RESUMO
An ongoing controversy in brain metabolism is whether increases in neural activity cause a local and rapid decrease in oxygen concentration (i.e., the "initial dip") preceding functional hyperemia. This initial dip has been suggested to cause a transient increase in vascular deoxyhemoglobin with several imaging techniques and stimulation paradigms, but not consistently. Here, we investigate contributors to this initial dip in a distinct neuronal network, an olfactory bulb (OB) glomerulus most sensitive to a specific odorant (ethyl tiglate [ET]) and a site of strong activation and energy consumption upon ET stimulation. Combining two-photon fluorescence and phosphorescence lifetime microscopy, and calcium, blood flow, and pO2 measurements, we characterized this initial dip in pO2 in mice chronically implanted with a glass cranial window, during both awake and anesthetized conditions. In anesthetized mice, a transient dip in vascular pO2 was detected in this glomerulus when functional hyperemia was slightly delayed, but its amplitude was minute (0.3 SD of resting baseline). This vascular pO2 dip was not observed in other glomeruli responding nonspecifically to ET, and it was poorly influenced by resting pO2. In awake mice, the dip in pO2 was absent in capillaries as well as, surprisingly, in the neuropil. These high-resolution pO2 measurements demonstrate that in awake mice recovered from brain surgery, neurovascular coupling was too fast and efficient to reveal an initial dip in pO2.
Assuntos
Encéfalo , Acoplamento Neurovascular , Oxigênio , Vigília , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Camundongos , Rede Nervosa , Neurônios/fisiologia , Bulbo Olfatório/metabolismo , Oxigênio/metabolismoRESUMO
In this study, our goal was to synthesize novel aryl tacrine derivatives and assess their potential as anticancer, antibacterial agents, and enzyme inhibitors. We adopted a two-step approach, initiating with the synthesis of dibromotacrine derivatives 3 and 4 through the Friedlander reaction. These intermediates underwent further transformation into diarylated tacrine derivatives 3a-e and 4a-e using a Suzuki-Miyaura cross-coupling reaction. Thorough characterization of these novel diarylated tacrines was achieved using various spectroscopic techniques. Our findings highlighted the potent anticancer effects of these innovative compounds across a range of cancer cell lines, including lung, gynecologic, bone, colon, and breast cancers, while demonstrating low cytotoxicity against normal cells. Notably, these compounds surpassed the control drug, 5-Fluorouracil, in terms of antiproliferative activity in numerous cancer cell lines. Moreover, our investigation included an analysis of the inhibitory properties of these novel compounds against various microorganisms and cytosolic carbonic anhydrase enzymes. The results suggest their potential for further exploration as cancer-specific, enzyme inhibitory, and antibacterial therapeutic agents. Notably, four compounds, namely, 5,7-bis(4-(methylthio)phenyl)tacrine (3d), 5,7-bis(4-(trifluoromethoxy)phenyl)tacrine (3e), 2,4-bis(4-(trifluoromethoxy)phenyl)-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-amine (4e), and 6,8-dibromotacrine (3), emerged as the most promising candidates for preclinical studies.
Assuntos
Antineoplásicos , Neoplasias , Feminino , Humanos , Tacrina/farmacologia , Tacrina/química , Antifúngicos/farmacologia , Anticonvulsivantes/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Inibidores Enzimáticos/farmacologia , Antineoplásicos/química , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
Kurut is a traditional dry dairy product mostly consumed in Central Asia. In this study, the distribution of the dominant bacteria present in kurut samples (n=84) originated from seven (Chuy, Issyk-Kul, Talas, Naryn, Jalal-Abad, Osh, and Batken) regions in Kyrgyzstan were analyzed with Illumina iSeq100 platform. The dominant phylum detected was Firmicutes followed by Proteobacteria, Actinobacteria, Cyanobacteria/Chloroplast, and Tenericutes. The most abundant family detected was Lactobacillaceae followed by Streptococcaceae, Enterococcaceae, Chloroplast, and Leuconostocaceae. At the genus level, Lactobacillus was the predominant one in samples and Streptococcus, Enterococcus, Lactococcus, and Streptophyta followed this. Further comprehensive characterization analyses in kurut samples may have potential applications both in industrial starter culture developments and also future therapeutic approaches based on potential strains with probiotic properties.
