RESUMEN
Dental pulp stem cells (DPSCs) are a promising alternative to the source of mesenchymal stem cells (MSCs), as they are readily available in minimally invasive procedures compared to more invasive methods associated with harvesting other MSCs sources. Despite the encouraging pre-clinical outcomes in animal disease models, culture-expanding procedures are needed to obtain a sufficient number of MSCs required for delivery to the damaged site. However, this contributes to increasing regulatory difficulties in translating stem cells and tissue engineering therapy to clinical use. Moreover, discussions continue as to which isolation method is to be preferred when obtaining DPSCs from extracted molars. This protocol describes a simple explant isolation technique of human dental pulp stem cells from the dental pulp of permanent teeth based upon the plastic adherence of MSCs and subsequent outgrowth of cells out of tissue fragments with high efficacy.
Asunto(s)
Separación Celular , Pulpa Dental , Células Madre Mesenquimatosas , Pulpa Dental/citología , Humanos , Separación Celular/métodos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular , Células Madre/citología , Células Cultivadas , Dentición Permanente , Ingeniería de Tejidos/métodosRESUMEN
Magnesium, an essential mineral for various physiological functions, is subject to tight regulation within the body. Understanding its absorption across epithelial cell monolayers is crucial for optimizing dietary magnesium intake and therapeutic strategies. The Caco-2 monolayer model, widely recognized for its relevance to the human intestinal epithelium, provides a suitable platform for this investigation. This protocol covers the step-by-step procedures for the cultivation of Caco-2 monolayer preparation of transwell systems. It provides guidance on the setup of magnesium transport experiments, which involve the application of magnesium salts to the apical side of the Caco-2 monolayer and monitoring their transport to the basolateral side.
Asunto(s)
Mucosa Intestinal , Magnesio , Humanos , Células CACO-2 , Mucosa Intestinal/metabolismo , Magnesio/metabolismo , Permeabilidad , Transporte Biológico , Técnicas de Cultivo de Célula/métodos , Absorción Intestinal/efectos de los fármacos , Sales (Química)/metabolismoRESUMEN
Background and Objectives: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. Materials and Methods: We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro, as well as their effects on the expression of angiogenic growth factors (VEGFA and HGF) and selected genes in apoptosis signalling pathways (BAX, BAK, CASP3, CASP9, and BCL2). Results: Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Conclusions: Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.
Asunto(s)
Apoptosis , Supervivencia Celular , Pulpa Dental , Diclofenaco , Ibuprofeno , Humanos , Pulpa Dental/efectos de los fármacos , Pulpa Dental/citología , Diclofenaco/farmacología , Apoptosis/efectos de los fármacos , Ibuprofeno/farmacología , Supervivencia Celular/efectos de los fármacos , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Células Madre/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células CultivadasRESUMEN
BACKGROUND: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with "no-option" critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy related to the therapeutic efficacy of BMCs treatment. METHODS: In the present study, we reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 mL of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (N = 22) were considered as responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (N = 13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression, and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors, and the risk of major amputation. RESULTS: Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI), and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP > 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (N = 22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (N = 20) had significantly reduced pain scale after BMCs transplant, compared to the non-RAS-acting agents group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (N = 17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. CONCLUSIONS: CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI, and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responders and previous treatment before BMCs transplant with RAS-acting agents alone or with atorvastatin were significant.
