Fast bicarbonate-chloride exchange between brain cells and brain extracellular fluid in respiratory acidosis

The extracellular pH, \(P_{CO_2 } \) , and [Cl^?] at the surface of the brain cortex, expiratory \(P_{CO_2 } \) and arterial blood pressure were continuously recorded in anaesthetized and artificially ventilated cats. The observations from such a preparation were:

1. In response to a nearly step increase in end-tidal \(P_{CO_2 } \) , the brain ECF pH, \(P_{CO_2 } \) , [Cl^?] and calculated [HCO ₃ ^? ] changed in the form of a nearly mono-exponential time function after a delay of 5–7 s.
2. The time constants of the changes in the extracellular pH, \(P_{CO_2 } \) , [Cl^?] and [HCO ₃ ^? ] were in the range of 30–40 s.
3. The extracellular [HCO ₃ ^? ] increased markedly at an initial rate of 4.22 mmol·l^?1·min^?1 after 36 s.
4. This increase occurred almost simultaneously with a decrease in the extracellular [Cl^?]. An [HCO ₃ ^? ]?[Cl^?] exchange ratio was determined which very closely approached one.

It is concluded that the brain extracellular bicarbonate concentration in respiratory acidosis increases because the H⁺ formed from the hydrated CO₂ reacts with the intracellular buffers of brain cells, mainly glial cells, and HCO ₃ ^? inside the cell is formed and exchanged for Cl^? outside the cell similar to the HCO ₃ ^? /Cl^? exchange which occurs between red cells and blood plasma during CO₂ loading. The described time constants of the anion exchange represent thewash in orwash out time of CO₂ in a tissue containing intracellular buffer.     

ArterialPa_{CO_2 } during chronic hyperthermia in sheep

This study was undertaken to determine if the decrease in and the concomitant increase in pH_a seen during acute (less than 24 h) hyperthermia in all mammals was modified when the hyperthermia was maintained for periods longer than 1 day. Catheters were placed in the descending aortas of anesthetized ewes (pentobarbital, 30 mg/kg, i.v.). After recovery from the surgery, arterial blood samples were drawn daily during a 7 day control period and an 8 day period of continuous hyperthermia. In all animals decreased and remained low during the entire hyperthermic period. (torr) andT _r (°C) were inversely correlated by the equation: = –6.08T _r+267.8 (r=0.84). There was an initial alkalosis with hyperthermia, however pH tended to decrease after the fifth day of hyperthermia. Calculated bicarbonate decreased during hyperthermia. The evidence suggested that when body temperature was increased in sheep, was maintained at a lower value. The low value was maintained independent of changes in pH_a.     

Transient and steady state responses of pulmonary ventilation to the medullary extracellular pH after approximately rectangular changes in alveolarP_{CO_2 }

The extracellular pH (pHe) either on the ventral surface of the medulla oblongata or the parietal cortex, the tidal volume, the expiratory PCO2 and the arterial blood pressure were continuously recorded in anaesthetized or unanaesthetized decerebrate cats. The concentration of the inspired CO2 was manipulated in order to obtain a nearly rectangular increase in the end-tidal PCO2. The responses of VT.f, VE and pH to such a change in PCO2 were observed. The observations from such a preparation were: 1. pHe responded with a delay of 5-7 s to a rectangular variation in end-tidal PCO2. 2. The time constant of the change in the medullary extracellular pH was in the range of 50 s and a similar value was found for VT and VE. 3. The response of VT or VE to a change in the medullary pHe was approximately linear in anaesthetized as well as in unanaesthetized decerebrate cats. The slope of the respiratory response of VT to pHe in decerebrate cats was about 3 times greater than that in anaesthetized cats. There were only slight differences in the relation of VT to pHe between the transient and steady state responses. This means that the "upstroke" of the on-transient of VT was approximately the same as the 'downstroke' of the off-transient. On the other hand, a slight delay was observed when VE was plotted against pHe. Pronounced delay occurred when respiratory frequency was plotted against pHe for on- and off-CO2 transients. 4. A marked hyteresis was observed when VT or VE was plotted against the cortical pHe for on- and off-CO2 inhalation. 5. Such a precise time correlation of the medullary surface pH and VT changes could only be possible if the pH on the ventral medullary surface is representative for the pH at the sensor.     

