RESUMO
OBJECTIVE: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. BACKGROUND: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. MATERIALS AND METHODS: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. RESULTS: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 µg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. CONCLUSIONS: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.
Assuntos
Canabidiol , Fibroblastos , Gengiva , Gengivite , Humanos , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Método Duplo-Cego , Fibroblastos/efeitos dos fármacos , Adulto , Masculino , Feminino , Gengiva/efeitos dos fármacos , Gengivite/tratamento farmacológico , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2 , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Clorexidina/uso terapêutico , Clorexidina/farmacologia , Clorexidina/análogos & derivados , Células Cultivadas , Interleucina-6/análise , Periodontite/tratamento farmacológico , Interleucina-8/efeitos dos fármacos , Heme Oxigenase-1RESUMO
BACKGROUND: Individuals with congenital solitary functioning kidney (SFK) are at an increased risk of kidney damage. According to some studies, the risk is higher in unilateral kidney agenesis (UKA) than in unilateral multicystic dysplastic kidney (UMCDK). We hypothesized that with early detection of children with UKA and UMCDK, there would be no difference in the presence of hypertension, proteinuria, and reduced glomerular filtration rate (GFR) between UKA and UMCDK. METHODS: Based on a long-term follow-up protocol, we evaluated a cohort of 160 children followed from birth for SFK (84 with UKA and 76 with UMCDK) detected by prenatal or routine neonatal ultrasound screening. Hypertension, proteinuria, and reduced GFR were monitored as markers of kidney damage. We compared the characteristics and outcomes of the subgroups of children with UKA and UMCDK. RESULTS: GFR was reduced in 42 (26.2%) children, of whom 41 showed only mild reduction. Hypertension and proteinuria were found in 22 (13.8%) and 14 (8.8%) children, respectively. Combined kidney damage was present in 57 (35.6%) children. The UMCDK and UKA subgroups differed in GFR at final examination, with UMCDK patients being significantly more likely to have normal GFR compared to UKA patients (82% vs. 67%; p = 0.039). CONCLUSIONS: One third of the children showed signs of SFK damage, albeit mild. Patients with UKA had reduced GFR significantly more often than those with UMCDK, but did not differ in the rates of hyperfiltration injury or congenital anomalies of the kidneys and urinary tract (CAKUT) in SFK.
Assuntos
Diagnóstico Precoce , Taxa de Filtração Glomerular , Rim , Rim Displásico Multicístico , Proteinúria , Rim Único , Humanos , Feminino , Rim Displásico Multicístico/diagnóstico , Rim Displásico Multicístico/complicações , Rim Displásico Multicístico/fisiopatologia , Masculino , Rim Único/complicações , Rim Único/diagnóstico , Rim Único/fisiopatologia , Rim/anormalidades , Rim/fisiopatologia , Rim/diagnóstico por imagem , Recém-Nascido , Prognóstico , Proteinúria/etiologia , Proteinúria/diagnóstico , Lactente , Pré-Escolar , Criança , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Seguimentos , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/diagnóstico por imagem , Triagem Neonatal/métodos , Nefropatias/congênitoRESUMO
This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm-2 ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment.
