RESUMO
The interplay between hepatitis B (HBV) and delta (HDV) viruses is complex and not always characterized during chronic HDV infection. We assessed the clinical usefulness of new quantitative assays for HBV and HDV serum markers in a retrospective cross-sectional study. Sera obtained from 122 HDV genotype 1 and HBV genotype D coinfected, anti-HIV-negative patients (71 males; median age 49.8 [21.7-66.9] years), recruited consecutively in two geographical areas (Italy 69 patients, Romania 53 patients) with different HBV and HDV epidemiology, were tested for HBsAg, HBV-DNA, HBcrAg, total anti-HBc, HDV-RNA, IgM and total anti-HDV using quantitative assays. Cirrhosis, which showed comparable prevalence in the two cohorts, was diagnosed in 97 of 122 (79.5%) patients. At multivariate analysis, cirrhosis was associated with lower total anti-HBc/IgM anti-HDV ratio (OR 0.990, 95% CI 0.981-0.999, P = .038), whereas disease activity was associated with higher total anti-HDV (OR 10.105, 95% CI 1.671-61.107, P = .012) and HDV-RNA levels (OR 2.366, 95% CI 1.456-3.844, P = .001). HDV-RNA serum levels showed a positive correlation with HBV-DNA (ρ = 0.276, P = .005), HBsAg (ρ = 0.404, P < .001) and HBcrAg (ρ = 0.332, P < .001). The combined quantitative profiling of HBV and HDV serum markers identifies specific patterns associated with activity and stage of chronic hepatitis D (CHD). HDV pathogenicity depends on the underlying active HBV infection in spite of the inhibition of its replication. HDV-RNA, IgM anti-HDV, total anti-HDV, total anti-HBc, HBsAg and HBcrAg serum levels qualify for prospective studies to predict progressive CHD and identify candidates to antiviral therapy.
Assuntos
Biomarcadores/sangue , Coinfecção/patologia , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatite D Crônica/patologia , Adulto , Idoso , Estudos Transversais , DNA Viral/sangue , Feminino , Genótipo , Anticorpos Anti-Hepatite/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Imunoglobulina M/sangue , Itália , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Romênia , Adulto JovemRESUMO
BACKGROUND: Hypertension (EH) and type 2 diabetes (T2DM) are major causes of chronic kidney disease (CKD) and identification of predictors of CKD onset is advisable. We aimed to assess whether dynamic renal resistive index (DRIN), as well as other markers of systemic vascular damage, are able to predict albuminuria onset and estimated glomerular filtration rate (eGFR) decline in patients with T2DM or EH. METHODS: In this prospective observational cohort study, 27 T2DM and 43 EH patients, free of CKD at baseline, were followed-up for 4.1 ± 0.6 years. Resistive Index (RI), endothelium-dependent (FMD) and independent vasodilation in the brachial artery (after glyceryl trinitrate - GTN - 25 µg s.l.), carotid-femoral Pulse Wave Velocity (PWV), Augmentation Index (AIx), DRIN (%RI change after GTN 25 µg s.l.) were evaluated. RESULTS: Patients developing microalbuminuria were older, more frequently T2DM, with higher UACR at baseline, and showed higher DRIN (-2.8 ± 6.7 vs -10.6 ± 6.4 %, p = 0.01) and PWV (9.9 ± 1.3 vs 7.9 ± 1.5 m/s, p = 0.004) at baseline. The best predictors of microalbuminuria onset were DRIN > -5.16 % in T2DM (sensitivity 0.83, specificity 0.80) and PWV > 8.6 m/s in EH (sensitivity 0.96, specificity 1.00). Individuals whose eGFR declined (n = 27) had higher eGFR at baseline, but similar vascular characteristics; however in EH showing eGFR decline, baseline DRIN and PWV were higher. PWV showed a steeper progression during follow-up in patients developing albuminuria (Visit-outcome interaction: p = 0.01), while DRIN was early compromised but no further impaired (Visit-outcome interaction: p = 0.04). CONCLUSIONS: PWV and DRIN are able to predict microalbuminuria onset in newly diagnosed EH and T2DM. DRIN is early compromised in T2DM patients developing microalbuminuria.