RESUMEN
Background and Objectives: Surgical revascularisation of patients with atherosclerosis of the ascending aorta remains a challenge. Different surgical strategies have been described in coronary surgical patients to offer alternative revascularisation strategies other than the conventional surgical revascularisation in patients unsuitable for it. The aim of this study is to compare the real-world outcomes between two groups of patients who underwent off-pump surgery (left internal mammary artery graft to the left anterior descending artery) or a hybrid with a percutaneous revascularisation procedure at a later stage. Materials and Methods: This is a single-centre retrospective observational study. Between the years 2010 and 2021, 91/6863 patients (1.33%) were diagnosed with severe atherosclerosis of the ascending aorta. All the patients were treated with off-pump revascularisation (91 patients), and the cardiologist would decide at a later stage whether the rest of the vessels would be treated with percutaneous revascularisation (25 patients). Results: There was no statistical difference in the various preoperative characteristics, except for coronary artery left main disease (30.30% vs. 64%; p = 0.0043). The two groups had no statistical differences in the perioperative characteristics and postoperative complications. The 1-, 5-, and 10-year mortality rates in the two groups were 6.1% vs. 0%, 59% vs. 80%, and 93.9% vs. 100%, respectively (off-pump vs. hybrid with percutaneous revascularisation procedure, p = 0.1958). Conclusions: Both strategies have high long-term comparable mortality. The off-pump surgery and the HCR procedure at a later stage may be solutions for these high-risk patients, but the target treatment should be complete HCR revascularisation during the index hospitalization.
Asunto(s)
Aterosclerosis , Puente de Arteria Coronaria Off-Pump , Enfermedad de la Arteria Coronaria , Humanos , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/etiología , Puente de Arteria Coronaria Off-Pump/efectos adversos , Puente de Arteria Coronaria Off-Pump/métodos , Aterosclerosis/complicaciones , Aterosclerosis/cirugía , Aorta/cirugía , Resultado del TratamientoRESUMEN
Pain is a serious subjective experience, which, although it has a protective nature, it physically and mentally exhausts the patient. The pharmacological field of development and research in the treatment and relief of pain has been dynamic and interesting ever since the isolation of salicylic acid. After discovering the molecular nature of cyclooxygenase and its inhibition, research focused on selective COX-2 inhibitors, but they were a big disappointment. Today, the possibility of contributing to safe and effective analgesic-antiphlogistic treatment for the patient with a combination of drugs is emerging again.
Asunto(s)
Antiinflamatorios no Esteroideos , Inhibidores de la Ciclooxigenasa 2 , Humanos , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/farmacología , Dolor/tratamiento farmacológicoRESUMEN
The aim of the study was to point out the contribution of new invasive therapeutic procedures in the treatment of advanced stages of Parkinson's disease (PD) in comparison with classical oral pharmacotherapy. Data originated from a group of 43 patients with PD, 39% (17) with classic treatment, 23% (10) with intestinal gel of methyl ester levodopa (Duodopa), 19% (8) of patients were using subcutaneous delivery of apomorphine (APO) and the same quantity of patients had undergone deep brain stimulation (DBS). Majority of patients had advanced stages of PD, stage 4, by standards of Hoehn and Yahr scale (Hoehn and Yahr, 1967). Research observed improvement in majority of patients with novel treatments. A positive effect was also noted in the reduced need for oral therapy, where there was a significant decrease in all new therapies. Benefits were observed in the amount of antiparkinsonic drugs taken per os, where we observed reduction in all new therapies. A positive effect of the new therapeutic approaches in reducing "off" periods in patients has also been noted. In the case of Duodopa and DBS, the "off" period was shortened up to 50% and in the apomorphine pump up to 40%. Patients also reported reduction of some symptoms like rigidity, tremor and bradykinesis while dyskinesis still remains suba challenge. On the basis of the obtained results, it can be concluded that new therapeutic procedures for PCh will make it possible to manage symptoms typical of advanced stages of the disease, which without these procedures would lead to disability, which is the main reason for their indication. However, in early stages, well responding patients or in slow progressing disease oral antiparkinsonics are remaining as golden standard of treatment. This is not just due to good response but also because these classic drug formulations are significantly less expensive. In Slovakia, novel treatments are accessible through healthcare insurance only after secondary revision by insurance company doctors.