Assuntos
Indóis , Isoindóis , Potencial da Membrana Mitocondrial , Compostos Organometálicos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Compostos de Zinco , Humanos , Fotoquimioterapia/métodos , Células HeLa , Indóis/farmacologia , Indóis/química , Compostos de Zinco/farmacologia , Compostos Organometálicos/farmacologia , Compostos Organometálicos/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Estresse Oxidativo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacosRESUMO
BACKGROUND: A psychosocial problem faced by people with early-stage dementia (PwESD) is the perception of threats to personal dignity. Insights into its dynamics are important for understanding how it changes as dementia advances and to develop suitable interventions. However, longitudinal studies on this change in PwESD are lacking. AIMS: To determine how perceptions of dignity and selected clinical and social factors change over 1 year in home-dwelling PwESD and the predictors associated with changes in perceptions of dignity over 1 year. RESEARCH DESIGN AND METHODS: A longitudinal study was conducted. The sample included 258 home-dwelling Czech PwESD. Data were collected using the Patient Dignity Inventory (PDI-CZ), Mini-Mental State Examination, Bristol Activities of Daily Living Scale, Geriatric Depression Scale and items related to social involvement. Questionnaires were completed by the PwESD at baseline and after 1 year. ETHICAL CONSIDERATIONS: The study was approved by the ethics committee and informed consent was provided by the participants. RESULTS: People with Early-Stage Dementia rated the threat to dignity as mild and the ratings did not change significantly after 1 year. Cognitive function, self-sufficiency, vision, and hearing worsened, and more PwESD lived with others rather than with a partner after 1 year. Worsened depression was the only predictor of change in perceived personal dignity after 1 year, both overall and in each of the PDI-CZ domains. Predictors of self-sufficiency and pain affected only some PDI-CZ domains. CONCLUSIONS: Perceptions of threat to dignity were mild in PwESD after 1 year, although worsened clinical factors represented a potential threat to dignity. Our findings lead us to hypothesise that perceived threats to personal dignity are not directly influenced by health condition, but rather by the social context.
Assuntos
Demência , Pessoalidade , Humanos , Estudos Longitudinais , Feminino , Demência/psicologia , Masculino , Idoso , Idoso de 80 Anos ou mais , Inquéritos e Questionários , República Tcheca , RespeitoRESUMO
OBJECTIVE: In the Czech Republic, it is possible, to carry out Medical Termination of Pregnancy (MToP) in the 1st trimester up until the 49th day of secondary amenorrhea. The aim of the study is to analyse the significance of serum/urine human chorionic gonadotropin (hCG) assessment and ultrasound (US) examination in pregnancy diagnosis and MToP follow-up. METHODS: In 2017-2018, MToP was carried out in a total of 109 women by administering a combination of mifepristone (600â mg orally) and misoprostol (400 mcg orally). Serum/urine (LSUP - low sensitivity urine pregnancy test) hCG assessment and US examination were performed at pregnancy diagnosis and MToP follow-up. RESULTS: At pregnancy diagnosis, there was a positive and medium strong correlation between serum hCG and size of the gestational sac - GS (R = 0.711; P â 1,000 IU/L and LSUP test was always positive). In 5.5% of women (6/109), a subsequent surgical intervention was carried out including those with ongoing pregnancy (N = 5); missed abortion (N = 1) was treated by additional misoprostol, where surgical intervention was not necessary. CONCLUSION: At pregnancy diagnosis, there is a positive and medium strong correlation between serum hCG and CRL. In MToP follow-up, a negative LSUP test enables reliable exclusion of ongoing pregnancy and missed abortion. In case of a positive LSUP test, US examination should be performed; however, surgical intervention should not be indicated solely on the basis of uterine cavity dilatation.
Assuntos
Aborto Induzido , Aborto Retido , Misoprostol , Gravidez , Feminino , Humanos , Seguimentos , Primeiro Trimestre da Gravidez , Mifepristona , Gonadotropina CoriônicaRESUMO
OBJECTIVE: To investigate factors influencing the frequency and type of microembolic signals (MES) detected using transcranial Doppler (TCD) in patients undergoing elective coronary intervention, and to correlate MES with silent stroke detected using magnetic resonance imaging (MRI) and cognitive dysfunction. METHODS: The subset study of a randomized clinical trial was conducted on 70 patients (58 males; mean age 59.9 ± 8.4 years) who underwent bilateral TCD monitoring of middle cerebral arteries (MCAs) during elective coronary interventions. Neurologic examination and brain MRI were performed prior to, and 24 h postintervention. Cognitive function tests were performed prior to, and on day 30 postintervention. RESULTS: The incidence of detected MES was 94.3 %. Eighteen (25.7 %) patients had new clinically asymptomatic ischemic lesions on MRI. The number of solid MES negatively correlated with changes in revised Addenbrooke's Cognitive Examination test (ACE-R) and, the number of solid MES and combinations of solid and gaseous MES negatively correlated with changes in Mini MentalState Examination (MMSE) conducted on day 30 after the intervention (p < 0.05 in all cases). CONCLUSION: Cardiac catheterization was associated with a high risk of cerebral embolism in our patients. A higher number of solid MES and combinations of solid and gaseous MES was associated with the deterioration in cognitive tests (Tab. 5, Fig. 3, Ref. 30).
