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The choice of models relating tritiated water absorption to subepithelial blood flow in the rumen of sheep.

1. The blood flow to the ruminoreticulum of anaesthetized sheep was varied by changing the proportion of CO2 in the gas stirring solutions confined to this organ. 2. Clearance of tritiated water was thereby varied fourfold, from 10 to 44ml./min.100 g epithelium, with negligible net water movement. 4. Subepithelial blood flow, observed with radioactive microspheres using the reference organ technique, varied tenfold, from 20 to 200 ml./min.100 g epithelium. 4. The relation between tritiated water absorption and blood water flow was approximated by a hyperbolic model, but was appreciably better described using a higher order term in blood flow consistent with a countercurrent exchange of tritiated water between arterioles and venules. 5. The distribution of blood flow between different regions of the organ and between epithelium and muscle is described.

Animals↗

Pneumococcal serotyping and antigen detection in pneumococcal pneumonia of adults.

A retrospective study of 125 patients presenting to the City Hospital, Edinburgh, with proven pneumococcal pneumonia showed that pneumococcus serotype 3 remains the most prevalent and that since 1970 the distribution of serotypes has remained virtually constant. The frequency of diagnosing pneumococcal pneumonia is increased by the use of countercurrent immuno-electrophoresis (CIE) of sputum. In this series, 25 per cent of patients with negative sputum culture but radiological evidence of pneumonia, were diagnosed by means of this method, which was overall more helpful in making the diagnosis than blood cultures. All nine deaths in this series were in those over 65 years of age.

Adolescent↗

Distribution of the myocardial tissue PO2 in the rat and the inhomogeneity of the coronary bed.

The structural inhomogeneity of the myocardial capillary bed is stimulated by microcirculatory units (MCU's) in a diffusion model. This stimulation is based on MCU's in which the arrangement of the capillary ends (concurrent structure, partial and total countercurrent (structure, helical structure) as well as the structure and supply parameters are varied. The variation of these parameters is based on own measurements of the intracapillary HbO2 saturation as well as on the following parameters from the literature: frequency distribution of capillary distance and capillary radius, mean capillary length or capillary section length respectively, arterial and mean venous PO2, mean coronary blood flow, mean O2 consumption and diffusion conductivity. The analysis of O2 supply of the normoxic rat heart shows that an O2 diffusion shunt is obligatory except of MCU's with an extremely large capillary distance or with a concurrent capillary structure. Therefore the minimal tissue PO2 lies at the level of the capillary venous PO2 of a MCU. The maximum of the total PO2 frequency distribution in the normoxic rat myocardium lies at 25 +/- 5 mm Hg, i.e. above the mean venous PO2 (20 mm Hg). Tissue PO2 values between 0 and 5 mm Hg amount to 0.5% i.e. they are extremely rare. Tissue PO2 values of 0-1 mm Hg represent less than 0.2%.

Animals↗

Concentrating defect in experimental nephrotic syndrone: altered expression of aquaporins and thick ascending limb Na+ transporters.

BACKGROUND: Several pathophysiological states associated with deranged water balance are associated with altered expression and/or intracellular distribution of aquaporin water channels. The possible role of dysregulation of thick ascending limb NaCl transporters, which are responsible for countercurrent multiplication in the kidney, has not been evaluated. METHODS: Semiquantitative immunoblotting and immunocytochemistry were carried out in the kidneys of rat with adriamycin-induced nephrotic syndrome and in vehicle-injected control rats. RESULTS: Preliminary studies confirmed the presence of a severe concentrating defect. Semiquantitative immunoblotting of outer medullary homogenates demonstrated a marked decrease in the abundance of three thick ascending limb Na+ transporters in nephrotic rats, namely the bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), the type 3 Na/H exchanger (NHE-3), and the alpha 1-subunit of the Na-K-ATPase. These results are predictive of a decrease in the NaCl transport capacity of the medullary thick ascending limb and therefore a decrease in countercurrent multiplication. Immunocytochemistry of outer medullary thin sections demonstrated broad (but highly variable) suppression of BSC-1 expression in the outer medullas of adriamycin-nephrotic rats. There was also a large decrease in outer medullary expression of two collecting duct water channels (aquaporin-2 and -3) and the major water channel of the thin descending limb of Henle's loop (aquaporin-1). CONCLUSION: The concentrating defect in adriamycin-induced nephrotic syndrome in rats is a consequence of multiple defects in water and solute transporter expression, which would alter both the generation of medullary interstitial hypertonicity and osmotic equilibration in the collecting duct. Whether a similar widespread defect in transporter expression is present in idiopathic nephrotic syndrome is, at this point, untested.