Asunto(s)
Enfermedad de Parkinson , Humanos , Apomorfina , Administración Oral , Ésteres , EslovaquiaRESUMEN
Stem cell transplantation represents a unique therapeutic tool in tissue engineering and regenerative medicine. However, it was shown that the post-injection survival of stem cells is poor, warranting a more comprehensive understanding of activated regenerative pathways. Numerous studies indicate that statins improve the therapeutic efficacy of stem cells in regenerative medicine. In the present study, we investigated the effect of the most widely prescribed statin, atorvastatin, on the characteristics and properties of bone-marrow-derived mesenchymal stem cells (BM-MSCs) cultured in vitro. We found that atorvastatin did not decrease the viability of BM-MSCs, nor did it change the expression of MSC cell surface markers. Atorvastatin upregulated the mRNA expression levels of VEGF-A and HGF, whereas the mRNA expression level of IGF-1 was decreased. In addition, the PI3K/AKT signaling pathway was modulated by atorvastatin as indicated by the high mRNA expression levels of PI3K and AKT. Moreover, our data revealed the upregulation of mTOR mRNA levels; however, no change was observed in the BAX and BCL-2 transcripts. We propose that atorvastatin benefits BM-MSC treatment due to its ability to upregulate angiogenesis-related genes expression and transcripts of the PI3K/AKT/mTOR pathway.
Asunto(s)
MicroARNs , Enfermedad de Parkinson , Humanos , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , MicroARNs/genética , Antiparkinsonianos/uso terapéutico , Infusiones Parenterales , Carbidopa/uso terapéutico , Combinación de MedicamentosRESUMEN
Pregnancy and postpartum period are associated with demanding physical and psychological changes that often lead to the development of psychological disorders. Depression is diagnosed in more than one in six women after childbirth. However, the prevalence of postpartum depression can be much higher because many cases are undiagnosed. In the case of severe depression, the patient is switched to pharmacological treatment, with sertraline being the most commonly used for this diagnosis. A new drug used in the treatment of postpartum depression is brexanolone, which was registered by FDA in 2019. The advantage over conventional therapy is its rapid onset of action. The structure represents the neuroactive steroid - allopregnanolone, which acts as an agonist on the δ-subunit of the GABA receptor and improves the symptoms of postpartum depression. In addition to the registered brexanolone, another steroidal drug, zuranolone, is available in the third phase of the clinical trial. The steroid structure was chemically altered to improve bioavailability and create an oral dosage form. Another synthetic analogue of neuroactive allopregnanolone, known as ganaxolone, did not show a significant reduction in depressive symptoms in the second phase of the clinical trial compared to placebo. Nevertheless, it has great therapeutic potential in the treatment of various types of epilepsy.
Asunto(s)
Depresión Posparto , Neuroesteroides , Depresión Posparto/tratamiento farmacológico , Femenino , Humanos , Neuroesteroides/uso terapéutico , Embarazo , Pregnanolona/uso terapéutico , Receptores de GABA/uso terapéutico , Sertralina/uso terapéuticoRESUMEN
BACKGROUND: Quantitative RT-PCR is a valuable tool for assessing the gene expression in different human tissues, particularly due to its exceptional sensitivity, accuracy and reliability. However, the choice of adequate control for normalization is a crucial step, greatly affecting the results of all subsequent analyses. So far, only a few studies were focused on the selection of optimal reference genes in left ventricles of failing human hearts, leading to several disparities in experimental results focused on differential gene expression in this area. Therefore, the main objective of this study was to identify a set of suitable reference genes in normal and failing left ventricle tissues, which could increase the reliability of RT-qPCR-based studies in the future. METHODS: We analyzed the expression of 15 commonly used housekeeping genes (ACTB, B2M, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, POLR2A, PPIA, RPLP0, TBP, TFRC, UBC and YWHAZ) in left ventricles of normal and failed hearts with two-step approach. In the first step, we excluded genes which are variantly expressed using ANOVA-based statistical method. Afterwards, the remaining genes were analyzed using geNorm, NormFinder and BestKeeper algorithms, together with delta Cq method. Finally, the geometric mean of gene rankings across all methods was calculated. RESULTS: Our analysis identified IPO8 and POLR2A as the most stably expressed genes, whereas ACTB and B2M were found to be expressed variantly, suggesting a potential role of these genes in the pathophysiological processes in failing human hearts. DISCUSSION/CONCLUSION: Using our two-step approach, we identified and validated two reference genes expressed invariantly in left ventricles of both healthy and failing human hearts, as well as provided a guideline for the selection of reference genes in studies comparing gene expression in these types of tissues.