Assuntos
Embolia Intracraniana , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia , Coração , Cateterismo Cardíaco , Encéfalo , CogniçãoRESUMO
BACKGROUND: Dementia is a serious problem in old age, that impacts an individual's ability to function and may threaten personal dignity. Given the variable features of the illness and the diversity of life experiences, many factors may contribute to the perception of dignity by men and women with dementia. The purpose of the study was to explore the factors that contribute to dignity and its domains in men and women with dementia. METHODS: This cross-sectional study involved 316 community-dwelling patients with early-stage dementia (aged ≥ 60) (PwD). We assessed the participants' sociodemographic and social involvement characteristics, health-related variables (pain, depression, physical performance, visual and hearing impairments), attitude to aging, and self-sufficiency in the activities of daily living (ADL). These factors were investigated as independent variables for the perception of dignity and of its domains in men and women. RESULTS: Multivariate regression analysis showed that PwD experienced minor dignity problems in the early stages of dementia. In both men and women higher rates of depression, negative attitudes to aging, and pain were associated with reductions in the perception of dignity. In men, but not in women visual impairment had a negative effect on overall dignity, and on the associated domains of 'Loss of Autonomy' and 'Loss of Confidence'. In women, lowered self-sufficiency in ADL contributed to reduced self-perception of dignity and in the associated domains of 'Loss of Purpose of Life', 'Loss of Autonomy', and 'Loss of Confidence'. Sociodemographic and social involvement characteristics, hearing impairment, and physical performance did not influence the participants' self-perception of dignity. CONCLUSION: The results suggested that several common factors (depression, attitudes to aging, and pain) contribute to the perception of dignity in both men and women. Other factors, visual impairments in men, and self-sufficiency in ADL in women, appear to be more gender specific. These differences might relate to their specific gender roles and experiences. The self-perception of dignity in PwD can be helped by supporting the individual, to the extent that their illness allows, in maintaining activities that are important to their gender roles, and that preserve their gender identity. TRIAL REGISTRATION: NCT04443621.
Assuntos
Demência , Respeito , Atividades Cotidianas , Idoso , Estudos Transversais , Demência/diagnóstico , Feminino , Identidade de Gênero , Humanos , Masculino , Dor , PercepçãoRESUMO
OBJECTIVES: Transcranial color-coded duplex sonography (TCCS) enables to measure blood flow characteristics in cerebral vessels, including vascular resistance and pulsatility. The study aims to identify factors influencing pulsatility (PI) and resistance (RI) indices measured using TCCS in patients with carotid atherosclerosis. METHODS: Self-sufficient patients with atherosclerotic plaque causing 20-70% carotid stenosis were consecutively enrolled to the study. All patients underwent duplex sonography of cervical arteries and TCCS with measurement of PI and RI in the middle cerebral artery, neurological, and physical examinations. Following data were recorded: age, gender, height, weight, body mass index, systolic and diastolic blood pressure, occurrence of current and previous diseases, surgery, medication, smoking, and daily dose of alcohol. Univariant and multivariant logistic regression analysis were used for identification of the factors influencing RI and PI. RESULTS: Totally 1863 subjects were enrolled to the study: 139 healthy controls (54 males, age 55.52 ± 7.05 years) in derivation cohort and 1724 patients (777 males, age 68.73 ± 9.39 years) in validation cohort. The cut off value for RI was 0.63 and for PI 1.21. Independent factors for increased RI/PI were age (odds ratio [OR] = 1.108/1.105 per 1 year), occurrence of diabetes mellitus (OR = 1.767/2.170), arterial hypertension (OR = 1.700 for RI only), width of the carotid plaque (OR = 1.260 per 10% stenosis for RI only), and male gender (OR = 1.530 for PI only; P Ë.01 in all cases). CONCLUSIONS: The independent predictors of increased cerebral arterial resistance and/or pulsatility in patients with carotid atherosclerosis were age, arterial hypertension, diabetes mellitus, carotid plaque width, and male gender.
