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Optic nerve atrophy is a pathomorphological consequence of diseases of the peripheral neuron of the visual pathway, manifested as atrophy of nerve fibers of varying severity. The toxic effect of methanol is mainly associated with formic acid and formaldehyde, which suppress the cytochrome system, inhibit oxidative phosphorylation, and thereby cause a deficiency of adenosine triphosphoric acid, to which brain and retinal tissues are especially susceptible. When formiate accumulates, tissue respiration is disrupted, leading to pronounced tissue hypoxia. As a result of such methanol metabolism, metabolic acidosis occurs. Tissue hypoxia develops in the first few hours as a result of the action of formic acid on the respiratory enzyme chain at the cytochrome oxidase level. Hypoxia and, as a consequence, a decrease in energy supply lead to a disruption of biological oxidation and the development of apoptosis in the optic nerve fibers. Understanding the process of optic nerve atrophy development at the pathogenetic level in methyl alcohol intoxication will help make a correct early diagnosis and prescribe timely treatment.
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Metanol , Nervo Óptico , Humanos , Metanol/intoxicação , Nervo Óptico/patologia , Nervo Óptico/efeitos dos fármacos , Atrofia Óptica/etiologia , Atrofia Óptica/diagnóstico , Atrofia Óptica/induzido quimicamenteRESUMO
DNA polymerases catalyze DNA synthesis during DNA replication, repair, and recombination. A number of DNA polymerases, such as the Taq enzyme from Thermus aquaticus, are used in various applications of molecular biology and biotechnology, in particular as DNA amplification tools. However, the efficiency of these enzymes depends on factors such as DNA origin, primer composition, template length, GC-content, and the ability to form stable secondary structures. These limitations in the use of currently known DNA polymerases lead to the search for new enzymes with improved properties. This review summarizes the main structural and molecular-kinetic features of the functioning of DNA-polymerases belonging to structural family A, including Taq polymerase. A phylogenetic analysis of these enzymes was carried out, which made it possible to establish a highly conserved consensus sequence containing 62 amino acid residues distributed over the structure of the enzyme. A comparative analysis of these amino acid residues among poorly studied DNA-polymerases revealed 7 enzymes that potentially have the properties necessary for use in DNA amplification.
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Replicação do DNA , DNA , Filogenia , Taq Polimerase/química , Taq Polimerase/genética , Taq Polimerase/metabolismo , DNA/genética , AminoácidosRESUMO
The important role of DNA damage in the occurrence of various diseases, including cancer, has led to study of the mechanisms of genetic information stability, that have been carried out since the discovery of DNA repair systems. The question of the relationship between the accumulation of DNA damage, disorders in DNA repair pathways, and increased risk of disease development is still relevant. Over the past few years, significant efforts have been made to develop methods for analyzing the activity of DNA repair enzymes in human cells. In this work, we developed fluorescent DNA probes that allow us to determine the activity of key enzymes of base excision DNA repair in cell extracts, namely the DNA glycosylases UNG2, SMUG1, MBD4, TDG, AAG, NEIL1, NTHL1, and OGG1 and the AP endonuclease APE1. The sensitivity of DNA probes was determined on pure enzyme preparations. Determination of the activity of repair enzymes in cell extracts of the human ovarian tumor lines TOV112, 79, OVCAR3, MESOV, SCOV3, and TOV21 revealed significant variability in the level of enzyme activity in these cell lines. These results may become a test system platform for analyzing the activity of the base excision DNA repair system in the human body.
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DNA Glicosilases , Neoplasias Ovarianas , Humanos , Feminino , Apoptose , Extratos Celulares , Linhagem Celular Tumoral , Reparo do DNA/genética , Dano ao DNA , DNA/metabolismo , Sondas de DNA , DNA Glicosilases/genética , DNA Glicosilases/metabolismoRESUMO
The efficiency of bone tissue regeneration by decellularized tooth matrix, demineralized tooth matrix, and commercial xenograft Bio-Oss Spongiosa was compared on the model of a critical-size circular defect in the alveolar bone of the upper jaw of adult Wistar rats. The defect healing dynamics was assessed using histological, histomorphometrical, and immunohistochemical methods on days 30 and 60. In contrast to demineralized matrix and commercial xenograft, decellularized matrix induces the formation of the new bone tissue by day 60. Decellularized matrix can be considered as a biomaterial for cell-free tissue engineering for alveolar bone restoration in dentistry and maxillofacial surgery.