Concentration of interleukin-1{beta} correlates with prostaglandin E2 and F2{alpha} in human pre-ovulatory follicular fluid

To investigate the role(s) of interleukin-1 (IL-1) in humanovarian function, we measured the concentrations of IL–1,prostaglandins (PGs) and steroids in follicular fluid of 90stimulated ovaries, with reference to oocyte maturation. Concentrationsof IL-1 were significantly higher in the follicles from whichmature oocytes were recovered than in follicles from which oocytescould not be recovered (P < 0.05). IL-1 concentrations alsoincreased in association with oocyte maturation. Positive significantcorrelations were seen between IL-1 and prostaglandin E2 (PGE2)(r = 0.47, P < 0.001), and between IL-1 and prostaglandinF₂ (PGF₂) (r = 0.22, P < 0.05) in pre-ovulatory follicularfluid, but not between IL–1 and oestradiol, or betweenIL-1 and oestradiol, or between IL-1 and progesterone. 0Follicularfluid IL-1 might contribute to prostaglandin-induced oocytematuration and ovulation.     

血糖改变时兔脑细胞外液与血液中葡萄糖及乳酸变化的差异

目的：观察不同血糖条件下兔脑细胞外液与血液中葡萄糖（Glu）及乳酸（Lac）含量变化的差异。 方法： 采用微透析技术，每10 min收集脑细胞外液并静脉采血1次，观察正常条件下，以及静注20% Glu 0-60 min、胰岛素0-70 min期间血液及脑细胞外液中Glu及Lac的动态变化。 结果： 正常状态下，脑细胞外液中Glu明显低于血液，仅为血浆的30%，而Lac却显著高于血液，为血浆的165%；在高血糖及低血糖期间，脑细胞外液中Glu随着血糖浓度的改变而变化，但时间较血糖延迟30 min左右；脑细胞外液中Glu波动期间，Lac的水平无明显变化。 结论： 脑细胞外液中Glu及Lac水平与血液有很大差异，Lac可能参与了中枢神经系统的能量代谢。     

Interstitial fluid: exchange of macromolecules between plasma and skin interstitium

Fluid was collected from blisters developed by suction on the abdominal skin in ten normal volunteers. During the same study the transcapillary escape rate of intravenously injected 131I-albumin and 125I-IgG together with the accumulation of these tracers in the blister fluid was measured. The ratios between the concentrations of endogenous albumin, transferrin, IgG and alpha 2-macroglobulin in the blister fluid (Cb) and serum (Cs) correlated directly with the free diffusion coefficients indicating that the sieving properties of the vascular endothelium remained intact during the suction. The ratios of intravascular to total masses of the four endogenous proteins calculated from plasma volume, Cs, Cb and extracellular fluid volume determined with inulin and Cb were very similar to those obtained in long-term metabolic turnover studies. The ratio between the accumulated IgG and albumin tracers in the blister fluid (0.80) was identical with the Cb/Cs ratio between endogenous IgG and albumin (0.78) but higher than the ratio between the IgG and albumin escape rates from the total microvasculature (0.58). From the protein tracer determinations it cannot be definitely excluded that suction increases the microvascular escape rates. If the distribution volume of inulin equates that of albumin in steady-state it can, however, be concluded from the data given on the endogenous plasma protein, that blister fluid from the abdominal skin corresponds to average interstitial tissue fluid.     

Arterial and mixed venousP_{CO_2 } and hydrogen ion,bicarbonate and base excess concentrations in water-depleted dogs

Summary The arterial (a), mixed venous ( ), and arterial-mixed venous differences (A-V) of hydrogen ion concentration ([H⁺]), , HCO ₃ ^– and base excess (BE) were measured during 3 h in control (C), water-depleted (WD) and water- and salt-depleted (WSD) dogs.In WD animals the difference in hydrogen ion concentration between venous and arterial blood increased because the [H⁺] increased more in venous than in arterial blood. In WSD animals (A-V) [H⁺] remained unchanged since both [H⁺] _a and increases were parallel. [H⁺] variations seem to represent the changes in fixed-acid concentration of blood. The difference between both groups of animals in (A-V) [H⁺] changes could be ascribed to variations.[HCO ₃ ^– ] values changed inconsistently. Arterial samples from the experimental groups showed a continuous decrease at the same rate of change. The mean values in WSD were lower than in WD. of WSD decreased slowly during the experiment. The rate of decreased of (A-V) [HCO ₃ ^– ] was higher in WD than in WSD. The different behavior of [HCO ₃ ^– ] between both arterial and mixed venous samples and among experimental groups disappeared if [HCO ₃ ^– ] changes were corrected for bicarbonate generation due to variation (respiratory bicarbonate). Thus [HCO ₃ ^– ] corrected for variation represents metabolic changes, in good agreement with both [H⁺] and BE variations. The metabolic acidosis cannot be explained only on the basis of the increase in blood lactate; it is suggested that other fixed acids might contribute to the decrease in blood bicarbonate.In both experimental groups increased continuously. The (A-V) showed the same rate of change. There is a good relationship between this increase and the degree of plasma volume change. It therefore might be that increase is a direct consequence of hemodynamic impairment.In WD and WSD, BE decreased progressively in both arterial and mixed venous samples. BE _a values were lower than values after the experiment began. (A-V) BE decreased in an exponential manner in both experimental groups; this change could be ascribed to the increased level of deoxygenated hemoglobin in mixed venous blood, thus giving rise to a decrease in fixed acid concentration.     