Assuntos
Bactérias , Leite , Animais , Bovinos , Feminino , Leite/microbiologia , Quirguistão , Lactobacillus , StreptococcusRESUMO
Domestic horses could be bred for leisure activities and meat production, as is already the case in many countries. Horse meat is consumed in various countries, including Kazakhstan and Kyrgyzstan, and with the increase in this consumption, horses are registered as livestock by the Food and Agricultural Organization. In this study, horse meat microbiota of horse samples (n = 56; 32 samples from Kazakhstan and 24 samples from Kyrgyzstan) from two countries, Kazakhstan (n = 3) and Kyrgyzstan (n = 1), were investigated for the first time by next-generation sequencing and metabarcoding analysis. The results demonstrated that Firmicutes, Proteobacteria, and Actinobacteria were the dominant bacterial phyla in all samples. In addition, three (5.4%) Staphylococcus strains were isolated from the Uzynagash region, Kazakhstan. Staphylococcus strains were identified as Staphylococcus warneri, S. epidermidis, and S. pasteuri by partial 16S rRNA DNA gene Sanger sequencing. All three Staphylococcus isolates were nonbiofilm formers; only the S. pasteuri was detected as multidrug-resistant (resistant to penicillin, cefoxitin, and oxacillin). In addition, S. pasteuri was found to carry mecA, mecC, and tetK genes. This is the first study to detect potentially pathogenic Staphylococcus spp. in horse meat samples originating from Kazakhstan. In conclusion, it should be carefully considered that undercooked horse meat may pose a risk to consumers in terms of pathogens such as antibiotic-resistant Staphylococcus isolates.
Assuntos
Antibacterianos , Biofilmes , Microbiota , RNA Ribossômico 16S , Staphylococcus , Cavalos/microbiologia , Animais , Biofilmes/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Staphylococcus/isolamento & purificação , Staphylococcus/genética , RNA Ribossômico 16S/genética , Antibacterianos/farmacologia , Cazaquistão , Carne/microbiologia , Testes de Sensibilidade Microbiana , Sequenciamento de Nucleotídeos em Larga Escala , Microbiologia de Alimentos , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
INTRODUCTION: Computed tomography (CT) is normally used in evaluation of patients with esthetic and functional nasal deformities. Stereophotogrammetry (SPG) is a measurement device that is an alternative to CT and does not harm human health. In this single-center retrospective study, we aimed to evaluate measurements obtained with CT and SPG. METHODS: The measurements of 18 patients who applied to our clinic between January 2022 and August 2022 and planned for septorhinoplasty were performed on both 3D images obtained with paranasal sinus CT and SPG device (SLR type Vectra H1 system). Measurements included that dorsocolumellar length, columella-filtral length, nasal tip projection ratio (dorsocolumellar length/columella-filtral length), columella-labial angle, nasofrontal angle, tip deviation direction, tip deviation angle, tip deviation distance and dorsal nasal hump. RESULTS: Most of patients were male (61.1%). Mean age was 24.5 years. Only columella-labial angle measurements showed a low level of significant difference (p < 0.05). However, there was no significance difference in other measurements (p > 0.05). A significant strong correlation was observed between all Vectra and CT measurements (p = 0.000). CONCLUSION: SPG device can be applied quickly in polyclinic without giving radiation to patient. Measurements can be taken automatically using a software. Its use in postoperative period does not carry any risk. Disadvantage of SPG is lack of information about internal nasal passage. However, there is a strong correlation between measurements obtained from both measurement devices. Therefore, SPG can be considered as an alternative to CT imaging in operation planning. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
RESUMO
BACKGROUND: Ferulago setifolia K. Koch (Apiaceae) has been the subject of this study, aiming to comprehensively determine its phenolic fingerprint and evaluate its various biological activities. The liquid chromatography-tandem mass spectrometry analysis of the 70% methanol extract of F. setifolia (FS) revealed the presence of 23 phytochemicals, among which chlorogenic acid, quinic acid, kaempferol-3-O-glucoside, and quercetin-3-O-glucoside were identified as the major phenolics in the extract. RESULTS: The biological screening included examinations of antioxidant, antibacterial, antiproliferative, and cytotoxic activities. The FS extract displayed moderate 2,2-diphenyl-1-picrylhydrazyl radical scavenging and ferric-reducing capacity, indicating moderate antioxidant activity. Furthermore, FS exhibited significant antiproliferative effects on cancer cells while showing low cytotoxicity on normal cells. The antibacterial activity findings revealed that FS demonstrated potent activity against Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus, and Escherichia coli. CONCLUSION: The findings of this study suggest that the methanolic extract of FS holds promise as a potential source of biologically active compounds. It can be utilized for the development of pharmaceutical formulations, thanks to its significant antiproliferative and antibacterial activities. Additionally, FS can serve as a valuable source of chlorogenic acid for industrial applications. © 2023 Society of Chemical Industry.