Asunto(s)
Perfilación de la Expresión Génica , Ventrículos Cardíacos , Perfilación de la Expresión Génica/métodos , Genes Esenciales , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reproducibilidad de los ResultadosRESUMEN
Improvement of adherence to pharmacotherapy in patients with Parkinson's disease (PD) is a challenge in routine clinical practice. Our study was aimed at the effect of pillbox organizers with alarms improving adherence to pharmacotherapy and its impact on clinical outcomes. Forty nonadherent patients with PD being treated with ≥ 3 daily doses of levodopa and/or dopamine agonists were pseudorandomized and consecutively ranked to groups A (early-start intervention) and B (delayed-start intervention). We used the following validated diagnostic instruments: MMAS-8 (adherence), PDQ-8 (quality of life, QoL), GDS (depression), NMSS (non-motor symptoms), MDS-UPDRS III (motor involvement), MDS-UPDRS IV, and WOQ-9 (motor and non-motor fluctuations and dyskinesias). We proved a significantly improved rate of adherence with the use of pillbox organizers with alarms. Moreover, after only four weeks of using the pillbox organizer, we detected an improvement in QoL scores, motor involvement, motor-, and non-motor fluctuations. Our study showed that pillbox organizers with alarms are efficient in improving adherence to pharmacotherapy in PD. It also could contribute to better motor states, less severe fluctuations, and improved QoL.
RESUMEN
OBJECTIVES: There is no consensus on specific serum 25-hydroxy vitamin D (25(OH) D) levels associated with higher risk of severe outcome in patients with coronavirus disease 2019 (COVID-19). According to the literature patients with serum 25(OH) D levels <12 ng/ml are clearly deficient at all ages. Our aim was to assess COVID-19 mortality in the settings of severe 25(OH) D deficiency. A cohort study of 357 patients with COVID-19 was conducted. Subjects were monitored until discharge or in-hospital death. At admission, severity parameters (C-reactive protein (CRP), IL-6, Charlson comorbidity index, etc.) were assessed. These parameters were compared regarding 25(OH) D levels threshold 12 ng/ml, where values below 12 ng/ml were considered absolute vitamin D deficiency. RESULTS: 25(OH) D levels at the time of admission were independently associated with mortality (p <0.05). Nonsurvivors (N = 168) had lower 25(OH) D levels, SO2, higher age, CRP, viral load, and Charlson comorbidity index in comparison to survivors. Patients with serum 25(OH) D levels <12 ng/ml had higher mortality (55% vs 45 %), viral load (21.5 vs 23.1), and Charlson comorbidity index (5.3 vs 4.4) than those with serum 25(OH) D levels >12 ng/ml (p <0.05). CONCLUSIONS: Patients with COVID-19 with serum 25(OH) D levels <12 ng/ml have higher mortality. Among other factors, severe vitamin D deficiency likely leads to poor outcome.
