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Liquid soaps are the basic cosmetics used to clean the skin of the hands. Frequent hand washing prevents viral contamination but may damage the skin's hydro-lipid layer, leading to various types of irritation. Therefore, four liquid soap formulas were developed with three amphoteric surfactants: Cocamidopropyl Betaine (LS II), CocamidopropylHydroxysultaine (LS III), and newly synthesized Evening PrimroseaamidopropylSulfobetaine (LS IV). We evaluated the skin irritating potential (zein number, bovine albumin test) and cytotoxicity (AlamarBlue™, Cell viability, and Cell cycle assays) on HaCaT cell line. We observed lower values of the zein number and bovine albumin tests after adding soaps with surfactants (the highest differences in LS IV) compared to the base soap (LS I). However, LS I and LS II did not differ in cytotoxic assays. Therefore, adding LS III and LS IV seems potentially more dangerous to the cells. However, it should be noted that cells were continuously exposed to liquid soaps for more than 24 h, so its cytotoxic effects after dermal use in humans may be unnoticeable. Concluding, results suggest that the newly synthesized LS IV should improve the safety of liquid hand washing soaps.
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Sabões , Zeína , Animais , Bovinos , Desinfecção das Mãos/métodos , Humanos , Soroalbumina Bovina , Sabões/farmacologia , Tensoativos/farmacologiaRESUMO
Traditional technologies applied for obtaining plant raw materials for cosmetic production are based primarily on high-level processing, which is reflected in the qualitative composition of the resulting materials. By using low-temperature drying, it is possible to retain in the raw materials a range of valuable ingredients. In this study, blue honeysuckle powder was used as an ingredient of cosmetic face masks. The stability of the masks was evaluated. Dynamic viscosity, yield point and texture analysis of the cosmetics was performed. The color of the emulsions and the level of skin hydration after face mask application was determined. Emulsions were found to be stable. A decrease in dynamic viscosity of the emulsions as a function of increasing concentrations of the additive and under the conditions of rising rotational speed were observed. Similarly, an increase in the concentration of blue honeysuckle in the emulsions resulted in a decrease in the value of the yield point. Based on the results, it can be stated that the addition of blue honeysuckle caused a decrease in hardness of the masks, while the opposite trend was observed for adhesive force. It was found that an increase in the concentration of blue honeysuckle gave a reddish-yellow color to the samples. Corneometric assessment confirmed proper skin hydration after the application of the emulsions.
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Cosméticos , Lonicera/química , Extratos Vegetais/química , Frutas/química , Humanos , Extratos Vegetais/uso terapêutico , Pós/química , Pós/farmacologia , TemperaturaRESUMO
One of the consequences of polycystic ovary syndrome (PCOS) is an increased risk of early development of cardiovascular diseases. Pentraxin-3 (PTX-3) is a new potential marker of endothelial dysfunction. The aim of the study was to assess PTX3 and other markers of endothelial dysfunction in PCOS women. The study enrolled 99 stable body mass PCOS women (17 normal weight, 21 overweight and 61 obese). Anthropometric measurements and serum/plasma levels of glucose, insulin, lipids, estradiol, testosterone, sex hormone binding globulin, 17-OH progesterone, free androgen index, pentraxin-3 (PTX3), soluble intercellular (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), endothelin-1 and total nitric oxide metabolites (tNO) concentrations were assessed. Groups were divided into tercile-subgroups according to PTX3 serum levels. Serum PTX3 tercile-subgroups significantly differed in respect to tNO, endothelin-1 and sVCAM-1, but not sICAM-1. The levels of tNO, endothelin-1 and sVCAM-1 were significantly decreased in the subgroup with the lowest PTX3 levels compared to both middle (tNO and endothelin 1) and upper tercile subgroups (all of them). There were significant positive correlations between log10(PTX3) and log10(tNO) (r = 0.34, p < .001), log10(endothelin-1) (r = 0.41, p < .001) as well as sVCAM-1 levels (r = 0.22, p < .05). Circulating PTX-3 levels seem to be a marker of endothelial dysfunction in PCOS women.