Assuntos
Apiaceae , Extratos Vegetais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ácido Clorogênico/farmacologia , Antioxidantes/química , Compostos Fitoquímicos/química , Fenóis/análise , Antibacterianos/farmacologiaRESUMO
BACKGROUND: The objective of this study is to investigate the antiproliferative, antioxidant, antimicrobial, and enzyme activity capacities and phytochemical compositions of Thymus pectinatus (TP), Thymus convolutus (TC), which are endemic to Türkiye. Quantitative analysis of phenolic compounds in the extracts was conducted using liquid chromatography-tandem mass spectrometry, targeting 53 phenolic compounds. RESULTS: Rosmarinic acid, quinic acid, and cynaroside were identified as the major compounds, exhibiting quantitative variation in both extracts. The extracts had a high total phenolic content, with 113.57 ± 0.58 mg gallic acid equivalents (GAE)/g extract for TP and 130.52 ± 1.05 mg GAE/g extract for TC. Furthermore, although both extracts exhibited high total flavonoid content; the TP extract (75.12 ± 1.65 mg quercitin equivalents (QE)/g extract) displayed a higher flavonoid content than the TC extract (30.24 ± 0.74 mg QE/g extract) did. The extracts had a promising antiproliferative effect on C6, HeLa, and HT29 cancer cell lines with a less cytotoxic effect (10.5-14.2%) against normal cells. Both extracts exhibited very potent inhibitory activity against the xanthine oxidase enzyme, with half-maximal inhibitory concentration values of respectively 2.07 ± 0.03 µg mL-1 and 2.76 ± 0.06 µg mL-1 and moderate activity against tyrosinase and α-glucosidase. Docking simulations proved that rosmarinic acid and cynaroside, the major components of the extracts, were the most potent inhibitors of xanthine oxidase. According to antimicrobial activity results, the TC extract exhibited moderate activity against Staphylococcus aureus, and the TP extract had strong activity against both Enterococcus faecium and S. aureus. CONCLUSION: These findings emphasize the beneficial effects of the two endemic Thymus species on human health and suggest their potential use as plant-derived bioactive agents. © 2024 Society of Chemical Industry.
Assuntos
Anti-Infecciosos , Pectinatus , Humanos , Antioxidantes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espectrometria de Massas em Tandem , Staphylococcus aureus , Xantina Oxidase , Anti-Infecciosos/farmacologia , Cromatografia Líquida , Flavonoides/farmacologia , Flavonoides/análise , Fenóis/análise , Células HeLa , Compostos Fitoquímicos/químicaRESUMO
ESBL-producing Escherichia coli strains threaten public health and obligate the use of last-resort antibiotics. This study identified 15 E. coli isolates through 16S rRNA and gyrB genes, specific to E. coli, in 120 egg samples (12.5%). Antibiotic resistance was detected according to the EUCAST and CLSI in E. coli isolates. 2 isolates were susceptible to all antibiotics, one isolate was resistant to one antibiotic, one isolate was resistant to 2 antibiotics, and 11 E. coli isolates (73.3%) had multidrug resistance. Most frequent antibiotic resistances were detected against ampicillin (80%), tetracycline (66.6%), and chloramphenicol (66.6%). A double-disc confirmation test was used to detect ESBL production, and blaTEM, blaSHV, blaCTX-M and blaOXA genes were searched by PCR. The blaTEM (100%) gene was found in all resistant E. coli isolates, and the blaCTX-M gene was detected in only 3 (20%) E. coli isolates. None of the E. coli isolates contained the genes responsible for carbapenem and colistin resistance. Our results show that multi-drug antibiotic resistance and the blaTEM gene are frequent in E. coli from table eggs in Istanbul. This is the first preliminary study on ESBL-producing E. coli isolates in table eggs in Türkiye.