Assuntos
Albuminúria/fisiopatologia , Artéria Braquial/diagnóstico por imagem , Diabetes Mellitus Tipo 2/fisiopatologia , Hipertensão/fisiopatologia , Rim/diagnóstico por imagem , Artéria Renal/diagnóstico por imagem , Vasodilatação/fisiologia , Adulto , Fatores Etários , Idoso , Albuminúria/epidemiologia , Artéria Braquial/fisiopatologia , Estudos de Coortes , Taxa de Filtração Glomerular , Humanos , Rim/irrigação sanguínea , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Artéria Renal/fisiopatologia , Circulação Renal , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , UltrassonografiaRESUMO
Nanoplastic debris, resulted from runoff and weathering breakdown of macro- and microplastics, represents an emerging concern for marine ecosystems. The aim of the present study was to investigate disposition and toxicity of polystyrene nanoparticles (NPs) in early development of sea urchin embryos (Paracentrotus lividus). NPs with two different surface charges where chosen, carboxylated (PS-COOH) and amine (PS-NH2) polystyrene, the latter being a less common variant, known to induce cell death in several in vitro cell systems. NPs stability in natural seawater (NSW) was measured while disposition and embryotoxicity were monitored within 48 h of postfertilization (hpf). Modulation of genes involved in cellular stress response (cas8, 14-3-3ε, p-38 MAPK, Abcb1, Abcc5) was investigated. PS-COOH forms microaggregates (PDI > 0.4) in NSW, whereas PS-NH2 results are better dispersed (89 ± 2 nm) initially, though they also aggregated partially with time. Their respectively anionic and cationic nature was confirmed by ζ-potential measurements. No embryotoxicity was observed for PS-COOH up to 50 µg mL(-1) whereas PS-NH2 caused severe developmental defects (EC50 3.85 µg mL(-1) 24 hpf and EC50 2.61 µg mL(-1) 48 hpf). PS-COOH accumulated inside embryo's digestive tract while PS-NH2 were more dispersed. Abcb1 gene resulted up-regulated at 48 hpf by PS-COOH whereas PS-NH2 induced cas8 gene at 24 hpf, suggesting an apoptotic pathway. In line with the results obtained with the same PS NPs in several human cell lines, also in sea urchin embryos, differences in surface charges and aggregation in seawater strongly affect their embryotoxicity.
Assuntos
Nanopartículas/toxicidade , Paracentrotus/efeitos dos fármacos , Poliestirenos/toxicidade , Poluentes Químicos da Água/toxicidade , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Caspase 8/genética , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Feminino , Trato Gastrointestinal/metabolismo , Nanopartículas/química , Paracentrotus/embriologia , Paracentrotus/genética , Paracentrotus/metabolismo , Poliestirenos/química , Água do Mar/química , Poluentes Químicos da Água/químicaRESUMO
BACKGROUND: Two types of detraining can be described: short-term detraining with a period of less than 4 weeks, and long-term detraining (period longer than 4 weeks). The purpose of this study is to verify the presence and eventually the magnitude of physiological cardiorespiratory changes in young team sport players after a period of long-term detraining. METHODS: Fourteen young soccer players (15 ± 1 year) were studied with two incremental tests at the end of the regular season and after a six-week total break period from training activities. Physiological variables were evaluated: heart rate (HR), oxygen uptake (VO2), volume of ventilation (VE), aerobic (VA) and anaerobic (Van) running speed at thresholds and maximum effort were recorded. RESULTS: This study shows the magnitude of the physiological changes in young players after a period of long-term detraining. The results showed significant decreases at the end of the detraining period of VO2 at VA of 22.7% (44.54 ± 4.56 vs. 34.41 ± 4.57 mL/kg/min, P<0.05), of 25.8% of VO2 at VAn (54.60 ± 5.81 vs. 40.48 ± 5.07 mL/kg/min, P<0.05) and of 21.2% in VO2 max (62.83 ± 5.77 vs. 49.46 ± 6.51 mL/kg/min, P<0.05). Speed at VA (11.5 ± 0.96 vs. 10.7 ± 0.97 km/h; P<0.05), speed at VAn (15.3 ± 1.05 vs. 14.2 ± 1.48 km/h; P<0.05), peak running speed (18.8 ± 1.20 vs. 17.2 ± 1.1 km/h; P<0.05). CONCLUSION: It is likely that alteration of metabolic parameters may significantly affect the range of physical condition and especially, aerobic-anaerobic resistance and maintenance training would be advisable in young athletes during the transition period. Given the relevance of worsening demonstrated by our data, coaches should avoid very long periods of complete rest (no more than 15 days) at the end of the season.