Assuntos
Doenças das Artérias Carótidas , Placa Aterosclerótica , Acidente Vascular Cerebral , Idoso , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Artérias Cerebrais , Humanos , Masculino , Pessoa de Meia-Idade , Resistência VascularRESUMO
Clinically approved photodynamic therapy (PDT) is a minimally invasive treatment procedure that uses three key components: photosensitization, a light source, and tissue oxygen. However, the photodynamic effect is limited by both the photophysical properties of photosensitizers as well as their low selectivity, leading to damage to adjacent normal tissue and/or inadequate biodistribution. Nanoparticles (NPs) represent a new option for PDT that can overcome most of the limitations of conventional photosensitizers and can also promote photosensitizer accumulation in target cells through enhanced permeation and retention effects. In this in vitro study, the photodynamic effect of TPP photosensitizers embedded in polystyrene nanoparticles was observed on the non-tumor NIH3T3 cell line and HeLa and G361 tumor cell lines. The efficacy was evaluated by viability assay, while reactive oxygen species production, changes in membrane mitochondrial potential, and morphological changes before and after treatment were imaged by atomic force microscopy. The tested nanoparticles with embedded TPP were found to become cytotoxic only after activation by blue light (414 nm) due to the production of reactive oxygen species. The photodynamic effect observed in this evaluation was significantly higher in both tumor lines than the effect observed in the non-tumor line, and the resulting phototoxicity depended on the concentration of photosensitizer and irradiation time.
Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Células NIH 3T3 , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/metabolismo , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Distribuição TecidualRESUMO
OBJECTIVES: This study explored the quality of life (QoL) and attitudes to aging in older adults with and without dementia, and ascertained the main factors that predict QoL and attitude to ageing. METHODS: A cross-sectional study involving 563 community-dwelling adults with (PwD) and without dementia (PwoD) >60 years of age was conducted in three Czech regions. A tools battery including the Quality of Life-Alzheimer's Disease Scale, Geriatric Depression Scale, Patient Dignity Inventory, Attitude to Aging Questionnaire (AAQ), Short Physical Performance Battery, and Barthel Index, were administered. RESULTS: PwD had worse scores in QoL and AAQ (both p = 0.0001). Less depression (p < 0.001), better sense of dignity (p < 0.05), and lower pain (p < 0.05) in PwoD predicted better scoring for QoL and AAQ. Physical ability in PwoD (p < 0.05), living alone (p < 0.05) and self-sufficiency (p < 0.001) in PwDwere predictors influencing QoL.Age (p < 0.01) in PwoD, gender (p < 0.05) and physical ability (p < 0.001) in PwD influenced AAQ. CONCLUSIONS: This research is the first study to show that dignity can influence the QoL and attitude to aging in community-dwelling older adults. Our findings suggest that depression and dignity are common predictors of QoL and AAQ in older adults with and without dementia.
