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1.
J Anim Physiol Anim Nutr (Berl) ; 101(6): 1324-1330, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28299839

RESUMO

In the present investigation, the impact of diet composition on urine pH in rabbits was compared with previous studies on rabbits, cats, dogs, pigs and horses. A total of 13 dwarf rabbits were fed six different diets with a cation-anion balance (CAB) between -39 and +320 mmol/kg dry matter (DM) using ammonium chloride (NH4 Cl) as an acidifier. CAB was calculated as follows: CAB (mmol/kg DM) = 49.9*Ca + 82.3*Mg +43.5*Na + 25.6*K - 59*P - 62.4*S - 28.2*Cl; minerals in g/kg DM. Urine, faeces and blood were collected. Urine pH ranged from 5.26 ± 0.22 at a CAB of -39 mmol/kg DM to 8.56 ± 0.24 at a CAB of +320 mmol/kg DM. A low CAB in the feed reduced blood pH and blood base excess significantly. Renal excretion of Ca, P, Na and Mg and water was significantly higher in rabbits eating acidifying diets. In comparison with other species, rabbits reacted to acidifying diets in a similar way as cats, dogs and pigs. Rabbits on a mildly alkalizing diet, however, had a trend to higher urine pH than other monogastric species on such diets (cats, dogs, pigs, horses).


Assuntos
Ração Animal/análise , Dieta/veterinária , Coelhos/urina , Urina/química , Fenômenos Fisiológicos da Nutrição Animal , Animais , Concentração de Íons de Hidrogênio , Especificidade da Espécie
2.
Arch. latinoam. nutr ; 63(2): 126-133, June 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-740232

RESUMO

Most childhood obesity research has classified participants by normative standards for Body Mass Index (BMI) through population percentiles or values corresponding to overweight adults (World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and the International Obesity Task Force (IOTF)). In 2006, criterion-referenced standards (FitnessGram®) were developed (revised in 2010) which directly associate BMI values with adverse health outcomes. This study assessed agreement between normative and criterion-referenced standards. Participants included 653 Mexican American 3rd to 5th graders living in the U.S.-Mexico border area who participated in a health promotion project. At baseline, agreement was compared between normative and criterion-referenced classifications. At follow-up, agreement between classifications on changes (e.g. from overweight to healthy weight) was assessed. According to FitnessGram® standards, 53.0% of participants were overweight or obese at baseline. Compared to FitnessGram®, the IOTF and CDC standards classified 15% fewer participants as obese/high risk. The WHO standards were closely related to FitnessGram® (kappa=.925) and showed significantly greater agreement with FitnessGram® than the CDC (kappa=.925 versus 0.722, p<.001) and IOTF standards (kappa=.925 versus .682, p<.001). Compared to the FitnessGram® (8.9%), the WHO and CDC (8.6%) were similar, but IOTF standards lower (6.5%) in how many children improved following the health program. Despite acceptable agreement between the different indices, several normative classifications may underestimate the proportion of children who are at risk for BMI-related adverse health consequences.


Muchos de los estudios sobre la obesidad infantil clasifican a los participantes por índices normativas para el índice de masa corporal (IMC) usando valores de percentil de población o valores correspondientes a adultos con sobrepeso (Organización Mundial de la Salud (WHO), Centros para el Control y Prevención de Enfermedades (CDC) y la Comisión International Sobre la Obesidad (OITF)). En 2006, índices con referencias a criterios (Fitness-Gram®) fueron creados asociando valores de IMC directamente a valores de impacto de salud adversos. Este estudio determino las equivalencias de los índices normativos y los con referencias a criterios. Los participantes incluyeron estudiantes (N=653), niveles 3°-5, viviendo en la frontera EEUU-México. Al inicio, se comparó la equivalencia entre el IMC basado en las clasificaciones normativas y los con referencias a criterios. La equivalencia entre las clasificaciones de los cambios fue evaluada. Según las normas Fitness-Gram®, 53.0% tenían sobrepeso o eran obesos aunque las normas OITF y CDC indicaron menos de 15% fueron clasificados con obesidad/alto riesgo. Las normas WHO fueron más cercanamente relacionadas con las de FitnessGram® (kappa=.925) y mostraron significativamente mayor equivalencia con las de FitnessGram® que a las del CDC (kappa= .925 V .722, p<.001) e IOTF (kappa=.925 V .669, p<.001). Los índices FitnessGram® (8.9%), WHO y CDC (8.6%) fueron similares en cuanto el número de niños que mejoraron siguiendo el programa, pero el índice IOTF fue menor (6.3%). Aunque había un acuerdo aceptable entre los índices diferentes, varios pueden subestimar la proporción a riesgo y las consecuencias adversas relacionadas al IMC.