Assuntos
Descanso/fisiologia , Futebol/fisiologia , Adolescente , Limiar Anaeróbio/fisiologia , Dióxido de Carbono/análise , Humanos , Estudos Longitudinais , Consumo de Oxigênio/fisiologia , Ventilação Pulmonar/fisiologia , Corrida/fisiologiaRESUMO
AIM/HYPOTHESIS: Renal resistive index is a useful measure for quantifying alterations in renal blood flow. In the present study we evaluated resistive index at baseline and after vasodilation induced by nitroglycerine in normoalbuminuric patients with type 2 diabetes or essential hypertension, relating the values to indices of systemic vascular dysfunction. METHODS: Newly diagnosed treatment-naïve type 2 diabetic (n = 32) and hypertensive patients (n = 49) were compared with 27 age- and sex-matched healthy controls. Renal resistive index was obtained by duplex ultrasound at baseline and after 25 µg sublingual nitroglycerine. Endothelium-dependent (flow-mediated dilation) and -independent (response to nitroglycerine) vasodilation in the brachial artery was assessed by computerised edge detection system. Carotid-femoral pulse-wave velocity and augmentation index were assessed by applanation tonometry. Nitrotyrosine levels, an index of oxidative stress, were also measured. RESULTS: Resistive index was higher in diabetic than in hypertensive patients and controls (p < 0.001), while changes in resistive index induced by nitroglycerine were lower in hypertensive patients compared with controls (p < 0.01), and were further reduced in type 2 diabetic patients. Hypertensive and diabetic patients showed significantly increased arterial stiffness, nitrotyrosine levels and reduced endothelial function than controls (p < 0.05). Changes in resistive index induced by nitroglycerine were independently related to serum glucose, reactive hyperaemia and aortic pulse-wave velocity in the overall population. CONCLUSIONS/INTERPRETATION: These results support the dynamic evaluation of renal resistive index as an early detector of renal vascular alterations in the presence of type 2 diabetes and hypertension, even before the onset of microalbuminuria.
Assuntos
Albuminúria/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Hipertensão/fisiopatologia , Rim/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Adulto , Albuminúria/sangue , Albuminúria/epidemiologia , Glicemia/metabolismo , Estudos de Casos e Controles , Comorbidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nitroglicerina/farmacologia , Estresse Oxidativo/fisiologia , Tirosina/análogos & derivados , Tirosina/sangue , Ultrassonografia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/farmacologiaRESUMO
BACKGROUND AND STUDY AIM: A catheter-type endocytoscope has recently been developed that is able to provide in vivo cellular images of gastrointestinal mucosa. Aberrant crypt foci (ACF) represent the earliest precursor of colorectal cancer featuring the dysplasia-carcinoma sequence. The aim of the current study was to assess the potential of the endocytoscopy system (ECS) in the "in vivo" detection of dysplasia in colorectal ACF. PATIENTS AND METHODS: Consecutive patients with colorectal ACF were studied with endocytoscopy. Blinded endoscopic and histological assessments were obtained. Lesions were excised en bloc for histology. RESULTS: A total of 48 colorectal lesions were examined in 41 patients. The mean duration of the ECS procedure was 44 +/- 12 minutes (range 31 - 62 minutes). The quality of ECS images was rated as good in 39/48, medium in six, and poor in three (6.2 %). It was possible to observe lesions at the cellular level and evaluate both cellular and structural atypia in vivo. In normal mucosa, crypts had preserved individuality and round-shaped contours. Nuclei were located at the basal third of the crypt in a single line, and the lumen was circular. In dysplastic ACF, crypt contours were polygonal, cell nuclei were elongated with pseudostratification toward the luminal half of the crypt and irregularly arranged, and the lumen was linear. In all, 23 endocytoscopic images were labeled as dysplastic and 25 as nondysplastic. Histology confirmed low-grade dysplasia in 21/23 cases (91.4 % sensitivity). Absence of dysplasia was confirmed in the remaining 25 cases (100 % specificity). Interobserver agreement between trained endoscopist and pathologist was good (wK 0.68; 95 % CI 0.59 - 0.78). CONCLUSIONS: Endocytoscopy provides real-time histological images in vivo, with clear visualization of cellular details and features of dysplasia in colorectal ACF.