Assuntos
Doença de Alzheimer , Qualidade de Vida , Idoso , Envelhecimento , Atitude , Estudos Transversais , Depressão , HumanosRESUMO
PURPOSE: Cerebral blood flow volume is an important factor for the accurate diagnosis of neurovascular diseases and treatment indication. This study aims to assess correlations of blood flow volume measurements in cervical and intracranial arteries between duplex sonography and quantitative magnetic resonance angiography (qMRA). MATERIALS AND METHODS: Consecutive patients with suspicion of cerebral vascular pathology underwent qMRA and duplex sonography of cervical and intracranial arteries with measurement of blood flow volume in bilateral common (CCA), internal (ICA) and external carotid arteries, vertebral and basilar arteries, middle, anterior, posterior cerebral and posterior communicating arteries using 2 different ultrasound machines. Ten patients underwent all examinations twice. Correlations between blood flow volume measurements were evaluated using Spearman's correlation coefficient and inter-class correlation coefficient (ICC). RESULTS: In total, 21 subjects (15 males, mean age: 56.3â± 6.2 years) were included in the study. Duplex sonography inter-investigator correlation was excellent (ICCâ=â0.972, pâ<â0.0001) as well as intra-investigator correlations of both qMRA and duplex sonography (ICCâËâ0.990, pâ<â0.0001). Mostly high correlations were recorded between qMRA and duplex sonography in particular cervical arteries but only low to moderate correlations were obtained for intracranial arteries. The mean differences between blood flow volume measurements were 10.9â±â8.1â% in the CCA and its branches when using qMRA and 15.0â±â11.9â% when using duplex sonography, 13.5â±â11.8â%/35.4â±â34.2â% in the ICA siphon and its branches when using qMRA/duplex sonography, and 24.1â±â19.7â%/44.9â± 44.0â% in both vertebral arteries and the basilar artery when using qMRA/duplex sonography. CONCLUSION: Duplex sonography as well as qMRA allow for highly reproducible measurement of blood flow volume in cervical and intracranial arteries in routine clinical practice.
Assuntos
Circulação Cerebrovascular , Angiografia por Ressonância Magnética , Ultrassonografia , Artérias , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: The aim of this study was to compare TFF3, AIF-1, S100-A11 and DKK1 serum levels in patients with cervical dysplasia, and in healthy female controls. METHODS: The first group included 59 patients with a histological dia-gnosis of precancerous disease CIN 1. The second group included 198 patients with a histological dia-gnosis of precancerous disease CIN 2 or CIN 3. The control group was comprised of 90 patients who underwent elective total hysterectomy for nonmalignant disorders. In all patients, preoperative serum samples were taken and separated; the sera were all stored at -80°C until the analysis for TFF3, AIF-1, S100-A11 and DKK1. RESULTS: The serum levels of S100A11 (P < 0.0001) and AIF-1 (P < 0.0001) were statistically significantly higher in patients with mild precancerous lesions (CIN 1) than in controls. The levels of TFF3 and DKK1 were not statistically significantly different in patients with CIN 1 and in the control group. The serum levels of S100A11 (P < 0.0001) and AIF-1 (P < 0.0001) were statistically significantly higher in patients with severe precancerous lesions (CIN 2/3) than in controls. TFF3 and DKK1 levels were not statistically significantly different in patients with CIN 2/3 compared to controls. CONCLUSION: S100-A11 and AIF-1 represent potential bio-markers in patients with cervical dysplasia.
Assuntos
Lesões Pré-Cancerosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Biomarcadores , Feminino , HumanosRESUMO
OBJECTIVE: The aim of this study was to compare the serum levels of TFF3, AIF-1, S100-A11 and DKK1 in surgically staged patients with cervical cancer, and in healthy female controls. METHODS: In total 85 consecutive patients dia-gnosed at the Department of Obstetrics and Gynecology, University Hospital in Olomouc with cervical cancer undergoing radical hysterectomy or fertility sparing surgery with pelvic lymphadenectomy were included. Ninety patients who underwent elective total hysterectomy for nonmalignant disorder represented a control group. In all patients, preoperative serum samples were taken and separated; the sera were all stored at -80 °C until analysis for TFF3, AIF-1, S100-A11 and DKK1. RESULTS: According to the final histopathological examination, 32 (40.5%) out of 79 cervical cancer patients with microscopically examined lymph nodes were lymph node-positive. S100A11 (P < 0.0001) and AIF-1 levels (P < 0.0001) were higher in cervical cancer patients than in controls. Furthermore, the serum levels of S100A11 (P > 0.04) and AIF-1 (P > 0.01) were significantly higher in lymph node-positive patients as compared to lymph node-negative patients. The levels of TFF3 and DKK1 were higher (P < 0.0001) in controls than in cervical cancer patients and were not different in groups with or without nodal involvement.. CONCLUSION: S100-A11 and AIF-1 represent potential bio-markers in patients with cervical cancer. Moreover, the levels of S100-A11 and AIF-1 increase in patients with lymph node involvement.
Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgiaRESUMO
Graft-versus-host disease (GVHD) represents a significant cause of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). NF-kB system is a master regulator of innate immunity responses. It controls the expression of various cytokines and chemokines many of which are involved in GVHD pathogenesis. Chemo(radio) therapy administered during conditioning induces DNA damage and activates DNA damage response (DDR) signaling resulting in irreversible cell cycle arrest - cellular senescence which has been described to be associated with robust pro-inflammatory secretion mostly controlled by NF-kB. The NFKB1 gene encodes the DNA-binding subunit of the NF-kB complex. Using the candidate gene approach, we analyzed possible association of two single-nucleotide polymorphisms (SNPs) rs3774937 C/T and rs3774959 A/G of the NFKB1 gene with GVHD and transplant-related mortality (TRM) occurrence in 109 recipients allografted from HLA-identical donor. Both SNPs in recipients were found to be strongly associated with acute GVHD. Nevertheless, no significant association with chronic GVHD and TRM was found. Presented pilot results contribute to pre-clinical observations and suggest that NF-kB may be an important regulator of HSCT-related inflammatory reactions such as acute GVHD. Novel pathogenic mechanisms of GVHD may arise from perspectives of DDR and cellular senescence where NF-kB plays an essential role.
Assuntos
Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas , Subunidade p50 de NF-kappa B/genética , Polimorfismo de Nucleotídeo Único , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Taxa de SobrevidaRESUMO
OBJECT: Idiopathic normal pressure hydrocephalus (iNPH) is the only variant of dementia disorders possibly treatable by neurosurgical intervention. iNPH is a neurodegenerative condition clinically characterized by gait ataxia, urinary incontinence, and memory disturbance. We present one of the largest single-center studies, which was designed to prove efficacy of our low-pressure setting of gravitational valve at all three symptoms of iNPH and to find statistically significant cut-off time for best clinical improvement according to the duration of symptoms. METHODS: Sixty-one consecutive patients (mean age 74.9 ± 5.3) with iNPH were prospectively observed from the time of surgery with minimal 6 months follow-up. All patients underwent implantation of the same type of gravitational valve with the same setting-pro GAV with low opening pressure at 5 cm H2O-and were operated by the same team of 2 neurosurgeons. We statistically evaluated gait disturbance, psychological changes, and incontinence preoperatively and at 6 months after surgery and timing of the surgery according to the duration of symptoms and to the age. RESULTS: Paired t test showed a statistically significant increase in MMSE, a statistically significant decrease in 10-m walk test and 360 deg. rotation test (p < 0.0001). The correlation among the change of the MMSE, the walk test, and the rotation test, and the age and time of symptoms' duration was verified by Pearson's correlation coefficient. Pearson's correlation coefficient showed a medium strong correlation between the change of MMSE and the time of symptoms (r = - 0.580; p < 0.0001) and between the change of the number of steps and the time of symptoms (r = 0.517, p < 0.0001). There was a statistically significant weak (poor) correlation between the change of the walk test and the time of symptoms (r = 0.351, p = 0.006). All 3 ROC tests confirmed optimal cut-off for the best improvement of symptoms as 9.5 months of the symptom duration. CONCLUSIONS: We proved statistical significant optimal cut-off for the best improvement of the symptoms as 9.5 months of the symptom duration. This study also confirmed successful treatment of iNPH with VP shunting using low pressure setting of gravitational valve with overall improvement in 75% and low over drainage complications in 5% We proved statistically significant increase in MMSE, decrease in 10 m walk test and number of steps test, p < 0.0001.