Assuntos
Criança , Feminino , Humanos , Masculino , Americanos Mexicanos/estatística & dados numéricos , Obesidade/epidemiologia , Índice de Massa Corporal , Estudos Transversais , Valores de Referência
3.
Arch Latinoam Nutr ; 63(2): 126-33, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24934068

RESUMO

Most childhood obesity research has classified participants by normative standards for Body Mass Index (BMI) through population percentiles or values corresponding to overweight adults (World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and the International Obesity Task Force (IOTF)). In 2006, criterion-referenced standards (FitnessGram) were developed (revised in 2010) which directly associate BMI values with adverse health outcomes. This study assessed agreement between normative and criterion-referenced standards. Participants included 653 Mexican American 3rd to 5th graders living in the U.S.-Mexico border area who participated in a health promotion project. At baseline, agreement was compared between normative and criterion-referenced classifications. At follow-up, agreement between classifications on changes (e.g., from overweight to healthy weight) was assessed. According to FitnessGram standards, 53.0% of participants were overweight or obese at baseline. Compared to FitnessGram, the IOTF and CDC standards classified 15% fewer participants as obese/high risk. The WHO standards were closely related to FitnessGram (kappa=.925) and showed significantly greater agreement with FitnessGram than the CDC (kappa=.925 versus 0.722, p < .001) and IOTF standards (kappa=.925 versus .682, p < .001). Compared to the FitnessGram (8.9%), the WHO and CDC (8.6%) were similar, but IOTF standards lower (6.5%) in how many children improved following the health program. Despite acceptable agreement between the different indices, several normative classifications may underestimate the proportion of children who are at risk for BMI-related adverse health consequences.


Assuntos
Americanos Mexicanos/estatística & dados numéricos , Obesidade/epidemiologia , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Valores de Referência
4.
Neth Heart J ; 18(2): 61-5, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20200610

RESUMO

Background/Objectives. Therapy for Hodgkin's lymphoma is disease specific and cannot be compared with treatment for other diseases. It often includes more extensive radiotherapy on the mediastinum than for other malignancies. Cardiac morbidity is known to occur in patients previously irradiated. This study describes the postoperative course after cardiac surgery of patients previously irradiated for Hodgkin's lymphoma.Methods. From January 1990 until June 2008, 12 patients underwent cardiac surgery in the University Medical Center Utrecht after previous irradiation for Hodgkin's lymphoma. Data on radiotherapy, surgery and follow-up were collected retrospectively. The postoperative functional status was assessed by a telephone questionnaire.Results. Atrial fibrillation (33%) and pleural effusion (25%) were the most common postoperative complications. After a mean followup of 2.6+/-2.9 years four patients had died. The remaining patients were all in a favourable New York Heart Association and Canadian Cardiothoracic Society class. The estimated one-, two- and four-year survival rates were 83, 69 and 46% respectively.Conclusion. The early postoperative outcome of cardiac surgery in this population is reasonably good. The long-term results may prove to be disappointing, but the cohort is small. (Neth Heart J 2010;18:61-5.).

5.
IEEE Trans Biomed Circuits Syst ; 4(6): 372-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23850754

RESUMO

We report on a compact (0.02 mm(2) ) buffer for both voltage and current stimulation of electrogenic cells on a complementary metal-oxide semiconductor microelectrode array. In voltage mode, the circuit is a high-current class-AB voltage follower, based on a local common-mode feedback (LCMFB) amplifier. In current mode, the circuit is a current conveyor of type II, using the same LCMFB amplifier with cascode stages to increase the gain. The circuit shows good linearity in the 0.5-3.5 V input range and has extensively been used for stimulation of neuronal cultures.

