A mathematical description of pressures in alveolar pores of Kohn

Small interalveolar holes within the lung are called pores of Kohn. Some researchers have correlated enlarged pore size with diseases, e.g. emphysema, that are characterized by tissue destruction. Mathematical models of the pressures generated in closed, fluid-filled and open, fluid-lined pores demonstrate that pressures capable of rupturing lung tissue can be developed in a pore due to the surface tension and shape of the air-liquid interface. Pore enlargement accompanied by tissue destruction is presented as a possible mechanism for the disease process observed during aging and the development of emphysema in the lung.     

Volume-related and volume-independent effects of posture on esophageal and transpulmonary pressures in healthy subjects.

Ventilator management decisions in acute lung injury could be better informed with knowledge of the patient's transpulmonary pressure, which can be estimated using measurements of esophageal pressure. Esophageal manometry is seldom used for this, however, in part because of a presumed postural artifact in the supine position. Here, we characterize the magnitude and variability of postural effects on esophageal pressure in healthy subjects to better assess its significance in patients with acute lung injury. We measured the posture-related changes in relaxation volume and total lung capacity in 10 healthy subjects in four postures: upright, supine, prone, and left lateral decubitus. Then, in the same subjects, we measured static pressure-volume characteristics of the lung over a wide range of lung volumes in each posture by using an esophageal balloon catheter. Transpulmonary pressure during relaxation (PLrel) averaged 3.7 (SD 2.0) cmH2O upright and -3.3 (SD 3.2) cmH2O supine. Approximately 58% of the decrease in PLrel between the upright and supine postures was due to a corresponding decrease in relaxation volume. The remaining 2.9-cmH2O difference is consistent with reported values of a presumed postural artifact. Relaxation volumes and pressures in prone and lateral postures were intermediate. To correct estimated transpulmonary pressure for the effect of lying supine, we suggest adding 3 cmH2O (95% confidence interval: -1 to +7 cmH2O). We conclude that postural differences in estimated transpulmonary pressure at a given lung volume are small compared with the substantial range of PLrel in patients with acute lung injury.     

The alveolar pores of Kohn in young postnatal rat lungs and their relation with type II pneumocytes.

In order to obtain more information on the development, morphology and function of the pores of Kohn, the lungs of Wistar rats are studied during their early postnatal period, up to 3 weeks of age, by scanning and transmission electron microscopy. The substantial development of the interalveolar pores on days 14 and 21 coincides with the period of septal rearrangement when secondary interalveolar septa become lengthened and thinner. The high frequency of transseptal type II pneumocytes from day 7 onwards, and their typical localization near the pores of Kohn at this period of lung development especially suggests that type II pneumocytes are engaged in the formation of the pores of Kohn. During early lung development, the pores of Kohn seem to serve as passageways for alveolar macrophages.     

Size of the pores created by an electric pulse: Microsecond vs millisecond pulses

Here, the sizes of the pores created by square-wave electric pulses with the duration of 100μs and 2ms are compared for pulses with the amplitudes close to the threshold of electroporation. Experiments were carried out with three types of cells: mouse hepatoma MH-22A cells, Chinese hamster ovary (CHO) cells, and human erythrocytes. In the case of a short pulse (square-wave with the duration of 100μs or exponential with the time constant of 22μs), in the large portion (30-60%) of electroporated (permeable to potassium ions) cells, an electric pulse created only the pores, which were smaller than the molecule of bleomycin (molecular mass of 1450Da, r≈0.8nm) or sucrose (molecular mass of 342.3Da, radius-0.44-0.52nm). In the case of a long 2-ms duration pulse, in almost all cells, which were electroporated, there were the pores larger than the molecules of bleomycin and/or sucrose. Kinetics of pore resealing depended on the pulse duration and was faster after the shorter pulse. After a short 100-μs duration pulse, the disappearance of the pores permeable to bleomycin was completed after 6-7min at 24-26°C, while after a long 2-ms duration pulse, this process was slower and lasted 15-20min. Thus, it can be concluded that a short 100-μs duration pulse created smaller pores than the longer 2-ms duration pulse. This could be attributed to the time inadequacy for pores to grow and expand during the pulse, in the case of short pulses.     

