A fifty-locus phylogenetic analysis provides deep insights into the phylogeny of Tricholoma (Tricholomataceae, Agaricales).

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.

Bisphosphonates therapy for osteoarthritis: a meta-analysis of randomized controlled trials.

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.

Hypoxia-induced miR-17-5p ameliorates the viability reduction of astrocytes via targeting p21.

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.

Radiotherapy with volumetric modulated arc therapy for hepatocellular carcinoma patients ineligible for surgery or ablative treatments.

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.

The role of toll-like receptor 4 in cisplatin-induced renal injury.

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.

Mesenchymal stem cells ameliorate tissue damages triggered by renal ischemia and reperfusion injury.

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.

The role of heme oxygenase 1 in rapamycin-induced renal dysfunction after ischemia and reperfusion injury.

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.

Vascular regulation of type II cell exocytosis.

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.

A combined solid-state and submerged cultivation integrated with adsorptive product extraction for production of Monascus red pigments.

A process taking advantages of combined solid-state and submerged cultivation of Monascus for red pigment production and integration of a product removal unit was developed. The solid-state cultivation was carried out in a 5 l fermentor, with rice being used not only as the substrate but also the support for Monascus. The inclusion of rice submergence and integration of product separation were achieved by intermittently rinsing the rice with monosodium glutamate (MSG) solutions every 12 h followed by an adsorptive extraction of the red pigment dissolved in the rinsing solution. With this new process, the Monascus red pigment production was increased by 24% as compared with that by the plain fixed-bed cultivation.

Rapid alveolar liquid removal by a novel convective mechanism.

Although alveoli clear liquid by active transport, the presence of surface-active material on the alveolar surface suggests that convective mechanisms for rapid liquid removal may exist. To determine such mechanisms, we held the isolated blood-perfused rat lung at a constant alveolar pressure (PA). Under videomicroscopy, we micropunctured a single alveolus to infuse saline or Ringer solution in approximately 10 adjacent alveoli. Infused alveoli were lost from view. However, as the infused liquid cleared, the alveoli reappeared and their diameters could be quantified. Hence the time-dependent determination of alveolar diameter provided a means for quantifying the time to complete liquid removal (C(t)) in single alveoli. All determinations were obtained at an PA of 5 cmH(2)O. C(t), which related inversely to alveolar diameter, averaged 4.5 s in alveoli with the fastest liquid removal. Injections of dye-stained liquid revealed that the liquid flowed from the injected alveoli to adjacent air-filled alveoli. Lung hyperinflations instituted by cycling PA between 5 and 15 cmH(2)O decreased C(t) by 50%. Chelation of intracellular Ca(2+) prolonged C(t) and abolished the inflation-induced enhancement of liquid removal. We conclude that when liquid is injected in a few alveoli, it rapidly flows to adjacent air-filled alveoli. The removal mechanisms are dependent on alveolar size, inflation, and intracellular Ca(2+). We speculate that removal of liquid from the alveolar surface is determined by the curvature and surface-active properties of the air-liquid interface.

Suspended rice particles for cultivation of Monascus purpureus in a tower-type bioreactor.

Cultivation of Monascus purpureus (CCRC 31615) for the production of natural pigments was investigated. Traditionally, Monascus species were grown on rice by solid-state culture. For large-scale cultivation, solid-state cultures were associated with some problems such as contamination and scale-up. By using submerged cultures with rice particles, a stirred-tank fermentor was not suitable for submerged cultures as the impeller tended to break the particles into small pieces. A conventional bubble column was also unsuitable as its mixing capability was poor. In the present study, a modified bubble column with wire-mesh draft tubes was employed for the cultivation of M. purpureus. The proposed column had a shorter mixing time and a higher oxygen transfer rate relative to the conventional bubble column. The production of pigments using the proposed column was up to 80% higher than that achieved using the conventional bubble column.

A novel signaling mechanism between gas and blood compartments of the lung.

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.

Pleural tissue hyaluronan produced by postmortem ventilation in rabbits.

We developed a method that used Alcian blue bound to hyaluronan to measure pleural hyaluronan in rabbits postmortem. Rabbits were killed, then ventilated with 21% O2--5% CO2--74% N2 for 3 h. The pleural liquid was removed by suction and 5 ml Alcian blue stock solution (0.33 mg/ml, 3.3 pH) was injected into each chest cavity. After 10 min, the Alcian blue solution was removed and the unbound Alcian blue solution (supernatant) separated by centrifugation and filtration. The supernatant transmissibility (T) was measured spectrophotometrically at 613 nm. Supernatant Alcian blue concentration (Cab) was obtained from a calibration curve of T versus dilutions of stock solution Cab. Alcian blue bound to pleural tissue hyaluronan was obtained by subtracting supernatant Cab from stock solution Cab. Pleural tissue hyaluronan was obtained from a calibration curve of hyaluronan versus Alcian blue bound to hyaluronan. Compared with control rabbits, pleural tissue hyaluronan (0.21 +/- 0.04 mg/kg) increased twofold, whereas pleural liquid volume decreased by 30% after 3 h of ventilation. Pleural effusions present 3 h postmortem without ventilation did not change pleural tissue hyaluronan from control values. Thus ventilation-induced pleural liquid shear stress, not increased filtration, was the stimulus for the increased hyaluronan produced from pleural mesothelial cells.

