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1.
Geophys Res Lett ; 49(23): e2022GL099211, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-37034393

RESUMO

During the Juno Mission's encounter with Ganymede on 7 June 2021, the Juno camera (JunoCam) acquired four images of Ganymede in color. These images covered one-sixth of Ganymede at scales from 840 m to ∼4 km/pixel. Most of this area was only previously imaged by Voyager 1 in 1979, at lower spatial resolution and poorer image quality. No changes were observed over this area of Ganymede in the 42 years since Voyager. JunoCam provided overlapping coverage, from which we developed a digital elevation model of the best-resolved area. A 3 km high dome at the subjovian point was confirmed, 450 km by 750 km. We used the JunoCam images to refine the geologic map of Ganymede in eastern Perrine Regio.

2.
Geophys Res Lett ; 45(8): 3445-3452, 2018 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-30034048

RESUMO

We have monitored a newly erupted volcanic island in the Kingdom of Tonga, unofficially known as Hunga Tonga Hunga Ha'apai, by means of relatively frequent high spatial resolution (~50 cm) satellite observations. The new ~1.8 km2 island formed as a tuff cone over the course of a month-long hydromagmatic eruption in early 2015 in the Tonga-Kermadec volcanic arc. Such ash-dominated eruptions usually produce fragile subaerial landscapes that wash away rapidly due to marine erosion, as occurred nearby in 2009. Our measured rates of erosion are ~0.00256 km3/year from derived digital topographic models. Preliminary measurements of the topographic expression of the primary tuff cone over ~30 months suggest a lifetime of ~19 years (and potentially up to 42 years). The ability to measure details of a young island's landscape evolution using satellite remote sensing has not previously been possible at these spatial and temporal resolutions.

3.
Childs Nerv Syst ; 32(8): 1359-62, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27312077

RESUMO

BACKGROUND: Central nervous system (CNS) germ cell tumors account for 3 % of all pediatric brain tumors in the USA. Presenting symptoms are typically location based with pineal tumors presenting with obstructive hydrocephalus and suprasellar tumors with hypothalamic/pituitary dysfunction and ophthalmologic abnormalities. Psychiatric manifestations such as psychosis and behavioral changes are atypical presentations of CNS germ cell tumors, with only 11 previously reported cases. METHODS: This is a retrospective case series describing patients with CNS germ cell tumors with an atypical presentation including psychiatric manifestations. Information regarding clinical presentation, treatment course, and outcome were obtained. RESULTS: We report seven patients who presented with psychiatric symptoms consisting of psychomotor delay as well as behavioral and mood changes. Six of the seven patients were diagnosed ≥6 months after onset of psychiatric symptoms. All of the seven are alive but five continue to have neurologic and psychiatric issues post treatment. CONCLUSIONS: Atypical presentations of CNS germ cell tumors can delay diagnosis and treatment and may be secondary to atypical locations as well as endocrine dysfunction manifesting as psychiatric symptoms. Delayed diagnosis did not appear to affect survival but earlier diagnosis may potentially be associated with better neurologic and psychiatric outcome. Patients who present with these symptoms and atypical neuroimaging should have a thorough evaluation for CNS germ cell tumors including serum and CSF markers. Clinicians should be aware of these less common presentations to aid in prompt diagnosis and treatment.


Assuntos
Neoplasias Encefálicas/complicações , Transtornos Mentais/etiologia , Neoplasias Embrionárias de Células Germinativas/complicações , Adolescente , Criança , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Estudos Retrospectivos , Adulto Jovem
4.
Space Sci Rev ; 218(8): 72, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36514324