The influence of red cell mechanical properties on flow through single capillary-sized pores

The resistive pulse technique was used to study the influence of specific mechanical properties of the red cell on its ability to enter and flow through single capillary-sized pores with diameters of 3.6, 5.0 and 6.3 micron and lengths of 11 micron. A two-fold increase in membrane shear elasticity resulted in a 40 percent increase in the cell's transit time through a 3.6 micron pore but produced no change in transit time through a 6.3 micron pore. A two-fold increase in membrane shear viscosity produced a 40 percent increase in transit time through the 3.6 micron pore and small but significant increases in transit times through the larger pores. Osmotically dehydrated cells showed no increase in transit time through a 6.3 micron pore, but showed increases in transit times of 50 to 70 percent through 5.0 and 3.6 micron pores. Dense red cells showed increased transit times through both 5.0 micron and 6.0 micron pores. These results indicate that for cells with normal geometric properties, the membrane's shear viscosity and elasticity only influence the cell's transit through pores of 5 micron or less in diameter. However, alterations in the cell's geometric properties can extend the influence of membrane shear properties to larger diameter pores.     

Reactive oxygen species: influence on cerebral vascular tone.

Reactive oxygen species have multiple effects on vascular cells. Defining the sources and the impact of the various reactive oxygen species within the vessel wall has emerged as a major area of study in vascular biology. This review will focus on recent findings related to effects of reactive oxygen species on cerebral vascular tone. Effects of superoxide radical, hydrogen peroxide, and the reactive nitrogen species peroxynitrite are summarized. Although higher concentrations may be important for cerebral vascular biology in disease, relatively low concentrations of reactive oxygen species may function as signaling molecules involved with normal regulation of cerebral vascular tone. The mechanisms by which reactive oxygen species affect vascular tone may be quite complex, and our understanding of these processes is increasing. Additionally, the role of reactive oxygen species as mediators of endothelium-dependent relaxation is addressed. Finally, the consequences of the molecular interactions of superoxide with nitric oxide and arachidonic acid are discussed.     

Genetics and cardiovascular system: influence of human genetic variants on vascular function

Candidate gene association studies in cardiovascular diseases have provided evidence on the molecular basis of phenotypic differences between individuals. The comprehension of how inherited genetic variants are able to affect protein functions has increased the knowledge of how genes interact with environment in order to modulate a particular phenotype. Although it is known that the human genome contains more than 10 million SNPs, only a minor part of them are supposed to be functional. A causative SNP in a particular gene may confer a small to moderate effect in complex phenotypes, such as functions important to cardiovascular homeostasis. This paper is a selective review of the literature on the evidence for interactions between vascular function and naturally occurring genetic variants in endothelial nitric oxide synthase (eNOS) and beta-2 adrenergic receptor (ADRB2), two genes among those influencing vascular phenotype and examples for which there is a strong evidence base. eNOS and ADRB2 will be characterized, as well as the mechanisms by which the enzyme and the receptor work to control vascular responses will be described. Understanding the molecular mechanisms underlying gene-mediated vascular function and their modification by genetic variants is expected to result in a better comprehension about individual's phenotypic differences.     

Computational assessment of the influence of vastus medialis obliquus function on patellofemoral pressures: Model evaluation

A study was performed to evaluate a computational model used to characterize the influence of vastus medialis obliquus (VMO) function on the patellofemoral pressure distribution. Ten knees were tested in vitro at 40°, 60° and 80° of knee flexion with quadriceps loads applied to represent a normal VMO, and with the VMO force decreased by approximately 50% to represent a weak VMO. The tests were performed with the cartilage intact and with a full thickness cartilage lesion centered on the lateral facet of the patella. The experimental tests were replicated computationally by applying discrete element analysis to a model of each knee constructed from MRI images. Repeated measures statistical comparisons were used to compare computational to experimental data and identify significant (p<0.05) differences due to the lesion and the applied VMO force. Neither the lateral force percentage nor the maximum lateral pressure varied significantly between the computational and experimental data. Creating a lesion significantly increased the maximum lateral pressure for all comparisons, except for the experimental data at 40°. Both computationally and experimentally, decrease in the VMO force increased the lateral force percentage by approximately 10% for all cases, and each increase was statistically significant. The maximum lateral pressure increase was typically less than 10% but was still significant for the majority of comparisons focused on the VMO strength. The results indicate that computational modeling can be used to characterize how varying quadriceps loading influences the patellofemoral force and pressure distributions while varying the condition of cartilage.     

