An Overview of Two Old Friends Associated with Platelet Redox Signaling, the Protein Disulfide Isomerase and NADPH Oxidase.

Oxidative stress participates at the baseline of different non-communicable pathologies such as cardiovascular diseases. Excessive formation of reactive oxygen species (ROS), above the signaling levels necessary for the correct function of organelles and cells, may contribute to the non-desired effects of oxidative stress. Platelets play a relevant role in arterial thrombosis, by aggregation triggered by different agonists, where excessive ROS formation induces mitochondrial dysfunction and stimulate platelet activation and aggregation. Platelet is both a source and a target of ROS, thus we aim to analyze both the platelet enzymes responsible for ROS generation and their involvement in intracellular signal transduction pathways. Among the proteins involved in these processes are Protein Disulphide Isomerase (PDI) and NADPH oxidase (NOX) isoforms. By using bioinformatic tools and information from available databases, a complete bioinformatic analysis of the role and interactions of PDI and NOX in platelets, as well as the signal transduction pathways involved in their effects was performed. We focused the study on analyzing whether these proteins collaborate to control platelet function. The data presented in the current manuscript support the role that PDI and NOX play on activation pathways necessary for platelet activation and aggregation, as well as on the platelet signaling imbalance produced by ROS production. Our data could be used to design specific enzyme inhibitors or a dual inhibition for these enzymes with an antiplatelet effect to design promising treatments for diseases involving platelet dysfunction.

Characterization by Gender of Frailty Syndrome in Elderly People according to Frail Trait Scale and Fried Frailty Phenotype.

Background: Frailty has emerged as one of the main geriatric syndromes to be prevented in order to improve quality of health and life in the elderly. In this sense, the characterization of this syndrome through reliable and feasible diagnostic tools for clinical use, such as the Frail Trait Scale 5 (FTS-5) and Frail Trait Scale 3 (FTS-3), represents the basis for this objective. Objectives: To characterize the frailty syndrome in a population of older adults using FTS-5, FTS-3, and Fried phenotype (FP) as frailty diagnostic tools. Design: Cross-sectional study. Participants: 300 adults ≥65 years recruited from different Family Health Centers and community groups of older people in Talca, Chile. Methods: The diagnosis of frailty was made according to FP, FTS-5, and FTS-3 tools. Data about sociodemographic characteristics and anthropometric measurements were collected by a clinical interview by a previously trained health professional. Results: A total prevalence of frailty according to the FP of 19.7% was observed; while in the group of women and men it was 21.4% and 15.0%, respectively. Concerning the FTS-5 tool, the total prevalence of frailty was 18%, while in the group of women and men was 18.0% and 17.5%, respectively. The FTS-3 tool shows a total prevalence of frailty of 23.3%, while in the group of women and men a prevalence of 22.7% and 25.0%, respectively. A significant difference is observed with respect to the presence of the Fried criteria of "weakness" (women: 21.4%, men: 38.8%) and "weight loss" (women: 16.8%, men: 7.5%; p < 0.05). A significant difference is observed concerning the average score of "Handgrip" criteria, "walking time", and "Physical Activity Scale for the Elderly" (PASE) between the group of women and men. Frailty, diagnosed by FTS-3, is significantly associated with the risk factors of overweight (body mass index ≥ 25) (OR: 10.225, 95% CI: 1.297−80.617) and advanced age (age ≥ 75 years) (OR: 1.839, 95% CI: 1.040−3.250). Conclusion: The prevalence of frailty observed with the FTS-5 (18%) and FTS-3 (23.3%) tools are similar to the prevalence observed through the FP (19.7%) and those reported in other observational studies. Considering the similar prevalence of frailty diagnosed with the three tools, FTS-3 should be a valuable tool for the screening of frailty in the community.

The Immune Response to SARS-CoV-2: Mechanisms, Aging, Sequelae, and Vaccines.

