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As an ectomycorrhizal fungal genus that contains matsutake and other edible mushrooms, Tricholoma has great economic and ecological significance. However, the phylogenetic relationships within the genus remain unsettled. To clarify the infrageneric relationships of Tricholoma, including the identification of monophyletic subgenera and sections, three phylogenetic analyses were conducted employing single-locus (ITS), five-locus (ITS/ RPB2/EF-1α/MCM7/mtSSU) and 50-locus (45 single-copy orthologous genes plus the aforementioned ones) DNA nucleotide sequences. Our data indicated that ITS sequences could serve the species delimitation of Tricholoma in most cases and monophyletic groups recognition in some cases, and the five-locus dataset could resolve a section-level phylogeny of this genus, while the 50-locus dataset could clarify the delimitation of subgenera and settle the relationships among sections within this genus. A fifty-locus dataset was firstly employed to construct a robust phylogeny of Tricholoma. Based on this, a new infrageneric arrangement for the genus Tricholoma, with four subgenera, of which two are in accordance with the previous subgenera Pardinicutis and Sericeicutis, and eleven sections, is suggested. Subgenus Pardinicutis, occupying the basal position, only harbors sect. Pardinicutis, while the subg. Sericeicutis comprises sects. Lasciva and Sericella located at the sub-basal position with good support. Subgenus Terrea is newly erected here and consists of sect. Terrea, sect. Atrosquamosa and two as yet unnamed phylogenetic lineages. Besides an unnamed section-level lineage, subg. Tricholoma consists of sects. Genuina, Muscaria, Rigida, Tricholoma, Fucata and Matsutake, of which the two latter are newly proposed. The previously defined subg. Contextocutis is clustered within subg. Tricholoma and is a synonym of the latter. Tricholoma colossus, T. acerbum and their allies, which used to be allocated in sect. Megatricholoma (or genus Megatricholoma), are relocated to sect. Genuina since they form a strongly supported monophyletic group and share rusty or black spots on lamellae with other species in this section. Taxonomic descriptions of the new infrageneric taxa and a key to subgenera and sections of the genus Tricholoma are presented. Citation: Ding XX, Xu X, Cui YY, et al. 2023. A fifty-locus phylogenetic analysis provides deep insights into the phylogeny of Tricholoma (Tricholomataceae, Agaricales). Persoonia 50: 1-26. https://doi.org/10.3767/persoonia.2023.50.01.
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PURPOSE: The aim of this article is to report the dosimetric and clinical findings in the treatment of primary hepatocellular carcinoma (HCC) with volumetric modulated arc therapy (VMAT, RapidArc). METHODS AND MATERIALS: A total of 138 patients were investigated. Dose prescription ranged from 45-66 Gy. Most patients (88.4 %) presented AJCC stage III or IV and 83 % were N0-M0. All were classified as Barcelona Clinic Liver Cancer (BCLC) stage A-C. All patients were treated using 10 MV photons with single or multiple, coplanar or non-coplanar arcs, and cone-down technique in case of early response of tumors. RESULTS: The patients' median age was 66 years (range 27-87 years), 83 % were treated with 60 Gy (12 % at 45 Gy, 6 % at 66 Gy), 62 % with cone-down, 98 % with multiple arcs. The mean initial planning target volume (PTV) was 777 ± 632 cm(3); the mean final PTV (after the cone-down) was 583 ± 548 cm(3). High target coverage was achieved. The final PTV was V98% > 98 %. Kidneys received on average 5 and 8 Gy (left and right), while the maximum dose to the spinal cord was 22 Gy; mean doses to esophagus and stomach were 23 Gy and 15 Gy, respectively. The average volume of healthy liver receiving more than 30 Gy was 294 ± 145 cm(3). Overall survival at 12 months was 45 %; median survival was 10.3 months (95 % confidence interval 7.2-13.3 months). Actuarial local control at 6 months was 95 % and 93.7 % at 12 months. The median follow-up was 9 months and a maximum of 28 months. CONCLUSION: This study showed from the dosimetric point of view the feasibility and technical appropriateness of RapidArc for the treatment of HCC. Clinical results were positive and might suggest, with appropriate care, to consider RapidArc as an additional therapeutic opportunity for these patients.
