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1.
Sci Total Environ ; 704: 135309, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31896213

RESUMO

Sediment quality monitoring is widely used to quantify extent of river pollution, but requires knowledge of pre-disturbance conditions in the potentially altered landscape. This has long been identified as a critical aspect to develop for addressing concerns of river pollution in the Alberta Oil Sands Region. Here, we use analyses of sediment cores from eight floodplain lakes spanning a 67 river-km transect across the Athabasca Delta to define pre-1920 (pre-industrial) baseline concentrations for vanadium and five primary pollutants. We then evaluate if sediment metals concentrations have become enriched above baseline since onset of oil sands development and other industrial activities. Results demonstrate no enrichment of metals concentrations (except zinc at one lake) and absence of consistent temporal increases above pre-industrial baselines. Thus, natural processes continue to dominate metal deposition in floodplain lakes of the Athabasca Delta -- an important finding to inform stewardship decisions. The pre-1920 metals concentrations baselines offer a useful tool for ongoing sediment monitoring in aquatic ecosystems of the Athabasca Delta.

2.
Sci Total Environ ; 675: 192-202, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31030127

RESUMO

Kejimkujik National Park, in Nova Scotia, Canada, is a sensitive region for metal(loid) contamination, such as mercury, in part due to long-range atmospheric deposition from global and regional industrial centers. The region is remote from industrial centres, but is downwind of major pollution sources in the Eastern United States and Canada, and historically had numerous gold mining sites. Due to a paucity of long-term atmospheric deposition monitoring in this region, little is known about the response of Kejimkujik lakes to multiple changing global, regional and local atmospheric Hg and metal(loid) sources. Here, we used multiple lake sediment cores to reconstruct anthropogenic depositional fluxes of metal(loid)s of concern for the last ~210years. Results showed that Kejimkujik lake sediments are highly enriched in lead (Pb), antimony (Sb) and tin (Sn), with post-industrial metal(loid) concentrations being >4-fold greater than natural baseline levels (prior to ~1800) and moderately enriched in silver (Ag), bismuth (Bi), cadmium (Cd), copper (Cu), mercury (Hg), rubidium (Rb), tellurium (Te), thallium (Tl), vanadium (V), tungsten (W) and zinc (Zn), with post-industrial metal(loid) concentrations being between 1.5 and 4-fold greater than natural baseline levels (prior to ~1800). Lake sediment core reconstructions of total atmospheric Hg deposition matched well with Hg wet deposition monitoring data from the overlapped period (1997-2010) being 9.1±2.7µg/m2/yr and 7.0±0.7µg/m2/yr respectively. Lakes closest to historic gold mining sites show spikes in Ag, Cd, Sb, Tl, Zn and W during mining periods (~1880 and 1950). Most of the enriched metal(loid)s (EF >1.5) (Ag, Bi, Cu, Hg, Pb, Sb, Sn, V and W) do not appear affected by redox and remobilisation issues. For the other enriched metal(loid)s (EF >1.5) (Cd, Tl, and Zn), remobilisation from upper sediments appears to be occurring within these acidic and DOC rich Kejimkujik lakes.

3.
Dysphagia ; 34(5): 615-626, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30673839

RESUMO

The pharynx is critical for correct swallowing, facilitating the transport of both air and food transport in a highly coordinated manner, and aberrant co-ordination causes swallowing disorders (dysphagia). In this work, an in vitro model of swallowing was designed to investigate the role of rheology in swallowing and for use as a pre-clinical tool for simulation of different routes to dysphagia. The model is based on the geometry of the human pharynx. Manometry is used for pressure measurements and ultrasonic analysis is performed to analyze the flow profiles and determine shear rate in the bolus, the latter being vital information largely missing in literature. In the fully automated model, bolus injection, epiglottis/nasopharynx movement, and ultrasound transducer positioning can be controlled. Simulation of closing of the airways and nasal cavity is modulated by the software, as is a clamping valve that simulates the upper esophageal sphincter. The actions can be timed and valves opened to different degrees, resembling pathologic swallowing conditions. To validate measurements of the velocity profile and manometry, continuous and bolus flow was performed. The respective velocity profiles demonstrated the accuracy and validity of the flow characterization necessary for determining bolus flow. A maximum bolus shear rate of 80 s-1 was noted for syrup-consistency fluids. Similarly, the manometry data acquired compared very well with clinical studies.