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Proteína C-Reativa/metabolismo , Endotélio Vascular/patologia , Síndrome do Ovário Policístico/sangue , Componente Amiloide P Sérico/metabolismo , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
INTRODUCTION: Rape and pedophilic child molestation are the most commonly convicted sexual offenses in Poland. Recent studies have suggested a possible genetic contribution toward pathologic sexual interests and behaviors. AIM: To analyze and compare functional polymorphisms of genes associated with the activity of the serotonin and dopamine systems in a group of paraphilic sexual offenders and control subjects. METHODS: The study sample (n = 97) consisted of two groups: paraphilic sexual offenders (65 pedophilic child molesters and 32 rapists) and controls (n = 76). Genetic polymorphisms previously associated with behavioral control, addictive behaviors, and sexual functions were chosen for analyses. Specifically, functional polymorphisms in dopamine receptors genes (DRD1, DRD2, DRD4), catechol-O-methyltransferase gene (COMT), dopamine transporter gene (DAT), serotonin transporter gene (SLC6A4), serotonin type 2A receptor gene (5HTR2A), tryptophan hydroxylase 2 gene (TPH2), monoamine oxidase A gene (MAOA), and brain-derived neurotrophic factor gene (BDNF) were analyzed. MAIN OUTCOME MEASURES: An association between a history of sexual offense and the distribution of genotypes and alleles in the analyzed polymorphisms. RESULTS: Our results found no association between a history of sexual offense and the distribution of genotypes or alleles in the analyzed polymorphisms. CONCLUSION: Although these results are limited by the small sample and are exploratory, they highlight a novel approach to sample selection in a population that is difficult to access and study. Future research should include larger samples and other relevant polymorphisms to advance this field of study.
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Criminosos , Dopamina/metabolismo , Pedofilia/genética , Serotonina/metabolismo , Adulto , Alelos , Estudos de Casos e Controles , Catecol O-Metiltransferase/genética , Criança , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Polimorfismo Genético , Delitos SexuaisRESUMO
Purpose: The STATIC-99 instrument is one of the tools used for the assessment of the risk of recidivism, in line with the actuarial approach. One of the risk factors indicated by the scientific literature as having the greatest significance is sexual preference disorder. The aim of the study was to verify whether sexual offenders diagnosed with sexual preference disorders have a higher risk of recidivism. The study also aimed to present, for the first time in Poland, a quantitative scoring of individual risk factors in STATIC-99R and their prevalence, allowing for the verification of the theoretical validity of the STATIC-99R instrument in the analysis of the population of sexual offenders in Poland. Methods: The study material consisted of 100 court and penitentiary files of perpetrators of crimes against sexual freedom from 11 Polish penal institutions and remand centers. We used the STATIC-99R to evaluate each case. Results: The distribution of the individual STATIC-99R risk factors in the population of the Polish sexual offenders is presented. The diagnosis of sexual preference disorders had no influence on the total STATIC-99R score but was associated with its individual factors. Conclusions: It can be concluded that the theoretical validity of the STATIC-99R tool is also relevant to the Polish study population and may be used in clinical practice.
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Paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia in adults. Its occurrence depends on the presence of the reentry circuit and the trigger of the paroxysm. Stress, emotional factors, and comorbidities favour the occurrence of such an episode. We hypothesized that the occurrence of PSVT follows extreme thermal episodes. The retrospective analysis was based on the data collected from three hospital emergency departments in Poland (Olsztyn, Radom, and Wroclaw) involving 816 admissions for PSVT in the period of 2016-2021. To test the hypothesis, we applied the Universal Climate Thermal Index (UTCI) to objectively determine exposure to cold or heat stress. The risk (RR) for PSVT increased to 1.37 (p = 0.006) in cold stress and 1.24 (p = 0.05) in heat stress when compared to thermoneutral conditions. The likelihood of PSVT during cold/heat stress is higher in women (RR = 1.59, p< 0.001 and RR = 1.36, p = 0.024, respectively) than in men (RR = 0.64 at p = 0.088 and RR = 0.78, p = 0.083, respectively). The susceptibility for PSVT was even higher in all groups of women after exclusion of perimenopausal group of women, in thermal stress (RR = 1.74, p< 0.001, RR = 1.56, p = 0.029, respectively). Females, particularly at the perimenopausal stage and men irrespective of age were less likely to develop PSVT under thermal stress as compared to thermoneutral conditions. Progress in climate change requires searching for universal methods and tools to monitor relationships between humans and climate. Our paper confirms that the UTCI is the universal tool describing the impact of thermal stress on the human body and its high usefulness in medical researches.