Animals↗

Histochemical and immunohistochemical localization of hexokinase isoenzymes in rat kidney.

Histochemical and immunohistochemical staining techniques have been used to investigate the localization of hexokinase isoenzymes within rat kidney tissue. Hexokinase type I was shown to be the major isoenzyme present. It was located mainly in the thin and thick limbs of loops of Henle, in distal tubules and in the transitional or dark cells in the initial portions of collecting ducts. The smooth muscle cells of arteries and arterioles, peripheral nerves and the transitional epithelial cells lining the renal pyramid also contained large amounts of the isoenzyme while smaller quantities were present in glomeruli and in collecting tubules near the papillary tip. The distribution pattern obtained in tubular epithelia agrees well with that demonstrated in earlier microdissection studies. It is also consistent with the suggestion that glycolysis provides the majority of the energy fuelling the sodium transport mechanisms which form such an essential feature of the countercurrent urine concentration system present within the renal medulla.

Animals↗

Absorption and preferential vagina-to-uterus distribution after vaginal administration of (99m)Tc-pertechnetate in postmenopausal women.

OBJECTIVE: To investigate in vivo and in humans the mechanisms and kinetics of vagina-to-uterus distribution. DESIGN: Controlled clinical study. SETTING: Volunteers in an academic research environment. PATIENT(S): Six postmenopausal women undergoing transabdominal hysterectomy were selected. INTERVENTION(S): Women received 0.2 mL of (99m)Tc-pertechnetate vaginally. In three patients the cervical canal was previously sealed by means of surgical glue. Six postmenopausal women who had received (99m)Tc-pertechnetate intravenously for a thyroid scintigraphy were considered as a control. MAIN OUTCOME MEASURE(S): Radioactivity was assessed every 30 minutes for 6 hours in the pelvis and in body regions where (99m)Tc-pertechnetate normally accumulates (thyroid, salivary glands, and stomach). RESULT(S): Uterine activity appeared after 60 minutes and peaked between 120 to 210 minutes. These same times were observed in the patients who had a sealed cervix. Thyroid uptake appeared after 180 minutes and peaked between 210 and 330 minutes. Uterine uptake did not occur in any of the intravenous patients; their thyroid uptake was rapid, appearing after 30 minutes. CONCLUSION(S): Preferential vagina-to-uterus distribution, at least in postmenopausal women, is not simply due an intracanalicular passage but is mediated by absorption of substances and probably by a countercurrent transfer mechanism.

Absorption↗

The simulation of continuous arteriovenous hemodialysis with a mathematical model.

We have developed a mathematical model that predicts the performance of continuous arteriovenous hemodialysis. Given patient (plasma protein concentration, hematocrit, mean arterial pressure, central venous pressure) and circuit (flow resistance, membrane hydraulic permeability, dialyzer mass transfer coefficient, ultrafiltrate column height, dialysate flow rate) characteristics as inputs, predictions of hydraulic and oncotic pressure distribution, filtration rate, blood flow, total, diffusive, and convective urea clearances are provided. The model was tested by perfusing a circuit with bovine blood under conditions of pure ultrafiltration, zero net ultrafiltration and dialysis, or combined ultrafiltration and dialysis (countercurrent dialysate flow at rates of 10, 20, and 30 ml/min). In order to permit computation, membrane hydraulic permeability and flow resistances were measured. Dialyzer mass transfer coefficient for urea could not be measured directly and so was determined by fitting model predictions to measured urea clearances. For all conditions of operation, a urea mass transfer coefficient of 0.014 cm/min successfully simulated the data. Predictions of blood flow, filtrate generation rate, and circuit pressure distribution were accurate. At lower dialysate flow rates, urea clearance approximated the sum of dialysate flow and filtration rate. At higher dialysate flows, however, departure from this ideal blood-dialysate equilibrium was observed. Model predictions regarding the relative contributions of diffusion and convection to urea clearance were explored. Under conditions of nearly perfect equilibration of urea between blood and dialysate at the blood inlet, the model predicts that the diffusive clearance of urea will increase with increasing rate of filtration and may exceed the rate of dialysate inflow.

Hemofiltration↗

Behavior of lanthanides in countercurrent chromatography using dihexyl-N,N-diethylcarbamoyl methylene phosphonate as stationary phase.

