monitor the adequacy of therapy. Routine laboratory PFT is performed using whole blood aggregation (WBA) which typically has a long turnaround time (4–5 hours) and may not be readily available. By contrast, platelet mapping by thromboelastography (TPM) can provide results within 45 minutes. The objective of this study was to compare the results of TPM with WBA. We compared platelet mapping maximal amplitude (MA) by TPM with that of arachidonic acid (AA) to WBA with AA by impedance. We analyzed paired samples where both TPM and WBA were available. Of 45 paired samples, 34 were from 29 MCS patients and 11 were from non-MCS patients. When applying institutional interpretation guidelines with an MAActivator cutoff of ≤40 mm, WBAAA vs TPM MAAA in non-MCS and MCS patients correlated well with an accuracy of 100 and 94.4%, respectively. MAActivator &gt;40 had poor correlation with an accuracy of 37.5%. Irrespective of MAActivator value, TPM AA inhibition expressed in percent of inhibition had poor accuracy. When used with proper guidelines for interpretation, specifically when MAActivator ≤ 40 mm, TPM is a suitable and reliable test to use for MCS patients on aspirin.