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Transtornos de Estresse por Calor , Taquicardia Paroxística , Taquicardia Supraventricular , Taquicardia Ventricular , Masculino , Adulto , Humanos , Feminino , Taquicardia Supraventricular/epidemiologia , Taquicardia Supraventricular/etiologia , Resposta ao Choque Frio , Estudos Retrospectivos , Taquicardia Paroxística/epidemiologia , Taquicardia Paroxística/etiologiaRESUMO
Nociplastic pain is a recently distinguished type of pain, distinct from neuropathic and nociceptive pain, and is well described in the literature. It is often mistaken for central sensitization. Pathophysiology has not been clearly established with regard to alteration of the concentration of spinal fluid elements, the structure of the white and gray matter of the brain, and psychological aspects. Many different diagnostic tools, i.e., the painDETECT and Douleur Neuropathique 4 questionnaires, have been developed to diagnose neuropathic pain, but they can also be applied for nociplastic pain; however, more standardized instruments are still needed in order to assess its occurrence and clinical presentation. Numerous studies have shown that nociplastic pain is present in many different diseases such as fibromyalgia, complex regional pain syndrome type 1, and irritable bowel syndrome. Current pharmacological and nonpharmacological treatments for nociceptive and neuropathic pain are not entirely suitable for treating nociplastic pain. There is an ongoing effort to establish the most efficient way to manage it. The significance of this field has led to several clinical trials being carried out in a short time. The aim of this narrative review was to discuss the currently available evidence on pathophysiology, associated diseases, treatment possibilities, and clinical trials. It is important that physicians widely discuss and acknowledge this relatively new concept in order to provide optimized pain control for patients.
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Introduction: The study aimed to estimate the cut-off value for homeostatic model assessment for insulin resistance (HOMA-IR) discriminating the insulin resistance based on the sex hormones binding globulin (SHBG) level in women with polycystic ovary syndrome (PCOS). Materials and methods: Data from medical records of 854 Caucasian women diagnosed with PCOS were analyzed. Anthropometric data, fasting plasma glucose, insulin and SHBG levels were measured. HOMA-IR was calculated with a standard formula. The cut-off value was calculated using receiver-operating characteristics. Results: Circulating SHBG levels below the normal range (26.1 nmol/L) were found in 25.4% of study participants. This subgroup had a significantly higher BMI, fasting glucose and insulin concentrations and HOMA-IR values. Empirical optimal cut-off values for HOMA-IR corresponding to low SHBG levels was ≥2.1 [area under the curve (AUC) 0.73, accuracy 0.65, sensitivity 72.3%, specificity 63.1%, positive predictive value (PPV) 40.0%, negative predictive value (NPV) 87.0%]. Conclusions: Our study suggests that the cut-off point for HOMA-IR discriminating the insulin resistance based on the SHBG level, in young Caucasian women with polycystic ovary syndrome is 2.1, and is consistent with the cut-off value adopted by the European Group for the Study of Insulin Resistance (above 2.0).
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Introduction: Changes in the proportion of pro-inflammatory and anti-inflammatory adipokines may reflect the accumulation of lipids in the liver and the development of insulin resistance. Both liver steatosis and insulin resistance result in decreased sex hormone-binding globulin (SHBG) synthesis. This study aimed to analyze associations between circulating SHBG and adipokines levels in women with polycystic ovary syndrome (PCOS). Material and methods: A cross-sectional cohort study involved 87 women with phenotype A of PCOS (39 normal weight and 48 obese). Body mass, height, and waist circumference were measured, and BMI was calculated. In addition, body composition was assessed using the bioimpedance method. Serum SHBG levels and plasma apelin-36 and apelin-12, adiponectin, leptin, omentin-1, and RBP-4 were determined by using the ELISA method. The participants were divided into subgroups with SHBG concentrations above and below this lower limit [N = 35 (40.2%) and N = 52 (59.8%), respectively]. Results: The median adiponectin, apelin-12, and apelin-36 levels were significantly lower, and leptin levels were significantly higher in the subgroup with low SHBG levels than that in the subgroup above the lower limit of the reference range, while there were no differences in median omentin-1 and RBP-4 between the study subgroups. There were positive correlations between SHBG and omentin-1, adiponectin, apelin-36, and apelin-12 levels, as well as negative correlation with leptin levels. However, after adjustment by BMI, waist circumference, and body fat percentage, only the association between SHBG and omentin-1 remained significant. Conclusion: Our results show associations between circulating SHBG and adipokine levels in women with PCOS and support the role of hormonal dysfunction of the adipose tissue in the pathogenesis of PCOS.