Counter-current chromatography is a real liquid-liquid chromatography. The retention volume of the solute can be calculated from the batch distribution ratio in organic separations. In the separations of metal ion, there are several complex and dissociation reactions involved in the two phases, and the retention volume cannot be always predicted from the batch distribution ratio. A mass transfer model is proposed in this paper and an expression of V(R) is derived. The retention volume of metal ion is determined not only by the batch distribution ratio but also by the mechanism of the extraction reaction. When 25% dihexyl-N,N-diethylcarbamoyl methylenephosphonate in cyclohexane is used as stationary phase and 2.91 mol/l HNO3 as mobile phase, the dynamic distribution ratios obtained from the chromatogram are not equal to but proportional to the batch distribution coefficients. These results are in agreement with the theoretical expression.

Calibration↗

Inner medullary lactate production and accumulation: a vasa recta model.

Since anaerobic glycolysis yields two lactates for each glucose consumed and since it is reported to be a major source of ATP for inner medullary (IM) cell maintenance, it is a likely source of "external" IM osmoles. It has long been known that such an osmole source could theoretically contribute to the "single-effect" of the urine concentrating mechanism, but there was previously no suggestion of a plausible source. I used numerical simulation to estimate axial gradients of lactate and glucose that might be accumulated by countercurrent recycling in IM vasa recta (IMVR). Based on measurements in other tissues, anaerobic glycolysis (assumed to be independent of diuretic state) was estimated to consume approximately 20% of the glucose delivered to the IM. IM tissue mass and axial distribution of loops and vasa recta were according to reported values for rat and other rodents. Lactate (P(LAC)) and glucose (P(GLU)) permeabilities were varied over a range of plausible values. The model results suggest that P(LAC) of 100 x 10(-5) cm/s (similar to measured permeabilities for other small solutes) is sufficiently high to ensure efficient lactate recycling. By contrast, it was necessary in the model to reduce P(GLU) to a small fraction of this value (1/25th) to avoid papillary glucose depletion by countercurrent shunting. The results predict that IM lactate production could suffice to build a significant steady-state axial lactate gradient in the IM interstitium. Other modeling studies (Jen JF and Stephenson JL. Bull Math Biol 56: 491-514, 1994; and Thomas SR and Wexler AS. Am J Physiol Renal Fluid Electrolyte Physiol 269: F159-F171, 1995) have shown that 20-100 mosmol/kgH(2)O of unspecified external, interstitial, osmolytes could greatly improve IM concentrating ability. The present study gives several plausible scenarios consistent with accumulation of metabolically produced lactate osmoles, although only to the lower end of this range. For example, if 20% of entering glucose is consumed, the model predicts that papillary lactate would attain about 15 mM assuming vasa recta outflow is increased 30% by fluid absorbed from the nephrons and collecting ducts and that this lactate gradient would double if IM blood flow were reduced by one-half, as may occur in antidiuresis. Several experimental tests of the hypothesis are indicated.

Animals↗

Heat transport mechanisms in vascular tissues: a model comparison.

We have conducted a parametric comparison of three different vascular models for describing heat transport in tissue. Analytical and numerical methods were used to predict the gross temperature distribution throughout the tissue and the small-scale temperature gradients associated with thermally significant blood vessels. The models are: an array of unidirectional vessels, an array of countercurrent vessels, and a set of large vessels feeding small vessels which then drain into large vessels. We show that three continuum formulations of bioheat transfer (directed perfusion, effective conductivity, and a temperature-dependent heat sink) are limiting cases of the vascular models with respect to the thermal equilibration length of the vessels. When this length is comparable to the width of the heated region of tissue, the local temperature changes near the vessels can be comparable to the gross temperature elevation. These results are important to the use of thermal techniques used to measure the blood perfusion rate and in the treatment of cancer with local hyperthermia.

Biomechanical Phenomena↗

Three-dimensional architecture of inner medullary vasa recta.

The manner in which vasa recta function and contribute to the concentrating mechanism depends on their three-dimensional relationships to each other and to tubular elements. We have examined the three-dimensional architecture of vasculature relative to tubular structures in the central region of rat kidney inner medulla from the base through the first 3 mm by combining immunohistochemistry and semiautomated image acquisition techniques with graphical modeling software. Segments of descending vasa recta (DVR), ascending vasa recta (AVR), descending thin limb (DTL), ascending thin limb (ATL), and collecting duct (CD) were identified with antibodies against segment-specific proteins associated with solute and water transport (urea channel B, PV-1, aquaporin-1, ClC-K1, aquaporin-2, respectively) by immunofluorescence. Results indicate: 1) DVR, like DTLs, are excluded from CD clusters that we have previously shown to be the organizing element for the inner medulla; 2) AVR, like ATLs, are nearly uniformly distributed transversely across the entire inner medulla outside of and within CD clusters; 3) DVR and AVR outside CD clusters appear to be sufficiently juxtaposed to permit good countercurrent exchange; 4) within CD clusters, about four AVR closely abut each CD, surrounding it in a highly symmetrical fashion; and 5) AVR abutting each CD and ATLs within CD clusters form repeating nodal interstitial spaces bordered by a CD on one side, one or more ATLs on the opposite side, and one AVR on each of the other two sides. These relationships may be highly significant for both establishing and maintaining the inner medullary osmotic gradient.

