RESUMO
Hemodynamic monitoring offers valuable information on cardiovascular performance in the critically ill, and has become a fundamental tool in the diagnostic approach and in the therapy guidance of those patients presenting with tissue hypoperfusion. From introduction of the pulmonary artery catheter to the latest less invasive technologies, hemodynamic monitoring has been surrounded by many questions regarding its usefulness and its ultimate impact on patient prognosis. The Cardiological Intensive Care and CPR Working Group (GTCIC-RCP) of the Spanish Society of Intensive Care and Coronary Units (SEMICYUC) has recently impulsed the development of an updating series in hemodynamic monitoring. Now, a final series of recommendations are presented in order to analyze essential issues in hemodynamics, with the purpose of becoming a useful tool for residents and critical care practitioners involved in the daily management of critically ill patients.
Assuntos
Cuidados Críticos/métodos , Estado Terminal , Hemodinâmica , Monitorização Fisiológica , Pressão Sanguínea , Lesões Encefálicas/fisiopatologia , Cuidados Críticos/normas , Técnicas de Diagnóstico Cardiovascular , Ecocardiografia , Hemorragia/fisiopatologia , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Hipóxia/prevenção & controle , Lactatos/sangue , Oxigênio/sangue , Substitutos do Plasma/uso terapêutico , Ressuscitação , Choque/fisiopatologiaRESUMO
OBJECTIVE: Identify and reach consensus on the variables that affect the measurement of oxygen saturation using pulse oximetry. METHODS: We applied inclusion and exclusion criteria to select relevant studies in databases such as Ebsco and PubMed. The search strategies, carried out until December 2023, focused on publications that addressed the technology of pulse oximeters and variables that influence their accuracy. We assessed the risk of bias of the included studies and used standardized methods for synthesis of results. RESULTS: 23 studies were included. The synthesis of the results highlighted that equipment with tetrapolar technology showed greater precision in oxygen saturation measurements. Increased skin pigmentation, hemoglobinopathies and high skin temperatures can lead to an overestimation of SpO2, while factors such as low perfusion, cold skin temperature, nail polish or tattoos, hypoxemia, anemia and high altitude training, they may underestimate it. On the other hand, motion artifacts, light pollution, frequency >150 beats per minute, electromagnetic interference and location of the sensor can cause distortion of the photoplethymography signal. CONCLUSIONS: The synthesis of the results highlighted that skin pigmentation and light interference can lead to an overestimation of SpO2, while other factors such as low perfusion and altitude tend to underestimate it. The studies presented variability and heterogeneity in their designs, evidencing limitations in the consistency and precision of the evidence. Despite these limitations, the results underscore the importance of considering multiple variables when interpreting pulse oximetry measurements to ensure their reliability. The findings have significant implications for clinical practice and future research.
Assuntos
Oximetria , Oximetria/métodos , Humanos , Saturação de Oxigênio , Reprodutibilidade dos Testes , Pigmentação da PeleRESUMO
This aim of this review is to provide a detailed review of the physiologic conditions and variables of the cardiac output, as well as review the different techniques available for its measurement. We also want to establish the clinical situations in which the measurement of cardiac output can add valuable information for the management of critically ill patients. The Fick technique, used in the beginning to calculate cardiac output, has been replaced today by thermodilution techniques (transcardiac or transpulmonary), lithium dilution, bioreactance, Doppler technique or echocardiography. Pulse wave analysis allows a continuous minimally invasive cardiac output measurement. Other methods, such bioreactance, Doppler technique or echocardiography currently provide a valid, fast and non-invasive measurement of cardiac output.