Assuntos
Ovos , Escherichia coli , beta-Lactamases , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Animais , Ovos/microbiologia , Turquia/epidemiologia , Antibacterianos/farmacologia , Galinhas/microbiologia , Farmacorresistência Bacteriana/genéticaRESUMO
A novel phenylethanoid, ferruginoside D, together with fourteen known compounds were isolated from the Verbascum leiocarpum for the first time. Chemical structures of isolated compounds were determined by spectroscopic analysis including HR-ESI-MS and NMR spectra. The antioxidant, α-glucosidase inhibitory properties, and antiproliferative activities against multiple cell lines (A172, C6, HeLa, A2780, SW620, HT29, Beas2B, RPE, and HSF) of the isolated compounds were evaluated inâ vitro. According to the results, iridoids, flavonoids (luteolin and apigenin), and phenylethanoids (poliumoside and isoverbascoside) with strong antiproliferative potential were also found to have cytostatic effects. Furthermore, the investigation revealed that compounds luteolin, poliumoside, verbascoside, isoverbascoside, ferruginoside C, ferruginoside D, and ursolic acid show potent alpha-glucosidase inhibitory activity, while compounds luteolin, verbascoside, and isoverbascoside exhibit substantial antioxidant activity. The new compound (ferruginoside D) was found moderately active against cancer cell lines, with strong alpha-glucosidase inhibitory activity, and moderate antioxidant properties.
Assuntos
Neoplasias Ovarianas , Verbascum , Feminino , Humanos , Antioxidantes/farmacologia , Verbascum/química , Linhagem Celular Tumoral , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Luteolina , alfa-GlucosidasesRESUMO
Understanding the relationships between biological processes is paramount to unravel pathophysiological mechanisms. These relationships can be modeled with Transfer Functions (TFs), with no need of a priori hypotheses as to the shape of the transfer function. Here we present Iliski, a software dedicated to TFs computation between two signals. It includes different pre-treatment routines and TF computation processes: deconvolution, deterministic and non-deterministic optimization algorithms that are adapted to disparate datasets. We apply Iliski to data on neurovascular coupling, an ensemble of cellular mechanisms that link neuronal activity to local changes of blood flow, highlighting the software benefits and caveats in the computation and evaluation of TFs. We also propose a workflow that will help users to choose the best computation according to the dataset. Iliski is available under the open-source license CC BY 4.0 on GitHub (https://github.com/alike-aydin/Iliski) and can be used on the most common operating systems, either within the MATLAB environment, or as a standalone application.
Assuntos
Software , Algoritmos , Biologia Computacional/métodos , Fluxo de TrabalhoRESUMO
Schiff bases are compounds that have gained importance in the paint industry due to their colorful nature and in the field of chemistry and biochemistry due to their biological activities. Various biological applications of Schiff bases, such as antitumor, antifungal, antibacterial, antioxidant, antituberculosis, and anthelmintic, have been widely studied. Within the scope of the study, 5-bromo-2-hydroxybenzaldehyde and amino acid methyl esters (isoleucine, phenylalanine, and methionine) and amino acid Schiff bases were synthesized first. The synthesis of the new Zn(II) complexes of these Schiff bases was carried out by the reaction of synthesized Schiff bases and Zn(OAc)2 ·2H2 O. The structures of the synthesized complexes were elucidated using elemental analysis, Fourier transform infrared, nuclear magnetic resonance, UV-visible, and thermal analysis spectroscopy techniques. These synthesized salts were found to be effective inhibitor compounds for the α-glycosidase, and acetylcholinesterase enzyme with Ki values in the range of 30.50 ± 3.82-38.17 ± 6.26 µM for α-glycosidase, 3.68 ± 0.54-10.27 ± 1.68 µM for butyrylcholinesterase, and 6.26 ± 0.83-15.73 ± 4.73 µM for acetylcholinesterase, respectively.