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Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Fígado/efeitos da radiação , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosAssuntos
Carcinoma Hepatocelular/radioterapia , Gastrite/etiologia , Neoplasias Hepáticas/radioterapia , Lesões por Radiação/etiologia , Estômago/efeitos da radiação , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Gastrite/diagnóstico , Humanos , Lesões por Radiação/diagnóstico , Estômago/patologiaRESUMO
Propagation of inflammatory signals from the airspace to the vascular space is pivotal in lung inflammation, but mechanisms of intercompartmental signaling are not understood. To define signaling mechanisms, we microinfused single alveoli of blood-perfused rat lung with TNF-alpha, and determined in situ cytosolic Ca(2+) concentration ([Ca(2+)](i)) by the fura-2 ratio method, cytosolic phospholipase A(2) (cPLA(2)) activation and P-selectin expression by indirect immunofluorescence. Alveolar TNF-alpha increased [Ca(2+)](i) and activated cPLA(2) in alveolar epithelial cells, and increased both endothelial [Ca(2+)](i) and P-selectin expression in adjoining perialveolar capillaries. All responses were blocked by pretreating alveoli with a mAb against TNF receptor 1 (TNFR1). Crosslinking alveolar TNFR1 also increased endothelial [Ca(2+)](i). However, the endothelial responses to alveolar TNF-alpha were blocked by alveolar preinjection of the intracellular Ca(2+) chelator BAPTA-AM, or the cPLA(2) blockers AACOCF(3) and MAFP. The gap-junction uncoupler heptanol had no effect. We conclude that TNF-alpha induces signaling between the alveolar and vascular compartments of the lung. The signaling is attributable to ligation of alveolar TNFR1 followed by receptor-mediated [Ca(2+)](i) increases and cPLA(2) activation in alveolar epithelium. These novel mechanisms may be relevant in the alveolar recruitment of leukocytes.
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Cálcio/metabolismo , Alvéolos Pulmonares/irrigação sanguínea , Alvéolos Pulmonares/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Antígenos CD/metabolismo , Capilares/metabolismo , Quelantes/farmacologia , Citosol/enzimologia , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Ativação Enzimática , Selectina-P/metabolismo , Fosfolipases A/antagonistas & inibidores , Fosfolipases A/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral , Vasculite/metabolismoRESUMO
BACKGROUND: Toll-like receptors recognize pattern-associated molecules found in pathogens as well as in endogen cells and in matrix degradation products. Despite the effectiveness of cisplatin against various solid tumors the administered dose is limited by its nephrotoxicity, namely, induction of tubular cell apoptosis. Herein, we investigated whether the cell toxicity of cisplatin was mediated by toll-like receptor 4 signaling. METHODS: C3H/He J (Toll-like receptor 4 deficient) and C3H/HePas (control) were treated with cisplatin (20 mg/kg). We evaluated renal function as well as expression of (HO-1) heme oxygenase 1 and MCP-1 mRNAs. RESULTS: Animals deficient in Toll-like receptor 4 showed less renal dysfunction after cisplatin therapy, which was more evident at later time points. Moreover, MCP-1 mRNA expression in kidneys from these animals were lower than controls, mainly at 96 hours after treatment. No differences were seen in HO-1 mRNA expression. CONCLUSIONS: These results suggested that cisplatin-induced renal toxicity is mediated in part though toll-like receptor 4.
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Cisplatino/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Receptor 4 Toll-Like/deficiência , Receptor 4 Toll-Like/fisiologia , Animais , Quimiocina CCL2/genética , Heme Oxigenase-1/genética , Testes de Função Renal , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , RNA Mensageiro/genéticaRESUMO
BACKGROUND: Ischemia and reperfusion injury (I/R) is the major cause of acute renal failure (ARF) with high mortality rates. Because alternative therapies are needed, we investigated the use of stem cell therapy to modulate inflammation in a renal I/R model. METHODS: To study kidney I/R injury, we clamped bilateral pedicles for 60 minutes. Mesenchymal stem cells (MSC), which had been isolated and cultivated in plastic flasks, were administered to mice 6 hours after injury. Real-time polymerase chain reaction was used to quantify interleukin (IL)-4 and IL-1beta mRNAs. Proliferative nuclear cell antigen (PCNA) was used to calculate tubular regeneration. RESULTS: Administration of MSC attenuated renal injury; serum creatinine and plasma urea levels were significantly reduced 24 hours after reperfusion. PCNA immunohistochemistry showed that regeneration occurred faster in renal tissues of animals that received MSC than in tissues of control animals. Analyses of cytokine expression in renal tissue demonstrated a greater level of anti-inflammatory cytokines in MSC-treated animals. CONCLUSION: These results showed an antiinflammatory pattern in MSC-treated animals, demonstrating the potential of MSC to modulate I/R, leading to earlier regeneration of damaged renal tissue.