Assuntos
Deglutição , Modelos Biológicos , Humanos , Manometria , Faringe/fisiologia , Pressão , Reologia
4.
Environ Sci Technol ; 53(3): 1175-1185, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30596413

RESUMO

Across the Arctic, glaciers are melting and permafrost is thawing at unprecedented rates, releasing not only water to downstream aquatic systems, but also contaminants like mercury, archived in ice over centuries. Using concentrations from samples collected over 4 years and calibrated modeled hydrology, we calculated methylmercury (MeHg) and total mercury (THg) mass balances for Lake Hazen, the world's largest High Arctic lake by volume, for 2015 and 2016. Glacial rivers were the most important source of MeHg and THg to Lake Hazen, accounting for up to 53% and 94% of the inputs, respectively. However, due to the MeHg and THg being primarily particle-bound, Lake Hazen was an annual MeHg and THg sink. Exports of MeHg and THg out the Ruggles River outflow were consequently very low, but erosion and permafrost slumping downstream of the lake increased river MeHg and THg concentrations significantly before entering coastal waters in Chandler Fjord. Since 2001, glacial MeHg and THg inputs to Lake Hazen have increased by 0.01 and 0.400 kg yr-1, respectively, in step with dramatic increases in glacial melt. This study highlights the potential for increases in mercury inputs to arctic ecosystems downstream of glaciers despite recent reductions in global mercury emissions.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Regiões Árticas , Canadá , Ecossistema , Monitoramento Ambiental , Lagos , Nunavut
5.
Sex Reprod Healthc ; 17: 35-42, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30193718

RESUMO

BACKGROUND: Becoming a parent is often a tumultuous experience and a great challenge. The transition when a child is born is described affecting the parents and their relationship psychically, physically, mentally and emotionally. Information within care should be relevant and supportive. Furthermore information within the context of care should be relevant, supportive and helpful to parents in handling their new situation and increasing their self-reliance. AIM: To provide a contextualised understanding of how parents experience postnatal care in relation to information and sense of security". METHOD: A systematic search was undertaken at PubMed and CINAHL database for literature published between January 2002 and August 2017. Inclusion criteria focused on postnatal care. Eight of the studies used qualitative methods and two of the studies used quantitative methods, as a result the findings could not be combined using meta-analysis or meta-synthesis, instead narrative synthesis of the findings were used. RESULTS: Ten studies were included. The analysis revealed three categories related to parent's experience of information and sense of security during the postnatal period. These categories were; Expectations on the care; Own resources; and Confirmation. Support from staff and family is described as significant for the parents' sense of security. During the first postnatal week, the emotions were characterized by anxiety and/or fear. Parents prefer a "non-judgmental" attitude from the staff and to be met as an individual. CONCLUSION: Family -centred care such as continuity, participation, individually adaptation, consistent, information and preparation for parenting appear to be important components for parents' sense of security in postnatal care.


Assuntos
Atitude , Pai/psicologia , Mães/psicologia , Poder Familiar/psicologia , Educação de Pacientes como Assunto , Cuidado Pós-Natal , Período Pós-Parto , Continuidade da Assistência ao Paciente , Emoções , Família , Feminino , Humanos , Participação do Paciente , Gravidez , Autoeficácia
6.
Acta Anaesthesiol Scand ; 58(8): 961-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24943197