This review seeks to clarify the factors involved in the various immune responses to SARSCoV- 2 infection and the mechanisms that influence the development of COVID-19 with severe evolution. The innate immune response that evolves against SARS-CoV-2 in a complex way is highlighted, integrating multiple pathways by coronaviruses to evade it, in addition to characterizing the adaptive immune response, which can lead to an effective immune response or can contribute to immunopathological imbalance. In turn, host-dependent biomarkers, such as age, gender, ABO blood group, and risk factors, that contribute to the critical and varied progress of COVID-19 immunopathogenesis are analyzed. Finally, the potential vaccine candidates are presented, capable of generating immune protection with humoral and/or cellular neutralizing responses, in favor of blocking and destroying both the new human coronavirus and its variants, which cause the current pandemic.

Role of Non-Coding RNA of Human Platelet in Cardiovascular Disease.

Cardiovascular diseases (CVD) are the major cause of death in the world. Numerous genetic studies involving transcriptomic approaches aimed at the detailed understanding of the disease and the development of new therapeutic strategies have been conducted over recent years. There has been an increase in research on platelets, which are implicated in CVD due to their capacity to release regulatory molecules that affect various pathways. Platelets secrete over 500 various kinds of molecules to plasma including large amounts of non-coding (nc) RNA (miRNA, lncRNA or circRNA). These ncRNA correspond to 98% of transcripts that are not translated into proteins as they are important regulators in physiology and disease. Thus, miRNAs can direct protein complexes to mRNAs through base-pairing interactions, thus causing translation blockage or/and transcript degradation. The lncRNAs act via different mechanisms by binding to transcription factors. Finally, circRNAs act as regulators of miRNAs, interfering with their action. Alteration in the repertoire and/or the amount of the platelet-secreted ncRNA can trigger CVD as well as other diseases. NcRNAs can serve as effective biomarkers for the disease or as therapeutic targets due to their disease involvement. In this review, we will focus on the most important ncRNAs that are secreted by platelets (9 miRNA, 9 lncRNA and 5 circRNA), their association with CVD, and the contribution of these ncRNA to CVD risk to better understand the relation between ncRNA of human platelet and CVD.

Non-nutrients and nutrients from Latin American fruits for the prevention of cardiovascular diseases.

Non-communicable diseases (NCDs) have been rapidly increasing; among them, cardiovascular diseases (CVDs) are responsible for around 1/3 of deaths in the world. Environmental factors play a central role in their development. Diet is a very important factor in this scenario, and the intake of fruits and vegetables has been considered as one of the critical strategies for reducing the risk of CVDs. Fruits are a source of micronutrients and bioactive compounds that could have cardioprotective effects through several distinct mechanisms, such as antioxidant, antithrombotic and antiplatelet activities, vasodilatation, improvement of plasma lipid profiles, and modulation of inflammatory signaling. Brazil has a very rich and unexplored biodiversity in its different biomes, with several types of fruit, which are a source of bioactive compounds and micronutrients with therapeutic properties. In this sense, this review shows the current knowledge regarding the cardioprotective properties of selected Latin American and Brazilian fruits, including their effects on the activation of platelets and on the inflammation processes involved in atherosclerosis and cardiovascular diseases.

Mitoquinone (MitoQ) Inhibits Platelet Activation Steps by Reducing ROS Levels.

Platelet activation plays a key role in cardiovascular diseases. The generation of mitochondrial reactive oxygen species (ROS) has been described as a critical step required for platelet activation. For this reason, it is necessary to find new molecules with antiplatelet activity and identify their mechanisms of action. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces mitochondrial overproduction of ROS. In this work, the antiplatelet effect of MitoQ through platelet adhesion and spreading, secretion, and aggregation was evaluated. Thus MitoQ, in a non-toxic effect, decreased platelet adhesion and spreading on collagen surface, and expression of P-selectin and CD63, and inhibited platelet aggregation induced by collagen, convulxin, thrombin receptor activator peptide-6 (TRAP-6), and phorbol 12-myristate 13-acetate (PMA). As an antiplatelet mechanism, we showed that MitoQ produced mitochondrial depolarization and decreased ATP secretion. Additionally, in platelets stimulated with antimycin A and collagen MitoQ significantly decreased ROS production. Our findings showed, for the first time, an antiplatelet effect of MitoQ that is probably associated with its mitochondrial antioxidant effect.