6.
Biosens Bioelectron ; 24(7): 2191-8, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19157842

RESUMO

There is an enduring quest for technologies that provide - temporally and spatially - highly resolved information on electric neuronal or cardiac activity in functional tissues or cell cultures. Here, we present a planar high-density, low-noise microelectrode system realized in microelectronics technology that features 11,011 microelectrodes (3,150 electrodes per mm(2)), 126 of which can be arbitrarily selected and can, via a reconfigurable routing scheme, be connected to on-chip recording and stimulation circuits. This device enables long-term extracellular electrical-activity recordings at subcellular spatial resolution and microsecond temporal resolution to capture the entire dynamics of the cellular electrical signals. To illustrate the device performance, extracellular potentials of Purkinje cells (PCs) in acute slices of the cerebellum have been analyzed. A detailed and comprehensive picture of the distribution and dynamics of action potentials (APs) in the somatic and dendritic regions of a single cell was obtained from the recordings by applying spike sorting and spike-triggered averaging methods to the collected data. An analysis of the measured local current densities revealed a reproducible sink/source pattern within a single cell during an AP. The experimental data substantiated compartmental models and can be used to extend those models to better understand extracellular single-cell potential patterns and their contributions to the population activity. The presented devices can be conveniently applied to a broad variety of biological preparations, i.e., neural or cardiac tissues, slices, or cell cultures can be grown or placed directly atop of the chips for fundamental mechanistic or pharmacological studies.


Assuntos
Potenciais de Ação/fisiologia , Cerebelo/citologia , Cerebelo/fisiologia , Estimulação Elétrica/métodos , Sistemas Microeletromecânicos/instrumentação , Microeletrodos , Rede Nervosa/fisiologia , Animais , Células Cultivadas , Humanos , Ratos , Ratos Long-Evans
7.
Artigo em Inglês | MEDLINE | ID: mdl-18001915

RESUMO

Recordings have been performed with a CMOS-based microelectrode array (MEA) featuring 11'016 metal electrodes and 126 channels, each of which comprises recording and stimulation electronics for extracellular, bidirectional communication with electrogenic cells. The important features of the device include (i) high spatial resolution at (sub) cellular level with 3'200 electrodes per mm(2) (diameter 7 microm, pitch 18 microm), (ii) a reconfigurable routing of the electrodes to the 126 channels, and (iii) low noise levels. Recordings from neonatal rat cardiomyocytes forming confluent layers and microtissues are shown. Moreover, signals from dissociated rat hippocampal neurons and from neurons in an acute cerebellar slice preparation are presented.


Assuntos
Dispositivos Lab-On-A-Chip , Miócitos Cardíacos/fisiologia , Neurônios/fisiologia , Animais , Galinhas , Eletrodos , Processamento de Imagem Assistida por Computador/instrumentação , Processamento de Imagem Assistida por Computador/métodos , Procedimentos Analíticos em Microchip/métodos , Microeletrodos , Ratos , Ratos Long-Evans
8.
Artigo em Inglês | MEDLINE | ID: mdl-18003402

RESUMO

A monolithic microsystem in CMOS (complementary metal oxide semiconductor) technology is presented that provides bidirectional communication (stimulation and recording) between standard microelectronics and cultured electrogenic cells. The 128-electrode chip can be directly used as a substrate for cell culturing. It features circuitry units for stimulation and immediate cell signal treatment near each electrode. In addition, it provides on-chip A/D conversion as well as a digital interface so that a fast interaction is possible at good signal quality. Spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the behavior and development of neural networks in vitro, to reveal the effects of neuronal plasticity and to study network activity in response to pharmacological treatments.


Assuntos
Potenciais de Ação/fisiologia , Técnicas de Cultura de Células/instrumentação , Estimulação Elétrica/instrumentação , Eletrônica/instrumentação , Microeletrodos , Neurônios/fisiologia , Processamento de Sinais Assistido por Computador/instrumentação , Amplificadores Eletrônicos , Conversão Análogo-Digital , Animais , Biotecnologia/instrumentação , Comunicação Celular/fisiologia , Técnicas de Cultura de Células/métodos , Células Cultivadas , Estimulação Elétrica/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização , Miócitos Cardíacos/fisiologia , Ratos
9.
J Neurosci Methods ; 164(1): 93-106, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17540452