Assuntos
Neoplasias Colorretais/patologia , Endoscópios , Endoscopia , Lesões Pré-Cancerosas/patologia , Idoso , Forma do Núcleo Celular , Tamanho do Núcleo Celular , Feminino , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Therapeutic ultrasound (1.5 W/cm(2)) was investigated for its effect upon testicular size and consistency and semen quality in five dogs. Dogs were treated every other day with a total of three treatments and were examined up to 2 weeks after treatment. There was some tenderness after treatment and a significant decrease in testicular size and semen quality. This method may provide a suitable contraception technique in dogs and requires further investigation.
Assuntos
Anticoncepção/veterinária , Testículo/diagnóstico por imagem , Ultrassom , Animais , Cães , Masculino , Sêmen/diagnóstico por imagem , Testículo/patologia , UltrassonografiaRESUMO
Facial pain remains a diagnostic and therapeutic challenge for both clinicians and patients. In clinical practice, patients suffering from facial pain generally undergo multiple repeated consultations with different specialists and receive various treatments, including surgery. Many patients, as well as their primary care physicians, mistakenly attribute their pain as being due to rhinosinusitis when this is not the case. It is important to exclude non-sinus-related causes of facial pain before considering sinus surgery to avoid inappropriate treatment. Unfortunately, a significant proportion of patients have persistent facial pain after endoscopic sinus surgery (ESS) due to erroneous considerations on aetiology of facial pain by physicians. It should be taken into account that neurological and sinus diseases may share overlapping symptoms, but they frequently co-exist as comorbidities. The aim of this review was to clarify the diagnostic criteria of facial pain in order to improve discrimination between sinogenic and non-sinogenic facial pain and provide some clinical and diagnostic criteria that may help clinicians in addressing differential diagnosis.
Assuntos
Dor Facial/diagnóstico , Dor Facial/etiologia , Rinite/complicações , Sinusite/complicações , HumanosRESUMO
XrpFI, first identified in the extract of Xenopus laevis oocyte nuclei, binds to a proximal sequence of the L14 ribosomal protein gene promoter. Its target sequence, 5'-TAACCGGAAGTTTGT-3', is required to fully activate the promoter, and the two G's of the central motif are essential for factor binding and transcriptional activation; our data also suggest that XrpFI may play a role in cap site positioning. The binding site of XrpFI is homologous to the sequence recognized by the family of ets genes. Antibodies specific for Ets-1 and Ets-2 proteins did not react with XrpFI, but those raised against the rat alpha and beta GA-binding proteins both supershifted the retarded bands formed by XrpFI. The Xenopus polypeptides related to GA-binding protein alpha interact with DNA both as monomers and as heterodimers associated with beta-related proteins. Oocyte nuclei contain multiple forms of alpha- and beta-related proteins: the alpha-like proteins remain throughout development, while the pattern of the beta species changes in the embryonic stages examined. beta-like proteins are undetectable in the cleavage period up to the neurula stage, but at later stages, when ribosomal protein genes are actively transcribed, two beta-related polypeptides reappear.