Polypharmacy Is Associated with Frailty, Nutritional Risk and Chronic Disease in Chilean Older Adults: Remarks from PIEI-ES Study.

AIM: To analyze the relationship between polypharmacy and variables as frailty and other chronic comorbidities in Chilean older adults. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand two hundred and five older adults aged 65 and older. METHODS: The presence or absence of frailty syndrome was determined according to Fried criteria. Data collection was made through questionnaires conducted by an interview. RESULTS: The prevalence of polypharmacy was 37.59%. The prevalence of hyperpolypharmacy was 2%. Increased prevalence of frailty was demonstrated regarding the progression of the state of polypharmacy. When analyzing the contribution of frailty respect polypharmacy condition, frail state, nutritional risk and obesity are founded as a factor associated with polypharmacy. Regarding chronic disease, hypertension (OR: 8.039, p<0.0001), type 2 diabetes (OR: 4.001, p<0.0001) and respiratory diseases (OR: 2.930, p<0.0001) were associated to polypharmacy. It was found a strong and significant positive correlation between polypharmacy prevalence and frailty score (polypharmacy condition, Spearman R: 0.89, p=0.033; hyperpolypharmacy condition, Spearman R: 0.94, p=0.016). When analyzing the contribution of the polypharmacy to the presence of frailty, polypharmacy condition (OR: 1.510, p<0.05), cognitive impairment (OR: 3.887, p<0.001), obesity (OR: 1.560, p<0.01) and nutritional risk (OR: 2.590, p<0.001) are associated to frailty. CONCLUSION: Frailty and chronic conditions as nutritional risk, obesity, hypertension, type 2 diabetes and respiratory disease are an important risk factor for the development of polypharmacy in Chilean older adults. Likewise, polypharmacy condition was observed to be a risk factor for frailty, demonstrating the bidirectional relationship between both conditions. Frailty syndrome evaluation in Chilean older adults could be an important alternative for polypharmacy prevention.

Synthesis of antiplatelet ortho-carbonyl hydroquinones with differential action on platelet aggregation stimulated by collagen or TRAP-6.

Cardiovascular diseases are the leading cause of death in the world. Platelets have a major role in cardiovascular events as they bind to the damaged endothelium activating and forming thrombi. Although some hydroquinone scaffold-containing compounds have known antiplatelet activities, currently there is a lack of evidence on the antiplatelet activity of hydroquinones carrying electron attractor groups. In this work, we evaluate the antiplatelet effect of a series of ortho-carbonyl hydroquinone derivatives on cytotoxicity and function of human platelets, using collagen and thrombin receptor activator peptide 6 (TRAP-6) as agonists. Our structure-activity relationship study shows that gem-diethyl/methyl substitutions and the addition/modifications of the third ring of ortho-carbonyl hydroquinone scaffold influence on the selective index (IC50 TRAP-6/IC50 Collagen) and the inhibitory capacity of platelet aggregation. Compounds 3 and 8 inhibit agonist-induced platelet aggregation in a non-competitive manner with IC50 values of 1.77 ± 2.09 µM (collagen) and 11.88 ± 4.59 µM (TRAP-6), respectively and show no cytotoxicity. Both compounds do not affect intracellular calcium levels and mitochondrial bioenergetics. Consistently, they reduce the expression of P-selectin, activation of glycoprotein IIb/IIIa, and release of adenosine triphosphate and CD63 from platelet. Our findings may be used for further development of new drugs in platelet-related thrombosis diseases.

In Vitro Assay of Quinoa (Chenopodium quinoa Willd.) and Lupin (Lupinus spp.) Extracts on Human Platelet Aggregation.