RESUMO

The NASA InSight Lander on Mars includes the Heat Flow and Physical Properties Package HP3 to measure the surface heat flow of the planet. The package uses temperature sensors that would have been brought to the target depth of 3-5 m by a small penetrator, nicknamed the mole. The mole requiring friction on its hull to balance remaining recoil from its hammer mechanism did not penetrate to the targeted depth. Instead, by precessing about a point midway along its hull, it carved a 7 cm deep and 5-6 cm wide pit and reached a depth of initially 31 cm. The root cause of the failure - as was determined through an extensive, almost two years long campaign - was a lack of friction in an unexpectedly thick cohesive duricrust. During the campaign - described in detail in this paper - the mole penetrated further aided by friction applied using the scoop at the end of the robotic Instrument Deployment Arm and by direct support by the latter. The mole tip finally reached a depth of about 37 cm, bringing the mole back-end 1-2 cm below the surface. It reversed its downward motion twice during attempts to provide friction through pressure on the regolith instead of directly with the scoop to the mole hull. The penetration record of the mole was used to infer mechanical soil parameters such as the penetration resistance of the duricrust of 0.3-0.7 MPa and a penetration resistance of a deeper layer ( > 30 cm depth) of 4.9 ± 0.4 MPa . Using the mole's thermal sensors, thermal conductivity and diffusivity were measured. Applying cone penetration theory, the resistance of the duricrust was used to estimate a cohesion of the latter of 2-15 kPa depending on the internal friction angle of the duricrust. Pushing the scoop with its blade into the surface and chopping off a piece of duricrust provided another estimate of the cohesion of 5.8 kPa. The hammerings of the mole were recorded by the seismometer SEIS and the signals were used to derive P-wave and S-wave velocities representative of the topmost tens of cm of the regolith. Together with the density provided by a thermal conductivity and diffusivity measurement using the mole's thermal sensors, the elastic moduli were calculated from the seismic velocities. Using empirical correlations from terrestrial soil studies between the shear modulus and cohesion, the previous cohesion estimates were found to be consistent with the elastic moduli. The combined data were used to derive a model of the regolith that has an about 20 cm thick duricrust underneath a 1 cm thick unconsolidated layer of sand mixed with dust and above another 10 cm of unconsolidated sand. Underneath the latter, a layer more resistant to penetration and possibly containing debris from a small impact crater is inferred. The thermal conductivity increases from 14 mW/m K to 34 mW/m K through the 1 cm sand/dust layer, keeps the latter value in the duricrust and the sand layer underneath and then increases to 64 mW/m K in the sand/gravel layer below. Supplementary Information: The online version contains supplementary material available at 10.1007/s11214-022-00941-z.

5.
Science ; 377(6603): 285-291, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35857591

RESUMO

Carbonaceous asteroids, such as (101955) Bennu, preserve material from the early Solar System, including volatile compounds and organic molecules. We report spacecraft imaging and spectral data collected during and after retrieval of a sample from Bennu's surface. The sampling event mobilized rocks and dust into a debris plume, excavating a 9-meter-long elliptical crater. This exposed material is darker, spectrally redder, and more abundant in fine particulates than the original surface. The bulk density of the displaced subsurface material was 500 to 700 kilograms per cubic meter, which is about half that of the whole asteroid. Particulates that landed on instrument optics spectrally resemble aqueously altered carbonaceous meteorites. The spacecraft stored 250 ± 101 grams of material, which will be delivered to Earth in 2023.

6.
Am J Physiol Renal Physiol ; 299(6): F1374-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20826574

RESUMO

In vitro experiments showed that the connecting tubule (CNT) sends a signal that dilates the afferent arteriole (Af-Art) when Na(+) reabsorption in the CNT lumen increases. We call this process CNT glomerular feedback (CTGF) to differentiate it from tubuloglomerular feedback (TGF), which is a cross talk between the macula densa (MD) and the Af-Art. In TGF, the MD signals the Af-Art to constrict when NaCl transport by the MD is enhanced by increased luminal NaCl. CTGF is mediated by CNT Na(+) transport via epithelial Na(+) channels (ENaC). However, we do not know whether CTGF occurs in vivo or whether it opposes the increase in Af-Art resistance caused by TGF. We hypothesized that CTGF occurs in vivo and opposes TGF. To test our hypothesis, we conducted in vivo micropuncture of individual rat nephrons, measuring stop-flow pressure (P(SF)) as an index of glomerular filtration pressure. To test whether activation of CTGF opposes TGF, we used benzamil to block CNT Na(+) transport and thus CTGF. CTGF inhibition with the ENaC blocker benzamil (1 µM) potentiated the decrease in P(SF) at 40 and 80 nl/min. Next, we tested whether we could augment CTGF by inhibiting NaCl reabsorption in the distal convoluted tubule with hydrochlorothiazide (HCTZ, 1 mM) to enhance NaCl delivery to the CNT. In the presence of HCTZ, benzamil potentiated the decrease in P(SF) at 20, 40, and 80 nl/min. We concluded that in vivo CTGF occurs and opposes the vasoconstrictor effect of TGF.