Assuntos
Débito Cardíaco , Monitorização Fisiológica/métodos , Algoritmos , Débito Cardíaco/fisiologia , Baixo Débito Cardíaco/diagnóstico , Baixo Débito Cardíaco/fisiopatologia , Ecocardiografia/métodos , Ecocardiografia Doppler , Impedância Elétrica , Humanos , Técnicas de Diluição do Indicador , Cloreto de Lítio , Modelos Cardiovasculares , Contração Miocárdica , Oxigênio/sangue , Consumo de Oxigênio , Pulso Arterial , Termodiluição/métodosRESUMO
BACKGROUND AND PURPOSE: Synchronous bilateral breast cancer (SBBC) accounts for 1-3.5% of breast cancer patients. The aim of this study was to evaluate dosimetric issues, clinical outcomes, and acute toxicities for SBBC patients receiving synchronous bilateral hypofractionated radiotherapy (SBHRT) and to compare them with patients treated with synchronous bilateral normofractionated RT schedule (SBNRT). MATERIALS AND METHODS: From April 2016 to March 2020, 39 SBBC patients were referred to our institution. Patients were divided according to their prescription dose: Group A: 50 Gy/25fx (fractions), B: 60-64 Gy/25fx, C: 40.05 Gy/15fx; D: 48 Gy/15fx. Toxicity was evaluated using Common Terminology Criteria for Adverse Events (CTCAE)v.5.0. RESULTS: 34 patients were finally evaluated. Median follow-up was 24 months for NF schedule and 9 months for HF schedule. In the HF schedule, no acute side-effects > G2 were observed and no dermatitis was reported in 6th month´s assessments. 95% of patients have no evidence of disease and only 1 patient presented local relapse in the first mammography after RT. No distant failures or deaths were observed. Regarding dosimetric issues, the inter-patient average Dmean for the heart was: Group A: 5.0 Gy (4.6-5.5), Group B: 4.4 Gy (4.1-5.4), Group C: 4.8 Gy (4.5-5.1) and Group D: 5.3 Gy (4.4-5.6). For the lungs, the inter-patient average Dmean was: Group A: 10.8 Gy (9.8-12.2), Group B: 11.5 Gy (11.3-12), Group C: 9.8 Gy (9.3-10.5) and Group D: 10.5 Gy (10-11.3). CONCLUSIONS: This is the first study reporting the safety, feasibility, and tolerability of 40.05 Gy/15fx over 3 weeks for the treatment of SBBC patients. Further study with larger accrual is mandatory.
Assuntos
Neoplasias da Mama/radioterapia , Neoplasias Primárias Múltiplas/radioterapia , Hipofracionamento da Dose de Radiação , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/cirurgia , Órgãos em Risco/efeitos da radiação , Estudos Prospectivos , Radioterapia de Intensidade Modulada/efeitos adversos , Fatores de TempoRESUMO
Healthcare-related Legionnaires' disease has a devastating impact on high risk patients, with a case fatality rate of 30-50%. Legionella prevention and control in hospitals is therefore crucial. To control Legionella water colonisation in a hospital setting we evaluated the effect of pipeline improvements and temperature increase, analysing 237 samples over a 2-year period (first year: 129, second year: 108). In the first year, 25.58% of samples were positive for Legionella and 16.67% for amoeba. Assessing the distance of the points analysed from the hot water tank, the most distal points presented higher proportion of Legionella colonisation and lower temperatures (nearest points: 6.4% colonised, and temperature 61.4 °C; most distal points: 50% and temperature 59.1 °C). After the first year, the hot water system was repaired and the temperature stabilised. This led to a dramatic reduction in Legionella colonisation, which was negative in all the samples analysed; however, amoeba colonisation remained stable. This study shows the importance of keeping the temperature stable throughout the circuit, at around 60 °C. Special attention should be paid to the most distal points of the circuit; a fall in temperature at these weak points would favour the colonisation and spread of Legionella, because amoeba (the main Legionella reservoir) are not affected by temperature.