Assuntos
Hidrocefalia de Pressão Normal/cirurgia , Complicações Pós-Operatórias/epidemiologia , Derivação Ventriculoperitoneal/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Derivação Ventriculoperitoneal/efeitos adversos , Derivação Ventriculoperitoneal/instrumentaçãoRESUMO
Background and Objectives: Our aim was to verify the optimal cut-off value for unenhanced CT attenuation and the percentage of negative voxels in the volume CT histogram analysis of adrenal masses. Materials and Methods: We retrospectively analyzed the CT data of patients who underwent an adrenalectomy in the period 2002-2019. In total, 413 adrenalectomies were performed. Out of these, 233 histologically verified masses (123 adenomas, 58 pheochromocytomas, 18 carcinomas, and 34 metastases) fulfilled the inclusion criteria and were selected for analysis. The mean unenhanced attenuation in Hounsfield units (HU) and the percentage of voxels with attenuation less than 0 HU (negative voxels) were measured in each mass. Results: The mean unenhanced attenuation with a cut-off value of 10 HU reached a sensitivity of 59.4% and a specificity of 99.1% for benign adenomas. The mean unenhanced attenuation with a cut-off value of 15 HU reached a sensitivity of 69.1% and a specificity of 98.2%. For the histogram analysis, a cut-off value of 10% of negative pixels reached a sensitivity of 82.9% and a specificity of 98.2%, whereas a cut-off value of 5% of negative pixels reached a sensitivity of 87.8% and a specificity of 75.5%. The percentage of negative voxels reached a slightly better area under the curve (0.919) than unenhanced attenuation (0.908). Conclusion: Mean unenhanced attenuation with a cut-off value of 10 HU represents a simple tool, and the most specific one, to distinguish adrenal adenomas from non-adenomas. CT histogram analysis with cut-off values of 10% of negative voxels improves sensitivity without any loss of specificity.
Assuntos
Neoplasias das Glândulas Suprarrenais , Tomografia Computadorizada por Raios X , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Diagnóstico Diferencial , Humanos , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Silent and symptomatic cerebral infarctions occur in up to 34% of patients after carotid endarterectomy (CEA). This prospective study compared the risk of new brain infarctions detected by magnetic resonance imaging (MRI) in patients with internal carotid artery stenosis undergoing CEA with local anesthesia (LA) vs general anesthesia (GA). METHODS: Consecutive patients with internal carotid artery stenosis indicated for CEA were screened at two centers. Patients without contraindication to LA or GA were randomly allocated to the LA or GA group by ZIP code randomization. Brain MRI was performed before and 24 hours after CEA. Neurologic examination was performed before and 24 hours and 30 days after surgery. The occurrence of new infarctions on the control magnetic resonance images, stroke, transient ischemic attack, and other complications was statistically evaluated. RESULTS: Of 210 randomized patients, 105 underwent CEA with LA (67 men; mean age, 68.3 ± 8.1 years) and 105 with GA (70 men; mean age, 63.4 ± 7.5 years). New infarctions were more frequently detected on control magnetic resonance images in patients after CEA under GA compared with LA (17.1% vs 6.7%; P = .031). Stroke or transient ischemic attack occurred within 30 days of CEA in three patients under GA and in two under LA (P = 1.000). There were no significant differences between the two types of anesthesia in terms of the occurrence of other complications (14.3% for GA and 21.0% for LA; P = .277). CONCLUSIONS: The risk of silent brain infarction after CEA as detected by MRI is higher under GA than under LA.