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Aim To study prognostic significance of the degree of stenosis of carotid and lower-extremity arteries (LEA) in patients at high and very high risk of cardiovascular complications (CVC).Material and methods The study included men and women aged 40-67 years at high and very high risk of CVC. Duplex ultrasound scanning of carotid arteries and LEA was performed for all patients. Laboratory tests included measurements of glucose, glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, uric acid, creatinine with estimation of glomerular filtration rate (GFR) using the CKD-EPI Creatinine Equation formula, and high-sensitivity C-reactive protein (hsCRP). Composite endpoint was death from CVC, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization.Results The study included 214 patients from groups of high and very high risk of CVC. Median age of patients was 59.0 [53.2; 64.0] years. A very high risk was identified in 141 (65.8 %) patients and a high risk of CVC in 73 (34.1 %). Atherosclerotic plaques in at least one vascular bed were found in 191 (89.3 %) patients. Duration of the follow-up period was 32.0 [13.7; 49.1] months. Outcomes comprising the composite endpoint were observed in 36 (16.8 %) patients. Presence of carotid stenosis ≥35 % was not statistically significantly associated with the occurrence of outcomes comprising the composite endpoint (relative risk, RR: 1.22; 95 % confidence interval, CI: 0.56-2.66; p=0.607). In contrast, the presence of LEA stenosis ≥35 % was associated with a 2.51 times increased RR of CVC (95 % CI: 1.02-6.23; p=0.044).Conclusion In patients from the groups of high risk and very high risk of CVC, the presence of LEA stenosis ≥35 % predicted the development of severe CVC with a 69.4% sensitivity and a 61.8% specificity. The presence of LEA stenosis ≥35 %, but not of carotid arteries, was an independent predictor of severe CVC (RR, 2.51; 95 % CI: 1.02-6.23; p=0.044) after adjustments for sex, age, presence of arterial hypertension, diabetes mellitus, ischemic heart disease, obesity, smoking, LDL-C, GFR, and drug therapy.
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Doenças Cardiovasculares , Estenose das Carótidas , Masculino , Humanos , Feminino , Constrição Patológica , Prognóstico , LDL-Colesterol , Creatinina , Fatores de Risco , Artérias Carótidas , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/diagnóstico por imagem , Extremidade Inferior , Fatores de Risco de Doenças CardíacasRESUMO
Hemangioblastoma is a benign tumor of the central nervous system arising sporadically or as a component of Von Hippel-Lindau disease. Von Hippel-Lindau disease is a rare autosomal dominant hereditary syndrome with various phenotypes caused by VHL gene variants. To date, only about 40 cases of optic nerve hemangioblastoma have been described in the literature. Stereotactic irradiation may be effective for supratentorial hemangioblastomas including lesions of optic nerves. The authors describe a rare case of stereotactic irradiation of intraorbital hemangioblastoma of the optic nerve in a patient with Von Hippel-Lindau disease.
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Hemangioblastoma , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/cirurgia , Doença de von Hippel-Lindau/genética , Hemangioblastoma/diagnóstico por imagem , Hemangioblastoma/cirurgia , Hemangioblastoma/complicações , Nervo Óptico/patologiaRESUMO
The low cardiovascular risk group according to SCORE in relation to the clinical and laboratory characteristics of patients is very heterogeneous, which leads to the presence of a residual risk of cardiovascular events. This category may include individuals with a family history of cardiovascular disease at a young age, with abdominal obesity (AO), endothelial dysfunction, and high levels of triglyceride-rich lipoproteins. In this regard, an active search is underway for new metabolic markers within the low cardiovascular risk group. The purpose of the study was to compare the nutrition, the adipose tissue distribution in low cardiovascular risk individuals, depending on the AO. Material and methods. The study included 86 healthy low risk (SCORE<1%) patients (mean age 42.6±2 years), who were divided into 2 groups: with AO [waist circumference (WC) >=94 cm in men and >=80 cm in women] - 44 patients (32% of men) and without AO - 42 patients (38% of men). The body composition was carried out using the bioimpedance analyzer. The distribution of ectopic fat deposits in the liver, pancreas and epicardial region was studied using ultrasound methods. A frequency questionnaire (Diet Risk Score) was used to assess nutrition. Results. In low risk patients with AO, signs of unhealthy diet are statistically significantly more common (in 52 in the main group vs 2% in the control group, p<0.01), ectopic deposition of adipose tissue in the liver (53 vs 9%, p<0.001), pancreas (56% in the main group, absent in the control group, p<0.001), epicardia l region (the epicardial fat thickness median is 4.24 mm in the main group vs 2.15 mm in the control group) compared with a control group. Conclusion. The low cardiovascular risk group is very heterogeneous. One of the markers of heterogeneity is central obesity - a marker of unhealthy diet, subclinical ectopic fat deposition and hypertriglyceridemia. Patients with AO of the low cardiovascular risk group require a more thorough examination with the obligatory determination of waist circumference, ultrasound assessment of the liver and pancreas parenchyma, and determination of the epicardial fat thickness. Using a short nutrition questionnaire allows you to quickly identify signs of unhealthy diet and discuss them with the patient.