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Nefropatias/terapia , Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão/terapia , Animais , Células da Medula Óssea/citologia , Inflamação/prevenção & controle , Interleucina-1beta/genética , Interleucina-4/genética , Masculino , Reação em Cadeia da Polimerase , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
High-turnover type bone metabolism derangement has been considered to be one of the major causes of osteoarthritis (OA). Bisphosphonates can attach to hydroxyapatite binding sites on bony surfaces, particularly those which are undergoing active bone resorption. To evaluate the effectiveness of bisphosphonates in OA treatment, literature databases were searched from inception to February 28, 2016 for clinical studies of bisphosphonates for OA treatment. All randomized controlled trials in which bisphosphonates therapy was compared with a placebo or a conventional medication, were selected. 15/1145 studies were eligible for analysis, which included 3566 participants. Bisphosphonates therapy improved pain, stiffness and function significantly in OA assessed by the Western Ontario and McMaster Universities Arthritis Index scale (MD = 4.59; 95 % CI 2.83-6.34; P < 0.00001; MD = 1.43; 95 % CI 0.83-2.23; P = 0.0005; MD = 2.01; 95 % CI 1.27-2.75; P < 0.00001). Bisphosphonates also reduced osteophyte score significantly (MD = -0.51; 95 % CI -0.84 to -0.19; P = 0.002). However, no significant differences were found in subjective improvement, osteoarthritis progression, the number of required acetaminophen treatment or joint replacement. In conclusion, bisphosphonates therapy is effective in relieving pain,stiffness and accelerating functional recovery in OA. Limitations of the studies we analysed included the differences in duration of bisphosphonates use, the doses and types of bisphosphonates and the lack of long-term data on OA joint structure modification after bisphosphonates therapy. More targeted studies are required to evaluate on the effectiveness of bisphosphonates for OA treatment.
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OBJECTIVE: Glial scars are widely seen as a mechanical barrier to central nervous system regeneration. Up to now, several studies have addressed and clarified how different lesion microenvironment properties affect astrogliosis. In particular, hypoxia induces the astrocyte astrogliosis, and thus promotes the formation of glial scars. However, little is known about the mechanism underlining such process. In the present study, we investigated the regulation by the miR-17-5p on the hypoxia-induced viability via targeting p21. MATERIALS AND METHODS: We examined the expression of miR-15a, miR-16, miR-17-5p, hypoxia inducible factor-1α (HIF-1α) and p21 in the astrocytes under hypoxia, with quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) methods. Then investigated the regulatory role of miR-17-5p on the level of HIF-1α and p21, with qRT-PCR, WB and luciferase reporting assay, and examined the activity of astrocytes under normoxia or hypoxia. RESULTS: Results demonstrated that miR-15a, miR-16, miR-17-5p were significantly upregulated, while HIF-1α and p21 were markedly downregulated in the hypoxia-treated astrocytes. And the transfection with miR-17-5p mimics significantly downregulated the expression of HIF-1α and p21 in such cells. And the luciferase reporter assay confirmed the targeting inhibiting of p21 by miR-17-5p in astrocytes. Moreover, the viability of astrocytes was significantly upregulated by the miR-17-5p mimics transfection under the hypoxia condition. CONCLUSIONS: Our novel data suggest that the upregulated miR-17-5p contributes to the proliferation of astrocytes, in response to hypoxia, implying the potential role of miR-17-5p in the formation of glial scars.
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Astrócitos/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , MicroRNAs/metabolismo , Hipóxia Celular/genética , Proliferação de Células , Humanos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
We examined the distribution of airflow-generated sound within a flexible model of canine airways. Sounds were picked up by a microphone adapted to a glass conical probe which was introduced through puncture holes in the wall of the model. We acquired 341 measurements in 31 airways between 2.0 and 19.0 mm in diameter at airflow rates from 0 to 2.5 L/s in the inspiratory and expiratory directions. We found that in the expiratory direction, the sound amplitude was approximately linearly related to airway cross-sectional area, with the greatest amplitude occurring in the largest airway. In the inspiratory direction the greatest amplitude occurred in airways of 5 to 8 mm in diameter. At all levels within the model, sound amplitude was approximately linearly related to the square of the airflow. Our findings suggest that in canine airways, the predominant vesicular lung sound-producing locations are the large airways for the expiratory component and the medium-sized airways for the inspiratory component.