Biocompatibility of amorphous silica nanoparticles: Size and charge effect on vascular function, in vitro

Synthetic amorphous silica is gaining popularity as the material of choice in the fabrication of nanoparticles for use in imaging diagnostics, medical therapeutics, and tissue engineering because of its biocompatible nature. However, recent evidence suggests that silica nanoparticles (SiNPs) show a concentration- and size-dependent toxic effect that is cell specific. We investigated the direct influence of SiNP uptake on the vasodilator responses of rat aortic vessels, in vitro, using fabricated SiNPs of defined size (97 ± 7.60 and 197 ± 7.50 nm) and charge (positive and nonmodified). Dilator responses to cumulative doses of endothelial-dependent [acetylcholine (Ach); 0.01 μM-1.0 mM] and endothelial-independent (sodium nitroprusside; 0.01-10 μM) agonists were determined before and 30 Min after incubation in SiNPs (at 1.1 × 10(11) nanoparticles/mL). Acute exposure to SiNPs led to their rapid uptake by the lining endothelial cells (as verified by transmission electron microscopy). SiNP uptake had no significant influence on dilator responses, although a greater degree of attenuation was evident after uptake of the 100 nm and positively charged SiNPs (significant at the highest 1.0 mM Ach concentration between positive and nonmodified 200 nm SiNPs; P < 0.05). In summary, our findings suggest that SiNP surface interactions, rather than mass, affect vasodilator function of aortic vessels.     

The influence and interactions of hydrostatic and osmotic pressures on the intracellular milieu of chondrocytes

The intracellular milieu of chondroctyes is regulated by an array of proteins in the cell membrane which operate as transport pathways, allowing ions and nutrients such as glucose and amino acids and metabolites such as lactate to cross the plasma membrane. Here we investigated the influence of hydrostatic pressure on intracellular calcium concentrations ([Ca(2+)](i)) in isolated bovine articular chondrocytes. We found that short applications of high hydrostatic pressures led to a significant increase in [Ca(2+)](i). The pressure-induced rise was abolished for long (240 sec) but not short (30 sec) pressure applications by removal of extracellular Ca(2+). The rise in pressure was also blocked by the inhibitors neomycin and thapsigargin confirming that pressure, by generating IP(3), led to an increase in [Ca(2+)](i) by mobilising the pool of Ca(2+) ions contained within intracellular stores. We also found that intracellular [Na(+)] was affected by a rise in osmotic pressure and further affected by application of hydrostatic pressure. The effect of hydrostatic pressure on sulphate incorporation depended strongly on extracellular osmolality. Since significant gradients in extracellular osmolality exist across intact cartilage, the results imply that responses of chondrocytes to the same pressure will vary depending on location in the joint. The results also indicate that hydrostatic pressures can affect several different transporter systems thus influencing the intracellular milieu and chondrocyte metabolism.     

Unequal distribution of nuclear pores in oryzalin-induced mini-nuclei in protonema cells of the mossFunaria hygrometrica: influence of the nucleolus

Summary Mini-nuclei, formed in tip cells ofFunaria caulonemata after oryzalin treatment, have unequally distributed nuclear pores. The region of the nuclear envelope near the nucleolus, in a distance of up to 3 m, is devoid of pores. In other areas pores occur with a high frequency.     

Peripheral and central vascular conductance influence on post-exercise hypotension

Background

Post-exercise hypotension (PEH) following prolonged dynamic exercise arises from increased total vascular conductance (TVC) via skeletal muscle vasodilation. However, arterial vasodilation of skeletal musculatures does not entirely account for the rise in TVC. The aim of the present study was to determine the contribution of vascular conductance (VC) of the legs, arms, kidneys and viscera to TVC during PEH.

Methods

Eight subjects performed a single period of cycling at 60% of heart rate (HR) reserve for 60 minutes. Blood flow in the right renal, superior mesenteric, right brachial and right femoral arteries was measured by Doppler ultrasonography in a supine position before exercise and during recovery. HR and mean arterial pressure (MAP) were measured continuously. MAP decreased significantly from approximately 25 minutes after exercise cessation compared with pre-exercise baseline. TVC significantly increased (approximately 23%; P <0.05) after exercise compared with baseline, which resulted from increased VC in the leg (approximately 33%) and arm (approximately 20%), but not in the abdomen.

Conclusion

PEH was not induced by decreased cardiac output, but by increased TVC, two-thirds of the rise in which can be attributed to increased VC in active and inactive limbs.     

Nuclear pore complex structure: unplugged and dynamic pores

Nuclear pore complexes (NPCs) are large protein assemblies embedded in the nuclear envelope that act as passageways for transport of molecules into and out of the nucleus. Two new studies, one in Nature Cell Biology and one in Science , offer direct evidence that the NPC is a highly dynamic structure.