Regional pleural filtration and absorption measured by fluorescent tracers in rabbits.

In prone anesthetized rabbits, we used Evans blue-dyed albumin (EBA) to study regional pleural filtration and FITC dextran to study regional pleural absorption. Evans blue was injected intravenously, and the animals were ventilated for 6 h at either of two levels of ventilation. Postmortem the right rib cage was frozen and thawed before study. EBA fluorescence emitted from the rib cage surface was measured along the cranial-caudal axis near the mid chest with fluorescence videomicroscopy. Fluorescent light intensity increased from the third to the eighth rib in a cyclic fashion, with peaks at the ribs and troughs at the intercostal spaces. This increase was greater at the higher ventilation. Fluorescent images of cross sections of a frozen rib cage verified a cranial-caudal gradient in filtration. Fluorescent images of FITC dextran absorbed from the pleural space into the rib cage surface indicated major areas of absorption at the ventral, caudal, and cranial regions adjacent to the lung margins and areas of absorption scattered in the intercostal spaces. Simultaneous measurements of EBA filtration and FITC absorption showed sites of maximal filtration that were different from sites of maximal absorption. Pleural uptake of fluorescent microspheres (2-microm diameter) located lymphatic stomata distributed randomly within clusters in the intercostal spaces and channels of lymphatic lacunae parallel to blood vessels. Diaphragmatic uptake of microspheres was confined mainly to the ventral surface of the central tendon. Visceral pleural absorption was minimal.

Effects of ventilation on hyaluronan and protein concentration in pleural liquid of anesthetized and conscious rabbits.

The hypothesis of this study is that pleural lubrication is enhanced by hyaluronan acting as a boundary lubricant in pleural liquid and by pleural filtration as reflected in changes in protein concentration with ventilation. Anesthetized rabbits were injected intravenously with Evans blue dye and ventilated with 100% O2 at either of two levels of ventilation for 6 h. Postmortem values of hyaluronan, total protein, and Evans blue-dyed albumin (EBA) concentrations in pleural liquid were greater at the higher ventilation, consistent with increases in boundary lubrication, pleural membrane permeability, and pleural filtration. To determine whether these effects were caused by hyperoxia or anesthesia, conscious rabbits were ventilated with either 3% CO2 or room air in a box for 6, 12, or 24 h. Similar to the anesthetized rabbits, pleural liquid hyaluronan concentration after 24 h was higher in the conscious rabbits with the hypercapnic-induced greater ventilation. By contrast, the time course of total protein and EBA in pleural liquid was similar in both groups of conscious rabbits, indicating no effect of ventilation on pleural permeability. The increase in pleural liquid hyaluronan concentration might be the result of mesothelial cell stimulation by a ventilation-induced increase in pleural liquid shear stress.

Effect of mechanical ventilation on regional variation of pleural liquid thickness in rabbits.

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.

Effect of blood flow on capillary transit time and oxygenation in excised rabbit lung.

We used an isolated perfused lung preparation of the rabbit to study the effect of increasing blood flow on pulmonary capillary transit time by two methods. In one method, capillary transit time was measured from fluorescent dye dilution curves from arterioles and venules of the subpleural microcirculation. Values of transit time were similar to those for the whole lung determined by dividing capillary blood volume by blood flow. Capillary transit times averaged 0.50-0.62 sec at a control blood flow of 80 ml min-1 kg-1 and decreased to 0.14-0.18 sec as blood flow increased to 6 times control. To determine whether the reduced transit time would limit O2 transport, we studied the effect of blood flow on oxygenation. Two isolated rabbit lungs were perfused in series. Blood from one lung deoxygenated by ventilation with a N2-CO2 mixture was oxygenated by the test lung ventilated with air. Ventilation was matched to blood flow. PO2 and PCO2 were measured in blood flowing into and out of the test lung. At all flows, no significant alveolar gas-to-end-capillary blood PO2 gradient (A-aDO2) was measured. The isolated perfused rabbit lung showed no transit time limitation to oxygenation for blood flows that are consistent with heavy exercise in vivo.

Chromosome aberrations induced in human lymphocytes after partial-body irradiation.

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.

Arterial, capillary, and venous transit times and dispersion measured in isolated rabbit lungs.

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.