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Brônquios/fisiologia , Ventilação Pulmonar , Sons Respiratórios/fisiologia , Traqueia/fisiologia , Animais , Cães , Modelos EstruturaisRESUMO
Chromosomal aberrations in peripheral blood lymphocytes obtained from two patients before and after they received one fraction of partial-body irradiation for palliative treatment were analyzed. Blood samples were taken 30 min and 24 h after radiation treatment. The yield of dicentrics obtained from case A 30 min after a partial-body (about 21%) treatment with 8 Gy was 0.066/cell, while the yield obtained 24 h after radiation treatment was 0.071/cell. The fraction of irradiated lymphocytes that reached metaphase at 52 h was 0.08 as evaluated by mixing cultures of in vitro irradiated and unirradiated blood. The yield of dicentrics for blood from case B 30 min after 6 Gy partial-body (about 24%) irradiation was 0.655/cell, while the yield 24 h after irradiation was 0.605/cell. The fraction of irradiated cells was 0.29. Estimation of doses and irradiated fractions for the two cases using the method proposed by Dolphin and the Qdr method is discussed. Although there was no significant difference between the mean yields of dicentrics per cell obtained 30 min and 24 h after radiation treatment, the data obtained at 24 h seemed more useful for the purpose of dose estimation. When a higher dose (8 Gy) was delivered to a smaller percentage of the body, underestimation of the dose was encountered.
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Aberrações Cromossômicas , Linfócitos/efeitos da radiação , Idoso , Humanos , Linfócitos/ultraestrutura , Masculino , Doses de RadiaçãoRESUMO
The thickness of the pleural space was measured by fluorescence video-microscopy during mechanical ventilation in anesthetized paralyzed rabbits. A transparent parietal pleural window was made in the fourth or sixth intercostal space near midchest by dissection of intercostal muscle and endothoracic fascia. Fluorescence-labeled (fluorescein isothiocyanate) dextran solution (1 ml) was injected into the pleural space via a rib capsule and allowed to mix with the pleural liquid. With the rabbit in the left lateral decubitus position and the pleural window superior, the light emitted from the pleural liquid through the pleural window was measured through the videomicroscope. Both ventilation frequency and tidal volume were varied. Pleural space thickness was determined by in vitro calibration of the pleural liquid at the end of the experiment. At a frequency of 40 breaths/min and a tidal volume of 20 ml, pleural space thickness averaged 35 +/- 15 (SD) microns (n = 7). When frequency was reduced to 8 breaths/min, this value was reduced by 40% to 22 +/- 11 microns. A reduction in tidal volume from 20 to 6 ml at a frequency of 40 breaths/min produced a similar reduction in pleural space thickness. During apnea, pleural space thickness averaged 11 +/- 3 microns. Cardiogenic motion had no measurable effect on pleural space thickness. The increased pleural space thickness with ventilation might serve to reduce the power dissipated due to sliding of the lung relative to the chest wall. Results support the concept of lubrication as the primary function of the pleural space.
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Pleura/anatomia & histologia , Mecânica Respiratória/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Animais , Apneia/fisiopatologia , Gasometria , Pressão Sanguínea/fisiologia , Coração/fisiologia , Frequência Cardíaca/fisiologia , Pulmão/anatomia & histologia , Microscopia de Fluorescência , Pleura/fisiologia , Coelhos , Respiração ArtificialRESUMO
In anesthetized, paralyzed, supine rabbits (3-4 kg) during apnea, we injected fluorescent dye or fluorescent microspheres (2 or 6 microns diam) into the dependent pleural space and observed the arrival and movement of the dye or microspheres at superior regions. Injection was through a rib capsule located in the dependent right chest. The dye or microspheres were observed through a pleural window overlying a lobar margin. The vertical distance between the capsule and window was 3-4 cm. The movement of the dye or microspheres was recorded via a fluorescence videomicroscope, and the signals were analyzed for dye transit time and microsphere velocity. The transit time of the dye to traverse the height of the pleural space was calculated from the light intensity vs. time curve. Transit time during apnea averaged 6.0 +/- 3.4 (SD) min (n = 4). Transit time measured after the onset of mechanical ventilation was < 1 min. The direction and speed of a microsphere moving in the relatively thick pleural space adjacent to the lobar margin depended on its distance from the lobar margin. Microspheres moved upward in the pleural space that was in proximity to the lobar margin but downward at farther distances from the lobar margin. Pleural liquid recirculation occurs via the pleural space adjacent to lobar margins.