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Obesity in adults and its complications are among the most important problems of public health. The search was conducted by using PubMed/MEDLINE, Cochrane Library, Science Direct, MEDLINE, and EBSCO databases from January 2010 to December 2022 for English language meta-analyses, systematic reviews, randomized clinical trials, and observational studies from all over the world. Six main topics were defined in the joint consensus statement of the Polish Association for the Study on Obesity, the Polish Association of Endocrinology, the Polish Association of Cardio-diabetology, the Polish Psychiatric Association, the Section of Metabolic and Bariatric Surgery of the Society of Polish Surgeons, and the College of Family Physicians in Poland: (1) the definition, causes and diagnosis of obesity; (2) treatment of obesity; (3) treatment of main complications of obesity; (4) bariatric surgery and its limitations; (5) the role of primary care in diagnostics and treatment of obesity and barriers; and (6) recommendations for general practitioners, regional authorities and the Ministry of Health. This statement outlines the role of an individual and the adequate approach to the treatment of obesity: overcoming obstacles in the treatment of obesity by primary health care. The approach to the treatment of obesity in patients with its most common complications is also discussed. Attention was drawn to the importance of interdisciplinary cooperation and considering the needs of patients in increasing the long-term effectiveness of obesity management.
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Cirurgia Bariátrica , Endocrinologia , Humanos , Adulto , Polônia/epidemiologia , Médicos de Família , Obesidade/complicações , Obesidade/cirurgia , Cirurgia Bariátrica/efeitos adversosRESUMO
Background: Resistin action links to conditions such as diabetes, obesity, but its role in hypertension is less well understood. This study aimed to estimate the relationship between resistin (-420G/C) single nucleotide variant (SNV) and markers associated with endothelial dysfunction in hypertension. Methods: The study enrolled 162 hypertensive patients (HT) and 165 non-hypertensive (NHT) patients. Resistin serum concentration was estimated with immuoenzymatic assay. Anthropometric measurements, blood pressure and arterial stiffness index (SI), uric acid (UA) serum concentration, and salty taste preference of normal (NS) or high (HS) were assessed in the study. Genotyping was achieved by polymerase chain reaction-restriction fragment length polymorphism. Results: Resistin concentration and SI do not differ significantly between HT and NHT individuals; UA significantly increased in HT subjects. Resistin, UA, and SI did not differ among particular resistin genotypes in HT, NHT, NS, or HS groups. GG and CG genotypes were more frequent (OR 1.57 (95% CI; 1.01-2.43); p = 0.04) in hypertensive individuals than the NHT group, but less frequent (OR 0.58 (95% CI; 0.37-0.91); p = 0.01) in HS patients compared to NS individuals. Concerning HT patients with different salt preferences, GG + CG genotypes were less frequent (OR 0.50 (95% CI; 0.26-0.97); p = 0.04) in the HS group than in NS individuals. HT carriers of GG and CG genotype have significantly increased UA concentrations compared to the respective NHT subjects. HS individuals carrying GG and CG genotypes have higher SI values than the NS group. Allele G of SNV (-420G/C) adjusted for age, BMI, serum resistin, UA concentration, salt taste preference, SI, and HR values increased the risk of developing hypertensive phenotype 1.8 fold. Conclusions: Resistin SNV (-420G/C) is related to several markers associated with endothelial dysfunction, including salt taste preference in hypertensive patients.