Assuntos
Retroalimentação/efeitos dos fármacos , Glomérulos Renais/fisiologia , Túbulos Renais/fisiologia , Amilorida/análogos & derivados , Amilorida/farmacologia , Animais , Arteríolas/efeitos dos fármacos , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Masculino , Néfrons/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
7.
J Cyst Fibros ; 19(2): 255-261, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31253541

RESUMO

BACKGROUND: This study aimed to improve our understanding of the natural history of cystic fibrosis (CF) by comparing lung function and body mass index z-score (zBMI) between patients with different genotypes and identify a genotype with outcomes most comparable to homozygous ΔF508 patients. METHODS: Data was obtained from the Canadian CF Registry between January 1st 2007-January 1st 2016. Patients were categorized into one of five groups based on their genotype. A mixed-effects model was conducted with adjustments for age, sex, age of diagnosis, and baseline clinical measures. RESULTS: Among 2612 patients, those with non-mild forms of CF, and particularly adult patients with the same functional allele classification were found to have a lung function trajectory comparable to individuals with the homozygous ∆F508 genotype (annual change in percent predicted forced expiratory volume in 1 s of -0.83, 95% CI: -0.93, -0.73). The rates of zBMI change over the study period were not significantly different between the genotype groups. CONCLUSION: This population-based study of Canadian CF patients provides adjusted rates of lung function decline and zBMI over ten years. The finding that there are different genotypes with comparable rates of lung function decline to patients of the homozygous ∆F508 group supports the use of multiple comparison groups to assess the long-term efficacy of emerging CF therapies.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística , Estado Nutricional , Testes de Função Respiratória , Adulto , Índice de Massa Corporal , Canadá/epidemiologia , Criança , Agonistas dos Canais de Cloreto/uso terapêutico , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/epidemiologia , Fibrose Cística/fisiopatologia , Feminino , Estudos de Associação Genética , Homozigoto , Humanos , Masculino , Mutação , Gravidade do Paciente , Sistema de Registros/estatística & dados numéricos , Testes de Função Respiratória/métodos , Testes de Função Respiratória/estatística & dados numéricos , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Nat Commun ; 11(1): 1014, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094337

RESUMO

The Interior Exploration using Seismic Investigations, Geodesy and Heat Transport (InSight) spacecraft landed successfully on Mars and imaged the surface to characterize the surficial geology. Here we report on the geology and subsurface structure of the landing site to aid in situ geophysical investigations. InSight landed in a degraded impact crater in Elysium Planitia on a smooth sandy, granule- and pebble-rich surface with few rocks. Superposed impact craters are common and eolian bedforms are sparse. During landing, pulsed retrorockets modified the surface to reveal a near surface stratigraphy of surficial dust, over thin unconsolidated sand, underlain by a variable thickness duricrust, with poorly sorted, unconsolidated sand with rocks beneath. Impact, eolian, and mass wasting processes have dominantly modified the surface. Surface observations are consistent with expectations made from remote sensing data prior to landing indicating a surface composed of an impact-fragmented regolith overlying basaltic lava flows.

9.
Science ; 292(5516): 488-91, 2001 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-11313491

RESUMO

During the Near Earth Asteroid Rendezvous (NEAR)-Shoemaker's low-altitude flyover of asteroid 433 Eros, observations by the NEAR Laser Rangefinder (NLR) have helped to characterize small-scale surface features. On scales from meters to hundreds of meters, the surface has a fractal structure with roughness dominated by blocks, structural features, and walls of small craters. This fractal structure suggests that a single process, possibly impacts, dominates surface morphology on these scales.