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Líquidos Corporais/fisiologia , Coração/fisiologia , Pleura/fisiologia , Animais , Gasometria , Corantes Fluorescentes , Microscopia de Fluorescência , Microesferas , Pleura/anatomia & histologia , CoelhosRESUMO
We used fluorescence videomicroscopy to measure the passage of fluorescent dye through the subpleural microcirculation of the lung. With the rabbit in the left lateral decubitus position, the subpleural microcirculation was viewed either through a transparent parietal pleural window located in the superior part of the chest or directly with the chest open. There was no physical contact with the chest or lung. The rabbit was anesthetized, paralyzed, and mechanically ventilated with 100% O2. The dye was injected into the right ventricle during a 2-min apneic period to eliminate lung movement due to ventilation. The video signal of the passage of the dye was analyzed frame by frame by use of digital image processing to compensate for cardiogenic oscillations of the lung surface. Gray scale levels of an arteriole and adjacent venule were measured every 1/30 s. Capillary transit time was determined from the difference between the concentration-weighted mean time values of the arteriolar and venular dye dilution curves. We studied the effect of airway pressure (0-20 cmH2O) on transit time. Cardiac output was measured at different airway pressures by the thermal dilution technique. Capillary transit time averaged 0.60 s at functional residual capacity. Right ventricular-to-arteriolar transit time was four times as large as the capillary transit time. An increase in airway pressure from 0-5 to 20 cmH2O resulted in a fourfold increase in both capillary and arterial transit times and a threefold decrease in cardiac output.
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Capilares/fisiologia , Circulação Pulmonar , Animais , Apneia/fisiopatologia , Débito Cardíaco , Fluoresceínas , Microscopia de Fluorescência , Pressão , Coelhos , Respiração Artificial , Fatores de Tempo , Gravação em VídeoRESUMO
Transit time and relative dispersion of the arterial, capillary, and venous segments of the pulmonary circulation were measured in isolated perfused rabbit lungs. Fluorescence videomicroscopy was used to record the passage of dye through the main pulmonary artery, subpleural microcirculation, and venous outflow. Dye dilution curves were obtained at the main pulmonary artery, subpleural arterioles and venules, and pulmonary vein. Measurements were made at 5-cmH2O airway pressure, at blood flows of approximately 80, 50, and 25 ml.min-1.kg-1, and at left atrial pressures of approximately 0 cmH2O (zone 2) and approximately 12 cmH2O (zone 3). The dye dilution curves were modeled as lagged normal density curves that were used to calculate transit time and relative dispersion between the pulmonary artery and arteriole (artery), arteriole and venule (capillary), venule and pulmonary vein (vein), and pulmonary artery and pulmonary vein (whole lung). In open-chest anesthetized dogs, the passage of dye was recorded from the subpleural arterioles and venules between the seventh and eighth ribs in the left lateral position. At comparable blood flows, capillary transit time was larger in the dog than in the rabbit lung [3.4 +/- 2.4 (SD) vs. 0.87 +/- 0.47 s]. In the rabbit lung, relative dispersion was greater in pulmonary capillaries (average values 0.83-1.6) and veins (0.91-1.6) than in arteries (0.39-0.50), which was similar to the whole lung dispersion (0.47-0.52). A similarly high dispersion (0.93) was measured in the dog's pulmonary capillaries. Thus high dispersion in pulmonary capillaries and veins cannot be detected by whole lung dispersion measurements.