Assuntos
Proteínas de Ligação a DNA/biossíntese , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/biossíntese , Animais , Sequência de Bases , DNA , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/imunologia , Proteínas de Ligação a DNA/metabolismo , Eletroforese em Gel de Poliacrilamida , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Proteína Proto-Oncogênica c-ets-1 , Proteínas Proto-Oncogênicas c-ets , Proteínas Ribossômicas/genética , Fatores de Transcrição/química , Fatores de Transcrição/imunologia , Transcrição Gênica , Xenopus laevisRESUMO
BACKGROUND: The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. METHODS AND RESULTS: We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for >/=6 months. Procedures lasted 290+/-58 minutes, including 80+/-22 minutes for acquisition of all maps, and 118+/-16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0. 08+/-0.02 mV) inside the circular line and by disparity in activation times (58+/-11 ms) across the lesion. After 9+/-3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (P:=NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. CONCLUSIONS: Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Adulto , Idoso , Ablação por Cateter/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF). METHODS AND RESULTS: We treated 251 consecutive patients with paroxysmal (n=179) or permanent (n=72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (n=124) or AF (n=127) using 3D electroanatomic guidance. Procedures lasted 148+/-26 minutes. Among 980 lesions surrounding individual PVs (n=956) or 2 ipsilateral veins with close openings or common ostium (n=24), 75% were defined as complete by a bipolar electrogram amplitude <0.1 mV inside the lesion and a delay >30 ms across the line. The amount of low-voltage encircled area was 3594+/-449 mm(2), which accounted for 23+/-9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4+/-4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher (P<0.001) in permanent AF patients with recurrence. The proportion of PVs with complete lesions was similar between patients with and without recurrence, but the latter had larger low-voltage encircled areas after radiofrequency (expressed as percent of LA surface area; P<0.001). CONCLUSIONS: Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Estudos de Coortes , Técnicas Eletrofisiológicas Cardíacas , Estudos de Viabilidade , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The minibody is a designed small beta-protein conceived to enable the construction of large libraries of minimal discontinuous epitopes displayed on the surface of filamentous phage. The 61 residue molecule consists of three strands from each of the two beta-sheets of the variable domain of immunoglobulins packed face to face, along with the exposed H1 and H2 hypervariable regions. We have previously shown that from a minibody repertoire of more than 50 million molecules displayed on phage, we were able to select a minibody with micromolar affinity for human interleukin-6 that behaves as a selective cytokine antagonist. The minibody exposes a surface composed of two constrained loops, which provides the possibility of improving IL-6 binding and specificity by swapping the hypervariable regions, followed by further selection. We established experimental conditions for "stringent" selection such as monovalent phage display, competitive selection and epitope masking. Here, we show that by virtue of the optimization/selection process, we have isolated a minibody with improved antagonistic potency and greater specificity. Furthermore, using hIL-6 mutants carrying amino acid substitutions in distinct surface sites it was possible to carefully define the cytokine region that binds the minibody.
Assuntos
Proteínas de Transporte/metabolismo , Imunoglobulinas/metabolismo , Interleucina-6/antagonistas & inibidores , Engenharia de Proteínas/métodos , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Bacteriófagos/genética , Sequência de Bases , Ligação Competitiva , Proteínas de Transporte/química , Proteínas de Transporte/genética , Linhagem Celular , Clonagem Molecular , Humanos , Imunoglobulinas/química , Imunoglobulinas/genética , Interleucina-6/química , Interleucina-6/metabolismo , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , Estrutura Secundária de Proteína , Análise de Sequência de DNARESUMO
AIM: In water polo, throwing is one of the most important and frequently used technical skills for the player. There is no scientific literature that provides information about differences in throwing between elite and sub-elite water polo players. The aim of our study was to study differences in throwing velocities and kinematic variables in elite and sub-elite level male water polo players. METHODS: We considered the variables under standardized conditions during a typical motion, the five-meter shot (penalty). Thirty-four athletes from the Men's First Division Water Polo Championship and forty-two players participating in the National Fourth Division League, took part in the study. Video analysis measures were taken with high-speed digital cameras and the videos were analyzed offline with Dartfish 5.0 Pro. RESULTS: No correlation was found between body mass, height and throwing velocity. Elite players had higher values âfor ball speed (22.8±2.4 m/s for elite team and 18.4±1.7 m/s for sub-elite team; P=0.002) and greater elbow angle (157.5±10.3 degree for elite team versus 146.7±8.9 degree for sub-elite team; P=0.002). In elite team the throwing time was lower (165.6±22.2 and 188.6±23.9 ms, respectively; P=0.05) and the shoulder angle was smaller (115.1±10.3 and 123.8±12.4 degree, respectively; P=0.03) than in sub-elite team. Head height was significantly greater in elite players (elite players 71.1±8.7 cm, sub-elite players 65.6±6.2 cm; P=0.03). CONCLUSION: Differences in kinematic characteristics between elite and sub-elite players were showed. Differences in elbow and shoulder action must be considered both in training and injury prevention.