Cardiovascular disease (CVD) is the leading cause of death throughout the world. A major risk factor for CVD is platelet aggregation. Various plant extracts exhibit anti-aggregatory action in vitro. The dietary intake of traditional plant crops such as quinoa (Chenopodium quinoa Willd) and lupin (Lupinus spp., Fabaceae family), highly recognized for their high nutritional value, is increasing worldwide. The aim of the study was to assay possible antiplatelet effects of quinoa and lupin bean extracts in vitro. The proximate chemical composition of quinoa grains and the three most widely known lupin cultivars: blue (L. angustifolius), yellow (L. luteus or mutabilis) and white (L. albus) grown in Chile were analyzed. The anti-aggregation activity of the ethanol extracts of the crops was assayed using flow cytometry in ADP-stimulated human platelets, and their inhibition of the maximal platelet aggregation was measured. All the lupin extracts exhibited a significant anti-aggregatory effect (p < 0.0001), while quinoa extracts did not exert this effect compared to control platelets. In conclusion, lupin beans extracts exhibited an anti-aggregatory effect on activated human platelets.

Older adults with frailty syndrome present an altered platelet function and an increased level of circulating oxidative stress and mitochondrial dysfunction biomarker GDF-15.

INTRODUCTION: The elderly population is increasing worldwide and in Chile, it is expected to grow rapidly. The World Health Organization (WHO) ICOPE guideline (Integrated Care for Older People) emphasizes the importance of frailty diagnosis to prevent dependence. Frailty in older adults is considered an indicator of vulnerability and poor health outcomes, of multifactorial etiology. Our objective was to investigate the association of activation of coagulation and increased risk of thrombosis with frailty in people older than 64 years. A prevalent-case control study was designed with 28 frail older and 27 robust older adults (non-frail, control group) older than 64 years. Frailty was defined by Fried's Phenotype, Platelet aggregation and activation plasma levels of Thromboxane B2 (TXB2), 8-isoprostane and Growth Differentiation Factor-15 (GDF-15) were determined. RESULTS: Compared to healthy controls, frail older adults, had a) higher percentage of platelet aggregation induction with ADP 4 µM (82.85% (3.35) and 73.41% (3.26), p-value = 0.024) and subaggregant dose of ADP (30.83% (7.47) and 13.25% (3.21), p-value = 0.002); b) higher platelet activation: P-selectin exposure (18.23% (4.41) and 6.96% (1.08), p-value = 0.011), and activated GPIIß-IIIα (21.51% (3.41) and 8.26% (1.18), p-value = 0.001), at the baseline level and against a subaggregant dose ADP: P-selectin exposure (46.93% (5.95) and 13.41% (3.35), p-value = 0.002) and activated GPIIß-IIIα (43.29% (6.04) and 26.71% (4.92), p-value = 0.024); c) higher plasma levels of TXB2 (201.8 ng/mL (59.53-236.3) and 45.77 ng/mL (25.14-98.26), p-value<0.0001), d) elevated plasma levels of 8-isoprostane (70.94 pg/mL, IQ: 65.89-99,96 and 56.24 pg/mL, IQ: 42.18-74.81, p-value = 0.001), and e) higher plasma GDF-15 levels (2,379 pg/mL, IQ: 1,845-4,121and 1367 pg/mL, IQ: 1190-1747, p-value = 0.0001). DISCUSSION: Older adults with frailty syndrome have an upregulated platelet activity that may contribute to an increased risk of thrombosis and aspirin resistance. The elevated oxidative stress and increases of GDF-15 levels might be related to altered platelet responsiveness in frail patients. CONCLUSION: The determination of biomarkers of platelet dysfunction, oxidative stress and cell senescence/mitochondrial dysfunction may contribute to frailty diagnosis, and approaches aimed at regulating platelet function in frail older adults could contribute to its prevention and treatment.

Natural Bioactive Compounds As Protectors Of Mitochondrial Dysfunction In Cardiovascular Diseases And Aging.