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Circulação Pulmonar , Animais , Artérias , Capilares , Cães , Técnicas In Vitro , Técnicas de Diluição do Indicador , Pulmão/fisiologia , Microscopia de Fluorescência , Microscopia de Vídeo , Coelhos , Fatores de Tempo , VeiasRESUMO
In a previous study, direct measurements of pulmonary capillary transit time by fluorescence video microscopy in anesthetized rabbits showed that chest inflation increased capillary transit time and decreased cardiac output. In isolated perfused rabbit lungs we measured the effect of lung volume, left atrial pressure (Pla), and blood flow on capillary transit time. At constant blood flow and constant transpulmonary pressure, a bolus of fluorescent dye was injected into the pulmonary artery and the passage of the dye through the subpleural microcirculation was recorded via the video microscope on videotape. During playback of the video signals, the light emitted from an arteriole and adjacent venule was measured using a video photoanalyzer. Capillary transit time was the difference between the mean time values of the arteriolar and venular dye dilution curves. We measured capillary transit time in three groups of lungs. In group 1, with airway pressure (Paw) at 5 cmH2O, transit time was measured at blood flow of approximately 80, approximately 40, and approximately 20 ml.min-1.kg-1. At each blood flow level, Pla was varied from 0 (Pla less than Paw, zone 2) to 11 cmH2O (Pla greater than Paw, zone 3). In group 2, at constant Paw of 15 cmH2O, Pla was varied from 0 (zone 2) to 22 cmH2O (zone 3) at the same three blood flow levels. In group 3, at each of the three blood flow levels, Paw was varied from 5 to 15 cmH2O while Pla was maintained at 0 cmH2O (zone 2).(ABSTRACT TRUNCATED AT 250 WORDS)
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Circulação Pulmonar/fisiologia , Mecânica Respiratória/fisiologia , Animais , Tempo de Circulação Sanguínea , Velocidade do Fluxo Sanguíneo , Capilares/fisiologia , Técnicas In Vitro , Medidas de Volume Pulmonar , Perfusão , Pressão , CoelhosRESUMO
Physical and mathematical models were used to study a mechanism that could maintain the layer of pleural fluid that covers the surface of the lung. The pleural space was modeled as a thin layer of viscous fluid lying between a membrane carrying tension (T), representing the lung, and a rigid wall, representing the chest wall. Flow of the fluid was driven by sliding between the membrane and wall. The physical model consisted of a cylindrical balloon with strings stretched along its surface. When the balloon was inflated inside a vertical circular cylinder containing a viscous fluid, the strings formed narrow vertical channels between broad regions in which the balloon pressed against the outer cylinder. The channels simulated the pleural space in the regions of lobar margins. Oscillatory rotation of the outer cylinder maintained a lubricating layer of fluid between the balloon and the cylinder. The thickness of the fluid layer (h), measured by fluorescence videomicroscopy, was larger for larger fluid viscosity (mu), larger sliding velocity (U), and smaller pressure difference (delta P) between the layer and the channel. A mathematical model of the flow in a horizontal section was analyzed, and numerical solutions were obtained for parameter values of mu, U, delta P, and T that matched those of the physical model. The computed results agreed reasonably well with the experimental results. Scaling laws yield the prediction that h is approximately (T/delta P)(microU/T)2/3. For physiological values of the parameters, the predicted value of h is approximately 10(-3) cm, in good agreement with the observed thickness of the pleural space.
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Líquidos Corporais/fisiologia , Pleura/fisiologia , Corantes Fluorescentes , Glicerol , Pulmão/fisiologia , Membranas Artificiais , Microscopia de Vídeo , Modelos Biológicos , Pressão , Mecânica Respiratória/fisiologia , Óleos de Silicone , ViscosidadeRESUMO
Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure in native and transplanted kidneys. In the transplantation field, immunosuppressive drugs may play an additional role in acute graft dysfunction. Rapamycin may impair renal regeneration post IRI. Heme oxygenase 1 (HO-1) is a protective gene with anti-inflammatory and anti-apoptotic actions. We investigated whether HO-1 played a role in rapamycin-induced renal dysfunction in an established model of IRI. Rapamycin (3 mg/kg) was administered to mice before being subjected to 45 min of ischemia. Animals subjected to IRI presented with impaired renal function that peaked at 24 h (2.05+/-0.23 mg/dl), decreasing thereafter. Treatment with rapamycin caused even more renal dysfunctions (2.30+/-0.33 mg/dl), sustained up to 120 h after reperfusion (1.54+/-0.4 mg/dl), when compared to the control (0.63+/-0.09 mg/dl, P<0.05). Rapamycin delayed tubular regeneration that was normally higher in the control group at day 5 (68.53+/-2.30 vs 43.63+/-3.11%, P<0.05). HO-1 was markedly upregulated after IRI and its expression was even enhanced by rapamycin (1.32-fold). However, prior induction of HO-1 by cobalt protoporphyrin improved the renal dysfunction imposed by rapamycin, mostly at later time points. These results demonstrated that rapamycin used in ischemic-injured organs could also negatively affect post-transplantation recovery. Modulation of HO-1 expression may represent a feasible approach to limit rapamycin acute toxicity.