10.
Science ; 234(4782): 1379-83, 1986 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-17755059

RESUMO

Multispectral images of the basaltic surface of Venus obtained by Venera 13 were processed to remove the effects of orange-colored incident radiation resulting from interactions with the thick Venusian atmosphere. At visible wavelengths the surface of Venus appears dark and without significant color. High-temperature laboratory reflectance spectra of basaltic materials indicate that these results are consistent with mineral assemblages bearing either ferric or ferrous iron. A high reflectance in the near-infrared region observed at neighboring Venera 9 and 10 sites, however, suggests that the basaltic surface material contains ferric minerals and thus may be relatively oxidized.

11.
Science ; 279(5357): 1686-92, 1998 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-9497281

RESUMO

The first 18 tracks of laser altimeter data across the northern hemisphere of Mars from the Mars Global Surveyor spacecraft show that the planet at latitudes north of 50 degrees is exceptionally flat; slopes and surface roughness increase toward the equator. The polar layered terrain appears to be a thick ice-rich formation with a non-equilibrium planform indicative of ablation near the periphery. Slope relations suggest that the northern Tharsis province was uplifted in the past. A profile across Ares Vallis channel suggests that the discharge through the channel was much greater than previously estimated. The martian atmosphere shows significant 1-micrometer atmospheric opacities, particularly in low-lying areas such as Valles Marineris.


Assuntos
Meio Ambiente Extraterreno , Marte , Atmosfera , Gelo , Astronave
12.
Science ; 284(5419): 1495-503, 1999 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-10348732

RESUMO

Elevations measured by the Mars Orbiter Laser Altimeter have yielded a high-accuracy global map of the topography of Mars. Dominant features include the low northern hemisphere, the Tharsis province, and the Hellas impact basin. The northern hemisphere depression is primarily a long-wavelength effect that has been shaped by an internal mechanism. The topography of Tharsis consists of two broad rises. Material excavated from Hellas contributes to the high elevation of the southern hemisphere and to the scarp along the hemispheric boundary. The present topography has three major drainage centers, with the northern lowlands being the largest. The two polar cap volumes yield an upper limit of the present surface water inventory of 3.2 to 4.7 million cubic kilometers.


Assuntos
Evolução Planetária , Marte , Água , Meio Ambiente Extraterreno , Gelo
13.
Science ; 282(5396): 2053-60, 1998 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-9851922

RESUMO

Elevations from the Mars Orbiter Laser Altimeter (MOLA) have been used to construct a precise topographic map of the martian north polar region. The northern ice cap has a maximum elevation of 3 kilometers above its surroundings but lies within a 5-kilometer-deep hemispheric depression that is contiguous with the area into which most outflow channels emptied. Polar cap topography displays evidence of modification by ablation, flow, and wind and is consistent with a primarily H2O composition. Correlation of topography with images suggests that the cap was more spatially extensive in the past. The cap volume of 1.2 x 10(6) to 1.7 x 10(6) cubic kilometers is about half that of the Greenland ice cap. Clouds observed over the polar cap are likely composed of CO2 that condensed out of the atmosphere during northern hemisphere winter. Many clouds exhibit dynamical structure likely caused by the interaction of propagating wave fronts with surface topography.


Assuntos
Dióxido de Carbono , Gelo , Marte , Água , Meio Ambiente Extraterreno
14.
BMJ Open ; 9(12): e029475, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31796474