Assuntos
Legionella/patogenicidade , Doença dos Legionários/microbiologia , Doença dos Legionários/prevenção & controle , Microbiologia da Água , Amoeba/patogenicidade , Infecção Hospitalar , Hospitais , Humanos , Legionella/crescimento & desenvolvimento , Doença dos Legionários/epidemiologia , Temperatura , Abastecimento de ÁguaRESUMO
BACKGROUND: The measurement of i-PTH circulating is not easy due to its analytical variablity. Variability that appears in the process that goes from the sample collection to the final result determination. There are several important aspects that can influence within the pre-test variability: type of sample (serum o plasma), temperature, time elapses from blood extraction to freezing and from freezing to i-PTH quantification. Blood coming from centres far from our laboratory do not always meet the required processing conditions. Our aim was to study the stability of i-PTH with varying conditions of temperature and time until freezing in patients with chronic kidney disease (CKD). METHODS: We have analyzed 294 blood samples of 49 patients with chronic kidney disease (18 transplantated patients (36.7%) and 31 patients in haemodyalisis (63.3%)). The blood samples were collected using tubes treated with ethylenediaminotetraacetic acid (EDTA); these samples were subjected to different conditions of temperature and time before they were frozen, constituting 6 groups: blood centrifuged and plasma immediately frozen (group A or reference group); blood maintained 1 hour at room temperature and plasma stored at 2-8 masculineC during 0, 8 and 24 hours (groups B,C,D); blood maintained 3 hours at room temperature and plasma stored at 2-8 masculineC during 0 and 8 hours (groups E,F). The intact PTH (i-PTH) was measured using the immunoradiometric assay (IRMA Total Intact Scantibodies assay). We have analyzed the differences between the PTH-i mean values in the referenced groud and the others. We have applied the tests of homogeneity variance and normality and we have perform a comparation by pairs with the t-test including the Bonferroni correction. RESULTS: The mean value of intact-PTH in the referente Group was 202.5+/-199.72 pg/ml. The means values of intact-PTH in the other groups were 196 +/- 203.23 pg/ml, 202.8 +/- 200.2 pg/ml, 200.06 +/- 194.87 pg/ml, 204.08 +/- 204.073 pg/ml, 197.94 +/- 182.31 pg/ml. The results were practically identical for each group. We did not find important differences with respect to the reference group (p = 0.87, p = 0,99, p = 0,95, p = 0,96, p = 0,90 when comparing with groups 2a, 2b, 2c, 3a y 3b). CONCLUSIONS: The use of EDTA maintain the PTH stability during a longer period without the necessity of freezing the samples immediately. These results can help to state strategies to management the samples in patients with ERC.
Assuntos
Hormônio Paratireóideo/sangue , Adulto , Feminino , Testes Hematológicos/métodos , Testes Hematológicos/normas , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We present two cases of strongyloides stercoralis infection in renal transplant recipients in our centre. We describe clinical presentation characteristics, treatment and resolution.
Assuntos
Transplante de Rim/efeitos adversos , Strongyloides stercoralis , Estrongiloidíase/etiologia , Animais , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Transplantation of kidneys from older donors is followed by an increase in delayed graft function (DGF) and acute rejection episodes (ARE). In these circumstances, induction treatment, whether with antithymocyte globulin or with interleukin-2 receptor blockers, may delay the introduction of calcineurin inhibitors (CNI) with effective prevention of ARE. We examined the efficacy and safety of induction treatment with 2 low doses of thymoglobulin compared with 2 doses of basiliximab. A group of 27 patients were treated with thymoglobulin and another 36 with basiliximab. CNI introduction was delayed until day 3 posttransplantation. The thymoglobulin group received 2 doses of 1.25 mg/kg on alternate days and the basiliximab group 2 doses of 20 mg. A trend to a lower incidence of DGF was observed in the thymoglobulin group (33% vs 55.6%; P = .08), with lower levels of serum creatinine on days 7 (P = .02) and 14 (P = .02) posttransplantation. No patient in the thymoglobulin group experienced ARE, but 11 patients (30.6%) in the basiliximab group did (P < .001), and 5 needed rescue treatment with thymoglobulin. We found no differences in the incidence of cytomegalovirus (CMV) disease (P = .945), admission due to infections (P = .274), or neoplasia (P = .340), or differences in graft (P = .69) and patient (P = .21) survivals at 1 and 3 years. Low-dose thymoglobulin was more effective at preventing DGF and ARE in renal transplant recipients of organs from older donors, with no differences in infectious complications or graft and patient survivals.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Basiliximab , Creatinina/sangue , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricosRESUMO
OBJECTIVE: To assess the functional effects of prostatic cryosurgery on micturition. MATERIAL AND METHODS: Prospective study of men who underwent cryosurgery (CS) for prostate cancer between 2013 - 2015. Low urinary tract symptoms (LUTS) and quality of life (QoL) were assessed 1 month before surgery using IPSS questionnaire, a three-day voiding diary (3DVD) and uroflowmetry with ultrasound-measured postvoid residual volume. Need of medical treatment for LUTS was also recorded. The same assessment was performed at 3, 6 and 12 months after CS. Outcomes after surgery were compared to those prior to surgery. RESULTS: Forty-five patients underwent a CS during the study period, of whom 25 patients could be recruited in the study. Mean age was 73.5 years (range 66-84). Nineteen CS (76%) were performed as a primary procedure, while 6 CS (24%) as a salvage procedure. No statistical differences were found comparing results of IPSS, QoL, D3vd or uroflowmetry and PVR at 3, 6 or 12 months after CS compared to before surgery. Before CS, 8 (32%) patients were on medical treatment for LUTS, while at 6 and 12 months after surgery, 3 (13.6%) and 2 (9.5%) patients required some medication, respectively. CONCLUSION: According to the punctuation of IPSS, QoL questionnaire, and a 3-day voiding diary, LUTS does not worsen after CS. Prostatic cryosurgery does not seem to impact uroflowmetry results.
Assuntos
Criocirurgia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Micção , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida , Autorrelato , Resultado do TratamentoRESUMO
Amyotrophic lateral sclerosis is a progressive degenerative neuromuscular disease of insidious onset. It involves upper and lower motor neurons and causes both spastic and atrophic muscular symptoms. More than one fourth of patients have complaints relating to the head and neck (bulbar palsy); thus, the otolaryngologist may be the first physician to see them. In bulbar forms of Amyotrophic Lateral Sclerosis, voice and/or swallowing difficulties are often the initial signs of disturbance. Predominant symptoms are slurred speech, hoarseness, dysphagia, and dyspnea. Muscular weakness, atrophy, and fasciculation are noted on examination. We show a case and revise bibliography.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Transtornos de Deglutição/etiologia , Distúrbios da Voz/etiologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients. METHODS: All patients had a negative complement-dependent cytotoxicity cross-match. The desensitization protocol included five to seven doses of thymoglobulin (1.25 mg/kg) and three sessions of plasmapheresis (PP) within the first week after transplantation, with intravenous immunoglobulin (500 mg/kg) after each PP session and one dose of rituximab on day 8. The presence of donor-specific antibodies (DSA) was analyzed by use of Luminex technology; levels between 1000 and 3000 mean fluorescence intensity were considered for desensitization. RESULTS: The median age was 44 years and median renal replacement therapy time was 9 years. All recipients presented 1 to 3 DSA specificities. There were no severe side effects related to PP, infusion of intravenous immunoglobulin, or rituximab. The median follow-up period was 19.3 months. Median serum creatinine level at last follow-up was 1.7 mg/dL. A kidney biopsy was performed in all patients. Graft and patient survival was 100%. CONCLUSIONS: Until now, few data are available concerning whether HLA-incompatible kidney transplantation after desensitization would benefit patients with ERSD. The desensitization strategy using the combination of PP, low doses of intravenous immunoglobulin, and rituximab at our center resulted in a satisfactory clinical outcome.