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Heme Oxigenase-1/metabolismo , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/fisiopatologia , Sirolimo/efeitos adversos , Injúria Renal Aguda/enzimologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Animais , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/genética , Heme Oxigenase-1/genética , Imunossupressores/farmacologia , Rim/patologia , Rim/fisiopatologia , Transplante de Rim/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Protoporfirinas/farmacologia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/enzimologia , Sirolimo/farmacologiaRESUMO
A method of producing flexible and strong models of canine airways is described. The animal's lungs are dried in inflation by using compressed air and then filled with silicone sealer. After this compound dries, the lung tissue is removed by corrosion by using NAOH. The result is a rugged, flexible, and anatomically faithful model of canine airways that is suitable for use in teaching.
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Pulmão/análise , Modelos Anatômicos , Fisiologia/educação , Animais , Cães , Pulmão/fisiologiaRESUMO
To determine whether lung capillary pressure regulates surfactant secretion, we viewed alveoli of the constantly inflated, isolated blood-perfused rat lung by fluorescence microscopy. By alveolar micropuncture we infused fura 2 and lamellar body (LB)-localizing dyes for fluorescence detection of, respectively, the alveolar cytosolic Ca(2+) concentration ([Ca(2+)](i)) and type II cell exocytosis. Increasing left atrial pressure (Pla) from 5 to 10 cmH(2)O increased septal capillary diameter by 26% and induced marked alveolar [Ca(2+)](i) oscillations that abated on relief of pressure elevation. The rate of loss of LB fluorescence that reflects the LB exocytosis rate increased fourfold after the pressure elevation and continued at the same rate even after pressure and [Ca(2+)](i) oscillations had returned to baseline. In alveoli pretreated with either 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, the intracellular Ca(2+) chelator, or heptanol, the gap junctional blocker, the pressure-induced exocytosis was completely inhibited. We conclude that capillary pressure and surfactant secretion are mechanically coupled. The secretion initiates in a Ca(2+)-dependent manner but is sustained by Ca(2+)-independent mechanisms.
Assuntos
Ácido Egtázico/análogos & derivados , Exocitose/fisiologia , Alvéolos Pulmonares/citologia , Alvéolos Pulmonares/fisiologia , Circulação Pulmonar/fisiologia , Animais , Cálcio/metabolismo , Capilares/fisiologia , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/fisiologia , Quelantes/farmacologia , Ácido Egtázico/farmacologia , Exocitose/efeitos dos fármacos , Corantes Fluorescentes , Junções Comunicantes/fisiologia , Heptanol/farmacologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Microscopia de Fluorescência , Alvéolos Pulmonares/irrigação sanguínea , Surfactantes Pulmonares/fisiologia , Ratos , Ratos Sprague-Dawley , Estresse MecânicoRESUMO
We studied the effect of ventilation on the regional distribution of pleural liquid thickness in anesthetized rabbits. Three transparent pleural windows were made between the second and eight intercostal space along the midaxillary line of the right chest. Fluorescein isothiocyanate-labeled dextran (1 ml) was injected into the pleural space through a rib capsule and allowed to mix with the pleural liquid. The light emitted from the pleural space beneath the windows was measured by fluorescence videomicroscopy at a constant tidal volume (20 ml) and two ventilation frequencies (20 and 40 breaths/min). Pleural liquid thickness was determined from the light measurements after in vitro calibration of pleural liquid collected postmortem. At 20 breaths/min, pleural liquid thickness increased with a cranial-caudal distance from 5 microns at the second to third intercostal space to 30 microns at the sixth through eighth intercostal space. At 40 breaths/min, pleural space thickness was unchanged at the second to third intercostal space but increased to 46 microns at the sixth through eighth intercostal space. To determine this effect on pleural liquid shear stress, we measured relative lung velocity from videomicroscopic images of the lung surface through the windows. Lung velocity amplitude increased with cranial-caudal distance and with ventilation frequency. Calculated shear stress amplitude was constant with cranial-caudal distance but increased with ventilation frequency. Thus, pleural liquid thickness is matched to the relative lung motion so as to maintain a spatially uniform shear stress amplitude in pleural liquid during mechanical ventilation.