RESUMO

OBJECTIVE: This study aimed to conduct a systematic review of preclinical and clinical evidence to chart the successful trajectory of talimogene laherparepvec (T-VEC) from the bench to the clinic. DESIGN: This study was a systematic review. The primary outcome of interest was the efficacy of treatment, determined by complete response. Abstract and full-text selection as well as data extraction were done by two independent reviewers. The Cochrane risk of bias tool was used to assess the risk of bias in studies. SETTING: Embase, Embase Classic and OvidMedline were searched from inception until May 2016 to assess its development trajectory to approval in 2015. PARTICIPANTS: Preclinical and clinical controlled comparison studies, as well as observational studies. INTERVENTIONS: T-VEC for the treatment of any malignancy. RESULTS: 8852 records were screened and five preclinical (n=150 animals) and seven clinical studies (n=589 patients) were included. We saw large decreases in T-VEC's efficacy as studies moved from the laboratory to patients, and as studies became more methodologically rigorous. Preclinical studies reported complete regression rates up to 100% for injected tumours and 80% for contralateral tumours, while the highest degree of efficacy seen in the clinical setting was a 24% complete response rate, with one study experiencing a complete response rate of 0%. We were unable to reliably assess safety due to the lack of reporting, as well as the heterogeneity seen in adverse event definitions. All preclinical studies had high or unclear risk of bias, and all clinical studies were at a high risk of bias in at least one domain. CONCLUSIONS: Our findings illustrate that even successful biotherapeutics may not demonstrate a clear translational road map. This emphasises the need to consider increasing rigour and transparency along the translational pathway. PROSPERO REGISTRATION NUMBER: CRD42016043541.


Assuntos
Produtos Biológicos/uso terapêutico , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos , Animais , Modelos Animais de Doenças , Herpesvirus Humano 1 , Humanos , Melanoma/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Mol Ther Oncolytics ; 14: 179-187, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31276026

RESUMO

Irreproducibility of preclinical findings could be a significant barrier to the "bench-to-bedside" development of oncolytic viruses (OVs). A contributing factor is the incomplete and non-transparent reporting of study methodology and design. Using the NIH Principles and Guidelines for Reporting Preclinical Research, a core set of seven recommendations, we evaluated the completeness of reporting of preclinical OV studies. We also developed an evidence map identifying the current trends in OV research. A systematic search of MEDLINE and Embase identified all relevant articles published over an 18 month period. We screened 1,554 articles, and 236 met our a priori-defined inclusion criteria. Adenovirus (43%) was the most commonly used viral platform. Frequently investigated cancers included colorectal (14%), skin (12%), and breast (11%). Xenograft implantation (61%) in mice (96%) was the most common animal model. The use of preclinical reporting guidelines was listed in 0.4% of articles. Biological and technical replicates were completely reported in 1% of studies, statistics in 49%, randomization in 1%, blinding in 2%, sample size estimation in 0%, and inclusion/exclusion criteria in 0%. Overall, completeness of reporting in the preclinical OV therapy literature is poor. This may hinder efforts to interpret, replicate, and ultimately translate promising preclinical OV findings.

16.
Surgeon ; 6(2): 88-93, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18488774

RESUMO

BACKGROUND: In response to the requirements of the European Working Time Directive (EWTD), a national implementation group was formed to liaise with local implementation groups at nine different pilot sites. As part of this process, a pilot EWTD compliant rota was run for six weeks amongst general surgical SHOs in University Hospital Galway. METHODS: A rota was devised for nine general surgical SHOs, the aim being to achieve EWTD compliance. SHOs were asked to complete questionnaires to assess the effectiveness of the pilot. RESULT: During the pilot SHOs were rostered for an average of 53.6 hours. Actual hours worked were 58.1 hours. Fifty-two point five per cent of working weeks were non-compliant with the provisions of the EWTD. Seventy per cent of the time SHOs felt that continuity of care was not achieved. Eighty-one per cent felt that patient care deteriorated during the pilot. SHOs spent an average of 2.5 days per week engaged in sessional commitments with their consultant. Fifty percent of SHOs missed elective operating sessions or outpatient clinics. SHOs attended an average of 1.3 emergency operations per week (range 0-8) and 5.5 elective procedures per week (range 0-12). All SHOs reported a deterioration in quantity or quality of training. However, 69% reported an improvement in their quality of life during the pilot. CONCLUSIONS: With this tightly defined shift system, hours worked were in breach of the provisions of the EWTD. Sixty-nine per cent of SHOs reported an improvement in quality of life, but all reported a deterioration in training and 81% felt that patient care suffered.