Asunto(s)
COVID-19 , Deficiencia de Vitamina D , Estudios de Cohortes , Mortalidad Hospitalaria , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Vitamina D/análogos & derivados , Deficiencia de Vitamina D/complicacionesRESUMEN
BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent used to reduce bleeding in major surgical procedures. This study evaluates the efficacy and safety of the systemic and topical intra-articular administration of TXA in total hip arthroplasty (THA). METHODS: Patients (Nâ=â123) scheduled for primary unilateral THA were divided into 3 treatment groups: control group; TXA, systemic, repeated 1âg bolus; TXA, topically intra-articularly, 2âg in 50âmL saline. Primary readouts used were intra- and postoperative bleeding, transfusion requirement, postoperative hemoglobin levels and complications. RESULTS: Both systemic and topical intra-articular TXA administrations decreased bleeding and transfusion requirements. Topical intra-articular use of TXA led to the reduction in intraoperative and postoperative bleeding and affected hemoglobin levels compared with control. Systemic administration of TXA led to a significant reduction of postoperative bleeding and transfusion rate compared with control and was not different in efficacy and complication incidence when compared to topical administration of TXA. CONCLUSIONS: The use of TXA to reduce blood loss and transfusion requirements in THA is an effective and safe concept in practice. The dose of 2âg TXA topically intra-articularly and a repeated bolus of 1âg TXA systematic led to lower intra- and postoperative bleeding and a significantly lower transfusion rate than the control group. Topical intra-articular TXA administration could be a reasonable alternative in high-risk patients.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Hemorragia Posoperatoria/prevención & control , Ácido Tranexámico , Administración Intravenosa/métodos , Anciano , Antifibrinolíticos/administración & dosificación , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Transfusión Sanguínea/estadística & datos numéricos , Monitoreo de Drogas , Femenino , Hemoglobinas/análisis , Humanos , Inyecciones Intraarticulares/métodos , Masculino , Hemorragia Posoperatoria/sangre , Ajuste de Riesgo/métodos , Eslovaquia , Ácido Tranexámico/administración & dosificación , Ácido Tranexámico/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with atrial fibrillation (AF) have a higher risk of fatal complications (e.g., stroke). This investigation was performed as an observational retrospective cohort study includes 137 patients (age 61â±â15; 34.3% women) with a primary diagnosis of AF (paroxysmal, persistent, and permanent). METHODS: We collected information about the drug therapy, comorbidities and survival of AF patients and determined their congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or TIA or thromboembolism, vascular disease, age, sex category (CHA2DS2-VASc) scores. Statistical analysis identified patients with high CHA2DS2-VASc scores and defined the predictive value of individual parameters, or their combination, with regards to the outcomes of stroke and mortality. RESULTS: CHA2DS2-VASc scores identified 43.8% of the patients as low to intermediate risk (score 0-1) and 56.2% of the patients as high risk (score ≥2). Increasing CHA2DS2-VASc scores were not only accompanied by an increase in the incidence of stroke (Ptrend < .001) but also by an increase in the 3 to 5 years mortality (Pâ=â.005). Comparison of anticoagulation and anti-aggregation treatment between the 3 groups of AF did not show any significant statistical difference. Highly significant predictors of death were the CHA2DS2-VASc score (OR 1.71, 95% CI 1.10-2.67, P < .017) as well as other risk factors not included in the CHA2DS2-VASc score such as valvular heart disease (OR 5.04, 95% CI 1.10-23.10, Pâ=â.037), hyperlipidemia (OR 4.82, 95% CI 1.03-22.63, Pâ=â.046) and chronic renal failure (OR 14.21, 95% CI 2.41-83.91, Pâ=â.003). The type of AF type did not affect survival (Pâ=â.158) nor the incidence of stroke (Pâ=â.466). Patients with paroxysmal AF were linked to significantly lower frequencies of ischemic heart disease (P < .0001), vascular disease (Pâ=â.002), diabetes mellitus (Pâ=â.047), valvular heart disease (Pâ=â.03) and heart failure/left ventricular dysfunction (Pâ=â.015). CONCLUSION: The CHA2DS2-VASc score correctly predicted the patients at high-risk for 3 to 5 years mortality and confirmed its significant predictive value in the patients with AF.