Animals↗

Bacterial meningitis in Egypt: analysis of CSF isolates from hospital patients in Cairo, 1977-78.

Bacterial meningitis remains a major cause of mortality and morbidity in many countries of the world despite effective antimicrobial therapy. Studies of the etiology and some laboratory characteristics of bacterial meningitis in Egypt were conducted during 1977-1978. All patients suspected of having bacterial meningitis were studied at the time of admission to the two fever hospitals of Cairo. Direct culture, serological identification of the capsular type, and countercurrent-immunoelectrophoresis of 1627 CSF specimens were done. Of these, 276 had bacteria identified either by culture or Gram stain. Pneumococci were the most common and the serotype distribution was similar to that reported from other parts of Africa; second were meningococci with groups C and B predominating; in third place was Haemophilus influenzae type b which caused the highest mortality and had an unusually young age distribution. There were 77 bacterial isolates (22%), including 11 species, designated as "other" because there was no predominant species. There were many "clear" CSF specimens that were found to contain pneumococci, meningococci or H. influenzae type b, confirming the need for more comprehensive laboratory facilities for accurate diagnosis of the etiology of bacterial meningitis.

Adolescent↗

Parametric studies on the three-layer microcirculatory model for surface tissue energy exchange.

The new three-layer microvascular mathematical model for surface tissue heat transfer developed in, which is based on detailed vascular casts and tissue temperature measurements in the rabbit thigh, is used to investigate the thermal characteristics of surface tissue under a wide variety of physiological conditions. Studies are carried out to examine the effects of vascular configuration, arterial blood supply rate, distribution of capillary perfusion, cutaneous blood circulation and metabolic heat production on the average tissue temperature profile, the local arterial-venous blood temperature difference in the thermally significant countercurrent vessels, and surface heat flux.

Body Temperature Regulation↗

A facilitative urea transporter is localized in the renal collecting tubule of the dogfish Triakis scyllia.

Reabsorption of filtered urea by the kidney tubule is essential for retaining high levels of urea in body fluids of marine elasmobranchs. To elucidate the mechanisms of urea reabsorption, we examined the distribution of a facilitative urea transporter (UT) in the kidney of the dogfish Triakis scyllia. We isolated a cDNA encoding a UT that is homologous to the facilitative UT cloned from another dogfish species, Squalus acanthias. The Triakis UT mRNA is abundantly expressed in the kidney, while low levels of expression were detected in the brain and liver. In the dogfish kidney, each nephron makes four turns and traverses repeatedly between bundle zone and sinus zone. In the bundle zone, the resulting five tubular segments are arranged in a countercurrent loop fashion. Immunohistochemistry using specific antibodies raised against the cloned UT revealed that, among the nephron segments, the UT is expressed exclusively in the final segment of the bundle zone, i.e. in the collecting tubule of the Triakis kidney. In contrast to the limited localization of UT, the transport enzyme Na+/K+-ATPase is distributed in the basolateral membrane of numerous tubular segments both in the sinus zone and the bundle zone. However, in the collecting tubule, Na+/K+-ATPase immunoreactivity was not detected. The present study suggests that the collecting tubule is responsible for the reabsorption of urea in the marine elasmobranch kidney. Other countercurrent segments may contribute to production of a driving force for facilitative diffusion of urea through the UT.

Amino Acid Sequence↗

A critical parameter for transcapillary exchange of small solutes in countercurrent systems.

Small solute transport by a countercurrent capillary loop was studied using a theoretical model. In the model, the afferent and the efferent limbs of the loop share a common interstitial space, with which exchange of solute occurs. Sources of solute, epithelial cells, exist near capillaries and secret solute into the interstitial fluid. Parameters based on experimental measurements on young Sprague-Dawley rats were used in the model, and asymptotic solutions were derived. Comparison of the solute distribution in the interstitium between a capillary loop and a single capillary reveals that the ratio of the product of permeability (P(1)) and surface area (A(1)) to flow (F(1)) of the afferent limb, gamma(1)=P(1)A(1)/F(1) is a critical parameter for the countercurrent exchange system. It alone determines whether the countercurrent arrangement of capillaries facilitates clearance of solute from the interstitial fluid, a greater axial gradient of solute in the interstitium from the base to the tip of the capillary loop and a greater effect of flow, F, upon this gradient. The properties of the efferent limb affect the results, but it is gamma(1) that determines the characteristic difference between a capillary loop and a single capillary.