Assuntos
Acetilcolinesterase , Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase/química , Inibidores da Colinesterase , Complexos de Coordenação , Simulação de Acoplamento Molecular , Zinco , Acetilcolinesterase/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/uso terapêutico , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/química , Humanos , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/uso terapêutico , Zinco/química , Zinco/uso terapêuticoRESUMO
BACKGROUND: The aging population and increasing chronic diseases make a tremendous burden on the health care system. The study evaluated the relationship between comorbidity indices and common geriatric syndromes. METHODS: A total of 366 patients who were hospitalized in a university geriatric inpatient service were included in the study. Sociodemographic characteristics, laboratory findings, and comprehensive geriatric assessment(CGA) parameters were recorded. Malnutrition, urinary incontinence, frailty, polypharmacy, falls, orthostatic hypotension, depression, and cognitive performance were evaluated. Comorbidities were ranked using the Charlson Comorbidity Index(CCI), Elixhauser Comorbidity Index(ECM), Geriatric Index of Comorbidity(GIC), and Medicine Comorbidity Index(MCI). Because, the CCI is a valid and reliable tool used in different clinical settings and diseases, patients with CCI score higher than four was accepted as multimorbid. Additionally, the relationship between geriatric syndromes and comorbidity indices was assessed with regression analysis. RESULTS: Patients' mean age was 76.2 ± 7.25 years(67.8% female). The age and sex of multimorbid patients according to the CCI were not different compared to others. The multimorbid group had a higher rate of dementia and polypharmacy among geriatric syndromes. All four indices were associated with frailty and polypharmacy(p < 0.05). CCI and ECM scores were related to dementia, polypharmacy, and frailty. Moreover, CCI was also associated with separately slow walking speed and low muscle strength. On the other hand, unlike CCI, ECM was associated with malnutrition. CONCLUSIONS: In the study comparing the four comorbidity indices, it is revealed that none of the indices is sufficient to use alone in geriatric practice. New indices should be developed considering the complexity of the geriatric cases and the limitations of the existing indices.
Assuntos
Demência , Fragilidade , Desnutrição , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Demência/epidemiologia , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Masculino , Desnutrição/epidemiologia , SíndromeRESUMO
Brucellosis is a multisystemic disease that can present with multiple signs and symptoms. Rarely, brucellosis can manifest as neurobrucellosis, with central or peripheral nervous system involvement. Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease that progresses rapidly, causing ascending muscle weakness, and is accompanied by areflexia/hyporeflexia. Regarding GBS etiology, it is thought to be an autoimmune disease, triggered by a previous bacterial or viral infection. There are a few Brucella-associated GBS case reports in the literature and in our opinion, only one of them is a pediatric patient. Herein we reported a case of GBS associated with neurobrucellosis, who was successfully treated with therapeutic plasmapheresis (TP) due to poor response to IVIG treatment.