RESUMO

BACKGROUND: To reduce blood loss during liver surgery, a low central venous pressure (CVP) is recommended. Nitroglycerine (NG) with its rapid onset and offset can be used to reduce CVP. In this study, the effect of NG on portal and hepatic venous pressures (PVP and HVP) in different body positions was assessed. METHODS: Thirteen patients undergoing liver resection were studied. Cardiac output (CO), mean arterial pressure (MAP) and CVP were measured. PVP and HVP were measured using tip manometer catheters at baseline (BL) in horizontal position; during NG infusion, targeting a MAP of 60 mmHg, with NG infusion and the patient placed in 10 head-down position. RESULTS: NG infusion reduced HVP from 9.7 ± 2.4 to 7.2 ± 2.4, PVP from 12.3 ± 2.2 to 9.7 ± 3.0 and CVP from 9.8 ± 1.9 to 7.2 ± 2.1 mmHg at BL. Head-down tilt during ongoing NG resulted in increases in HVP to 8.2 ± 2.1, PVP to 10.7 ± 3 and CVP to 11 ± 1.9 mmHg. CO at BL was 6.3 ± 1.1, which was reduced by NG to 5.8 ± 1.2. Head-down tilt together with NG infusion restored CO to 6.3 ± 1.0 l/min. CONCLUSION: NG infusion leads to parallel reductions in CVP, HVP and PVP at horizontal body position. Thus, CVP can be used to guide NG dosage and fluid administration at horizontal position. NG infusion can be used to reduce HVP. Head-down tilt can be used during NG infusion to improve both blood pressure and CO without substantial increase in liver venous pressure. In head-down tilt, CVP dissociates from HVP and PVP.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hepatectomia , Nitroglicerina/farmacologia , Posicionamento do Paciente , Vasodilatadores/farmacologia , Idoso , Anti-Hipertensivos/uso terapêutico , Perda Sanguínea Cirúrgica , Carcinoma/secundário , Carcinoma/cirurgia , Débito Cardíaco/efeitos dos fármacos , Feminino , Veias Hepáticas , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão Portal/fisiopatologia , Período Intraoperatório , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Veia Porta
7.
Acta Anaesthesiol Scand ; 55(9): 1106-12, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22092208

RESUMO

BACKGROUND: It has been suggested that blood loss during liver resection may be reduced if central venous pressure (CVP) is kept at a low level. This can be achieved by changing patient position but it is not known how position changes affect portal (PVP) and hepatic (HVP) venous pressures. The aim of the study was to assess if changes in body position result in clinically significant changes in these pressures. METHODS: We studied 10 patients undergoing liver resection. Mean arterial pressure (MAP) and CVP were measured using fluid-filled catheters, PVP and HVP with tip manometers. Measurements were performed in the horizontal, head up and head down tilt position with two positive end expiratory pressure (PEEP) levels. RESULTS: A 10° head down tilt at PEEP 5 cm H(2) O significantly increased CVP (11 ± 3 to 15 ± 3 mmHg) and MAP (72 ± 8 to 76 ± 8 mmHg) while head up tilt at PEEP 5 cm H(2) O decreased CVP (11 ± 3 to 6 ± 4 mmHg) and MAP (72 ± 8 to 63 ± 7 mmHg) with minimal changes in transhepatic venous pressures. Increasing PEEP from 5 to 10 resulted in small increases, around 1 mmHg in CVP, PVP and HVP. There was no significant correlation between changes in CVP vs. PVP and HVP during head up tilt and only a weak correlation between CVP and HVP by head down tilt. CONCLUSIONS: Changes of body position resulted in marked changes in CVP but not in HVPs. Head down or head up tilt to reduce venous pressures in the liver may therefore not be effective measures to reduce blood loss during liver surgery.