The influence of changes inp_{CO_2 } on the fractional packed cell volume of whole blood

In order to investigate the influence of changes in on the fractional packed cell volume (FPCV, hematocrit) of whole blood, a device for measuring the conductivity was developed. This method allows an instantaneous and continous determination of the FPCV, because the erythrocyte membrane has insulating properties, and, consequently, the resistance of blood depends on the relative cell volume. The steady state and transient relationships between FPCV and acid-base levels were investigated by combining this method with simultaneous recordings of .The experiments showed that addition of CO₂ caused an increase in the resistance of whole blood, whereas the resistance of separated plasma decreased slightly and the resistance of true plasma remained almost constant. The change in the FPCV (H) can be described by a linear function of pH or log The transient response of the resistance, after a stepwise increase in the CO₂ content, was found to be the slowest process in attaining an acid-base equilibriu. In blood with acetazolamide, the time courses of changes in pH and were retarded, whereas the time course of the resistance change reflecting the swelling of the erythrocytes was nearly the same (T ₅₀4 s). This may indicate a rate-limited water shift due to a slight water permeability of the erythrocyte membrane.Supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 114 (Bionach)     

IL-4-induced B cell migration involves transient interactions between {beta}1 integrins and extracellular matrix components

IL-4 has previously been shown to stimulate motile responsesin murine B lymphocytes. This was studied as acquisition ofmotile morphology and migration through filters in microchemotaxischambers. In this paper, we investigated IL-4-stimulated migrationof B cells into gels of native collagen fibers, which may bea more physiologically relevant assay. When IL-4 was presentin the gel and/or in the medium above, B cells were able toinvade the collagen gel. Migration was dependent on the doseof IL-4 and was optimal after 45 h of incubation. It appearedthat IL-4 acted by inducing both chemokinesis and chemotaxis.Fibronectin (FN) was found to be an important factor for B celllocomotion, since low concentrations of FCS or FN in the gelmatrix greatly improved migration. B cell locomotion was inhibitedby antibodies specific for ß1, 4 and 5 integrins,indicating the presence of integrin-extracellular matrix (ECM)interactions in lymphocyte motility responses. Migration wasnot associated with an up-regulatlon of ß1, 4 or 5integrins. The adhesion between substrate and cells is likelyto be of low affinity, since IL-4-stimulated, as well as non-stimulatedB cells, did not adhere to ECM-coated culture wells. Our datasuggest that transient interactions between integrins and theECM matrix may favour B cell migration.     

IL-4 producing CD4+ TCR{alpha} {beta}int liver lymphocytes: influence of thymus, {beta}2-microglobulin and NK1.1 expression

The present report describes developmental, phenotypic and functionalfeatures of unconventional CD4⁺ TCRß lymphocytes.In C57BL/6 mice, the majority of liver lymphocytes expressingintermediate intensity of TCRß (TCRß^int)are CD4⁺NK1.1⁺ and express a highly restricted TCR V_ßrepertoire, dominated by V_ß8 with some contributionby V^ß7 and V^ß2. Although these cells expressthe CD4 co-receptor, they are present in H2-l Aß (Aß)^+/–gene disruption mutants but are markedly reduced in ß₂-microglobulin(ß₂m)^–/– mutant mice and hence are ß₂mdependent. Thymocytes expressing the CD4⁺NK1.1⁺ TCR ßphenotype are also (ß₂m) contingent, suggesting thatthese two T lymphocyte populations are related. The CD4⁺NK1.1⁺TCRßlymphocytes in liver and thymus share several markers such asLFA-1⁺, CD44⁺, CD5⁺, LECAM-1^– and IL-2Rßa. TheCD4⁺NK1.1 ⁺ TCRß^int liver lymphocytes were not detectedin athymic nuinu mice. We conclude that ß₂m expressionis crucial for development of the CD4⁺NK1.1⁺ TCRß^intliver lymphocytes and that thymus plays a major role. CD4⁺ TCRß^intliver lymphocytes were also identified in NK1.1⁺ mouse strains,there lacking the NK1.1 marker. We assume that the NK1.1 moleculeis a characteristic marker of the CD4⁺TCR"^int liver lymphocytesin NK1.1⁺ mouse strains, although its expression is not obligatoryfor their development. The liver lymphocytes from +₂m^+/–,but not from +₂m^–/–mice are potent IL-4 producersin response to CD3 or TCRß engagement and the IL-4production by liver lymphocytes was markedly reduced by treatmentwith anti-NK1.1 mAb. We conclude that the CD4+NK1.1⁺ TCRß^intliver lymphocytes are capable of producing IL-4 in responseto TCR stimulation.