RESUMO

We report on the system integration of a CMOS chip that is capable of bidirectionally communicating (stimulation and recording) with electrogenic cells such as neurons or cardiomyocytes and that is targeted at investigating electrical signal propagation within cellular networks in vitro. The overall system consists of three major subunits: first, the core component is a 6.5 mm x 6.5 mm CMOS chip, on top of which the cells are cultured. It features 128 bidirectional electrodes, each equipped with dedicated analog filters and amplification stages and a stimulation buffer. The electrodes are sampled at 20 kHz with 8-bit resolution. The measured input-referred circuitry noise is 5.9 microV root mean square (10 Hz to 100 kHz), which allows to reliably detect the cell signals ranging from 1 mVpp down to 40 microVpp. Additionally, temperature sensors, a digital-to-analog converter for stimulation, and a digital interface for data transmission are integrated. Second, there is a reconfigurable logic device, which provides chip control, event detection, data buffering and an USB interface, capable of processing the 2.56 million samples per second. The third element includes software that is running on a standard PC performing data capturing, processing, and visualization. Experiments involving the stimulation of neurons with two different spatio-temporal patterns and the recording of the triggered spiking activity have been carried out. The response patterns have been successfully classified (83% correct) with respect to the different stimulation patterns. The advantages over current microelectrode arrays, as has been demonstrated in the experiments, include the capability to stimulate (voltage stimulation, 8 bit, 60 kHz) spatio-temporal patterns on arbitrary sets of electrodes and the fast stimulation reset mechanism that allows to record neuronal signals on a stimulating electrode 5 ms after stimulation (instantaneously on all other electrodes). Other advantages of the overall system include the small number of needed electrical connections due to the digital interface and the short latency time that allows to initiate a stimulation less than 2 ms after the detection of an action potential in closed-loop configurations.


Assuntos
Eletrônica Médica/instrumentação , Eletrofisiologia/instrumentação , Rede Nervosa/fisiologia , Neurônios/fisiologia , Neurofisiologia/instrumentação , Potenciais de Ação/fisiologia , Animais , Animais Recém-Nascidos , Técnicas de Cultura de Células/métodos , Células Cultivadas , Eletrônica Médica/métodos , Eletrofisiologia/métodos , Microeletrodos/normas , Microeletrodos/tendências , Rede Nervosa/citologia , Neurônios/citologia , Neurofisiologia/métodos , Ratos , Ratos Sprague-Dawley , Tempo de Reação/fisiologia , Processamento de Sinais Assistido por Computador/instrumentação , Software
10.
Biosens Bioelectron ; 22(11): 2546-53, 2007 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-17097869

RESUMO

A high degree of connectivity and the coordinated electrical activity of neural cells or networks are believed to be the reason that the brain is capable of highly sophisticated information processing. Likewise, the effectiveness of an animal heart largely depends on such coordinated cell activity. To advance our understanding of these complex biological systems, high spatiotemporal-resolution techniques to monitor the cell electrical activity and an ideally seamless interaction between cells and recording devices are desired. Here we present a monolithic microsystem in complementary metal oxide semiconductor (CMOS) technology that provides bidirectional communication (stimulation and recording) between standard electronics technology and cultured electrogenic cells. The microchip can be directly used as a substrate for cell culturing, it features circuitry units per electrode for stimulation and immediate cell signal treatment, and it provides on-chip signal transformation as well as a digital interface so that a very fast, almost real-time interaction (2 ms loop time from event recognition to, e.g., a defined stimulation) is possible at remarkable signal quality. The corresponding spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the development of neural networks, reveal the effects of neuronal plasticity and study cellular or network activity in response to pharmacological treatments.


Assuntos
Potenciais de Ação/fisiologia , Amplificadores Eletrônicos , Estimulação Elétrica/instrumentação , Microeletrodos , Miócitos Cardíacos/fisiologia , Neurônios/fisiologia , Técnicas de Patch-Clamp/instrumentação , Animais , Células Cultivadas , Galinhas , Estimulação Elétrica/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização , Ratos , Transistores Eletrônicos
11.
Biosens Bioelectron ; 22(7): 1426-33, 2007 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-17055243

RESUMO

A strategy for patterned cell adhesion based on chemical surface modification is presented. To confine cell adhesion to specific locations, an engineered surface for high-contrast protein adsorption and, hence, cell attachment has been developed. Surface functionalization is based on selective molecular-assembly patterning (SMAP). An amine-terminated self-assembled monolayer is used to define areas of cell adhesion. A protein-repellent grafted copolymer, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG), is used to render the surrounding silicon dioxide resistant to protein adsorption. X-ray photoelectron spectroscopy, scanning ellipsometry and fluorescence microscopy techniques were used to monitor the individual steps of the patterning process. Successful guided growth using these layers is demonstrated with primary neonatal rat cardiomyocytes, up to 4 days in vitro, and with the HL-1 cardiomyocyte cell line, up to 7 days in vitro. The advantage of the presented method is that high-resolution engineered surfaces can be realized using a simple, cost-effective, dip-and-rinse process. The technique has been developed for application on a CMOS cell-based biosensor, which comprises an array of microelectrodes to extracellularly record electrical activity from cardiomyocytes.