Diet, particularly the Mediterranean diet, has been considered as a protective factor against the development of cardiovascular diseases, the main cause of death in the world. Aging is one of the major risk factors for cardiovascular diseases, which have an oxidative pathophysiological component, being the mitochondria one of the key organelles in the regulation of oxidative stress. Certain natural bioactive compounds have the ability to regulate oxidative phosphorylation, the production of reactive oxygen species and the expression of mitochondrial proteins; but their efficacy within the mitochondrial physiopathology of cardiovascular diseases has not been clarified yet. The following review has the purpose of evaluating several natural compounds with evidence of mitochondrial effect in cardiovascular disease models, ascertaining the main cellular mechanisms and their potential use as functional foods for prevention of cardiovascular disease and healthy aging.

Increased platelet function during frailty.

Frailty is highly associated with cardiovascular diseases (CVD) and diabetes mellitus (DM). Aging, CVD, and DM are all associated with an increase in platelet function. Therefore, the aim of this study was to evaluate platelet function during frailty. We selected a total of 37 older adults who were divided into two groups, frail (n = 16) and robust (n = 21), with a mean age of 72.4 ± 4.4 years (range: 65-84 years) in robust adults and 72.6 ± 6.6 years (range: 65-88 years) in frail adults; 20 young healthy volunteers, with a mean age of 22.9 ± 2.7 years (range: 20-30 years), were included as a control platelet function was determined using the lumi-aggregometer (aggregation) and flow cytometry (platelet activation). We also performed Western blot to evaluate the intraplatelet activation pathways involved in activation. Platelet count decreased and mean platelet volume, aggregation, and P-selectin expression increased during aging compared with young adults was found. We observed an increase in P-selectin expression in frail adults compared with robust adults. We also evaluated the characteristics of the study population to explain this difference and found a higher prevalence of DM and a tendency toward hyperglycemia in frail adults compared with robust adults. In agreement with this, high doses of glucose were able to increase platelet aggregation and P-selectin expression through thrombin receptors and p38 phosphorylation.

Decoding the Role of Platelets and Related MicroRNAs in Aging and Neurodegenerative Disorders.

Platelets are anucleate cells that circulate in blood and are essential components of the hemostatic system. During aging, platelet numbers decrease and their aggregation capacity is reduced. Platelet dysfunctions associated with aging can be linked to molecular alterations affecting several cellular systems that include cytoskeleton rearrangements, signal transduction, vesicular trafficking, and protein degradation. Age platelets may adopt a phenotype characterized by robust secretion of extracellular vesicles that could in turn account for about 70-90% of blood circulating vesicles. Interestingly these extracellular vesicles are loaded with messenger RNAs and microRNAs that may have a profound impact on protein physiology at the systems level. Age platelet dysfunction is also associated with accumulation of reactive oxygen species. Thereby understanding the mechanisms of aging in platelets as well as their age-dependent dysfunctions may be of interest when evaluating the contribution of aging to the onset of age-dependent pathologies, such as those affecting the nervous system. In this review we summarize the findings that link platelet dysfunctions to neurodegenerative diseases including Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, Huntington's Disease, and Amyotrophic Lateral Sclerosis. We discuss the role of platelets as drivers of protein dysfunctions observed in these pathologies, their association with aging and the potential clinical significance of platelets, and related miRNAs, as peripheral biomarkers for diagnosis and prognosis of neurodegenerative diseases.

Methodology of generation and purification of anti-beta 2 glycoprotein I antibodies.

In this Method Article we are showing the methodology for generation and purification of Anti-Beta 2 Glycoprotein I (ß2GPI) antibodies. First ß2GPI was purified from human plasma, and recognized by Western Blot and anti-ß2GPI antibodies of serum from patients with antiphospholipid syndrome (APS). The C57BL/6 mice were immunized intraperitonealy with 150 µg of protein in adjuvant (ß2GPI or bovine serum albumin) on days 1, 8 and 14. Then the anti-ß2GPI antibodies were purified by affinity chromatography (Affi-Gel protein A sepharose) and affinity column using human ß2GPI coupled to CNBr-activated Sepharose 4B. Titles of anti-ß2GPI antibodies were determined by ELISA assays. •We purified ß2GPI with great efficacy and that is recognized antigenically by serum from patients with SAP or an anti-ß2gpi antibody.•We found that our purified antibody had 13 fold increased activity in ELISA test compared with the control and in Western Blot recognized with ß2GPI (reference and purified).