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Doenças Cardiovasculares , Obesidade Abdominal , Masculino , Humanos , Feminino , Adulto , Obesidade Abdominal/epidemiologia , Doenças Cardiovasculares/epidemiologia , Distribuição Tecidual , Fatores de Risco , Obesidade , Fatores de Risco de Doenças CardíacasRESUMO
Anthracnose of strawberry caused by Colletotrichum fungi is a dangerous disease associated with serious damage in berry plantations. Colletotrichum nymphaeae, C. lineola, and C. godetiae have been found in Russian and international planting material of strawberry plants. The cultural and morphological characteristics are described for the isolates and nucleotide ITS1-5.8S-ITS2 sequences of fragments received are identified. It is shown that the fragments of glyceraldehyde 3-phosphate dehydrogenase and actin genes can be used to efficiently differentiate the C. lineola species from the closely related С. dematium. Two diagnostic test systems for acutatum complex identification are compared. The studied test systems do not demonstrate any false-positive results; the prepared set of С. acutatum complex-RT (ZAO Sintol) shows specificity only for the C. nymphaeae and C. fioriniae species and turned out to be nonspecific to the C. godetiae species included in the acutatum complex. The test system elaborated by Garrido et al. is found to be highly sensitive and specific to the target species of the acutatum complex.
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Fragaria , Fragaria/microbiologia , Doenças das Plantas/microbiologia , Frutas , Federação RussaRESUMO
The novel molecular subtype of breast cancer (BC), named "claudin-low", was described in 2007. It was characterized by the consistently low expression of genes involved in the formation of epithelial tight junctions in combination with the high activation of genes associated with the epithelial-to-mesenchymal transition, as well as tumor stem cell markers. The similar claudin- low subtype was later identified at the transcriptional level in bladder cancer, gastric cancer, and serous ovarian cancer. However, only in relation to BC, attempts were made to create a surrogate panel for immunohistochemical identification of this subtype in a manner like the intrinsic molecular BC subtypes identified using three main markers, such as ER, PR, and HER-2. At the same time, the ambiguity in the expression of claudins among the subtypes of BC, which is defined by various authors at the immunohistochemical level, as well as the absence of both the confirmed set of immunohistochemical criteria and a unified approach to their assessment, complicate these efforts. The purpose of the review is to show that the immunohistochemical identification of claudin-low subtype of BC is a separate problem that has significant limitations, needs standardization and has not yet reached diagnostic value.
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Neoplasias da Mama , Cistadenocarcinoma Seroso , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Claudinas/genética , Transição Epitelial-Mesenquimal , Feminino , Humanos , Células-Tronco Neoplásicas , FenótipoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is the most common and difficult to treat form of pancreas cancer. PDAC and other solid cancers contain both tumor cells and normal connective tissue cells called stromal cells, which are responsible for the excess production of extracellular matrix. It is known that in more than 90% of PDAC tumors and in many other types of cancer, mutations of the KRAS gene are observed, the reciprocal signaling of which has been shown between tumor and stromal cells in vitro. Pancreatic stromal stellate cells are considered precursors of activated or tumor-associated fibroblasts (CAFs), which are an increasing population of cells that proliferate in situ or are recruited into the tumor. CAFs are a heterogeneous population of stromal fibroblasts with different molecular profiles that change during tumorigenesis. Both immunosuppressive and immunosuppressive subsets of CAFs can coexist in the stroma of a single tumor. Based on the heterogeneity of the intertumor stroma, attempts are being made to classify PDAC and predict the course of the disease.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Progressão da Doença , Humanos , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Células Estromais/patologia , Microambiente Tumoral/genética , Neoplasias PancreáticasRESUMO
BACKGROUND: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. METHODS: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885. RESULTS: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period. CONCLUSIONS: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.