Assuntos
Atitude do Pessoal de Saúde , Reivindicações Trabalhistas , Cirurgia Geral/organização & administração , Admissão e Escalonamento de Pessoal/legislação & jurisprudência , Europa (Continente) , Hospitais Universitários , Humanos , Satisfação no Emprego , Projetos Piloto
17.
Can J Public Health ; 109(3): 419-426, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29981081

RESUMO

OBJECTIVES: This study examined Twitter for public health surveillance during a mass gathering in Canada with two objectives: to explore the feasibility of acquiring, categorizing and using geolocated Twitter data and to compare Twitter data against other data sources used for Pan Parapan American Games (P/PAG) surveillance. METHODS: Syndrome definitions were created using keyword categorization to extract posts from Twitter. Categories were developed iteratively for four relevant syndromes: respiratory, gastrointestinal, heat-related illness, and influenza-like illness (ILI). All data sources corresponded to the location of Toronto, Canada. Twitter data were acquired from a publicly available stream representing a 1% random sample of tweets from June 26 to September 10, 2015. Cross-correlation analyses of time series data were conducted between Twitter and comparator surveillance data sources: emergency department visits, telephone helpline calls, laboratory testing positivity rate, reportable disease data, and temperature. RESULTS: The frequency of daily tweets that were classified into syndromes was low, with the highest mean number of daily tweets being for ILI and respiratory syndromes (22.0 and 21.6, respectively) and the lowest, for the heat syndrome (4.1). Cross-correlation analyses of Twitter data demonstrated significant correlations for heat syndrome with two data sources: telephone helpline calls (r = 0.4) and temperature data (r = 0.5). CONCLUSION: Using simple syndromes based on keyword classification of geolocated tweets, we found a correlation between tweets and two routine data sources for heat alerts, the only public health event detected during P/PAG. Further research is needed to understand the role for Twitter in surveillance.


Assuntos
Vigilância em Saúde Pública/métodos , Mídias Sociais , Esportes , Canadá , Aglomeração , Estudos de Viabilidade , Humanos
18.
J Clin Invest ; 93(6): 2572-7, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8200994

RESUMO

The effect of endothelin-1 (ET-1) on the proximal tubule remains unclear. This may be due to a biphasic effect on transport in this segment. We hypothesized that ET-1 has a biphasic effect on fluid absorption (Jv) in the proximal straight tubule and that its inhibitory effect is superimposed on its stimulatory effect. ET-1 (10(-13) M) stimulated Jv from 0.68 +/- 0.07 to 1.11 +/- 0.20 nl/mm/min, a 60% increase (P < 0.04). 10(-12) and 10(-10) M ET-1 had no significant effect. 10(-9) M ET-1 reduced Jv from 0.81 +/- 0.19 to 0.44 +/- 0.15 nl/mm/min (P < 0.009). Staurosporine (STP, 10(-8) M) prevented both 10(-9) and 10(-13) M ET-1 from altering Jv significantly indicating that protein kinase C (PKC) is involved. Indomethacin (10(-5) M) blocked the inhibition produced by 10(-9) M ET-1. ETI (10(-6) M), a lipoxygenase inhibitor, also blocked ET-1 inhibition of Jv. Interestingly ET-1 (10(-9) M) stimulated Jv in the presence of both indomethacin and ETI. When 10(-9) M ET-1 was added in the presence of 10(-5) M quinacrine, a phospholipase (PL) inhibitor, Jv also increased from 1.02 +/- 0.20 to 1.23 +/- 0.22 nl/mm/min (P < 0.03). STP blocked this increase. We conclude that (a) 10(-13) M ET-1 stimulates fluid absorption by activating PKC; (b) 10(-9) M ET-1 decreases Jv by PKC-, PL-, cyclooxygenase-, and lipoxygenase-dependent mechanisms; and (c) the inhibitory effect of ET-1 on Jv is superimposed on the stimulatory effect.


