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1.
Neural Plast ; 2019: 7638675, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214256

RESUMO

Background: Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited disorders affecting predominantly the motor cortex and pyramidal tract, which results in slowly progressing gait disorders, as well as spasticity and weakness of lower extremities. Repetitive transcranial magnetic stimulation (rTMS) has been previously investigated as a therapeutic tool for similar motor deficits in a number of neurologic conditions. The aim of this randomized, controlled trial was to investigate the therapeutic potential of rTMS in various forms of HSP, including pure and complicated forms, as well as adrenomyeloneuropathy. Methods: We recruited 15 patients (five women and 10 men; mean age 43.7 ± 10.6 years) with the mentioned forms of HSP. The intervention included five sessions of bilateral 10 Hz rTMS over primary motor areas of the muscles of lower extremities and five sessions of similar sham stimulation. Results: One patient dropped out due to seizure, and 14 patients completed the study protocol. After real stimulation, the strength of the proximal and distal muscles of lower extremities increased, and the spasticity of the proximal muscles decreased. Change in spasticity was still present during follow-up assessment. No effect was observed regarding gait velocity. No changes were seen after sham stimulation. A post hoc analysis revealed an inverse relation between motor threshold and the change of the strength after active rTMS. Conclusions: rTMS may have potential in improving weakness and spasticity of lower extremities in HSP, especially of proximal muscles whose motor areas are located more superficially. This trial is registered with Clinicaltrials.gov NCT03627416.


Assuntos
Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Paraplegia Espástica Hereditária/terapia , Estimulação Magnética Transcraniana/métodos , Caminhada/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraplegia Espástica Hereditária/fisiopatologia , Resultado do Tratamento , Adulto Jovem
2.
Eur J Prev Cardiol ; 26(9): 930-949, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30776916

RESUMO

Regulation of pro-protein convertase subtilisin/kexin type 9 (PCSK9) by drugs has led to the development of a still small number of agents with powerful activity on low-density lipoprotein cholesterol levels, associated with a significant reduction of cardiovascular events in patients in secondary prevention. The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) studies, with the two available PCSK9 antagonists, i.e. evolocumab and alirocumab, both reported a 15% reduction in major adverse cardiovascular events. Regulation of PCSK9 expression is dependent upon a number of factors, partly genetic and partly associated to a complex transcriptional system, mainly controlled by sterol regulatory element binding proteins. PCSK9 is further regulated by concomitant drug treatments, particularly by statins, enhancing PCSK9 secretion but decreasing its stimulatory phosphorylated form (S688). These complex transcriptional mechanisms lead to variable circulating levels making clinical measurements of plasma PCSK9 for cardiovascular risk assessment a debated matter. Determination of total PCSK9 levels may provide a diagnostic tool for explaining an apparent resistance to PCSK9 inhibitors, thus indicating the need for other approaches. Newer agents targeting PCSK9 are in clinical development with a major interest in those with a longer duration of action, e.g. RNA silencing, allowing optimal patient compliance. Interest has been expanded to areas not only limited to low-density lipoprotein cholesterol reduction but also investigating other non-lipid pathways raising cardiovascular risk, in particular inflammation associated to raised high-sensitivity C-reactive protein levels, not significantly affected by the present PCSK9 antagonists.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de PCSK9 , Pró-Proteína Convertase 9/sangue , Inibidores de Serina Proteinase/uso terapêutico , Animais , Doenças Cardiovasculares/epidemiologia , Resistência a Medicamentos , Dislipidemias/sangue , Dislipidemias/enzimologia , Dislipidemias/epidemiologia , Regulação Enzimológica da Expressão Gênica , Humanos , Fosforilação , Pró-Proteína Convertase 9/genética , Terapêutica com RNAi , Fatores de Risco
3.
Expert Opin Pharmacother ; 20(7): 791-803, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30810432