Assuntos
Anticorpos/imunologia , Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Transplante de Rim/métodos , Adulto , Anticorpos/análise , Soro Antilinfocitário/administração & dosagem , Esquema de Medicação , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Antígenos HLA/análise , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Imunossupressores/administração & dosagem , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Plasmaferese , Rituximab/administração & dosagemRESUMO
OBJECTIVE: To analyze the relationship between the age--adjusted Charlson Comorbidity Index (aCCI) and pathological outcomes of transurethral resection of de novo bladder tumours (BT). MATERIAL AND METHODS: Data from 208 patients who underwent a transurethral resection (TUR) of a de novo BT between 2007 and 2008 were collected. We recorded the following variables: age, sex, tobacco consumption, comorbidities assessed according to the ICCa (score and mortality rate), disease stage, tumour grade and risk of recurrence and progression. The relationship between the preoperative variables and the final pathological characteristics was analyzed. The multivariate study was conducted with the significant variables (P<.05) from the univariate analysis. RESULTS: The mean age of the patients was 69.5 ± 12 years, and 77% were men. The mean ICCa was 6.4 ± 2.5. The final pathology results showed a Tx, T0, Ta, T1 and T ≥ 2 in 5.3, 6.7, 31.7, 26.9, and 28.8% of the cases, respectively. 33.3% of the tumours were low-grade and 66.7% were high-grade. 14.3% of the tumours were associated with carcinoma in situ. Among those non musculo-invasive bladder tumour (non-MIBT), 34.7% had a low risk of recurrence and progression, 18.1% had an intermediate risk and 47.2% had a high risk. The patients with a ICCa ≥ 5 had an increased number of MIBT (RR: 2.29; 1.1-4.8; P=.032), high-grade tumours (RR: 3.1; CI: 1.6-6; P=.001) and tumours with a high risk of recurrence and progression (RR: 2.9; CI: 1.4-5.9; P<.001). CONCLUSION: The ICCa is related to the pathological characteristics of de novo BT. Patients with greater comorbidity can present more aggressive tumours. The ICCa could therefore be useful in clinical practice for identifying patients with worse prognosis.
Assuntos
Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/patologia , Idoso , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
X-ray diffraction patterns have been recorded from sciatic nerve myelin by means of dynamic X-ray diffraction either from frogs, during the early stages of anesthesia in vivo induced by n-pentane inhalation, and from frog and rat sciatic nerves isolated immediately after the animal was anesthetized. This approach has enabled to resolve minor changes in myelin structure that occur during anesthesia which were found to be similar in frogs and mammals. The X-ray patterns show a reversible slight decrease in intensity of the even reflections during anesthesia. The electron density profiles from myelin of anesthetized and recovered nerves revealed that the unit membrane structure is practically identical in both circumstances. However, during anesthesia myelin membrane pairs move toward the cytoplasmic side becoming more closely packed by 1.6 A. Physiological activity was estimated during the recovery process: compound action potential recovered its maximal amplitude before myelin recovered its native structure. On the contrary, the conduction velocity seemed to be closely related to the structural recovery. This work provides evidence that early stages of anesthesia by n-pentane in vivo does not change membrane bilayer structure but perturbs the surface interactions between adjacent membrane pairs.
Assuntos
Anestesia , Bainha de Mielina/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Técnicas In Vitro , Cinética , Membranas/efeitos dos fármacos , Bainha de Mielina/fisiologia , Pentanos/farmacologia , Rana pipiens , Ratos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Difração de Raios XRESUMO
Changes induced in the structure and electrical activity of myelin were recorded simultaneously from frog sciatic nerves treated with n-alkanes. The results suggest that the effect of n-alkanes seems to be two-fold: (a) there is an initial reversible phase, in which a significant modification of the X-ray diffraction patterns, concomitant with the continuous fall of the action potential, is observed; (b) there is a final phase which is irreversible. This occurs some time after the complete abolition of the electrical activity. At this stage, further changes of the X-ray diffraction patterns are detected, the most significant of them being in the n-pentane-treated myelin, and consist of an increase in the membrane bilayer thickness.
Assuntos
Alcanos/farmacologia , Anestésicos/farmacologia , Bainha de Mielina/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Fenômenos Químicos , Química , Rana pipiens , Difração de Raios XRESUMO
The structural changes induced in the myelin sheath by n-pentane nerve impulse blockage were studied by small-angle X-ray diffraction using a linear position-sensitive detector. The results show that the thickness of the myelin period lattice increases from 170 to 180 A during n-pentane treatment.