Assuntos
Desempenho Atlético/fisiologia , Esportes/fisiologia , Adulto , Braço/fisiologia , Fenômenos Biomecânicos , Estatura/fisiologia , Índice de Massa Corporal , Articulação do Cotovelo/fisiologia , Humanos , Masculino , Tempo de Reação , Articulação do Ombro/fisiologia , Tronco/fisiologia , Gravação em Vídeo/métodos , Articulação do Punho/fisiologia , Adulto JovemRESUMO
Several studies have shown the potential of biocompatible lipid nanocapsules as hydrophobic drug delivery systems. Understanding the factors that determine the interactions of these oil-in-water nanoemulsions with cells is a necessary step to guide the design of the most effective formulations. The aim of this study was to probe the ability of two surfactants with a markedly different nature, a non-ionic poloxamer, and a charged phospholipid, to prepare formulations with shells of different composition and different surface properties. Thus we determined their effects on the interaction with biological environments. In particular, we investigated how the shell formulation affected the adsorption of biomolecules from the surrounding biological fluids on the nanocapsule surface (corona formation). A complete physicochemical characterization including an isothermal titration calorimetry (ITC) study revealed that the use of poloxamer led to nanocapsules with a marked reduction in the number of protein-binding sites. Surface hydrophilicity and changes in corona formation strongly correlated to changes in uptake by cancer cells and by macrophages. Our results indicate that the nature and concentration of surfactants in the nanocapsules can be easily manipulated to effectively modulate their surface architecture with the aim of controlling the environmental interactions, thus optimizing functionality for in vivo applications. In particular, addition of surfactants that reduce protein binding can modulate nanoparticle clearance by the immune system, but also screens the desired interactions with cells, leading to lower uptake, thus lower therapeutic efficacy. The two effects need to be balanced in order to obtain successful formulations.
Assuntos
Macrófagos/química , Nanocápsulas/química , Neoplasias Experimentais/tratamento farmacológico , Fosfolipídeos/química , Coroa de Proteína/química , Taxoides/administração & dosagem , Absorção Fisico-Química , Adsorção , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Difusão , Docetaxel , Humanos , Nanocápsulas/ultraestrutura , Neoplasias Experimentais/química , Neoplasias Experimentais/patologia , Tensoativos/química , Taxoides/química , Resultado do TratamentoRESUMO
Successful aging, characterized by little or no loss in physiological functions, should be the usual aging process in centenarians. It is known that well-preserved physiological functions depend on the proper functioning of cell systems. In this article we focus on cell membrane integrity and study the red blood cell membrane to evaluate the effect of physiological aging in centenarians. Fifteen healthy, self-sufficient centenarians, mean age 103 years, were examined by assessing hemocytometric values and some relevant characteristics of the erythrocyte membrane, i.e., the cholesterol/phospholipid molar ratio, the distribution of phospholipid classes and their fatty acid composition, the integral and skeletal protein profiles. The centenarians showed a significant decrease in the red blood cell count (p < 0.0002), hemoglobin (p < 0.0002), and hematocrit (p < 0.0005). The red blood cell membrane showed a significantly increased cholesterol/phospholipid molar ratio (p < 0.01), with a concomitant increase in polyunsaturated fatty acids in phosphatidylcholine (p < 0.001) and, to a lesser extent, in phosphatidylethanolamine. The electrophoretic pattern of membrane proteins was qualitatively normal compared to controls but the densitometric analysis showed a significant increase in the integral protein band 4.2 (p < 0.05) and in the skeletal protein actin (p < 0.001). Extreme longevity seems to be associated with a substantial integrity of the erythrocyte membrane. Moreover, the evident increase in polyunsaturated fatty acids and in actin are likely to improve the membrane fluidity and to strengthen the membrane structure.