Assuntos
Pressão Venosa Central , Hepatectomia/métodos , Posicionamento do Paciente , Respiração com Pressão Positiva , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Veias Hepáticas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Veia Porta/fisiopatologia , Pressão Venosa
8.
Intensive Care Med ; 29(6): 955-962, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12690438

RESUMO

OBJECTIVES: We evaluated an algorithm for continuous on-line monitoring of alveolar pressure over time in a lung model with lower and upper inflection points and variable resistance ratios and in patients with acute lung injury. The algorithm is based on "static" pressure/volume curves obtained from tracheal pressure measurements under dynamic conditions. DESIGN AND SETTING: Experimental and clinical evaluation of algorithm in a university hospital laboratory and intensive care unit. PATIENTS: Ten patients undergoing postoperative respiratory therapy (feasibility of tracheal measurement) and ten patients with acute lung injury undergoing ventilator treatment (evaluation of algorithm). MEASUREMENTS AND RESULTS: Direct tracheal pressure measurements with a catheter inserted through the endotracheal tube. Comparison of measured alveolar and the dynostatic alveolar pressure vs. time in a lung model with changes in five ventilatory parameters. Examples of clinical monitoring are reported. In the model there was excellent agreement between alveolar pressures obtained by the algorithm, the dynostatic alveolar pressure, and measured alveolar pressure at all ventilator settings. For inspiratory/expiratory resistance ratios between 1:2.1-2.1:1, the dynostatic alveolar pressure was within +/-1.5 cm H(2)O of measured alveolar pressure. In patients the technique for direct tracheal pressure measurement using a catheter inserted through the endotracheal tube functioned satisfactorily with intermittent air flushes for cleansing. CONCLUSIONS: Using a thin tracheal pressure catheter inserted through the endotracheal tube alveolar pressure allows continuous bedside monitoring with ease and precision using the dynostatic algorithm. The method is unaffected by tube and connector geometry or by secretions.


Assuntos
Intubação Intratraqueal/métodos , Modelos Biológicos , Monitorização Fisiológica/métodos , Alvéolos Pulmonares/fisiopatologia , Síndrome do Desconforto Respiratório/fisiopatologia , Traqueia/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Resistência das Vias Respiratórias , Algoritmos , Estudos de Viabilidade , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/normas , Complacência Pulmonar , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/normas , Respiração com Pressão Positiva , Pressão , Pressão Propulsora Pulmonar , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , Mecânica Respiratória , Volume de Ventilação Pulmonar
9.
Acta Anaesthesiol Scand ; 45(2): 173-9, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11167162

RESUMO

BACKGROUND: All monitoring of respiratory mechanics should depend on tracheal pressures (Trach-P) as endotracheal tube resistance (ETT-Res) will otherwise distort them. The aim of this study was to investigate factors that may vary ETT-Res, causing difficulties in ETT-Res estimation clinically, and to evaluate a method for direct Trach-P measurements to obviate these problems. METHODS: In a model we studied: 1) The influence on ETT-Res caused by different connectors and secretions; 2) Direct Trach-P measurements with a catheter (o.d. 2 mm, i.d. 0.9 mm) with either end or side hole, filled with either air or liquid, introduced through the ETT lumen and evaluated regarding response time and position. RESULTS: The pressure drop between trachea and Y-piece increased by 15% when respectively a swivel connector and a humidification device were connected to the ETT. When injecting 1 ml and 2 ml gel into the ETT lumen the inspiratory resistance increased 100% and 600% respectively. The response time of all catheters was < or = 12 ms. During constant flow in inspiratory and expiratory directions the pressure difference between an end hole catheter positioned from 2 cm above the ETT tip to 4 cm below and a reference pressure in the artificial trachea was less than 1.5 cmH2O. CONCLUSIONS: ETT connections and secretions cause a variance in resistance. Tracheal pressure can be measured with high precision with an air- or liquid-filled catheter. An end hole catheter placed within 2 cm above or below the ETT tip will give sufficiently precise measurements for clinical purposes.