Animals↗

How well mixed is inert gas in tissues?

The washout of inert gas from tissues typically follows multiexponential curves rather than monoexponential curves as would be expected from homogeneous, well-mixed compartment. This implies that the ratio for the square root of the variance of the distribution of transit times to the mean (relative dispersion) must be greater than 1. Among the possible explanations offered for multiexponential curves are heterogeneous capillary flow, uneven capillary spacing, and countercurrent exchange in small veins and arteries. By means of computer simulations of the random walk of gas molecules across capillary beds with parameters of skeletal muscle, we find that heterogeneity involving adjacent capillaries does not suffice to give a relative dispersion greater than one. Neither heterogeneous flow, nor variations in spacing, nor countercurrent exchange between capillaries can account for the multiexponential character of experimental tissue washout curves or the large relative dispersions that have been measured. Simple diffusion calculations are used to show that many gas molecules can wander up to several millimeters away from their entry point during an average transit through a tissue bed. Analytical calculations indicate that an inert gas molecule in an arterial vessel will usually make its first vascular exit from a vessel larger than 20 micron and will wander in and out of tissue and microvessels many times before finally returning to the central circulation. The final exit from tissue will nearly always be into a vessel larger than 20 micron. We propose the hypothesis that the multiexponential character of skeletal muscle tissue inert gas washout curves must be almost entirely due to heterogeneity between tissue regions separated by 3 mm or more, or to countercurrent exchanges in vessels larger than 20 micron diam.

Capillaries↗

Fermentation of corn stover to carboxylic acids.

This article describes countercurrent fermentation to anaerobically convert corn stover and pig manure to mixed carboxylic acids using a mixed culture of mesophilic microorganisms. Corn stover was pretreated with lime to increase digestibility. The Continuum Particle Distribution Model (CPDM) was used to simulate continuous fermentors based on data collected from batch experiments. This model saves considerable time in determining optimum operating conditions. For 80% corn stover/20% pig manure, the highest total carboxylic acid productivity was 1.81 g/(L of liquid. d) at a concentration of 21.4 g total acid/L. The highest total acid selectivity, yield, and conversion were 0.714 g total acid/g volatile solids (VS) digested, 0.550 g total acid/g VS fed, and 0.770 g VS digested/g VS fed, respectively, at a concentration of 16.0 g total acid/L. CPDM predicted the acid concentration and conversion within 13.4 and 11.6%, respectively.

Animals↗

EVIDENCE OF REGULATORY MECHANISMS FOR THE DISTRIBUTION OF BLOOD BETWEEN THE ARTERIAL AND THE VENOUS COMPARTMENTS IN THE HAGFISH GILL POUCH

Of the extant vertebrate animals, the hagfishes are generally considered to be the group which diverged first from the ancestral vertebrate lineage, although molecular sequence analysis has recently suggested that they form a monophyletic group with lampreys (Stock and Whitt, 1992). The circulatory system of hagfishes has features that have been described as 'primitive' (Burggren et al. 1985), but their gills are effective gas exchangers. The gills are contained within discrete muscular pouches, and the anatomy of the blood system and ventilatory ducts has an ideal countercurrent arrangement (Mallatt and Paulsen, 1986; Elger, 1987). Reite (1969) first reported effects of catecholamines and other drugs on the branchial vasculature of hagfish. Recent studies of both perfused gills in situ and of blood flow in vivo have suggested that blood flow through the gills of hagfish is under tonic control by catecholamines (Axelsson et al. 1990; Forster et al. 1992). In teleosts, several studies have shown that adrenergic control mechanisms are involved in the distribution of blood between the arterio-arterial and the arterio-venous pathways of the gill vasculature (see Nilsson, 1983). Anatomical and ultrastructural studies have demonstrated the existence of similar pathways in hagfish (Cole, 1925; Mallatt and Paulsen, 1986; Elger, 1987). The experiments reported here demonstrate that, in the hagfish gill pouch, both adrenaline and isoprenaline can increase the proportion of fluid leaving via the efferent arterial route, at the expense of the venous outflow. Hagfish (Eptatretus cirrhatus Forster) were collected off Motunau, North Canterbury, New Zealand, and held in seawater aquaria until used. The masses of the 11 animals used in these experiments ranged from 680 to 1720 g with a mean of 1140±110 g (s.e.m.). Animals were anaesthetized in a 0.4 % solution of benzocaine in sea water. The hagfish were opened ventrally to expose the gills and their blood supply. Individual gill pouches were prepared for perfusion studies.

Journal Article↗