Assuntos
Envelhecimento/sangue , Membrana Eritrocítica/química , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Longevidade , Masculino , Lipídeos de Membrana/sangue , Proteínas de Membrana/sangueRESUMO
We report on a 10-year-old boy with generalized deficiency of both NADH-methemoglobin reductase and aspartylglucosaminidase. Although the two enzymatic defects, both autosomal recessive traits, are associated with severe mental retardation, the patient was less retarded than his sister who had only aspartylglucosaminuria.
Assuntos
Amidoidrolases/deficiência , Aspartilglucosaminúria , Citocromo-B(5) Redutase/deficiência , Deficiência Intelectual/genética , Metemoglobinemia/genética , NADH NADPH Oxirredutases/deficiência , Acetilglucosamina/análogos & derivados , Acetilglucosamina/urina , Adulto , Criança , Feminino , Humanos , Deficiência Intelectual/enzimologia , Masculino , Metemoglobinemia/complicações , Metemoglobinemia/enzimologia , LinhagemRESUMO
BACKGROUND: Treatment of maternal tachyarrhythmias in pregnancy is a major clinical issue. Pharmacological treatment raises important concerns regarding partial efficacy and side effects. Radiofrequency ablation of arrhythmogenic substrate has rarely been performed during pregnancy because of the fetal risks related to x-ray exposure and potential fetomaternal procedural complications. CASES: Three women affected by supraventricular tachycardias refractory to pharmacological therapy underwent successful radiofrequency catheter ablation at 29 to 30 weeks' pregnancy. All patients had cesarean delivery of newborns with normal Apgar scores. CONCLUSION: Radiofrequency catheter ablation is an effective treatment of drug refractory maternal supraventricular tachycardias in advanced pregnancy. Further studies are required to establish its long-term fetal safety.
Assuntos
Ablação por Cateter , Complicações Cardiovasculares na Gravidez/cirurgia , Taquicardia Supraventricular/cirurgia , Adulto , Feminino , Humanos , GravidezRESUMO
Platelet monoamine oxidase (MAO) activity was determined in a large population of drug-free and haloperidol-treated schizophrenic patients and healthy controls and, in a second study, in a sample of schizophrenics after a wash-out period and at different times during treatment with haloperidol. Enzyme activity was significantly decreased in both acute and chronic haloperidol-treated schizophrenics, but not in drug-free schizophrenics, compared with normal controls. No significant difference was observed between drug-free schizophrenics with a family history of the illness and those without such history, and between healthy relatives of schizophrenic patients and normal controls without a family history of schizophrenia. MAO activity was significantly reduced after 14 and 21 days of haloperidol treatment, and such reduction did not correlate with response to treatment. These data strongly support the idea that neuroleptic intake may, at least in part, explain low MAO values repeatedly reported in schizophrenics.
Assuntos
Plaquetas/enzimologia , Haloperidol/farmacologia , Monoaminoxidase/metabolismo , Esquizofrenia/enzimologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genéticaRESUMO
A comprehensive assessment of computed tomography (CT) with respect to clinical, historical and neuropsychological variables has been carried out in a sample of DSM III schizophrenics fairly heterogeneous with respect to duration and severity of illness and in a normal control group matched for sex, age and educational level. The mean value of ventricular brain ratio (VBR) was significantly higher in schizophrenics than controls. Seven patients (21.2%) who had VBRs exceeding 2 SD of the control mean showed a significantly longer duration of illness than the other schizophrenics with significantly higher scores on the subscales alogia, effective flattening and attentional impairment of SANS, on the scales self-care and behaviour in crises and emergencies of DAS, on the scales rhythm, tactile, visual, reading, arithmetic, memory and left hemisphere of LNNB, and on the subtests arithmetic, digit span, digit symbol and block design of WAIS. These results confirm earlier reports of an enlargement of lateral cerebral ventricles in a subset of schizophrenics, and its association with a higher degree of cognitive and neuropsychological impairment, social maladjustment and defectual symptomatology. Moreover, they suggest that the neuropathological process likely to underlie the increase of cerebral ventricular size progresses during the course of the illness rather than predating its onset.