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Dermatite Atópica , Eczema , Adulto , Anticorpos Monoclonais/efeitos adversos , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Humanos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Human apurinic/apyrimidinic endonuclease 1 (APE1) participates in the DNA repair system. It is believed that the main biological function of APE1 is Mg^(2+)-dependent hydrolysis of AP-sites in DNA. On the base of structural data, kinetic studies, and mutation analysis, the key stages of APE1 interaction with damaged DNA were established. It has been shown recently that APE1 can act as an endoribonuclease that catalyzes mRNA hydrolysis at certain pyrimidine-purine sites and thus controls the level of certain transcripts. In addition, the presence of Mg^(2+) ions was shown to be not required for the endoribonuclease activity of APE1, in contrast to the AP-endonuclease activity. This indicates differences in mechanisms of APE1 catalysis on RNA and DNA substrates, but the reasons for these differences remain unclear. Here, the analysis of endoribonuclease hydrolysis of model RNA substrates with wild type APE1 enzyme and its mutant forms Y171F, R177F, R181A, D210N, N212A, T268D, M270A, and D308A, was performed. It was shown that mutation of Asn212, Asp210, and Tyr171 residues leads to the decrease of AP-endonuclease activity while endoribonuclease activity is retained. Also, T268D and M270A APE1 mutants lose specificity to pyrimidine-purine sequences. R177F and R181A did not show a significant decrease in enzyme activity, whereas D308A demonstrated a decrease of endoribonuclease activity.
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DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Endonucleases , Reparo do DNA/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Endorribonucleases/genética , Humanos , Cinética , MutaçãoRESUMO
The prognostic models assessing the risk of prehypertension in coming 1-2-year period for 30-60-year-old subjects were developed with the help of computer recognition technology using 6 recognition methods. These models are based on the content of molecular markers in blood serum and the risk factors for the development of prehypertension in men and women who had "optimal" BP for last 3 years and in patients with newly diagnosed prehypertension. The models were compared for their prediction power. The most effective model was obtained with gradient boosting method based on the content of molecular markers. It is characterized with a high predictive power (ROC AUC=0.76), specificity (96.4%), and overall accuracy (86.6%) accompanied with close relationship between prognosis and actual symptoms of prehypertension (p=0.001).
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Pré-Hipertensão/patologia , Adulto , Biomarcadores/metabolismo , Pressão Sanguínea/fisiologia , Humanos , Pessoa de Meia-Idade , Pré-Hipertensão/fisiopatologia , PrognósticoRESUMO
Aim To identify clinical and laboratory indexes related with the atherosclerotic plaque (ASP) echogenicity based on results of the analysis of grey-scale median (GSM) in patients aged 40-64 years.Material and methods The study included patients aged 40-64 years with carotid atherosclerosis. The carotid duplex scanning was performed for all patients. The GSM analysis of obtained images was performed with the Adobe Photoshop CS6 software.Results Atherosclerotic cardiovascular diseases were found in 31 (21.4â%) patients. Correlation analysis determined inverse interrelationships between GSM and the body weight index (BWI) (r=-0.359; p<0.0001), waist circumference (r=-0.357; p<0.0001), and levels of uric acid (r=-0.244; p=0.021) and glucose (r=-0.205; p=0.032). According to the regression, statistically significant correlations remained between GSM and BWI as well as the waist circumference after the adjustment for sex and age.Conclusion In patients with carotid atherosclerosis aged 40-64 years, the decrease in ASP GSM was associated with increases in BWI and waist circumference.