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Hipertensão , Resistina , Biomarcadores , Predisposição Genética para Doença , Genótipo , Humanos , Hipertensão/genética , Nucleotídeos , Polimorfismo de Nucleotídeo Único , Resistina/genética , Paladar/genéticaRESUMO
OBJECTIVE: Decreased synthesis of sex hormone-binding globulin (SHBG) related to hyperinsulinemia is one of the disturbances characteristic of polycystic ovary syndrome (PCOS). Hyperinsulinemia is a compensatory mechanism for liver insulin resistance (IR); thus, SHBG may be considered as a surrogate marker of liver IR. Therefore, this study aimed to assess the prediction of IR and impaired fasting glucose (IFG) based on SHBG levels in women with PCOS. METHODS: This analysis included data retrieved from medical records of 854 patients with PCOS hospitalized in the Gynecological Endocrinology Clinic from 2012 to 2019. Data including anthropometric parameters, fasting plasma glucose, insulin, and SHBG levels were analyzed. BMI and HOMA-IR were calculated with standard formulas. RESULTS: IFG and IR assessed based on HOMA-IR values > 2.0 were found in 19.5% and 47.8% of the study group, respectively. Empirical optimal cutoff values for SHBG levels were ≤41.5 nmol/L typical for IR (AUC 0.711, sensitivity 61.1%, specificity 71.6%, positive predictive value (PPV) 70.7%, and negative predictive value (NPV) 62.1%). The probability of insulin resistance occurrence for SHBG concentration 26.1 nmol/L (the lower normal range) was 61.6% (95% CI: 57.4%-65.8%). The SHBG concentration of 36.4 nmol/L and 8.1 nmol/L was related to a 10% and 20% probability of IFG, respectively. CONCLUSION: In conclusion, this is the first study estimating the probability of liver IR and IFG occurrence based on SHBG levels in women with PCOS. Despite the low sensitivity, SHBG level below 42 nmol/L should cause closer monitoring for the fatty liver and prediabetes.
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BACKGROUND: The consumption of breakfast, salty meals, red meat, whole grain products, and dark chocolate are dietary habits that influence health, but the effects on arterial stiffness have not been well-investigated. Aim. To assess the effects of selected dietary patterns on arterial stiffness, liver and renal function, inflammation, and glucose and lipid biochemical parameters. METHODS: 829 patients completed health and food frequency questionnaires, and underwent anthropometric, arterial stiffness, and blood pressure measurements. Serum concentrations of lipids, glucose, alanine and aspartate aminotransferases, creatinine, uric acid, and C-reactive protein were determined. RESULTS: The aspartate aminotransferase serum concentration was lower in the breakfast-consuming group (25.88 ±7.05 U/L) compared to non-consumers (27.75 ±10.67 U/L). A lower concentration of creatinine and alanine aminotransferase and a higher concentration of C-reactive protein was found in whole grain product consumers. Individuals consuming more red meat had higher alanine aminotransferase and low-density lipoprotein serum concentrations. Individuals with greater dark chocolate consumption had higher serum concentrations of uric acid (5.20 ±1.46 vs. 4.72 ±1.18) and more intensified arterial stiffness (peak-to-peak time 213.86 ±54.98 ms vs. 238.70 ±60.83 ms). CONCLUSIONS: The investigated dietary patterns had a significant impact on serum lipid concentrations, biochemical markers of liver and renal function and inflammation, and arterial stiffness. High consumption of red meat and dark chocolate intensified cardiovascular risk, contrary to the intake of whole grain products.
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Dieta , Comportamento Alimentar , Rim , Metabolismo dos Lipídeos , Fígado , Rigidez Vascular , Adolescente , Adulto , Idoso , Desjejum , Proteína C-Reativa/metabolismo , Cacau , Chocolate , Creatinina/sangue , Feminino , Humanos , Rim/fisiologia , Lipoproteínas LDL/sangue , Fígado/enzimologia , Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Polônia , Carne Vermelha , Ácido Úrico/sangue , Grãos Integrais , Adulto JovemRESUMO
no summary.
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COVID-19/epidemiologia , Comportamento Alimentar/psicologia , Estilo de Vida , Obesidade/terapia , Índice de Massa Corporal , Humanos , Estado NutricionalRESUMO
OBJECTIVE: The aim of the study was to assess PTX3 levels in PCOS and non-PCOS women in relation to nutritional status and circulating markers of inflammation. METHODS: The study enrolled 99 stable body mass PCOS women (17 normal weight, 21 overweight, and 61 obese) and 61 non-PCOS women (24 normal weight, 19 overweight, and 18 obese). Body composition was assessed by bioimpedance, and plasma levels of pentraxin 3 (PTX3), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein 1 (MCP-1) were measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was made. RESULTS: Plasma PTX3, TNF-α, and IL-6 levels and HOMA-IR were higher in PCOS than in non-PCOS group (p < 0.001). There were positive correlations between log10 (PTX3) and log10 (BMI), waist circumference and fat percentage, as well as log10 (HOMA-IR) and free androgen index but negative between log10 (estradiol) levels in PCOS. While in the non-PCOS group, the correlations between log10 (PTX3) and log10 (BMI), waist circumference and fat percentage, as well as log10 (HOMA-IR) were negative. The positive correlations between PTX3 and MPC-1 and log10 (IL-6) were shown in the PCOS group only. In multivariate regression analyses, variability in PTX3 levels in the PCOS group was proportional to log10 (BMI), waist circumference, and fat percentage, but inversely proportional to log10 (estradiol) levels. While in the non-PCOS group, PTX3 levels were inversely proportional to all anthropometric parameters. CONCLUSIONS: Our results show that the decrease in PTX3 levels observed in obese is distorted in PCOS by microinflammation, and possibly, dysfunction of stroma adipose tissue and liver steatosis is reflected by enhanced insulin resistance.