Assuntos
Anestesia Geral/efeitos adversos , Anestesia Local/efeitos adversos , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Infarto Cerebral/etiologia , Endarterectomia das Carótidas/efeitos adversos , Idoso , Doenças Assintomáticas , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , República Tcheca , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Human serum albumin (HSA) is a multifunctional protein with ligand binding, transporting and buffering properties. Posttranslational modifications and ligand binding processes are closely related to albumin final functional status. In the last few decades, HSA has been characterized using a broad spectrum of methods, but quantitative data on the HSA's modifications among individuals have not been reported. The investigations presented here are based on the non-denaturing electrocatalytic screening of HSA samples isolated from the blood serum of healthy subjects. The electrocatalytic responses of the native protein (Rnat) varied depending on its modifications among individuals, which enable us to express the inter-individual variability. Consequently, the native HSA samples were subjected to ex vivo carbonylation with 50â¯mM methylglyoxal for 36â¯h. The differences between Rnat and the responses of artificially carbonylated protein (Rmod) corresponded with inter-individual binding capacity variations (ΔRâ¯=â¯Rnat-Rmod). The coefficients of variation for the Rnat and ΔR values of purified HSA samples were estimated to be 8.5 and 23.2%, respectively. A sensitive non-denaturing electrocatalytic assay was utilized to provide new data about albumin inter-individual variations and evaluate its oxidative modifications and binding capacity, which could be used for further studies targeting not only on HSA but also other clinically important proteins.
Assuntos
Técnicas Eletroquímicas/métodos , Carbonilação Proteica , Albumina Sérica Humana/metabolismo , Adulto , Feminino , Humanos , MasculinoRESUMO
BACKGROUND/AIMS: The aim of this study was to perform a psychometric validation of the Czech version of the Quality of Life - Alzheimer's Disease scale (QoL-AD) for patients with early-stage dementia. METHODS: The sample included 212 patient-proxy pairs. For convergent validity, the Czech version of the Bristol Activities of Daily Living Scale (BADLS-CZ), the Short Physical Performance Battery (SPPB), and the Geriatric Depression Scale (GDS) were used. RESULTS: The reliability of the QoL-AD for patients and caregivers was good (Cronbach's α = 0.85, ICC = 0.25-0.54). A positive correlation existed between the QoL-AD and the SPPB, and negative correlations existed between the QoL-AD and the BADLS-CZ as well as between the QoL-AD and the GDS. Factor analysis resulted in a three-factor solution (physical and mental health, family life, and social security). CONCLUSION: The Czech version of the QoL-AD has good psychometric properties in compliance with international recommendations.
Assuntos
Doença de Alzheimer/psicologia , Escala de Avaliação Comportamental/estatística & dados numéricos , Psicometria/estatística & dados numéricos , Qualidade de Vida/psicologia , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , República Tcheca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Quality of life (QoL) is one of the main endpoints in stroke prevention or acute stroke treatment studies. The aim of the current study was to identify risk factors affecting the QoL of patients with carotid stenosis in stroke prevention. METHODS: Self-sufficient patients (50-80 years of age) with ≥20% carotid artery stenosis followed in the neurosonology laboratory, and without any severe illnesses within the last 12 months, dementia, or psychiatric disorders were selected for the study after signing informed consent. Patients completed two standardized QoL questionnaires (WHOQoL-BREF and EQ-5D-3 L) and a visual pain scale, provided covariate variables (medication, age, gender, education, and social situation), and the blood pressure and body mass indexes were recorded. Logistic regression (forward stepwise method) was used to identify factors affecting the individual domains of QoL questionnaires. RESULTS: Of the 584 consecutive patients, 502 met the inclusion criteria and 344 completely filled both QoL questionnaires (164 men; mean age, 69.7 ± 7.8 years). An independent predictor of worse QoL in all domains was pain. Independent factors decreasing the QoL were lower level of education and blood pressure in the physical health domain, female gender in the psychological domain, and male gender in the social relationships domain. Independent factors decreasing satisfaction with health status were female gender and higher blood pressure. Factors negatively influencing the satisfaction with the QoL were living alone, lower level of education, and higher diastolic blood pressure (WHOQoL-BREF). Factors negatively influencing mobility were age, male gender, living alone, lower level of education, and higher body mass index (EQ-5D-3 L; p < 0.05 in all cases). CONCLUSIONS: Pain, blood pressure, body mass index, education, living alone, gender, and age were associated with the QoL in patients with carotid stenosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02360137 . Registered on 26 January 2015.