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Aterosclerose , Doenças das Artérias Carótidas , Estenose das Carótidas , Placa Aterosclerótica , Adulto , Aterosclerose/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Fatores de Risco , UltrassonografiaRESUMO
Many natural substances exhibit anti-inflammatory activity and considerable potential in prophylaxis and treatment of allergies. Knowing exact molecular targets, which is required for developing these as medicinal products, is often challenging for multicomponent compositions. In the present study we examined novel polyphenolic substance, a water-soluble fraction of wood lignin (laboratory code BP-Cx-1). In our previous study, a number of polyphenolic components of BP-Cx-1 (flavonoids, sapogenins, phenanthrenes etc.) were identified as the major carriers of biological activity of BP-Cx drug family, and several molecular targets involved in cancer and/or inflammation signaling pathways were proposed based on the results of the in vitro and in silico screening studies. In the present study, half maximal inhibitory concentration (IC50) of BP-Cx-1 was established with a radioligand method and a range of IC50 values between 22.8 and 40.3 µg/ml were obtained for adenosine receptors A1, A2A and prostaglandin receptors EP2, IP (PGI2). IC50 for serotonin 5-HT1 and for glucocorticoid GR receptors were 3.0 µg/ml and 12.6 µg/ml, respectively, both being within the range of BP-Cx-1 concentrations achievable in in vivo models. Further, distribution of [3H] labelled BP-Cx-1 in NIH3T3 murine fibroblasts and MCF7/R carcinoma cells was studied with autoradiography. [3H]-BP-Cx-1 (visualized as silver grains produced by tritium beta particles) was mainly localized along the cell membrane, in the perinuclear region and in the nucleus, suggesting ability of BP-Cx-1 to enter cells and bind to membrane or cytosol receptors. In our experiment, we observed the effect of BP-Cx-1 on maturation of dendritic cells (DCs): downregulation of expression of the lipid-presentation molecule CD1a, co-stimulatory molecules CD80, CD83 and CD 40, decreased production of pro-inflammatory cytokines IL-4 and TNF-α and increased production of anti-inflammatory cytokine IL-10. It is hypothesized that [3H]-BP-Cx-1 detectable in the nucleus is part of the activated GR complex, known to be involved in regulation of transcription of genes responsible for the anti-inflammatory response. Based on IC50, cell distribution data and results of the experiment with DCs it is suggested that the in vivo effects of BP-Cx-1 are mediated via GR and 5-HT1 receptors thus promoting development of tolerogenic effector function in dendritic cells.
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Células Dendríticas , Lignina , Animais , Citocinas , Camundongos , Células NIH 3T3 , ÁguaRESUMO
Binase is an extracellular guanyl-preferring ribonuclease from Bacillus pumilus. The main biological function of binase is RNA degradation with the formation of guanosine-2',3'-cyclic phosphate and its subsequent hydrolysis to 3'-phosphate. Extracellular RNases are believed to be key agents that affect the functional activity of the body, as they directly interact with epithelial and immune cells. The biological effects of the enzyme may consist of both direct RNA degradation, and the accumulation of 2',3'-cGMP in the human body. In this work, we have performed a comparative analysis of the cleavage efficiency of model RNA substrates, i.e., short hairpin structures that contain guanosine at various positions. It has been shown that the hydrolysis efficiency of the model RNA substrates depends on the position of guanosine. We have also demonstrated the influence of various divalent metal ions and low molecular weight nucleotide compounds on the binase-catalyzed endoribonucleolytic reaction.
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Bacillus pumilus/enzimologia , Proteínas de Bactérias/metabolismo , Endorribonucleases/metabolismo , RNA/metabolismo , Hidrólise , Íons , Peso Molecular , NucleotídeosRESUMO
The concentrations of the key factors of molecular pathogenesis of prehypertension (angiotensin II, HLDF24, S100b, endothelin, autoantibodies to these molecules, and VEGF) were analyzed in subjects with optimal BP (<120/80 mm Hg) and prehypertension (120-139/80-89 mm Hg). Comparative and correlation analysis of the levels of these molecules was performed. A statistically significant decrease in HLDF24 level in prehypertension in comparison optimal BP was observed. Specific features and interactions between the studied factors in optimal BP and in prehypertension were studied. The mechanisms underlying the observed associations between serum concentration of HLFF24 and the development of prehypertension were discussed.