Roles of Phenolic Compounds in the Reduction of Risk Factors of Cardiovascular Diseases.

The population is now living longer during the period classified as "elderly" (60 years and older), exhibiting multimorbidity associated to the lengthening of the average life span. The dietary intake of phenolic compounds (PC) may affect the physiology, disease development and progression during the aging process, reducing risk factors of age related diseases. The aim of this review is to briefly describe some of the possible effects of a series of PC on the reduction of risk factors of the onset of cardiovascular diseases, considering their potential mechanisms of action. The main actions described for PC are associated with reduced platelet activity, anti-inflammatory effects, and the protection from oxidation to reduce LDL and the generation of advanced glycation end products. Preclinical and clinical evidence of the physiological effects of various PC is presented, as well as the health claims approved by regulatory agencies.

Analysis of the characteristics and components for the frailty syndrome in older adults from central Chile. The PIEI-ES study.

OBJECTIVE: To determine the prevalence and to characterize frailty in elderly subjects in four urban provincial capitals and two rural communes from Maule Region in Chile. DESIGN: Cross-sectional study. PARTICIPANTS: 1205 participants aged 65 and older. METHODS: The dataset was obtained from the PIEI-ES Study. Frailty syndrome was determined according to the criteria proposed by Fried. Data collection included questionnaires. RESULTS: The study sample included 1205 individuals, of which 68% were females. Mean age was 73 years. The overall prevalence of frailty was 24.6%. Increase prevalence of frailty was observed in people 80 years old and older, both in women and men. Using adjusted logistic regression, advanced frailty state was more likely to occur in subjects with cognitive impairment. CONCLUSION: This study provides evidence that frailty may be related with cognitive functioning, educational level and nutritional status in older adults.

Buddleja globosa (matico) prevents collagen-induced platelet activation by decreasing phospholipase C-gamma 2 and protein kinase C phosphorylation signaling.

Platelets play a key role in thrombosis and cardiovascular diseases. Medicinal plants could be one of the most important factors that influence risks for platelet activation. Buddleja globosa (known as "matico") is a medicinal plant with many biological activities. The high content of polyphenols suggest that matico could have antiplatelet activity. The present study was aimed at evaluating mechanisms of antiplatelet action of an extract of matico. We demonstrated that matico extract at low concentrations and in a concentration dependent manner (0.05-1 mg/mL) was a potent inhibitor of platelet aggregation in response to collagen, convulsion and ADP (IC50 values was 61 µg/mL, 72 µg/mL and 290 µg/mL, respectively). In this sense matico extract exerted the greatest antiaggregant activity induced by collagen. Similarly, matico showed a decrease in % of positive platelet for P-selectina (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 32 ± 2%, 29 ± 2 (p < 0.05), 19 ± 1 (p < 0.01), 15 ± 2 (p < 0.01), 10 ± 1% (p < 0.01) and 7 ± 2% (p < 0.01), respectively) and PAC-1 binding (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 59 ± 1, 58 ± 3 (n.s), 55 ± 2 (p < 0.05), 50 ± 2 (p < 0.01), 38 ± 1 (p < 0.01), 36 ± 2 (p < 0.01). The cellular mechanism for the antiplatelet activity of matico might be mediated by the inhibition of phospholipase C-gamma 2 and protein kinase C phosphorylation. This beneficial property of matico may be of importance in thrombosis, in which platelet activation and aggregation are important determinants of thrombus initiation and development, and may contribute to the beneficial effects of matico intake in the prevention of cardiovascular diseases.

Standardization of a fast and effective method for the generation and detection of platelet-derived microparticles by a flow cytometer.

The Flow Cytometry is the principal method used to measure platelet-derived microparticles (PDMPs), by fluorescent properties analysis. PDMPs (0.1-1.0 µm) are abundant in circulation, accounting for approximately 90% of the microparticles and are associated with Cardiovascular Disease, the leading cause of death in the world.