Assuntos
Bainha de Mielina/ultraestrutura , Pentanos/farmacologia , Anestésicos , Animais , Anuros , Bainha de Mielina/efeitos dos fármacos , Rana pipiens , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/ultraestrutura , Difração de Raios XRESUMO
The phases of simple systems involving one type of protein (lysozyme or cytochrome c) and one type of lipid (phosphatidic acid) have been characterized by X-ray crystallography, chemical analysis and spin-labeling technique as a function of temperature. They are of the lamellar type with alternative protein monolayers and lipid bilayers. According to the pH, two types of lamellar phases are obtained, one where the lipid-protein interactions are mainly hydrophobic, the other where they are electrostatic. In both cases, a phase transition occurs as temperature is lowered, between a high temperature phase, where all the lipids are in the liquid-like state, and another phase where some lipid chains are rigid. In the case of the phases with electrostatic interaction, it is shown that the onset of the order-disorder transition is shifted towards low temperature as compared with the homologous lipid-water phase and that the protein content of the phase decreases as the ratio of the liquid to rigid hydrocarbon chains decreases. This leads us to suggest that in the systems studied in this work the proteins interact only with lipid in the liquid-like state. In the case of the phases with hydrophobic interaction, it is shown that the extent of hydrophobic interaction between protein and lipid increases as the unsaturation of the hydrocarbon chains increases. The onset of the order-disorder transition shows a greater shift towards low temperature than the one observed in the case of the phase with electrostatic interaction.
Assuntos
Grupo dos Citocromos c , Muramidase , Ácidos Fosfatídicos , Espectroscopia de Ressonância de Spin Eletrônica , Ácidos Graxos , Cinética , Membranas Artificiais , Modelos Biológicos , Conformação Molecular , Conformação Proteica , Relação Estrutura-Atividade , Difração de Raios XRESUMO
The structural stability of human plasma low-density lipoproteins (LDL) has been studied kinetically by means of dynamic X-ray scattering techniques. At 37 degrees C, rapid deterioration of the lipoproteins present in the insoluble complex which is formed on mixing solutions of LDL and human arterial proteoglycans is observed. This is evidenced by the progressive blurring of the X-ray scattering spectra. At 4 degrees C the X-ray patterns from the insoluble complex show a single reflection centered at 34 A-1, which is characteristic of pure cholesteryl esters organized in a smectic phase. This behaviour contrasted with the high stability exhibited by free LDL at 37 degrees C. Our results show that, in the form of insoluble complex, the lipoprotein molecules are rapidly disrupted and that the neutral lipids segregated with formation of a lipid phase. This suggests that LDL particles become destabilized by their interaction with arterial proteoglycans.
Assuntos
Aorta Torácica/metabolismo , Lipoproteínas LDL/sangue , Proteoglicanas/metabolismo , Colesterol/análise , Ésteres do Colesterol/análise , Estabilidade de Medicamentos , Humanos , Cinética , Fosfolipídeos/análise , Conformação Proteica , Espalhamento de Radiação , Triglicerídeos/análise , Raios XRESUMO
An algorithm is developed for the analysis of the X-ray scattering spectra of lamellar systems, by reference to a precise physical model. The model consists of identical planar lamellae (the motif), all parallel and stacked in a one-dimensional crystal with four types of defect: stacking disorder, finite size of the crystallites, and presence of diffuse and blank scattering. In addition, the spectra are distorted by collimation aberrations. In order to evaluate the effects of these distortions, the following assumptions are made: (1) beyond some point Slimit the intensity curve can be expressed as a function of a (small) number of parameters; (2) the blank scattering, restricted to very small angles, can be identified and eliminated; and (3) the diffuse scattering is entirely defined by the values of idiff(h/D) at the lattice Sh = h/D (h is a positive integer less than or equal to DSlimit). These assumptions lead to an expression of the whole of the intensity curve as a function of a finite number of parameters: the average D and the variance sigma 2D of the repeat distance, the average number [N] of lamellae per crystallite, the set [idiff(h/D)] and the set [imotif(k/2D)] (where k is a positive integer), which defines the structure of the motif. An algorithm is proposed to determine the value of the various parameters. The derivation of the algorithm involves several operations: construction in real space of periodic functions whose motifs are step-sections of the autocorrelation function; expression in reciprocal space, and in terms of the experimental scattering curves, of the Fourier transform of those periodic functions; analysis of the properties of the two functions. The algorithm is tested using a variety of simulated scattering curves whose parameters [imotif(k/2D)], [idiff(2/D)], D, sigma D, [N] (and collimation distortions) are within the range commonly encountered in experimental conditions. The results show that the values of the parameters retrieved by the algorithms are very close to those used in the simulation. The calculations are fast and easy to implement on a computer. The main virtues of the algorithm are (1) to determine the values of all the parameters at once, eliminating most of the intermediate (and questionable) manipulations (separation of signal from noise, discrimination of overlapping reflections, integration of the intensities) and (2) to yield the continuous intensity curve of a single motif.