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Biomarcadores/sangue , Proteínas de Neoplasias/sangue , Fragmentos de Peptídeos/sangue , Pré-Hipertensão/sangue , Angiotensina II/sangue , Autoanticorpos/sangue , Pressão Sanguínea/fisiologia , Endotelinas/sangue , Feminino , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Subunidade beta da Proteína Ligante de Cálcio S100/sangueRESUMO
OBJECTIVES: Five to eight per cent of HIV-positive individuals initiating abacavir (ABC) experience potentially fatal hypersensitivity reactions (HSRs). We sought to describe the proportion of individuals initiating ABC and to describe the incidence and factors associated with HSR among those prescribed ABC. METHODS: We calculated the proportion of EuroSIDA individuals receiving ABC-based combination antiretroviral therapy (cART) among those receiving cART after 1 January 2009. Poisson regression was used to identify demographic, and current clinical and laboratory factors associated with ABC utilization and discontinuation. RESULTS: Between 2009 and 2016, of 10 076 individuals receiving cART, 3472 (34%) had ever received ABC-based cART. Temporal trends of ABC utilization were also heterogeneous, with 28% using ABC in 2009, dropping to 26% in 2010 and increasing to 31% in 2016, and varied across regions and over time. Poisson models showed lower ABC utilization in older individuals, and in those with higher CD4 cell counts, higher cART lines, and prior AIDS. Higher ABC utilization was associated with higher HIV RNA and poor renal function, and was more common in Central-East and Eastern Europe and lowest during 2014. During 779 person-years of follow-up (PYFU) in 2139 individuals starting ABC after 1 January 2009, 113 discontinued ABC within 6 weeks of initiation for any reason [incidence rate (IR) 14.5 (95% confidence interval (CI) 12.1, 17.5) per 100 PYFU], 13 because of reported HSR [IR 0.3 (95% CI 0.1, 1.0) per 100 PYFU] and 35 because of reported HSR/any toxicity [IR 4.5 (95% CI 3.2, 6.3) per 100 PYFU]. There were no factors significantly associated with ABC discontinuation because of reported HSR/any toxicity. CONCLUSIONS: ABC remains commonly used across Europe and the incidence of discontinuation because of reported HSR was low in our study population.
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Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Infecções por HIV/tratamento farmacológico , Adulto , Estudos de Coortes , Hipersensibilidade a Drogas/etiologia , Uso de Medicamentos , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Distribuição de PoissonRESUMO
AIMS: The objective of this work was to assess the antibacterial effect of 2-mercaptobenzothiazole (MBT), used as model-biocide, immobilized in a layered double hydroxide (LDH) structure, under different conditions of pH and salinity, envisaging possible applications of the system in active antifouling and anticorrosion coatings. METHODS AND RESULTS: Biological effects of MBT immobilized in LDH were assessed by monitoring bacterial bioluminescence of cell suspensions of either Allivibrio fischeri or a recombinant strain of Escherichia coli, as a proxy for bacterial activity. Salinity (1, 2 and 3% NaCl) and pH (4, 5, 6 and 7) of the suspension media were experimentally manipulated and biocide release tests were performed in parallel. The release profiles obtained by UV-visible spectrophotometry indicated a fast release of biocide from MBT@LDH, slightly enhanced in 3% NaCl and under alkaline conditions. However, biological effects were more pronounced at 1% NaCl and at neutral pH. CONCLUSIONS: The release and toxic effect of MBT immobilized in LDH is dependent on the concentration of solutes in the suspension medium. SIGNIFICANCE AND IMPACT OF THE STUDY: The results confirm LDH as a biologically compatible material with potential to be used for biocide delivery.
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Antibacterianos/farmacologia , Benzotiazóis/farmacologia , Hidróxidos/química , Antibacterianos/química , Benzotiazóis/química , Composição de Medicamentos , Escherichia coli/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Cinética , Nanoestruturas/químicaRESUMO
We present data on the species composition of helminths in brown bears (Ursus arctos) from the Murmansk Region, Russia. The absence of any information about helminths of brown bear in the region necessitated the conduct of these studies. Samples were collected in 2014 and 2015 in the southern part of the Kola Peninsula from the White Sea coastal habitats. Annually, in the study area, 1-3 bears are legally hunted and biological samples for examination are very difficult to obtain. Therefore, we used fecal samples. We studied 93 feces and identified parasite eggs identified in 43 of them by morphometric criteria. The surveys revealed eggs of the following helminths: Dicrocoelium sp., Diphyllobothrium sp., Anoplocephalidae, Capillariidae, Baylisascaris sp., Strongylida 1, and Strongylida 2. These results represent the first reconnaissance stage, which allowed characterizing the taxonomic diversity and prevalence of parasites of brown bears of the Kola Peninsula.