New insights into the gene expression associated to amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most prevalent neuromuscular disease worldwide. It is a lethal and progressive neurodegenerative disease, principally affecting motor neurons; patient clinical characteristics are muscle weakness, dysphagia and respiratory failure. The mean age is related to family history (40years, familial ALS or FALS) or with no family history (50years), but it is more common in people aged 60-69years. The cause of ALS is not known and it is not known yet why it affects some people and not others. However expert consensus is that molecular alterations in different cells are involved in the development and progression of the disease. For example, motor neuron death is caused by a variety of cellular defects, including the processing of RNA molecules, water channels, and calcium levels, increasing evidence that these alterations of cells in the nervous system play an important role in ALS. Here we will systematically examine different genes (AQP1, SLC14A1, MT1X, DSCR1L1, PCP4, UCHL1, GABRA1, EGR1, OLFM1 and VSNL1) that are "up or down" regulated in the motor cortex and spinal cord and their association with ALS risk. These could be novel biomarkers associated with ALS risk. We built an interaction Network with Cytoscape, this was used to identify pathways, miRNA and drugs associated to ALS. The most important affected pathway is PI3K-Akt signaling. Thirteen microRNAs (miRNA-19B1, miRNA-107, miRNA-124-1, miRNA-124-2, miRNA-9-2, miRNA-29A, miRNA-9-3, miRNA-328, miRNA-19B2, miRNA-29B2, miRNA-124-3, miRNA-15A and miRNA-9-1) and four drugs (Estradiol, Acetaminophen, Progesterone and resveratrol) for new possible treatments were identified.

Síndrome de hiperviscosidad como presentación de la macroglobulinemia de waldenström: Reporte de caso / Waldenström's macroglobulinemia presenting as hyperviscosity syndrome. Case report

La Macroglobulinemia de Waldenström (MW) es una neoplasia hematológica infrecuente, caracterizada por presentar gammapatía monoclonal de IgM e infiltración linfoplasmocítica en la médula ósea. Representa cerca del 1-2% de las neoplasias malignas hematológicas y es importante diferenciarla de otros procesos linfoproliferativos como la gammapatía monoclonal de significado incierto (MGUS) y de otros trastornos asociados a IgM.Suele debutar con síntomas inespecíficos, o ser un hallazgo de laboratorio, pudiendo presentar malestar general, astenia, baja de peso, o bien un cuadro poco frecuente producido por el aumento de la concentración de IgM sérica, denominado síndrome de hiperviscosidad. Éste corresponde a una urgencia hematológica que debe ser tratada precozmente ya que conlleva consecuencias graves para el paciente. Reportamos el caso de una mujer de 64 años con antecedente de MGUS IgM que progresa a Macroglobulinemia de Waldenström con síndrome de hiperviscosidad, presentado manifestaciones clínicas inespecíficas que al inicio minimiza, pero que conlleva a lesiones retinianas extensas. Dado la gravedad del cuadro, requiere manejo con plasmaféresis en unidad de paciente crítico.

Waldenström's macroglobulinemia is an infrequent hematological neoplasm characterized by Ig M monoclonal gammopathy and lymphoplasmacytic infiltration of the bone marrow. It accounts for 1-2% of malignant hematological neoplasms and it is important to distinguish it from other lymphoproliferative disorders such as monoclonal gammopathy of undetermined significance and other disorders involving IgM. It usually presents with non-specific symptoms, or is a laboratory finding, and may present as general malaise, weakness, weight loss or, rarely, hyperviscosity syndrome caused by a rise in the levels of circulating IgM. This is a hematological emergency which must be treated at once as it can have serious consequences for the patient. We report a case of a 64 year old woman with previously diagnosed monoclonal gammopathy of undetermined significance who progressed to Waldenström´s macroglobulinemia with hyperviscosity syndrome and minimal non-specific clinical signs which led to extensive retinal lesions. Given the seriousness of her condition she was treated with plasmapheresis in Intensive Care.