Assuntos
Técnicas Biossensoriais/instrumentação , Animais , Animais Recém-Nascidos , Adesão Celular , Linhagem Celular , Células Cultivadas , Metais , Óxidos , Polietilenoglicóis , Polilisina/análogos & derivados , Ratos , Semicondutores
12.
Biosens Bioelectron ; 20(2): 358-66, 2004 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-15308242

RESUMO

Signal degradation and an array size dictated by the number of available interconnects are the two main limitations inherent to standalone microelectrode arrays (MEAs). A new biochip consisting of an array of microelectrodes with fully-integrated analog and digital circuitry realized in an industrial CMOS process addresses these issues. The device is capable of on-chip signal filtering for improved signal-to-noise ratio (SNR), on-chip analog and digital conversion, and multiplexing, thereby facilitating simultaneous stimulation and recording of electrogenic cell activity. The designed electrode pitch of 250 microm significantly limits the space available for circuitry: a repeated unit of circuitry associated with each electrode comprises a stimulation buffer and a bandpass filter for readout. The bandpass filter has corner frequencies of 100 Hz and 50 kHz, and a gain of 1000. Stimulation voltages are generated from an 8-bit digital signal and converted to an analog signal at a frequency of 120 kHz. Functionality of the read-out circuitry is demonstrated by the measurement of cardiomyocyte activity. The microelectrode is realized in a shifted design for flexibility and biocompatibility. Several microelectrode materials (platinum, platinum black and titanium nitride) have been electrically characterized. An equivalent circuit model, where each parameter represents a macroscopic physical quantity contributing to the interface impedance, has been successfully fitted to experimental results.


Assuntos
Potenciais de Ação/fisiologia , Amplificadores Eletrônicos , Técnicas de Cultura de Células/instrumentação , Estimulação Elétrica/instrumentação , Eletrofisiologia/instrumentação , Microeletrodos , Miócitos Cardíacos/fisiologia , Animais , Técnicas de Cultura de Células/métodos , Embrião de Galinha , Galinhas , Estimulação Elétrica/métodos , Eletrofisiologia/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização , Transistores Eletrônicos
13.
Br J Clin Pharmacol ; 58(3): 329-31, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15327594

RESUMO

Few published human data are available concerning the acute toxicity of the new antiepileptic drug oxcarbazepine of which the metabolite 10- monohydroxy derivate (MHD) is the pharmacologically effective compound. Two hours after a documented overdosage of more than 100 tablets oxcarbazepine, the serum level of the parent compound was 10-fold higher than the therapeutic dosage (31.6 mg l(-1)). However, the concentration of MHD, which peaked 7 h after intake, was only twofold higher (59.0 mg l(-1)). No life-threatening situations occurred and the patient fully recovered. The fact that oxcarbazepine is a prodrug and that the formation of the active MHD metabolite is a rate-limiting process may contribute to the relative low toxicity of the drug in overdose.


Assuntos
Anticonvulsivantes/intoxicação , Carbamazepina/análogos & derivados , Carbamazepina/intoxicação , Epilepsia/tratamento farmacológico , Adulto , Overdose de Drogas , Humanos , Masculino , Oxcarbazepina
14.
Am J Kidney Dis ; 30(4): 466-74, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9328359