RESUMO

INTRODUCTION: Tolerability problems in treating hypercholesterolemic patients undergoing statin treatment are of growing concern to physicians and patients, thus underlining the need for an agent with a similar mechanism but minimal side effects. A drug with a somewhat similar mechanism to statins but free of muscular side effects is ETC-1002 (bempedoic acid). It inhibits cholesterol biosynthesis at a step preceding HMG-CoA reductase, i.e. ATP citrate lyase (ACLY). A prodrug, ETC-1002 is converted to the active agent only in liver, not in skeletal muscle, and this may prevent any myotoxic activity. Area covered: The mechanism of ETC-1002 activity is described in detail, considering that ACLY inhibition markedly attenuated atherosclerosis in animal models. Clinical studies are also reported. Expert opinion: Present day LDL-C lowering treatments lead to significant reductions of cardiovascular (CV) events but, at times, the need to interrupt statin treatment appears to be dangerous due to a rapid rise in CV risk. The excellent tolerability of ETC-1002 makes it a useful alternative, either alone or as an adjunct to ezetimibe, for patients with statin intolerance needing to achieve significant CV risk reduction. ETC-1002 is also associated with a marked fall in high-sensitivity C-reactive protein.


Assuntos
Anticolesterolemiantes/uso terapêutico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hiperlipidemias/tratamento farmacológico , ATP Citrato (pro-S)-Liase/antagonistas & inibidores , ATP Citrato (pro-S)-Liase/genética , ATP Citrato (pro-S)-Liase/metabolismo , Animais , Anticolesterolemiantes/efeitos adversos , Aterosclerose/tratamento farmacológico , Proteína C-Reativa/metabolismo , Ensaios Clínicos como Assunto , Ácidos Dicarboxílicos/efeitos adversos , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Ácidos Graxos/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fígado/metabolismo
4.
Med Klin Intensivmed Notfmed ; 113(2): 101-107, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28364184

RESUMO

BACKGROUND: Thrombocytosis is a common phenomenon in critically ill patients. Although thrombocytosis is an independent risk factor for complications, it does not seem to influence mortality in intensive care (ICU) patients. OBJECTIVES: Our investigation aimed to evaluate the etiological and clinical relevance of a platelet count greater than 450 × 109/l in ICU patients. MATERIALS AND METHODS: Patients admitted for a minimum of 4 days to an interdisciplinary ICU during a 45-month period were enrolled in this retrospective observational study. Thrombocytopenic patients (platelet count <150 × 109/l in at least one measurement) were excluded. The study patients were divided into two groups: thrombocytosis group (thrombocytes >450 × 109/l in at least one measurement) and control group (thrombocytes = 150 - 450 × 109/l during ICU stay). Univariate and multiple regression analysis were used to determine the influence of severe co-morbidities on the development of thrombocytosis and the association of elevated platelet count with thrombotic embolism, length of stay (LOS) in ICU, and mortality. RESULTS: A total of 307 patients were analyzed, of whom thrombocytosis was observed in 119 cases. Independent risk factors for the development of thrombocytosis included SIRS, mechanical ventilation, and acute bleeding. Increasing age reduced the risk of thrombocytosis. Thromboembolism occurred in 16 patients (13.4%) with an elevated platelet count and only in nine patients (4.7%) with physiological platelet values (OR: 3.1; 95% CI: 1.3-7.2; p = 0.009). Mean duration of LOS was significantly longer in patients with thrombocytosis (25.2 vs.11.7 days, p < 0.0001). Elevated platelet count showed a negative correlation with ICU mortality (OR: 0.32; 95%-CI: 0.12-0.83; p = 0.019). CONCLUSION: In our retrospective analysis the occurrence of thrombocytosis in a cohort of interdisciplinary ICU patients was associated with a higher rate of complications and longer LOS in the ICU. Despite these findings, thrombocytosis seems to reduce mortality in critical ill patients.