Assuntos
Testes de Função Respiratória/métodos , Mecânica Respiratória/fisiologia , Traqueia/fisiologia , Pressão do Ar , Cateterismo , Humanos , Intubação Intratraqueal , Pulmão/fisiologia , Modelos Anatômicos , Monitorização Intraoperatória , Testes de Função Respiratória/efeitos adversos , Testes de Função Respiratória/instrumentação , Espirometria/métodos
10.
Acta Anaesthesiol Scand ; 44(5): 578-85, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10786746

RESUMO

BACKGROUND: Lung mechanics are usually measured using static or quasistatic methods, abandoning normal ventilatory treatment. We have developed a method to calculate the alveolar pressure during dynamic/therapeutic conditions, "the dynostatic pressure" (P(dyn)), using airway pressure (P) measured in the trachea and volume (V) and flow (V) at the Y-piece. METHODS: P(dyn) is calculated according to the formula P(dyn)= (P(insp) x V(exp)-P(exp) x V(insp))/(V(exp)-V(insp)), making the assumption that inspiratory and expiratory resistances are equal at isovolume. The method was evaluated in a lung model during dynamic conditions comparing measured alveolar pressure (P(alv)) and P(dyn) at equal and unequal inspiratory and expiratory resistances and P/V-curves obtained during static and dynamic conditions. The algorithm was then applied in patients with acute lung injury (ALI). RESULTS: When inspiratory and expiratory resistances were equal there was an excellent agreement between the P(dyn) and the P(alv), irrespective of ventilator settings, r(2)=0.995 (range 0.981-0.999). P(dyn) derived compliance was equal to static values. When the ratio between inspiratory and expiratory resistance was varied between 2.3:1 and 1:2.3 the r(2) was above 0.95 (range 0.952-0.996). Development of intrinsic PEEP and overdistension was easily revealed in patients, as shown by the dynostatic P/V-curve. CONCLUSION: The dynostatic method gives a breath-by-breath reflection of the interaction between ventilatory settings and lung mechanics in patients during ordinary ventilator treatment. It is only marginally affected by the moderate differences in inspiratory versus expiratory resistances present in patients with ALI.


Assuntos
Respiração Artificial/métodos , Mecânica Respiratória , Resistência das Vias Respiratórias , Humanos , Modelos Estruturais , Pressão , Alvéolos Pulmonares/fisiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , Espirometria
11.
Acta Anaesthesiol Scand ; 44(5): 571-7, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10786745

RESUMO

BACKGROUND: The aim of this study was to evaluate and compare information about lung mechanics obtained by dynamic pressure/volume loops based on Y-piece and intratracheal airway pressure. METHODS: Airway pressure was measured simultaneously at the Y-piece and trachea. Flow/tidal volume was measured by sidestream spirometry at the Y-piece. The effect of an intraluminal catheter in the tube was evaluated in a lung model. Ten adults with acute lung injury and mechanical ventilation were studied. Measurements were performed during volume-(VC) and pressure-controlled (PC) ventilation at different ventilator settings. RESULTS: Lung model: There was a statistically significant difference (P<0.001) between trachea and Y-piece pressure/volume loop areas during both VC and PC ventilation. The ratio trachea area/Y-piece area decreased with increased endotracheal tube resistance (r=0.96). PATIENTS: The difference between trachea and Y-piece P/V-loops was statistically significant at all 21 ventilatory settings (P<0.05-0.001). The tracheal loop revealed clearly intrinsic PEEP and lowered compliance during overinflation, which was difficult or impossible to see in the Y-piece pressure/volume loop. CONCLUSION: By measuring airway pressure at the trachea the effect of endotracheal tube resistance during inspiration is excluded while it is included during expiration, yielding correct end-points of inspiration and expiration. This makes it possible to calculate accurately total compliance of the respiratory system during dynamic conditions. By monitoring of airway pressure in the trachea, respiratory mechanics can be assessed more accurately and ventilatory settings adjusted to attenuate ventilator induced lung injury.