RESUMO

The influence of hypervolemia on hemodynamics and interdialytic blood pressure, as well as in relation to vascular compliance, was investigated in 10 hemodialysis patients who were not receiving vasoactive medication. All subjects were studied during a relative normovolemic interdialytic period (from 1 kg below dry weight postdialytic until dry weight predialytic) and a hypervolemic interdialytic period (from 1 kg above dry weight postdialytic until 3 kg above dry weight predialytic). Interdialytic blood pressure was measured with an ambulatory blood pressure monitor. Cardiac output was echographically measured and total peripheral resistance calculated postdialytic, mid-interdialytic, and predialytic. At the same time, a blood sample was drawn for analyzing vasoactive hormones, sodium, and hematocrit. In all patients, ideal dry weight was estimated by echography of the caval vein. Arterial and venous compliance were measured with an ultrasound vessel wall movement detector system and a strain-gauge plethysmograph. After fluid load, an increase in intravascular volume, an increase in caval vein diameter and cardiac output, and a decrease in peripheral resistance was observed. No significant influence of a 3-L fluid load was found on interdialytic blood pressure course (153+/-24 mm Hg/90+/-19 mm Hg in the hypervolemic period and 146+/-27 mm Hg/89+/-22 mm Hg in the normovolemic period). Sodium and osmolality were similar in the hypervolemic and normovolemic interdialytic periods. After fluid load, a decrease in arginine vasopressin and angiotensin II was observed, which probably contributed to the decreased systemic vascular resistance. Catecholamines were not influenced by fluid load, but increased during the interdialytic period, suggesting accumulation after dialysis. Three of the 10 patients had higher systolic but not diastolic blood pressures after fluid load (159+/-13 mm Hg/81+/-22 mm Hg in the hypervolemic period and 135+/-16 mm Hg/81+/-22 mm Hg in the normovolemic period). No correlation could be found between arterial or venous compliance and blood pressure changes. We concluded that a 3-L interdialytic fluid load does not result in higher blood pressure in most hemodialysis patients.


Assuntos
Volume Sanguíneo/fisiologia , Hemodinâmica/fisiologia , Hipertensão Renal/fisiopatologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Diálise Renal , Pressão Sanguínea/fisiologia , Peso Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/fisiopatologia
16.
Kidney Int ; 51(5): 1596-601, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9150478

RESUMO

Thin glomerular basement membrane (GBM) nephropathy, also called familial benign hematuria, is characterized by chronic hematuria and uniform thinning of the lamina densa of the glomerular basement membrane. It generally holds an excellent renal prognosis. Alport syndrome in early stages can also show attenuation of the GBM; conversely, renal insufficiency has been reported in familial benign hematuria. To discern early Alport syndrome from thin GBM nephropathy, we carried out a prospective epidemiological study in which 19 normotensive and non-azotemic adult patients with chronic microscopic (18 of 19) and macroscopic (1 of 19) hematuria and biopsy-proven thin GBM nephropathy were followed for a median of 12 years (range 9 to 15 years). Renal biopsies of thin GBM patients at entry showed an increased incidence of focal global glomerulosclerosis when compared to disease controls as IgA nephropathy (P = 0.047) and normal renal tissue (P = 0.0075). All renal biopsies showed the presence of the Goodpasture antigen when tested immunohistochemically. Presence of Alport syndrome was excluded clinically as none of the patients had complaints of hearing loss or abnormalities by audiography and ophthalmology. At the end of follow-up, the incidence of hypertension in thin GBM nephropathy (35%) exceeded that of healthy clinical controls (P = 0.048), and one hypertensive patient developed mild renal failure. In the normotensive patients, the glomerular filtration rate at follow-up as measured by inulin clearance was reduced in three out of seven; these were over 50 years of age. Although no family members were known to have renal disease at inclusion, within four families six elderly first degree relatives had developed unexplained renal insufficiency at the end of follow-up. Thus, thin GBM nephropathy predisposes to premature glomerular obsolescence, leading in time to increased incidences of hypertension and late onset renal insufficiency.


Assuntos
Hematúria/genética , Hipertensão/etiologia , Glomérulos Renais/patologia , Insuficiência Renal/etiologia , Adolescente , Adulto , Idoso , Membrana Basal , Feminino , Seguimentos , Hematúria/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Hereditária/complicações , Estudos Prospectivos
17.
Phytomedicine ; 4(2): 109-15, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23195397

RESUMO

The antiarrhythmic action of 6-benzoylheteratisine (6-bh), a C(19) diterpenoid alkaloid from Aconitum tanguticum (Maxim.) Stapf was investigated in left and right guinea pig isolated atria. Furthermore, possible effects on transmembrane action potential of isolated papillary muscles were studied using microelectrode techniques. At concentrations of more than 6 × 10(-8) mol/1, preincubation with 6-bh suppressed arrhythmias induced by aconitine, veratridine and ouabain. Bradycardia of the right atria as a sign of toxicity occurred at 1 × 10(-6) mol/1. The alkaloid significantly reduced the maximum rate of rise of the action potential as well as the action potential amplitude, indicating inhibition of voltage-dependent sodium channels as a functional principle. Additionally, a use-dependent mode of drug-action could be demonstrated. We conclude therefore, that 6-bh is a naturally occurring class-I antiarrhythmic substance. The compound is a main alkaloid of Aconitum tanguticum, a plant used to prepare a poison antidote in Chinese and Tibetan folk medicine. It may be speculated that the poison antidote effect is at least partially based on the antiarrhythmic properties of 6-bh.