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Papillary thyroid carcinoma (PTC), the most common thyroid cancer, is predominantly driven by mutations in BRAF (primarily p. V600E) and RAS oncogenes. Ultrasound (US) examination provides significant diagnostic data in the management of thyroid nodules, as many sonographic features of thyroid lesions are correlated with the potential risk of thyroid carcinoma. The aim of the study was to analyze the current literature in regard to the potential associations between genetic landscape and sonographic features of PTC. Based on the current literature, sonographic features of PTCs correlate with their molecular drivers, particularly between tumors harboring BRAFV600E versus activating RAS mutations, although many of these findings appear to be dependent on the tumor variant. Suspicious US findings, such as hypoechogenicity, spiculated/microlobulated margins, non-parallel orientation/taller-than-wide shape, and the presence of microcalcifications, are typical for PTC positive for BRAFV600E mutations. On the contrary, tumors with RAS mutations are most frequently hypo- or isoechoic and ovoid-to-round in shape, with smooth margins and without calcifications. There are also some US features typical for PTCs harboring other mutations, including BRAFK601E, RET/PTC rearrangements, PAX8-PPARγ, CTNNB1, and APC. However, further research is necessary, as some rare PTC variants still cannot be reliably analyzed due to the scarce published data.
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We describe the role of plasma and platelet cholesterol content in the ability of acetylsalicylic acid (ASA) to acetylate platelet proteins and inhibit platelet function. Platelet susceptibility to ASA was monitored in subjects differing in plasma total cholesterol and in suspensions of cholesterol-enriched or cholesterol-depleted platelets. Platelets from subjects with higher plasma cholesterol (>6 mmol/l) showed reduced platelet sensitivity to ASA (inhibition of platelet aggregation and thromboxane generation by 60% and 68% in 'lower-' vs. 32% and 56% in 'higher-cholesterol' donors; n=13 in each group; p=0.056 and p<0.04, respectively). [Acetyl-1-(14)C] incorporation to platelet proteins in subjects with higher plasma cholesterol was significantly reduced (11.0 vs. 14.6 nmol/g protein, p<0.0001) and correlated significantly with blood total cholesterolemia (R(K)=-0.430, p<0.003) and LDL-cholesterol (R(K)=-0.349, p<0.012), but not with platelet cholesterol content. In conclusion, elevated plasma cholesterol is an important determinant of ASA-induced acetylation of platelets and platelet diminished sensitivity to ASA. The molecular basis of such an association remains obscure, notwithstanding it may constitute a link between sub-optimal platelet response to aspirin and lipid metabolic disorders.
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Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Colesterol/sangue , Acetilação , Plaquetas/metabolismo , Humanos , Bicamadas Lipídicas , Agregação Plaquetária/efeitos dos fármacos , Tromboxanos/antagonistas & inibidores , Tromboxanos/biossínteseRESUMO
Detection of reduced aspirin effectiveness has gained significant importance since clinical consequences of aspirin resistance were reported. Nevertheless, due to differentiated molecular basis of aspirin resistance, the conflicting choice of referential method for detection of acetylsalicylic acid ineffectiveness has become troublesome. This study, using a rat model of antiplatelet therapy, examines the aptitude of selected TXB2 metabolism-based methods in the detection of acetylsalicylic acid effectiveness. We hypothesized that ex-vivo whole blood spontaneous TXB2 generation assay could be, contrary to basal TXB2 and urine 11-dTXB2, a novel surrogate measure for impaired acetylsalicylic acid-dependent inhibition of thromboxane synthesis. To address this hypothesis, we evaluated the sensitivity of TXB2 generation assay in hirudinized whole blood to detect acetylsalicylic acid-mediated inhibition of cyclooxygenase activity in healthy rats and diabetic rats treated with acetylsalicylic acid. In diabetic and control animals, both acetylsalicylic acid drenches in the dose-independent manner contributed to significant attenuation of basal plasma TXB2 and urinary 11-dTXB2 formation. Urinary concentrations of 11-dTXB2 were, contrary to basal TXB2, significantly higher, regardless of acetylsalicylic acid dose, among all diabetic groups, compared with corresponding control groups. Determination of TXB2 generation in whole blood enabled sensitive detection of dose-related acetylsalicylic acid effect in both groups, as well as increased TXB2 formation in diabetes. We showed for the first time that evaluation of spontaneous generation of TXB2 in hirudinized whole blood enables, contrary to basal plasma TXB2 and urine 11-dTXB2 concentrations, to sensitively determine the acetylsalicylic acid effect in healthy and diabetic subjects.