Assuntos
Unidades de Terapia Intensiva , Contagem de Plaquetas , Trombocitose , Adulto , Idoso , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Trombocitose/diagnóstico
5.
Biochimie ; 144: 74-84, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29054801

RESUMO

Proteins whose presence prevents water from freezing in living organisms at temperatures below 0 °C are referred to as antifreeze proteins. This group includes molecules of varying size (from 30 to over 300 aa) and variable secondary/supersecondary conformation. Some of these proteins also contain peculiar structural motifs called solenoids. We have applied the fuzzy oil drop model in the analysis of four categories of antifreeze proteins: 1 - very small proteins, i.e. helical peptides (below 40 aa); 2 - small globular proteins (40-100 aa); 3 - large globular proteins (>100 aa) and 4 - proteins containing solenoids. The FOD model suggests a mechanism by which antifreeze proteins prevent freezing. In accordance with this theory, the presence of the protein itself produces an ordering of water molecules which counteracts the formation of ice crystals. This conclusion is supported by analysis of the ordering of hydrophobic and hydrophilic residues in antifreeze proteins, revealing significant variability - from perfect adherence to the fuzzy oil drop model through structures which lack a clearly defined hydrophobic core, all the way to linear arrangement of alternating local minima and maxima propagating along the principal axis of the solenoid (much like in amyloids). The presented model - alternative with respect to the ice docking model - explains the antifreeze properties of compounds such as saccharides and fatty acids. The fuzzy oil drop model also enables differentiation between amyloids and antifreeze proteins.


Assuntos
Proteínas Anticongelantes/química , Proteínas Anticongelantes/metabolismo , Modelos Moleculares , Peptídeos/química , Peptídeos/metabolismo , Conformação Proteica em alfa-Hélice
6.
Heliyon ; 3(2): e00235, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28217749

RESUMO

Formal assessment of structural similarity is - next to protein structure prediction - arguably the most important unsolved problem in proteomics. In this paper we propose a similarity criterion based on commonalities between the proteins' hydrophobic cores. The hydrophobic core emerges as a result of conformational changes through which each residue reaches its intended position in the protein body. A quantitative criterion based on this phenomenon has been proposed in the framework of the CASP challenge. The structure of the hydrophobic core - including the placement and scope of any deviations from the idealized model - may indirectly point to areas of importance from the point of view of the protein's biological function. Our analysis focuses on an arbitrarily selected target from the CASP11 challenge. The proposed measure, while compliant with CASP criteria (70-80% correlation), involves certain adjustments which acknowledge the presence of factors other than simple spatial arrangement of solids.

7.
Neoplasma ; 63(4): 617-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27268926

RESUMO

Cold-induced neuropathy is the most observed side effect of oxaliplatin. Presence of neuropathy is routinely assessed by electroneurographical examination. The use of electroneurography has not been a part of typical oncological monitoring and treatment protocols, leading to untreated, irreversible damage to patients' peripheral nerves, undiagnosed for long periods of time. 36 colorectal cancer patients followed FOLFOX4 with/without bevacizumab or XELOX were enrolled between February 2013 and January 2015 in the study at the University Hospital Oncological Department, Krakow, Poland. Electroneurography was performed prior to the first cycle of chemotherapy and after the 4th cycle. 32 out of 36 enrolled patients completed neurological evaluation. Pre-treatment neurographic examination revealed presence of peripheral neuropathy in 10 (31.25%) patients; 6 (18.75%) had sensory neuropathy and 4 (12.5%) had mixed, sensorimotor neuropathy. After treatment examination revealed significant increase in the number of neuropathic patients; presence of peripheral neuropathy was observed in 19 patients (59%), sensory polyneuropathy was diagnosed in10 patients (31.25%) and mixed neuropathy was diagnosed in 9 patients (28.13%). Early electrophysiological monitoring followed by a symptom dependent oxaliplatin regimen would be highly beneficial for patients undergoing oxaliplatin treatment, improving their well-being and positively affecting their life quality.