Assuntos
Doenças Autoimunes , Brucelose , Síndrome de Guillain-Barré , Doenças Autoimunes/terapia , Brucelose/tratamento farmacológico , Brucelose/terapia , Criança , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Plasmaferese/efeitos adversosRESUMO
Background and Objectives: In patients with paroxysmal atrial fibrillation (AF) undergoing CABG or aortic valve surgery, many surgeons are not willing to open the left atrium to perform a complete left-sided Cox-Maze lesion set. Pulmonary vein isolation (PVI) is often favored in those patients. We investigated the outcome of patients with isolated pulmonary vein isolation compared to those receiving an extended left atrial (LA) lesion set. Materials and Methods: Between 2003 and 2016, 817 patients received concomitant surgical AF ablation in our institution. A total of 268 patients with paroxysmal AF were treated by surgical ablation concomitant to AVR or CABG. Of those, 86 patients underwent a complete left-sided lesion set, while 182 patients were treated with an isolated pulmonary vein isolation. The primary endpoint was freedom from atrial fibrillation at 12 months' follow-up. Results: There were no statistically significant differences regarding baseline characteristics. No major ablation-related complications were observed in any of the groups. In the PVI group, three patients (1.6%) had an intraoperative stroke, while two (2.3%) patients experienced a stroke in the LA ablation group (p = 0.98). In-hospital mortality was 3.4% in the PVI group, and 2.8% in the extended LA group (p = 0.33). Freedom from AF at 12 months' follow-up was 76% in the extended LA ablation group and 70% in the PVI group, showing no statistically significant difference (p = 0.32). Conclusion: Surgical AF ablation concomitant to CABG or AVR in patients with paroxysmal AF is safe and effective. There was no statistically significant difference between the compared lesion sets in terms of freedom from AF, survival or stroke rate after 12 months.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Acidente Vascular Cerebral , Humanos , Veias Pulmonares/cirurgia , Resultado do Tratamento , Átrios do Coração/cirurgia , Ablação por Cateter/efeitos adversos , Ponte de Artéria Coronária , Acidente Vascular Cerebral/complicações , RecidivaRESUMO
In this work, due to the biological activity evaluation, a series of hydroxy methoxy benzoins (1-8), benzils (10-16) and methoxy benzoin/benzil-O-ß-d-glucosides (17-28) were synthesized. Antioxidant (FRAP, CUPRAC, DPPH), antimicrobial (16 microorganisms, and two yeast), enzyme inhibition (α-amylase, α-glucosidase, AChE, BChE, and tyrosinase) of all synthesized benzoin/benzil analogs were investigated. Benzoins (1-8) showed the most effective antioxidant properties compared to all three methods. Compound 28 against α-amylase, compound 9 against α-glucosidase, compound 11 against AChE, compound 2 against BChE, and compound 13 against tyrosinase showed the best activities with the better or similar IC50 values as used standards. Hydroxy methoxy benzoin compounds (1-8) among all four groups were seen as the most effective against the tested microorganism. Molecular docking analysis showed that all tested compounds 1-28 (0.01-2.22 µM) had the best binding affinity against AChE enzyme. Cytotoxic effects of the many of compounds (1-16, 21, and 24) also investigated and it was found that they caused different effects in different cells. The LDH tests of compounds 1a + b, 4, 7, 8, 9, 11, 12, 21, and 24, seemed to be effective compared to the positive control cisplatin. The cytotoxicity of compounds 6 (9.24%) for MCF7 cancer cells, 8 (5.16%) and 4 (8.26%) for HT29 cancer cells, 24 (9.84%) for Hep3B cells and 8 (8.52%), 7 (5.70%), 4 (6.94) and 9 (7.22%) for C6 cells were at normal values. And also cytotoxic activity of four compounds (5, 9, 21, and 24) among the all synthetic groups, were evaluated to the HeLa and RPE. Compound 5 showed anticancer activity on HeLa and RPE cancer cells as much as or better than cisplatin which was used as standard.