19.
Nephrol Dial Transplant ; 11(2): 323-8, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8671787

RESUMO

BACKGROUND: It is well known that vascular reactivity is impaired during combined ultrafiltration-haemodialysis as compared to isolated ultrafiltration and haemofiltration, which might be related to differences in plasma osmolality. Therefore vascular reactivity was studied during combined ultrafiltration-haemodialysis in relation to sodium-related differences in plasma osmolality/tonicity. METHODS: With each patient serving as his or her own control, nine stable dialysis patients (23-71 years) were studied during 2 h of combined ultrafiltration-haemodialysis (bicarbonate; UF rate 1.0 l/h)) at two different dialysate sodium concentrations: 134 and 144 mmol/l. Before dialysis as well as every 20 min during dialysis, blood pressure (Dinamap), heart rate (ECG), and forearm vascular resistance and venous tone (strain-gauge plethysmography) were measured. Relative blood volume was monitored continuously by an optical reflection method (Haemoguard 2000), while before and after dialysis blood was obtained for the estimation of plasma prostaglandin E2. RESULTS: High-sodium dialysis resulted in a significantly higher post-dialysis plasma sodium concentration (139. 9 vs 135.0 mmol/l; P<0.01) while the decrease in relative blood volume was significantly smaller as compared to low-sodium dialysis (-8.4 vs -18.4%; P<0.01). There were no significant differences in the different haemodynamic parameters between the two treatment modalities. Both high- and low-sodium dialysis were associated with a significant increase in forearm vascular resistance while venous tone remained unchanged. Although there was no significant difference in plasma PGE2 between the two treatment modalities, PGE2 increased significantly only during low-sodium dialysis. We found no relationship between changes in PGE2 and vascular reactivity. CONCLUSIONS: We conclude that vascular reactivity during combined ultrafiltration-haemodialysis is not directly influenced by sodium-related changes in plasma tonicity. Although not directly studied, the reported improved haemodynamic stability with high-sodium dialysis is probably only mediated through a better preservation of plasma volume. Finally, an increase in plasma PGE2 as observed during low-sodium dialysis does not lead to a decrease in vascular tone.


Assuntos
Soluções para Diálise , Hemodiafiltração/efeitos adversos , Diálise Renal/efeitos adversos , Sódio/sangue , Resistência Vascular , Adulto , Idoso , Feminino , Antebraço/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar
20.
Kidney Int ; 49(1): 222-5, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8770971

RESUMO

In a prospective study of idiopathic glomerulonephritis we determined the natural history of 49 adult patients (12 primary IgA nephropathy, 13 thin GBM nephropathy, 20 normal renal tissue and 4 miscellaneous nephropathies) who presented with idiopathic non-proteinuric non-azotemic hematuria of at least six months duration, in the absence of hypertension and with a negative urological work-up. The median follow-up was 11 years with a range of 8 to 14 years. At the end of the follow-up, renal function had remained stable in all subsets except for those with miscellaneous disease. Hematuria was still present in all patients with thin GBM nephropathy, in all but two patients with IgA nephropathy who went into immunopathological remission, in three out of four miscellaneous nephropathies, and in seven out of 20 patients with normal renal tissue. Of the latter patients five had a history suggestive of urolithiasis at follow-up, which was in the absence of hypercalciuria and hyperuricosuria. Seven thin GBM patients, five IgA nephropathy patients and three miscellaneous nephropathies developed hypertension; the incidence of hypertension in each subset was significantly higher than in patients with normal renal tissue. This study shows that in young adults with idiopathic chronic non-proteinuric hematuria of four years duration, renal biopsy will give a definite diagnosis in 86% of the patients, and that those patients with so-called minor glomerular diseases are at high risk for hypertension. Those patients with normal renal tissue have a high incidence of urolithiasis and should have a urological follow-up.


Assuntos
Glomerulonefrite/complicações , Hematúria/etiologia , Adolescente , Adulto , Idoso , Biópsia , Feminino , Seguimentos , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Hematúria/metabolismo , Hematúria/patologia , Humanos , Hipertensão Renal/complicações , Hipertensão Renal/metabolismo , Hipertensão Renal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
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