Assuntos
Eletrodiagnóstico/métodos , Condução Nervosa/fisiologia , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Fenômenos Eletrofisiológicos , Humanos , Oxaliplatina/uso terapêutico , Qualidade de Vida
8.
Clin Biomech (Bristol, Avon) ; 32: 72-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26851563

RESUMO

BACKGROUND: The object of the study was to assess the impact of one-level stabilization of the cervical spine for both anterior static and dynamic plates. Segments C2-C6 of the cervical spine, were investigated, from which was determined the stress and strain fields in the region of implantation and adjacent motion segments. The purpose was the comparison of changes that affect the individual stabilizers. METHODS: For testing we used finite element analysis. The cervical spine model takes into account local spondylodesis. The study includes both an intact anatomical model and a model with implant stabilization. FINDINGS: The analysis covered the model loaded with a moment of force for 1 Nm in the sagittal plane during movement. We compared both the modeled response of the whole fragment C2-C6 and the response of individual motion segments. The largest limitation of range of motion occurred after implantation with static plates. The study also showed that the introduction of the one-level stabilization resulted in an increase in stress in intervertebral disc endplates of adjacent segments. INTERPRETATION: The results indicate that the increase in stress caused by stiffening may result in disorders in remodeling of bone structures. The use of dynamic plates showed improved continuity strains in the tested spine, thereby causing remodeling most similar to the physiological state and reducing the stresses in adjacent segments.


Assuntos
Vértebras Cervicais/cirurgia , Disco Intervertebral/cirurgia , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Adulto , Materiais Biocompatíveis , Fenômenos Biomecânicos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Vértebras Cervicais/fisiologia , Simulação por Computador , Análise de Elementos Finitos , Humanos , Disco Intervertebral/fisiologia , Imageamento por Ressonância Magnética , Masculino , Modelos Anatômicos , Movimento (Física) , Pressão , Próteses e Implantes , Desenho de Prótese , Amplitude de Movimento Articular/fisiologia , Tomografia Computadorizada por Raios X
9.
Curr Med Chem ; 21(25): 2881-91, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24735362

RESUMO

High-density lipoproteins (HDL) are classified as atheroprotective because they are involved in transport of cholesterol to the liver, known as "reverse cholesterol transport (RCT)" exerting antioxidant and anti-inflammatory activities. There is also evidence for cytoprotective, vasodilatory, antithrombotic, and anti-infectious activities for these lipoproteins. HDLs are known by structural, metabolic and biologic heterogeneity. Thus, different methods are able to distinguish several subclasses of HDL. Different separation techniques appear to support different HDL fractions as being atheroprotective or related with lower cardiovascular (CV) risk. However, HDL particles are not always protective. Modification of constituents of HDL particles (primarily in proteins and lipids) can lead to the decrease in their activity and induce proatherogenic properties, especially when isolated from patients with augmented systemic inflammation. According to available studies, it seems that HDL functionality may be a better therapeutic target than HDL cholesterol quantity; however, it is still disputable which subfractions are most beneficial. There is mounting evidence supporting HDL subclasses as an important biomarker to predict and/or reduce CV risk. In this review we discuss recent notices on atheroprotective and functional characteristic of different HDL subfractions. Also, we provide a brief overview of the different methods used by clinicians and researchers to separate HDL subfractions. Ongoing and future investigations will yield important new information if any given separation method might represent a 'gold standard', and which subfractions are reliable markers of CV risk and/or potential targets of novel, more focused, and effective therapies.


Assuntos
Lipoproteínas HDL/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Humanos , Fatores de Risco
10.
Curr Med Chem ; 21(25): 2927-46, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24606514

RESUMO

Many pharmacological and non-pharmacological strategies have been used to increase high-density lipoprotein- cholesterol (HDL-C) levels, but the results obtained have not been consistently associated with effective cardiovascular risk reduction. Therefore, research is now focused to improve HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to its heterogeneity caused by various lipids, proteins, vitamins, hormones and small RNAs that are associated with HDL. These components could act as potential HDL-related biomarkers, which may guide effective therapeutic interventions. Evaluation of HDL functionality seems to be more relevant, given the current evidence of the pleiotropic potentially atheroprotective functions of HDL. It is relevant to understand which HDL-related properties involved in its cardioprotective functions, in order to develop pharmacological and nonpharmacological therapies to improve HDL functionality.