Asunto(s)
Fibrilación Atrial/complicaciones , Proyectos de Investigación/normas , Medición de Riesgo/métodos , Accidente Cerebrovascular/mortalidad , Factores de Edad , Anciano , Fibrilación Atrial/mortalidad , Estudios de Cohortes , Diabetes Mellitus/clasificación , Femenino , Insuficiencia Cardíaca/clasificación , Insuficiencia Cardíaca/complicaciones , Humanos , Hipertensión/clasificación , Hipertensión/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/fisiopatología , Tromboembolia/clasificación , Tromboembolia/complicacionesRESUMEN
Background: Once-daily treatment formulation is associated with better adherence in comparison to more complex medication regimens. The study aimed to detect the extent of adherence to pharmacotherapy in Parkinson disease (PD) patients who take a minimum of three daily doses of drugs, and to identify factors associated with lower levels of adherence. Methods: The cohort was selected from non-demented PD patients. The 8-Item Morisky Medication Adherence Scale (MMAS-8), 8-Item Parkinson's Disease Questionnaire (PDQ-8), Geriatric Depression Scale (GDS), Non-Motor Symptom Assessment Scale (NMSS), 9-Item Wearing-off Questionnaire (WOQ-9), MDS-UPDRS III (motor examination), and IV (motor complications) scales were used in this study. Results: From a total of 124 subjects, 33.9% reported a high level of adherence, 29.8% reported a medium level of adherence, and 36.3% reported a low level of adherence to their pharmacotherapy. The level of non-adherence correlated with gender, longer disease duration, higher scores of PDQ-8, NMSS, WOQ-9, and MDS-UPDRS IV. Detailed analysis of NMSS demonstrated a correlation between the level of adherence and domains sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, and urinary symptoms. Independent risk factors for non-adherence were excessive daytime sleepiness, anhedonia, and forgetfulness. Conclusion: Non-adherence to more complicated medication regimens is frequent in PD patients and is associated with gender, longer PD duration, poorer quality of life, frequency and severity of non-motor symptoms, and more severe motor and non-motor fluctuations. Non-adherence was predicted by non-motor symptoms including fatigue, mood disturbances, and subjective cognitive complaints.
RESUMEN
Objectives: Many studies indicate the involvement of transient receptor potential (TRP) channels in the development of heart hypertrophy. However, the data is often conflicted and has originated in animal models. Here, we provide systematic analysis of TRP channels expression in human failing myocardium. Methods and results: Left-ventricular tissue samples were isolated from explanted hearts of NYHA III-IV patients undergoing heart transplants (n = 43). Quantitative real-time PCR was performed to assess the mRNA levels of TRPC, TRPM and TRPV channels. Analysis of functional, clinical and biochemical data was used to confirm an end-stage heart failure diagnosis. Compared to myocardium samples from healthy donor hearts (n = 5), we detected a distinct increase in the expression of TRPC1, TRPC5, TRPM4 and TRPM7, and decreased expression of TRPC4 and TRPV2. These changes were not dependent on gender, clinical or biochemical parameters, nor functional parameters of the heart. We detected, however, a significant correlation of TRPC1 and MEF2c expression. Conclusions: The end-stage heart failure displays distinct expressional changes of TRP channels. Our findings provide a systematic description of TRP channel expression in human heart failure. The results highlight the complex interplay between TRP channels and the need for deeper analysis of early stages of hypertrophy and heart failure development.