Assuntos
Intubação Intratraqueal , Respiração Artificial , Mecânica Respiratória , Idoso , Resistência das Vias Respiratórias , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estruturais , Respiração com Pressão Positiva , Respiração por Pressão Positiva Intrínseca , Pressão , Ventilação Pulmonar , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , Espirometria , Volume de Ventilação Pulmonar , Traqueia/fisiopatologia
12.
Life Sci ; 62(26): 2359-68, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9651102

RESUMO

A novel, time- and BMP-saving in vitro method for the detection and quantitation of bone morphogenetic protein (BMP) activity was developed based on the measurable effects of BMP on rat skeletal muscle myoblasts (L6). Calcium incorporation, stimulation of alkaline phosphatase activity and production of osteocalcin were used as markers of bone cell metabolism and on-going morphogenesis. The morphological change was confirmed by Chlorantine fast red and von Kossa staining. The response of various BMPs was purity-dependent and consistent with intramuscular implantations of the same materials. Neither TGF-beta1 nor insulin could induce the same actions. The data from this study indicate that at least in part in vivo implantations of BMP extracts can be replaced by in vitro measurement of osteoinductivity. Considerable saving of time, BMP and experimental animals can be achieved using cell culture conditions for the determination of bone-forming activity.


Assuntos
Desenvolvimento Ósseo/fisiologia , Proteínas Morfogenéticas Ósseas/biossíntese , Músculo Esquelético/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Bioensaio , Biomarcadores , Radioisótopos de Cálcio , Bovinos , Humanos , Músculo Esquelético/citologia , Osteocalcina/metabolismo , Ratos , Timidina/metabolismo
14.
Acta Otolaryngol ; 110(5-6): 321-7, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2284906

RESUMO

The significance to human postural control of pressor information from the feet was investigated during vestibular disturbance in seven normal subjects who were exposed to bipolar biaural galvanic stimulation of the vestibular nerves before and after their feet were anaesthetized with hypothermia. The increase in body sway in the lateral plane induced by the galvanic stimulus was enhanced when the feet were anaesthetized, and adaptation of postural control to the galvanic stimulus was delayed. It is concluded that pressor information from the feet contributes significantly to postural control in humans and is important in compensating for vestibular disturbance.


Assuntos
Pé/inervação , Mecanorreceptores/fisiologia , Postura/fisiologia , Nervo Vestibular/fisiologia , Adaptação Fisiológica , Adolescente , Adulto , Estimulação Elétrica , Pé/fisiologia , Humanos , Hipotermia Induzida , Movimento , Pressão
15.
Acta Otolaryngol ; 110(1-2): 11-7, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2386025

RESUMO

Anterior-posterior body sway was evoked with monopolar bi-aural galvanic stimulus of the vestibular nerves in normal subjects and recorded with a force platform, two experiments being conducted. In an experiment of paired design, 9 normal subjects showed an increase in anterior-posterior sway as compared with lateral sway when exposed to the stimulus. In a second experiment another group of 10 normal subjects were exposed to a galvanic stimulus between a neck electrode and two electrodes placed on the arms, but there was no change in the relationship between anterior-posterior and lateral body sway. It is concluded that monopolar galvanic stimulus of the vestibular nerves can induce anterior-posterior body sway, a phenomenon which can be utilised to investigate the vestibulo-spinal contribution in postural control in the anterior-posterior plane.


Assuntos
Resposta Galvânica da Pele/fisiologia , Postura/fisiologia , Nervo Vestibular/fisiologia , Adulto , Análise de Variância , Estimulação Elétrica , Feminino , Humanos , Masculino , Movimento , Valores de Referência
16.
Endocrinology ; 111(4): 1140-9, 1982 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7117195