Assuntos
HDL-Colesterol/sangue , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Humanos , Fatores de Risco
11.
Curr Med Chem ; 21(25): 2892-901, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24606516

RESUMO

The electrophoretic separation of lipoproteins on polyacrylamide gels enables the quantification of nonatherogenic and atherogenic plasma lipoproteins including small dense low density lipoprotein (sdLDL) particles, which represent the atherogenic lipoprotein subpopulations in plasma. This methodology could help distinguish between nonatherogenic hyperlipidemia, normolipidemia with an atherogenic lipoprotein profile, non-atherogenic normolipidemia, and atherogenic hyperlipidemia. According to our pilot research of a normolipidemic population, the atherogenic lipoprotein profile might be present in about 6% of normolipidemic young healthy individuals. Therefore, if confirmed by other studies, it will be necessary to consider a different diagnostic approach and risk stratification for patients with atherogenic normolipidemia (as well as non-atherogenic hypercholesterolemia).


Assuntos
Aterosclerose/metabolismo , Dislipidemias/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Lipoproteínas/metabolismo , Fatores de Risco
12.
J Biomol Struct Dyn ; 32(10): 1583-600, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23998258

RESUMO

This work analyzes proteins which contain an immunoglobulin fold, focusing on their hydrophobic core structure. The "fuzzy oil drop" model was used to measure the regularity of hydrophobicity distribution in globular domains belonging to proteins which exhibit the above-mentioned fold. Light-chain IgG domains are found to frequently contain regular hydrophobic cores, unlike the corresponding heavy-chain domains. Enzymes and DNA binding proteins present in the data-set are found to exhibit poor accordance with the hydrophobic core model.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Imunoglobulinas/química , Proteínas de Ligação a DNA/química , Bases de Dados de Proteínas , Enzimas/química , Modelos Moleculares , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
14.
J Theor Biol ; 283(1): 60-70, 2011 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-21635900

RESUMO

This paper introduces a new model that enables researchers to conduct protein folding simulations. A two-step in silico process is used in the course of structural analysis of a set of fast-folding proteins. The model assumes an early stage (ES) that depends solely on the backbone conformation, as described by its geometrical properties--specifically, by the V-angle between two sequential peptide bond planes (which determines the radius of curvature, also called R-radius, according to a second-degree polynomial form). The agreement between the structure under consideration and the assumed model is measured in terms of the magnitude of dispersion of both parameters with respect to idealized values. The second step, called late-stage folding (LS), is based on the "fuzzy oil drop" model, which involves an external hydrophobic force field described by a three-dimensional Gauss function. The degree of conformance between the structure under consideration and its idealized model is expressed quantitatively by means of the Kullback-Leibler entropy, which is a measure of disparity between the observed and expected hydrophobicity distributions. A set of proteins, representative of the fast-folding group - specifically, cold shock proteins - is shown to agree with the proposed model.


Assuntos
Modelos Moleculares , Dobramento de Proteína , Proteínas e Peptídeos de Choque Frio/química , Simulação por Computador , Processamento Eletrônico de Dados/métodos , Entropia , Interações Hidrofóbicas e Hidrofílicas , Modelos Químicos , Chaperonas Moleculares/química , Relação Estrutura-Atividade
15.
Int J Clin Pract ; 64(8): 1148-54, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20642713

RESUMO

Levosimendan is a 'Ca(2+)sensitiser', which exerts its inotropic effect by increasing the affinity of troponin C for Ca(2+), directly stabilising the Ca(2+)-induced conformation of troponin C. It leads to a positive inotropic effect without impairing diastolic relaxation and causing cytosolic Ca(2+) ion overload, which might result in cardiac myocyte dysfunction, arrhythmias and cell death. Levosimendan may also have significant anti-inflammatory properties. Data from various studies suggest that levosimendan might have anti-arrhythmic effects, although the outcome of clinical trials on the effect of this agent in (for example) atrial fibrillation (AF) remains controversial. Currently, on the basis of available data, it is especially worth emphasising the potential role of this drug in the termination of AF after cardiac surgery, which significantly influences early- and long-term morbidity and mortality. This review considers the putative anti-arrhythmic properties of levosimendan and discusses the potential clinical application of such a drug.


Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Cardiotônicos/farmacologia , Hidrazonas/farmacologia , Piridazinas/farmacologia , Antiarrítmicos/efeitos adversos , Anti-Inflamatórios/farmacologia , Fibrilação Atrial/induzido quimicamente , Cardiotônicos/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hidrazonas/efeitos adversos , Piridazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Simendana
16.
J Hum Hypertens ; 24(11): 713-20, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20613782

RESUMO

It has been shown that vascular endothelial cells functionally express a local circuit autocrine-paracrine regulatory pathway driven by endogenously expressed chemically authentic morphine, its cognate opiate alkaloid-selective mu3 and mu4 receptors, and constitutive nitric oxide (NO). Accordingly, the aim of the study was to examine morphine-mediated changes in hypertension-associated gene expression in two independent cell models: primary cultures of human white blood cells (WBCs) and human multilineage progenitor cells (MLPCs). In separate incubations, primary cultures of human WBC and MLPC were treated with morphine at a final concentration of 1 µM morphine for 2-4 h. After RNA extraction and reverse transcription, Human Genome Survey Arrays were used to construct and differentially analyze by strict statistical criteria transcriptional/gene expression profiles of WBC and undifferentiated human MLPC in three independent experiments. The Applied Biosystems Human Genome Survey Array contains 31,700 60-mer oligonucleotide probes representing a set of 27,868 individual human genes and >1000 control probes. After DNA microarray analyses, a variety of hypertension-associated genes from both cell types were observed to be significantly downregulated. The only genes expressed in both cell types were ß-adrenergic receptor kinase 2 (ADRBK2) and coding protein kinase WNK1 (PRKWNK1); however, only PRKWNK1 showed downregulation of its expression after morphine exposure. Only two genes were observed to be significantly upregulated after morphine treatment: ADRBK2 in stem cells and ß3-adrenergic receptor in WBC. Morphine administration to primary cultures of human WBC and MLPC altered the expression profile of 16 candidate hypertension-associated genes. The majority of relevant genes was observed to be downregulated, suggesting ongoing homeostatic regulation by endogenous morphine coupled to NO production and release. In sum, these data suggest a predominantly antihypertensive role for endogenous morphine/NO signaling events.


Assuntos
Linhagem da Célula , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão/genética , Leucócitos/efeitos dos fármacos , Morfina/farmacologia , Células-Tronco/efeitos dos fármacos , Células Cultivadas , Quinase 3 de Receptor Acoplado a Proteína G/genética , Perfilação da Expressão Gênica/métodos , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Peptídeos e Proteínas de Sinalização Intracelular , Leucócitos/metabolismo , Antígenos de Histocompatibilidade Menor , Óxido Nítrico/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Peptídeos Opioides/metabolismo , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/sangue , Receptores Adrenérgicos beta 3/genética , Células-Tronco/metabolismo , Fatores de Tempo , Proteína Quinase 1 Deficiente de Lisina WNK
17.
Curr Med Chem ; 16(30): 4020-31, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19747125

RESUMO

The natriuretic peptide family is comprised of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), dendroaspis natriuretic peptide - DNP and urodilatin. They play a role in the diagnosis of several diseases, especially those involving the cardiovascular system. Sepsis is a complex condition that can lead to multiorgan failure, shock and death. The number of people developing sepsis is still increasing (approximately 750,000 cases of sepsis occur annually in the USA). Both ANP and pro-ANP have attracted interest as new markers for sepsis. Reports indicate that ANP or BNP levels are elevated in septic patients. However, many mechanisms are still unexplained. This situation is complicated by the fact that contradictory results have been published. There are several reasons for this controversy including differences in the techniques used to assay natriuretic peptides. Nevertheless, natriuretic peptides might eventually prove useful for the diagnosis and/or the treatment of septic patients.