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Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Resistência a Medicamentos , Tromboxano A2/sangue , Tromboxano A2/urina , Animais , Masculino , Modelos Biológicos , Ratos , Ratos Wistar , Tromboxano B2/sangue , Tromboxano B2/urinaRESUMO
There is a growing number of contradictory reports indicating that adenosine diphosphate (ADP) can be a useful agonist in monitoring of the antiplatelet action of acetylsalicylic acid (ASA) in humans and animals. In the current study, we aimed to determine the conditions for using ADP to trigger platelet aggregation in order to detect ASA-mediated inhibition of rat platelet reactivity. Initially, we examined the usefulness of different ADP concentrations (0.25, 0.5, 1, 5 and 10 microM) in detecting the in vitro ASA mediated platelet inhibition using whole blood aggregometry, as well as we monitored the role of ADP in generation of thromboxane A(2) (TXA(2)). To study ex vivo ASA inhibitory potential on platelet aggregation induced by a range of ADP concentrations, animals were subjected to one or 10-day ASA administration at the dose of 50 mg/kg. Our experiment shows that ADP in a concentration-dependent manner induces TXA(2) generation in the whole blood with hirudin as an anticoagulant. However, in vitro and ex vivo examination of ASA inhibitory potential on platelet aggregation revealed that irrespectively of administration regimen, ASA failed to block platelet aggregation induced by ADP at the concentrations higher than 0.5 microM. Our findings suggest that the mechanism of ADP-induced platelet aggregation depends on agonist concentration. It appears that only low ADP concentrations (up to 0.5 microM) induce TXA(2)-dependent rat platelet aggregation. Therefore, ADP could be considered a useful platelet agonist for monitoring of ASA-mediated platelet inhibition only if used at much lower concentrations than those commonly employed.
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Difosfato de Adenosina/farmacologia , Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Análise de Variância , Animais , Plaquetas/metabolismo , Relação Dose-Resposta a Droga , Resistência a Medicamentos/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Testes de Função Plaquetária/métodos , Ratos , Ratos Wistar , Tromboxano A2/antagonistas & inibidores , Tromboxano A2/biossínteseRESUMO
UNLABELLED: The frequency of onset of acute coronary syndromes and sudden cardiac death has been reported to have circadian variations, with a peak incidence in early morning hours. It has also been known that acute ischemia is a potent stimulus to increased dispersion of repolarization and development of malignant arrhythmias. QT dispersion (QTd) is used as an index of heterogenity of the ventricular repolarization and increases in patients with ischemic heart disease. The aim of the study was to investigate diurnal variations of QTd in patient with triple-vessel coronary artery disease (CAD) with and without diabetes mellitus type 2 (DM). MATERIAL AND METHODS: We investigated of 28 patients with stable triple-vessel CAD and 32 patients with similar advancement of changes in coronary circulation with co-existing DM. We excluded patients with prior myocardial infarction, taking oral medications which might alter QT interval and patients in which measurements of QT were difficult to perform or impossible. QTd measurements were taken semi-automatically every hour from 24 hours 12 leads Holter monitoring system (SUPRIMA 12). Measurements were verified independently by three observers. RESULTS: CAD patients without DM had QTd significantly greater in the morning hours (6 a.m. to 9 a.m.) in comparison with the other times (p < 0.01). The shortest QTd was measured during the night between 10 p.m. and 1 a.m. We did not observed circadian variations of QTd in patients with co-existent DM and values of QTd in this group was significantly greater then in CAD without DM group (p < 0.001). CONCLUSIONS: Our data proved that QTd in patients with CAD had a circadian variation with a peak value in the morning hours shortly after awakening. Patients with DM and CAD had not circadian variation of QTd but QTd values, during whole day and night, were significantly greater then patients without DM.