Assuntos
Anti-Infecciosos/química , Antineoplásicos/química , Antioxidantes/química , Benzoína/análogos & derivados , Inibidores Enzimáticos/química , Fenilglioxal/análogos & derivados , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/farmacologia , Benzoína/síntese química , Benzoína/farmacologia , Linhagem Celular Tumoral , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Fenilglioxal/síntese química , Fenilglioxal/química , Fenilglioxal/farmacologiaRESUMO
BACKGROUND: It is crucial to evaluate the causes of morbidity and mortality in elderly patients with dementia, such as orthostatic hypotension (OH), which may affect their daily life activities, reduce the quality of life, and increase the caregiver burden. OBJECTIVE: We aimed to investigate the relationship between OH and the most common subtypes of dementia in detail. METHODS: A total of 268 older adults with dementia diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and behavioral variant frontotemporal dementia (bvFTD), and 539 older adults without dementia were included in this prospective study. Comprehensive geriatric assessment including comorbidity, medication evaluation, and the head-up tilt test was also performed. RESULTS: Of the participants, 13.8, 8.3, 6.4, and 4.8% had AD, DLB, bvFTD, and VaD, respectively. After adjusting for age, gender, the presence of comorbidities, and usage of OH-induced drugs; AD, DLB, and VaD were associated with OH (odds ratio [OR]: 2.23 confidence interval [CI] 95% 1.31-3.80; p = 0.003; OR: 3.68 CI 95% 1.98-6.83; p < 0.001, and OR: 3.56 CI 95% 1.46-8.69; p = 0.005, respectively). Furthermore, VaD was independently related to diastolic OH (OR: 4.19 CI 95% 1.66-10.57; p = 0.002), whereas AD and DLB were not. CONCLUSIONS: This study shows that elderly patients with DLB, AD, and VaD often have OH, a disabling autonomic dysfunction feature. Moreover, diastolic OH may play a role in the development of VaD. Therefore, considering potential complications of OH, it is essential to evaluate OH in the follow-up and management of those patients.
Assuntos
Demência/classificação , Demência/complicações , Hipotensão Ortostática/complicações , Idoso , Doença de Alzheimer/classificação , Doença de Alzheimer/complicações , Demência/diagnóstico , Demência/fisiopatologia , Demência Vascular/classificação , Demência Vascular/complicações , Feminino , Humanos , Doença por Corpos de Lewy/classificação , Doença por Corpos de Lewy/complicações , Masculino , Estudos Prospectivos , Qualidade de VidaRESUMO
A series of new 2-amino-4-aryl-6-pyridopyrimidines, and their N-alkyl bromide derivatives were designed and synthesized by employing methyl substituted azachalcones. These novel compounds were evaluated and compared to the well-known chemotherapeutics in terms of their anti-cancer and anti-microbial functions, and their DNA/protein binding affinities. In order for the cell proliferation, cytotoxicity and microdilution features to be observed, various cancer cell lines (Hep3B, A549, HeLa, C6, HT29, MCF7) were treated with 2-amino-4-aryl-6-pyridopyrimidines (1-9) and their N-alkyl bromide derivatives (2a-c, 3a-c,5a-c,6a-c, 8a-c, 9a-c). Studies on the cells revealed that both pyrimidines and their alkyl derivatives (i) have a high anti-proliferative and anti-microbial activities, (ii) cause cell rounding, cytoplasmic blebs, and anomalous globular structure, and (iii) strongly bound to DNA/BSA macromolecules. Especially the length of the alkyl chain of the N-alkyl bromides has an increasing effect on the antiproliferative, antibacterial and cytotoxic functions, also DNA/protein binding affinity. Those results indicate the novel compounds to be promising antiproliferative agents, and their anti-cancer potential makes them candidates to be used for cancer therapy.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , DNA/química , Pirimidinas/farmacologia , Soroalbumina Bovina/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Bovinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Women aged 65 years and over are at increased risk of falling. Falls in this age group increase the risk of morbidity and mortality. AIMS: The aim of the present study was to find the most common factors that increase the risk of falling in older women, by using four different assessment methods. METHODS: 682 women, who attended a geriatric outpatient clinic and underwent comprehensive geriatric assessment, were included in the study. History of falling last year, the Timed Up and Go (TUG) test, Performance-Oriented Mobility Assessment (POMA), and 4-m walking speed test were carried out on all patients. RESULTS: The mean age (SD) of patients were 74.4 (8.5) years. 