Assuntos
Peptídeos Natriuréticos/sangue , Sepse/sangue , Choque Séptico/sangue , Sequência de Aminoácidos , Humanos , Dados de Sequência Molecular
18.
Acta Chir Belg ; 108(5): 557-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19051466

RESUMO

BACKGROUND: The transperitoneal approach (TP) to the aorta is the most widely accepted surgical approach in aortic surgery as it is simple, fast and provides excellent exposure of the intra-abdominal cavity and vascular structures. In recent years, there has been an increasing interest in the retroperitoneal (RP) approach to the aorta since it has been described as having a better outcome, i.e., preserving pulmonary function and gastro-intestinal physiology, reducing the intra-operative blood loss, minimising patient discomfort or pain, decreasing the incidence of wound complications and shortening ICU and hospital stay. The aim of this study is to compare the transperitoneal and retroperitoneal approaches in aortic surgery for aorto-iliac occlusive disease (AIOD). METHODS: From December 2003 to June 2006, a total of 153 consecutive patients who had undergone aortic surgery for AIOD, were studied retrospectively. The TP approach was used in 85 patients and the RP approach in 68 patients. Demographic features, intra-operative and postoperative data were analysed and compared according to the approach used. RESULTS: The mean operating time (83.6 +/- 23 vs. 104.4 +/- 30 min, p < 0.001) and mean aortic cross-clamp time (18.4 +/- 3 vs. 15.2 +/- 3 min, p < 0.0412) were significantly longer in the RP group. Peri-operative blood loss (700 +/- 350 vs. 650 +/- 330 ml, p < 0.683) and mortality rate < or = 30 day (1/1.2% vs. 0/0.0%, p < 0.896) were similar between the groups. The operative 30 day mortality rate was 0.7% (1 of 153) overall. The RP group had an earlier return of bowel functions (17.1 < or = 3 vs. 24.2 < or = 5 hrs, p < 0.001), earlier resumption of diet (26.4 < or = 4 vs. 31.4 < or = 5 hrs, p < 0.001), shorter period of intubation (3.5 < or = 2 vs. 6.5 < or = 3 hrs, p < 0.001), ICU stay (1.5 < or = 1 vs. 4.2 < or = 1 hrs, p < 0.001) and hospital stay (4.0 < or = 1 vs. 5.9 < or = 1 days, p < 0.001). Mean effort-pain scores were significantly lower in the RP group (3.8 < or = 1 vs. 5.3 < or = 1, p < 0.001). Incidence of pulmonary complications (4.4%, 3 of 68 vs. 7.3%, 8 of 85, p < 0.001), paralytic ileus (1.5%, 1 of 68 vs. 3.5%. 3 of 85, p < 0.001) were also lower in the RP group. Wound complications were more common in the TP group (4.7%, 4 of 85 vs. 10.3%, 7 of 86, p < 0.001). Most cases in both groups were related to incisional hernia or evisceration. CONCLUSION: This report presents our experience with the use of TP and RP approaches in a patient population merely consisting of AIOD. The RP approach was associated with a significantly lower incidence of postoperative pulmonary complications, rapid recovery of gastro-intestinal functions, shorter ICU and hospital stay, less peri-operative blood loss and lower mean effort-pain scores. We conclude that the RP approach is a safe and feasible technique that exposes patients to less postoperative complications.


Assuntos
Aorta Abdominal/cirurgia , Arteriopatias Oclusivas/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Perda Sanguínea Cirúrgica , Constrição , Feminino , Humanos , Pseudo-Obstrução Intestinal/etiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Pneumonia/etiologia , Complicações Pós-Operatórias , Recuperação de Função Fisiológica , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Fatores de Tempo
19.
Cardiovasc J Afr ; 19(2): 84-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18516353