Assuntos
Modelos Biológicos , Bainha de Mielina , Algoritmos , Espalhamento de Radiação , Raios XRESUMO
X-ray scattering and electrophysiological experiments performed on toad sciatic nerves as a function of the exposure to either low temperature or tetracaine yielded the following results: (i) the main structural effect is to thicken the individual membranes, thus to stiffen the acyl chains and increase the repeat distance of the one-dimensional lattice, phenomena that are typical of lipid-containing systems with disordered chains; (ii) the electrophysiological effect is to decrease the amplitude and velocity of the compound action potential; (iii) the structural and physiological effects of the two agents are practically identical. Since the structural and the electrophysiological parameters have different origins in the nerves (the structure regards the myelin sheath, the electrical signals originate at the nodes of Ranvier) it is inferred that tetracaine and low temperature exert similar effects on the membranes of both the myelin sheath and the nodes of Ranvier. Also, since local anesthetics act by inhibiting the Na+ channels, these observations suggest that the acyl chain conformation modulates the channel function and thus the generation of action potential.
Assuntos
Anestésicos Locais/farmacologia , Metabolismo dos Lipídeos , Fibras Nervosas Mielinizadas/fisiologia , Nervo Isquiático/fisiologia , Tetracaína/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Bufo marinus , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Elétrons , Eletrofisiologia , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/metabolismo , Nervo Óptico/citologia , Nervo Óptico/fisiologia , Nós Neurofibrosos/efeitos dos fármacos , Nós Neurofibrosos/metabolismo , Ratos , Nervo Isquiático/citologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Bloqueadores dos Canais de Sódio , Canais de Sódio/fisiologia , Temperatura , Fatores de Tempo , Difração de Raios XRESUMO
The algorithm described in the accompanying paper was applied to X-ray scattering experiments performed with rat sciatic nerves, either as a function of the age of the animal (4 to 30 days), or with adult nerves swollen in non-isotonic media. The results were all consistent with the model of disorder used in the theoretical treatment. The algorithm leads, in one step, from the data to the numerical values of the parameters, avoiding all intermediate manipulation. For each experiment a variety of parameters was determined: the average D and the variance sigma 2D of the repeat distance, the average number [N] of motifs per crystallite, the set [idiff(h/D)], which defines the diffuse scattering, the fraction alphaloose of myelin that does not belong to the compact sheaths, and the set [imotif (k/2D)], which suffices to define the continuous intensity curve of the motif imotif(s). Note the remarkable wealth of information, especially by contrast with conventional analyses which, as a rule, only yield the values of D and of the set [imotif(h/D)] (insufficient to determine the function imotif(s]. The function imotif(s) and the parameters D and sigma D (and thus the local structure of the myelin sheaths) were shown to be almost invariant in the course of myelinogenesis; what varies is mainly the total amount of myelin in the nerve and the number of membranes per sheath. Swelling agents have a dramatic influence on the X-ray scattering spectra, but in spite of the conspicuous variation of D, sigma D and [N] the structure of the motif is invariant. The structure of the motif was shown to be quite different in the native and in the swollen samples; the stacking disorder appears to involve mainly the cytoplasmic space in native myelin, the external space in swollen nerves. The very notion of electron density profile, when disorder is present, is discussed. Two criteria were proposed to select the "best" signs of the reflections: two sets came out at almost the same rank, one corresponding to Caspar & Kirschner's the other to Worthington & McIntosh's proposals, neither of which can be ruled out according to the criteria used in this work.