Assuntos
Água Corporal/metabolismo , Endotelinas/farmacologia , Túbulos Renais Proximais/metabolismo , Absorção , Animais , Transporte Biológico/efeitos dos fármacos , Indometacina/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Fosfolipases/fisiologia , Proteína Quinase C/fisiologia , Ratos , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/fisiologia
19.
J Clin Invest ; 95(6): 2741-8, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7769114

RESUMO

Flow may be a physiological stimulus of the endothelial release of nitric oxide (NO) and prostaglandins (PGs). We tested the hypothesis that pressure-induced constriction of the glomerular afferent arteriole (Af-Art) is modulated by luminal flow via endothelial production of NO. We microdissected the terminal segment of an interlobular artery together with two Af-Arts, their glomeruli (GL) and efferent arterioles (Ef-Art). The two Af-Arts were perfused simultaneously from the interlobular artery, while one Ef-Art was occluded. Since the arteriolar perfusate contained 5% albumin, oncotic pressure built up in the glomerulus with the occluded Ef-Art and opposed the force of filtration, resulting in little or no flow through the corresponding Af-Art. Thus this preparation allowed us to observe free-flow and no-flow Af-Arts simultaneously during stepwise 30-mmHg increases in intraluminal pressure (from 30 to 120 mmHg). Pressure-induced constriction was weaker in free-flow than no-flow Af-Arts, with the luminal diameter decreasing by 11.1 +/- 1.7 and 25.6 +/- 2.3% (n = 30), respectively, at 120 mmHg. To examine whether flow modulates myogenic constriction through endothelium-derived NO and/or PGs, we examined pressure-induced constriction before and after (a) disruption of the endothelium, (b) inhibition of NO synthesis with NW-nitro-L-arginine methyl ester (L-NAME), or (c) inhibition of cyclooxygenase with indomethacin. Both endothelial disruption and L-NAME augmented pressure-induced constriction in free-flow but not no-flow Af-Arts, abolishing the differences between the two. However, indomethacin had no effect in either free-flow or no-flow Af-Arts. These results suggest that intraluminal flow attenuates pressure-induced constriction in Af-Arts via endothelium-derived NO. Thus flow-stimulated NO release may be important in the fine control of glomerular hemodynamics.


Assuntos
Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiologia , Óxido Nítrico/fisiologia , Vasoconstrição , Animais , Pressão Sanguínea , Indometacina/farmacologia , Glomérulos Renais/irrigação sanguínea , Masculino , Prostaglandinas/fisiologia , Coelhos , Fluxo Sanguíneo Regional
20.
J Clin Invest ; 78(4): 989-96, 1986 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3760195

RESUMO

We determined whether a spontaneous luminal disequilibrium pH, pHdq (pH measured - pH equilibrium), was present in isolated perfused rabbit S2 and S3 proximal tubules. Luminal pH was measured by perfusing with the fluorescent pH probe 1,4-DHPN, and the equilibrium pH was calculated from the measured collected total CO2 and dissolved CO2 concentrations. S2 tubules failed to generate a spontaneous pHdq. S3 tubules generated a spontaneous acidic pHdq of -0.46 +/- 0.15 (P less than 0.05), which was obliterated following the addition of carbonic anhydrase (0.1 mg/ml) to the perfusate. In S3 tubules perfused and bathed in 4 mM total ammonia, luminal total ammonia rose from 4.08 +/- 0.05 mM (perfusate) to 4.95 +/- 0.20 mM (collected fluid) (P less than 0.02). Carbonic anhydrase added to the perfusate prevented the rise in the collected total ammonia concentration. We conclude that the rabbit S3 proximal tubule lacks functional luminal carbonic anhydrase. The acidic pHdq in the S3 segment enhances the diffusion of NH3 into the lumen. In contrast, the S2 segment has functional luminal carbonic anhydrase.


Assuntos
Amônia/metabolismo , Bicarbonatos/metabolismo , Homeostase , Concentração de Íons de Hidrogênio , Túbulos Renais Proximais/metabolismo , Animais , Transporte Biológico , Fluorescência , Perfusão , Coelhos
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