RESUMO

The aim of the study was to estimate the effect of calcium supplementation on cholesterol concentrations in patients with hyperlipidaemia and previous viral hepatitis. The study comprised 43 patients, aged 28 to 82 years (21 with type 2 hyperlipidaemia). The control group included 22 healthy subjects. After four weeks of a hypolipaemic diet (wash-out period), the patients with type 2 hyperlipidaemia were recruited to a group administered a complex preparation containing 170 mg of calcium lactate and 60 mg of vitamin C (Calcium C, Polfa-Lodz SA, Poland) at a dose of one tablet three times a day. After four weeks of active therapy, the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) decreased by 4, 6 and 8%, respectively. Statistical significance was obtained for only TC (p = 0.03) when comparing the group of patients with hypercholesterolaemia before and after the therapy with the calcium preparation. A statistically insignificant increase of high-density lipoprotein cholesterol (HDL-C) of 1% was observed. Within the four-week period of calcium supplementation at a dose of 510 mg/24 h, the total concentration of calcium decreased by 3%, whereas the concentration of ionised calcium increased by 7%. None of the obtained values was of statistical significance. In patients with type 2 hyperlipidaemia and previous viral hepatitis, a four-week supplementation of calcium in a calcium lactate preparation beneficially modified the lipid profile. I t statistically significantly decreased the total cholesterol concentration by 4% (p = 0.03), did not cause any significant changes in serum calcium concentration, was well tolerated and did not induce any side effects.


Assuntos
Anticolesterolemiantes/uso terapêutico , Compostos de Cálcio/uso terapêutico , Colesterol/sangue , Suplementos Nutricionais , Hepatite Viral Humana/complicações , Hipercolesterolemia/tratamento farmacológico , Lactatos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/administração & dosagem , Ácido Ascórbico/uso terapêutico , Biomarcadores/sangue , Compostos de Cálcio/administração & dosagem , LDL-Colesterol/sangue , Esquema de Medicação , Feminino , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/metabolismo , Lactatos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Comprimidos , Resultado do Tratamento , Triglicerídeos/sangue
20.
Thorac Cardiovasc Surg ; 56(1): 20-3, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18200462

RESUMO

BACKGROUND: Preoperative atrial fibrillation is one of the predictors of increased morbidity and mortality in patients undergoing surgical revascularization, and consequently, prolongs the duration of stay in the ICU and of overall hospitalization. METHODS: The study included 3000 patients subjected to primary isolated coronary artery bypass grafting from 2000 to 2004. Of the 3000 patients, 5.8 % (n = 174) had electrocardiographically documented, preoperative atrial fibrillation. To evaluate the relationship between preoperative AF and postoperative outcome, all patients were observed for about three years. RESULTS: Patients with preoperative atrial fibrillation were older (P < 0.05), had a lower ejection fraction (P < 0.001), a higher incidence of heart failure (P < 0.001), hypertension (P < 0.001), and more coexistent morbidities including diabetes (P < 0.05), obturative pulmonary disease (P < 0.0001) and mild renal failure (P < 0.001). Statistical analysis showed that survival rates at 6 and 30 days, 6 and 12 months, and 3 years following surgical revascularization of patients with vs. those without preoperative atrial fibrillation were: 96.4% vs. 98.1%, and 94.5% vs. 97.3% (P = ns), 86.2% vs. 93.0% (P < 0.03), and 74.7% vs. 91.0% (P < 0.02), and 70.7% vs. 90.6% (P < 0.01). After 3 years' observation there was a survival difference of 19.9%. We showed that preoperative atrial fibrillation triple increased the risk of postoperative AF and was an independent risk factor for in-hospital death (P < 0.001). CONCLUSIONS: Preoperative atrial fibrillation is a predictor of postoperative complications, including death, and of a significant reduction in patients' long-term survival. Patients with preoperative atrial fibrillation should be considered as high-risk patients with potential postoperative complications and should be well protected with antiarrhythmic and anticoagulant therapy.


Assuntos
Fibrilação Atrial/mortalidade , Ponte de Artéria Coronária/mortalidade , Revascularização Miocárdica/mortalidade , Complicações Pós-Operatórias/mortalidade , Idoso , Ponte de Artéria Coronária/métodos , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polônia/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Taxa de Sobrevida , Resultado do Tratamento
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