31.5% of women had a history of falling in the last year. 11%, 36.5%, and 33.3% of patients had a falling risk according to POMA, TUG and 4-m walking speed test, respectively. We identified the following risk factors that increase the risk of falling, according to these four methods: urinary incontinence, dizziness and imbalance, using a walking stick, frailty, dynapenia, higher Charlson Comorbidity Index and Geriatric Depression Scale score, and lower basic and instrumental activities of daily living scores (p < 0.05). We found a significant correlation between all the assessment methods (p < 0.001). CONCLUSION: There is a strong relationship between fall risk and dizziness, using a walking stick, dynapenia, high number of comorbidities, low functionality, and some geriatric syndromes such as depression, frailty, and urinary incontinence in older women. Therefore, older women should routinely be screened for these risk factors.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Atividades Cotidianas , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Fragilidade/complicações , Humanos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Despite differences between the studies regarding methods for estimating low muscle mass, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends use of two standard deviations (SDs) below the reference sex-specific means of healthy young adults. AIMS: The aim of this study was to determine the cutoff points of skeletal muscle mass index (SMI) and handgrip strength (HS) in Turkish population and to compare the power of different cutoff points to predict comprehensive geriatric assessment (CGA) parameters. METHODS: Two hundred and eight young healthy volunteers (104 women, 104 men) were included in the study to define SMI, HS cutoff values. 1150 older adults (784 women, 366 men) underwent CGA, including physical performance, activities of daily living (ADL), HS and frailty. Body composition was obtained from every participant by bioimpedance analysis (BIA). CGA parameters of sarcopenic patients according to EWGSOP and new Turkish cutoff points were compared. RESULTS: SMI cutoff points were defined 5.70 kg/m2 for women, 8.33 kg/m2 for men. HS thresholds were calculated as 14 kg for women, 28 kg for men using measurements of healthy young adult reference. Considering the new threshold values, the prevalence of sarcopenia was 10% (7% women, 17% men). When new sarcopenia criteria were applied and covariates were adjusted, sarcopenia was found to be more closely related to ADL impairment, balance, frailty in men, and balance, slow walking speed, ADL impairment, frailty in women (p < 0.05). DISCUSSION: Muscle mass and strength may vary between populations because of ethnicity and other related discrepancies. The evaluation of sarcopenia according to the present guidelines may cause overdiagnosis in some populations. CONCLUSION: Cutoff points specific to populations should be determined.
Assuntos
Força da Mão , Sarcopenia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Feminino , Avaliação Geriátrica , Humanos , Masculino , Força Muscular , Sarcopenia/diagnóstico , Sarcopenia/epidemiologiaRESUMO
BACKGROUND: Patients scheduled for surgery after unsuccessful MitraClip® intervention present increasingly with multiple comorbidities, and they are often referred to the heart team to suggest the most appropriate intervention. The publication of successful results of initial patient cohorts treated with the MitraClip device has resulted in recruitment of more seriously ill patients, who otherwise would have been denied catheter-based/surgical treatment. There has been increasingly reports on conventional surgery after failed mitral valve repair with the MitraClip device. However, data on such procedures remain scarce and mostly focused on individual case studies. The inevitable increase in use of MitraClip, however, will raise the number of patients in need of surgery post MitraClip, making it imperative for surgeons to understand challenges and outcome data related with surgery in this patient cohort. We present our long-term institutional experience with surgery after MitraClip intervention in highest risk patients. METHODS: Eighteen patients underwent surgery of the mitral valve at our Institution between January 2015 and June 2020. These patients developed recurrent mitral regurgitation grade more than 2° at various intervals after MitraClip. Mitral valve repair was performed where possible and gross examination Valve/MitraClip were intra-operatively documented. Implanted MitraClip devices were analyzed histopathologically to evaluate the healing process and rule out inflammation. Regular patient follow-up was performed. RESULTS: Mean patient age was 74 (±9 years) and MitraClip implantation was performed at various tertiary institutions. Sixteen out of eighteen (16/18) patients received mitral valve replacement, whereas the remaining two patients received mitral valve repair and extracorporal membrane oxygenation, respectively. Four patients died of sepsis and intractable multi organ failure in-hospital. The remaining patients were discharged alive out of hospital to different rehabilitation centers. Follow-up was complete in all patients. CONCLUSIONS: Surgery is demanding when patients require surgery for persistent or recurrent mitral regurgitation after MitraClip therapy and can be successfully implemented as a possible therapy option for selective cases as an interdisciplinary approach despite calculated high perioperative mortality risk. These patients should not be denied surgery outright.