RESUMO

Anterior pituitary nuclei isolated from rats were used in an in vitro DNA synthesis assay. The rate of in vitro synthesis was increased by prior in vivo estrogen treatment in a time-dependent and dose-dependent manner, and the observed increase was similar in magnitude to that measured by [3H] thymidine incorporation in whole tissue. In vitro DNA synthesis was sensitive to N-ethylmaleimide but resistant to dideoxythymidine triphosphate. Rates of pituitary DNA synthesis were compared in the Fischer 344 (F344) rat, a strain highly susceptible to diethylstilbestrol-induced pituitary tumors, and in the Holtzman rat, a strain resistant to rapid tumor induction by diethylstilbestrol. After chronic treatment (8 weeks) with estrogen, elevated DNA synthesis (2- to 3-fold) was observed in F344 pituitaries but not in Holtzman pituitaries. After short term (2-4 days) treatment with estrogen, however, DNA synthesis increased 2-fold in both Holtzman and F344 pituitary nuclei. The elevated DNA synthesis declined in the Holtzman strain after 5 or 6 days of additional estrogen treatment, but elevated DNA synthesis persisted in the F344 strain. These results suggest that the genetic difference is due to the lack of a proliferation control mechanism in the F344 strain that functions in the Holtzman strain to shut off estrogen-stimulated cell proliferation.


Assuntos
DNA/biossíntese , Estradiol/farmacologia , Adeno-Hipófise/metabolismo , Neoplasias Hipofisárias/genética , Animais , Divisão Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , Dietilestilbestrol , Cinética , Neoplasias Hipofisárias/induzido quimicamente , Ratos , Ratos Endogâmicos F344/genética , Ratos Endogâmicos/genética
18.
Endocrinology ; 109(5): 1708-14, 1981 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7297501

RESUMO

An 8-week period of continuous diethylstilbestrol (DES) treatment results in the development of pituitary tumors in 100% of male or female F344 rats. Similar treatment of Holtzman male or female rats results in a very low incidence of pituitary tumor development (2-6%). A series of crosses was performed between F344 and Holtzman rats to produce the F1 hybrid, the F2 generation, and the backcrosses of the F1 hybrid to either the F344 parent or the Holtzman parent. The incidence of DES-induced pituitary tumors was measured in these animals. The results indicate that pituitary tumor susceptibility does not result from the expression of genes that are simple dominant or recessive genes, since the tumor's incidence in the F1 hybrid is intermediate to that in the parental strains. However, the data are compatible with the involvement of a small number of genetic loci. We present a genetic model involving three independently segregating loci which agrees reasonably well with the experimental results. In the model, the Holtzman strain has normal alleles at these loci which prevent uncontrolled proliferation. The highly inbred F344 strain is homozygous mutant at these three loci and in unable to control DES-induced proliferation.


Assuntos
Neoplasias Hipofisárias/genética , Animais , Cruzamentos Genéticos , Dietilestilbestrol , Feminino , Genótipo , Hibridização Genética , Masculino , Modelos Genéticos , Neoplasias Experimentais/genética , Tamanho do Órgão , Fenótipo , Hipófise/anatomia & histologia , Hipófise/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344
19.
Adv Exp Med Biol ; 138: 151-63, 1981.
Artigo em Inglês | MEDLINE | ID: mdl-7342713

RESUMO

We presented evidence that primary cultures of rat pituitary cells respond to estradiol by increased incorporation of precursors into prolactin. The response is specific for estrogenic hormones and is maximal at physiological concentrations of estradiol. The time course and magnitude of the response in cultured cells is in agreement with that observed under in vivo conditions, suggesting that estrogen exerts its effect mainly through a direct action on the pituitary gland. The data presented indicate that estrogen stimulates prolactin synthesis predominantly through increased prolactin mRNA accumulation, and to a lesser extent, through mammotroph cell proliferation. Chronic treatment with DES caused sustained proliferation of pituitary cells leading to prolactin producing pituitary tumors in the Fischer 344 rat, but not in the Holtzman rat. The genetic basis for these differences are currently under investigation.


Assuntos
Estrogênios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipófise/metabolismo , Prolactina/biossíntese , Animais , Divisão Celular , DNA/biossíntese , Dietilestilbestrol/toxicidade , Hipófise/citologia , Neoplasias Hipofisárias/induzido quimicamente , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Especificidade da Espécie
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