Asunto(s)
Insuficiencia Cardíaca/fisiopatología , Trasplante de Corazón/efectos adversos , Canales de Potencial de Receptor Transitorio/análisis , Análisis de Varianza , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Trasplante de Corazón/métodos , Humanos , Masculino , Persona de Mediana Edad , Proteínas Serina-Treonina Quinasas/análisis , Proteínas Serina-Treonina Quinasas/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estadísticas no Paramétricas , Canales Catiónicos TRPC/análisis , Canales Catiónicos TRPC/sangre , Canales Catiónicos TRPM/análisis , Canales Catiónicos TRPM/sangre , Canales de Potencial de Receptor Transitorio/sangre , Canales de Potencial de Receptor Transitorio/farmacologíaRESUMEN
AIM: The safety and effectiveness of a preparation containing a mix of Cucurbita Pepo Seed extract, Equisetum arvense and Linum usitatissimum - Flax A (CELcomplex®) on stress urinary incontinence (SUI) was evaluated in female patients recruited from 20 urological and gynaecological outpatient clinics in Slovakia. METHODS: A total of 86 women aged from 32 to 88 with SUI (grade 1 = 44, grade 2 = 42) were enrolled in the study and followed-up for six weeks (point 1) and twelve weeks (point 2). The primary outcome of the study was evaluated by changes in day-time and nocturnal urinary frequency (bathroom visits) and urinary incontinence episodes (leaks). Also, adverse events were quantified as well as the self-perceived effectiveness of the treatment. Research Ethics Board approval was obtained for this study. RESULTS: After 12 weeks of treatment there was a 30% (grade 1 SUI, p < 0.01), and 35% (grade 2 SUI, p < 0.01) improvement in urinary incontinence episodes, a 40% (grade 1 SUI, p < 0.01) and 26% (grade 2 SUI, p < 0.01) improvement in day-time urination frequency and 64% (grade 1 SUI, p < 0.01) and 54% (grade 2 SUI, p < 0.01) improvement in nocturnal urinary frequency. Reported side effects were: headache (3.5%), flatulence (4.1%) and gastrointestinal discomfort (3%). A total of 89.4 % of women in the study reported no side effects from this therapy and 97% acknowledged improvement of symptoms. CONCLUSION: This clinical study demonstrated that a 12 week treatment with a mix of Cucurbita Pepo Seed extract, Equisetum arvense and Linum usitatissimum - Flax A (CELcomplex®) is highly effective on stress urinary incontinence (SUI) with minimum adverse events. Further studies may be needed in order to determine the effectiveness and efficacy of this phytotherapy in other populations.
RESUMEN
Selenium as an antioxidant has attracted attention because of its anticancer activity. This review presents a view on selenium and its compounds exerting influence against cancer in the soft tissues. The results reveal a significant strong association between a low selenium level in blood and a cancer risk. Seleno-supplementation is important in the prevention of metastatic cancer. These results help to elucidate the anticancer effect of selenium providing further evidence to exploit novel anticancer agents targeting selenium-containing organic compounds. Key words: selenium ⢠cancer prevention ⢠cancer treatment ⢠soft tissues.
Asunto(s)
Selenio/farmacología , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/prevención & control , Antioxidantes , HumanosRESUMEN
BACKGROUND: Parkinson disease (PD) is the second most common neurodegenerative disease with various motor and nonmotor symptoms. Progressive course of PD requires frequent medication adjustments. Various combinations of drugs and dose regimens could be used to control symptoms. Thus, not surprisingly, adherence to pharmacotherapy is frequently suboptimal in these patients having negative effect on motor control and patient's quality of life. METHODS: In this article, we offer up-to-date review of adherence in PD compared with other chronic conditions. In addition, we summarize factors influencing level of adherence, ways of measuring, and methods of adherence optimization. For the review of adherence in PD, a literature search was undertaken using PubMed database and relevant search terms. Articles were screened for suitability and data relevance. RESULTS: PubMed and Scopus databases were systematically searched in 2016 and data extraction was a multistep process based on the PRISMA Guidelines. CONCLUSION: According to the recent data, sufficient control of motor symptoms and adequate quality of life are primary goals in the treatment of PD. Adherence to pharmacotherapy play a key role in this process, thus the medication should be tailored for each patient. In order to improve level of suboptimal adherence, these patients should have got recommended various dosing devices or alarms. Good communication with the patients and their relatives or caregivers is also essential.